MEDICATION SAFETY ISSUES
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
SPECIAL ALERTS
Alemtuzumab: Reports of Infection-Related Fatalities - November 2008
Bayer HealthCare and Genzyme, in conjunction with Health Canada, have issued notice to Canadian hospitals concerning reports of infection-related fatalities in patients receiving consolidation therapy with MabCampath® (alemtuzumab). Preliminary safety data from the ongoing phase II U.S. clinical trial CALGB10101 has reported fatalities in 6 out of 51 patients with B-cell chronic lymphocytic leukemia (B-CLL) receiving fludarabine and rituximab induction therapy followed by alemtuzumab therapy for remission consolidation.
Fatal infections included viral meningitis, Listeria meningitis, Legionella pneumonia, cytomegalovirus (CMV), Pneumocystis jiroveci pneumonia (PCP), and Epstein-Barr virus (EBV) associated lymphoproliferative disorder.
The potential contributory role of any of the three chemotherapeutic agents is not clear based on available data. The infectious complications may have resulted from prolonged immunosuppression. An additional noninfection-related fatality, thought to be transfusion-associated graft-versus-host disease (TAGVHD), has also been reported.
Use of alemtuzumab as consolidation therapy is presently not approved in Canada. An updated product monograph including this new important safety information is forthcoming. Further information can be found at http://www.hc-sc.gc.ca/dhp-mps/medeff/advisories-avis/prof/_2008/mabcampath_nth-aah-eng.php
U.S. BRAND NAMES — Campath®
PHARMACOLOGIC CATEGORY
Antineoplastic Agent, Monoclonal Antibody
DOSING: ADULTS — Note: Dose escalation is required; usually accomplished in 3-7 days. Single doses >30 mg or cumulative doses >90 mg/week increase the incidence of pancytopenia. Pretreatment (with acetaminophen and diphenhydramine) is recommended prior to the first dose, with dose escalations, and as clinically indicated; I.V. hydrocortisone may be used for severe infusion-related reactions. Reinitiate with gradual dose escalation if treatment is withheld ≥ 7 days.
B-cell CLL:
I.V. infusion: Initial: 3 mg/day beginning on day 1; if tolerated (infusion reaction ≤ grade 2), increase to 10 mg/day; if tolerated (infusion reaction ≤ grade 2), increase to maintenance of 30 mg/dose 3 times/week on alternate days for a total duration of therapy of up to 12 weeks
SubQ (unlabeled route): Initial: 3 mg on day 1; if tolerated 10 mg on day 3; if tolerated increase to 30 mg on day 5; maintenance: 30 mg/dose 3 times/week for a maximum of 18 weeks (Lundin, 2002) or 3 mg on day 1; if tolerated 10 mg on day 2; if tolerated 30 mg on day 3, followed by 30 mg/dose 3 times/week for 4-12 weeks (Stilgenbauer, 2009)
Cutaneous T-cell lymphoma (unlabeled use): I.V. infusion: 3 mg on day 1; if tolerated increase the next dose to 10 mg; if tolerated increase the next dose to 30 mg; Maintenance dose: 30 mg/dose 3 times/week for up to 12 weeks (Lundin, 2003)
Peripheral T-cell lymphoma (unlabeled use):I.V. infusion: 3 mg on day 1; 10 mg on day 3, followed by 30 mg/dose 3 times/week for a duration of therapy of up to 12 weeks (Enblad, 2004)
T-cell prolymphocytic leukemia (unlabeled use):I.V. infusion: Initial test dose 3 mg or 10 mg, followed by dose escalation to 30 mg/dose 3 times/week as tolerated (Dearden, 2001)
or
Week 1: 3 mg on day 1; 10 mg on day 2; 30 mg on day 3, followed in subsequent weeks by 30 mg/dose on alternate days 3 times/week for a total of 4-12 weeks (Ferrajoli, 2003)
or
Initial dose: 3 mg day 1, if tolerated increase to 10 mg day 2, if tolerated increase to 30 mg on day 3 (days 1, 2, and 3 are consecutive days), followed by 30 mg/dose every Monday, Wednesday, Friday for a total of 4-12 weeks (Keating, 2002)
DOSING: ELDERLY — Refer to adult dosing.
DOSING: ADJUSTMENT FOR TOXICITY
Dosage adjustment for nonhematologic toxicity:
Grade 3 or 4 infusion reaction: Withhold infusion.
Serious infection or other serious adverse reaction: Withhold alemtuzumab until resolution.
Autoimmune anemia or autoimmune thrombocytopenia: Discontinue alemtuzumab.
Dosage adjustment for hematologic toxicity (severe neutropenia or thrombocytopenia, not autoimmune):
First occurrence: ANC <250/µL and/or platelet count ≤ 25,000/µL: Hold therapy; resume at 30 mg/dose when ANC ≥ 500/µL and platelet count ≥ 50,000/µL.
Second occurrence: ANC <250/µL and/or platelet count ≤ 25,000/µL: Hold therapy; resume at 10 mg/dose when ANC ≥ 500/µL and platelet count ≥ 50,000/µL.
Third occurrence: ANC <250/µL and/or platelet count ≤ 25,000/µL: Discontinue alemtuzumab.
Patients with a baseline ANC ≤ 250/µL and/or a baseline platelet count ≤ 25,000/µL at initiation of therapy: If ANC and/or platelet counts decrease to ≤ 50% of the baseline value, hold therapy.
First occurrence: When ANC and/or platelet count return to baseline, resume therapy at 30 mg/dose.
Second occurrence: When ANC and/or platelet count return to baseline, resume therapy at 10 mg/dose.
Third occurrence: Discontinue alemtuzumab.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution [preservative free]:
Campath®: 30 mg/mL (1 mL) [contains polysorbate 80; disodium edetate]
DOSAGE FORMS: CONCISE
Injection, solution [preservative free]:
Campath®: 30 mg/mL (1 mL)
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Administer by I.V. infusion over 2 hours. Consider premedicating with diphenhydramine 50 mg and acetaminophen 500-1000 mg 30 minutes before initiation of infusion. Hydrocortisone 200 mg has been effective in decreasing severe infusion-related events. Start anti-infective prophylaxis. Other drugs should not be added to or simultaneously infused through the same I.V. line. Do not give I.V. push.
SubQ (unlabeled route): SubQ administration has been studied (Lundin, 2002; Stilgenbauer, 2009); an increased rate of injection site reactions has been observed, with only rare incidences of chills or infusion-like reactions typically observed with I.V. infusion. A longer dose escalation time (1-2 weeks) may be needed due to injection site reactions (Lundin, 2002). Premedication and anti-infective prophylaxis regimens should be given as are recommended with I.V. administration.
COMPATIBILITY — Stable in D5W, NS. Medications should not be added to the solution or simultaneously infused through the same I.V. line.
USE — Treatment of B-cell chronic lymphocytic leukemia (B-CLL)
USE - UNLABELED / INVESTIGATIONAL — Treatment of cutaneous T-cell lymphoma, peripheral T-cell lymphoma, refractory T-cell prolymphocytic leukemia, refractory or resistant autoimmune cytopenias; preconditioning regimen and prophylaxis of graft-versus-host disease (GVHD) in allogeneic stem cell transplant; immunosuppressant in solid organ transplant (induction and rejection)
ADVERSE REACTIONS SIGNIFICANT
>10%:
Cardiovascular: Hypotension (15% to 32%), peripheral edema (13%), hypertension (11% to 15%), dysrhythmia/tachycardia/SVT (10% to 14%)
Central nervous system: Fever (69% to 85%), chills (53%), fatigue (22% to 34%), headache (13% to 24%), dysthesias (15%), dizziness (12%)
Dermatologic: Rash (13% to 40%), urticaria (16% to 30%), pruritus (14% to 24%)
Gastrointestinal: Nausea (47% to 54%), vomiting (33% to 41%), anorexia (20%), diarrhea (10% to 22%), stomatitis/mucositis (14%), abdominal pain (11%)
Hematologic: Lymphopenia (grades 3/4: 97%), neutropenia (77% to 85%; grade 3/4: 42% to 70% [median onset: 31 days, median duration: 28-37 days]), anemia (76% to 80%; grade 3/4: 12% to 47% [median onset: 31 days, median duration 8 days]), thrombocytopenia (71% to 72%; grade 3/4: 13% to 52% [median onset: 9 days; median duration: 14-21 days])
Local: Injection site reaction (SubQ administration: 90%)
Neuromuscular & skeletal: Rigors (86% to 89%), skeletal pain (24%), weakness (13%), myalgia (11%)
Respiratory: Dyspnea (14% to 26%), cough (25%), bronchitis/pneumonitis (21%), pneumonia (16%), pharyngitis (12%)
Miscellaneous: Infection (43% to 74%; grades 3/4: 21% to 37%; incidence is lower if prophylactic anti-infectives are utilized), CMV viremia (55%), infusion reactions (grades 3/4: 10% to 35%), diaphoresis (19%), CMV infection (6% to 16%), sepsis (15%; grades 3/4: 3% to 10%), herpes viral infections (1% to 11%)
1% to 10%:
Cardiovascular: Chest pain (10%)
Central nervous system: Insomnia (10%), malaise (9%), anxiety (8%), depression (7%), temperature change sensation (5%), somnolence (5%)
Dermatologic: Purpura (8%), erythema (4%)
Gastrointestinal: Dyspepsia (10%), constipation (9%)
Hematologic: Neutropenic fever (10%; grades 3/4: 5% to 10%), pancytopenia/marrow hypoplasia (5% to 6%; grade 3/4: 3%), positive Coombs' test without hemolysis (2%), autoimmune thrombocytopenia (2%), autoimmune hemolytic anemia (1%)
Neuromuscular & skeletal: Back pain (10%), tremor (3% to 7%)
Respiratory: Bronchospasm (9%), epistaxis (7%), rhinitis (7%)
Miscellaneous: Moniliasis (8%)
<1% (Limited to important or life-threatening): Acidosis, acute renal failure, acute respiratory distress syndrome, agranulocytosis, alkaline phosphatase increased, allergic reactions, anaphylactoid reactions, angina pectoris, angioedema, anuria, aphasia, aplastic anemia, arrhythmia, ascites, asthma, atrial fibrillation, bacterial infection, biliary pain, bone marrow aplasia, bullous eruption, capillary fragility, cardiac arrest, cardiac failure, cardiac insufficiency, cardiomyopathy, cellulitis, cerebral hemorrhage, cerebrovascular disorder, chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), coagulation abnormality, colitis, coma, COPD, coronary artery disorder, cyanosis, deep vein thrombosis, dehydration, diabetes mellitus exacerbation, disseminated intravascular coagulation (DIC), duodenal ulcer, ejection fraction decreased, endophthalmitis, Epstein-Barr virus associated lymphoproliferative disorder, esophagitis, fluid overload, flu-like syndrome, gastrointestinal hemorrhage, Goodpasture's syndrome, Graves' disease, Guillain-Barre syndrome, hallucinations, hematemesis, hematoma, hematuria, hemolysis, hemolytic anemia, hemoptysis, hepatic failure, hepatocellular damage, HF, hyperbilirubinemia, hyper-/hypoglycemia, hyper-/hypokalemia, hypersensitivity, hyperthyroidism, hypoalbuminemia, hyponatremia, hypovolemia, hypoxia, idiopathic thrombocytopenic purpura (ITP), interstitial pneumonitis, intestinal obstruction, intestinal perforation, intracranial hemorrhage, Legionella pneumonia, Listeria meningitis, lymphadenopathy, marrow depression, melena, MI, mouth edema, myositis, optic neuropathy, osteomyelitis, pancreatitis, paralysis, paralytic ileus, paroxysmal nocturnal hemoglobinuria-like monocytes, peptic ulcer, pericarditis, peritonitis, plasma cell dyscrasia, phlebitis, pleural effusion, pleurisy, Pneumocystis jiroveci pneumonia, pneumothorax, polymyositis, progressive multifocal leukoencephalopathy, pseudomembranous colitis, pulmonary edema, pulmonary embolism, pulmonary fibrosis, pulmonary infiltration, pure red cell aplasia, purpuric rash, renal dysfunction, respiratory alkalosis, respiratory arrest, respiratory depression, respiratory insufficiency, seizure (grand mal), serum sickness, sinus bradycardia, splenic infarction, splenomegaly, stridor, subarachnoid hemorrhage, syncope, toxic nephropathy, thrombocythemia, thrombophlebitis, throat tightness, transfusion-associated GVHD, tuberculosis, tumor lysis syndrome, ureteric obstruction, urinary retention, urinary tract infection, ventricular arrhythmia, ventricular tachycardia, viral meningitis, virus reactivation (latent)
CONTRAINDICATIONS — There are no contraindications listed in the manufacturer's labeling
WARNINGS / PRECAUTIONS
Boxed warnings: Hematologic toxicity: See "Concerns related to adverse effects" below. Infections: See "Concerns related to adverse effects" below. Infusion reactions: See "Concerns related to adverse effects" below.
Special handling: Hazardous agent: Use appropriate precautions for handling and disposal.
Concerns related to adverse effects: Hematologic toxicity: [U.S. Boxed Warning]: Serious and fatal cytopenias (including pancytopenia, bone marrow hypoplasia, autoimmune hemolytic anemia, and autoimmune idiopathic thrombocytopenia) have occurred. Single doses >30 mg or cumulative weekly doses >90 mg are associated with an increased incidence of pancytopenia. Severe prolonged myelosuppression, hemolytic anemia, pure red cell aplasia, and bone marrow aplasia have also been reported. Discontinue therapy during serious hematologic or other serious toxicity (except lymphopenia) until the event resolves. Permanently discontinue if autoimmune anemia or autoimmune thrombocytopenia occurs. Patients receiving blood products should only receive irradiated blood products due to the potential for transfusion-associated GVHD during lymphopenia. Infections: [U.S. Boxed Warning]: Serious and potentially fatal infections (bacterial, viral, fungal, and protozoan) have been reported. Prophylactic medications against PCP pneumonia and herpes viral infections are recommended upon initiation of therapy and for at least 2 months following last dose or until CD4+ counts are ≥ 200 cells/µL (whichever is later). Severe and prolonged lymphopenia may occur; CD4+ counts usually return to ≥ 200 cells/µL within 2-6 months; however, CD4+ and CD8+ lymphocyte counts may not return to baseline levels for more than 1 year. Withhold treatment during serious infections; may be reinitiated upon resolution of infection. Monitor for CMV infection (during and for at least 2 months after completion of therapy); initiate appropriate antiviral treatment and withhold alemtuzumab for CMV infection or confirmed CMV viremia (withhold alemtuzumab during CMV antiviral treatment). Infusion reactions: [U.S. Boxed Warning]: Serious and potentially fatal infusion-related reactions may occur; withhold treatment for grade 3 or 4 infusion reactions. Gradual escalation to the recommended maintenance dose is required at initiation and with therapy interruption (for ≥ 7 days) to minimize infusion-related reactions. Infusion reaction symptoms may include acute respiratory distress syndrome, anaphylactic shock, angioedema, bronchospasm, cardiac arrest, cardiac arrhythmias, chills, dyspnea, fever, hypotension, myocardial infarction, pulmonary infiltrates, rash, rigors, syncope, or urticaria. The incidence of infusion reaction is highest during the first week of treatment. Premedication with acetaminophen and an oral antihistamine is recommended. Medications for the treatment of reactions should be available for immediate use. Use caution and carefully monitor blood pressure in patients with ischemic heart disease and patients on antihypertensive therapy. Reinitiate with gradual dose escalation if treatment is withheld ≥ 7 days.
Special populations: Men of reproductive potential: Should use effective contraceptive methods during treatment and for a minimum of 6 months following therapy. Pediatrics: Safety and efficacy have not been established in children. Women of childbearing potential: Should use effective contraceptive methods during treatment and for a minimum of 6 months following therapy.
Other warnings/precautions: Immunizations: Patients should not be immunized with live, viral vaccines during or recently after treatment. The ability to respond to any vaccine following therapy is unknown.
DRUG INTERACTIONS
Abciximab: May enhance the potential for allergic or hypersensitivity reactions to Monoclonal Antibodies. Also may cause thrombocytopenia or diminished therapeutic effects. Risk C: Monitor therapy
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Risk D: Consider therapy modification
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Risk X: Avoid combination
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Risk C: Monitor therapy
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Risk C: Monitor therapy
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Vaccinial infections may develop. Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination
ETHANOL / NUTRITION / HERB INTERACTIONS — Herb/Nutraceutical: Echinacea may diminish the therapeutic effect of alemtuzumab.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Human IgG is known to cross the placental barrier; therefore, alemtuzumab may also cross the barrier and cause fetal B- and T-lymphocyte depletion. Well-controlled human trials have not been done. Use during pregnancy only if the benefit to the mother outweighs the potential risk to the fetus. Effective contraception is recommended during and for 6 months after treatment for women of childbearing potential and men of reproductive potential.
LACTATION — Excretion in breast milk unknown/not recommended
BREAST-FEEDING CONSIDERATIONS — Human IgG is excreted in breast milk; therefore, alemtuzumab may also be excreted in milk. Breast-feeding should be discontinued during treatment and for at least 3 months following the last dose.
PRICING — (data from drugstore.com)
Solution (Campath)
30 mg/mL (3): $5999.53
MONITORING PARAMETERS — Vital signs; carefully monitor BP especially in patient with ischemic heart disease or on antihypertensive medications; CBC with differential and platelets (weekly, more frequent if worsening); signs and symptoms of infection; CD4+ lymphocyte counts (after treatment until recovery); CMV antigen (every 1-2 weeks). Monitor closely for infusion reactions (including hypotension, rigors, fever, shortness of breath, bronchospasm, chills, and/or rash).
CANADIAN BRAND NAMES — MabCampath®
INTERNATIONAL BRAND NAMES — Campath (AR, PE, UY); MabCampath (AT, AU, BE, BG, CH, CO, CZ, DE, DK, ES, FI, FR, GB, GR, HK, HN, ID, IE, IL, IT, KP, MY, NL, NO, PT, RU, SE, SG, TR, ZA); Mabcampath (PL)
MECHANISM OF ACTION — Binds to CD52, a nonmodulating antigen present on the surface of B and T lymphocytes, a majority of monocytes, macrophages, NK cells, and a subpopulation of granulocytes. After binding to CD52+ cells, an antibody-dependent lysis of leukemic cells occurs.
PHARMACODYNAMICS / KINETICS
Distribution: Vd: I.V.: 0.1-0.4 L/kg
Metabolism: Clearance decreases with repeated dosing (due to loss of CD52 receptors in periphery), resulting in a sevenfold increase in AUC.
Half-life elimination: I.V.: 11 hours (following first 30 mg dose; range: 2-32 hours); 6 days (following the last 30 mg dose; range: 1-14 days)
PATIENT INFORMATION — You will need frequent laboratory tests during course of therapy. Do not use any prescription or OTC medications unless approved by your prescriber. Maintain adequate hydration (2-3 L/day unless otherwise instructed) and nutrition (frequent small meals will help). You may experience abdominal pain, mouth sores, nausea, or vomiting (small frequent meals, good mouth care with soft toothbrush or swabs, sucking lozenges or chewing gum, and avoidance of spicy or salty foods may help). Report unresolved gastrointestinal problems, persistent fever, chills, muscle pain, skin rash, unusual bleeding or bruising, signs of infection (mouth sores, sore throat, white plaques in mouth or perianal area, burning on urination); swelling of extremities; difficulty breathing; chest pain or palpitations; or other persistent adverse reactions.
Monday, May 24, 2010
Alemtuzumab
MEDICATION SAFETY ISSUES
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
SPECIAL ALERTS
Alemtuzumab: Reports of Infection-Related Fatalities - November 2008
Bayer HealthCare and Genzyme, in conjunction with Health Canada, have issued notice to Canadian hospitals concerning reports of infection-related fatalities in patients receiving consolidation therapy with MabCampath® (alemtuzumab). Preliminary safety data from the ongoing phase II U.S. clinical trial CALGB10101 has reported fatalities in 6 out of 51 patients with B-cell chronic lymphocytic leukemia (B-CLL) receiving fludarabine and rituximab induction therapy followed by alemtuzumab therapy for remission consolidation.
Fatal infections included viral meningitis, Listeria meningitis, Legionella pneumonia, cytomegalovirus (CMV), Pneumocystis jiroveci pneumonia (PCP), and Epstein-Barr virus (EBV) associated lymphoproliferative disorder.
The potential contributory role of any of the three chemotherapeutic agents is not clear based on available data. The infectious complications may have resulted from prolonged immunosuppression. An additional noninfection-related fatality, thought to be transfusion-associated graft-versus-host disease (TAGVHD), has also been reported.
Use of alemtuzumab as consolidation therapy is presently not approved in Canada. An updated product monograph including this new important safety information is forthcoming. Further information can be found at http://www.hc-sc.gc.ca/dhp-mps/medeff/advisories-avis/prof/_2008/mabcampath_nth-aah-eng.php
U.S. BRAND NAMES — Campath®
PHARMACOLOGIC CATEGORY
Antineoplastic Agent, Monoclonal Antibody
DOSING: ADULTS — Note: Dose escalation is required; usually accomplished in 3-7 days. Single doses >30 mg or cumulative doses >90 mg/week increase the incidence of pancytopenia. Pretreatment (with acetaminophen and diphenhydramine) is recommended prior to the first dose, with dose escalations, and as clinically indicated; I.V. hydrocortisone may be used for severe infusion-related reactions. Reinitiate with gradual dose escalation if treatment is withheld ≥ 7 days.
B-cell CLL:
I.V. infusion: Initial: 3 mg/day beginning on day 1; if tolerated (infusion reaction ≤ grade 2), increase to 10 mg/day; if tolerated (infusion reaction ≤ grade 2), increase to maintenance of 30 mg/dose 3 times/week on alternate days for a total duration of therapy of up to 12 weeks
SubQ (unlabeled route): Initial: 3 mg on day 1; if tolerated 10 mg on day 3; if tolerated increase to 30 mg on day 5; maintenance: 30 mg/dose 3 times/week for a maximum of 18 weeks (Lundin, 2002) or 3 mg on day 1; if tolerated 10 mg on day 2; if tolerated 30 mg on day 3, followed by 30 mg/dose 3 times/week for 4-12 weeks (Stilgenbauer, 2009)
Cutaneous T-cell lymphoma (unlabeled use): I.V. infusion: 3 mg on day 1; if tolerated increase the next dose to 10 mg; if tolerated increase the next dose to 30 mg; Maintenance dose: 30 mg/dose 3 times/week for up to 12 weeks (Lundin, 2003)
Peripheral T-cell lymphoma (unlabeled use):I.V. infusion: 3 mg on day 1; 10 mg on day 3, followed by 30 mg/dose 3 times/week for a duration of therapy of up to 12 weeks (Enblad, 2004)
T-cell prolymphocytic leukemia (unlabeled use):I.V. infusion: Initial test dose 3 mg or 10 mg, followed by dose escalation to 30 mg/dose 3 times/week as tolerated (Dearden, 2001)
or
Week 1: 3 mg on day 1; 10 mg on day 2; 30 mg on day 3, followed in subsequent weeks by 30 mg/dose on alternate days 3 times/week for a total of 4-12 weeks (Ferrajoli, 2003)
or
Initial dose: 3 mg day 1, if tolerated increase to 10 mg day 2, if tolerated increase to 30 mg on day 3 (days 1, 2, and 3 are consecutive days), followed by 30 mg/dose every Monday, Wednesday, Friday for a total of 4-12 weeks (Keating, 2002)
DOSING: ELDERLY — Refer to adult dosing.
DOSING: ADJUSTMENT FOR TOXICITY
Dosage adjustment for nonhematologic toxicity:
Grade 3 or 4 infusion reaction: Withhold infusion.
Serious infection or other serious adverse reaction: Withhold alemtuzumab until resolution.
Autoimmune anemia or autoimmune thrombocytopenia: Discontinue alemtuzumab.
Dosage adjustment for hematologic toxicity (severe neutropenia or thrombocytopenia, not autoimmune):
First occurrence: ANC <250/µL and/or platelet count ≤ 25,000/µL: Hold therapy; resume at 30 mg/dose when ANC ≥ 500/µL and platelet count ≥ 50,000/µL.
Second occurrence: ANC <250/µL and/or platelet count ≤ 25,000/µL: Hold therapy; resume at 10 mg/dose when ANC ≥ 500/µL and platelet count ≥ 50,000/µL.
Third occurrence: ANC <250/µL and/or platelet count ≤ 25,000/µL: Discontinue alemtuzumab.
Patients with a baseline ANC ≤ 250/µL and/or a baseline platelet count ≤ 25,000/µL at initiation of therapy: If ANC and/or platelet counts decrease to ≤ 50% of the baseline value, hold therapy.
First occurrence: When ANC and/or platelet count return to baseline, resume therapy at 30 mg/dose.
Second occurrence: When ANC and/or platelet count return to baseline, resume therapy at 10 mg/dose.
Third occurrence: Discontinue alemtuzumab.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution [preservative free]:
Campath®: 30 mg/mL (1 mL) [contains polysorbate 80; disodium edetate]
DOSAGE FORMS: CONCISE
Injection, solution [preservative free]:
Campath®: 30 mg/mL (1 mL)
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Administer by I.V. infusion over 2 hours. Consider premedicating with diphenhydramine 50 mg and acetaminophen 500-1000 mg 30 minutes before initiation of infusion. Hydrocortisone 200 mg has been effective in decreasing severe infusion-related events. Start anti-infective prophylaxis. Other drugs should not be added to or simultaneously infused through the same I.V. line. Do not give I.V. push.
SubQ (unlabeled route): SubQ administration has been studied (Lundin, 2002; Stilgenbauer, 2009); an increased rate of injection site reactions has been observed, with only rare incidences of chills or infusion-like reactions typically observed with I.V. infusion. A longer dose escalation time (1-2 weeks) may be needed due to injection site reactions (Lundin, 2002). Premedication and anti-infective prophylaxis regimens should be given as are recommended with I.V. administration.
COMPATIBILITY — Stable in D5W, NS. Medications should not be added to the solution or simultaneously infused through the same I.V. line.
USE — Treatment of B-cell chronic lymphocytic leukemia (B-CLL)
USE - UNLABELED / INVESTIGATIONAL — Treatment of cutaneous T-cell lymphoma, peripheral T-cell lymphoma, refractory T-cell prolymphocytic leukemia, refractory or resistant autoimmune cytopenias; preconditioning regimen and prophylaxis of graft-versus-host disease (GVHD) in allogeneic stem cell transplant; immunosuppressant in solid organ transplant (induction and rejection)
ADVERSE REACTIONS SIGNIFICANT
>10%:
Cardiovascular: Hypotension (15% to 32%), peripheral edema (13%), hypertension (11% to 15%), dysrhythmia/tachycardia/SVT (10% to 14%)
Central nervous system: Fever (69% to 85%), chills (53%), fatigue (22% to 34%), headache (13% to 24%), dysthesias (15%), dizziness (12%)
Dermatologic: Rash (13% to 40%), urticaria (16% to 30%), pruritus (14% to 24%)
Gastrointestinal: Nausea (47% to 54%), vomiting (33% to 41%), anorexia (20%), diarrhea (10% to 22%), stomatitis/mucositis (14%), abdominal pain (11%)
Hematologic: Lymphopenia (grades 3/4: 97%), neutropenia (77% to 85%; grade 3/4: 42% to 70% [median onset: 31 days, median duration: 28-37 days]), anemia (76% to 80%; grade 3/4: 12% to 47% [median onset: 31 days, median duration 8 days]), thrombocytopenia (71% to 72%; grade 3/4: 13% to 52% [median onset: 9 days; median duration: 14-21 days])
Local: Injection site reaction (SubQ administration: 90%)
Neuromuscular & skeletal: Rigors (86% to 89%), skeletal pain (24%), weakness (13%), myalgia (11%)
Respiratory: Dyspnea (14% to 26%), cough (25%), bronchitis/pneumonitis (21%), pneumonia (16%), pharyngitis (12%)
Miscellaneous: Infection (43% to 74%; grades 3/4: 21% to 37%; incidence is lower if prophylactic anti-infectives are utilized), CMV viremia (55%), infusion reactions (grades 3/4: 10% to 35%), diaphoresis (19%), CMV infection (6% to 16%), sepsis (15%; grades 3/4: 3% to 10%), herpes viral infections (1% to 11%)
1% to 10%:
Cardiovascular: Chest pain (10%)
Central nervous system: Insomnia (10%), malaise (9%), anxiety (8%), depression (7%), temperature change sensation (5%), somnolence (5%)
Dermatologic: Purpura (8%), erythema (4%)
Gastrointestinal: Dyspepsia (10%), constipation (9%)
Hematologic: Neutropenic fever (10%; grades 3/4: 5% to 10%), pancytopenia/marrow hypoplasia (5% to 6%; grade 3/4: 3%), positive Coombs' test without hemolysis (2%), autoimmune thrombocytopenia (2%), autoimmune hemolytic anemia (1%)
Neuromuscular & skeletal: Back pain (10%), tremor (3% to 7%)
Respiratory: Bronchospasm (9%), epistaxis (7%), rhinitis (7%)
Miscellaneous: Moniliasis (8%)
<1% (Limited to important or life-threatening): Acidosis, acute renal failure, acute respiratory distress syndrome, agranulocytosis, alkaline phosphatase increased, allergic reactions, anaphylactoid reactions, angina pectoris, angioedema, anuria, aphasia, aplastic anemia, arrhythmia, ascites, asthma, atrial fibrillation, bacterial infection, biliary pain, bone marrow aplasia, bullous eruption, capillary fragility, cardiac arrest, cardiac failure, cardiac insufficiency, cardiomyopathy, cellulitis, cerebral hemorrhage, cerebrovascular disorder, chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), coagulation abnormality, colitis, coma, COPD, coronary artery disorder, cyanosis, deep vein thrombosis, dehydration, diabetes mellitus exacerbation, disseminated intravascular coagulation (DIC), duodenal ulcer, ejection fraction decreased, endophthalmitis, Epstein-Barr virus associated lymphoproliferative disorder, esophagitis, fluid overload, flu-like syndrome, gastrointestinal hemorrhage, Goodpasture's syndrome, Graves' disease, Guillain-Barre syndrome, hallucinations, hematemesis, hematoma, hematuria, hemolysis, hemolytic anemia, hemoptysis, hepatic failure, hepatocellular damage, HF, hyperbilirubinemia, hyper-/hypoglycemia, hyper-/hypokalemia, hypersensitivity, hyperthyroidism, hypoalbuminemia, hyponatremia, hypovolemia, hypoxia, idiopathic thrombocytopenic purpura (ITP), interstitial pneumonitis, intestinal obstruction, intestinal perforation, intracranial hemorrhage, Legionella pneumonia, Listeria meningitis, lymphadenopathy, marrow depression, melena, MI, mouth edema, myositis, optic neuropathy, osteomyelitis, pancreatitis, paralysis, paralytic ileus, paroxysmal nocturnal hemoglobinuria-like monocytes, peptic ulcer, pericarditis, peritonitis, plasma cell dyscrasia, phlebitis, pleural effusion, pleurisy, Pneumocystis jiroveci pneumonia, pneumothorax, polymyositis, progressive multifocal leukoencephalopathy, pseudomembranous colitis, pulmonary edema, pulmonary embolism, pulmonary fibrosis, pulmonary infiltration, pure red cell aplasia, purpuric rash, renal dysfunction, respiratory alkalosis, respiratory arrest, respiratory depression, respiratory insufficiency, seizure (grand mal), serum sickness, sinus bradycardia, splenic infarction, splenomegaly, stridor, subarachnoid hemorrhage, syncope, toxic nephropathy, thrombocythemia, thrombophlebitis, throat tightness, transfusion-associated GVHD, tuberculosis, tumor lysis syndrome, ureteric obstruction, urinary retention, urinary tract infection, ventricular arrhythmia, ventricular tachycardia, viral meningitis, virus reactivation (latent)
CONTRAINDICATIONS — There are no contraindications listed in the manufacturer's labeling
WARNINGS / PRECAUTIONS
Boxed warnings: Hematologic toxicity: See "Concerns related to adverse effects" below. Infections: See "Concerns related to adverse effects" below. Infusion reactions: See "Concerns related to adverse effects" below.
Special handling: Hazardous agent: Use appropriate precautions for handling and disposal.
Concerns related to adverse effects: Hematologic toxicity: [U.S. Boxed Warning]: Serious and fatal cytopenias (including pancytopenia, bone marrow hypoplasia, autoimmune hemolytic anemia, and autoimmune idiopathic thrombocytopenia) have occurred. Single doses >30 mg or cumulative weekly doses >90 mg are associated with an increased incidence of pancytopenia. Severe prolonged myelosuppression, hemolytic anemia, pure red cell aplasia, and bone marrow aplasia have also been reported. Discontinue therapy during serious hematologic or other serious toxicity (except lymphopenia) until the event resolves. Permanently discontinue if autoimmune anemia or autoimmune thrombocytopenia occurs. Patients receiving blood products should only receive irradiated blood products due to the potential for transfusion-associated GVHD during lymphopenia. Infections: [U.S. Boxed Warning]: Serious and potentially fatal infections (bacterial, viral, fungal, and protozoan) have been reported. Prophylactic medications against PCP pneumonia and herpes viral infections are recommended upon initiation of therapy and for at least 2 months following last dose or until CD4+ counts are ≥ 200 cells/µL (whichever is later). Severe and prolonged lymphopenia may occur; CD4+ counts usually return to ≥ 200 cells/µL within 2-6 months; however, CD4+ and CD8+ lymphocyte counts may not return to baseline levels for more than 1 year. Withhold treatment during serious infections; may be reinitiated upon resolution of infection. Monitor for CMV infection (during and for at least 2 months after completion of therapy); initiate appropriate antiviral treatment and withhold alemtuzumab for CMV infection or confirmed CMV viremia (withhold alemtuzumab during CMV antiviral treatment). Infusion reactions: [U.S. Boxed Warning]: Serious and potentially fatal infusion-related reactions may occur; withhold treatment for grade 3 or 4 infusion reactions. Gradual escalation to the recommended maintenance dose is required at initiation and with therapy interruption (for ≥ 7 days) to minimize infusion-related reactions. Infusion reaction symptoms may include acute respiratory distress syndrome, anaphylactic shock, angioedema, bronchospasm, cardiac arrest, cardiac arrhythmias, chills, dyspnea, fever, hypotension, myocardial infarction, pulmonary infiltrates, rash, rigors, syncope, or urticaria. The incidence of infusion reaction is highest during the first week of treatment. Premedication with acetaminophen and an oral antihistamine is recommended. Medications for the treatment of reactions should be available for immediate use. Use caution and carefully monitor blood pressure in patients with ischemic heart disease and patients on antihypertensive therapy. Reinitiate with gradual dose escalation if treatment is withheld ≥ 7 days.
Special populations: Men of reproductive potential: Should use effective contraceptive methods during treatment and for a minimum of 6 months following therapy. Pediatrics: Safety and efficacy have not been established in children. Women of childbearing potential: Should use effective contraceptive methods during treatment and for a minimum of 6 months following therapy.
Other warnings/precautions: Immunizations: Patients should not be immunized with live, viral vaccines during or recently after treatment. The ability to respond to any vaccine following therapy is unknown.
DRUG INTERACTIONS
Abciximab: May enhance the potential for allergic or hypersensitivity reactions to Monoclonal Antibodies. Also may cause thrombocytopenia or diminished therapeutic effects. Risk C: Monitor therapy
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Risk D: Consider therapy modification
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Risk X: Avoid combination
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Risk C: Monitor therapy
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Risk C: Monitor therapy
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Vaccinial infections may develop. Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination
ETHANOL / NUTRITION / HERB INTERACTIONS — Herb/Nutraceutical: Echinacea may diminish the therapeutic effect of alemtuzumab.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Human IgG is known to cross the placental barrier; therefore, alemtuzumab may also cross the barrier and cause fetal B- and T-lymphocyte depletion. Well-controlled human trials have not been done. Use during pregnancy only if the benefit to the mother outweighs the potential risk to the fetus. Effective contraception is recommended during and for 6 months after treatment for women of childbearing potential and men of reproductive potential.
LACTATION — Excretion in breast milk unknown/not recommended
BREAST-FEEDING CONSIDERATIONS — Human IgG is excreted in breast milk; therefore, alemtuzumab may also be excreted in milk. Breast-feeding should be discontinued during treatment and for at least 3 months following the last dose.
PRICING — (data from drugstore.com)
Solution (Campath)
30 mg/mL (3): $5999.53
MONITORING PARAMETERS — Vital signs; carefully monitor BP especially in patient with ischemic heart disease or on antihypertensive medications; CBC with differential and platelets (weekly, more frequent if worsening); signs and symptoms of infection; CD4+ lymphocyte counts (after treatment until recovery); CMV antigen (every 1-2 weeks). Monitor closely for infusion reactions (including hypotension, rigors, fever, shortness of breath, bronchospasm, chills, and/or rash).
CANADIAN BRAND NAMES — MabCampath®
INTERNATIONAL BRAND NAMES — Campath (AR, PE, UY); MabCampath (AT, AU, BE, BG, CH, CO, CZ, DE, DK, ES, FI, FR, GB, GR, HK, HN, ID, IE, IL, IT, KP, MY, NL, NO, PT, RU, SE, SG, TR, ZA); Mabcampath (PL)
MECHANISM OF ACTION — Binds to CD52, a nonmodulating antigen present on the surface of B and T lymphocytes, a majority of monocytes, macrophages, NK cells, and a subpopulation of granulocytes. After binding to CD52+ cells, an antibody-dependent lysis of leukemic cells occurs.
PHARMACODYNAMICS / KINETICS
Distribution: Vd: I.V.: 0.1-0.4 L/kg
Metabolism: Clearance decreases with repeated dosing (due to loss of CD52 receptors in periphery), resulting in a sevenfold increase in AUC.
Half-life elimination: I.V.: 11 hours (following first 30 mg dose; range: 2-32 hours); 6 days (following the last 30 mg dose; range: 1-14 days)
PATIENT INFORMATION — You will need frequent laboratory tests during course of therapy. Do not use any prescription or OTC medications unless approved by your prescriber. Maintain adequate hydration (2-3 L/day unless otherwise instructed) and nutrition (frequent small meals will help). You may experience abdominal pain, mouth sores, nausea, or vomiting (small frequent meals, good mouth care with soft toothbrush or swabs, sucking lozenges or chewing gum, and avoidance of spicy or salty foods may help). Report unresolved gastrointestinal problems, persistent fever, chills, muscle pain, skin rash, unusual bleeding or bruising, signs of infection (mouth sores, sore throat, white plaques in mouth or perianal area, burning on urination); swelling of extremities; difficulty breathing; chest pain or palpitations; or other persistent adverse reactions.
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
SPECIAL ALERTS
Alemtuzumab: Reports of Infection-Related Fatalities - November 2008
Bayer HealthCare and Genzyme, in conjunction with Health Canada, have issued notice to Canadian hospitals concerning reports of infection-related fatalities in patients receiving consolidation therapy with MabCampath® (alemtuzumab). Preliminary safety data from the ongoing phase II U.S. clinical trial CALGB10101 has reported fatalities in 6 out of 51 patients with B-cell chronic lymphocytic leukemia (B-CLL) receiving fludarabine and rituximab induction therapy followed by alemtuzumab therapy for remission consolidation.
Fatal infections included viral meningitis, Listeria meningitis, Legionella pneumonia, cytomegalovirus (CMV), Pneumocystis jiroveci pneumonia (PCP), and Epstein-Barr virus (EBV) associated lymphoproliferative disorder.
The potential contributory role of any of the three chemotherapeutic agents is not clear based on available data. The infectious complications may have resulted from prolonged immunosuppression. An additional noninfection-related fatality, thought to be transfusion-associated graft-versus-host disease (TAGVHD), has also been reported.
Use of alemtuzumab as consolidation therapy is presently not approved in Canada. An updated product monograph including this new important safety information is forthcoming. Further information can be found at http://www.hc-sc.gc.ca/dhp-mps/medeff/advisories-avis/prof/_2008/mabcampath_nth-aah-eng.php
U.S. BRAND NAMES — Campath®
PHARMACOLOGIC CATEGORY
Antineoplastic Agent, Monoclonal Antibody
DOSING: ADULTS — Note: Dose escalation is required; usually accomplished in 3-7 days. Single doses >30 mg or cumulative doses >90 mg/week increase the incidence of pancytopenia. Pretreatment (with acetaminophen and diphenhydramine) is recommended prior to the first dose, with dose escalations, and as clinically indicated; I.V. hydrocortisone may be used for severe infusion-related reactions. Reinitiate with gradual dose escalation if treatment is withheld ≥ 7 days.
B-cell CLL:
I.V. infusion: Initial: 3 mg/day beginning on day 1; if tolerated (infusion reaction ≤ grade 2), increase to 10 mg/day; if tolerated (infusion reaction ≤ grade 2), increase to maintenance of 30 mg/dose 3 times/week on alternate days for a total duration of therapy of up to 12 weeks
SubQ (unlabeled route): Initial: 3 mg on day 1; if tolerated 10 mg on day 3; if tolerated increase to 30 mg on day 5; maintenance: 30 mg/dose 3 times/week for a maximum of 18 weeks (Lundin, 2002) or 3 mg on day 1; if tolerated 10 mg on day 2; if tolerated 30 mg on day 3, followed by 30 mg/dose 3 times/week for 4-12 weeks (Stilgenbauer, 2009)
Cutaneous T-cell lymphoma (unlabeled use): I.V. infusion: 3 mg on day 1; if tolerated increase the next dose to 10 mg; if tolerated increase the next dose to 30 mg; Maintenance dose: 30 mg/dose 3 times/week for up to 12 weeks (Lundin, 2003)
Peripheral T-cell lymphoma (unlabeled use):I.V. infusion: 3 mg on day 1; 10 mg on day 3, followed by 30 mg/dose 3 times/week for a duration of therapy of up to 12 weeks (Enblad, 2004)
T-cell prolymphocytic leukemia (unlabeled use):I.V. infusion: Initial test dose 3 mg or 10 mg, followed by dose escalation to 30 mg/dose 3 times/week as tolerated (Dearden, 2001)
or
Week 1: 3 mg on day 1; 10 mg on day 2; 30 mg on day 3, followed in subsequent weeks by 30 mg/dose on alternate days 3 times/week for a total of 4-12 weeks (Ferrajoli, 2003)
or
Initial dose: 3 mg day 1, if tolerated increase to 10 mg day 2, if tolerated increase to 30 mg on day 3 (days 1, 2, and 3 are consecutive days), followed by 30 mg/dose every Monday, Wednesday, Friday for a total of 4-12 weeks (Keating, 2002)
DOSING: ELDERLY — Refer to adult dosing.
DOSING: ADJUSTMENT FOR TOXICITY
Dosage adjustment for nonhematologic toxicity:
Grade 3 or 4 infusion reaction: Withhold infusion.
Serious infection or other serious adverse reaction: Withhold alemtuzumab until resolution.
Autoimmune anemia or autoimmune thrombocytopenia: Discontinue alemtuzumab.
Dosage adjustment for hematologic toxicity (severe neutropenia or thrombocytopenia, not autoimmune):
First occurrence: ANC <250/µL and/or platelet count ≤ 25,000/µL: Hold therapy; resume at 30 mg/dose when ANC ≥ 500/µL and platelet count ≥ 50,000/µL.
Second occurrence: ANC <250/µL and/or platelet count ≤ 25,000/µL: Hold therapy; resume at 10 mg/dose when ANC ≥ 500/µL and platelet count ≥ 50,000/µL.
Third occurrence: ANC <250/µL and/or platelet count ≤ 25,000/µL: Discontinue alemtuzumab.
Patients with a baseline ANC ≤ 250/µL and/or a baseline platelet count ≤ 25,000/µL at initiation of therapy: If ANC and/or platelet counts decrease to ≤ 50% of the baseline value, hold therapy.
First occurrence: When ANC and/or platelet count return to baseline, resume therapy at 30 mg/dose.
Second occurrence: When ANC and/or platelet count return to baseline, resume therapy at 10 mg/dose.
Third occurrence: Discontinue alemtuzumab.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution [preservative free]:
Campath®: 30 mg/mL (1 mL) [contains polysorbate 80; disodium edetate]
DOSAGE FORMS: CONCISE
Injection, solution [preservative free]:
Campath®: 30 mg/mL (1 mL)
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Administer by I.V. infusion over 2 hours. Consider premedicating with diphenhydramine 50 mg and acetaminophen 500-1000 mg 30 minutes before initiation of infusion. Hydrocortisone 200 mg has been effective in decreasing severe infusion-related events. Start anti-infective prophylaxis. Other drugs should not be added to or simultaneously infused through the same I.V. line. Do not give I.V. push.
SubQ (unlabeled route): SubQ administration has been studied (Lundin, 2002; Stilgenbauer, 2009); an increased rate of injection site reactions has been observed, with only rare incidences of chills or infusion-like reactions typically observed with I.V. infusion. A longer dose escalation time (1-2 weeks) may be needed due to injection site reactions (Lundin, 2002). Premedication and anti-infective prophylaxis regimens should be given as are recommended with I.V. administration.
COMPATIBILITY — Stable in D5W, NS. Medications should not be added to the solution or simultaneously infused through the same I.V. line.
USE — Treatment of B-cell chronic lymphocytic leukemia (B-CLL)
USE - UNLABELED / INVESTIGATIONAL — Treatment of cutaneous T-cell lymphoma, peripheral T-cell lymphoma, refractory T-cell prolymphocytic leukemia, refractory or resistant autoimmune cytopenias; preconditioning regimen and prophylaxis of graft-versus-host disease (GVHD) in allogeneic stem cell transplant; immunosuppressant in solid organ transplant (induction and rejection)
ADVERSE REACTIONS SIGNIFICANT
>10%:
Cardiovascular: Hypotension (15% to 32%), peripheral edema (13%), hypertension (11% to 15%), dysrhythmia/tachycardia/SVT (10% to 14%)
Central nervous system: Fever (69% to 85%), chills (53%), fatigue (22% to 34%), headache (13% to 24%), dysthesias (15%), dizziness (12%)
Dermatologic: Rash (13% to 40%), urticaria (16% to 30%), pruritus (14% to 24%)
Gastrointestinal: Nausea (47% to 54%), vomiting (33% to 41%), anorexia (20%), diarrhea (10% to 22%), stomatitis/mucositis (14%), abdominal pain (11%)
Hematologic: Lymphopenia (grades 3/4: 97%), neutropenia (77% to 85%; grade 3/4: 42% to 70% [median onset: 31 days, median duration: 28-37 days]), anemia (76% to 80%; grade 3/4: 12% to 47% [median onset: 31 days, median duration 8 days]), thrombocytopenia (71% to 72%; grade 3/4: 13% to 52% [median onset: 9 days; median duration: 14-21 days])
Local: Injection site reaction (SubQ administration: 90%)
Neuromuscular & skeletal: Rigors (86% to 89%), skeletal pain (24%), weakness (13%), myalgia (11%)
Respiratory: Dyspnea (14% to 26%), cough (25%), bronchitis/pneumonitis (21%), pneumonia (16%), pharyngitis (12%)
Miscellaneous: Infection (43% to 74%; grades 3/4: 21% to 37%; incidence is lower if prophylactic anti-infectives are utilized), CMV viremia (55%), infusion reactions (grades 3/4: 10% to 35%), diaphoresis (19%), CMV infection (6% to 16%), sepsis (15%; grades 3/4: 3% to 10%), herpes viral infections (1% to 11%)
1% to 10%:
Cardiovascular: Chest pain (10%)
Central nervous system: Insomnia (10%), malaise (9%), anxiety (8%), depression (7%), temperature change sensation (5%), somnolence (5%)
Dermatologic: Purpura (8%), erythema (4%)
Gastrointestinal: Dyspepsia (10%), constipation (9%)
Hematologic: Neutropenic fever (10%; grades 3/4: 5% to 10%), pancytopenia/marrow hypoplasia (5% to 6%; grade 3/4: 3%), positive Coombs' test without hemolysis (2%), autoimmune thrombocytopenia (2%), autoimmune hemolytic anemia (1%)
Neuromuscular & skeletal: Back pain (10%), tremor (3% to 7%)
Respiratory: Bronchospasm (9%), epistaxis (7%), rhinitis (7%)
Miscellaneous: Moniliasis (8%)
<1% (Limited to important or life-threatening): Acidosis, acute renal failure, acute respiratory distress syndrome, agranulocytosis, alkaline phosphatase increased, allergic reactions, anaphylactoid reactions, angina pectoris, angioedema, anuria, aphasia, aplastic anemia, arrhythmia, ascites, asthma, atrial fibrillation, bacterial infection, biliary pain, bone marrow aplasia, bullous eruption, capillary fragility, cardiac arrest, cardiac failure, cardiac insufficiency, cardiomyopathy, cellulitis, cerebral hemorrhage, cerebrovascular disorder, chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), coagulation abnormality, colitis, coma, COPD, coronary artery disorder, cyanosis, deep vein thrombosis, dehydration, diabetes mellitus exacerbation, disseminated intravascular coagulation (DIC), duodenal ulcer, ejection fraction decreased, endophthalmitis, Epstein-Barr virus associated lymphoproliferative disorder, esophagitis, fluid overload, flu-like syndrome, gastrointestinal hemorrhage, Goodpasture's syndrome, Graves' disease, Guillain-Barre syndrome, hallucinations, hematemesis, hematoma, hematuria, hemolysis, hemolytic anemia, hemoptysis, hepatic failure, hepatocellular damage, HF, hyperbilirubinemia, hyper-/hypoglycemia, hyper-/hypokalemia, hypersensitivity, hyperthyroidism, hypoalbuminemia, hyponatremia, hypovolemia, hypoxia, idiopathic thrombocytopenic purpura (ITP), interstitial pneumonitis, intestinal obstruction, intestinal perforation, intracranial hemorrhage, Legionella pneumonia, Listeria meningitis, lymphadenopathy, marrow depression, melena, MI, mouth edema, myositis, optic neuropathy, osteomyelitis, pancreatitis, paralysis, paralytic ileus, paroxysmal nocturnal hemoglobinuria-like monocytes, peptic ulcer, pericarditis, peritonitis, plasma cell dyscrasia, phlebitis, pleural effusion, pleurisy, Pneumocystis jiroveci pneumonia, pneumothorax, polymyositis, progressive multifocal leukoencephalopathy, pseudomembranous colitis, pulmonary edema, pulmonary embolism, pulmonary fibrosis, pulmonary infiltration, pure red cell aplasia, purpuric rash, renal dysfunction, respiratory alkalosis, respiratory arrest, respiratory depression, respiratory insufficiency, seizure (grand mal), serum sickness, sinus bradycardia, splenic infarction, splenomegaly, stridor, subarachnoid hemorrhage, syncope, toxic nephropathy, thrombocythemia, thrombophlebitis, throat tightness, transfusion-associated GVHD, tuberculosis, tumor lysis syndrome, ureteric obstruction, urinary retention, urinary tract infection, ventricular arrhythmia, ventricular tachycardia, viral meningitis, virus reactivation (latent)
CONTRAINDICATIONS — There are no contraindications listed in the manufacturer's labeling
WARNINGS / PRECAUTIONS
Boxed warnings: Hematologic toxicity: See "Concerns related to adverse effects" below. Infections: See "Concerns related to adverse effects" below. Infusion reactions: See "Concerns related to adverse effects" below.
Special handling: Hazardous agent: Use appropriate precautions for handling and disposal.
Concerns related to adverse effects: Hematologic toxicity: [U.S. Boxed Warning]: Serious and fatal cytopenias (including pancytopenia, bone marrow hypoplasia, autoimmune hemolytic anemia, and autoimmune idiopathic thrombocytopenia) have occurred. Single doses >30 mg or cumulative weekly doses >90 mg are associated with an increased incidence of pancytopenia. Severe prolonged myelosuppression, hemolytic anemia, pure red cell aplasia, and bone marrow aplasia have also been reported. Discontinue therapy during serious hematologic or other serious toxicity (except lymphopenia) until the event resolves. Permanently discontinue if autoimmune anemia or autoimmune thrombocytopenia occurs. Patients receiving blood products should only receive irradiated blood products due to the potential for transfusion-associated GVHD during lymphopenia. Infections: [U.S. Boxed Warning]: Serious and potentially fatal infections (bacterial, viral, fungal, and protozoan) have been reported. Prophylactic medications against PCP pneumonia and herpes viral infections are recommended upon initiation of therapy and for at least 2 months following last dose or until CD4+ counts are ≥ 200 cells/µL (whichever is later). Severe and prolonged lymphopenia may occur; CD4+ counts usually return to ≥ 200 cells/µL within 2-6 months; however, CD4+ and CD8+ lymphocyte counts may not return to baseline levels for more than 1 year. Withhold treatment during serious infections; may be reinitiated upon resolution of infection. Monitor for CMV infection (during and for at least 2 months after completion of therapy); initiate appropriate antiviral treatment and withhold alemtuzumab for CMV infection or confirmed CMV viremia (withhold alemtuzumab during CMV antiviral treatment). Infusion reactions: [U.S. Boxed Warning]: Serious and potentially fatal infusion-related reactions may occur; withhold treatment for grade 3 or 4 infusion reactions. Gradual escalation to the recommended maintenance dose is required at initiation and with therapy interruption (for ≥ 7 days) to minimize infusion-related reactions. Infusion reaction symptoms may include acute respiratory distress syndrome, anaphylactic shock, angioedema, bronchospasm, cardiac arrest, cardiac arrhythmias, chills, dyspnea, fever, hypotension, myocardial infarction, pulmonary infiltrates, rash, rigors, syncope, or urticaria. The incidence of infusion reaction is highest during the first week of treatment. Premedication with acetaminophen and an oral antihistamine is recommended. Medications for the treatment of reactions should be available for immediate use. Use caution and carefully monitor blood pressure in patients with ischemic heart disease and patients on antihypertensive therapy. Reinitiate with gradual dose escalation if treatment is withheld ≥ 7 days.
Special populations: Men of reproductive potential: Should use effective contraceptive methods during treatment and for a minimum of 6 months following therapy. Pediatrics: Safety and efficacy have not been established in children. Women of childbearing potential: Should use effective contraceptive methods during treatment and for a minimum of 6 months following therapy.
Other warnings/precautions: Immunizations: Patients should not be immunized with live, viral vaccines during or recently after treatment. The ability to respond to any vaccine following therapy is unknown.
DRUG INTERACTIONS
Abciximab: May enhance the potential for allergic or hypersensitivity reactions to Monoclonal Antibodies. Also may cause thrombocytopenia or diminished therapeutic effects. Risk C: Monitor therapy
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Risk D: Consider therapy modification
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Risk X: Avoid combination
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Risk C: Monitor therapy
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Risk C: Monitor therapy
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Vaccinial infections may develop. Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination
ETHANOL / NUTRITION / HERB INTERACTIONS — Herb/Nutraceutical: Echinacea may diminish the therapeutic effect of alemtuzumab.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Human IgG is known to cross the placental barrier; therefore, alemtuzumab may also cross the barrier and cause fetal B- and T-lymphocyte depletion. Well-controlled human trials have not been done. Use during pregnancy only if the benefit to the mother outweighs the potential risk to the fetus. Effective contraception is recommended during and for 6 months after treatment for women of childbearing potential and men of reproductive potential.
LACTATION — Excretion in breast milk unknown/not recommended
BREAST-FEEDING CONSIDERATIONS — Human IgG is excreted in breast milk; therefore, alemtuzumab may also be excreted in milk. Breast-feeding should be discontinued during treatment and for at least 3 months following the last dose.
PRICING — (data from drugstore.com)
Solution (Campath)
30 mg/mL (3): $5999.53
MONITORING PARAMETERS — Vital signs; carefully monitor BP especially in patient with ischemic heart disease or on antihypertensive medications; CBC with differential and platelets (weekly, more frequent if worsening); signs and symptoms of infection; CD4+ lymphocyte counts (after treatment until recovery); CMV antigen (every 1-2 weeks). Monitor closely for infusion reactions (including hypotension, rigors, fever, shortness of breath, bronchospasm, chills, and/or rash).
CANADIAN BRAND NAMES — MabCampath®
INTERNATIONAL BRAND NAMES — Campath (AR, PE, UY); MabCampath (AT, AU, BE, BG, CH, CO, CZ, DE, DK, ES, FI, FR, GB, GR, HK, HN, ID, IE, IL, IT, KP, MY, NL, NO, PT, RU, SE, SG, TR, ZA); Mabcampath (PL)
MECHANISM OF ACTION — Binds to CD52, a nonmodulating antigen present on the surface of B and T lymphocytes, a majority of monocytes, macrophages, NK cells, and a subpopulation of granulocytes. After binding to CD52+ cells, an antibody-dependent lysis of leukemic cells occurs.
PHARMACODYNAMICS / KINETICS
Distribution: Vd: I.V.: 0.1-0.4 L/kg
Metabolism: Clearance decreases with repeated dosing (due to loss of CD52 receptors in periphery), resulting in a sevenfold increase in AUC.
Half-life elimination: I.V.: 11 hours (following first 30 mg dose; range: 2-32 hours); 6 days (following the last 30 mg dose; range: 1-14 days)
PATIENT INFORMATION — You will need frequent laboratory tests during course of therapy. Do not use any prescription or OTC medications unless approved by your prescriber. Maintain adequate hydration (2-3 L/day unless otherwise instructed) and nutrition (frequent small meals will help). You may experience abdominal pain, mouth sores, nausea, or vomiting (small frequent meals, good mouth care with soft toothbrush or swabs, sucking lozenges or chewing gum, and avoidance of spicy or salty foods may help). Report unresolved gastrointestinal problems, persistent fever, chills, muscle pain, skin rash, unusual bleeding or bruising, signs of infection (mouth sores, sore throat, white plaques in mouth or perianal area, burning on urination); swelling of extremities; difficulty breathing; chest pain or palpitations; or other persistent adverse reactions.
Alefacept
U.S. BRAND NAMES — Amevive®
PHARMACOLOGIC CATEGORY
Monoclonal Antibody
DOSING: ADULTS — Psoriasis (moderate-to-severe chronic plaque psoriasis):
I.M.: 15 mg once weekly; usual duration of treatment: 12 weeks
Second course: A second course of treatment may be initiated at least 12 weeks after completion of the initial course of treatment, provided CD4+ T-lymphocyte counts are within the normal range.
Note: CD4+ T-lymphocyte counts should be monitored before initiation of treatment and every 2 weeks during therapy. Dosing should be withheld if CD4+ counts are <250 cells/µL, and dosing should be permanently discontinued if CD4+ lymphocyte counts remain at <250 cells/µL for longer than 1 month.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — No dosage adjustment required.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution:
Amevive®: 15 mg [for I.M. administration; contains sucrose 12.5 mg; supplied with SWFI]
DOSAGE FORMS: CONCISE
Injection, powder for reconstitution [I.M. administration]:
Amevive®: 15 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — I.M. injections should be administered at least 1 inch from previous administration sites.
COMPATIBILITY — Do not mix with other medications or solutions.
USE — Treatment of moderate-to-severe chronic plaque psoriasis in adults who are candidates for systemic therapy or phototherapy
ADVERSE REACTIONS SIGNIFICANT
≥ 10%:
Hematologic: Lymphopenia (up to 10% of patients required temporary discontinuation, up to 17% during a second course of therapy)
Local: Injection site reactions (up to 16% of patients; includes pain, inflammation, bleeding, edema, or other reaction)
1% to 10%:
Central nervous system: Chills (6%; primarily during intravenous administration), dizziness (≥ 2%)
Dermatologic: Pruritus (≥ 2%)
Gastrointestinal: Nausea (≥ 2%)
Neuromuscular & skeletal: Myalgia (≥ 2%)
Respiratory: Pharyngitis (≥ 2%), cough increased (≥ 2%)
Miscellaneous: Malignancies (1% vs 0.5% in placebo), antibodies to alefacept (3%; significance unknown), infection (1% requiring hospitalization)
<1% (Limited to important or life-threatening): Anaphylaxis, allergic reaction, angioedema, headache, hepatitis, hepatic failure, MI, transaminases increased (≥ 3 times ULN), urticaria
CONTRAINDICATIONS — Hypersensitivity to alefacept or any component of the formulation; history of severe malignancy; patients with HIV infection or other clinically-important infections
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Hepatic injury: In post-marketing reports, significant transaminase elevations, as well as rare cases of hepatitis, fatty liver, decompensation of cirrhosis, and acute hepatic failure have occurred (causal relationship not established). Discontinue if signs and symptoms of hepatic injury occur. Hypersensitivity reactions: Has been associated with hypersensitivity reactions; rare anaphylaxis also reported. Discontinue use if severe reaction occurs. Immune suppression: May increase the risk of infection and may reactivate latent infection; monitor for new infections. Avoid use in patients receiving other immunosuppressant drugs or phototherapy. Infusion reactions: Acute infusion reactions may occur. Medication and equipment for management should be available for immediate use. Lymphopenia: Induces a decline in circulating T-lymphocytes (CD4+ and CD8+); CD4+ lymphocyte counts should be monitored every 2 weeks throughout therapy. Do not initiate in pre-existing depression of CD4+ lymphocytes and withhold treatment in any patient who develops a depressed CD4+ lymphocyte count (<250 cells/µL) during treatment; permanently discontinue if CD4+ lymphocyte counts remain <250 cells/µL for 1 month. Malignancy: May increase the risk of malignancies; use caution in patients at high risk for malignancy. Discontinue if malignancy develops during therapy.
Special populations: Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Immunizations: Patients should be brought up to date with all immunizations before initiating therapy. Live vaccines should not be given concurrently; there is no data available concerning secondary transmission of live vaccines in patients receiving therapy.
RESTRICTIONS — Alefacept will be distributed directly to physician offices or to a specialty pharmacy; injections are intended to be administered in the physician's office
DRUG INTERACTIONS
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Risk D: Consider therapy modification
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Risk X: Avoid combination
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Risk C: Monitor therapy
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Risk C: Monitor therapy
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Vaccinial infections may develop. Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Avoid ethanol (may increase risk of liver toxicity).
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Effects in pregnancy are not known. Teratogenic effects have not been observed in animal studies. Patients who become pregnant during therapy or within 8 weeks of treatment are advised to enroll in pregnancy registry (866-263-8483).
LACTATION — Excretion in breast milk unknown/not recommended
BREAST-FEEDING CONSIDERATIONS — It is not known whether alefacept is excreted in breast milk. Since alefacept is an immunosuppressant, and transfer of proteins into breast milk may occur, breast-feeding women are cautioned to discontinue breast-feeding or to discontinue use of the drug while breast-feeding (recommendations per manufacturer).
MONITORING PARAMETERS — Baseline CD4+ T-lymphocyte counts prior to initiation and every 2 weeks during treatment course; severity of psoriatic lesions; signs and symptoms of infection
CANADIAN BRAND NAMES — Amevive®
INTERNATIONAL BRAND NAMES — Amevive (AR, CH, IL, NO)
MECHANISM OF ACTION — Binds to CD2, a receptor on the surface of lymphocytes, inhibiting their interaction with leukocyte functional antigen 3 (LFA-3). Interaction between CD2 and LFA-3 is important for the activation of T lymphocytes in psoriasis. Activated T lymphocytes secrete a number of inflammatory mediators, including interferon gamma, which are involved in psoriasis. Since CD2 is primarily expressed on T lymphocytes, treatment results in a reduction in CD4+ and CD8+ T lymphocytes, with lesser effects on other cell populations (NK and B lymphocytes).
PHARMACODYNAMICS / KINETICS
Distribution: Vd: 0.094 L/kg
Bioavailability: 63% (following I.M. administration)
Half-life: 270 hours (following I.V. administration)
Excretion: Clearance: 0.25 mL/hour/kg
PATIENT INFORMATION — Report headache or unusual fatigue; increased nausea or abdominal pain; cough, runny nose, difficulty breathing; chest pain or persistent dizziness; fatigue, muscle pain or weakness, back pain; fever or chills; mouth sores; vaginal itching or discharge; sore throat; unhealed sores; or frequent infections. May cause liver damage; report persistent nausea, anorexia, fatigue, vomiting, abdominal pain, jaundice, dark urine, pale stools, easy bruising. It is important to keep appointments for blood cell monitoring. Notify prescriber if pregnancy occurs during therapy or within 8 weeks of treatment.
PHARMACOLOGIC CATEGORY
Monoclonal Antibody
DOSING: ADULTS — Psoriasis (moderate-to-severe chronic plaque psoriasis):
I.M.: 15 mg once weekly; usual duration of treatment: 12 weeks
Second course: A second course of treatment may be initiated at least 12 weeks after completion of the initial course of treatment, provided CD4+ T-lymphocyte counts are within the normal range.
Note: CD4+ T-lymphocyte counts should be monitored before initiation of treatment and every 2 weeks during therapy. Dosing should be withheld if CD4+ counts are <250 cells/µL, and dosing should be permanently discontinued if CD4+ lymphocyte counts remain at <250 cells/µL for longer than 1 month.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — No dosage adjustment required.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution:
Amevive®: 15 mg [for I.M. administration; contains sucrose 12.5 mg; supplied with SWFI]
DOSAGE FORMS: CONCISE
Injection, powder for reconstitution [I.M. administration]:
Amevive®: 15 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — I.M. injections should be administered at least 1 inch from previous administration sites.
COMPATIBILITY — Do not mix with other medications or solutions.
USE — Treatment of moderate-to-severe chronic plaque psoriasis in adults who are candidates for systemic therapy or phototherapy
ADVERSE REACTIONS SIGNIFICANT
≥ 10%:
Hematologic: Lymphopenia (up to 10% of patients required temporary discontinuation, up to 17% during a second course of therapy)
Local: Injection site reactions (up to 16% of patients; includes pain, inflammation, bleeding, edema, or other reaction)
1% to 10%:
Central nervous system: Chills (6%; primarily during intravenous administration), dizziness (≥ 2%)
Dermatologic: Pruritus (≥ 2%)
Gastrointestinal: Nausea (≥ 2%)
Neuromuscular & skeletal: Myalgia (≥ 2%)
Respiratory: Pharyngitis (≥ 2%), cough increased (≥ 2%)
Miscellaneous: Malignancies (1% vs 0.5% in placebo), antibodies to alefacept (3%; significance unknown), infection (1% requiring hospitalization)
<1% (Limited to important or life-threatening): Anaphylaxis, allergic reaction, angioedema, headache, hepatitis, hepatic failure, MI, transaminases increased (≥ 3 times ULN), urticaria
CONTRAINDICATIONS — Hypersensitivity to alefacept or any component of the formulation; history of severe malignancy; patients with HIV infection or other clinically-important infections
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Hepatic injury: In post-marketing reports, significant transaminase elevations, as well as rare cases of hepatitis, fatty liver, decompensation of cirrhosis, and acute hepatic failure have occurred (causal relationship not established). Discontinue if signs and symptoms of hepatic injury occur. Hypersensitivity reactions: Has been associated with hypersensitivity reactions; rare anaphylaxis also reported. Discontinue use if severe reaction occurs. Immune suppression: May increase the risk of infection and may reactivate latent infection; monitor for new infections. Avoid use in patients receiving other immunosuppressant drugs or phototherapy. Infusion reactions: Acute infusion reactions may occur. Medication and equipment for management should be available for immediate use. Lymphopenia: Induces a decline in circulating T-lymphocytes (CD4+ and CD8+); CD4+ lymphocyte counts should be monitored every 2 weeks throughout therapy. Do not initiate in pre-existing depression of CD4+ lymphocytes and withhold treatment in any patient who develops a depressed CD4+ lymphocyte count (<250 cells/µL) during treatment; permanently discontinue if CD4+ lymphocyte counts remain <250 cells/µL for 1 month. Malignancy: May increase the risk of malignancies; use caution in patients at high risk for malignancy. Discontinue if malignancy develops during therapy.
Special populations: Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Immunizations: Patients should be brought up to date with all immunizations before initiating therapy. Live vaccines should not be given concurrently; there is no data available concerning secondary transmission of live vaccines in patients receiving therapy.
RESTRICTIONS — Alefacept will be distributed directly to physician offices or to a specialty pharmacy; injections are intended to be administered in the physician's office
DRUG INTERACTIONS
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Risk D: Consider therapy modification
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Risk X: Avoid combination
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Risk C: Monitor therapy
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Risk C: Monitor therapy
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Vaccinial infections may develop. Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Avoid ethanol (may increase risk of liver toxicity).
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Effects in pregnancy are not known. Teratogenic effects have not been observed in animal studies. Patients who become pregnant during therapy or within 8 weeks of treatment are advised to enroll in pregnancy registry (866-263-8483).
LACTATION — Excretion in breast milk unknown/not recommended
BREAST-FEEDING CONSIDERATIONS — It is not known whether alefacept is excreted in breast milk. Since alefacept is an immunosuppressant, and transfer of proteins into breast milk may occur, breast-feeding women are cautioned to discontinue breast-feeding or to discontinue use of the drug while breast-feeding (recommendations per manufacturer).
MONITORING PARAMETERS — Baseline CD4+ T-lymphocyte counts prior to initiation and every 2 weeks during treatment course; severity of psoriatic lesions; signs and symptoms of infection
CANADIAN BRAND NAMES — Amevive®
INTERNATIONAL BRAND NAMES — Amevive (AR, CH, IL, NO)
MECHANISM OF ACTION — Binds to CD2, a receptor on the surface of lymphocytes, inhibiting their interaction with leukocyte functional antigen 3 (LFA-3). Interaction between CD2 and LFA-3 is important for the activation of T lymphocytes in psoriasis. Activated T lymphocytes secrete a number of inflammatory mediators, including interferon gamma, which are involved in psoriasis. Since CD2 is primarily expressed on T lymphocytes, treatment results in a reduction in CD4+ and CD8+ T lymphocytes, with lesser effects on other cell populations (NK and B lymphocytes).
PHARMACODYNAMICS / KINETICS
Distribution: Vd: 0.094 L/kg
Bioavailability: 63% (following I.M. administration)
Half-life: 270 hours (following I.V. administration)
Excretion: Clearance: 0.25 mL/hour/kg
PATIENT INFORMATION — Report headache or unusual fatigue; increased nausea or abdominal pain; cough, runny nose, difficulty breathing; chest pain or persistent dizziness; fatigue, muscle pain or weakness, back pain; fever or chills; mouth sores; vaginal itching or discharge; sore throat; unhealed sores; or frequent infections. May cause liver damage; report persistent nausea, anorexia, fatigue, vomiting, abdominal pain, jaundice, dark urine, pale stools, easy bruising. It is important to keep appointments for blood cell monitoring. Notify prescriber if pregnancy occurs during therapy or within 8 weeks of treatment.
Alefacept
U.S. BRAND NAMES — Amevive®
PHARMACOLOGIC CATEGORY
Monoclonal Antibody
DOSING: ADULTS — Psoriasis (moderate-to-severe chronic plaque psoriasis):
I.M.: 15 mg once weekly; usual duration of treatment: 12 weeks
Second course: A second course of treatment may be initiated at least 12 weeks after completion of the initial course of treatment, provided CD4+ T-lymphocyte counts are within the normal range.
Note: CD4+ T-lymphocyte counts should be monitored before initiation of treatment and every 2 weeks during therapy. Dosing should be withheld if CD4+ counts are <250 cells/µL, and dosing should be permanently discontinued if CD4+ lymphocyte counts remain at <250 cells/µL for longer than 1 month.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — No dosage adjustment required.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution:
Amevive®: 15 mg [for I.M. administration; contains sucrose 12.5 mg; supplied with SWFI]
DOSAGE FORMS: CONCISE
Injection, powder for reconstitution [I.M. administration]:
Amevive®: 15 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — I.M. injections should be administered at least 1 inch from previous administration sites.
COMPATIBILITY — Do not mix with other medications or solutions.
USE — Treatment of moderate-to-severe chronic plaque psoriasis in adults who are candidates for systemic therapy or phototherapy
ADVERSE REACTIONS SIGNIFICANT
≥ 10%:
Hematologic: Lymphopenia (up to 10% of patients required temporary discontinuation, up to 17% during a second course of therapy)
Local: Injection site reactions (up to 16% of patients; includes pain, inflammation, bleeding, edema, or other reaction)
1% to 10%:
Central nervous system: Chills (6%; primarily during intravenous administration), dizziness (≥ 2%)
Dermatologic: Pruritus (≥ 2%)
Gastrointestinal: Nausea (≥ 2%)
Neuromuscular & skeletal: Myalgia (≥ 2%)
Respiratory: Pharyngitis (≥ 2%), cough increased (≥ 2%)
Miscellaneous: Malignancies (1% vs 0.5% in placebo), antibodies to alefacept (3%; significance unknown), infection (1% requiring hospitalization)
<1% (Limited to important or life-threatening): Anaphylaxis, allergic reaction, angioedema, headache, hepatitis, hepatic failure, MI, transaminases increased (≥ 3 times ULN), urticaria
CONTRAINDICATIONS — Hypersensitivity to alefacept or any component of the formulation; history of severe malignancy; patients with HIV infection or other clinically-important infections
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Hepatic injury: In post-marketing reports, significant transaminase elevations, as well as rare cases of hepatitis, fatty liver, decompensation of cirrhosis, and acute hepatic failure have occurred (causal relationship not established). Discontinue if signs and symptoms of hepatic injury occur. Hypersensitivity reactions: Has been associated with hypersensitivity reactions; rare anaphylaxis also reported. Discontinue use if severe reaction occurs. Immune suppression: May increase the risk of infection and may reactivate latent infection; monitor for new infections. Avoid use in patients receiving other immunosuppressant drugs or phototherapy. Infusion reactions: Acute infusion reactions may occur. Medication and equipment for management should be available for immediate use. Lymphopenia: Induces a decline in circulating T-lymphocytes (CD4+ and CD8+); CD4+ lymphocyte counts should be monitored every 2 weeks throughout therapy. Do not initiate in pre-existing depression of CD4+ lymphocytes and withhold treatment in any patient who develops a depressed CD4+ lymphocyte count (<250 cells/µL) during treatment; permanently discontinue if CD4+ lymphocyte counts remain <250 cells/µL for 1 month. Malignancy: May increase the risk of malignancies; use caution in patients at high risk for malignancy. Discontinue if malignancy develops during therapy.
Special populations: Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Immunizations: Patients should be brought up to date with all immunizations before initiating therapy. Live vaccines should not be given concurrently; there is no data available concerning secondary transmission of live vaccines in patients receiving therapy.
RESTRICTIONS — Alefacept will be distributed directly to physician offices or to a specialty pharmacy; injections are intended to be administered in the physician's office
DRUG INTERACTIONS
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Risk D: Consider therapy modification
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Risk X: Avoid combination
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Risk C: Monitor therapy
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Risk C: Monitor therapy
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Vaccinial infections may develop. Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Avoid ethanol (may increase risk of liver toxicity).
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Effects in pregnancy are not known. Teratogenic effects have not been observed in animal studies. Patients who become pregnant during therapy or within 8 weeks of treatment are advised to enroll in pregnancy registry (866-263-8483).
LACTATION — Excretion in breast milk unknown/not recommended
BREAST-FEEDING CONSIDERATIONS — It is not known whether alefacept is excreted in breast milk. Since alefacept is an immunosuppressant, and transfer of proteins into breast milk may occur, breast-feeding women are cautioned to discontinue breast-feeding or to discontinue use of the drug while breast-feeding (recommendations per manufacturer).
MONITORING PARAMETERS — Baseline CD4+ T-lymphocyte counts prior to initiation and every 2 weeks during treatment course; severity of psoriatic lesions; signs and symptoms of infection
CANADIAN BRAND NAMES — Amevive®
INTERNATIONAL BRAND NAMES — Amevive (AR, CH, IL, NO)
MECHANISM OF ACTION — Binds to CD2, a receptor on the surface of lymphocytes, inhibiting their interaction with leukocyte functional antigen 3 (LFA-3). Interaction between CD2 and LFA-3 is important for the activation of T lymphocytes in psoriasis. Activated T lymphocytes secrete a number of inflammatory mediators, including interferon gamma, which are involved in psoriasis. Since CD2 is primarily expressed on T lymphocytes, treatment results in a reduction in CD4+ and CD8+ T lymphocytes, with lesser effects on other cell populations (NK and B lymphocytes).
PHARMACODYNAMICS / KINETICS
Distribution: Vd: 0.094 L/kg
Bioavailability: 63% (following I.M. administration)
Half-life: 270 hours (following I.V. administration)
Excretion: Clearance: 0.25 mL/hour/kg
PATIENT INFORMATION — Report headache or unusual fatigue; increased nausea or abdominal pain; cough, runny nose, difficulty breathing; chest pain or persistent dizziness; fatigue, muscle pain or weakness, back pain; fever or chills; mouth sores; vaginal itching or discharge; sore throat; unhealed sores; or frequent infections. May cause liver damage; report persistent nausea, anorexia, fatigue, vomiting, abdominal pain, jaundice, dark urine, pale stools, easy bruising. It is important to keep appointments for blood cell monitoring. Notify prescriber if pregnancy occurs during therapy or within 8 weeks of treatment.
PHARMACOLOGIC CATEGORY
Monoclonal Antibody
DOSING: ADULTS — Psoriasis (moderate-to-severe chronic plaque psoriasis):
I.M.: 15 mg once weekly; usual duration of treatment: 12 weeks
Second course: A second course of treatment may be initiated at least 12 weeks after completion of the initial course of treatment, provided CD4+ T-lymphocyte counts are within the normal range.
Note: CD4+ T-lymphocyte counts should be monitored before initiation of treatment and every 2 weeks during therapy. Dosing should be withheld if CD4+ counts are <250 cells/µL, and dosing should be permanently discontinued if CD4+ lymphocyte counts remain at <250 cells/µL for longer than 1 month.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — No dosage adjustment required.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution:
Amevive®: 15 mg [for I.M. administration; contains sucrose 12.5 mg; supplied with SWFI]
DOSAGE FORMS: CONCISE
Injection, powder for reconstitution [I.M. administration]:
Amevive®: 15 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — I.M. injections should be administered at least 1 inch from previous administration sites.
COMPATIBILITY — Do not mix with other medications or solutions.
USE — Treatment of moderate-to-severe chronic plaque psoriasis in adults who are candidates for systemic therapy or phototherapy
ADVERSE REACTIONS SIGNIFICANT
≥ 10%:
Hematologic: Lymphopenia (up to 10% of patients required temporary discontinuation, up to 17% during a second course of therapy)
Local: Injection site reactions (up to 16% of patients; includes pain, inflammation, bleeding, edema, or other reaction)
1% to 10%:
Central nervous system: Chills (6%; primarily during intravenous administration), dizziness (≥ 2%)
Dermatologic: Pruritus (≥ 2%)
Gastrointestinal: Nausea (≥ 2%)
Neuromuscular & skeletal: Myalgia (≥ 2%)
Respiratory: Pharyngitis (≥ 2%), cough increased (≥ 2%)
Miscellaneous: Malignancies (1% vs 0.5% in placebo), antibodies to alefacept (3%; significance unknown), infection (1% requiring hospitalization)
<1% (Limited to important or life-threatening): Anaphylaxis, allergic reaction, angioedema, headache, hepatitis, hepatic failure, MI, transaminases increased (≥ 3 times ULN), urticaria
CONTRAINDICATIONS — Hypersensitivity to alefacept or any component of the formulation; history of severe malignancy; patients with HIV infection or other clinically-important infections
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Hepatic injury: In post-marketing reports, significant transaminase elevations, as well as rare cases of hepatitis, fatty liver, decompensation of cirrhosis, and acute hepatic failure have occurred (causal relationship not established). Discontinue if signs and symptoms of hepatic injury occur. Hypersensitivity reactions: Has been associated with hypersensitivity reactions; rare anaphylaxis also reported. Discontinue use if severe reaction occurs. Immune suppression: May increase the risk of infection and may reactivate latent infection; monitor for new infections. Avoid use in patients receiving other immunosuppressant drugs or phototherapy. Infusion reactions: Acute infusion reactions may occur. Medication and equipment for management should be available for immediate use. Lymphopenia: Induces a decline in circulating T-lymphocytes (CD4+ and CD8+); CD4+ lymphocyte counts should be monitored every 2 weeks throughout therapy. Do not initiate in pre-existing depression of CD4+ lymphocytes and withhold treatment in any patient who develops a depressed CD4+ lymphocyte count (<250 cells/µL) during treatment; permanently discontinue if CD4+ lymphocyte counts remain <250 cells/µL for 1 month. Malignancy: May increase the risk of malignancies; use caution in patients at high risk for malignancy. Discontinue if malignancy develops during therapy.
Special populations: Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Immunizations: Patients should be brought up to date with all immunizations before initiating therapy. Live vaccines should not be given concurrently; there is no data available concerning secondary transmission of live vaccines in patients receiving therapy.
RESTRICTIONS — Alefacept will be distributed directly to physician offices or to a specialty pharmacy; injections are intended to be administered in the physician's office
DRUG INTERACTIONS
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Risk D: Consider therapy modification
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Risk X: Avoid combination
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Risk C: Monitor therapy
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Risk C: Monitor therapy
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Vaccinial infections may develop. Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Avoid ethanol (may increase risk of liver toxicity).
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Effects in pregnancy are not known. Teratogenic effects have not been observed in animal studies. Patients who become pregnant during therapy or within 8 weeks of treatment are advised to enroll in pregnancy registry (866-263-8483).
LACTATION — Excretion in breast milk unknown/not recommended
BREAST-FEEDING CONSIDERATIONS — It is not known whether alefacept is excreted in breast milk. Since alefacept is an immunosuppressant, and transfer of proteins into breast milk may occur, breast-feeding women are cautioned to discontinue breast-feeding or to discontinue use of the drug while breast-feeding (recommendations per manufacturer).
MONITORING PARAMETERS — Baseline CD4+ T-lymphocyte counts prior to initiation and every 2 weeks during treatment course; severity of psoriatic lesions; signs and symptoms of infection
CANADIAN BRAND NAMES — Amevive®
INTERNATIONAL BRAND NAMES — Amevive (AR, CH, IL, NO)
MECHANISM OF ACTION — Binds to CD2, a receptor on the surface of lymphocytes, inhibiting their interaction with leukocyte functional antigen 3 (LFA-3). Interaction between CD2 and LFA-3 is important for the activation of T lymphocytes in psoriasis. Activated T lymphocytes secrete a number of inflammatory mediators, including interferon gamma, which are involved in psoriasis. Since CD2 is primarily expressed on T lymphocytes, treatment results in a reduction in CD4+ and CD8+ T lymphocytes, with lesser effects on other cell populations (NK and B lymphocytes).
PHARMACODYNAMICS / KINETICS
Distribution: Vd: 0.094 L/kg
Bioavailability: 63% (following I.M. administration)
Half-life: 270 hours (following I.V. administration)
Excretion: Clearance: 0.25 mL/hour/kg
PATIENT INFORMATION — Report headache or unusual fatigue; increased nausea or abdominal pain; cough, runny nose, difficulty breathing; chest pain or persistent dizziness; fatigue, muscle pain or weakness, back pain; fever or chills; mouth sores; vaginal itching or discharge; sore throat; unhealed sores; or frequent infections. May cause liver damage; report persistent nausea, anorexia, fatigue, vomiting, abdominal pain, jaundice, dark urine, pale stools, easy bruising. It is important to keep appointments for blood cell monitoring. Notify prescriber if pregnancy occurs during therapy or within 8 weeks of treatment.
Aldesleukin
MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Aldesleukin may be confused with oprelvekin
Proleukin® may be confused with oprelvekin
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
U.S. BRAND NAMES — Proleukin®
PHARMACOLOGIC CATEGORY
Antineoplastic Agent, Miscellaneous
Biological Response Modulator
DOSING: ADULTS — Refer to individual protocols.
Renal cell carcinoma: I.V.: 600,000 int. units/kg every 8 hours for a maximum of 14 doses; repeat after 9 days for a total of 28 doses per course. Retreat if needed 7 weeks after previous course.
Melanoma:
I.V.:
Single-agent use: 600,000 int. units/kg every 8 hours for a maximum of 14 doses; repeat after 9 days for a total of 28 doses per course. Retreat if needed 7 weeks after previous course.
In combination with cytotoxic agents (unlabeled use): 24 million int. units/m2 days 12-16 and 19-23
SubQ (unlabeled route):
Single-agent doses: 3-18 million int. units/day for 5 days each week, up to 6 weeks
In combination with interferon:
5 million int. units/m2 3 times/week
1.8 million int. units/m2 twice daily 5 days/week for 6 weeks
Investigational regimen: SubQ: 11 million int. units (flat dose) daily for 4 days per week for 4 consecutive weeks; repeat every 6 weeks
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — No specific recommendations by manufacturer. Use with caution.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution:
Proleukin®: 22 x 106 int. units [18 million int. units/mL = 1.1 mg/mL when reconstituted]
DOSAGE FORMS: CONCISE
Injection, powder for reconstitution:
Proleukin®: 22 x 106 int. units
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Administer as I.V. infusion over 15 minutes (do not administer with an inline filter). Flush before and after with D5W, particularly if maintenance I.V. line contains sodium chloride. May also be administered by SubQ injection (unlabeled route)
Management of symptoms related to vascular leak syndrome:
If actual body weight increases >10% above baseline, or rales or rhonchi are audible:
Administer furosemide at dosage determined by patient response
Administer dopamine hydrochloride 1-5 mcg/kg/minute to maintain renal blood flow and urine output
If patient has dyspnea at rest: Administer supplemental oxygen by face mask
If patient has severe respiratory distress: Intubate patient and provide mechanical ventilation; administer ranitidine (as the hydrochloride salt) 50 mg I.V. every 8-12 hours as prophylaxis against stress ulcers
COMPATIBILITY — Stable in D5W.
Y-site administration: Compatible: Amikacin, amphotericin B, calcium gluconate, co-trimoxazole, diphenhydramine, dopamine, fat emulsion 10%, fluconazole, foscarnet, gentamicin, heparin, magnesium sulfate, metoclopramide, morphine, ondansetron, piperacillin, potassium chloride, ranitidine, thiethylperazine, ticarcillin, tobramycin. Incompatible: Ganciclovir, lorazepam, NS, pentamidine, prochlorperazine edisylate, promethazine.
Compatibility when admixed: Incompatible with NS.
USE — Treatment of metastatic renal cell cancer, metastatic melanoma
USE - UNLABELED / INVESTIGATIONAL — HIV infection, and AIDS; non-Hodgkin's lymphoma
ADVERSE REACTIONS SIGNIFICANT
>10%:
Cardiovascular: Hypotension (71%; grade 4: 3%), peripheral edema (28%), tachycardia (23%), edema (15%), vasodilation (13%), cardiovascular disorder (11%; includes blood pressure changes, CHF and ECG changes)
Central nervous system: Chills (52%), confusion (34%), fever (29%; grade 4: 1%), malaise (27%), somnolence (22%), anxiety (12%), pain (12%), dizziness (11%)
Dermatologic: Rash (42%), pruritus (24%), exfoliative dermatitis (18%)
Endocrine & metabolic: Acidosis (12%), hypomagnesemia (12%), hypocalcemia (11%)
Gastrointestinal: Diarrhea (67%), vomiting (19% to 50%), nausea (19% to 35%), stomatitis (22%), anorexia (20%), weight gain (18%), abdominal pain (11%)
Hematologic: Thrombocytopenia (37%; grade 4: 1%), anemia (29%), leukopenia (16%)
Hepatic: Hyperbilirubinemia (40%), AST increased (23%)
Neuromuscular & skeletal: Weakness (23%)
Renal: Oliguria (63%; grade 4: 6%), creatinine increased (33%)
Respiratory: Dyspnea (43%), lung disorder (24%; includes pulmonary congestion, rales, and rhonchi), cough (11%), respiratory disorder (11%; includes acute respiratory distress syndrome, infiltrates and pulmonary changes)
Miscellaneous: Infection (13%; grade 4: 1%)
1% to 10%:
Cardiovascular: Arrhythmia (10%), cardiac arrest (grade 4: 1%), MI (grade 4: 1%), supraventricular tachycardia (grade 4: 1%), ventricular tachycardia (grade 4: 1%)
Gastrointestinal: Abdomen enlarged (10%)
Hematologic: Coagulation disorder (grade 4: 1%)
Hepatic: Alkaline phosphatase increased (10%)
Renal: Anuria (grade 4: 5%), acute renal failure (grade 4: 1%)
Respiratory: Rhinitis (10%), apnea (grade 4: 1%)
Miscellaneous: Sepsis (grade 4: 1%)
<1% (Limited to important or life-threatening): Acute tubular necrosis, allergic interstitial nephritis, allergic reactions, anaphylaxis, atrial arrhythmia, AV block, blindness (transient or permanent), bowel necrosis, bradycardia, bullous pemphigoid, BUN increased, cardiomyopathy, cellulitis, cerebral edema, cerebral lesions, cerebral vasculitis, CHF, cholecystitis, colitis, coma, crescentic IgA glomuleronephritis, Crohn's disease exacerbation, depression (severe; leading to suicide), diabetes mellitus, duodenal ulcer, encephalitis, endocarditis, extrapyramidal syndrome, gastrointestinal hemorrhage, hematemesis, hemoptysis, hemorrhage, hepatic failure, hepatitis, hepatosplenomegaly, hypertension, hyperuricemia, hyperventilation, hypothermia, hyperthyroidism, hypoventilation, hypoxia, inflammatory arthritis, injection site necrosis, intestinal obstruction, intestinal perforation, leukocytosis, malignant hyperthermia, meningitis, myocardial ischemia, myocarditis, myopathy, myositis, neuritis, neuropathy, neutropenia, oculobulbar myasthenia gravis, optic neuritis, pancreatitis, pericardial effusion, pericarditis, peripheral gangrene, phlebitis, pneumonia, pneumothorax, pulmonary edema, pulmonary embolus, renal failure, respiratory acidosis, respiratory arrest, respiratory failure, retroperitoneal hemorrhage, rhabdomyolysis, scleroderma, seizure (including grand mal), shock, Stevens-Johnson syndrome, stroke, syncope, thrombosis, thyroiditis, tracheoesophageal fistula, transient ischemic attack, urticaria, ventricular extrasystoles
CONTRAINDICATIONS — Hypersensitivity to aldesleukin or any component of the formulation; patients with abnormal thallium stress or pulmonary function tests; patients who have had an organ allograft; retreatment in patients who have experienced sustained ventricular tachycardia (≥ 5 beats), refractory cardiac rhythm disturbances, recurrent chest pain with ECG changes consistent with angina or myocardial infarction, intubation ≥ 72 hours, pericardial tamponade, renal dialysis for ≥ 72 hours, coma or toxic psychosis lasting ≥ 48 hours, repetitive or refractory seizures, bowel ischemia/perforation, GI bleeding requiring surgery
WARNINGS / PRECAUTIONS
Boxed warnings: Capillary leak syndrome (CLS): . Experienced physician: . Infection: . Lethargy/somnolence: .
Special handling: Hazardous agent: Use appropriate precautions for handling and disposal.
Concerns related to adverse effects: Adverse effects: Are frequent and sometimes fatal. Capillary leak syndrome (CLS): [U.S. Boxed Warning]: High-dose aldesleukin therapy has been associated with capillary leak syndrome (CLS) resulting in hypotension and reduced organ perfusion which may be severe and can result in death. Therapy should be restricted to patients with normal cardiac and pulmonary functions as defined by thallium stress and formal pulmonary function testing. Extreme caution should be used in patients with a history of prior cardiac or pulmonary disease. Patients must have a serum creatinine ≤ 1.5 mg/dL prior to treatment. CNS effects: Mental status changes (irritability, confusion, depression) can occur and may indicate bacteremia, hypoperfusion, CNS malignancy, or CNS toxicity. Infection: [U.S. Boxed Warning]: Impaired neutrophil function is associated with treatment; patients are at risk for sepsis, bacterial endocarditis, and central line-related gram-positive infections. Antibiotic prophylaxis which has been associated with a reduced incidence of staphylococcal infections in aldesleukin studies includes the use of oxacillin, nafcillin, ciprofloxacin, or vancomycin. Lethargy/somnolence: [U.S. Boxed Warning]: Withhold treatment for patients developing moderate-to-severe lethargy or somnolence; continued treatment may result in coma.
Disease-related concerns: Autoimmune/inflammatory disorders: Use with caution in patients with autoimmune disease or inflammatory disorders; may exacerbate condition. CNS metastases: Patients should be evaluated and treated for CNS metastases and have a negative scan prior to treatment.
Concurrent drug therapy issues: Supportive care for high-dose treatment: Standard prophylactic supportive care during high-dose aldesleukin treatment includes acetaminophen to relieve constitutional symptoms and an H2 antagonist to reduce the risk of GI ulceration and/or bleeding.
Special populations: Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Experienced physician: [U.S. Boxed Warning]: Should be administered under the supervision of an experienced cancer chemotherapy physician in a facility with cardiopulmonary or intensive specialists and intensive care facilities available.
DRUG INTERACTIONS
Contrast Media (Non-ionic): May enhance the potential for allergic or hypersensitivity reactions to Aldesleukin. Risk C: Monitor therapy
Interferons (Alfa): May enhance the adverse/toxic effect of Aldesleukin. In particular, risks of myocardial and renal toxicity may be increased by this combination. Risk D: Consider therapy modification
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: May increase CNS adverse effects.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Maternal toxicity and embryocidal effects were noted in animal studies. There are no adequate and well-controlled studies in pregnant women; use during pregnancy only if benefits to the mother outweigh potential risk to the fetus. Contraception is recommended for fertile males or females using this medication.
LACTATION — Excretion in breast milk unknown/not recommended
BREAST-FEEDING CONSIDERATIONS — Due to the potential for serious adverse reactions in the nursing infant, breast-feeding should be discontinued during treatment.
PRICING — (data from drugstore.com)
Solution (reconstituted) (Proleukin)
22000000 unit (1): $855.71
MONITORING PARAMETERS
The following clinical evaluations are recommended for all patients prior to beginning treatment and then frequently during drug administration:
CBC with differential, blood chemistries including electrolytes, renal and hepatic function tests
Chest x-rays
Monitoring during therapy should include vital signs (temperature, pulse, blood pressure, and respiration rate) and weight; in a patient with a decreased blood pressure, especially <90 mm Hg, cardiac monitoring for rhythm should be conducted. If an abnormal complex or rhythm is seen, an ECG should be performed; vital signs in these hypotension patients should be taken hourly and central venous pressure (CVP) checked; monitor for change in mental status.
Pulmonary function (baseline and periodic) basis.
CANADIAN BRAND NAMES — Proleukin®
INTERNATIONAL BRAND NAMES — Interleukina 2 (PY); Interleukina II (CN); Proleukin (AR, AT, BE, BR, CH, CO, CZ, DE, DK, EC, EG, ES, FI, FR, GB, GR, HK, HN, HU, IE, IL, IT, KP, NL, NZ, PE, PL, PT, TW, UY)
MECHANISM OF ACTION — Aldesleukin promotes proliferation, differentiation, and recruitment of T and B cells, natural killer (NK) cells, and thymocytes; causes cytolytic activity in a subset of lymphocytes and subsequent interactions between the immune system and malignant cells; can stimulate lymphokine-activated killer (LAK) cells and tumor-infiltrating lymphocytes (TIL) cells.
PHARMACODYNAMICS / KINETICS
Distribution: Vd: 4-7 L; primarily in plasma and then in the lymphocytes
Half-life elimination: I.V.: Initial: 6-13 minutes; Terminal: 80-120 minutes
Sound-alike/look-alike issues:
Aldesleukin may be confused with oprelvekin
Proleukin® may be confused with oprelvekin
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
U.S. BRAND NAMES — Proleukin®
PHARMACOLOGIC CATEGORY
Antineoplastic Agent, Miscellaneous
Biological Response Modulator
DOSING: ADULTS — Refer to individual protocols.
Renal cell carcinoma: I.V.: 600,000 int. units/kg every 8 hours for a maximum of 14 doses; repeat after 9 days for a total of 28 doses per course. Retreat if needed 7 weeks after previous course.
Melanoma:
I.V.:
Single-agent use: 600,000 int. units/kg every 8 hours for a maximum of 14 doses; repeat after 9 days for a total of 28 doses per course. Retreat if needed 7 weeks after previous course.
In combination with cytotoxic agents (unlabeled use): 24 million int. units/m2 days 12-16 and 19-23
SubQ (unlabeled route):
Single-agent doses: 3-18 million int. units/day for 5 days each week, up to 6 weeks
In combination with interferon:
5 million int. units/m2 3 times/week
1.8 million int. units/m2 twice daily 5 days/week for 6 weeks
Investigational regimen: SubQ: 11 million int. units (flat dose) daily for 4 days per week for 4 consecutive weeks; repeat every 6 weeks
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — No specific recommendations by manufacturer. Use with caution.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution:
Proleukin®: 22 x 106 int. units [18 million int. units/mL = 1.1 mg/mL when reconstituted]
DOSAGE FORMS: CONCISE
Injection, powder for reconstitution:
Proleukin®: 22 x 106 int. units
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Administer as I.V. infusion over 15 minutes (do not administer with an inline filter). Flush before and after with D5W, particularly if maintenance I.V. line contains sodium chloride. May also be administered by SubQ injection (unlabeled route)
Management of symptoms related to vascular leak syndrome:
If actual body weight increases >10% above baseline, or rales or rhonchi are audible:
Administer furosemide at dosage determined by patient response
Administer dopamine hydrochloride 1-5 mcg/kg/minute to maintain renal blood flow and urine output
If patient has dyspnea at rest: Administer supplemental oxygen by face mask
If patient has severe respiratory distress: Intubate patient and provide mechanical ventilation; administer ranitidine (as the hydrochloride salt) 50 mg I.V. every 8-12 hours as prophylaxis against stress ulcers
COMPATIBILITY — Stable in D5W.
Y-site administration: Compatible: Amikacin, amphotericin B, calcium gluconate, co-trimoxazole, diphenhydramine, dopamine, fat emulsion 10%, fluconazole, foscarnet, gentamicin, heparin, magnesium sulfate, metoclopramide, morphine, ondansetron, piperacillin, potassium chloride, ranitidine, thiethylperazine, ticarcillin, tobramycin. Incompatible: Ganciclovir, lorazepam, NS, pentamidine, prochlorperazine edisylate, promethazine.
Compatibility when admixed: Incompatible with NS.
USE — Treatment of metastatic renal cell cancer, metastatic melanoma
USE - UNLABELED / INVESTIGATIONAL — HIV infection, and AIDS; non-Hodgkin's lymphoma
ADVERSE REACTIONS SIGNIFICANT
>10%:
Cardiovascular: Hypotension (71%; grade 4: 3%), peripheral edema (28%), tachycardia (23%), edema (15%), vasodilation (13%), cardiovascular disorder (11%; includes blood pressure changes, CHF and ECG changes)
Central nervous system: Chills (52%), confusion (34%), fever (29%; grade 4: 1%), malaise (27%), somnolence (22%), anxiety (12%), pain (12%), dizziness (11%)
Dermatologic: Rash (42%), pruritus (24%), exfoliative dermatitis (18%)
Endocrine & metabolic: Acidosis (12%), hypomagnesemia (12%), hypocalcemia (11%)
Gastrointestinal: Diarrhea (67%), vomiting (19% to 50%), nausea (19% to 35%), stomatitis (22%), anorexia (20%), weight gain (18%), abdominal pain (11%)
Hematologic: Thrombocytopenia (37%; grade 4: 1%), anemia (29%), leukopenia (16%)
Hepatic: Hyperbilirubinemia (40%), AST increased (23%)
Neuromuscular & skeletal: Weakness (23%)
Renal: Oliguria (63%; grade 4: 6%), creatinine increased (33%)
Respiratory: Dyspnea (43%), lung disorder (24%; includes pulmonary congestion, rales, and rhonchi), cough (11%), respiratory disorder (11%; includes acute respiratory distress syndrome, infiltrates and pulmonary changes)
Miscellaneous: Infection (13%; grade 4: 1%)
1% to 10%:
Cardiovascular: Arrhythmia (10%), cardiac arrest (grade 4: 1%), MI (grade 4: 1%), supraventricular tachycardia (grade 4: 1%), ventricular tachycardia (grade 4: 1%)
Gastrointestinal: Abdomen enlarged (10%)
Hematologic: Coagulation disorder (grade 4: 1%)
Hepatic: Alkaline phosphatase increased (10%)
Renal: Anuria (grade 4: 5%), acute renal failure (grade 4: 1%)
Respiratory: Rhinitis (10%), apnea (grade 4: 1%)
Miscellaneous: Sepsis (grade 4: 1%)
<1% (Limited to important or life-threatening): Acute tubular necrosis, allergic interstitial nephritis, allergic reactions, anaphylaxis, atrial arrhythmia, AV block, blindness (transient or permanent), bowel necrosis, bradycardia, bullous pemphigoid, BUN increased, cardiomyopathy, cellulitis, cerebral edema, cerebral lesions, cerebral vasculitis, CHF, cholecystitis, colitis, coma, crescentic IgA glomuleronephritis, Crohn's disease exacerbation, depression (severe; leading to suicide), diabetes mellitus, duodenal ulcer, encephalitis, endocarditis, extrapyramidal syndrome, gastrointestinal hemorrhage, hematemesis, hemoptysis, hemorrhage, hepatic failure, hepatitis, hepatosplenomegaly, hypertension, hyperuricemia, hyperventilation, hypothermia, hyperthyroidism, hypoventilation, hypoxia, inflammatory arthritis, injection site necrosis, intestinal obstruction, intestinal perforation, leukocytosis, malignant hyperthermia, meningitis, myocardial ischemia, myocarditis, myopathy, myositis, neuritis, neuropathy, neutropenia, oculobulbar myasthenia gravis, optic neuritis, pancreatitis, pericardial effusion, pericarditis, peripheral gangrene, phlebitis, pneumonia, pneumothorax, pulmonary edema, pulmonary embolus, renal failure, respiratory acidosis, respiratory arrest, respiratory failure, retroperitoneal hemorrhage, rhabdomyolysis, scleroderma, seizure (including grand mal), shock, Stevens-Johnson syndrome, stroke, syncope, thrombosis, thyroiditis, tracheoesophageal fistula, transient ischemic attack, urticaria, ventricular extrasystoles
CONTRAINDICATIONS — Hypersensitivity to aldesleukin or any component of the formulation; patients with abnormal thallium stress or pulmonary function tests; patients who have had an organ allograft; retreatment in patients who have experienced sustained ventricular tachycardia (≥ 5 beats), refractory cardiac rhythm disturbances, recurrent chest pain with ECG changes consistent with angina or myocardial infarction, intubation ≥ 72 hours, pericardial tamponade, renal dialysis for ≥ 72 hours, coma or toxic psychosis lasting ≥ 48 hours, repetitive or refractory seizures, bowel ischemia/perforation, GI bleeding requiring surgery
WARNINGS / PRECAUTIONS
Boxed warnings: Capillary leak syndrome (CLS): . Experienced physician: . Infection: . Lethargy/somnolence: .
Special handling: Hazardous agent: Use appropriate precautions for handling and disposal.
Concerns related to adverse effects: Adverse effects: Are frequent and sometimes fatal. Capillary leak syndrome (CLS): [U.S. Boxed Warning]: High-dose aldesleukin therapy has been associated with capillary leak syndrome (CLS) resulting in hypotension and reduced organ perfusion which may be severe and can result in death. Therapy should be restricted to patients with normal cardiac and pulmonary functions as defined by thallium stress and formal pulmonary function testing. Extreme caution should be used in patients with a history of prior cardiac or pulmonary disease. Patients must have a serum creatinine ≤ 1.5 mg/dL prior to treatment. CNS effects: Mental status changes (irritability, confusion, depression) can occur and may indicate bacteremia, hypoperfusion, CNS malignancy, or CNS toxicity. Infection: [U.S. Boxed Warning]: Impaired neutrophil function is associated with treatment; patients are at risk for sepsis, bacterial endocarditis, and central line-related gram-positive infections. Antibiotic prophylaxis which has been associated with a reduced incidence of staphylococcal infections in aldesleukin studies includes the use of oxacillin, nafcillin, ciprofloxacin, or vancomycin. Lethargy/somnolence: [U.S. Boxed Warning]: Withhold treatment for patients developing moderate-to-severe lethargy or somnolence; continued treatment may result in coma.
Disease-related concerns: Autoimmune/inflammatory disorders: Use with caution in patients with autoimmune disease or inflammatory disorders; may exacerbate condition. CNS metastases: Patients should be evaluated and treated for CNS metastases and have a negative scan prior to treatment.
Concurrent drug therapy issues: Supportive care for high-dose treatment: Standard prophylactic supportive care during high-dose aldesleukin treatment includes acetaminophen to relieve constitutional symptoms and an H2 antagonist to reduce the risk of GI ulceration and/or bleeding.
Special populations: Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Experienced physician: [U.S. Boxed Warning]: Should be administered under the supervision of an experienced cancer chemotherapy physician in a facility with cardiopulmonary or intensive specialists and intensive care facilities available.
DRUG INTERACTIONS
Contrast Media (Non-ionic): May enhance the potential for allergic or hypersensitivity reactions to Aldesleukin. Risk C: Monitor therapy
Interferons (Alfa): May enhance the adverse/toxic effect of Aldesleukin. In particular, risks of myocardial and renal toxicity may be increased by this combination. Risk D: Consider therapy modification
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: May increase CNS adverse effects.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Maternal toxicity and embryocidal effects were noted in animal studies. There are no adequate and well-controlled studies in pregnant women; use during pregnancy only if benefits to the mother outweigh potential risk to the fetus. Contraception is recommended for fertile males or females using this medication.
LACTATION — Excretion in breast milk unknown/not recommended
BREAST-FEEDING CONSIDERATIONS — Due to the potential for serious adverse reactions in the nursing infant, breast-feeding should be discontinued during treatment.
PRICING — (data from drugstore.com)
Solution (reconstituted) (Proleukin)
22000000 unit (1): $855.71
MONITORING PARAMETERS
The following clinical evaluations are recommended for all patients prior to beginning treatment and then frequently during drug administration:
CBC with differential, blood chemistries including electrolytes, renal and hepatic function tests
Chest x-rays
Monitoring during therapy should include vital signs (temperature, pulse, blood pressure, and respiration rate) and weight; in a patient with a decreased blood pressure, especially <90 mm Hg, cardiac monitoring for rhythm should be conducted. If an abnormal complex or rhythm is seen, an ECG should be performed; vital signs in these hypotension patients should be taken hourly and central venous pressure (CVP) checked; monitor for change in mental status.
Pulmonary function (baseline and periodic) basis.
CANADIAN BRAND NAMES — Proleukin®
INTERNATIONAL BRAND NAMES — Interleukina 2 (PY); Interleukina II (CN); Proleukin (AR, AT, BE, BR, CH, CO, CZ, DE, DK, EC, EG, ES, FI, FR, GB, GR, HK, HN, HU, IE, IL, IT, KP, NL, NZ, PE, PL, PT, TW, UY)
MECHANISM OF ACTION — Aldesleukin promotes proliferation, differentiation, and recruitment of T and B cells, natural killer (NK) cells, and thymocytes; causes cytolytic activity in a subset of lymphocytes and subsequent interactions between the immune system and malignant cells; can stimulate lymphokine-activated killer (LAK) cells and tumor-infiltrating lymphocytes (TIL) cells.
PHARMACODYNAMICS / KINETICS
Distribution: Vd: 4-7 L; primarily in plasma and then in the lymphocytes
Half-life elimination: I.V.: Initial: 6-13 minutes; Terminal: 80-120 minutes
Aldesleukin
MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Aldesleukin may be confused with oprelvekin
Proleukin® may be confused with oprelvekin
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
U.S. BRAND NAMES — Proleukin®
PHARMACOLOGIC CATEGORY
Antineoplastic Agent, Miscellaneous
Biological Response Modulator
DOSING: ADULTS — Refer to individual protocols.
Renal cell carcinoma: I.V.: 600,000 int. units/kg every 8 hours for a maximum of 14 doses; repeat after 9 days for a total of 28 doses per course. Retreat if needed 7 weeks after previous course.
Melanoma:
I.V.:
Single-agent use: 600,000 int. units/kg every 8 hours for a maximum of 14 doses; repeat after 9 days for a total of 28 doses per course. Retreat if needed 7 weeks after previous course.
In combination with cytotoxic agents (unlabeled use): 24 million int. units/m2 days 12-16 and 19-23
SubQ (unlabeled route):
Single-agent doses: 3-18 million int. units/day for 5 days each week, up to 6 weeks
In combination with interferon:
5 million int. units/m2 3 times/week
1.8 million int. units/m2 twice daily 5 days/week for 6 weeks
Investigational regimen: SubQ: 11 million int. units (flat dose) daily for 4 days per week for 4 consecutive weeks; repeat every 6 weeks
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — No specific recommendations by manufacturer. Use with caution.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution:
Proleukin®: 22 x 106 int. units [18 million int. units/mL = 1.1 mg/mL when reconstituted]
DOSAGE FORMS: CONCISE
Injection, powder for reconstitution:
Proleukin®: 22 x 106 int. units
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Administer as I.V. infusion over 15 minutes (do not administer with an inline filter). Flush before and after with D5W, particularly if maintenance I.V. line contains sodium chloride. May also be administered by SubQ injection (unlabeled route)
Management of symptoms related to vascular leak syndrome:
If actual body weight increases >10% above baseline, or rales or rhonchi are audible:
Administer furosemide at dosage determined by patient response
Administer dopamine hydrochloride 1-5 mcg/kg/minute to maintain renal blood flow and urine output
If patient has dyspnea at rest: Administer supplemental oxygen by face mask
If patient has severe respiratory distress: Intubate patient and provide mechanical ventilation; administer ranitidine (as the hydrochloride salt) 50 mg I.V. every 8-12 hours as prophylaxis against stress ulcers
COMPATIBILITY — Stable in D5W.
Y-site administration: Compatible: Amikacin, amphotericin B, calcium gluconate, co-trimoxazole, diphenhydramine, dopamine, fat emulsion 10%, fluconazole, foscarnet, gentamicin, heparin, magnesium sulfate, metoclopramide, morphine, ondansetron, piperacillin, potassium chloride, ranitidine, thiethylperazine, ticarcillin, tobramycin. Incompatible: Ganciclovir, lorazepam, NS, pentamidine, prochlorperazine edisylate, promethazine.
Compatibility when admixed: Incompatible with NS.
USE — Treatment of metastatic renal cell cancer, metastatic melanoma
USE - UNLABELED / INVESTIGATIONAL — HIV infection, and AIDS; non-Hodgkin's lymphoma
ADVERSE REACTIONS SIGNIFICANT
>10%:
Cardiovascular: Hypotension (71%; grade 4: 3%), peripheral edema (28%), tachycardia (23%), edema (15%), vasodilation (13%), cardiovascular disorder (11%; includes blood pressure changes, CHF and ECG changes)
Central nervous system: Chills (52%), confusion (34%), fever (29%; grade 4: 1%), malaise (27%), somnolence (22%), anxiety (12%), pain (12%), dizziness (11%)
Dermatologic: Rash (42%), pruritus (24%), exfoliative dermatitis (18%)
Endocrine & metabolic: Acidosis (12%), hypomagnesemia (12%), hypocalcemia (11%)
Gastrointestinal: Diarrhea (67%), vomiting (19% to 50%), nausea (19% to 35%), stomatitis (22%), anorexia (20%), weight gain (18%), abdominal pain (11%)
Hematologic: Thrombocytopenia (37%; grade 4: 1%), anemia (29%), leukopenia (16%)
Hepatic: Hyperbilirubinemia (40%), AST increased (23%)
Neuromuscular & skeletal: Weakness (23%)
Renal: Oliguria (63%; grade 4: 6%), creatinine increased (33%)
Respiratory: Dyspnea (43%), lung disorder (24%; includes pulmonary congestion, rales, and rhonchi), cough (11%), respiratory disorder (11%; includes acute respiratory distress syndrome, infiltrates and pulmonary changes)
Miscellaneous: Infection (13%; grade 4: 1%)
1% to 10%:
Cardiovascular: Arrhythmia (10%), cardiac arrest (grade 4: 1%), MI (grade 4: 1%), supraventricular tachycardia (grade 4: 1%), ventricular tachycardia (grade 4: 1%)
Gastrointestinal: Abdomen enlarged (10%)
Hematologic: Coagulation disorder (grade 4: 1%)
Hepatic: Alkaline phosphatase increased (10%)
Renal: Anuria (grade 4: 5%), acute renal failure (grade 4: 1%)
Respiratory: Rhinitis (10%), apnea (grade 4: 1%)
Miscellaneous: Sepsis (grade 4: 1%)
<1% (Limited to important or life-threatening): Acute tubular necrosis, allergic interstitial nephritis, allergic reactions, anaphylaxis, atrial arrhythmia, AV block, blindness (transient or permanent), bowel necrosis, bradycardia, bullous pemphigoid, BUN increased, cardiomyopathy, cellulitis, cerebral edema, cerebral lesions, cerebral vasculitis, CHF, cholecystitis, colitis, coma, crescentic IgA glomuleronephritis, Crohn's disease exacerbation, depression (severe; leading to suicide), diabetes mellitus, duodenal ulcer, encephalitis, endocarditis, extrapyramidal syndrome, gastrointestinal hemorrhage, hematemesis, hemoptysis, hemorrhage, hepatic failure, hepatitis, hepatosplenomegaly, hypertension, hyperuricemia, hyperventilation, hypothermia, hyperthyroidism, hypoventilation, hypoxia, inflammatory arthritis, injection site necrosis, intestinal obstruction, intestinal perforation, leukocytosis, malignant hyperthermia, meningitis, myocardial ischemia, myocarditis, myopathy, myositis, neuritis, neuropathy, neutropenia, oculobulbar myasthenia gravis, optic neuritis, pancreatitis, pericardial effusion, pericarditis, peripheral gangrene, phlebitis, pneumonia, pneumothorax, pulmonary edema, pulmonary embolus, renal failure, respiratory acidosis, respiratory arrest, respiratory failure, retroperitoneal hemorrhage, rhabdomyolysis, scleroderma, seizure (including grand mal), shock, Stevens-Johnson syndrome, stroke, syncope, thrombosis, thyroiditis, tracheoesophageal fistula, transient ischemic attack, urticaria, ventricular extrasystoles
CONTRAINDICATIONS — Hypersensitivity to aldesleukin or any component of the formulation; patients with abnormal thallium stress or pulmonary function tests; patients who have had an organ allograft; retreatment in patients who have experienced sustained ventricular tachycardia (≥ 5 beats), refractory cardiac rhythm disturbances, recurrent chest pain with ECG changes consistent with angina or myocardial infarction, intubation ≥ 72 hours, pericardial tamponade, renal dialysis for ≥ 72 hours, coma or toxic psychosis lasting ≥ 48 hours, repetitive or refractory seizures, bowel ischemia/perforation, GI bleeding requiring surgery
WARNINGS / PRECAUTIONS
Boxed warnings: Capillary leak syndrome (CLS): . Experienced physician: . Infection: . Lethargy/somnolence: .
Special handling: Hazardous agent: Use appropriate precautions for handling and disposal.
Concerns related to adverse effects: Adverse effects: Are frequent and sometimes fatal. Capillary leak syndrome (CLS): [U.S. Boxed Warning]: High-dose aldesleukin therapy has been associated with capillary leak syndrome (CLS) resulting in hypotension and reduced organ perfusion which may be severe and can result in death. Therapy should be restricted to patients with normal cardiac and pulmonary functions as defined by thallium stress and formal pulmonary function testing. Extreme caution should be used in patients with a history of prior cardiac or pulmonary disease. Patients must have a serum creatinine ≤ 1.5 mg/dL prior to treatment. CNS effects: Mental status changes (irritability, confusion, depression) can occur and may indicate bacteremia, hypoperfusion, CNS malignancy, or CNS toxicity. Infection: [U.S. Boxed Warning]: Impaired neutrophil function is associated with treatment; patients are at risk for sepsis, bacterial endocarditis, and central line-related gram-positive infections. Antibiotic prophylaxis which has been associated with a reduced incidence of staphylococcal infections in aldesleukin studies includes the use of oxacillin, nafcillin, ciprofloxacin, or vancomycin. Lethargy/somnolence: [U.S. Boxed Warning]: Withhold treatment for patients developing moderate-to-severe lethargy or somnolence; continued treatment may result in coma.
Disease-related concerns: Autoimmune/inflammatory disorders: Use with caution in patients with autoimmune disease or inflammatory disorders; may exacerbate condition. CNS metastases: Patients should be evaluated and treated for CNS metastases and have a negative scan prior to treatment.
Concurrent drug therapy issues: Supportive care for high-dose treatment: Standard prophylactic supportive care during high-dose aldesleukin treatment includes acetaminophen to relieve constitutional symptoms and an H2 antagonist to reduce the risk of GI ulceration and/or bleeding.
Special populations: Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Experienced physician: [U.S. Boxed Warning]: Should be administered under the supervision of an experienced cancer chemotherapy physician in a facility with cardiopulmonary or intensive specialists and intensive care facilities available.
DRUG INTERACTIONS
Contrast Media (Non-ionic): May enhance the potential for allergic or hypersensitivity reactions to Aldesleukin. Risk C: Monitor therapy
Interferons (Alfa): May enhance the adverse/toxic effect of Aldesleukin. In particular, risks of myocardial and renal toxicity may be increased by this combination. Risk D: Consider therapy modification
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: May increase CNS adverse effects.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Maternal toxicity and embryocidal effects were noted in animal studies. There are no adequate and well-controlled studies in pregnant women; use during pregnancy only if benefits to the mother outweigh potential risk to the fetus. Contraception is recommended for fertile males or females using this medication.
LACTATION — Excretion in breast milk unknown/not recommended
BREAST-FEEDING CONSIDERATIONS — Due to the potential for serious adverse reactions in the nursing infant, breast-feeding should be discontinued during treatment.
PRICING — (data from drugstore.com)
Solution (reconstituted) (Proleukin)
22000000 unit (1): $855.71
MONITORING PARAMETERS
The following clinical evaluations are recommended for all patients prior to beginning treatment and then frequently during drug administration:
CBC with differential, blood chemistries including electrolytes, renal and hepatic function tests
Chest x-rays
Monitoring during therapy should include vital signs (temperature, pulse, blood pressure, and respiration rate) and weight; in a patient with a decreased blood pressure, especially <90 mm Hg, cardiac monitoring for rhythm should be conducted. If an abnormal complex or rhythm is seen, an ECG should be performed; vital signs in these hypotension patients should be taken hourly and central venous pressure (CVP) checked; monitor for change in mental status.
Pulmonary function (baseline and periodic) basis.
CANADIAN BRAND NAMES — Proleukin®
INTERNATIONAL BRAND NAMES — Interleukina 2 (PY); Interleukina II (CN); Proleukin (AR, AT, BE, BR, CH, CO, CZ, DE, DK, EC, EG, ES, FI, FR, GB, GR, HK, HN, HU, IE, IL, IT, KP, NL, NZ, PE, PL, PT, TW, UY)
MECHANISM OF ACTION — Aldesleukin promotes proliferation, differentiation, and recruitment of T and B cells, natural killer (NK) cells, and thymocytes; causes cytolytic activity in a subset of lymphocytes and subsequent interactions between the immune system and malignant cells; can stimulate lymphokine-activated killer (LAK) cells and tumor-infiltrating lymphocytes (TIL) cells.
PHARMACODYNAMICS / KINETICS
Distribution: Vd: 4-7 L; primarily in plasma and then in the lymphocytes
Half-life elimination: I.V.: Initial: 6-13 minutes; Terminal: 80-120 minutes
Sound-alike/look-alike issues:
Aldesleukin may be confused with oprelvekin
Proleukin® may be confused with oprelvekin
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
U.S. BRAND NAMES — Proleukin®
PHARMACOLOGIC CATEGORY
Antineoplastic Agent, Miscellaneous
Biological Response Modulator
DOSING: ADULTS — Refer to individual protocols.
Renal cell carcinoma: I.V.: 600,000 int. units/kg every 8 hours for a maximum of 14 doses; repeat after 9 days for a total of 28 doses per course. Retreat if needed 7 weeks after previous course.
Melanoma:
I.V.:
Single-agent use: 600,000 int. units/kg every 8 hours for a maximum of 14 doses; repeat after 9 days for a total of 28 doses per course. Retreat if needed 7 weeks after previous course.
In combination with cytotoxic agents (unlabeled use): 24 million int. units/m2 days 12-16 and 19-23
SubQ (unlabeled route):
Single-agent doses: 3-18 million int. units/day for 5 days each week, up to 6 weeks
In combination with interferon:
5 million int. units/m2 3 times/week
1.8 million int. units/m2 twice daily 5 days/week for 6 weeks
Investigational regimen: SubQ: 11 million int. units (flat dose) daily for 4 days per week for 4 consecutive weeks; repeat every 6 weeks
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — No specific recommendations by manufacturer. Use with caution.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution:
Proleukin®: 22 x 106 int. units [18 million int. units/mL = 1.1 mg/mL when reconstituted]
DOSAGE FORMS: CONCISE
Injection, powder for reconstitution:
Proleukin®: 22 x 106 int. units
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Administer as I.V. infusion over 15 minutes (do not administer with an inline filter). Flush before and after with D5W, particularly if maintenance I.V. line contains sodium chloride. May also be administered by SubQ injection (unlabeled route)
Management of symptoms related to vascular leak syndrome:
If actual body weight increases >10% above baseline, or rales or rhonchi are audible:
Administer furosemide at dosage determined by patient response
Administer dopamine hydrochloride 1-5 mcg/kg/minute to maintain renal blood flow and urine output
If patient has dyspnea at rest: Administer supplemental oxygen by face mask
If patient has severe respiratory distress: Intubate patient and provide mechanical ventilation; administer ranitidine (as the hydrochloride salt) 50 mg I.V. every 8-12 hours as prophylaxis against stress ulcers
COMPATIBILITY — Stable in D5W.
Y-site administration: Compatible: Amikacin, amphotericin B, calcium gluconate, co-trimoxazole, diphenhydramine, dopamine, fat emulsion 10%, fluconazole, foscarnet, gentamicin, heparin, magnesium sulfate, metoclopramide, morphine, ondansetron, piperacillin, potassium chloride, ranitidine, thiethylperazine, ticarcillin, tobramycin. Incompatible: Ganciclovir, lorazepam, NS, pentamidine, prochlorperazine edisylate, promethazine.
Compatibility when admixed: Incompatible with NS.
USE — Treatment of metastatic renal cell cancer, metastatic melanoma
USE - UNLABELED / INVESTIGATIONAL — HIV infection, and AIDS; non-Hodgkin's lymphoma
ADVERSE REACTIONS SIGNIFICANT
>10%:
Cardiovascular: Hypotension (71%; grade 4: 3%), peripheral edema (28%), tachycardia (23%), edema (15%), vasodilation (13%), cardiovascular disorder (11%; includes blood pressure changes, CHF and ECG changes)
Central nervous system: Chills (52%), confusion (34%), fever (29%; grade 4: 1%), malaise (27%), somnolence (22%), anxiety (12%), pain (12%), dizziness (11%)
Dermatologic: Rash (42%), pruritus (24%), exfoliative dermatitis (18%)
Endocrine & metabolic: Acidosis (12%), hypomagnesemia (12%), hypocalcemia (11%)
Gastrointestinal: Diarrhea (67%), vomiting (19% to 50%), nausea (19% to 35%), stomatitis (22%), anorexia (20%), weight gain (18%), abdominal pain (11%)
Hematologic: Thrombocytopenia (37%; grade 4: 1%), anemia (29%), leukopenia (16%)
Hepatic: Hyperbilirubinemia (40%), AST increased (23%)
Neuromuscular & skeletal: Weakness (23%)
Renal: Oliguria (63%; grade 4: 6%), creatinine increased (33%)
Respiratory: Dyspnea (43%), lung disorder (24%; includes pulmonary congestion, rales, and rhonchi), cough (11%), respiratory disorder (11%; includes acute respiratory distress syndrome, infiltrates and pulmonary changes)
Miscellaneous: Infection (13%; grade 4: 1%)
1% to 10%:
Cardiovascular: Arrhythmia (10%), cardiac arrest (grade 4: 1%), MI (grade 4: 1%), supraventricular tachycardia (grade 4: 1%), ventricular tachycardia (grade 4: 1%)
Gastrointestinal: Abdomen enlarged (10%)
Hematologic: Coagulation disorder (grade 4: 1%)
Hepatic: Alkaline phosphatase increased (10%)
Renal: Anuria (grade 4: 5%), acute renal failure (grade 4: 1%)
Respiratory: Rhinitis (10%), apnea (grade 4: 1%)
Miscellaneous: Sepsis (grade 4: 1%)
<1% (Limited to important or life-threatening): Acute tubular necrosis, allergic interstitial nephritis, allergic reactions, anaphylaxis, atrial arrhythmia, AV block, blindness (transient or permanent), bowel necrosis, bradycardia, bullous pemphigoid, BUN increased, cardiomyopathy, cellulitis, cerebral edema, cerebral lesions, cerebral vasculitis, CHF, cholecystitis, colitis, coma, crescentic IgA glomuleronephritis, Crohn's disease exacerbation, depression (severe; leading to suicide), diabetes mellitus, duodenal ulcer, encephalitis, endocarditis, extrapyramidal syndrome, gastrointestinal hemorrhage, hematemesis, hemoptysis, hemorrhage, hepatic failure, hepatitis, hepatosplenomegaly, hypertension, hyperuricemia, hyperventilation, hypothermia, hyperthyroidism, hypoventilation, hypoxia, inflammatory arthritis, injection site necrosis, intestinal obstruction, intestinal perforation, leukocytosis, malignant hyperthermia, meningitis, myocardial ischemia, myocarditis, myopathy, myositis, neuritis, neuropathy, neutropenia, oculobulbar myasthenia gravis, optic neuritis, pancreatitis, pericardial effusion, pericarditis, peripheral gangrene, phlebitis, pneumonia, pneumothorax, pulmonary edema, pulmonary embolus, renal failure, respiratory acidosis, respiratory arrest, respiratory failure, retroperitoneal hemorrhage, rhabdomyolysis, scleroderma, seizure (including grand mal), shock, Stevens-Johnson syndrome, stroke, syncope, thrombosis, thyroiditis, tracheoesophageal fistula, transient ischemic attack, urticaria, ventricular extrasystoles
CONTRAINDICATIONS — Hypersensitivity to aldesleukin or any component of the formulation; patients with abnormal thallium stress or pulmonary function tests; patients who have had an organ allograft; retreatment in patients who have experienced sustained ventricular tachycardia (≥ 5 beats), refractory cardiac rhythm disturbances, recurrent chest pain with ECG changes consistent with angina or myocardial infarction, intubation ≥ 72 hours, pericardial tamponade, renal dialysis for ≥ 72 hours, coma or toxic psychosis lasting ≥ 48 hours, repetitive or refractory seizures, bowel ischemia/perforation, GI bleeding requiring surgery
WARNINGS / PRECAUTIONS
Boxed warnings: Capillary leak syndrome (CLS): . Experienced physician: . Infection: . Lethargy/somnolence: .
Special handling: Hazardous agent: Use appropriate precautions for handling and disposal.
Concerns related to adverse effects: Adverse effects: Are frequent and sometimes fatal. Capillary leak syndrome (CLS): [U.S. Boxed Warning]: High-dose aldesleukin therapy has been associated with capillary leak syndrome (CLS) resulting in hypotension and reduced organ perfusion which may be severe and can result in death. Therapy should be restricted to patients with normal cardiac and pulmonary functions as defined by thallium stress and formal pulmonary function testing. Extreme caution should be used in patients with a history of prior cardiac or pulmonary disease. Patients must have a serum creatinine ≤ 1.5 mg/dL prior to treatment. CNS effects: Mental status changes (irritability, confusion, depression) can occur and may indicate bacteremia, hypoperfusion, CNS malignancy, or CNS toxicity. Infection: [U.S. Boxed Warning]: Impaired neutrophil function is associated with treatment; patients are at risk for sepsis, bacterial endocarditis, and central line-related gram-positive infections. Antibiotic prophylaxis which has been associated with a reduced incidence of staphylococcal infections in aldesleukin studies includes the use of oxacillin, nafcillin, ciprofloxacin, or vancomycin. Lethargy/somnolence: [U.S. Boxed Warning]: Withhold treatment for patients developing moderate-to-severe lethargy or somnolence; continued treatment may result in coma.
Disease-related concerns: Autoimmune/inflammatory disorders: Use with caution in patients with autoimmune disease or inflammatory disorders; may exacerbate condition. CNS metastases: Patients should be evaluated and treated for CNS metastases and have a negative scan prior to treatment.
Concurrent drug therapy issues: Supportive care for high-dose treatment: Standard prophylactic supportive care during high-dose aldesleukin treatment includes acetaminophen to relieve constitutional symptoms and an H2 antagonist to reduce the risk of GI ulceration and/or bleeding.
Special populations: Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Experienced physician: [U.S. Boxed Warning]: Should be administered under the supervision of an experienced cancer chemotherapy physician in a facility with cardiopulmonary or intensive specialists and intensive care facilities available.
DRUG INTERACTIONS
Contrast Media (Non-ionic): May enhance the potential for allergic or hypersensitivity reactions to Aldesleukin. Risk C: Monitor therapy
Interferons (Alfa): May enhance the adverse/toxic effect of Aldesleukin. In particular, risks of myocardial and renal toxicity may be increased by this combination. Risk D: Consider therapy modification
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: May increase CNS adverse effects.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Maternal toxicity and embryocidal effects were noted in animal studies. There are no adequate and well-controlled studies in pregnant women; use during pregnancy only if benefits to the mother outweigh potential risk to the fetus. Contraception is recommended for fertile males or females using this medication.
LACTATION — Excretion in breast milk unknown/not recommended
BREAST-FEEDING CONSIDERATIONS — Due to the potential for serious adverse reactions in the nursing infant, breast-feeding should be discontinued during treatment.
PRICING — (data from drugstore.com)
Solution (reconstituted) (Proleukin)
22000000 unit (1): $855.71
MONITORING PARAMETERS
The following clinical evaluations are recommended for all patients prior to beginning treatment and then frequently during drug administration:
CBC with differential, blood chemistries including electrolytes, renal and hepatic function tests
Chest x-rays
Monitoring during therapy should include vital signs (temperature, pulse, blood pressure, and respiration rate) and weight; in a patient with a decreased blood pressure, especially <90 mm Hg, cardiac monitoring for rhythm should be conducted. If an abnormal complex or rhythm is seen, an ECG should be performed; vital signs in these hypotension patients should be taken hourly and central venous pressure (CVP) checked; monitor for change in mental status.
Pulmonary function (baseline and periodic) basis.
CANADIAN BRAND NAMES — Proleukin®
INTERNATIONAL BRAND NAMES — Interleukina 2 (PY); Interleukina II (CN); Proleukin (AR, AT, BE, BR, CH, CO, CZ, DE, DK, EC, EG, ES, FI, FR, GB, GR, HK, HN, HU, IE, IL, IT, KP, NL, NZ, PE, PL, PT, TW, UY)
MECHANISM OF ACTION — Aldesleukin promotes proliferation, differentiation, and recruitment of T and B cells, natural killer (NK) cells, and thymocytes; causes cytolytic activity in a subset of lymphocytes and subsequent interactions between the immune system and malignant cells; can stimulate lymphokine-activated killer (LAK) cells and tumor-infiltrating lymphocytes (TIL) cells.
PHARMACODYNAMICS / KINETICS
Distribution: Vd: 4-7 L; primarily in plasma and then in the lymphocytes
Half-life elimination: I.V.: Initial: 6-13 minutes; Terminal: 80-120 minutes
Alclometasone
MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Aclovate® may be confused with Accolate®
U.S. BRAND NAMES — Aclovate®
PHARMACOLOGIC CATEGORY
Corticosteroid, Topical
DOSING: ADULTS — Steroid-responsive dermatoses: Topical: Apply a thin film to the affected area 2-3 times/day. Note: Therapy should be discontinued when control is achieved; if no improvement is seen within 2 weeks, reassessment of diagnosis may be necessary.
DOSING: PEDIATRIC — Steroid-responsive dermatoses: Topical: Children ≥ 1 year: Apply thin film to affected area 2-3 times/day. Note: Therapy should be discontinued when control is achieved; if no improvement is seen within 2 weeks, reassessment of diagnosis may be necessary. Do not use for >3 weeks.
(For additional information see "Alclometasone: Pediatric drug information")
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Cream, as dipropionate: 0.05% (15 g, 45 g, 60 g)
Aclovate®: 0.05% (15 g, 60 g)
Ointment, as dipropionate: 0.05% (15 g, 45 g, 60 g)
Aclovate®: 0.05% (15 g, 45 g, 60 g)
DOSAGE FORMS: CONCISE
Cream: 0.05% (15 g, 45 g, 60 g)
Aclovate®: 0.05% (15 g, 60 g)
Ointment: 0.05% (15 g, 45 g, 60 g)
Aclovate®: 0.05% (15 g, 45 g, 60 g)
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — For external use only. Do not use on open wounds. Should not be used in the presence of open or weeping lesions. Apply sparingly to occlusive dressings.
USE — Treatment of inflammation of corticosteroid-responsive dermatosis (low to medium potency topical corticosteroid)
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Dermatologic: Acne, allergic dermatitis, hypopigmentation, maceration of the skin, perioral dermatitis, skin atrophy, striae, miliaria, telangiectasia
Endocrine & metabolic: HPA suppression, Cushing's syndrome, growth retardation
Local: Burning, erythema, itching, irritation, dryness, folliculitis, hypertrichosis, papular rash
Miscellaneous: Secondary infection
CONTRAINDICATIONS — Hypersensitivity to alclometasone or any component of the formulation; viral, fungal, or tubercular skin lesions
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Adrenal suppression: Systemic absorption of topical corticosteroids may cause hypothalamic-pituitary-adrenal (HPA) axis suppression (reversible) particularly in younger children. HPA axis suppression may lead to adrenal crisis. Risk is increased when used over large surface areas, for prolonged periods, or with occlusive dressings. Contact dermatitis: Allergic contact dermatitis can occur, it is usually diagnosed by failure to heal rather than clinical exacerbation. Kaposi's sarcoma: Prolonged treatment with corticosteroids has been associated with the development of Kaposi's sarcoma (case reports); if noted, discontinuation of therapy should be considered. Systemic effects: Adverse systemic effects including hyperglycemia, glycosuria, fluid and electrolyte changes, and HPA suppression may occur when used on large surface areas, for prolonged periods, or with an occlusive dressing.
Special populations: Pediatrics: Safety and efficacy have not been established in children <1 year of age. Chronic use of corticosteroids in children may interfere with growth and development. Not for the treatment of diaper dermatitis.
DRUG INTERACTIONS
Corticorelin: Corticosteroids may diminish the therapeutic effect of Corticorelin. Specifically, the plasma ACTH response to corticorelin may be blunted by recent or current corticosteroid therapy. Risk C: Monitor therapy
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Teratogenic effects have been observed in animals administered topical corticosteroids.
PRICING — (data from drugstore.com)
Cream (Aclovate)
0.05% (45): $73.99
Cream (Alclometasone Dipropionate)
0.05% (45): $38.99
0.05% (60): $52.99
Ointment (Aclovate)
0.05% (15): $44.99
Ointment (Alclometasone Dipropionate)
0.05% (15): $16.99
0.05% (60): $35.99
INTERNATIONAL BRAND NAMES — Aclosone (NL); Almeta (JP); Cloderm (ID); Delonal (DE); Demiderm (VE); Legederm (IT); Logoderm (NZ); Lomesone (GR); Miloderme (PT); Modraderm (BE); Modrasone (GB); Perderm (AE, BH, CY, EG, HK, HN, ID, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE)
MECHANISM OF ACTION — Stimulates the synthesis of enzymes needed to decrease inflammation, suppress mitotic activity, and cause vasoconstriction
PHARMACODYNAMICS / KINETICS
Absorption: Topical: ~3% absorbed systemically after 8 hours when applied to intact skin
PATIENT INFORMATION — Before applying, gently wash area to reduce risk of infection. Apply a thin film to cleansed area and rub in gently and thoroughly until medication vanishes. Avoid exposure to sunlight; severe sunburn may occur.
Sound-alike/look-alike issues:
Aclovate® may be confused with Accolate®
U.S. BRAND NAMES — Aclovate®
PHARMACOLOGIC CATEGORY
Corticosteroid, Topical
DOSING: ADULTS — Steroid-responsive dermatoses: Topical: Apply a thin film to the affected area 2-3 times/day. Note: Therapy should be discontinued when control is achieved; if no improvement is seen within 2 weeks, reassessment of diagnosis may be necessary.
DOSING: PEDIATRIC — Steroid-responsive dermatoses: Topical: Children ≥ 1 year: Apply thin film to affected area 2-3 times/day. Note: Therapy should be discontinued when control is achieved; if no improvement is seen within 2 weeks, reassessment of diagnosis may be necessary. Do not use for >3 weeks.
(For additional information see "Alclometasone: Pediatric drug information")
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Cream, as dipropionate: 0.05% (15 g, 45 g, 60 g)
Aclovate®: 0.05% (15 g, 60 g)
Ointment, as dipropionate: 0.05% (15 g, 45 g, 60 g)
Aclovate®: 0.05% (15 g, 45 g, 60 g)
DOSAGE FORMS: CONCISE
Cream: 0.05% (15 g, 45 g, 60 g)
Aclovate®: 0.05% (15 g, 60 g)
Ointment: 0.05% (15 g, 45 g, 60 g)
Aclovate®: 0.05% (15 g, 45 g, 60 g)
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — For external use only. Do not use on open wounds. Should not be used in the presence of open or weeping lesions. Apply sparingly to occlusive dressings.
USE — Treatment of inflammation of corticosteroid-responsive dermatosis (low to medium potency topical corticosteroid)
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Dermatologic: Acne, allergic dermatitis, hypopigmentation, maceration of the skin, perioral dermatitis, skin atrophy, striae, miliaria, telangiectasia
Endocrine & metabolic: HPA suppression, Cushing's syndrome, growth retardation
Local: Burning, erythema, itching, irritation, dryness, folliculitis, hypertrichosis, papular rash
Miscellaneous: Secondary infection
CONTRAINDICATIONS — Hypersensitivity to alclometasone or any component of the formulation; viral, fungal, or tubercular skin lesions
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Adrenal suppression: Systemic absorption of topical corticosteroids may cause hypothalamic-pituitary-adrenal (HPA) axis suppression (reversible) particularly in younger children. HPA axis suppression may lead to adrenal crisis. Risk is increased when used over large surface areas, for prolonged periods, or with occlusive dressings. Contact dermatitis: Allergic contact dermatitis can occur, it is usually diagnosed by failure to heal rather than clinical exacerbation. Kaposi's sarcoma: Prolonged treatment with corticosteroids has been associated with the development of Kaposi's sarcoma (case reports); if noted, discontinuation of therapy should be considered. Systemic effects: Adverse systemic effects including hyperglycemia, glycosuria, fluid and electrolyte changes, and HPA suppression may occur when used on large surface areas, for prolonged periods, or with an occlusive dressing.
Special populations: Pediatrics: Safety and efficacy have not been established in children <1 year of age. Chronic use of corticosteroids in children may interfere with growth and development. Not for the treatment of diaper dermatitis.
DRUG INTERACTIONS
Corticorelin: Corticosteroids may diminish the therapeutic effect of Corticorelin. Specifically, the plasma ACTH response to corticorelin may be blunted by recent or current corticosteroid therapy. Risk C: Monitor therapy
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Teratogenic effects have been observed in animals administered topical corticosteroids.
PRICING — (data from drugstore.com)
Cream (Aclovate)
0.05% (45): $73.99
Cream (Alclometasone Dipropionate)
0.05% (45): $38.99
0.05% (60): $52.99
Ointment (Aclovate)
0.05% (15): $44.99
Ointment (Alclometasone Dipropionate)
0.05% (15): $16.99
0.05% (60): $35.99
INTERNATIONAL BRAND NAMES — Aclosone (NL); Almeta (JP); Cloderm (ID); Delonal (DE); Demiderm (VE); Legederm (IT); Logoderm (NZ); Lomesone (GR); Miloderme (PT); Modraderm (BE); Modrasone (GB); Perderm (AE, BH, CY, EG, HK, HN, ID, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE)
MECHANISM OF ACTION — Stimulates the synthesis of enzymes needed to decrease inflammation, suppress mitotic activity, and cause vasoconstriction
PHARMACODYNAMICS / KINETICS
Absorption: Topical: ~3% absorbed systemically after 8 hours when applied to intact skin
PATIENT INFORMATION — Before applying, gently wash area to reduce risk of infection. Apply a thin film to cleansed area and rub in gently and thoroughly until medication vanishes. Avoid exposure to sunlight; severe sunburn may occur.
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