Zanmbeel

Monday, August 2, 2010

Amsacrine

PHARMACOLOGIC CATEGORY
Antineoplastic Agent

DOSING: ADULTS — Details concerning dosing in combination regimens should also be consulted.

Acute leukemia: I.V.:
Induction: 75-125 mg/m2/day for 5 days every 3-4 weeks (125 mg/m2/day is preferred; two courses may be necessary to achieve induction; increase dose by 20% in second and subsequent cycles if marrow hypoplasia not achieved and in absence of significant toxicity in previous course.)
Maintenance: Once remission has been achieved, maintenance dose should be ~50% of induction dose, administered every 4-8 weeks, depending on blood counts and marrow recovery

DOSING: ELDERLY — Refer to adult dosing.

DOSING: RENAL IMPAIRMENT
Dosage reduction recommended; specific guidelines from the manufacturer are not available; the following guidelines have been used by some clinicians:

Hall, 1983:
Serum creatinine 1.2-1.8 mg/dL: No adjustment recommended
Serum creatinine 2-3 mg/dL, oliguric patients: Administer 60% to 70% of dose; may increase subsequent dose based on toxicity.

Hornedo, 1985: BUN >20 mg/dL or serum creatinine >1.5 mg/dL: Administer 75% of dose

DOSING: HEPATIC IMPAIRMENT — Bilirubin >2 mg/dL: Dosage reduction recommended; specific guidelines from the manufacturer are not available; the following guidelines have been used by some clinicians:

Hall, 1983: Bilirubin >2 mg/dL: Administer 60% to 70% of dose; may increase subsequent dose based on toxicity.

Hornedo, 1985: Bilirubin >2 mg/dL: Administer 75% of dose

Koren, 1992: Severe hepatic dysfunction: Administer ≤ 50% of dose

DOSING: ADJUSTMENT FOR TOXICITY — Consider decreasing dose by 20% if life-threatening infection or hemorrhage occurred in previous cycle; delay second and subsequent cycles until recovery from myelosuppression or evidence of leukemic infiltrate is evident.

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [CAN] = Canadian brand name

Injection, solution [preservative free]:
AMSA PD [CAN]: 50 mg/mL (1.5 mL) [supplied with L-lactic acid 0.0353 M 13.5 mL] [not available in the U.S.]

DOSAGE FORMS: CONCISE
Injection, solution [preservative free]:
AMSA PD [CAN]: 50 mg/mL (1.5 mL) [not available in the U.S.]

GENERIC EQUIVALENT AVAILABLE — No

ADMINISTRATION — I.V.: Infuse over 60-90 minutes; avoid extravasation.

COMPATIBILITY — Stable in D5W; incompatible with BNS, D5NS, D51/4NS, D51/2NS, D5LR, D10NS, NSS, LR, chloride ion. Amsacrine forms an immediate precipitate in the presence of chloride ion; do not mix with drugs that are chloride or hydrochloride salts.

Y-site administration: Compatible: Amikacin, chlorpromazine, clindamycin, cytarabine, dexamethasone, diphenhydramine, famotidine, fludarabine, gentamicin, granisetron, haloperidol, hydrocortisone sodium succinate, hydromorphone, lorazepam, morphine, prochlorperazine, promethazine, ranitidine, sodium bicarbonate, tobramycin, vancomycin. Incompatible: Acyclovir, amphotericin, aztreonam, calcium chloride, ceftazidime, ceftriaxone, cephalothin, cimetidine, cisplatin, filgrastim, furosemide, ganciclovir, heparin, methylprednisolone, metoclopramide, ondansetron, potassium chloride, sargramostim.

Compatibility when admixed: Compatible: Sodium bicarbonate, bleomycin

USE — Canada: Refractory acute leukemia

USE - UNLABELED / INVESTIGATIONAL — Acute myeloid leukemia (AML)

ADVERSE REACTIONS SIGNIFICANT
>10%:
Gastrointestinal: Nausea (>10%), vomiting (>10%), stomatitis (>10%), diarrhea (>10%), perirectal abscess (>10%), abdominal pain (>10%)
Hematologic: Myelosuppression, leukopenia (nadir: 11-13 days; recovery: days 17-25)

Frequency not defined:

Cardiovascular: Atrial tachyarrhythmia, atrial tachycardia, atrial fibrillation, bradycardia, cardiomyopathy (rare), cardiopulmonary arrest, CHF (rare); ECG changes (QT prolongation, nonspecific ST segment or T wave changes); ejection fraction decreased, hypotension, sinus tachycardia, tachycardia, ventricular arrhythmia, ventricular extrasystoles, ventricular fibrillation, ventricular tachyarrhythmia

Central nervous system: Confusion, dizziness, emotional lability, fever, headache, hypoesthesia, lethargy, seizure

Dermatologic: Alopecia, cutaneous inflammatory reaction, dermatologic reaction, purpura, rash (purpuric or maculopapular), urticaria

Gastrointestinal: Anorexia, dysphagia, gingivitis, gum hemorrhage, hematemesis, weight changes

Genitourinary: Orange-red discoloration of the urine

Hematologic: Anemia, granulocytopenia, hemorrhage, pancytopenia, thrombocytopenia

Hepatic: Alkaline phosphatase increased, AST increased, bilirubin increased, hepatic insufficiency, hepatitis, hepatotoxicity, jaundice, progressive liver failure

Local: Injection site inflammation, phlebitis

Neuromuscular & skeletal: Musculoskeletal pain, paresthesia, weakness

Renal: BUN increased, creatinine increased, hematuria, proteinuria, renal failure

Respiratory: Dyspnea

Miscellaneous: Allergic reaction, infection

CONTRAINDICATIONS — Hypersensitivity to amsacrine, acridine derivatives, or any component of the formulation; pre-existing bone marrow suppression due to chemotherapy or radiation therapy

WARNINGS / PRECAUTIONS
Special handling: Hazardous agent: Use appropriate precautions for handling and disposal.

Concerns related to adverse effects: Bone marrow suppression: Myelosuppression, including transient leukopenia, is a common toxicity; prolonged marrow aplasia may occur. May require dose reduction, therapy interruption or treatment delay. Cardiovascular effects: Acute cardiotoxicity, including arrhythmia, ECG changes, and rarely, cardiomyopathy and CHF, have been reported with use, although generally not considered to be a cumulative dose effect. Risk factors for cardiotoxicity may include hypokalemia and a history of anthracycline therapy. Correct fluid and electrolyte imbalance prior to treatment initiation. Use with caution in patients with underlying cardiovascular disease. Tumor lysis syndrome: Tumor lysis syndrome may occur; adequate hydration and prophylactic uric acid reduction should be considered prior to or during treatment; monitor closely.

Disease-related concerns: Hepatic impairment: Use with caution in patients with significant hepatic impairment (bilirubin >2 mg/dL); toxicity may be increased. Hepatic metabolism and biliary excretion are major routes of elimination. Dosage reductions may be recommended. Evaluate hepatic function prior to and during treatment. Hypokalemia: Serum potassium should be >4 mEq/L prior to administration (Arlin, 1988). The risk for arrhythmia is decreased by ensuring normal potassium levels. Renal impairment: Use with caution in patients with significant renal impairment (BUN >20 mg/dL; serum creatinine >1.2 mg/dL); toxicity may be increased. Dosage reductions may be recommended. Evaluate renal function prior to and during treatment.

Concurrent drug therapy issues: Anthracyclines: Use with caution in patients who have received high cumulative doses of anthracyclines (may increase the risk for cardiotoxicity). Vaccinations: Avoid vaccination with live virus vaccines during treatment.

RESTRICTIONS — Not available in U.S.

DRUG INTERACTIONS
Cardiac Glycosides: Antineoplastic Agents may decrease the absorption of Cardiac Glycosides. This may only affect digoxin tablets. Exceptions: Digitoxin. 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

Vitamin K Antagonists (eg, warfarin): Antineoplastic Agents may enhance the anticoagulant effect of Vitamin K Antagonists. Antineoplastic Agents may diminish the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

PREGNANCY IMPLICATIONS — Animal reproduction studies have not been conducted. Women of childbearing potential should avoid becoming pregnant while receiving treatment.

LACTATION — Excretion in breast milk unknown/not recommended

BREAST-FEEDING CONSIDERATIONS — Breast-feeding should be discontinued prior to treatment.

MONITORING PARAMETERS
CBC with differential, bone marrow studies, serum potassium, hepatic function, renal function; ECG (during and after infusion)

CANADIAN BRAND NAMES — AMSA PD

INTERNATIONAL BRAND NAMES — Amekrin (DK, SE); Amsidine (BE, NL); Amsidyl (AU)

MECHANISM OF ACTION — Amsacrine has been shown to inhibit DNA synthesis by binding to, and intercalating with, DNA; inhibits topoisomerase II activity.

PHARMACODYNAMICS / KINETICS
Distribution: Vd: 1.67 L/kg; minimal CNS penetration

Protein binding: 96% to 98%

Metabolism: Hepatic, to inactive metabolites (major metabolite is 5' glutathione conjugate)

Half-life elimination: 1.4-5 hours; Terminal: 8-9 hours

Excretion: Bile; urine (35%; 20% as unchanged drug)

PATIENT INFORMATION — This drug may cause darkening or discoloration of the urine for 24-48 hours. Watch for fever, malaise, bleeding, bruising, sore throat or mouth, difficulty swallowing, or for pain, redness, or swelling at the injection site.

Amsacrine

Ampicillin and sulbactam

U.S. BRAND NAMES — Unasyn®

PHARMACOLOGIC CATEGORY
Antibiotic, Penicillin

DOSING: ADULTS — Doses expressed as ampicillin/sulbactam combination.

Susceptible infections: I.M., I.V.: 1.5-3 g every 6 hours (maximum: Unasyn® 12 g)

Amnionitis, cholangitis, diverticulitis, endometritis, endophthalmitis, epididymitis/orchitis, liver abscess, osteomyelitis (diabetic foot), peritonitis: I.V.: 3 g every 6 hours

Endocarditis: I.V.: 3 g every 6 hours with gentamicin or vancomycin for 4-6 weeks

Orbital cellulitis: I.V.: 1.5 g every 6 hours

Parapharyngeal space infections: I.V.: 3 g every 6 hours

Pasteurella multocida(human, canine/feline bites): I.V.: 1.5-3 g every 6 hours

Pelvic inflammatory disease: I.V.: 3 g every 6 hours with doxycycline

Peritonitis (CAPD): Intraperitoneal:
Anuric, intermittent: 3 g every 12 hours
Anuric, continuous: Loading dose: 1.5 g; maintenance dose: 150 mg

Pneumonia:
Aspiration, community-acquired: I.V.: 1.5-3 g every 6 hours
Hospital-acquired: I.V.: 3 g every 6 hours

Urinary tract infections, pyelonephritis: I.V.: 3 g every 6 hours for 14 days

DOSING: PEDIATRIC

(For additional information see "Ampicillin and sulbactam: Pediatric drug information")
Susceptible infections: Children ≥ 1 year: I.V.: 100-400 mg ampicillin/kg/day divided every 6 hours (maximum: 8 g ampicillin/day, 12 g Unasyn®). Note: The American Academy of Pediatrics recommends a dose of up to 300 mg/kg/day for severe infection in infants >1 month of age.

Epiglottitis: Children ≥ 1 year: I.V.: 100-200 mg ampicillin/kg/day divided in 4 doses

Mild-to-moderate infections: Children ≥ 1 year: I.V.: 100-200 mg ampicillin/kg/day (150-300 mg Unasyn®) divided every 6 hours (maximum: 8 g ampicillin/day, 12 g Unasyn®)

Peritonsillar and retropharyngeal abscess: Children ≥ 1 year: I.V.: 50 mg ampicillin/kg/dose every 6 hours

Severe infections: Children ≥ 1 year: I.V.: 200-400 mg ampicillin/kg/day divided every 6 hours (maximum: 8 g ampicillin/day, 12 g Unasyn®)

DOSING: ELDERLY — Refer to adult dosing.

DOSING: RENAL IMPAIRMENT
Clcr 15-29 mL/minute: Administer every 12 hours

Clcr 5-14 mL/minute: Administer every 24 hours

Hemodialysis: Give dose after hemodialysis

Continuous ambulatory peritoneal dialysis (CAPD): 3 g every 24 hours

Continuous renal replacement therapy (CRRT): Drug clearance is highly dependent on the method of renal replacement, filter type, and flow rate. Appropriate dosing requires close monitoring of pharmacologic response, signs of adverse reactions due to drug accumulation, as well as drug levels in relation to target trough (if appropriate). The following are general recommendations only (based on dialysate flow/ultrafiltration rates of 1 L/hour) and should not supersede clinical judgment:
CVVH: 3 g every 12 hours
CVVHD/CVVHDF: 3 g every 8 hours

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Injection, powder for reconstitution: 1.5 g: Ampicillin 1 g and sulbactam 0.5 g [contains sodium 115 mg (5 mEq)/1.5 g)]; 3 g: Ampicillin 2 g and sulbactam 1 g [contains sodium 115 mg (5 mEq)/1.5 g)]; 15 g: Ampicillin 10 g and sulbactam 5 g [bulk package; contains sodium 115 mg (5 mEq)/1.5 g]
Unasyn®:
1.5 g: Ampicillin 1 g and sulbactam 0.5 g [contains sodium 115 mg (5 mEq)/1.5 g)]
3 g: Ampicillin 2 g and sulbactam 1 g [contains sodium 115 mg (5 mEq)/1.5 g)]
15 g: Ampicillin 10 g and sulbactam 5 g [bulk package; contains sodium 115 mg (5 mEq)/1.5 g)]

DOSAGE FORMS: CONCISE
Injection, powder for reconstitution: 1.5 g [ampicillin 1 g and sulbactam 0.5 g]; 3 g [ampicillin 2 g and sulbactam 1 g]; 15 g [ampicillin 10 g and sulbactam 5 g]
Unasyn®: 1.5 g [ampicillin 1 g and sulbactam 0.5 g]; 3 g [ampicillin 2 g and sulbactam 1 g]; 15 g [ampicillin 10 g and sulbactam 5 g]; 15 g [ampicillin 10 g and sulbactam 5 g

GENERIC EQUIVALENT AVAILABLE — Yes

ADMINISTRATION — Administer around-the-clock to promote less variation in peak and trough serum levels. Administer by slow injection over 10-15 minutes or I.V. over 15-30 minutes. Ampicillin and gentamicin should not be mixed in the same I.V. tubing.

Some penicillins (eg, carbenicillin, ticarcillin, and piperacillin) have been shown to inactivate aminoglycosides in vitro. This has been observed to a greater extent with tobramycin and gentamicin, while amikacin has shown greater stability against inactivation. Concurrent use of these agents may pose a risk of reduced antibacterial efficacy in vivo, particularly in the setting of profound renal impairment. However, definitive clinical evidence is lacking. If combination penicillin/aminoglycoside therapy is desired in a patient with renal dysfunction, separation of doses (if feasible), and routine monitoring of aminoglycoside levels, CBC, and clinical response should be considered.

COMPATIBILITY — Stable in NS; variable stability (consult detailed reference) in D51/2NS, D5W, LR.

Y-site administration: Compatible: Amifostine, aztreonam, cefepime, docetaxel, enalaprilat, etoposide, famotidine, filgrastim, fluconazole, fludarabine, gatifloxacin, gemcitabine, granisetron, heparin, insulin (regular), linezolid, meperidine, morphine, paclitaxel, remifentanil, tacrolimus, teniposide, theophylline, thiotepa. Incompatible: Aminoglycosides (gentamicin, tobramycin), amphotericin B cholesteryl sulfate complex, ciprofloxacin, idarubicin, ondansetron, sargramostim. Variable (consult detailed reference): Cisatracurium, diltiazem, vancomycin.

Compatibility when admixed: Compatible: Aztreonam. Incompatible: Aminoglycosides.

USE — Treatment of susceptible bacterial infections involved with skin and skin structure, intra-abdominal infections, gynecological infections; spectrum is that of ampicillin plus organisms producing beta-lactamases such as S. aureus, H. influenzae, E. coli, Klebsiella, Acinetobacter, Enterobacter, and anaerobes

ADVERSE REACTIONS SIGNIFICANT — Also see Ampicillin.

>10%: Local: Pain at injection site (I.M.)

1% to 10%:
Dermatologic: Rash
Gastrointestinal: Diarrhea
Local: Pain at injection site (I.V.), thrombophlebitis
Miscellaneous: Allergic reaction (may include serum sickness, urticaria, bronchospasm, hypotension, etc)

<1% (Limited to important or life-threatening): Abdominal distension, candidiasis, chest pain, chills, dysuria, edema, epistaxis, erythema, facial swelling, fatigue, flatulence, glossitis, hairy tongue, headache, interstitial nephritis, itching, liver enzymes increased, malaise, mucosal bleeding, nausea, pseudomembranous colitis, seizure, substernal pain, throat tightness, thrombocytopenia, urine retention, vomiting

CONTRAINDICATIONS — Hypersensitivity to ampicillin, sulbactam, penicillins, or any component of the formulations

WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Anaphylactoid/hypersensitivity reactions: Serious and occasionally severe or fatal hypersensitivity (anaphylactoid) reactions have been reported in patients on penicillin therapy, especially with a history of beta-lactam hypersensitivity, history of sensitivity to multiple allergens, or previous IgE-mediated reactions (eg, anaphylaxis, angioedema, urticaria). Use with caution in asthmatic patients. Rash: Appearance of a rash should be carefully evaluated to differentiate a nonallergic ampicillin rash from a hypersensitivity reaction; rash occurs in 5% to 10% of children and is a generalized dull red, maculopapular rash, generally appearing 3-14 days after the start of therapy. It normally begins on the trunk and spreads over most of the body. It may be most intense at pressure areas, elbows, and knees. Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.

Disease-related concerns: Infectious mononucleosis: A high percentage of patients with infectious mononucleosis have developed rash during therapy; ampicillin-class antibiotics not recommended in these patients. Renal impairment: Use with caution in patients with renal impairment; dosage adjustment recommended.

Special populations: Pediatrics: Safety and efficacy have not been established in children <1 year of age.

DRUG INTERACTIONS
Allopurinol: May enhance the potential for allergic or hypersensitivity reactions to Ampicillin. Risk C: Monitor therapy

Atenolol: Ampicillin may decrease the bioavailability of Atenolol. Risk C: Monitor therapy

Fusidic Acid: May diminish the therapeutic effect of Penicillins. Risk D: Consider therapy modification

Methotrexate: Penicillins may decrease the excretion of Methotrexate. Risk C: Monitor therapy

Mycophenolate: Penicillins may decrease serum concentrations of the active metabolite(s) of Mycophenolate. This effect appears to be the result of impaired enterohepatic recirculation. Risk C: Monitor therapy

Tetracycline Derivatives: May diminish the therapeutic effect of Penicillins. Risk D: Consider therapy modification

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Risk D: Consider therapy modification

Uricosuric Agents: May decrease the excretion of Penicillins. Risk C: Monitor therapy

PREGNANCY RISK FACTOR — B (show table)

PREGNANCY IMPLICATIONS — Adverse events have not been observed in animal studies; therefore, ampicillin/sulbactam is classified as pregnancy category B. Both ampicillin and sulbactam cross the placenta. When used during pregnancy, pharmacokinetic changes have been observed with ampicillin alone (refer to the Ampicillin monograph for details).

LACTATION — Enters breast milk/use caution

BREAST-FEEDING CONSIDERATIONS — Ampicillin and sulbactam are both excreted into breast milk in low concentrations. The manufacturer recommends that caution be used if administering to lactating women. Nondose-related effects could include modification of bowel flora and allergic sensitization of the infant. The maternal dose of sulbactam does not need altered in the postpartum period. Also refer to the Ampicillin monograph.

DIETARY CONSIDERATIONS — Sodium content of 1.5 g injection: 115 mg (5 mEq)

MONITORING PARAMETERS — With prolonged therapy, monitor hematologic, renal, and hepatic function; monitor for signs of anaphylaxis during first dose

CANADIAN BRAND NAMES — Unasyn®

INTERNATIONAL BRAND NAMES — Ampibactan (VE); Amplisul (EC); Ansulina (TW); Baccillin (KP); Bactacin (KP); Bactesyn (ID); Easyn (MY); Picyn (ID); Prixin (PY); Rukasyn (KP); Sulbaccin (TH); Sulbacin (IN, KP, MY, PH); Sultamicilina (AR); Ubacillin (KP); Ubactam (KP); Unacid (DE); Unacim (FR); Unasyn (AE, AT, BF, BH, BJ, BR, CI, CL, CN, CO, CR, CY, CZ, EC, EE, EG, ET, GH, GM, GN, GT, HK, HN, ID, IL, IQ, IR, IT, JO, KE, KP, KW, LB, LR, LY, MA, ML, MR, MU, MW, MY, NE, NG, NI, OM, PA, PE, PH, QA, SA, SC, SD, SL, SN, SV, SY, TN, TW, TZ, UG, YE, ZA, ZM, ZW); Unasyna (AR, UY)

MECHANISM OF ACTION — The addition of sulbactam, a beta-lactamase inhibitor, to ampicillin extends the spectrum of ampicillin to include some beta-lactamase-producing organisms; inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs) which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested.

PHARMACODYNAMICS / KINETICS
Ampicillin: See Ampicillin.

Sulbactam:
Distribution: Bile, blister, and tissue fluids
Protein binding: 38%
Half-life elimination: Normal renal function: 1-1.3 hours
Excretion: Urine (~75% to 85% as unchanged drug) within 8 hours

Ampicillin and sulbactam

Ampicillin

MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Ampicillin may be confused with aminophylline

PHARMACOLOGIC CATEGORY
Antibiotic, Penicillin

DOSING: ADULTS
Usual dosage range:
Oral: 250-500 mg every 6 hours
I.M., I.V.: 250-500 mg every 6 hours

Actinomycosis: I.V.: 50 mg/kg/day for 4-6 weeks then oral amoxicillin

Cholangitis (acute): I.V.: 2 g every 4 hours with gentamicin

Diverticulitis: I.M., I.V.: 2 g every 6 hours with metronidazole

Endocarditis:
Infective: I.V.: 12 g/day via continuous infusion or divided every 4 hours
Prophylaxis: Dental, oral, or respiratory tract procedures: I.M., I.V.: 2 g within 30-60 minutes prior to procedure in patients not allergic to penicillin and unable to take oral amoxicillin. Intramuscular injections should be avoided in patients who are receiving anticoagulant therapy. In these circumstances, orally administered regimens should be given whenever possible. Intravenously administered antibiotics should be used for patients who are unable to tolerate or absorb oral medications. Note: American Heart Association (AHA) guidelines now recommend prophylaxis only in patients undergoing invasive procedures and in whom underlying cardiac conditions may predispose to a higher risk of adverse outcomes should infection occur.
Prophylaxis in total joint replacement patient: I.M., I.V.: 2 g 1 hour prior to the procedure
Genitourinary and gastrointestinal tract procedures: I.M., I.V.:
High-risk patients: 2 g within 30 minutes prior to procedure, followed by ampicillin 1 g (or amoxicillin 1g orally) 6 hours later; must be used in combination with gentamicin. Note: As of April 2007, routine prophylaxis for GI/GU procedures is no longer recommended by the AHA.
Moderate-risk patients: 2 g within 30 minutes prior to procedure

Group B strep prophylaxis (intrapartum): I.V.: 2 g initial dose, then 1 g every 4 hours until delivery

Listeria infections: I.V.: 2 g every 4 hours (consider addition of aminoglycoside)

Sepsis/meningitis: I.M., I.V.: 150-250 mg/kg/day divided every 3-4 hours (range: 6-12 g/day)

Urinary tract infections (enterococcus suspected): I.V.: 1-2 g every 6 hours with gentamicin

DOSING: PEDIATRIC

(For additional information see "Ampicillin: Pediatric drug information")
Usual dosage range: Infants and Children:
Oral: 50-100 mg/kg/day in doses divided every 6 hours (maximum: 2-4 g/day)
I.M., I.V.: 100-400 mg/kg/day in divided doses every 6 hours (maximum: 12 g/day)

Endocarditis prophylaxis: Infants and Children: I.M., I.V.:
Dental, oral, or respiratory tract procedures: 50 mg/kg within 30-60 minutes prior to procedure in patients not allergic to penicillin and unable to take oral amoxicillin. Intramuscular injections should be avoided in patients who are receiving anticoagulant therapy. In these circumstances, orally administered regimens should be given whenever possible. Intravenously administered antibiotics should be used for patients who are unable to tolerate or absorb oral medications.
Note: American Heart Association (AHA) guidelines now recommend prophylaxis only in patients undergoing invasive procedures and in whom underlying cardiac conditions may predispose to a higher risk of adverse outcomes should infection occur.
Genitourinary and gastrointestinal tract procedures:
High-risk patients: 50 mg/kg (maximum: 2 g) within 30 minutes prior to procedure, followed by ampicillin 25 mg/kg (or amoxicillin 25 mg/kg orally) 6 hours later; must be used in combination with gentamicin. Note: As of April 2007, routine prophylaxis for GI/GU procedures is no longer recommended by the AHA.
Moderate-risk patients: 50 mg/kg within 30 minutes prior to procedure.

Mild-to-moderate infections: Infants and Children:
Oral: 50-100 mg/kg/day in doses divided every 6 hours (maximum: 2-4 g/day)
I.M., I.V.: 100-150 mg/kg/day in divided doses every 6 hours (maximum: 2-4 g/day)

Severe infections/meningitis: Infants and Children: I.M., I.V.: 200-400 mg/kg/day in divided doses every 6 hours (maximum: 6-12 g/day)

DOSING: ELDERLY — Administer usual adult dose unless renal function is markedly reduced.

DOSING: RENAL IMPAIRMENT
Clcr >50 mL/minute: Administer every 6 hours

Clcr 10-50 mL/minute: Administer every 6-12 hours

Clcr <10 mL/minute: Administer every 12-24 hours

Hemodialysis: Moderately dialyzable (20% to 50%); administer dose after dialysis

Peritoneal dialysis: Moderately dialyzable (20% to 50%)
Administer 250 mg every 12 hours

Continuous arteriovenous or venovenous hemofiltration effects: Dose as for Clcr 10-50 mL/minute; ~50 mg of ampicillin per liter of filtrate is removed

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule: 250 mg, 500 mg

Injection, powder for reconstitution, as sodium: 125 mg, 250 mg, 500 mg, 1 g, 2 g, 10 g

Powder for oral suspension: 125 mg/5 mL (100 mL, 200 mL); 250 mg/5 mL (100 mL, 200 mL)

DOSAGE FORMS: CONCISE
Capsule: 250 mg, 500 mg

Injection, powder for reconstitution: 125 mg, 250 mg, 500 mg, 1 g, 2 g, 10 g

Powder for oral suspension: 125 mg/5 mL, 250 mg/5 mL

GENERIC EQUIVALENT AVAILABLE — Yes

ADMINISTRATION — Administer around-the-clock to promote less variation in peak and trough serum levels.

Oral: Administer on an empty stomach (ie, 1 hour prior to, or 2 hours after meals) to increase total absorption.

I.V.: Administer over 3-5 minutes (125-500 mg) or over 10-15 minutes (1-2 g). More rapid infusion may cause seizures. Ampicillin and gentamicin should not be mixed in the same I.V. tubing.

Some penicillins (eg, carbenicillin, ticarcillin, and piperacillin) have been shown to inactivate aminoglycosides in vitro. This has been observed to a greater extent with tobramycin and gentamicin, while amikacin has shown greater stability against inactivation. Concurrent use of these agents may pose a risk of reduced antibacterial efficacy in vivo, particularly in the setting of profound renal impairment. However, definitive clinical evidence is lacking. If combination penicillin/aminoglycoside therapy is desired in a patient with renal dysfunction, separation of doses (if feasible), and routine monitoring of aminoglycoside levels, CBC, and clinical response should be considered.

COMPATIBILITY — Incompatible in D5W, D5NS, D10W, fat emulsion 10%, hetastarch 6%, LR; variable stability (consult detailed reference) in NS.

Y-site administration: Compatible: Acyclovir, amifostine, aztreonam, clarithromycin, cyclophosphamide, docetaxel, doxorubicin liposome, enalaprilat, esmolol, etoposide, famotidine, filgrastim, fludarabine, foscarnet, gatifloxacin, gemcitabine, granisetron, heparin, heparin with hydrocortisone sodium succinate, insulin (regular), labetalol, levofloxacin, linezolid, magnesium sulfate, melphalan, meperidine, morphine, multivitamins, ofloxacin, perphenazine, phytonadione, potassium chloride, propofol, remifentanil, tacrolimus, teniposide, theophylline, thiotepa, tolazoline, vitamin B complex with C. Incompatible: Amphotericin B cholesteryl sulfate complex, epinephrine, fluconazole, hydralazine, midazolam, ondansetron, sargramostim, verapamil, vinorelbine. Variable (consult detailed reference): Calcium gluconate, cisatracurium, diltiazem, hetastarch, hydromorphone, vancomycin.

Compatibility in syringe: Compatible: Chloramphenicol, colistimethate, diatrizoate meglumine 52%, diatrizoate sodium 8%, diatrizoate sodium 60%, heparin, iohexol, iopamidol, iothalamate meglumine 60%, ioxaglate meglumine 39.3%, ioxaglate 19.6%, procaine. Incompatible: Erythromycin lactobionate, gentamicin, hydromorphone, kanamycin, lincomycin, metoclopramide. Variable (consult detailed reference): Lidocaine, polymyxin B sulfate, streptomycin.

Compatibility when admixed: Compatible: Clindamycin, erythromycin lactobionate, floxacillin, furosemide. Incompatible: Amikacin, chlorpromazine, dopamine, gentamicin, hydralazine, prochlorperazine. Variable (consult detailed reference): Aztreonam, cefepime, cimetidine, heparin, hydrocortisone sodium succinate, metronidazole, metronidazole with sodium bicarbonate, ranitidine, sodium bicarbonate, verapamil.

USE — Treatment of susceptible bacterial infections (nonbeta-lactamase-producing organisms); treatment or prophylaxis of infective endocarditis; susceptible bacterial infections caused by streptococci, pneumococci, nonpenicillinase-producing staphylococci, Listeria, meningococci; some strains of H. influenzae, Salmonella, Shigella, E. coli, Enterobacter, and Klebsiella

ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.

Central nervous system: Fever, penicillin encephalopathy, seizure

Dermatologic: Erythema multiforme, exfoliative dermatitis, rash, urticaria
Note: Appearance of a rash should be carefully evaluated to differentiate (if possible) nonallergic ampicillin rash from hypersensitivity reaction. Incidence is higher in patients with viral infection, Salmonella infection, lymphocytic leukemia, or patients that have hyperuricemia.

Gastrointestinal: Black hairy tongue, diarrhea, enterocolitis, glossitis, nausea, pseudomembranous colitis, sore mouth or tongue, stomatitis, vomiting, oral candidiasis

Hematologic: Agranulocytosis, anemia, hemolytic anemia, eosinophilia, leukopenia, thrombocytopenia purpura

Hepatic: AST increased

Renal: Interstitial nephritis (rare)

Respiratory: Laryngeal stridor

Miscellaneous: Anaphylaxis, serum sickness-like reaction

CONTRAINDICATIONS — Hypersensitivity to ampicillin, any component of the formulation, or other penicillins

WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Anaphylactoid/hypersensitivity reactions: Serious and occasionally severe or fatal hypersensitivity (anaphylactoid) reactions have been reported in patients on penicillin therapy, especially with a history of beta-lactam hypersensitivity, history of sensitivity to multiple allergens, or previous IgE-mediated reactions (eg, anaphylaxis, angioedema, urticaria). Use with caution in asthmatic patients. Rash: Appearance of a rash should be carefully evaluated to differentiate a nonallergic ampicillin rash from a hypersensitivity reaction; rash occurs in 5% to 10% of children and is a generalized dull red, maculopapular rash, generally appearing 3-14 days after the start of therapy. It normally begins on the trunk and spreads over most of the body. It may be most intense at pressure areas, elbows, and knees. Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.

Disease-related concerns: Infectious mononucleosis: A high percentage of patients with infectious mononucleosis have developed rash during therapy; ampicillin-class antibiotics not recommended in these patients. Renal impairment: Use with caution in patients with renal impairment; dosage adjustment recommended.

DRUG INTERACTIONS
Allopurinol: May enhance the potential for allergic or hypersensitivity reactions to Ampicillin. Risk C: Monitor therapy

Atenolol: Ampicillin may decrease the bioavailability of Atenolol. Risk C: Monitor therapy

Fusidic Acid: May diminish the therapeutic effect of Penicillins. Risk D: Consider therapy modification

Methotrexate: Penicillins may decrease the excretion of Methotrexate. Risk C: Monitor therapy

Mycophenolate: Penicillins may decrease serum concentrations of the active metabolite(s) of Mycophenolate. This effect appears to be the result of impaired enterohepatic recirculation. Risk C: Monitor therapy

Tetracycline Derivatives: May diminish the therapeutic effect of Penicillins. Risk D: Consider therapy modification

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Risk D: Consider therapy modification

Uricosuric Agents: May decrease the excretion of Penicillins. Risk C: Monitor therapy

ETHANOL / NUTRITION / HERB INTERACTIONS — Food: Food decreases ampicillin absorption rate; may decrease ampicillin serum concentration.

PREGNANCY RISK FACTOR — B (show table)

PREGNANCY IMPLICATIONS — Adverse events have not been observed in animal studies; therefore, ampicillin is classified as pregnancy category B. Ampicillin crosses the human placenta, providing detectable concentrations in the cord serum and amniotic fluid. Most studies have not identified a teratogenic potential for ampicillin use during pregnancy. Two possible associations (congenital heart disease and cleft palate) have been noted; each of these was observed in a single study, was not substantiated by other studies, and may have been chance associations. Ampicillin is recommended for use in pregnant women for the management of premature rupture of membranes. Ampicillin is considered an acceptable alternative to penicillin for the prevention of early-onset Group B Streptococcal (GBS) disease in newborns.

The volume of distribution of ampicillin is increased during pregnancy and the half-life is decreased. As a result, serum concentrations in pregnant patients are approximately 50% of those in nonpregnant patients receiving the same dose. Higher doses may be needed during pregnancy. Although oral absorption is not altered during pregnancy, oral ampicillin is poorly-absorbed during labor.

LACTATION — Enters breast milk/use caution

BREAST-FEEDING CONSIDERATIONS — Ampicillin is excreted in breast milk. The manufacturer recommends that caution be exercised when administering ampicillin to nursing women. Due to the low concentrations in human milk, minimal toxicity would be expected in the nursing infant. Nondose-related effects could include modification of bowel flora and allergic sensitization.

DIETARY CONSIDERATIONS — Take on an empty stomach 1 hour before or 2 hours after meals.

Sodium content of 5 mL suspension (250 mg/5 mL): 10 mg (0.4 mEq)

Sodium content of 1 g: 66.7 mg (3 mEq)

PRICING — (data from drugstore.com)
Capsules (Ampicillin)
250 mg (30): $12.99
250 mg (90): $31.95
500 mg (100): $49.99

MONITORING PARAMETERS — With prolonged therapy, monitor renal, hepatic, and hematologic function periodically; observe signs and symptoms of anaphylaxis during first dose

CANADIAN BRAND NAMES — Apo-Ampi®; Novo-Ampicillin; Nu-Ampi

INTERNATIONAL BRAND NAMES — Alphacin (AU, NZ); Alphapen (MX); Ambiopi (ID); Amcopen (PK); Amfipen (AE, BH, CY, EG, GB, IE, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Amipenix (JP); Ampecu (EC); Ampen (VE); Ampenolet (GR); Ampiblan (CO); Ampicher (EC); Ampicil (BR); Ampicilina (EC); Ampicillin (PL); Ampicin (PH); Ampiclox (SG); Ampico (PH); Ampicyn (AU); Ampidar (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Ampifen (NL); Ampiflex (PE); Ampiger (BR); Ampilag (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW); Ampilin (IN); Ampillin (MY); Ampimedin (PY); Ampipen (IN, ZA); Ampitenk (AR); Ampitrex (PH); Ampivral (CO); Ampliblan (CO); Ampolin (TW); Amsapen (MX); Ancillin (TW); Binotal (AT, BR, CO, EC, MX, UY); Biocil (MY); Bridopen (PH); Brupen (MX); Camicil (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW); Cilisod (TW); Citicil (IT); Clovillin (PH); Dhacillin (HK, MY); Dibacilina (MX); Doktacillin (SE); Duacillin (MY); Eurocin (PH); Excillin (PH); Extrapen (AE, BF, BH, BJ, CI, CY, EG, ET, GH, GM, GN, IL, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, OM, QA, SA, SC, SD, SL, SN, SY, TN, TZ, UG, YE, ZA, ZM, ZW); Flamicina (MX); Gramcil (PH); Ibimycin (AU); Intramed (ZA); Iwacillin (JP); Julphapen (PE); Magnapen (PE); Marovilina (MX); Maxipen (CO); Microcilin (PH); Omnipen (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, MX, OM, PE, QA, SA, SY, YE); Pamecil (BF, BJ, CI, ET, GH, GM, GN, HK, KE, LR, MA, ML, MR, MU, MW, MY, NE, NG, SC, SD, SG, SL, SN, TN, TZ, UG, ZA, ZM, ZW); Panacta (PH); Pelitin (TW); Penbritin (AE, BF, BH, BJ, CI, CY, EG, ET, GH, GM, GN, HK, IE, IL, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, MX, MY, NE, NG, OM, QA, SA, SC, SD, SL, SN, SY, TN, TZ, UG, YE, ZA, ZM, ZW); Penibrin (IL); Pentrexyl (BE, BF, BJ, CI, DK, ET, GB, GH, GM, GN, GR, IT, KE, LR, MA, ML, MR, MU, MW, MX, NE, NG, NL, NO, PE, SC, SD, SL, SN, TH, TN, TZ, UG, ZA, ZM, ZW); Petercillin (ZA); Picaplin (TW); Polypen (PH); Primapen (ID); Promecilina (MX); Radiocillina (AE, BF, BH, BJ, CI, CY, EG, ET, GH, GM, GN, IL, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, OM, QA, SA, SC, SD, SL, SN, SY, TN, TZ, UG, YE, ZA, ZM, ZW); Rimacillin (AE, BB, BF, BH, BJ, BM, BS, BZ, CI, CY, EG, ET, GH, GM, GN, GY, IL, IQ, IR, JM, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, NL, OM, QA, SA, SC, SD, SL, SN, SR, SY, TN, TT, TZ, UG, YE, ZA, ZM, ZW); Roscillin (IN); Sanpicillin (ID); Semicillin (HN); Shacillin (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Sintelin (PE); Standacillin (AE, BG, BH, CY, EE, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Standcillin (MY); Synthocilin (IN); Totapen (FR); Tricil (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW); Trifalicina (AR); Trilaxin (PH); Vacillin (TH); Viccillin (ID); Vidopen (GB, IE); Virucil (CO); Winpicillin (TW)

MECHANISM OF ACTION — Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs) which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested.

PHARMACODYNAMICS / KINETICS
Absorption: Oral: 50%

Distribution: Bile, blister, and tissue fluids; penetration into CSF occurs with inflamed meninges only, good only with inflammation (exceeds usual MICs)
Normal meninges: Nil; Inflamed meninges: 5% to 10%

Protein binding: 15% to 25%

Half-life elimination:
Children and Adults: 1-1.8 hours
Anuria/end-stage renal disease: 7-20 hours

Time to peak: Oral: Within 1-2 hours

Excretion: Urine (~90% as unchanged drug) within 24 hours

PATIENT INFORMATION — Report diarrhea promptly; take entire course of medication; females should report onset of symptoms of candidal vaginitis

Ampicillin

Amphotericin B lipid complex

MEDICATION SAFETY ISSUES
Safety issues:
Lipid-based amphotericin formulations (Abelcet®) may be confused with conventional formulations (Amphocin®, Fungizone®)
Large overdoses have occurred when conventional formulations were dispensed inadvertently for lipid-based products. Single daily doses of conventional amphotericin formulation never exceed 1.5 mg/kg.

High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.

U.S. BRAND NAMES — Abelcet®

PHARMACOLOGIC CATEGORY
Antifungal Agent, Parenteral

DOSING: ADULTS — Note: Premedication: For patients who experience infusion-related immediate reactions, premedicate with the following drugs 30-60 minutes prior to drug administration: A nonsteroidal anti-inflammatory agent +/- diphenhydramine or acetaminophen with diphenhydramine or hydrocortisone 50-100 mg. If the patient experiences rigors during the infusion, meperidine may be administered.

Usual dosage: I.V.: 2.5-5 mg/kg/day as a single infusion

DOSING: PEDIATRIC — Refer to adult dosing.

(For additional information see "Amphotericin B lipid complex: Pediatric drug information")

DOSING: ELDERLY — Refer to adult dosing.

DOSING: RENAL IMPAIRMENT — The effects of renal impairment on drug pharmacokinetics or pharmacodynamics are currently unknown. The dose of amphotericin B lipid complex may be adjusted or drug administration may have to be interrupted in patients with acute kidney dysfunction to reduce the magnitude of renal impairment.

Hemodialysis: Supplemental dose is not necessary.

Peritoneal dialysis: Supplemental dose is not necessary.

Continuous renal replacement therapy (CRRT): No supplemental dosage necessary

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Injection, suspension [preservative free]:
Abelcet®: 5 mg/mL (20 mL)

DOSAGE FORMS: CONCISE
Injection, suspension [preservative free]:
Abelcet®: 5 mg/mL (20 mL)

GENERIC EQUIVALENT AVAILABLE — No

ADMINISTRATION — For patients who experience nonanaphylactic infusion-related reactions, premedicate 30-60 minutes prior to drug administration with a nonsteroidal anti-inflammatory agent +/- diphenhydramine or acetaminophen with diphenhydramine or hydrocortisone 50-100 mg. If the patient experiences rigors during the infusion, meperidine may be administered.

Administer at an infusion rate of 2.5 mg/kg/hour (over 2 hours). Invert infusion container several times prior to administration and every 2 hours during infusion if it exceeds 2 hours.

COMPATIBILITY
Incompatible with any blood products, intravenous drugs, or intravenous fluids other than D5W when admixed or as Y-site administration.

USE — Treatment of aspergillosis or any type of progressive fungal infection in patients who are refractory to or intolerant of conventional amphotericin B therapy

USE - UNLABELED / INVESTIGATIONAL — Effective in patients with serious Candida species infections

ADVERSE REACTIONS SIGNIFICANT — Nephrotoxicity and infusion-related hyperpyrexia, rigor, and chilling are reduced relative to amphotericin deoxycholate.

>10%:
Central nervous system: Chills, fever
Renal: Serum creatinine increased
Miscellaneous: Multiple organ failure

1% to 10%:
Cardiovascular: Hypotension, cardiac arrest
Central nervous system: Headache, pain
Dermatologic: Rash
Endocrine & metabolic: Bilirubinemia, hypokalemia, acidosis
Gastrointestinal: Nausea, vomiting, diarrhea, gastrointestinal hemorrhage, abdominal pain
Renal: Renal failure
Respiratory: Respiratory failure, dyspnea, pneumonia

CONTRAINDICATIONS — Hypersensitivity to amphotericin or any component of the formulation

WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Anaphylaxis: Has been reported with amphotericin B-containing drugs; facilities for cardiopulmonary resuscitation should be available during administration due to the possibility of anaphylactic reaction. If severe respiratory distress occurs, the infusion should be immediately discontinued; during the initial dosing, the drug should be administered under close clinical observation. Infusion reactions: Acute reactions (including fever and chills) may occur 1-3 hours after starting an intravenous infusion. These reactions are usually more common with the first few doses and generally diminish with subsequent doses.

Special populations: Neutropenic patients: Pulmonary reactions may occur in neutropenic patients receiving leukocyte transfusions; separation of the infusions as much as possible is advised.

DRUG INTERACTIONS
Aminoglycosides: Amphotericin B may enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy

Antifungal Agents (Azole Derivatives, Systemic): May diminish the therapeutic effect of Amphotericin B. Risk C: Monitor therapy

Colistimethate: Amphotericin B may enhance the nephrotoxic effect of Colistimethate. Risk D: Consider therapy modification

Corticosteroids (Orally Inhaled): May enhance the hypokalemic effect of Amphotericin B. Risk C: Monitor therapy

Corticosteroids (Systemic): May enhance the hypokalemic effect of Amphotericin B. Risk C: Monitor therapy

CycloSPORINE: Amphotericin B may enhance the nephrotoxic effect of CycloSPORINE. Risk C: Monitor therapy

Flucytosine: Amphotericin B may enhance the adverse/toxic effect of Flucytosine. This may be related to the adverse effects of amphotericin B on renal function. Risk C: Monitor therapy

Gallium Nitrate: Amphotericin B may enhance the nephrotoxic effect of Gallium Nitrate. Risk X: Avoid combination

Saccharomyces boulardii: Antifungal Agents may diminish the therapeutic effect of Saccharomyces boulardii. Risk D: Consider therapy modification

PREGNANCY RISK FACTOR — B (show table)

LACTATION — Enters breast milk/contraindicated

BREAST-FEEDING CONSIDERATIONS — Due to limited data, consider discontinuing nursing during therapy.

MONITORING PARAMETERS — Renal function (monitor frequently during therapy), electrolytes (especially potassium and magnesium), liver function tests, temperature, PT/PTT, CBC; monitor input and output; monitor for signs of hypokalemia (muscle weakness, cramping, drowsiness, ECG changes, etc)

CANADIAN BRAND NAMES — Abelcet®; Amphotec®

INTERNATIONAL BRAND NAMES — Abelcet (AR, AT, BE, BR, CZ, DK, FI, FR, GB, GR, HN, IE, NL, NO, NZ, SE); Ambisome (AU, FR, HK, IL, KP); Ampholip (IN)

MECHANISM OF ACTION — Binds to ergosterol altering cell membrane permeability in susceptible fungi and causing leakage of cell components with subsequent cell death. Proposed mechanism suggests that amphotericin causes an oxidation-dependent stimulation of macrophages.

PHARMACODYNAMICS / KINETICS
Distribution: Vd: Increases with higher doses; reflects increased uptake by tissues (131 L/kg with 5 mg/kg/day)

Half-life elimination: ~24 hours

Excretion: Clearance: Increases with higher doses (5 mg/kg/day): 400 mL/hour/kg

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Monday, August 2, 2010