U.S. BRAND NAMES — Differin®
PHARMACOLOGIC CATEGORY Acne ProductsTopical Skin Product, Acne
DOSING: ADULTS — Acne: Topical: Apply once daily before bedtime; results appear after 8-12 weeks of therapy.
DOSING: PEDIATRIC — Children >12 years: Refer to adult dosing.
(For additional information see "Adapalene: Pediatric drug information")
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Cream, topical: 0.1% (15 g, 45 g)
Gel, topical: 0.1% (15 g, 45 g) [alcohol free]
Pledget, topical: 0.1% (60s) [DSC]
Solution, topical: 0.1% (30 mL) [DSC]
DOSAGE FORMS: CONCISE Cream, topical: Differin®: 0.1% (15 g, 45 g)
Gel, topical: Differin®: 0.1% (15 g, 45 g)
GENERIC EQUIVALENT AVAILABLE — No
USE — Treatment of acne vulgaris
ADVERSE REACTIONS SIGNIFICANT >10%: Dermatologic: Erythema, scaling, dryness, pruritus, burning, pruritus or burning immediately after application
<1% (Limited to important or life-threatening): Acne flares, conjunctivitis, contact dermatitis, dermatitis, eczema, eyelid edema, skin discoloration, skin irritation, stinging sunburn, rash (topical cream)
CONTRAINDICATIONS — Hypersensitivity to adapalene or any component in the vehicle gel
WARNINGS / PRECAUTIONS — Use with caution in patients with eczema. Avoid excessive exposure to sunlight and sunlamps. Avoid contact with abraded skin, mucous membranes, eyes, mouth, angles of the nose.
Certain cutaneous signs and symptoms such as erythema, dryness, scaling, burning, or pruritus may occur during treatment; these are most likely to occur during the first 2-4 weeks and will usually lessen with continued use.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — There are no adequate and well-controlled studies in pregnant women. Use only if benefit outweighs the potential risk to fetus.
LACTATION — Excretion in breast milk unknown/use caution
PRICING — (data from drugstore.com)Cream (Differin) 0.1% (45): $132.93
Gel (Differin) 0.1% (45): $117.28
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Toxic signs of an overdose commonly respond to drug discontinuation, and generally return to normal spontaneously within a few days to weeks. When confronted with signs of increased intracranial pressure, treatment with mannitol (0.25 g/kg I.V. up to 1 g/kg/dose repeated every 5 minutes as needed), dexamethasone (1.5 mg/kg I.V. load followed with 0.375 mg/kg every 6 hours for 5 days), and/or hyperventilation should be employed.
CANADIAN BRAND NAMES — Differin® XP; Differin®
INTERNATIONAL BRAND NAMES — Acure (HK, TW); Adaferin (CR, DO, GT, HN, IN, MX, NI, PA, SV); Adaferin Gel (IL); Differin (AR, AU, BR, CA, CL, EE, FI, HK, HU, KR, MY, NZ, PE, PH, PL, PY, SG, TH, TW, UY, VE, ZA); Differin Gel (AT, BE, CH, DE, GB, IE, IL, IT, SE); Differin XP (CA); Differine (ES, FR); Klenzit (PH); Panalene (AR); Redap (DK)
MECHANISM OF ACTION — Retinoid-like compound which is a modulator of cellular differentiation, keratinization, and inflammatory processes, all of which represent important features in the pathology of acne vulgaris
PHARMACODYNAMICS / KINETICS Absorption: Topical: Minimal
Excretion: Bile
PATIENT INFORMATION — Thoroughly wash hands after applying. Avoid hydration of skin immediately before application. Minimize exposure to sunlight. Avoid washing face more frequently than 2-3 times/day. If severe irritation occurs, discontinue medication temporarily and adjust dose when irritation subsides. Avoid using topical preparations with high alcoholic content during treatment period. Do not exceed prescribed dose.
Sunday, January 20, 2008
Adapalene
U.S. BRAND NAMES — Differin®
PHARMACOLOGIC CATEGORY Acne ProductsTopical Skin Product, Acne
DOSING: ADULTS — Acne: Topical: Apply once daily before bedtime; results appear after 8-12 weeks of therapy.
DOSING: PEDIATRIC — Children >12 years: Refer to adult dosing.
(For additional information see "Adapalene: Pediatric drug information")
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Cream, topical: 0.1% (15 g, 45 g)
Gel, topical: 0.1% (15 g, 45 g) [alcohol free]
Pledget, topical: 0.1% (60s) [DSC]
Solution, topical: 0.1% (30 mL) [DSC]
DOSAGE FORMS: CONCISE Cream, topical: Differin®: 0.1% (15 g, 45 g)
Gel, topical: Differin®: 0.1% (15 g, 45 g)
GENERIC EQUIVALENT AVAILABLE — No
USE — Treatment of acne vulgaris
ADVERSE REACTIONS SIGNIFICANT >10%: Dermatologic: Erythema, scaling, dryness, pruritus, burning, pruritus or burning immediately after application
<1% (Limited to important or life-threatening): Acne flares, conjunctivitis, contact dermatitis, dermatitis, eczema, eyelid edema, skin discoloration, skin irritation, stinging sunburn, rash (topical cream)
CONTRAINDICATIONS — Hypersensitivity to adapalene or any component in the vehicle gel
WARNINGS / PRECAUTIONS — Use with caution in patients with eczema. Avoid excessive exposure to sunlight and sunlamps. Avoid contact with abraded skin, mucous membranes, eyes, mouth, angles of the nose.
Certain cutaneous signs and symptoms such as erythema, dryness, scaling, burning, or pruritus may occur during treatment; these are most likely to occur during the first 2-4 weeks and will usually lessen with continued use.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — There are no adequate and well-controlled studies in pregnant women. Use only if benefit outweighs the potential risk to fetus.
LACTATION — Excretion in breast milk unknown/use caution
PRICING — (data from drugstore.com)Cream (Differin) 0.1% (45): $132.93
Gel (Differin) 0.1% (45): $117.28
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Toxic signs of an overdose commonly respond to drug discontinuation, and generally return to normal spontaneously within a few days to weeks. When confronted with signs of increased intracranial pressure, treatment with mannitol (0.25 g/kg I.V. up to 1 g/kg/dose repeated every 5 minutes as needed), dexamethasone (1.5 mg/kg I.V. load followed with 0.375 mg/kg every 6 hours for 5 days), and/or hyperventilation should be employed.
CANADIAN BRAND NAMES — Differin® XP; Differin®
INTERNATIONAL BRAND NAMES — Acure (HK, TW); Adaferin (CR, DO, GT, HN, IN, MX, NI, PA, SV); Adaferin Gel (IL); Differin (AR, AU, BR, CA, CL, EE, FI, HK, HU, KR, MY, NZ, PE, PH, PL, PY, SG, TH, TW, UY, VE, ZA); Differin Gel (AT, BE, CH, DE, GB, IE, IL, IT, SE); Differin XP (CA); Differine (ES, FR); Klenzit (PH); Panalene (AR); Redap (DK)
MECHANISM OF ACTION — Retinoid-like compound which is a modulator of cellular differentiation, keratinization, and inflammatory processes, all of which represent important features in the pathology of acne vulgaris
PHARMACODYNAMICS / KINETICS Absorption: Topical: Minimal
Excretion: Bile
PATIENT INFORMATION — Thoroughly wash hands after applying. Avoid hydration of skin immediately before application. Minimize exposure to sunlight. Avoid washing face more frequently than 2-3 times/day. If severe irritation occurs, discontinue medication temporarily and adjust dose when irritation subsides. Avoid using topical preparations with high alcoholic content during treatment period. Do not exceed prescribed dose.
PHARMACOLOGIC CATEGORY Acne ProductsTopical Skin Product, Acne
DOSING: ADULTS — Acne: Topical: Apply once daily before bedtime; results appear after 8-12 weeks of therapy.
DOSING: PEDIATRIC — Children >12 years: Refer to adult dosing.
(For additional information see "Adapalene: Pediatric drug information")
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Cream, topical: 0.1% (15 g, 45 g)
Gel, topical: 0.1% (15 g, 45 g) [alcohol free]
Pledget, topical: 0.1% (60s) [DSC]
Solution, topical: 0.1% (30 mL) [DSC]
DOSAGE FORMS: CONCISE Cream, topical: Differin®: 0.1% (15 g, 45 g)
Gel, topical: Differin®: 0.1% (15 g, 45 g)
GENERIC EQUIVALENT AVAILABLE — No
USE — Treatment of acne vulgaris
ADVERSE REACTIONS SIGNIFICANT >10%: Dermatologic: Erythema, scaling, dryness, pruritus, burning, pruritus or burning immediately after application
<1% (Limited to important or life-threatening): Acne flares, conjunctivitis, contact dermatitis, dermatitis, eczema, eyelid edema, skin discoloration, skin irritation, stinging sunburn, rash (topical cream)
CONTRAINDICATIONS — Hypersensitivity to adapalene or any component in the vehicle gel
WARNINGS / PRECAUTIONS — Use with caution in patients with eczema. Avoid excessive exposure to sunlight and sunlamps. Avoid contact with abraded skin, mucous membranes, eyes, mouth, angles of the nose.
Certain cutaneous signs and symptoms such as erythema, dryness, scaling, burning, or pruritus may occur during treatment; these are most likely to occur during the first 2-4 weeks and will usually lessen with continued use.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — There are no adequate and well-controlled studies in pregnant women. Use only if benefit outweighs the potential risk to fetus.
LACTATION — Excretion in breast milk unknown/use caution
PRICING — (data from drugstore.com)Cream (Differin) 0.1% (45): $132.93
Gel (Differin) 0.1% (45): $117.28
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Toxic signs of an overdose commonly respond to drug discontinuation, and generally return to normal spontaneously within a few days to weeks. When confronted with signs of increased intracranial pressure, treatment with mannitol (0.25 g/kg I.V. up to 1 g/kg/dose repeated every 5 minutes as needed), dexamethasone (1.5 mg/kg I.V. load followed with 0.375 mg/kg every 6 hours for 5 days), and/or hyperventilation should be employed.
CANADIAN BRAND NAMES — Differin® XP; Differin®
INTERNATIONAL BRAND NAMES — Acure (HK, TW); Adaferin (CR, DO, GT, HN, IN, MX, NI, PA, SV); Adaferin Gel (IL); Differin (AR, AU, BR, CA, CL, EE, FI, HK, HU, KR, MY, NZ, PE, PH, PL, PY, SG, TH, TW, UY, VE, ZA); Differin Gel (AT, BE, CH, DE, GB, IE, IL, IT, SE); Differin XP (CA); Differine (ES, FR); Klenzit (PH); Panalene (AR); Redap (DK)
MECHANISM OF ACTION — Retinoid-like compound which is a modulator of cellular differentiation, keratinization, and inflammatory processes, all of which represent important features in the pathology of acne vulgaris
PHARMACODYNAMICS / KINETICS Absorption: Topical: Minimal
Excretion: Bile
PATIENT INFORMATION — Thoroughly wash hands after applying. Avoid hydration of skin immediately before application. Minimize exposure to sunlight. Avoid washing face more frequently than 2-3 times/day. If severe irritation occurs, discontinue medication temporarily and adjust dose when irritation subsides. Avoid using topical preparations with high alcoholic content during treatment period. Do not exceed prescribed dose.
Adalimumab
U.S. BRAND NAMES — Humira®
PHARMACOLOGIC CATEGORY Antirheumatic, Disease ModifyingMonoclonal AntibodyTumor Necrosis Factor (TNF) Blocking Agent
DOSING: ADULTS Rheumatoid arthritis: SubQ: 40 mg every other week; may be administered with other DMARDs; patients not taking methotrexate may increase dose to 40 mg every week
Ankylosing spondylitis, psoriatic arthritis: SubQ: 40 mg every other week
Crohn's disease: Initial: 160 mg divided into 4 doses given on day 1 or over 2 days, then 80 mg at week 2; Maintenance: 40 mg every other week beginning at week 4
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution [preservative free]: Humira®: 40 mg/0.8 mL (1 mL) [prefilled glass syringe or Humira® pen; packaged with alcohol preps; needle cover contains latex]
DOSAGE FORMS: CONCISE Injection, solution [preservative free]: Humira®: 40 mg/0.8 mL (1 mL)
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — For SubQ injection; rotate injection sites. Do not use if solution is discolored. Do not administer to skin which is red, tender, bruised, or hard; rotate injection sites.
USE Treatment of active rheumatoid arthritis, active psoriatic arthritis (moderate-to-severe), or ankylosing spondylitis; may be used alone or in combination with disease-modifying antirheumatic drugs (DMARDs).
Treatment of moderate-to-severe active Crohn's disease which has inadequate response to conventional treatment, or which has lost response to or is intolerant of infliximab
ADVERSE REACTIONS SIGNIFICANT — Frequency > placebo in rheumatoid arthritis studies:
>10%: Central nervous system: Headache (12%) Dermatologic: Rash (12%) Local: Injection site reaction (12% to 20%; includes erythema, itching, hemorrhage, pain, swelling) Respiratory: Upper respiratory tract infection (17%), sinusitis (11%)
5% to 10%: Cardiovascular: Hypertension (5%) Endocrine & metabolic: Hyperlipidemia (7%), hypercholesterolemia (6%) Gastrointestinal: Nausea (9%), abdominal pain (7%) Genitourinary: Urinary tract infection (8%) Hepatic: Alkaline phosphatase increased (5%) Local: Injection site reaction (8%; other than erythema, itching, hemorrhage, pain, swelling) Neuromuscular & skeletal: Back pain (6%) Renal: Hematuria (5%) Miscellaneous: Accidental injury (10%), flu-like syndrome (7%)
<5%: Cardiovascular: Arrhythmia, atrial fibrillation, chest pain, CHF, coronary artery disorder, heart arrest, MI, palpitation, pericardial effusion, pericarditis, peripheral edema, syncope, tachycardia, thrombosis (leg), vascular disorder Central nervous system: Confusion, fever, hypertensive encephalopathy, multiple sclerosis, subdural hematoma Dermatologic: Cellulitis, erysipelas Endocrine & metabolic: Dehydration, menstrual disorder, parathyroid disorder Gastrointestinal: Diverticulitis, esophagitis, gastroenteritis, gastrointestinal hemorrhage, vomiting Genitourinary: Cystitis, pelvic pain Hematologic: Agranulocytosis, granulocytopenia, leukopenia, pancytopenia, paraproteinemia, polycythemia Hepatic: Cholecystitis, cholelithiasis, hepatic necrosis Neuromuscular & skeletal: Arthritis, bone fracture, bone necrosis, joint disorder, muscle cramps, myasthenia, pain in extremity, paresthesia, pyogenic arthritis, synovitis, tendon disorder, tremor Ocular: Cataract Renal: Kidney calculus, pyelonephritis Respiratory: Asthma, bronchospasm, dyspnea, lung function decreased, pleural effusion, pneumonia Miscellaneous: Adenoma, allergic reactions (1%), carcinoma (including breast, gastrointestinal, skin, urogenital), healing abnormality, herpes zoster, ketosis, lupus erythematosus syndrome, lymphoma, melanoma, postsurgical infection, sepsis, tuberculosis (reactivation of latent infection; miliary, lymphatic, peritoneal and pulmonary)
Postmarketing and/or case reports: Anaphylactoid reaction, anaphylaxis, angioneurotic edema, aplastic anemia, cutaneous vasculitis, cytopenia, fixed drug eruption, infections (viral, fungal and protozoal), interstitial lung disease (eg, pulmonary fibrosis), septic arthritis, thrombocytopenia, transaminases increased, urticaria
CONTRAINDICATIONS — Hypersensitivity to adalimumab or any component of the formulation
WARNINGS / PRECAUTIONS Box warnings: Fatal infections: See "Concerns related to adverse effects" below. Tuberculosis evaluation: See "Concerns related to adverse effects" below.
Concerns related to adverse effects: Anaphylaxis/hypersensitivity reactions: May cause hypersensitivity, anaphylaxis, or anaphylactoid reactions; medications for the treatment of hypersensitivity reactions should be available for immediate use. Autoimmune disorder: Positive antinuclear antibody titers have been detected in patients (with negative baselines). Rare cases of autoimmune disorder, including lupus-like syndrome, have been reported; monitor and discontinue if symptoms develop. Fatal infections: [U.S. Boxed Warning]: Serious and potential fatal infections (including invasive fungal and other opportunistic infections) have been reported in patients receiving TNF-blocking agents, including adalimumab. Many of the serious infections have occurred in patients on concomitant immunosuppressive therapy. Other opportunistic infections included Histoplasma, Aspergillus, and Nocardia. Use with caution in patients who have resided in regions where histoplasmosis is endemic. Caution should be exercised when considering the use in patients with chronic infection, history of recurrent infection, or predisposition to infection. Do not give to patients with an active chronic or localized infection. Patients who develop a new infection while undergoing treatment should be monitored closely. If a patient develops a serious infection, therapy should be discontinued. Hepatitis B: Rare reactivation of hepatitis B has occurred in chronic virus carriers; evaluate prior to initiation and during treatment. Malignancy: Use may affect defenses against malignancies; impact on the development and course of malignancies is not fully defined. As compared to the general population, an increased risk of lymphoma has been noted in clinical trials; however, rheumatoid arthritis has been previously associated with an increased rate of lymphoma. Pancytopenia: Rare cases of pancytopenia (including aplastic anemia) have been reported with TNF-blocking agents; with significant hematologic abnormalities, consider discontinuing therapy. Tuberculosis evaluation: Tuberculosis (disseminated or extrapulmonary) has been reactivated while on adalimumab; most cases have been reported within the first 8 months of treatment. [U.S. Boxed Warnings]: Patients should be evaluated for latent tuberculosis infection with a tuberculin skin test prior to therapy. Treatment of latent tuberculosis should be initiated before use. Patients with initial negative tuberculin skin tests should receive continued monitoring for tuberculosis throughout treatment; active tuberculosis has developed in this population during treatment.
Disease-related concerns: Congestive heart failure: Use with caution in patients with CHF or decreased left ventricular function; worsening and new-onset CHF has been reported. Demyelinating CNS disease: Use with caution in patients with pre-existing or recent onset CNS demyelinating disorders; rare cases of optic neuritis and demyelinating disease have been reported.
Special populations: Pediatrics: Safety and efficacy have not been established in children.
Dosage form specific issues: Latex: The packaging (needle cover) contains latex.
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 the effects of therapy on vaccination or secondary transmission of live vaccines in patients receiving therapy.
DRUG INTERACTIONS Abatacept: Concurrent use may increase the risk of infection; avoid concurrent use.
Abciximab: Allergic reactions may be increased in patients who have received diagnostic or therapeutic monoclonal antibodies due to the presence of HACA; may also cause thrombocytopenia or decreased therapeutic effect.
Anakinra: Concomitant use may increase risk of infections; not recommended.
Vaccines (killed organism or component): Adalimumab may decrease the effect of vaccines; monitor.
Vaccines (live organism): Adalimumab may increase the risk of vaccinal infection; avoid concurrent use.
ETHANOL / NUTRITION / HERB INTERACTIONS — Herb/nutraceutical: Echinacea may decrease the therapeutic effects of adalimumab; avoid concurrent use.
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Teratogenic effects were not observed in animal studies, however, there are no adequate and well-controlled studies in pregnant women. Use during pregnancy only if clearly needed. A pregnancy registry has been established to monitor outcomes of women exposed to adalimumab during pregnancy (877-311-8972).
LACTATION — Excretion in breast milk unknown/not recommended
BREAST-FEEDING CONSIDERATIONS — It is not known whether adalimumab is secreted in human milk. Because many immunoglobulins are secreted in milk and the potential for serious adverse reactions exists, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
PRICING — (data from drugstore.com)Kit (Humira) 40 mg/0.8 mL (2): $1415.88
MONITORING PARAMETERS — Place and read PPD before initiation. Monitor improvement of symptoms and physical function assessments; CBC; signs of infection, bleeding or bruising.
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Doses of up to 10 mg/kg have been tolerated in clinical trials. In case of overdose, treatment should be symptom-directed and supportive.
CANADIAN BRAND NAMES — Humira®
INTERNATIONAL BRAND NAMES — Humira (AE, AR, AT, AU, BE, BG, BH, CA, CH, CL, CO, CY, CZ, DE, DK, EG, ES, FI, FR, GB, GR, HK, HU, IE, IL, IQ, IR, IT, JO, KW, LB, LY, MX, NL, NO, NZ, OM, PE, PT, PY, QA, RU, SA, SE, SG, SY, TR, UY, YE); Trudexa (AT, BE, BG, CH, CZ, DE, DK, ES, FI, FR, GB, GR, HU, IE, IT, NL, NO, PT, RU, SE, TR)
MECHANISM OF ACTION — Adalimumab is a recombinant monoclonal antibody that binds to human tumor necrosis factor alpha (TNF-alpha), thereby interfering with binding to TNFalpha receptor sites and subsequent cytokine-driven inflammatory processes. Elevated TNF levels in the synovial fluid are involved in the pathologic pain and joint destruction in immune-mediated arthritis. Adalimumab decreases signs and symptoms of psoriatic arthritis, rheumatoid arthritis, and ankylosing spondylitis. It inhibits progression of structural damage of rheumatoid and psoriatic arthritis.
PHARMACODYNAMICS / KINETICS Distribution: Vd: 4.7-6 L; Synovial fluid concentrations: 31% to 96% of serum
Bioavailability: Absolute: 64%
Half-life elimination: Terminal: ~2 weeks (range 10-20 days)
Time to peak, serum: SubQ: 131 +/- 56 hours
Excretion: Clearance increased in the presence of antiadalimumab antibodies; decreased in patients 40 years and older
PATIENT INFORMATION — May cause headache, nausea, or stomach pain. Notify prescriber of any signs of infection.
PHARMACOLOGIC CATEGORY Antirheumatic, Disease ModifyingMonoclonal AntibodyTumor Necrosis Factor (TNF) Blocking Agent
DOSING: ADULTS Rheumatoid arthritis: SubQ: 40 mg every other week; may be administered with other DMARDs; patients not taking methotrexate may increase dose to 40 mg every week
Ankylosing spondylitis, psoriatic arthritis: SubQ: 40 mg every other week
Crohn's disease: Initial: 160 mg divided into 4 doses given on day 1 or over 2 days, then 80 mg at week 2; Maintenance: 40 mg every other week beginning at week 4
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution [preservative free]: Humira®: 40 mg/0.8 mL (1 mL) [prefilled glass syringe or Humira® pen; packaged with alcohol preps; needle cover contains latex]
DOSAGE FORMS: CONCISE Injection, solution [preservative free]: Humira®: 40 mg/0.8 mL (1 mL)
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — For SubQ injection; rotate injection sites. Do not use if solution is discolored. Do not administer to skin which is red, tender, bruised, or hard; rotate injection sites.
USE Treatment of active rheumatoid arthritis, active psoriatic arthritis (moderate-to-severe), or ankylosing spondylitis; may be used alone or in combination with disease-modifying antirheumatic drugs (DMARDs).
Treatment of moderate-to-severe active Crohn's disease which has inadequate response to conventional treatment, or which has lost response to or is intolerant of infliximab
ADVERSE REACTIONS SIGNIFICANT — Frequency > placebo in rheumatoid arthritis studies:
>10%: Central nervous system: Headache (12%) Dermatologic: Rash (12%) Local: Injection site reaction (12% to 20%; includes erythema, itching, hemorrhage, pain, swelling) Respiratory: Upper respiratory tract infection (17%), sinusitis (11%)
5% to 10%: Cardiovascular: Hypertension (5%) Endocrine & metabolic: Hyperlipidemia (7%), hypercholesterolemia (6%) Gastrointestinal: Nausea (9%), abdominal pain (7%) Genitourinary: Urinary tract infection (8%) Hepatic: Alkaline phosphatase increased (5%) Local: Injection site reaction (8%; other than erythema, itching, hemorrhage, pain, swelling) Neuromuscular & skeletal: Back pain (6%) Renal: Hematuria (5%) Miscellaneous: Accidental injury (10%), flu-like syndrome (7%)
<5%: Cardiovascular: Arrhythmia, atrial fibrillation, chest pain, CHF, coronary artery disorder, heart arrest, MI, palpitation, pericardial effusion, pericarditis, peripheral edema, syncope, tachycardia, thrombosis (leg), vascular disorder Central nervous system: Confusion, fever, hypertensive encephalopathy, multiple sclerosis, subdural hematoma Dermatologic: Cellulitis, erysipelas Endocrine & metabolic: Dehydration, menstrual disorder, parathyroid disorder Gastrointestinal: Diverticulitis, esophagitis, gastroenteritis, gastrointestinal hemorrhage, vomiting Genitourinary: Cystitis, pelvic pain Hematologic: Agranulocytosis, granulocytopenia, leukopenia, pancytopenia, paraproteinemia, polycythemia Hepatic: Cholecystitis, cholelithiasis, hepatic necrosis Neuromuscular & skeletal: Arthritis, bone fracture, bone necrosis, joint disorder, muscle cramps, myasthenia, pain in extremity, paresthesia, pyogenic arthritis, synovitis, tendon disorder, tremor Ocular: Cataract Renal: Kidney calculus, pyelonephritis Respiratory: Asthma, bronchospasm, dyspnea, lung function decreased, pleural effusion, pneumonia Miscellaneous: Adenoma, allergic reactions (1%), carcinoma (including breast, gastrointestinal, skin, urogenital), healing abnormality, herpes zoster, ketosis, lupus erythematosus syndrome, lymphoma, melanoma, postsurgical infection, sepsis, tuberculosis (reactivation of latent infection; miliary, lymphatic, peritoneal and pulmonary)
Postmarketing and/or case reports: Anaphylactoid reaction, anaphylaxis, angioneurotic edema, aplastic anemia, cutaneous vasculitis, cytopenia, fixed drug eruption, infections (viral, fungal and protozoal), interstitial lung disease (eg, pulmonary fibrosis), septic arthritis, thrombocytopenia, transaminases increased, urticaria
CONTRAINDICATIONS — Hypersensitivity to adalimumab or any component of the formulation
WARNINGS / PRECAUTIONS Box warnings: Fatal infections: See "Concerns related to adverse effects" below. Tuberculosis evaluation: See "Concerns related to adverse effects" below.
Concerns related to adverse effects: Anaphylaxis/hypersensitivity reactions: May cause hypersensitivity, anaphylaxis, or anaphylactoid reactions; medications for the treatment of hypersensitivity reactions should be available for immediate use. Autoimmune disorder: Positive antinuclear antibody titers have been detected in patients (with negative baselines). Rare cases of autoimmune disorder, including lupus-like syndrome, have been reported; monitor and discontinue if symptoms develop. Fatal infections: [U.S. Boxed Warning]: Serious and potential fatal infections (including invasive fungal and other opportunistic infections) have been reported in patients receiving TNF-blocking agents, including adalimumab. Many of the serious infections have occurred in patients on concomitant immunosuppressive therapy. Other opportunistic infections included Histoplasma, Aspergillus, and Nocardia. Use with caution in patients who have resided in regions where histoplasmosis is endemic. Caution should be exercised when considering the use in patients with chronic infection, history of recurrent infection, or predisposition to infection. Do not give to patients with an active chronic or localized infection. Patients who develop a new infection while undergoing treatment should be monitored closely. If a patient develops a serious infection, therapy should be discontinued. Hepatitis B: Rare reactivation of hepatitis B has occurred in chronic virus carriers; evaluate prior to initiation and during treatment. Malignancy: Use may affect defenses against malignancies; impact on the development and course of malignancies is not fully defined. As compared to the general population, an increased risk of lymphoma has been noted in clinical trials; however, rheumatoid arthritis has been previously associated with an increased rate of lymphoma. Pancytopenia: Rare cases of pancytopenia (including aplastic anemia) have been reported with TNF-blocking agents; with significant hematologic abnormalities, consider discontinuing therapy. Tuberculosis evaluation: Tuberculosis (disseminated or extrapulmonary) has been reactivated while on adalimumab; most cases have been reported within the first 8 months of treatment. [U.S. Boxed Warnings]: Patients should be evaluated for latent tuberculosis infection with a tuberculin skin test prior to therapy. Treatment of latent tuberculosis should be initiated before use. Patients with initial negative tuberculin skin tests should receive continued monitoring for tuberculosis throughout treatment; active tuberculosis has developed in this population during treatment.
Disease-related concerns: Congestive heart failure: Use with caution in patients with CHF or decreased left ventricular function; worsening and new-onset CHF has been reported. Demyelinating CNS disease: Use with caution in patients with pre-existing or recent onset CNS demyelinating disorders; rare cases of optic neuritis and demyelinating disease have been reported.
Special populations: Pediatrics: Safety and efficacy have not been established in children.
Dosage form specific issues: Latex: The packaging (needle cover) contains latex.
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 the effects of therapy on vaccination or secondary transmission of live vaccines in patients receiving therapy.
DRUG INTERACTIONS Abatacept: Concurrent use may increase the risk of infection; avoid concurrent use.
Abciximab: Allergic reactions may be increased in patients who have received diagnostic or therapeutic monoclonal antibodies due to the presence of HACA; may also cause thrombocytopenia or decreased therapeutic effect.
Anakinra: Concomitant use may increase risk of infections; not recommended.
Vaccines (killed organism or component): Adalimumab may decrease the effect of vaccines; monitor.
Vaccines (live organism): Adalimumab may increase the risk of vaccinal infection; avoid concurrent use.
ETHANOL / NUTRITION / HERB INTERACTIONS — Herb/nutraceutical: Echinacea may decrease the therapeutic effects of adalimumab; avoid concurrent use.
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Teratogenic effects were not observed in animal studies, however, there are no adequate and well-controlled studies in pregnant women. Use during pregnancy only if clearly needed. A pregnancy registry has been established to monitor outcomes of women exposed to adalimumab during pregnancy (877-311-8972).
LACTATION — Excretion in breast milk unknown/not recommended
BREAST-FEEDING CONSIDERATIONS — It is not known whether adalimumab is secreted in human milk. Because many immunoglobulins are secreted in milk and the potential for serious adverse reactions exists, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
PRICING — (data from drugstore.com)Kit (Humira) 40 mg/0.8 mL (2): $1415.88
MONITORING PARAMETERS — Place and read PPD before initiation. Monitor improvement of symptoms and physical function assessments; CBC; signs of infection, bleeding or bruising.
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Doses of up to 10 mg/kg have been tolerated in clinical trials. In case of overdose, treatment should be symptom-directed and supportive.
CANADIAN BRAND NAMES — Humira®
INTERNATIONAL BRAND NAMES — Humira (AE, AR, AT, AU, BE, BG, BH, CA, CH, CL, CO, CY, CZ, DE, DK, EG, ES, FI, FR, GB, GR, HK, HU, IE, IL, IQ, IR, IT, JO, KW, LB, LY, MX, NL, NO, NZ, OM, PE, PT, PY, QA, RU, SA, SE, SG, SY, TR, UY, YE); Trudexa (AT, BE, BG, CH, CZ, DE, DK, ES, FI, FR, GB, GR, HU, IE, IT, NL, NO, PT, RU, SE, TR)
MECHANISM OF ACTION — Adalimumab is a recombinant monoclonal antibody that binds to human tumor necrosis factor alpha (TNF-alpha), thereby interfering with binding to TNFalpha receptor sites and subsequent cytokine-driven inflammatory processes. Elevated TNF levels in the synovial fluid are involved in the pathologic pain and joint destruction in immune-mediated arthritis. Adalimumab decreases signs and symptoms of psoriatic arthritis, rheumatoid arthritis, and ankylosing spondylitis. It inhibits progression of structural damage of rheumatoid and psoriatic arthritis.
PHARMACODYNAMICS / KINETICS Distribution: Vd: 4.7-6 L; Synovial fluid concentrations: 31% to 96% of serum
Bioavailability: Absolute: 64%
Half-life elimination: Terminal: ~2 weeks (range 10-20 days)
Time to peak, serum: SubQ: 131 +/- 56 hours
Excretion: Clearance increased in the presence of antiadalimumab antibodies; decreased in patients 40 years and older
PATIENT INFORMATION — May cause headache, nausea, or stomach pain. Notify prescriber of any signs of infection.
Adalimumab
U.S. BRAND NAMES — Humira®
PHARMACOLOGIC CATEGORY Antirheumatic, Disease ModifyingMonoclonal AntibodyTumor Necrosis Factor (TNF) Blocking Agent
DOSING: ADULTS Rheumatoid arthritis: SubQ: 40 mg every other week; may be administered with other DMARDs; patients not taking methotrexate may increase dose to 40 mg every week
Ankylosing spondylitis, psoriatic arthritis: SubQ: 40 mg every other week
Crohn's disease: Initial: 160 mg divided into 4 doses given on day 1 or over 2 days, then 80 mg at week 2; Maintenance: 40 mg every other week beginning at week 4
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution [preservative free]: Humira®: 40 mg/0.8 mL (1 mL) [prefilled glass syringe or Humira® pen; packaged with alcohol preps; needle cover contains latex]
DOSAGE FORMS: CONCISE Injection, solution [preservative free]: Humira®: 40 mg/0.8 mL (1 mL)
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — For SubQ injection; rotate injection sites. Do not use if solution is discolored. Do not administer to skin which is red, tender, bruised, or hard; rotate injection sites.
USE Treatment of active rheumatoid arthritis, active psoriatic arthritis (moderate-to-severe), or ankylosing spondylitis; may be used alone or in combination with disease-modifying antirheumatic drugs (DMARDs).
Treatment of moderate-to-severe active Crohn's disease which has inadequate response to conventional treatment, or which has lost response to or is intolerant of infliximab
ADVERSE REACTIONS SIGNIFICANT — Frequency > placebo in rheumatoid arthritis studies:
>10%: Central nervous system: Headache (12%) Dermatologic: Rash (12%) Local: Injection site reaction (12% to 20%; includes erythema, itching, hemorrhage, pain, swelling) Respiratory: Upper respiratory tract infection (17%), sinusitis (11%)
5% to 10%: Cardiovascular: Hypertension (5%) Endocrine & metabolic: Hyperlipidemia (7%), hypercholesterolemia (6%) Gastrointestinal: Nausea (9%), abdominal pain (7%) Genitourinary: Urinary tract infection (8%) Hepatic: Alkaline phosphatase increased (5%) Local: Injection site reaction (8%; other than erythema, itching, hemorrhage, pain, swelling) Neuromuscular & skeletal: Back pain (6%) Renal: Hematuria (5%) Miscellaneous: Accidental injury (10%), flu-like syndrome (7%)
<5%: Cardiovascular: Arrhythmia, atrial fibrillation, chest pain, CHF, coronary artery disorder, heart arrest, MI, palpitation, pericardial effusion, pericarditis, peripheral edema, syncope, tachycardia, thrombosis (leg), vascular disorder Central nervous system: Confusion, fever, hypertensive encephalopathy, multiple sclerosis, subdural hematoma Dermatologic: Cellulitis, erysipelas Endocrine & metabolic: Dehydration, menstrual disorder, parathyroid disorder Gastrointestinal: Diverticulitis, esophagitis, gastroenteritis, gastrointestinal hemorrhage, vomiting Genitourinary: Cystitis, pelvic pain Hematologic: Agranulocytosis, granulocytopenia, leukopenia, pancytopenia, paraproteinemia, polycythemia Hepatic: Cholecystitis, cholelithiasis, hepatic necrosis Neuromuscular & skeletal: Arthritis, bone fracture, bone necrosis, joint disorder, muscle cramps, myasthenia, pain in extremity, paresthesia, pyogenic arthritis, synovitis, tendon disorder, tremor Ocular: Cataract Renal: Kidney calculus, pyelonephritis Respiratory: Asthma, bronchospasm, dyspnea, lung function decreased, pleural effusion, pneumonia Miscellaneous: Adenoma, allergic reactions (1%), carcinoma (including breast, gastrointestinal, skin, urogenital), healing abnormality, herpes zoster, ketosis, lupus erythematosus syndrome, lymphoma, melanoma, postsurgical infection, sepsis, tuberculosis (reactivation of latent infection; miliary, lymphatic, peritoneal and pulmonary)
Postmarketing and/or case reports: Anaphylactoid reaction, anaphylaxis, angioneurotic edema, aplastic anemia, cutaneous vasculitis, cytopenia, fixed drug eruption, infections (viral, fungal and protozoal), interstitial lung disease (eg, pulmonary fibrosis), septic arthritis, thrombocytopenia, transaminases increased, urticaria
CONTRAINDICATIONS — Hypersensitivity to adalimumab or any component of the formulation
WARNINGS / PRECAUTIONS Box warnings: Fatal infections: See "Concerns related to adverse effects" below. Tuberculosis evaluation: See "Concerns related to adverse effects" below.
Concerns related to adverse effects: Anaphylaxis/hypersensitivity reactions: May cause hypersensitivity, anaphylaxis, or anaphylactoid reactions; medications for the treatment of hypersensitivity reactions should be available for immediate use. Autoimmune disorder: Positive antinuclear antibody titers have been detected in patients (with negative baselines). Rare cases of autoimmune disorder, including lupus-like syndrome, have been reported; monitor and discontinue if symptoms develop. Fatal infections: [U.S. Boxed Warning]: Serious and potential fatal infections (including invasive fungal and other opportunistic infections) have been reported in patients receiving TNF-blocking agents, including adalimumab. Many of the serious infections have occurred in patients on concomitant immunosuppressive therapy. Other opportunistic infections included Histoplasma, Aspergillus, and Nocardia. Use with caution in patients who have resided in regions where histoplasmosis is endemic. Caution should be exercised when considering the use in patients with chronic infection, history of recurrent infection, or predisposition to infection. Do not give to patients with an active chronic or localized infection. Patients who develop a new infection while undergoing treatment should be monitored closely. If a patient develops a serious infection, therapy should be discontinued. Hepatitis B: Rare reactivation of hepatitis B has occurred in chronic virus carriers; evaluate prior to initiation and during treatment. Malignancy: Use may affect defenses against malignancies; impact on the development and course of malignancies is not fully defined. As compared to the general population, an increased risk of lymphoma has been noted in clinical trials; however, rheumatoid arthritis has been previously associated with an increased rate of lymphoma. Pancytopenia: Rare cases of pancytopenia (including aplastic anemia) have been reported with TNF-blocking agents; with significant hematologic abnormalities, consider discontinuing therapy. Tuberculosis evaluation: Tuberculosis (disseminated or extrapulmonary) has been reactivated while on adalimumab; most cases have been reported within the first 8 months of treatment. [U.S. Boxed Warnings]: Patients should be evaluated for latent tuberculosis infection with a tuberculin skin test prior to therapy. Treatment of latent tuberculosis should be initiated before use. Patients with initial negative tuberculin skin tests should receive continued monitoring for tuberculosis throughout treatment; active tuberculosis has developed in this population during treatment.
Disease-related concerns: Congestive heart failure: Use with caution in patients with CHF or decreased left ventricular function; worsening and new-onset CHF has been reported. Demyelinating CNS disease: Use with caution in patients with pre-existing or recent onset CNS demyelinating disorders; rare cases of optic neuritis and demyelinating disease have been reported.
Special populations: Pediatrics: Safety and efficacy have not been established in children.
Dosage form specific issues: Latex: The packaging (needle cover) contains latex.
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 the effects of therapy on vaccination or secondary transmission of live vaccines in patients receiving therapy.
DRUG INTERACTIONS Abatacept: Concurrent use may increase the risk of infection; avoid concurrent use.
Abciximab: Allergic reactions may be increased in patients who have received diagnostic or therapeutic monoclonal antibodies due to the presence of HACA; may also cause thrombocytopenia or decreased therapeutic effect.
Anakinra: Concomitant use may increase risk of infections; not recommended.
Vaccines (killed organism or component): Adalimumab may decrease the effect of vaccines; monitor.
Vaccines (live organism): Adalimumab may increase the risk of vaccinal infection; avoid concurrent use.
ETHANOL / NUTRITION / HERB INTERACTIONS — Herb/nutraceutical: Echinacea may decrease the therapeutic effects of adalimumab; avoid concurrent use.
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Teratogenic effects were not observed in animal studies, however, there are no adequate and well-controlled studies in pregnant women. Use during pregnancy only if clearly needed. A pregnancy registry has been established to monitor outcomes of women exposed to adalimumab during pregnancy (877-311-8972).
LACTATION — Excretion in breast milk unknown/not recommended
BREAST-FEEDING CONSIDERATIONS — It is not known whether adalimumab is secreted in human milk. Because many immunoglobulins are secreted in milk and the potential for serious adverse reactions exists, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
PRICING — (data from drugstore.com)Kit (Humira) 40 mg/0.8 mL (2): $1415.88
MONITORING PARAMETERS — Place and read PPD before initiation. Monitor improvement of symptoms and physical function assessments; CBC; signs of infection, bleeding or bruising.
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Doses of up to 10 mg/kg have been tolerated in clinical trials. In case of overdose, treatment should be symptom-directed and supportive.
CANADIAN BRAND NAMES — Humira®
INTERNATIONAL BRAND NAMES — Humira (AE, AR, AT, AU, BE, BG, BH, CA, CH, CL, CO, CY, CZ, DE, DK, EG, ES, FI, FR, GB, GR, HK, HU, IE, IL, IQ, IR, IT, JO, KW, LB, LY, MX, NL, NO, NZ, OM, PE, PT, PY, QA, RU, SA, SE, SG, SY, TR, UY, YE); Trudexa (AT, BE, BG, CH, CZ, DE, DK, ES, FI, FR, GB, GR, HU, IE, IT, NL, NO, PT, RU, SE, TR)
MECHANISM OF ACTION — Adalimumab is a recombinant monoclonal antibody that binds to human tumor necrosis factor alpha (TNF-alpha), thereby interfering with binding to TNFalpha receptor sites and subsequent cytokine-driven inflammatory processes. Elevated TNF levels in the synovial fluid are involved in the pathologic pain and joint destruction in immune-mediated arthritis. Adalimumab decreases signs and symptoms of psoriatic arthritis, rheumatoid arthritis, and ankylosing spondylitis. It inhibits progression of structural damage of rheumatoid and psoriatic arthritis.
PHARMACODYNAMICS / KINETICS Distribution: Vd: 4.7-6 L; Synovial fluid concentrations: 31% to 96% of serum
Bioavailability: Absolute: 64%
Half-life elimination: Terminal: ~2 weeks (range 10-20 days)
Time to peak, serum: SubQ: 131 +/- 56 hours
Excretion: Clearance increased in the presence of antiadalimumab antibodies; decreased in patients 40 years and older
PATIENT INFORMATION — May cause headache, nausea, or stomach pain. Notify prescriber of any signs of infection.
PHARMACOLOGIC CATEGORY Antirheumatic, Disease ModifyingMonoclonal AntibodyTumor Necrosis Factor (TNF) Blocking Agent
DOSING: ADULTS Rheumatoid arthritis: SubQ: 40 mg every other week; may be administered with other DMARDs; patients not taking methotrexate may increase dose to 40 mg every week
Ankylosing spondylitis, psoriatic arthritis: SubQ: 40 mg every other week
Crohn's disease: Initial: 160 mg divided into 4 doses given on day 1 or over 2 days, then 80 mg at week 2; Maintenance: 40 mg every other week beginning at week 4
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution [preservative free]: Humira®: 40 mg/0.8 mL (1 mL) [prefilled glass syringe or Humira® pen; packaged with alcohol preps; needle cover contains latex]
DOSAGE FORMS: CONCISE Injection, solution [preservative free]: Humira®: 40 mg/0.8 mL (1 mL)
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — For SubQ injection; rotate injection sites. Do not use if solution is discolored. Do not administer to skin which is red, tender, bruised, or hard; rotate injection sites.
USE Treatment of active rheumatoid arthritis, active psoriatic arthritis (moderate-to-severe), or ankylosing spondylitis; may be used alone or in combination with disease-modifying antirheumatic drugs (DMARDs).
Treatment of moderate-to-severe active Crohn's disease which has inadequate response to conventional treatment, or which has lost response to or is intolerant of infliximab
ADVERSE REACTIONS SIGNIFICANT — Frequency > placebo in rheumatoid arthritis studies:
>10%: Central nervous system: Headache (12%) Dermatologic: Rash (12%) Local: Injection site reaction (12% to 20%; includes erythema, itching, hemorrhage, pain, swelling) Respiratory: Upper respiratory tract infection (17%), sinusitis (11%)
5% to 10%: Cardiovascular: Hypertension (5%) Endocrine & metabolic: Hyperlipidemia (7%), hypercholesterolemia (6%) Gastrointestinal: Nausea (9%), abdominal pain (7%) Genitourinary: Urinary tract infection (8%) Hepatic: Alkaline phosphatase increased (5%) Local: Injection site reaction (8%; other than erythema, itching, hemorrhage, pain, swelling) Neuromuscular & skeletal: Back pain (6%) Renal: Hematuria (5%) Miscellaneous: Accidental injury (10%), flu-like syndrome (7%)
<5%: Cardiovascular: Arrhythmia, atrial fibrillation, chest pain, CHF, coronary artery disorder, heart arrest, MI, palpitation, pericardial effusion, pericarditis, peripheral edema, syncope, tachycardia, thrombosis (leg), vascular disorder Central nervous system: Confusion, fever, hypertensive encephalopathy, multiple sclerosis, subdural hematoma Dermatologic: Cellulitis, erysipelas Endocrine & metabolic: Dehydration, menstrual disorder, parathyroid disorder Gastrointestinal: Diverticulitis, esophagitis, gastroenteritis, gastrointestinal hemorrhage, vomiting Genitourinary: Cystitis, pelvic pain Hematologic: Agranulocytosis, granulocytopenia, leukopenia, pancytopenia, paraproteinemia, polycythemia Hepatic: Cholecystitis, cholelithiasis, hepatic necrosis Neuromuscular & skeletal: Arthritis, bone fracture, bone necrosis, joint disorder, muscle cramps, myasthenia, pain in extremity, paresthesia, pyogenic arthritis, synovitis, tendon disorder, tremor Ocular: Cataract Renal: Kidney calculus, pyelonephritis Respiratory: Asthma, bronchospasm, dyspnea, lung function decreased, pleural effusion, pneumonia Miscellaneous: Adenoma, allergic reactions (1%), carcinoma (including breast, gastrointestinal, skin, urogenital), healing abnormality, herpes zoster, ketosis, lupus erythematosus syndrome, lymphoma, melanoma, postsurgical infection, sepsis, tuberculosis (reactivation of latent infection; miliary, lymphatic, peritoneal and pulmonary)
Postmarketing and/or case reports: Anaphylactoid reaction, anaphylaxis, angioneurotic edema, aplastic anemia, cutaneous vasculitis, cytopenia, fixed drug eruption, infections (viral, fungal and protozoal), interstitial lung disease (eg, pulmonary fibrosis), septic arthritis, thrombocytopenia, transaminases increased, urticaria
CONTRAINDICATIONS — Hypersensitivity to adalimumab or any component of the formulation
WARNINGS / PRECAUTIONS Box warnings: Fatal infections: See "Concerns related to adverse effects" below. Tuberculosis evaluation: See "Concerns related to adverse effects" below.
Concerns related to adverse effects: Anaphylaxis/hypersensitivity reactions: May cause hypersensitivity, anaphylaxis, or anaphylactoid reactions; medications for the treatment of hypersensitivity reactions should be available for immediate use. Autoimmune disorder: Positive antinuclear antibody titers have been detected in patients (with negative baselines). Rare cases of autoimmune disorder, including lupus-like syndrome, have been reported; monitor and discontinue if symptoms develop. Fatal infections: [U.S. Boxed Warning]: Serious and potential fatal infections (including invasive fungal and other opportunistic infections) have been reported in patients receiving TNF-blocking agents, including adalimumab. Many of the serious infections have occurred in patients on concomitant immunosuppressive therapy. Other opportunistic infections included Histoplasma, Aspergillus, and Nocardia. Use with caution in patients who have resided in regions where histoplasmosis is endemic. Caution should be exercised when considering the use in patients with chronic infection, history of recurrent infection, or predisposition to infection. Do not give to patients with an active chronic or localized infection. Patients who develop a new infection while undergoing treatment should be monitored closely. If a patient develops a serious infection, therapy should be discontinued. Hepatitis B: Rare reactivation of hepatitis B has occurred in chronic virus carriers; evaluate prior to initiation and during treatment. Malignancy: Use may affect defenses against malignancies; impact on the development and course of malignancies is not fully defined. As compared to the general population, an increased risk of lymphoma has been noted in clinical trials; however, rheumatoid arthritis has been previously associated with an increased rate of lymphoma. Pancytopenia: Rare cases of pancytopenia (including aplastic anemia) have been reported with TNF-blocking agents; with significant hematologic abnormalities, consider discontinuing therapy. Tuberculosis evaluation: Tuberculosis (disseminated or extrapulmonary) has been reactivated while on adalimumab; most cases have been reported within the first 8 months of treatment. [U.S. Boxed Warnings]: Patients should be evaluated for latent tuberculosis infection with a tuberculin skin test prior to therapy. Treatment of latent tuberculosis should be initiated before use. Patients with initial negative tuberculin skin tests should receive continued monitoring for tuberculosis throughout treatment; active tuberculosis has developed in this population during treatment.
Disease-related concerns: Congestive heart failure: Use with caution in patients with CHF or decreased left ventricular function; worsening and new-onset CHF has been reported. Demyelinating CNS disease: Use with caution in patients with pre-existing or recent onset CNS demyelinating disorders; rare cases of optic neuritis and demyelinating disease have been reported.
Special populations: Pediatrics: Safety and efficacy have not been established in children.
Dosage form specific issues: Latex: The packaging (needle cover) contains latex.
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 the effects of therapy on vaccination or secondary transmission of live vaccines in patients receiving therapy.
DRUG INTERACTIONS Abatacept: Concurrent use may increase the risk of infection; avoid concurrent use.
Abciximab: Allergic reactions may be increased in patients who have received diagnostic or therapeutic monoclonal antibodies due to the presence of HACA; may also cause thrombocytopenia or decreased therapeutic effect.
Anakinra: Concomitant use may increase risk of infections; not recommended.
Vaccines (killed organism or component): Adalimumab may decrease the effect of vaccines; monitor.
Vaccines (live organism): Adalimumab may increase the risk of vaccinal infection; avoid concurrent use.
ETHANOL / NUTRITION / HERB INTERACTIONS — Herb/nutraceutical: Echinacea may decrease the therapeutic effects of adalimumab; avoid concurrent use.
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Teratogenic effects were not observed in animal studies, however, there are no adequate and well-controlled studies in pregnant women. Use during pregnancy only if clearly needed. A pregnancy registry has been established to monitor outcomes of women exposed to adalimumab during pregnancy (877-311-8972).
LACTATION — Excretion in breast milk unknown/not recommended
BREAST-FEEDING CONSIDERATIONS — It is not known whether adalimumab is secreted in human milk. Because many immunoglobulins are secreted in milk and the potential for serious adverse reactions exists, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
PRICING — (data from drugstore.com)Kit (Humira) 40 mg/0.8 mL (2): $1415.88
MONITORING PARAMETERS — Place and read PPD before initiation. Monitor improvement of symptoms and physical function assessments; CBC; signs of infection, bleeding or bruising.
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Doses of up to 10 mg/kg have been tolerated in clinical trials. In case of overdose, treatment should be symptom-directed and supportive.
CANADIAN BRAND NAMES — Humira®
INTERNATIONAL BRAND NAMES — Humira (AE, AR, AT, AU, BE, BG, BH, CA, CH, CL, CO, CY, CZ, DE, DK, EG, ES, FI, FR, GB, GR, HK, HU, IE, IL, IQ, IR, IT, JO, KW, LB, LY, MX, NL, NO, NZ, OM, PE, PT, PY, QA, RU, SA, SE, SG, SY, TR, UY, YE); Trudexa (AT, BE, BG, CH, CZ, DE, DK, ES, FI, FR, GB, GR, HU, IE, IT, NL, NO, PT, RU, SE, TR)
MECHANISM OF ACTION — Adalimumab is a recombinant monoclonal antibody that binds to human tumor necrosis factor alpha (TNF-alpha), thereby interfering with binding to TNFalpha receptor sites and subsequent cytokine-driven inflammatory processes. Elevated TNF levels in the synovial fluid are involved in the pathologic pain and joint destruction in immune-mediated arthritis. Adalimumab decreases signs and symptoms of psoriatic arthritis, rheumatoid arthritis, and ankylosing spondylitis. It inhibits progression of structural damage of rheumatoid and psoriatic arthritis.
PHARMACODYNAMICS / KINETICS Distribution: Vd: 4.7-6 L; Synovial fluid concentrations: 31% to 96% of serum
Bioavailability: Absolute: 64%
Half-life elimination: Terminal: ~2 weeks (range 10-20 days)
Time to peak, serum: SubQ: 131 +/- 56 hours
Excretion: Clearance increased in the presence of antiadalimumab antibodies; decreased in patients 40 years and older
PATIENT INFORMATION — May cause headache, nausea, or stomach pain. Notify prescriber of any signs of infection.
Acyclovir
U.S. BRAND NAMES — Zovirax®
PHARMACOLOGIC CATEGORY Antiviral Agent
DOSING: ADULTS — Note: Obese patients should be dosed using ideal body weight
Genital HSV: I.V.: Immunocompetent: Initial episode, severe: 5 mg/kg every 8 hours for 5-7 days Oral: Initial episode: 200 mg every 4 hours while awake (5 times/day) for 10 days (per manufacturer's labeling); 400 mg 3 times/day for 5-10 days has also been reported Recurrence: 200 mg every 4 hours while awake (5 times/day) for 5 days (per manufacturer's labeling; begin at earliest signs of disease); 400 mg 3 times/day for 5 days has also been reported Chronic suppression: 400 mg twice daily or 200 mg 3-5 times/day, for up to 12 months followed by re-evaluation (per manufacturer's labeling); 400-1200 mg/day in 2-3 divided doses has also been reported Topical: Immunocompromised: Ointment: Initial episode: 1/2" ribbon of ointment for a 4" square surface area every 3 hours (6 times/day) for 7 days
Herpes labialis (cold sores): Topical: Apply 5 times/day for 4 days
Herpes zoster (shingles): Oral: Immunocompetent: 800 mg every 4 hours (5 times/day) for 7-10 days I.V.: Immunocompromised: 10 mg/kg/dose or 500 mg/m2/dose every 8 hours for 7 days
HSV encephalitis: I.V.: 10 mg/kg/dose every 8 hours for 10 days (per manufacturer's labeling); 10-15 mg/kg/dose every 8 hours for 14-21 days also reported
Mucocutaneous HSV: I.V.: Immunocompromised: 5 mg/kg/dose every 8 hours for 7 days (per manufacturer's labeling); dosing for up to 14 days also reported Oral: Immunocompromised (unlabeled use): 400 mg 5 times a day for 7-14 days Topical: Ointment: Nonlife-threatening, immunocompromised: 1/2" ribbon of ointment for a 4" square surface area every 3 hours (6 times/day) for 7 days
Varicella-zoster (chickenpox): Begin treatment within the first 24 hours of rash onset: Oral: >40 kg (immunocompetent): 800 mg/dose 4 times a day for 5 days I.V.: Immunocompromised (unlabeled use): 1500 mg/m2/day divided every 8 hours or 10 mg/kg/dose every 8 hours for 7-10 days
Prevention of HSV reactivation in HIV-positive patients, for use only when recurrences are frequent or severe (unlabeled use): Oral: 200 mg 3 times/day or 400 mg 2 times/day
Prevention of HSV reactivation in HSCT (unlabeled use): Note: Start at the beginning of conditioning therapy and continue until engraftment or until mucositis resolves (~30 days) Oral: 200 mg 3 times/day I.V.: 250 mg/m2/dose every 12 hours
Bone marrow transplant recipients (unlabeled use): I.V.: Allogeneic patients who are HSV and CMV seropositive: 500 mg/m2/dose (10 mg/kg) every 8 hours; for clinically-symptomatic CMV infection, consider replacing acyclovir with ganciclovir
DOSING: PEDIATRIC — Note: Obese patients should be dosed using ideal body weight
(For additional information see "Acyclovir: Pediatric drug information")
Genital HSV: I.V.: Children 12 years: Refer to adult dosing. Oral: Initial episode (unlabeled use): 40-80 mg/kg/day divided into 3-4 doses for 5-10 days (maximum: 1 g/day) Chronic suppression (unlabeled use; limited data): 80 mg/kg/day in 3 divided doses (maximum: 1 g/day), re-evaluate after 12 months of treatment
Herpes labialis (cold sores): Topical: Children 12 years: Refer to adult dosing.
Herpes zoster (shingles): I.V.: Children <12 years (immunocompromised): 20 mg/kg/dose every 8 hours for 7 days Children 12 years: Refer to adult dosing.
HSV encephalitis: I.V.: Children 3 months to 12 years: 20 mg/kg/dose every 8 hours for 10 days (per manufacturer's labeling); dosing for 14-21 days also reported Children 12 years: Refer to adult dosing.
Mucocutaneous HSV: I.V.: Children <12 years (immunocompromised): 10 mg/kg/dose every 8 hours for 7 days Children 12 years: Refer to adult dosing.
Neonatal HSV: I.V.: Neonate: Birth to 3 months: 10 mg/kg/dose every 8 hours for 10 days (manufacturer's labeling); 15 mg/kg/dose or 20 mg/kg/dose every 8 hours for 14-21 days has also been reported
Varicella-zoster (chickenpox): Begin treatment within the first 24 hours of rash onset: Oral: Children 2 years and 40 kg (immunocompetent): 20 mg/kg/dose (up to 800 mg/dose) 4 times/day for 5 days Children >40 kg: Refer to adult dosing. I.V.: Children <1 year (immunocompromised, unlabeled use): 10 mg/kg/dose every 8 hours for 7-10 days Children 1 year: Refer to adult dosing.
Prevention of HSV reactivation in HIV-positive patients, for use only when recurrences are frequent or severe (unlabeled use): Oral: 80 mg/kg/day in 3-4 divided doses
Prevention of HSV reactivation in HSCT (unlabeled use): Note: Start at the beginning of conditioning therapy and continue until engraftment or until mucositis resolves (~30 days): I.V.: 250 mg/m2/dose every 8 hours or 125 mg/m2/dose every 6 hours
Bone marrow transplant recipients (unlabeled use): I.V.: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT Oral: Clcr 10-25 mL/minute/1.73 m2: Normal dosing regimen 800 mg every 4 hours: Administer 800 mg every 8 hours Clcr <10 mL/minute/1.73 m2: Normal dosing regimen 200 mg every 4 hours, 200 mg every 8 hours, or 400 mg every 12 hours: Administer 200 mg every 12 hours Normal dosing regimen 800 mg every 4 hours: Administer 800 mg every 12 hours
I.V.: Clcr 25-50 mL/minute/1.73 m2: Administer recommended dose every 12 hours Clcr 10-25 mL/minute/1.73 m2: Administer recommended dose every 24 hours Clcr <10 mL/minute/1.73 m2: Administer 50% of recommended dose every 24 hours
Hemodialysis: Administer dose after dialysis
Peritoneal dialysis: No supplemental dose needed
CAVH: 3.5 mg/kg/day
CVVHD/CVVH: Adjust dose based upon Clcr 30 mL/minute
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule: 200 mg Zovirax®: 200 mg
Cream, topical: Zovirax®: 5% (2 g, 5 g)
Injection, powder for reconstitution, as sodium: 500 mg, 1000 mg Zovirax®: 500 mg [DSC]
Injection, solution, as sodium [preservative free]: 25 mg/mL (20 mL, 40 mL); 50 mg/mL (10 mL, 20 mL)
Ointment, topical: Zovirax®: 5% (15 g)
Suspension, oral: 200 mg/5 mL (480 mL) Zovirax®: 200 mg/5 mL (480 mL) [banana flavor]
Tablet: 400 mg, 800 mg Zovirax®: 400 mg, 800 mg
DOSAGE FORMS: CONCISE Capsule: 200 mg Zovirax®: 200 mg
Cream, topical: Zovirax®: 5% (2 g, 5 g)
Injection, powder for reconstitution: 500 mg, 1000 mg
Injection, solution [preservative free]: 25 mg/mL (20 mL, 40 mL); 50 mg/mL (10 mL, 20 mL)
Ointment, topical: Zovirax®: 5% (15 g)
Suspension, oral: 200 mg/5 mL Zovirax®: 200 mg/5 mL
Tablet: 400 mg, 800 mg Zovirax®: 400 mg, 800 mg
GENERIC EQUIVALENT AVAILABLE — Yes: Excludes cream, ointment
ADMINISTRATION Oral: May be administered with or without food.
I.V.: Avoid rapid infusion; infuse over 1 hour to prevent renal damage; maintain adequate hydration of patient; check for phlebitis and rotate infusion sites
Topical: Not for use in the eye. Apply using a finger cot or rubber glove to avoid transmission to other parts of the body or to other persons.
COMPATIBILITY — Stable in D5W, D5NS, D51/4NS, D51/2NS, LR, NS.
Incompatible with blood products and protein-containing solutions.
Y-site administration: Compatible: Allopurinol, amikacin, amphotericin B cholesteryl sulfate complex, ampicillin, cefamandole, cefazolin, cefoperazone, cefotaxime, cefoxitin, ceftazidime, ceftizoxime, ceftriaxone, cefuroxime, chloramphenicol, cimetidine, clindamycin, co-trimoxazole, dexamethasone, dimenhydrinate, diphenhydramine, docetaxel, doxorubicin liposome, doxycycline, erythromycin lactobionate, etoposide, famotidine, filgrastim, fluconazole, gatifloxacin, gentamicin, granisetron, heparin, hydrocortisone sodium succinate, hydromorphone, imipenem/cilastatin, linezolid, lorazepam, magnesium sulfate, melphalan, methylprednisolone sodium succinate, metoclopramide, metronidazole, multivitamins, nafcillin, oxacillin, paclitaxel, penicillin G potassium, pentobarbital, perphenazine, piperacillin, potassium chloride, propofol, ranitidine, remifentanil, sodium bicarbonate, tacrolimus, teniposide, theophylline, thiotepa, ticarcillin, tobramycin, vancomycin, zidovudine. Incompatible: Amifostine, amsacrine, aztreonam, cefepime, dobutamine, dopamine, fludarabine, foscarnet, gemcitabine, idarubicin, levofloxacin, ondansetron, piperacillin/tazobactam, sargramostim, vinorelbine. Variable (consult detailed reference): Cisatracurium, diltiazem, meperidine, meropenem, morphine, TPN.
Compatibility when admixed: Compatible: Fluconazole. Incompatible: Dobutamine, dopamine. Variable (consult detailed reference): Meropenem.
USE — Treatment of genital herpes simplex virus (HSV), herpes labialis (cold sores), herpes zoster (shingles), HSV encephalitis, neonatal HSV, mucocutaneous HSV in immunocompromised patients, varicella-zoster (chickenpox)
USE - UNLABELED / INVESTIGATIONAL — Prevention of HSV reactivation in HIV-positive patients; prevention of HSV reactivation in hematopoietic stem-cell transplant (HSCT); prevention of HSV reactivation during periods of neutropenia in patients with acute leukemia
ADVERSE REACTIONS SIGNIFICANT Systemic: Oral:
>10%: Central nervous system: Malaise (12%)
1% to 10%: Central nervous system: Headache (2%) Gastrointestinal: Nausea (2% to 5%), vomiting (3%), diarrhea (2% to 3%)
Systemic: Parenteral:
1% to 10%: Dermatologic: Hives (2%), itching (2%), rash (2%) Gastrointestinal: Nausea/vomiting (7%) Hepatic: Liver function tests increased (1% to 2%) Local: Inflammation at injection site or phlebitis (9%) Renal: BUN increased (5% to 10%), creatinine increased (5% to 10%), acute renal failure
Topical:
>10%: Dermatologic: Mild pain, burning, or stinging (ointment 30%)
1% to 10%: Dermatologic: Pruritus (ointment 4%), itching
All forms: <1% (Limited to important or life-threatening): Abdominal pain, aggression, agitation, alopecia, anaphylaxis, anemia, angioedema, anorexia, ataxia, coma, confusion, consciousness decreased, delirium, desquamation, diarrhea, disseminated intravascular coagulopathy (DIC), dizziness, dry lips, dysarthria, encephalopathy, erythema multiforme, fatigue, fever, gastrointestinal distress, hallucinations, hematuria, hemolysis, hepatitis, hyperbilirubinemia, hypotension, insomnia, jaundice, leukocytoclastic vasculitis, leukocytosis, leukopenia, local tissue necrosis (following extravasation), lymphadenopathy, mental depression, myalgia, neutrophilia, paresthesia, peripheral edema, photosensitization, pruritus, psychosis, renal failure, seizure, somnolence, sore throat, Stevens-Johnson syndrome, thrombocytopenia, thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), thrombocytosis, toxic epidermal necrolysis, tremor, urticaria, visual disturbances
CONTRAINDICATIONS — Hypersensitivity to acyclovir, valacyclovir, or any component of the formulation
WARNINGS / PRECAUTIONS — Use with caution in immunocompromised patients; thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) has been reported. Use caution in the elderly, pre-existing renal disease, or in those receiving other nephrotoxic drugs. Maintain adequate hydration during oral or intravenous therapy. Use I.V. preparation with caution in patients with underlying neurologic abnormalities, serious hepatic or electrolyte abnormalities, or substantial hypoxia.
Safety and efficacy of oral formulations have not been established in pediatric patients <2 years of age.
Chickenpox: Treatment should begin within 24 hours of appearance of rash; oral route not recommended for routine use in otherwise healthy children with varicella, but may be effective in patients at increased risk of moderate to severe infection (>12 years of age, chronic cutaneous or pulmonary disorders, long-term salicylate therapy, corticosteroid therapy).
Genital herpes: Physical contact should be avoided when lesions are present; transmission may also occur in the absence of symptoms. Treatment should begin with the first signs or symptoms.
Herpes labialis: For external use only to the lips and face; do not apply to eye or inside the mouth or nose. Treatment should begin with the first signs or symptoms.
Herpes zoster: Acyclovir should be started within 72 hours of appearance of rash to be effective.
ETHANOL / NUTRITION / HERB INTERACTIONS — Food: Does not affect absorption of oral acyclovir.
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Teratogenic effects were not observed in animal studies. Acyclovir has been shown to cross the human placenta. There are no adequate and well-controlled studies in pregnant women. Results from a pregnancy registry, established in 1984 and closed in 1999, did not find an increase in the number of birth defects with exposure to acyclovir when compared to those expected in the general population. However, due to the small size of the registry and lack of long-term data, the manufacturer recommends using during pregnancy with caution and only when clearly needed. Data from the pregnancy registry may be obtained from GlaxoSmithKline.
LACTATION — Enters breast milk/use with caution (AAP rates "compatible")
BREAST-FEEDING CONSIDERATIONS — Nursing mothers with herpetic lesions near or on the breast should avoid breast-feeding. Limited data suggest exposure to the nursing infant of ~0.3 mg/kg/day following oral administration of acyclovir to the mother.
DIETARY CONSIDERATIONS — May be taken with or without food. Acyclovir 500 mg injection contains sodium ~50 mg (~2 mEq).
PRICING — (data from drugstore.com)Capsules (Acyclovir) 200 mg (30): $12.99
Capsules (Zovirax) 200 mg (30): $66.50
Cream (Zovirax) 5% (2): $42.53 5% (5): $94.81
Ointment (Zovirax) 5% (15): $105.18
Suspension (Acyclovir) 200 mg/5 mL (473): $82.68
Suspension (Zovirax) 200 mg/5 mL (473): $183.41
Tablets (Acyclovir) 400 mg (60): $28.99 800 mg (30): $24.99
Tablets (Zovirax) 400 mg (60): $242.78 800 mg (30): $236.13
MONITORING PARAMETERS — Urinalysis, BUN, serum creatinine, liver enzymes, CBC
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Overdoses of up to 20 g have been reported. Symptoms of overdose include agitation, seizures, somnolence, confusion, elevated serum creatinine, and renal failure. In the event of overdose, sufficient urine flow must be maintained to avoid drug precipitation within renal tubules. Hemodialysis has resulted in up to 60% reduction in serum acyclovir levels.
CANADIAN BRAND NAMES — Apo-Acyclovir®; Gen-Acyclovir; Nu-Acyclovir; ratio-Acyclovir; Zovirax®
INTERNATIONAL BRAND NAMES — Abbovir (PL); ACERPES (DE); Acic Creme (DE); Acicloftal (IT); Aciclor (VE); Aciclosina (PE); Aciclovir (PL); Aciclovir-BC IV (AU); Acihexal (AU); Acivir Cream (IL, IN); Acivir Eye (IN); Acix (PL); Aclova (KR); Aclovir (HR, TH, TW); Aclovirax (HK); ACS (KR); Activir (FR); Acyclo-V (AU, BH); Acyclostad (PL); Acyclovir (PL); Acyclovir Stada (PL); Acyklowir (PL); Acylene (MY); Acyrova (KR); Acyvir (EC, HK, IT); Aias (KR); Antivir (PL); Apicol (CO); Apo-Acyclovir (CA, PL); Avorax (HK, MY, SG); Avorax Cream (MY); Awirol (PL); Azovir (ID); Bearax (SG); Cicloferon (MX); Cicloviral (CO); Clinovir (ID, TH); Clovicin (TW); Clovir (BR); Cloviran (CL); Colsor (TH); Cusiviral (ES, HK, MY, PL, SG); Cyclivex (ZA); Cyclomed (IL); Cyclorax (HK); Cyclostad (PH); Cyclovir (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TZ, UG, ZM, ZW); Cyllanvir (PH); Danovir (SG); Deherp (TH, TW); Dravyr (SG); Duvimex (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Entir (SG, TH); Erlvirax (SG); Euroclovir (HK); Eurovir (PY); Exavir (BR); Expit (UY); Gen-Acyclovir (CA); Hascovir (PL); Herpefug (DE); Herpesin (PL); Herpex (BH, IN, PL); Herpoviric (DE); Herpoviric Rp Creme (DE); Heviran (PL); Inmerax (CL); Juviral (DE); Laciken (MX); Lermex (TH); Libravir (EC); Lisovyr (AR, CL); Lovir (AU, HK, MY, NZ, SG); Lovire (ZA); Marvir (TH); Matrovir (ID); Maynor (ES); Medovir (AE, BF, BG, BH, BJ, CI, CY, EG, ET, GH, GM, GN, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, MY, NE, NG, OM, QA, SA, SC, SD, SG, SL, SN, SY, TZ, UG, YE, ZM, ZW); Nevirz (ID); Norum (TH); Nu-Acyclovir (CA); Olvit (MX); Oppvir (TH, TW); Opthavir (MX); Poviral (EC); Proviral (AR); Qualiclovir (HK); Quavir (ID); Ranvir (TH); Ranviran (PL); ratio-Acyclovir (CA); Skirax (TW); Supra-Vir (IL); Supraviran (DE, PL); Supraviran Creme (AE, BH, CY, DE, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Syntovir (HK); Vacrax (MY); Vermis (TH); Vicorax (TH, TW); Viraban (NZ); Viracir (PL); Viralex-DS (PH); Virax (KR); Vircella (ID); Virest (MY, SG); Virex (CO); Virless (CN, TW); Viroclear (HK); Virogon (TH); Virolan (TW); Virolex (HR, PL); Viromed (TH); Virucid (HK); Virules (HK); Vivir (KR); Warviron (HK); Zetavir (MX); Zeven Cream (MY); Zevin (HK, TH); Zoral (HK, SG); Zoral Cream (MY); Zorax (SG); Zorel (ID); Zoter (ID); Zovir (DK); Zovirax [tabs./susp./ungt.] (PL); Zovirax (AE, AN, AR, AT, AU, BB, BD, BE, BF, BG, BH, BJ, BM, BO, BR, BS, BZ, CA, CH, CI, CL, CN, CR, CY, CZ, DE, DK, DO, EG, ES, ET, FI, FR, GB, GH, GM, GN, GR, GT, GY, HK, HN, HR, HU, ID, IE, IL, IN, IQ, IR, IT, JM, JO, JP, KE, KR, KW, LB, LR, LY, MA, ML, MR, MU, MW, MX, MY, NE, NG, NI, NL, NO, NZ, OM, PA, PE, PH, PK, PR, PT, PY, QA, RU, SA, SC, SD, SE, SL, SN, SR, SV, SY, TR, TT, TW, TZ, UG, UY, YE, ZA, ZM, ZW); Zumasid (ID); Zyclir (AU); Zyclorax (ID); Zyvir (KE)
MECHANISM OF ACTION — Acyclovir is converted to acyclovir monophosphate by virus-specific thymidine kinase then further converted to acyclovir triphosphate by other cellular enzymes. Acyclovir triphosphate inhibits DNA synthesis and viral replication by competing with deoxyguanosine triphosphate for viral DNA polymerase and being incorporated into viral DNA.
PHARMACODYNAMICS / KINETICS Absorption: Oral: 15% to 30%
Distribution: Vd: 0.8 L/kg (63.6 L): Widely (eg, brain, kidney, lungs, liver, spleen, muscle, uterus, vagina, CSF)
Protein binding: 9% to 33%
Metabolism: Converted by viral enzymes to acyclovir monophosphate, and further converted to diphosphate then triphosphate (active form) by cellular enzymes
Bioavailability: Oral: 10% to 20% with normal renal function (bioavailability decreases with increased dose)
Half-life elimination: Terminal: Neonates: 4 hours; Children 1-12 years: 2-3 hours; Adults: 3 hours
Time to peak, serum: Oral: Within 1.5-2 hours
Excretion: Urine (62% to 90% as unchanged drug and metabolite)
PATIENT INFORMATION — This is not a cure for herpes (recurrences tend to continually reappear every 3-6 months after original infection), nor will this medication reduce the risk of transmission to others when lesions are present; avoid sexual intercourse when visible lesions are present. Take as directed for full course of therapy; do not discontinue even if feeling better. Oral doses may be taken with food.
PHARMACOLOGIC CATEGORY Antiviral Agent
DOSING: ADULTS — Note: Obese patients should be dosed using ideal body weight
Genital HSV: I.V.: Immunocompetent: Initial episode, severe: 5 mg/kg every 8 hours for 5-7 days Oral: Initial episode: 200 mg every 4 hours while awake (5 times/day) for 10 days (per manufacturer's labeling); 400 mg 3 times/day for 5-10 days has also been reported Recurrence: 200 mg every 4 hours while awake (5 times/day) for 5 days (per manufacturer's labeling; begin at earliest signs of disease); 400 mg 3 times/day for 5 days has also been reported Chronic suppression: 400 mg twice daily or 200 mg 3-5 times/day, for up to 12 months followed by re-evaluation (per manufacturer's labeling); 400-1200 mg/day in 2-3 divided doses has also been reported Topical: Immunocompromised: Ointment: Initial episode: 1/2" ribbon of ointment for a 4" square surface area every 3 hours (6 times/day) for 7 days
Herpes labialis (cold sores): Topical: Apply 5 times/day for 4 days
Herpes zoster (shingles): Oral: Immunocompetent: 800 mg every 4 hours (5 times/day) for 7-10 days I.V.: Immunocompromised: 10 mg/kg/dose or 500 mg/m2/dose every 8 hours for 7 days
HSV encephalitis: I.V.: 10 mg/kg/dose every 8 hours for 10 days (per manufacturer's labeling); 10-15 mg/kg/dose every 8 hours for 14-21 days also reported
Mucocutaneous HSV: I.V.: Immunocompromised: 5 mg/kg/dose every 8 hours for 7 days (per manufacturer's labeling); dosing for up to 14 days also reported Oral: Immunocompromised (unlabeled use): 400 mg 5 times a day for 7-14 days Topical: Ointment: Nonlife-threatening, immunocompromised: 1/2" ribbon of ointment for a 4" square surface area every 3 hours (6 times/day) for 7 days
Varicella-zoster (chickenpox): Begin treatment within the first 24 hours of rash onset: Oral: >40 kg (immunocompetent): 800 mg/dose 4 times a day for 5 days I.V.: Immunocompromised (unlabeled use): 1500 mg/m2/day divided every 8 hours or 10 mg/kg/dose every 8 hours for 7-10 days
Prevention of HSV reactivation in HIV-positive patients, for use only when recurrences are frequent or severe (unlabeled use): Oral: 200 mg 3 times/day or 400 mg 2 times/day
Prevention of HSV reactivation in HSCT (unlabeled use): Note: Start at the beginning of conditioning therapy and continue until engraftment or until mucositis resolves (~30 days) Oral: 200 mg 3 times/day I.V.: 250 mg/m2/dose every 12 hours
Bone marrow transplant recipients (unlabeled use): I.V.: Allogeneic patients who are HSV and CMV seropositive: 500 mg/m2/dose (10 mg/kg) every 8 hours; for clinically-symptomatic CMV infection, consider replacing acyclovir with ganciclovir
DOSING: PEDIATRIC — Note: Obese patients should be dosed using ideal body weight
(For additional information see "Acyclovir: Pediatric drug information")
Genital HSV: I.V.: Children 12 years: Refer to adult dosing. Oral: Initial episode (unlabeled use): 40-80 mg/kg/day divided into 3-4 doses for 5-10 days (maximum: 1 g/day) Chronic suppression (unlabeled use; limited data): 80 mg/kg/day in 3 divided doses (maximum: 1 g/day), re-evaluate after 12 months of treatment
Herpes labialis (cold sores): Topical: Children 12 years: Refer to adult dosing.
Herpes zoster (shingles): I.V.: Children <12 years (immunocompromised): 20 mg/kg/dose every 8 hours for 7 days Children 12 years: Refer to adult dosing.
HSV encephalitis: I.V.: Children 3 months to 12 years: 20 mg/kg/dose every 8 hours for 10 days (per manufacturer's labeling); dosing for 14-21 days also reported Children 12 years: Refer to adult dosing.
Mucocutaneous HSV: I.V.: Children <12 years (immunocompromised): 10 mg/kg/dose every 8 hours for 7 days Children 12 years: Refer to adult dosing.
Neonatal HSV: I.V.: Neonate: Birth to 3 months: 10 mg/kg/dose every 8 hours for 10 days (manufacturer's labeling); 15 mg/kg/dose or 20 mg/kg/dose every 8 hours for 14-21 days has also been reported
Varicella-zoster (chickenpox): Begin treatment within the first 24 hours of rash onset: Oral: Children 2 years and 40 kg (immunocompetent): 20 mg/kg/dose (up to 800 mg/dose) 4 times/day for 5 days Children >40 kg: Refer to adult dosing. I.V.: Children <1 year (immunocompromised, unlabeled use): 10 mg/kg/dose every 8 hours for 7-10 days Children 1 year: Refer to adult dosing.
Prevention of HSV reactivation in HIV-positive patients, for use only when recurrences are frequent or severe (unlabeled use): Oral: 80 mg/kg/day in 3-4 divided doses
Prevention of HSV reactivation in HSCT (unlabeled use): Note: Start at the beginning of conditioning therapy and continue until engraftment or until mucositis resolves (~30 days): I.V.: 250 mg/m2/dose every 8 hours or 125 mg/m2/dose every 6 hours
Bone marrow transplant recipients (unlabeled use): I.V.: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT Oral: Clcr 10-25 mL/minute/1.73 m2: Normal dosing regimen 800 mg every 4 hours: Administer 800 mg every 8 hours Clcr <10 mL/minute/1.73 m2: Normal dosing regimen 200 mg every 4 hours, 200 mg every 8 hours, or 400 mg every 12 hours: Administer 200 mg every 12 hours Normal dosing regimen 800 mg every 4 hours: Administer 800 mg every 12 hours
I.V.: Clcr 25-50 mL/minute/1.73 m2: Administer recommended dose every 12 hours Clcr 10-25 mL/minute/1.73 m2: Administer recommended dose every 24 hours Clcr <10 mL/minute/1.73 m2: Administer 50% of recommended dose every 24 hours
Hemodialysis: Administer dose after dialysis
Peritoneal dialysis: No supplemental dose needed
CAVH: 3.5 mg/kg/day
CVVHD/CVVH: Adjust dose based upon Clcr 30 mL/minute
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule: 200 mg Zovirax®: 200 mg
Cream, topical: Zovirax®: 5% (2 g, 5 g)
Injection, powder for reconstitution, as sodium: 500 mg, 1000 mg Zovirax®: 500 mg [DSC]
Injection, solution, as sodium [preservative free]: 25 mg/mL (20 mL, 40 mL); 50 mg/mL (10 mL, 20 mL)
Ointment, topical: Zovirax®: 5% (15 g)
Suspension, oral: 200 mg/5 mL (480 mL) Zovirax®: 200 mg/5 mL (480 mL) [banana flavor]
Tablet: 400 mg, 800 mg Zovirax®: 400 mg, 800 mg
DOSAGE FORMS: CONCISE Capsule: 200 mg Zovirax®: 200 mg
Cream, topical: Zovirax®: 5% (2 g, 5 g)
Injection, powder for reconstitution: 500 mg, 1000 mg
Injection, solution [preservative free]: 25 mg/mL (20 mL, 40 mL); 50 mg/mL (10 mL, 20 mL)
Ointment, topical: Zovirax®: 5% (15 g)
Suspension, oral: 200 mg/5 mL Zovirax®: 200 mg/5 mL
Tablet: 400 mg, 800 mg Zovirax®: 400 mg, 800 mg
GENERIC EQUIVALENT AVAILABLE — Yes: Excludes cream, ointment
ADMINISTRATION Oral: May be administered with or without food.
I.V.: Avoid rapid infusion; infuse over 1 hour to prevent renal damage; maintain adequate hydration of patient; check for phlebitis and rotate infusion sites
Topical: Not for use in the eye. Apply using a finger cot or rubber glove to avoid transmission to other parts of the body or to other persons.
COMPATIBILITY — Stable in D5W, D5NS, D51/4NS, D51/2NS, LR, NS.
Incompatible with blood products and protein-containing solutions.
Y-site administration: Compatible: Allopurinol, amikacin, amphotericin B cholesteryl sulfate complex, ampicillin, cefamandole, cefazolin, cefoperazone, cefotaxime, cefoxitin, ceftazidime, ceftizoxime, ceftriaxone, cefuroxime, chloramphenicol, cimetidine, clindamycin, co-trimoxazole, dexamethasone, dimenhydrinate, diphenhydramine, docetaxel, doxorubicin liposome, doxycycline, erythromycin lactobionate, etoposide, famotidine, filgrastim, fluconazole, gatifloxacin, gentamicin, granisetron, heparin, hydrocortisone sodium succinate, hydromorphone, imipenem/cilastatin, linezolid, lorazepam, magnesium sulfate, melphalan, methylprednisolone sodium succinate, metoclopramide, metronidazole, multivitamins, nafcillin, oxacillin, paclitaxel, penicillin G potassium, pentobarbital, perphenazine, piperacillin, potassium chloride, propofol, ranitidine, remifentanil, sodium bicarbonate, tacrolimus, teniposide, theophylline, thiotepa, ticarcillin, tobramycin, vancomycin, zidovudine. Incompatible: Amifostine, amsacrine, aztreonam, cefepime, dobutamine, dopamine, fludarabine, foscarnet, gemcitabine, idarubicin, levofloxacin, ondansetron, piperacillin/tazobactam, sargramostim, vinorelbine. Variable (consult detailed reference): Cisatracurium, diltiazem, meperidine, meropenem, morphine, TPN.
Compatibility when admixed: Compatible: Fluconazole. Incompatible: Dobutamine, dopamine. Variable (consult detailed reference): Meropenem.
USE — Treatment of genital herpes simplex virus (HSV), herpes labialis (cold sores), herpes zoster (shingles), HSV encephalitis, neonatal HSV, mucocutaneous HSV in immunocompromised patients, varicella-zoster (chickenpox)
USE - UNLABELED / INVESTIGATIONAL — Prevention of HSV reactivation in HIV-positive patients; prevention of HSV reactivation in hematopoietic stem-cell transplant (HSCT); prevention of HSV reactivation during periods of neutropenia in patients with acute leukemia
ADVERSE REACTIONS SIGNIFICANT Systemic: Oral:
>10%: Central nervous system: Malaise (12%)
1% to 10%: Central nervous system: Headache (2%) Gastrointestinal: Nausea (2% to 5%), vomiting (3%), diarrhea (2% to 3%)
Systemic: Parenteral:
1% to 10%: Dermatologic: Hives (2%), itching (2%), rash (2%) Gastrointestinal: Nausea/vomiting (7%) Hepatic: Liver function tests increased (1% to 2%) Local: Inflammation at injection site or phlebitis (9%) Renal: BUN increased (5% to 10%), creatinine increased (5% to 10%), acute renal failure
Topical:
>10%: Dermatologic: Mild pain, burning, or stinging (ointment 30%)
1% to 10%: Dermatologic: Pruritus (ointment 4%), itching
All forms: <1% (Limited to important or life-threatening): Abdominal pain, aggression, agitation, alopecia, anaphylaxis, anemia, angioedema, anorexia, ataxia, coma, confusion, consciousness decreased, delirium, desquamation, diarrhea, disseminated intravascular coagulopathy (DIC), dizziness, dry lips, dysarthria, encephalopathy, erythema multiforme, fatigue, fever, gastrointestinal distress, hallucinations, hematuria, hemolysis, hepatitis, hyperbilirubinemia, hypotension, insomnia, jaundice, leukocytoclastic vasculitis, leukocytosis, leukopenia, local tissue necrosis (following extravasation), lymphadenopathy, mental depression, myalgia, neutrophilia, paresthesia, peripheral edema, photosensitization, pruritus, psychosis, renal failure, seizure, somnolence, sore throat, Stevens-Johnson syndrome, thrombocytopenia, thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), thrombocytosis, toxic epidermal necrolysis, tremor, urticaria, visual disturbances
CONTRAINDICATIONS — Hypersensitivity to acyclovir, valacyclovir, or any component of the formulation
WARNINGS / PRECAUTIONS — Use with caution in immunocompromised patients; thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) has been reported. Use caution in the elderly, pre-existing renal disease, or in those receiving other nephrotoxic drugs. Maintain adequate hydration during oral or intravenous therapy. Use I.V. preparation with caution in patients with underlying neurologic abnormalities, serious hepatic or electrolyte abnormalities, or substantial hypoxia.
Safety and efficacy of oral formulations have not been established in pediatric patients <2 years of age.
Chickenpox: Treatment should begin within 24 hours of appearance of rash; oral route not recommended for routine use in otherwise healthy children with varicella, but may be effective in patients at increased risk of moderate to severe infection (>12 years of age, chronic cutaneous or pulmonary disorders, long-term salicylate therapy, corticosteroid therapy).
Genital herpes: Physical contact should be avoided when lesions are present; transmission may also occur in the absence of symptoms. Treatment should begin with the first signs or symptoms.
Herpes labialis: For external use only to the lips and face; do not apply to eye or inside the mouth or nose. Treatment should begin with the first signs or symptoms.
Herpes zoster: Acyclovir should be started within 72 hours of appearance of rash to be effective.
ETHANOL / NUTRITION / HERB INTERACTIONS — Food: Does not affect absorption of oral acyclovir.
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Teratogenic effects were not observed in animal studies. Acyclovir has been shown to cross the human placenta. There are no adequate and well-controlled studies in pregnant women. Results from a pregnancy registry, established in 1984 and closed in 1999, did not find an increase in the number of birth defects with exposure to acyclovir when compared to those expected in the general population. However, due to the small size of the registry and lack of long-term data, the manufacturer recommends using during pregnancy with caution and only when clearly needed. Data from the pregnancy registry may be obtained from GlaxoSmithKline.
LACTATION — Enters breast milk/use with caution (AAP rates "compatible")
BREAST-FEEDING CONSIDERATIONS — Nursing mothers with herpetic lesions near or on the breast should avoid breast-feeding. Limited data suggest exposure to the nursing infant of ~0.3 mg/kg/day following oral administration of acyclovir to the mother.
DIETARY CONSIDERATIONS — May be taken with or without food. Acyclovir 500 mg injection contains sodium ~50 mg (~2 mEq).
PRICING — (data from drugstore.com)Capsules (Acyclovir) 200 mg (30): $12.99
Capsules (Zovirax) 200 mg (30): $66.50
Cream (Zovirax) 5% (2): $42.53 5% (5): $94.81
Ointment (Zovirax) 5% (15): $105.18
Suspension (Acyclovir) 200 mg/5 mL (473): $82.68
Suspension (Zovirax) 200 mg/5 mL (473): $183.41
Tablets (Acyclovir) 400 mg (60): $28.99 800 mg (30): $24.99
Tablets (Zovirax) 400 mg (60): $242.78 800 mg (30): $236.13
MONITORING PARAMETERS — Urinalysis, BUN, serum creatinine, liver enzymes, CBC
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Overdoses of up to 20 g have been reported. Symptoms of overdose include agitation, seizures, somnolence, confusion, elevated serum creatinine, and renal failure. In the event of overdose, sufficient urine flow must be maintained to avoid drug precipitation within renal tubules. Hemodialysis has resulted in up to 60% reduction in serum acyclovir levels.
CANADIAN BRAND NAMES — Apo-Acyclovir®; Gen-Acyclovir; Nu-Acyclovir; ratio-Acyclovir; Zovirax®
INTERNATIONAL BRAND NAMES — Abbovir (PL); ACERPES (DE); Acic Creme (DE); Acicloftal (IT); Aciclor (VE); Aciclosina (PE); Aciclovir (PL); Aciclovir-BC IV (AU); Acihexal (AU); Acivir Cream (IL, IN); Acivir Eye (IN); Acix (PL); Aclova (KR); Aclovir (HR, TH, TW); Aclovirax (HK); ACS (KR); Activir (FR); Acyclo-V (AU, BH); Acyclostad (PL); Acyclovir (PL); Acyclovir Stada (PL); Acyklowir (PL); Acylene (MY); Acyrova (KR); Acyvir (EC, HK, IT); Aias (KR); Antivir (PL); Apicol (CO); Apo-Acyclovir (CA, PL); Avorax (HK, MY, SG); Avorax Cream (MY); Awirol (PL); Azovir (ID); Bearax (SG); Cicloferon (MX); Cicloviral (CO); Clinovir (ID, TH); Clovicin (TW); Clovir (BR); Cloviran (CL); Colsor (TH); Cusiviral (ES, HK, MY, PL, SG); Cyclivex (ZA); Cyclomed (IL); Cyclorax (HK); Cyclostad (PH); Cyclovir (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TZ, UG, ZM, ZW); Cyllanvir (PH); Danovir (SG); Deherp (TH, TW); Dravyr (SG); Duvimex (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Entir (SG, TH); Erlvirax (SG); Euroclovir (HK); Eurovir (PY); Exavir (BR); Expit (UY); Gen-Acyclovir (CA); Hascovir (PL); Herpefug (DE); Herpesin (PL); Herpex (BH, IN, PL); Herpoviric (DE); Herpoviric Rp Creme (DE); Heviran (PL); Inmerax (CL); Juviral (DE); Laciken (MX); Lermex (TH); Libravir (EC); Lisovyr (AR, CL); Lovir (AU, HK, MY, NZ, SG); Lovire (ZA); Marvir (TH); Matrovir (ID); Maynor (ES); Medovir (AE, BF, BG, BH, BJ, CI, CY, EG, ET, GH, GM, GN, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, MY, NE, NG, OM, QA, SA, SC, SD, SG, SL, SN, SY, TZ, UG, YE, ZM, ZW); Nevirz (ID); Norum (TH); Nu-Acyclovir (CA); Olvit (MX); Oppvir (TH, TW); Opthavir (MX); Poviral (EC); Proviral (AR); Qualiclovir (HK); Quavir (ID); Ranvir (TH); Ranviran (PL); ratio-Acyclovir (CA); Skirax (TW); Supra-Vir (IL); Supraviran (DE, PL); Supraviran Creme (AE, BH, CY, DE, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Syntovir (HK); Vacrax (MY); Vermis (TH); Vicorax (TH, TW); Viraban (NZ); Viracir (PL); Viralex-DS (PH); Virax (KR); Vircella (ID); Virest (MY, SG); Virex (CO); Virless (CN, TW); Viroclear (HK); Virogon (TH); Virolan (TW); Virolex (HR, PL); Viromed (TH); Virucid (HK); Virules (HK); Vivir (KR); Warviron (HK); Zetavir (MX); Zeven Cream (MY); Zevin (HK, TH); Zoral (HK, SG); Zoral Cream (MY); Zorax (SG); Zorel (ID); Zoter (ID); Zovir (DK); Zovirax [tabs./susp./ungt.] (PL); Zovirax (AE, AN, AR, AT, AU, BB, BD, BE, BF, BG, BH, BJ, BM, BO, BR, BS, BZ, CA, CH, CI, CL, CN, CR, CY, CZ, DE, DK, DO, EG, ES, ET, FI, FR, GB, GH, GM, GN, GR, GT, GY, HK, HN, HR, HU, ID, IE, IL, IN, IQ, IR, IT, JM, JO, JP, KE, KR, KW, LB, LR, LY, MA, ML, MR, MU, MW, MX, MY, NE, NG, NI, NL, NO, NZ, OM, PA, PE, PH, PK, PR, PT, PY, QA, RU, SA, SC, SD, SE, SL, SN, SR, SV, SY, TR, TT, TW, TZ, UG, UY, YE, ZA, ZM, ZW); Zumasid (ID); Zyclir (AU); Zyclorax (ID); Zyvir (KE)
MECHANISM OF ACTION — Acyclovir is converted to acyclovir monophosphate by virus-specific thymidine kinase then further converted to acyclovir triphosphate by other cellular enzymes. Acyclovir triphosphate inhibits DNA synthesis and viral replication by competing with deoxyguanosine triphosphate for viral DNA polymerase and being incorporated into viral DNA.
PHARMACODYNAMICS / KINETICS Absorption: Oral: 15% to 30%
Distribution: Vd: 0.8 L/kg (63.6 L): Widely (eg, brain, kidney, lungs, liver, spleen, muscle, uterus, vagina, CSF)
Protein binding: 9% to 33%
Metabolism: Converted by viral enzymes to acyclovir monophosphate, and further converted to diphosphate then triphosphate (active form) by cellular enzymes
Bioavailability: Oral: 10% to 20% with normal renal function (bioavailability decreases with increased dose)
Half-life elimination: Terminal: Neonates: 4 hours; Children 1-12 years: 2-3 hours; Adults: 3 hours
Time to peak, serum: Oral: Within 1.5-2 hours
Excretion: Urine (62% to 90% as unchanged drug and metabolite)
PATIENT INFORMATION — This is not a cure for herpes (recurrences tend to continually reappear every 3-6 months after original infection), nor will this medication reduce the risk of transmission to others when lesions are present; avoid sexual intercourse when visible lesions are present. Take as directed for full course of therapy; do not discontinue even if feeling better. Oral doses may be taken with food.
Acyclovir
U.S. BRAND NAMES — Zovirax®
PHARMACOLOGIC CATEGORY Antiviral Agent
DOSING: ADULTS — Note: Obese patients should be dosed using ideal body weight
Genital HSV: I.V.: Immunocompetent: Initial episode, severe: 5 mg/kg every 8 hours for 5-7 days Oral: Initial episode: 200 mg every 4 hours while awake (5 times/day) for 10 days (per manufacturer's labeling); 400 mg 3 times/day for 5-10 days has also been reported Recurrence: 200 mg every 4 hours while awake (5 times/day) for 5 days (per manufacturer's labeling; begin at earliest signs of disease); 400 mg 3 times/day for 5 days has also been reported Chronic suppression: 400 mg twice daily or 200 mg 3-5 times/day, for up to 12 months followed by re-evaluation (per manufacturer's labeling); 400-1200 mg/day in 2-3 divided doses has also been reported Topical: Immunocompromised: Ointment: Initial episode: 1/2" ribbon of ointment for a 4" square surface area every 3 hours (6 times/day) for 7 days
Herpes labialis (cold sores): Topical: Apply 5 times/day for 4 days
Herpes zoster (shingles): Oral: Immunocompetent: 800 mg every 4 hours (5 times/day) for 7-10 days I.V.: Immunocompromised: 10 mg/kg/dose or 500 mg/m2/dose every 8 hours for 7 days
HSV encephalitis: I.V.: 10 mg/kg/dose every 8 hours for 10 days (per manufacturer's labeling); 10-15 mg/kg/dose every 8 hours for 14-21 days also reported
Mucocutaneous HSV: I.V.: Immunocompromised: 5 mg/kg/dose every 8 hours for 7 days (per manufacturer's labeling); dosing for up to 14 days also reported Oral: Immunocompromised (unlabeled use): 400 mg 5 times a day for 7-14 days Topical: Ointment: Nonlife-threatening, immunocompromised: 1/2" ribbon of ointment for a 4" square surface area every 3 hours (6 times/day) for 7 days
Varicella-zoster (chickenpox): Begin treatment within the first 24 hours of rash onset: Oral: >40 kg (immunocompetent): 800 mg/dose 4 times a day for 5 days I.V.: Immunocompromised (unlabeled use): 1500 mg/m2/day divided every 8 hours or 10 mg/kg/dose every 8 hours for 7-10 days
Prevention of HSV reactivation in HIV-positive patients, for use only when recurrences are frequent or severe (unlabeled use): Oral: 200 mg 3 times/day or 400 mg 2 times/day
Prevention of HSV reactivation in HSCT (unlabeled use): Note: Start at the beginning of conditioning therapy and continue until engraftment or until mucositis resolves (~30 days) Oral: 200 mg 3 times/day I.V.: 250 mg/m2/dose every 12 hours
Bone marrow transplant recipients (unlabeled use): I.V.: Allogeneic patients who are HSV and CMV seropositive: 500 mg/m2/dose (10 mg/kg) every 8 hours; for clinically-symptomatic CMV infection, consider replacing acyclovir with ganciclovir
DOSING: PEDIATRIC — Note: Obese patients should be dosed using ideal body weight
(For additional information see "Acyclovir: Pediatric drug information")
Genital HSV: I.V.: Children 12 years: Refer to adult dosing. Oral: Initial episode (unlabeled use): 40-80 mg/kg/day divided into 3-4 doses for 5-10 days (maximum: 1 g/day) Chronic suppression (unlabeled use; limited data): 80 mg/kg/day in 3 divided doses (maximum: 1 g/day), re-evaluate after 12 months of treatment
Herpes labialis (cold sores): Topical: Children 12 years: Refer to adult dosing.
Herpes zoster (shingles): I.V.: Children <12 years (immunocompromised): 20 mg/kg/dose every 8 hours for 7 days Children 12 years: Refer to adult dosing.
HSV encephalitis: I.V.: Children 3 months to 12 years: 20 mg/kg/dose every 8 hours for 10 days (per manufacturer's labeling); dosing for 14-21 days also reported Children 12 years: Refer to adult dosing.
Mucocutaneous HSV: I.V.: Children <12 years (immunocompromised): 10 mg/kg/dose every 8 hours for 7 days Children 12 years: Refer to adult dosing.
Neonatal HSV: I.V.: Neonate: Birth to 3 months: 10 mg/kg/dose every 8 hours for 10 days (manufacturer's labeling); 15 mg/kg/dose or 20 mg/kg/dose every 8 hours for 14-21 days has also been reported
Varicella-zoster (chickenpox): Begin treatment within the first 24 hours of rash onset: Oral: Children 2 years and 40 kg (immunocompetent): 20 mg/kg/dose (up to 800 mg/dose) 4 times/day for 5 days Children >40 kg: Refer to adult dosing. I.V.: Children <1 year (immunocompromised, unlabeled use): 10 mg/kg/dose every 8 hours for 7-10 days Children 1 year: Refer to adult dosing.
Prevention of HSV reactivation in HIV-positive patients, for use only when recurrences are frequent or severe (unlabeled use): Oral: 80 mg/kg/day in 3-4 divided doses
Prevention of HSV reactivation in HSCT (unlabeled use): Note: Start at the beginning of conditioning therapy and continue until engraftment or until mucositis resolves (~30 days): I.V.: 250 mg/m2/dose every 8 hours or 125 mg/m2/dose every 6 hours
Bone marrow transplant recipients (unlabeled use): I.V.: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT Oral: Clcr 10-25 mL/minute/1.73 m2: Normal dosing regimen 800 mg every 4 hours: Administer 800 mg every 8 hours Clcr <10 mL/minute/1.73 m2: Normal dosing regimen 200 mg every 4 hours, 200 mg every 8 hours, or 400 mg every 12 hours: Administer 200 mg every 12 hours Normal dosing regimen 800 mg every 4 hours: Administer 800 mg every 12 hours
I.V.: Clcr 25-50 mL/minute/1.73 m2: Administer recommended dose every 12 hours Clcr 10-25 mL/minute/1.73 m2: Administer recommended dose every 24 hours Clcr <10 mL/minute/1.73 m2: Administer 50% of recommended dose every 24 hours
Hemodialysis: Administer dose after dialysis
Peritoneal dialysis: No supplemental dose needed
CAVH: 3.5 mg/kg/day
CVVHD/CVVH: Adjust dose based upon Clcr 30 mL/minute
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule: 200 mg Zovirax®: 200 mg
Cream, topical: Zovirax®: 5% (2 g, 5 g)
Injection, powder for reconstitution, as sodium: 500 mg, 1000 mg Zovirax®: 500 mg [DSC]
Injection, solution, as sodium [preservative free]: 25 mg/mL (20 mL, 40 mL); 50 mg/mL (10 mL, 20 mL)
Ointment, topical: Zovirax®: 5% (15 g)
Suspension, oral: 200 mg/5 mL (480 mL) Zovirax®: 200 mg/5 mL (480 mL) [banana flavor]
Tablet: 400 mg, 800 mg Zovirax®: 400 mg, 800 mg
DOSAGE FORMS: CONCISE Capsule: 200 mg Zovirax®: 200 mg
Cream, topical: Zovirax®: 5% (2 g, 5 g)
Injection, powder for reconstitution: 500 mg, 1000 mg
Injection, solution [preservative free]: 25 mg/mL (20 mL, 40 mL); 50 mg/mL (10 mL, 20 mL)
Ointment, topical: Zovirax®: 5% (15 g)
Suspension, oral: 200 mg/5 mL Zovirax®: 200 mg/5 mL
Tablet: 400 mg, 800 mg Zovirax®: 400 mg, 800 mg
GENERIC EQUIVALENT AVAILABLE — Yes: Excludes cream, ointment
ADMINISTRATION Oral: May be administered with or without food.
I.V.: Avoid rapid infusion; infuse over 1 hour to prevent renal damage; maintain adequate hydration of patient; check for phlebitis and rotate infusion sites
Topical: Not for use in the eye. Apply using a finger cot or rubber glove to avoid transmission to other parts of the body or to other persons.
COMPATIBILITY — Stable in D5W, D5NS, D51/4NS, D51/2NS, LR, NS.
Incompatible with blood products and protein-containing solutions.
Y-site administration: Compatible: Allopurinol, amikacin, amphotericin B cholesteryl sulfate complex, ampicillin, cefamandole, cefazolin, cefoperazone, cefotaxime, cefoxitin, ceftazidime, ceftizoxime, ceftriaxone, cefuroxime, chloramphenicol, cimetidine, clindamycin, co-trimoxazole, dexamethasone, dimenhydrinate, diphenhydramine, docetaxel, doxorubicin liposome, doxycycline, erythromycin lactobionate, etoposide, famotidine, filgrastim, fluconazole, gatifloxacin, gentamicin, granisetron, heparin, hydrocortisone sodium succinate, hydromorphone, imipenem/cilastatin, linezolid, lorazepam, magnesium sulfate, melphalan, methylprednisolone sodium succinate, metoclopramide, metronidazole, multivitamins, nafcillin, oxacillin, paclitaxel, penicillin G potassium, pentobarbital, perphenazine, piperacillin, potassium chloride, propofol, ranitidine, remifentanil, sodium bicarbonate, tacrolimus, teniposide, theophylline, thiotepa, ticarcillin, tobramycin, vancomycin, zidovudine. Incompatible: Amifostine, amsacrine, aztreonam, cefepime, dobutamine, dopamine, fludarabine, foscarnet, gemcitabine, idarubicin, levofloxacin, ondansetron, piperacillin/tazobactam, sargramostim, vinorelbine. Variable (consult detailed reference): Cisatracurium, diltiazem, meperidine, meropenem, morphine, TPN.
Compatibility when admixed: Compatible: Fluconazole. Incompatible: Dobutamine, dopamine. Variable (consult detailed reference): Meropenem.
USE — Treatment of genital herpes simplex virus (HSV), herpes labialis (cold sores), herpes zoster (shingles), HSV encephalitis, neonatal HSV, mucocutaneous HSV in immunocompromised patients, varicella-zoster (chickenpox)
USE - UNLABELED / INVESTIGATIONAL — Prevention of HSV reactivation in HIV-positive patients; prevention of HSV reactivation in hematopoietic stem-cell transplant (HSCT); prevention of HSV reactivation during periods of neutropenia in patients with acute leukemia
ADVERSE REACTIONS SIGNIFICANT Systemic: Oral:
>10%: Central nervous system: Malaise (12%)
1% to 10%: Central nervous system: Headache (2%) Gastrointestinal: Nausea (2% to 5%), vomiting (3%), diarrhea (2% to 3%)
Systemic: Parenteral:
1% to 10%: Dermatologic: Hives (2%), itching (2%), rash (2%) Gastrointestinal: Nausea/vomiting (7%) Hepatic: Liver function tests increased (1% to 2%) Local: Inflammation at injection site or phlebitis (9%) Renal: BUN increased (5% to 10%), creatinine increased (5% to 10%), acute renal failure
Topical:
>10%: Dermatologic: Mild pain, burning, or stinging (ointment 30%)
1% to 10%: Dermatologic: Pruritus (ointment 4%), itching
All forms: <1% (Limited to important or life-threatening): Abdominal pain, aggression, agitation, alopecia, anaphylaxis, anemia, angioedema, anorexia, ataxia, coma, confusion, consciousness decreased, delirium, desquamation, diarrhea, disseminated intravascular coagulopathy (DIC), dizziness, dry lips, dysarthria, encephalopathy, erythema multiforme, fatigue, fever, gastrointestinal distress, hallucinations, hematuria, hemolysis, hepatitis, hyperbilirubinemia, hypotension, insomnia, jaundice, leukocytoclastic vasculitis, leukocytosis, leukopenia, local tissue necrosis (following extravasation), lymphadenopathy, mental depression, myalgia, neutrophilia, paresthesia, peripheral edema, photosensitization, pruritus, psychosis, renal failure, seizure, somnolence, sore throat, Stevens-Johnson syndrome, thrombocytopenia, thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), thrombocytosis, toxic epidermal necrolysis, tremor, urticaria, visual disturbances
CONTRAINDICATIONS — Hypersensitivity to acyclovir, valacyclovir, or any component of the formulation
WARNINGS / PRECAUTIONS — Use with caution in immunocompromised patients; thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) has been reported. Use caution in the elderly, pre-existing renal disease, or in those receiving other nephrotoxic drugs. Maintain adequate hydration during oral or intravenous therapy. Use I.V. preparation with caution in patients with underlying neurologic abnormalities, serious hepatic or electrolyte abnormalities, or substantial hypoxia.
Safety and efficacy of oral formulations have not been established in pediatric patients <2 years of age.
Chickenpox: Treatment should begin within 24 hours of appearance of rash; oral route not recommended for routine use in otherwise healthy children with varicella, but may be effective in patients at increased risk of moderate to severe infection (>12 years of age, chronic cutaneous or pulmonary disorders, long-term salicylate therapy, corticosteroid therapy).
Genital herpes: Physical contact should be avoided when lesions are present; transmission may also occur in the absence of symptoms. Treatment should begin with the first signs or symptoms.
Herpes labialis: For external use only to the lips and face; do not apply to eye or inside the mouth or nose. Treatment should begin with the first signs or symptoms.
Herpes zoster: Acyclovir should be started within 72 hours of appearance of rash to be effective.
ETHANOL / NUTRITION / HERB INTERACTIONS — Food: Does not affect absorption of oral acyclovir.
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Teratogenic effects were not observed in animal studies. Acyclovir has been shown to cross the human placenta. There are no adequate and well-controlled studies in pregnant women. Results from a pregnancy registry, established in 1984 and closed in 1999, did not find an increase in the number of birth defects with exposure to acyclovir when compared to those expected in the general population. However, due to the small size of the registry and lack of long-term data, the manufacturer recommends using during pregnancy with caution and only when clearly needed. Data from the pregnancy registry may be obtained from GlaxoSmithKline.
LACTATION — Enters breast milk/use with caution (AAP rates "compatible")
BREAST-FEEDING CONSIDERATIONS — Nursing mothers with herpetic lesions near or on the breast should avoid breast-feeding. Limited data suggest exposure to the nursing infant of ~0.3 mg/kg/day following oral administration of acyclovir to the mother.
DIETARY CONSIDERATIONS — May be taken with or without food. Acyclovir 500 mg injection contains sodium ~50 mg (~2 mEq).
PRICING — (data from drugstore.com)Capsules (Acyclovir) 200 mg (30): $12.99
Capsules (Zovirax) 200 mg (30): $66.50
Cream (Zovirax) 5% (2): $42.53 5% (5): $94.81
Ointment (Zovirax) 5% (15): $105.18
Suspension (Acyclovir) 200 mg/5 mL (473): $82.68
Suspension (Zovirax) 200 mg/5 mL (473): $183.41
Tablets (Acyclovir) 400 mg (60): $28.99 800 mg (30): $24.99
Tablets (Zovirax) 400 mg (60): $242.78 800 mg (30): $236.13
MONITORING PARAMETERS — Urinalysis, BUN, serum creatinine, liver enzymes, CBC
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Overdoses of up to 20 g have been reported. Symptoms of overdose include agitation, seizures, somnolence, confusion, elevated serum creatinine, and renal failure. In the event of overdose, sufficient urine flow must be maintained to avoid drug precipitation within renal tubules. Hemodialysis has resulted in up to 60% reduction in serum acyclovir levels.
CANADIAN BRAND NAMES — Apo-Acyclovir®; Gen-Acyclovir; Nu-Acyclovir; ratio-Acyclovir; Zovirax®
INTERNATIONAL BRAND NAMES — Abbovir (PL); ACERPES (DE); Acic Creme (DE); Acicloftal (IT); Aciclor (VE); Aciclosina (PE); Aciclovir (PL); Aciclovir-BC IV (AU); Acihexal (AU); Acivir Cream (IL, IN); Acivir Eye (IN); Acix (PL); Aclova (KR); Aclovir (HR, TH, TW); Aclovirax (HK); ACS (KR); Activir (FR); Acyclo-V (AU, BH); Acyclostad (PL); Acyclovir (PL); Acyclovir Stada (PL); Acyklowir (PL); Acylene (MY); Acyrova (KR); Acyvir (EC, HK, IT); Aias (KR); Antivir (PL); Apicol (CO); Apo-Acyclovir (CA, PL); Avorax (HK, MY, SG); Avorax Cream (MY); Awirol (PL); Azovir (ID); Bearax (SG); Cicloferon (MX); Cicloviral (CO); Clinovir (ID, TH); Clovicin (TW); Clovir (BR); Cloviran (CL); Colsor (TH); Cusiviral (ES, HK, MY, PL, SG); Cyclivex (ZA); Cyclomed (IL); Cyclorax (HK); Cyclostad (PH); Cyclovir (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TZ, UG, ZM, ZW); Cyllanvir (PH); Danovir (SG); Deherp (TH, TW); Dravyr (SG); Duvimex (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Entir (SG, TH); Erlvirax (SG); Euroclovir (HK); Eurovir (PY); Exavir (BR); Expit (UY); Gen-Acyclovir (CA); Hascovir (PL); Herpefug (DE); Herpesin (PL); Herpex (BH, IN, PL); Herpoviric (DE); Herpoviric Rp Creme (DE); Heviran (PL); Inmerax (CL); Juviral (DE); Laciken (MX); Lermex (TH); Libravir (EC); Lisovyr (AR, CL); Lovir (AU, HK, MY, NZ, SG); Lovire (ZA); Marvir (TH); Matrovir (ID); Maynor (ES); Medovir (AE, BF, BG, BH, BJ, CI, CY, EG, ET, GH, GM, GN, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, MY, NE, NG, OM, QA, SA, SC, SD, SG, SL, SN, SY, TZ, UG, YE, ZM, ZW); Nevirz (ID); Norum (TH); Nu-Acyclovir (CA); Olvit (MX); Oppvir (TH, TW); Opthavir (MX); Poviral (EC); Proviral (AR); Qualiclovir (HK); Quavir (ID); Ranvir (TH); Ranviran (PL); ratio-Acyclovir (CA); Skirax (TW); Supra-Vir (IL); Supraviran (DE, PL); Supraviran Creme (AE, BH, CY, DE, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Syntovir (HK); Vacrax (MY); Vermis (TH); Vicorax (TH, TW); Viraban (NZ); Viracir (PL); Viralex-DS (PH); Virax (KR); Vircella (ID); Virest (MY, SG); Virex (CO); Virless (CN, TW); Viroclear (HK); Virogon (TH); Virolan (TW); Virolex (HR, PL); Viromed (TH); Virucid (HK); Virules (HK); Vivir (KR); Warviron (HK); Zetavir (MX); Zeven Cream (MY); Zevin (HK, TH); Zoral (HK, SG); Zoral Cream (MY); Zorax (SG); Zorel (ID); Zoter (ID); Zovir (DK); Zovirax [tabs./susp./ungt.] (PL); Zovirax (AE, AN, AR, AT, AU, BB, BD, BE, BF, BG, BH, BJ, BM, BO, BR, BS, BZ, CA, CH, CI, CL, CN, CR, CY, CZ, DE, DK, DO, EG, ES, ET, FI, FR, GB, GH, GM, GN, GR, GT, GY, HK, HN, HR, HU, ID, IE, IL, IN, IQ, IR, IT, JM, JO, JP, KE, KR, KW, LB, LR, LY, MA, ML, MR, MU, MW, MX, MY, NE, NG, NI, NL, NO, NZ, OM, PA, PE, PH, PK, PR, PT, PY, QA, RU, SA, SC, SD, SE, SL, SN, SR, SV, SY, TR, TT, TW, TZ, UG, UY, YE, ZA, ZM, ZW); Zumasid (ID); Zyclir (AU); Zyclorax (ID); Zyvir (KE)
MECHANISM OF ACTION — Acyclovir is converted to acyclovir monophosphate by virus-specific thymidine kinase then further converted to acyclovir triphosphate by other cellular enzymes. Acyclovir triphosphate inhibits DNA synthesis and viral replication by competing with deoxyguanosine triphosphate for viral DNA polymerase and being incorporated into viral DNA.
PHARMACODYNAMICS / KINETICS Absorption: Oral: 15% to 30%
Distribution: Vd: 0.8 L/kg (63.6 L): Widely (eg, brain, kidney, lungs, liver, spleen, muscle, uterus, vagina, CSF)
Protein binding: 9% to 33%
Metabolism: Converted by viral enzymes to acyclovir monophosphate, and further converted to diphosphate then triphosphate (active form) by cellular enzymes
Bioavailability: Oral: 10% to 20% with normal renal function (bioavailability decreases with increased dose)
Half-life elimination: Terminal: Neonates: 4 hours; Children 1-12 years: 2-3 hours; Adults: 3 hours
Time to peak, serum: Oral: Within 1.5-2 hours
Excretion: Urine (62% to 90% as unchanged drug and metabolite)
PATIENT INFORMATION — This is not a cure for herpes (recurrences tend to continually reappear every 3-6 months after original infection), nor will this medication reduce the risk of transmission to others when lesions are present; avoid sexual intercourse when visible lesions are present. Take as directed for full course of therapy; do not discontinue even if feeling better. Oral doses may be taken with food.
PHARMACOLOGIC CATEGORY Antiviral Agent
DOSING: ADULTS — Note: Obese patients should be dosed using ideal body weight
Genital HSV: I.V.: Immunocompetent: Initial episode, severe: 5 mg/kg every 8 hours for 5-7 days Oral: Initial episode: 200 mg every 4 hours while awake (5 times/day) for 10 days (per manufacturer's labeling); 400 mg 3 times/day for 5-10 days has also been reported Recurrence: 200 mg every 4 hours while awake (5 times/day) for 5 days (per manufacturer's labeling; begin at earliest signs of disease); 400 mg 3 times/day for 5 days has also been reported Chronic suppression: 400 mg twice daily or 200 mg 3-5 times/day, for up to 12 months followed by re-evaluation (per manufacturer's labeling); 400-1200 mg/day in 2-3 divided doses has also been reported Topical: Immunocompromised: Ointment: Initial episode: 1/2" ribbon of ointment for a 4" square surface area every 3 hours (6 times/day) for 7 days
Herpes labialis (cold sores): Topical: Apply 5 times/day for 4 days
Herpes zoster (shingles): Oral: Immunocompetent: 800 mg every 4 hours (5 times/day) for 7-10 days I.V.: Immunocompromised: 10 mg/kg/dose or 500 mg/m2/dose every 8 hours for 7 days
HSV encephalitis: I.V.: 10 mg/kg/dose every 8 hours for 10 days (per manufacturer's labeling); 10-15 mg/kg/dose every 8 hours for 14-21 days also reported
Mucocutaneous HSV: I.V.: Immunocompromised: 5 mg/kg/dose every 8 hours for 7 days (per manufacturer's labeling); dosing for up to 14 days also reported Oral: Immunocompromised (unlabeled use): 400 mg 5 times a day for 7-14 days Topical: Ointment: Nonlife-threatening, immunocompromised: 1/2" ribbon of ointment for a 4" square surface area every 3 hours (6 times/day) for 7 days
Varicella-zoster (chickenpox): Begin treatment within the first 24 hours of rash onset: Oral: >40 kg (immunocompetent): 800 mg/dose 4 times a day for 5 days I.V.: Immunocompromised (unlabeled use): 1500 mg/m2/day divided every 8 hours or 10 mg/kg/dose every 8 hours for 7-10 days
Prevention of HSV reactivation in HIV-positive patients, for use only when recurrences are frequent or severe (unlabeled use): Oral: 200 mg 3 times/day or 400 mg 2 times/day
Prevention of HSV reactivation in HSCT (unlabeled use): Note: Start at the beginning of conditioning therapy and continue until engraftment or until mucositis resolves (~30 days) Oral: 200 mg 3 times/day I.V.: 250 mg/m2/dose every 12 hours
Bone marrow transplant recipients (unlabeled use): I.V.: Allogeneic patients who are HSV and CMV seropositive: 500 mg/m2/dose (10 mg/kg) every 8 hours; for clinically-symptomatic CMV infection, consider replacing acyclovir with ganciclovir
DOSING: PEDIATRIC — Note: Obese patients should be dosed using ideal body weight
(For additional information see "Acyclovir: Pediatric drug information")
Genital HSV: I.V.: Children 12 years: Refer to adult dosing. Oral: Initial episode (unlabeled use): 40-80 mg/kg/day divided into 3-4 doses for 5-10 days (maximum: 1 g/day) Chronic suppression (unlabeled use; limited data): 80 mg/kg/day in 3 divided doses (maximum: 1 g/day), re-evaluate after 12 months of treatment
Herpes labialis (cold sores): Topical: Children 12 years: Refer to adult dosing.
Herpes zoster (shingles): I.V.: Children <12 years (immunocompromised): 20 mg/kg/dose every 8 hours for 7 days Children 12 years: Refer to adult dosing.
HSV encephalitis: I.V.: Children 3 months to 12 years: 20 mg/kg/dose every 8 hours for 10 days (per manufacturer's labeling); dosing for 14-21 days also reported Children 12 years: Refer to adult dosing.
Mucocutaneous HSV: I.V.: Children <12 years (immunocompromised): 10 mg/kg/dose every 8 hours for 7 days Children 12 years: Refer to adult dosing.
Neonatal HSV: I.V.: Neonate: Birth to 3 months: 10 mg/kg/dose every 8 hours for 10 days (manufacturer's labeling); 15 mg/kg/dose or 20 mg/kg/dose every 8 hours for 14-21 days has also been reported
Varicella-zoster (chickenpox): Begin treatment within the first 24 hours of rash onset: Oral: Children 2 years and 40 kg (immunocompetent): 20 mg/kg/dose (up to 800 mg/dose) 4 times/day for 5 days Children >40 kg: Refer to adult dosing. I.V.: Children <1 year (immunocompromised, unlabeled use): 10 mg/kg/dose every 8 hours for 7-10 days Children 1 year: Refer to adult dosing.
Prevention of HSV reactivation in HIV-positive patients, for use only when recurrences are frequent or severe (unlabeled use): Oral: 80 mg/kg/day in 3-4 divided doses
Prevention of HSV reactivation in HSCT (unlabeled use): Note: Start at the beginning of conditioning therapy and continue until engraftment or until mucositis resolves (~30 days): I.V.: 250 mg/m2/dose every 8 hours or 125 mg/m2/dose every 6 hours
Bone marrow transplant recipients (unlabeled use): I.V.: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT Oral: Clcr 10-25 mL/minute/1.73 m2: Normal dosing regimen 800 mg every 4 hours: Administer 800 mg every 8 hours Clcr <10 mL/minute/1.73 m2: Normal dosing regimen 200 mg every 4 hours, 200 mg every 8 hours, or 400 mg every 12 hours: Administer 200 mg every 12 hours Normal dosing regimen 800 mg every 4 hours: Administer 800 mg every 12 hours
I.V.: Clcr 25-50 mL/minute/1.73 m2: Administer recommended dose every 12 hours Clcr 10-25 mL/minute/1.73 m2: Administer recommended dose every 24 hours Clcr <10 mL/minute/1.73 m2: Administer 50% of recommended dose every 24 hours
Hemodialysis: Administer dose after dialysis
Peritoneal dialysis: No supplemental dose needed
CAVH: 3.5 mg/kg/day
CVVHD/CVVH: Adjust dose based upon Clcr 30 mL/minute
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule: 200 mg Zovirax®: 200 mg
Cream, topical: Zovirax®: 5% (2 g, 5 g)
Injection, powder for reconstitution, as sodium: 500 mg, 1000 mg Zovirax®: 500 mg [DSC]
Injection, solution, as sodium [preservative free]: 25 mg/mL (20 mL, 40 mL); 50 mg/mL (10 mL, 20 mL)
Ointment, topical: Zovirax®: 5% (15 g)
Suspension, oral: 200 mg/5 mL (480 mL) Zovirax®: 200 mg/5 mL (480 mL) [banana flavor]
Tablet: 400 mg, 800 mg Zovirax®: 400 mg, 800 mg
DOSAGE FORMS: CONCISE Capsule: 200 mg Zovirax®: 200 mg
Cream, topical: Zovirax®: 5% (2 g, 5 g)
Injection, powder for reconstitution: 500 mg, 1000 mg
Injection, solution [preservative free]: 25 mg/mL (20 mL, 40 mL); 50 mg/mL (10 mL, 20 mL)
Ointment, topical: Zovirax®: 5% (15 g)
Suspension, oral: 200 mg/5 mL Zovirax®: 200 mg/5 mL
Tablet: 400 mg, 800 mg Zovirax®: 400 mg, 800 mg
GENERIC EQUIVALENT AVAILABLE — Yes: Excludes cream, ointment
ADMINISTRATION Oral: May be administered with or without food.
I.V.: Avoid rapid infusion; infuse over 1 hour to prevent renal damage; maintain adequate hydration of patient; check for phlebitis and rotate infusion sites
Topical: Not for use in the eye. Apply using a finger cot or rubber glove to avoid transmission to other parts of the body or to other persons.
COMPATIBILITY — Stable in D5W, D5NS, D51/4NS, D51/2NS, LR, NS.
Incompatible with blood products and protein-containing solutions.
Y-site administration: Compatible: Allopurinol, amikacin, amphotericin B cholesteryl sulfate complex, ampicillin, cefamandole, cefazolin, cefoperazone, cefotaxime, cefoxitin, ceftazidime, ceftizoxime, ceftriaxone, cefuroxime, chloramphenicol, cimetidine, clindamycin, co-trimoxazole, dexamethasone, dimenhydrinate, diphenhydramine, docetaxel, doxorubicin liposome, doxycycline, erythromycin lactobionate, etoposide, famotidine, filgrastim, fluconazole, gatifloxacin, gentamicin, granisetron, heparin, hydrocortisone sodium succinate, hydromorphone, imipenem/cilastatin, linezolid, lorazepam, magnesium sulfate, melphalan, methylprednisolone sodium succinate, metoclopramide, metronidazole, multivitamins, nafcillin, oxacillin, paclitaxel, penicillin G potassium, pentobarbital, perphenazine, piperacillin, potassium chloride, propofol, ranitidine, remifentanil, sodium bicarbonate, tacrolimus, teniposide, theophylline, thiotepa, ticarcillin, tobramycin, vancomycin, zidovudine. Incompatible: Amifostine, amsacrine, aztreonam, cefepime, dobutamine, dopamine, fludarabine, foscarnet, gemcitabine, idarubicin, levofloxacin, ondansetron, piperacillin/tazobactam, sargramostim, vinorelbine. Variable (consult detailed reference): Cisatracurium, diltiazem, meperidine, meropenem, morphine, TPN.
Compatibility when admixed: Compatible: Fluconazole. Incompatible: Dobutamine, dopamine. Variable (consult detailed reference): Meropenem.
USE — Treatment of genital herpes simplex virus (HSV), herpes labialis (cold sores), herpes zoster (shingles), HSV encephalitis, neonatal HSV, mucocutaneous HSV in immunocompromised patients, varicella-zoster (chickenpox)
USE - UNLABELED / INVESTIGATIONAL — Prevention of HSV reactivation in HIV-positive patients; prevention of HSV reactivation in hematopoietic stem-cell transplant (HSCT); prevention of HSV reactivation during periods of neutropenia in patients with acute leukemia
ADVERSE REACTIONS SIGNIFICANT Systemic: Oral:
>10%: Central nervous system: Malaise (12%)
1% to 10%: Central nervous system: Headache (2%) Gastrointestinal: Nausea (2% to 5%), vomiting (3%), diarrhea (2% to 3%)
Systemic: Parenteral:
1% to 10%: Dermatologic: Hives (2%), itching (2%), rash (2%) Gastrointestinal: Nausea/vomiting (7%) Hepatic: Liver function tests increased (1% to 2%) Local: Inflammation at injection site or phlebitis (9%) Renal: BUN increased (5% to 10%), creatinine increased (5% to 10%), acute renal failure
Topical:
>10%: Dermatologic: Mild pain, burning, or stinging (ointment 30%)
1% to 10%: Dermatologic: Pruritus (ointment 4%), itching
All forms: <1% (Limited to important or life-threatening): Abdominal pain, aggression, agitation, alopecia, anaphylaxis, anemia, angioedema, anorexia, ataxia, coma, confusion, consciousness decreased, delirium, desquamation, diarrhea, disseminated intravascular coagulopathy (DIC), dizziness, dry lips, dysarthria, encephalopathy, erythema multiforme, fatigue, fever, gastrointestinal distress, hallucinations, hematuria, hemolysis, hepatitis, hyperbilirubinemia, hypotension, insomnia, jaundice, leukocytoclastic vasculitis, leukocytosis, leukopenia, local tissue necrosis (following extravasation), lymphadenopathy, mental depression, myalgia, neutrophilia, paresthesia, peripheral edema, photosensitization, pruritus, psychosis, renal failure, seizure, somnolence, sore throat, Stevens-Johnson syndrome, thrombocytopenia, thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), thrombocytosis, toxic epidermal necrolysis, tremor, urticaria, visual disturbances
CONTRAINDICATIONS — Hypersensitivity to acyclovir, valacyclovir, or any component of the formulation
WARNINGS / PRECAUTIONS — Use with caution in immunocompromised patients; thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) has been reported. Use caution in the elderly, pre-existing renal disease, or in those receiving other nephrotoxic drugs. Maintain adequate hydration during oral or intravenous therapy. Use I.V. preparation with caution in patients with underlying neurologic abnormalities, serious hepatic or electrolyte abnormalities, or substantial hypoxia.
Safety and efficacy of oral formulations have not been established in pediatric patients <2 years of age.
Chickenpox: Treatment should begin within 24 hours of appearance of rash; oral route not recommended for routine use in otherwise healthy children with varicella, but may be effective in patients at increased risk of moderate to severe infection (>12 years of age, chronic cutaneous or pulmonary disorders, long-term salicylate therapy, corticosteroid therapy).
Genital herpes: Physical contact should be avoided when lesions are present; transmission may also occur in the absence of symptoms. Treatment should begin with the first signs or symptoms.
Herpes labialis: For external use only to the lips and face; do not apply to eye or inside the mouth or nose. Treatment should begin with the first signs or symptoms.
Herpes zoster: Acyclovir should be started within 72 hours of appearance of rash to be effective.
ETHANOL / NUTRITION / HERB INTERACTIONS — Food: Does not affect absorption of oral acyclovir.
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Teratogenic effects were not observed in animal studies. Acyclovir has been shown to cross the human placenta. There are no adequate and well-controlled studies in pregnant women. Results from a pregnancy registry, established in 1984 and closed in 1999, did not find an increase in the number of birth defects with exposure to acyclovir when compared to those expected in the general population. However, due to the small size of the registry and lack of long-term data, the manufacturer recommends using during pregnancy with caution and only when clearly needed. Data from the pregnancy registry may be obtained from GlaxoSmithKline.
LACTATION — Enters breast milk/use with caution (AAP rates "compatible")
BREAST-FEEDING CONSIDERATIONS — Nursing mothers with herpetic lesions near or on the breast should avoid breast-feeding. Limited data suggest exposure to the nursing infant of ~0.3 mg/kg/day following oral administration of acyclovir to the mother.
DIETARY CONSIDERATIONS — May be taken with or without food. Acyclovir 500 mg injection contains sodium ~50 mg (~2 mEq).
PRICING — (data from drugstore.com)Capsules (Acyclovir) 200 mg (30): $12.99
Capsules (Zovirax) 200 mg (30): $66.50
Cream (Zovirax) 5% (2): $42.53 5% (5): $94.81
Ointment (Zovirax) 5% (15): $105.18
Suspension (Acyclovir) 200 mg/5 mL (473): $82.68
Suspension (Zovirax) 200 mg/5 mL (473): $183.41
Tablets (Acyclovir) 400 mg (60): $28.99 800 mg (30): $24.99
Tablets (Zovirax) 400 mg (60): $242.78 800 mg (30): $236.13
MONITORING PARAMETERS — Urinalysis, BUN, serum creatinine, liver enzymes, CBC
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Overdoses of up to 20 g have been reported. Symptoms of overdose include agitation, seizures, somnolence, confusion, elevated serum creatinine, and renal failure. In the event of overdose, sufficient urine flow must be maintained to avoid drug precipitation within renal tubules. Hemodialysis has resulted in up to 60% reduction in serum acyclovir levels.
CANADIAN BRAND NAMES — Apo-Acyclovir®; Gen-Acyclovir; Nu-Acyclovir; ratio-Acyclovir; Zovirax®
INTERNATIONAL BRAND NAMES — Abbovir (PL); ACERPES (DE); Acic Creme (DE); Acicloftal (IT); Aciclor (VE); Aciclosina (PE); Aciclovir (PL); Aciclovir-BC IV (AU); Acihexal (AU); Acivir Cream (IL, IN); Acivir Eye (IN); Acix (PL); Aclova (KR); Aclovir (HR, TH, TW); Aclovirax (HK); ACS (KR); Activir (FR); Acyclo-V (AU, BH); Acyclostad (PL); Acyclovir (PL); Acyclovir Stada (PL); Acyklowir (PL); Acylene (MY); Acyrova (KR); Acyvir (EC, HK, IT); Aias (KR); Antivir (PL); Apicol (CO); Apo-Acyclovir (CA, PL); Avorax (HK, MY, SG); Avorax Cream (MY); Awirol (PL); Azovir (ID); Bearax (SG); Cicloferon (MX); Cicloviral (CO); Clinovir (ID, TH); Clovicin (TW); Clovir (BR); Cloviran (CL); Colsor (TH); Cusiviral (ES, HK, MY, PL, SG); Cyclivex (ZA); Cyclomed (IL); Cyclorax (HK); Cyclostad (PH); Cyclovir (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TZ, UG, ZM, ZW); Cyllanvir (PH); Danovir (SG); Deherp (TH, TW); Dravyr (SG); Duvimex (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Entir (SG, TH); Erlvirax (SG); Euroclovir (HK); Eurovir (PY); Exavir (BR); Expit (UY); Gen-Acyclovir (CA); Hascovir (PL); Herpefug (DE); Herpesin (PL); Herpex (BH, IN, PL); Herpoviric (DE); Herpoviric Rp Creme (DE); Heviran (PL); Inmerax (CL); Juviral (DE); Laciken (MX); Lermex (TH); Libravir (EC); Lisovyr (AR, CL); Lovir (AU, HK, MY, NZ, SG); Lovire (ZA); Marvir (TH); Matrovir (ID); Maynor (ES); Medovir (AE, BF, BG, BH, BJ, CI, CY, EG, ET, GH, GM, GN, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, MY, NE, NG, OM, QA, SA, SC, SD, SG, SL, SN, SY, TZ, UG, YE, ZM, ZW); Nevirz (ID); Norum (TH); Nu-Acyclovir (CA); Olvit (MX); Oppvir (TH, TW); Opthavir (MX); Poviral (EC); Proviral (AR); Qualiclovir (HK); Quavir (ID); Ranvir (TH); Ranviran (PL); ratio-Acyclovir (CA); Skirax (TW); Supra-Vir (IL); Supraviran (DE, PL); Supraviran Creme (AE, BH, CY, DE, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Syntovir (HK); Vacrax (MY); Vermis (TH); Vicorax (TH, TW); Viraban (NZ); Viracir (PL); Viralex-DS (PH); Virax (KR); Vircella (ID); Virest (MY, SG); Virex (CO); Virless (CN, TW); Viroclear (HK); Virogon (TH); Virolan (TW); Virolex (HR, PL); Viromed (TH); Virucid (HK); Virules (HK); Vivir (KR); Warviron (HK); Zetavir (MX); Zeven Cream (MY); Zevin (HK, TH); Zoral (HK, SG); Zoral Cream (MY); Zorax (SG); Zorel (ID); Zoter (ID); Zovir (DK); Zovirax [tabs./susp./ungt.] (PL); Zovirax (AE, AN, AR, AT, AU, BB, BD, BE, BF, BG, BH, BJ, BM, BO, BR, BS, BZ, CA, CH, CI, CL, CN, CR, CY, CZ, DE, DK, DO, EG, ES, ET, FI, FR, GB, GH, GM, GN, GR, GT, GY, HK, HN, HR, HU, ID, IE, IL, IN, IQ, IR, IT, JM, JO, JP, KE, KR, KW, LB, LR, LY, MA, ML, MR, MU, MW, MX, MY, NE, NG, NI, NL, NO, NZ, OM, PA, PE, PH, PK, PR, PT, PY, QA, RU, SA, SC, SD, SE, SL, SN, SR, SV, SY, TR, TT, TW, TZ, UG, UY, YE, ZA, ZM, ZW); Zumasid (ID); Zyclir (AU); Zyclorax (ID); Zyvir (KE)
MECHANISM OF ACTION — Acyclovir is converted to acyclovir monophosphate by virus-specific thymidine kinase then further converted to acyclovir triphosphate by other cellular enzymes. Acyclovir triphosphate inhibits DNA synthesis and viral replication by competing with deoxyguanosine triphosphate for viral DNA polymerase and being incorporated into viral DNA.
PHARMACODYNAMICS / KINETICS Absorption: Oral: 15% to 30%
Distribution: Vd: 0.8 L/kg (63.6 L): Widely (eg, brain, kidney, lungs, liver, spleen, muscle, uterus, vagina, CSF)
Protein binding: 9% to 33%
Metabolism: Converted by viral enzymes to acyclovir monophosphate, and further converted to diphosphate then triphosphate (active form) by cellular enzymes
Bioavailability: Oral: 10% to 20% with normal renal function (bioavailability decreases with increased dose)
Half-life elimination: Terminal: Neonates: 4 hours; Children 1-12 years: 2-3 hours; Adults: 3 hours
Time to peak, serum: Oral: Within 1.5-2 hours
Excretion: Urine (62% to 90% as unchanged drug and metabolite)
PATIENT INFORMATION — This is not a cure for herpes (recurrences tend to continually reappear every 3-6 months after original infection), nor will this medication reduce the risk of transmission to others when lesions are present; avoid sexual intercourse when visible lesions are present. Take as directed for full course of therapy; do not discontinue even if feeling better. Oral doses may be taken with food.
Acrivastine and pseudoephedrine
U.S. BRAND NAMES — Semprex®-D
PHARMACOLOGIC CATEGORY Antihistamine
DOSING: ADULTS — Rhinitis, nasal congestion, allergic symptoms: Oral: 1 capsule 3-4 times/day
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — Do not use.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule: Acrivastine 8 mg and pseudoephedrine hydrochloride 60 mg
DOSAGE FORMS: CONCISE Capsule: Semprex®-D: Acrivastine 8 mg and pseudoephedrine 60 mg
GENERIC EQUIVALENT AVAILABLE — No
USE — Temporary relief of nasal congestion, decongest sinus openings, running nose, itching of nose or throat, and itchy, watery eyes due to hay fever or other upper respiratory allergies
ADVERSE REACTIONS SIGNIFICANT >10%: Central nervous system: Drowsiness, headache
1% to 10%: Cardiovascular: Tachycardia, palpitation Central nervous system: Nervousness, dizziness, insomnia, vertigo, lightheadedness, fatigue Gastrointestinal: Nausea, vomiting, xerostomia, diarrhea Genitourinary: Dysuria Neuromuscular & skeletal: Weakness Respiratory: Pharyngitis, cough increased Miscellaneous: Diaphoresis
CONTRAINDICATIONS — Hypersensitivity to pseudoephedrine, acrivastine (or other alkylamine antihistamines), or any component of the formulation; MAO inhibitor therapy within 14 days of initiating therapy; severe hypertension, severe coronary artery disease; renal impairment (Clcr 48 mL/minute)
WARNINGS / PRECAUTIONS Disease-related concerns: Asthma: Use with caution in patients with asthma. Cardiovascular disease: Use with caution in patients with high blood pressure and/or ischemic heart disease. Diabetes: Use with caution in patients with diabetes mellitus. GI obstruction: Use with caution in patients with GI obstruction. Increased intraocular pressure: Use with caution in patients with increased intraocular pressure. Prostatic hyperplasia/urinary obstruction: Use with caution in patients with prostatic hyperplasia and/or GU obstruction. Thyroid dysfunction: Use with caution in patients with thyroid dysfunction.
Special populations: Elderly: Use with caution in patients >60 years of age. Pediatrics: Not recommended for use in children.
DRUG INTERACTIONS Decreased effect of guanethidine, reserpine, methyldopa, and beta-blockers
Increased toxicity with MAO inhibitors (hypertensive crisis), sympathomimetics, CNS depressants, ethanol (sedation)
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Avoid ethanol (may increase sedation)
PREGNANCY RISK FACTOR — B (show table)
LACTATION — Enters breast milk/contraindicated
PRICING — (data from drugstore.com)Capsules (Semprex-D) 8-60 mg (30): $37.47
MECHANISM OF ACTION — Refer to Pseudoephedrine; acrivastine is an analogue of triprolidine and it is considered to be relatively less sedating than traditional antihistamines; believed to involve competitive blockade of H1-receptor sites resulting in the inability of histamine to combine with its receptor sites and exert its usual effects on target cells
PHARMACODYNAMICS / KINETICS Pseudoephedrine: See Pseudoephedrine.
Acrivastine: Metabolism: Minimally hepatic Time to peak: ~1.1 hours Excretion: Urine (84%); feces (13%)
PHARMACOLOGIC CATEGORY Antihistamine
DOSING: ADULTS — Rhinitis, nasal congestion, allergic symptoms: Oral: 1 capsule 3-4 times/day
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — Do not use.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule: Acrivastine 8 mg and pseudoephedrine hydrochloride 60 mg
DOSAGE FORMS: CONCISE Capsule: Semprex®-D: Acrivastine 8 mg and pseudoephedrine 60 mg
GENERIC EQUIVALENT AVAILABLE — No
USE — Temporary relief of nasal congestion, decongest sinus openings, running nose, itching of nose or throat, and itchy, watery eyes due to hay fever or other upper respiratory allergies
ADVERSE REACTIONS SIGNIFICANT >10%: Central nervous system: Drowsiness, headache
1% to 10%: Cardiovascular: Tachycardia, palpitation Central nervous system: Nervousness, dizziness, insomnia, vertigo, lightheadedness, fatigue Gastrointestinal: Nausea, vomiting, xerostomia, diarrhea Genitourinary: Dysuria Neuromuscular & skeletal: Weakness Respiratory: Pharyngitis, cough increased Miscellaneous: Diaphoresis
CONTRAINDICATIONS — Hypersensitivity to pseudoephedrine, acrivastine (or other alkylamine antihistamines), or any component of the formulation; MAO inhibitor therapy within 14 days of initiating therapy; severe hypertension, severe coronary artery disease; renal impairment (Clcr 48 mL/minute)
WARNINGS / PRECAUTIONS Disease-related concerns: Asthma: Use with caution in patients with asthma. Cardiovascular disease: Use with caution in patients with high blood pressure and/or ischemic heart disease. Diabetes: Use with caution in patients with diabetes mellitus. GI obstruction: Use with caution in patients with GI obstruction. Increased intraocular pressure: Use with caution in patients with increased intraocular pressure. Prostatic hyperplasia/urinary obstruction: Use with caution in patients with prostatic hyperplasia and/or GU obstruction. Thyroid dysfunction: Use with caution in patients with thyroid dysfunction.
Special populations: Elderly: Use with caution in patients >60 years of age. Pediatrics: Not recommended for use in children.
DRUG INTERACTIONS Decreased effect of guanethidine, reserpine, methyldopa, and beta-blockers
Increased toxicity with MAO inhibitors (hypertensive crisis), sympathomimetics, CNS depressants, ethanol (sedation)
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Avoid ethanol (may increase sedation)
PREGNANCY RISK FACTOR — B (show table)
LACTATION — Enters breast milk/contraindicated
PRICING — (data from drugstore.com)Capsules (Semprex-D) 8-60 mg (30): $37.47
MECHANISM OF ACTION — Refer to Pseudoephedrine; acrivastine is an analogue of triprolidine and it is considered to be relatively less sedating than traditional antihistamines; believed to involve competitive blockade of H1-receptor sites resulting in the inability of histamine to combine with its receptor sites and exert its usual effects on target cells
PHARMACODYNAMICS / KINETICS Pseudoephedrine: See Pseudoephedrine.
Acrivastine: Metabolism: Minimally hepatic Time to peak: ~1.1 hours Excretion: Urine (84%); feces (13%)
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