Abacavir-Ziagen

U.S. BRAND NAMES — Ziagen®
PHARMACOLOGIC CATEGORY Antiretroviral Agent, Reverse Transcriptase Inhibitor (Nucleoside)
DOSING: ADULTS — HIV treatment: Oral: 300 mg twice daily or 600 mg once daily in combination with other antiretroviral agents
DOSING: PEDIATRIC — HIV treatment: Oral: 3 months to 16 years: 8 mg/kg body weight twice daily (maximum: 300 mg twice daily) in combination with other antiretroviral agents
(For additional information see "Abacavir: Pediatric drug information")
DOSING: ELDERLY — Refer to adult dosing.
DOSING: HEPATIC IMPAIRMENT Mild dysfunction (Child-Pugh score 5-6): 200 mg twice daily (oral solution is recommended)
Moderate-to-severe dysfunction: Use is contraindicated by the manufacturer
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, oral: Ziagen®: 20 mg/mL (240 mL) [strawberry-banana flavor]
Tablet: 300 mg
DOSAGE FORMS: CONCISE Solution, oral: Ziagen®: 20 mg/mL
Tablet: Ziagen®: 300 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — May be administered with or without food.
USE — Treatment of HIV infections in combination with other antiretroviral agents
ADVERSE REACTIONS SIGNIFICANT — Hypersensitivity reactions (which may be fatal) occur in ~5% of patients (see Warnings/Precautions). Symptoms may include anaphylaxis, fever, rash (including erythema multiforme), fatigue, diarrhea, abdominal pain; respiratory symptoms (eg, pharyngitis, dyspnea, cough, adult respiratory distress syndrome, or respiratory failure); headache, malaise, lethargy, myalgia, myolysis, arthralgia, edema, paresthesia, nausea and vomiting, mouth ulcerations, conjunctivitis, lymphadenopathy, hepatic failure, and renal failure.
Note: Rates of adverse reactions were defined during combination therapy with other antiretrovirals (lamivudine and efavirenz or lamivudine and zidovudine). Only reactions which occurred at a higher frequency in adults (except where noted) than in the comparator group are noted. Adverse reaction rates attributable to abacavir alone are not available.
>10%: Central nervous system: Headache (7% to 13%) Gastrointestinal: Nausea (7% to 19%, children 9%)
1% to 10%: Central nervous system: Depression (6%), fever/chills (6%, children 9%), anxiety (5%) Dermatologic: Rash (5% to 6%, children 7%) Endocrine & metabolic: Triglycerides increased (2% to 6%) Gastrointestinal: Diarrhea (7%), vomiting (children 9%), amylase increased (2%) Hematologic: Thrombocytopenia (1%) Hepatic: AST increased (6%) Neuromuscular and skeletal: Musculoskeletal pain (5% to 6%) Miscellaneous: Hypersensitivity reactions (2% to 9%; may include reactions to other components of antiretroviral regimen), infection (EENT 5%)
<1% (Limited to important or life-threatening): Erythema multiforme, fat redistribution, GGT increased, hepatic steatosis, hepatomegaly, hepatotoxicity, lactic acidosis, pancreatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis
CONTRAINDICATIONS — Hypersensitivity to abacavir or any component of the formulation (do not rechallenge patients who have experienced hypersensitivity to abacavir); moderate-to-severe hepatic impairment
WARNINGS / PRECAUTIONS Box warnings: Hypersensitivity reactions: See "Concerns related to adverse effects" below. Lactic acidosis/hepatomegaly: See "Concerns related to adverse effects" below.
Concerns related to adverse effects: Fat redistribution: May cause redistribution of fat (eg, buffalo hump, peripheral wasting with increased abdominal girth, cushingoid appearance). Hypersensitivity reactions: [U.S. Boxed Warning]: Serious and sometimes fatal hypersensitivity reactions have occurred. Patients exhibiting symptoms from two or more of the following: Fever, skin rash, constitutional symptoms (malaise, fatigue, aches), respiratory symptoms (eg, pharyngitis, dyspnea, cough), and GI symptoms (eg, abdominal pain, diarrhea, nausea, vomiting) should discontinue therapy immediately and call for medical attention. Abacavir should be permanently discontinued if hypersensitivity cannot be ruled out, even when other diagnoses are possible. Abacavir SHOULD NOT be restarted because more severe symptoms may occur within hours, including LIFE-THREATENING HYPOTENSION AND DEATH. Fatal hypersensitivity reactions have occurred following the reintroduction of abacavir in patients whose therapy was interrupted (ie, interruption in drug supply, temporary discontinuation while treating other conditions). Reactions occurred within hours. In some cases, signs of hypersensitivity may have been previously present, but attributed to other medical conditions (eg, acute onset respiratory diseases, gastroenteritis, reactions to other medications). If abacavir is restarted following an interruption in therapy, evaluate the patient for previously unsuspected symptoms of hypersensitivity. Do not restart if hypersensitivity is suspected or if hypersensitivity cannot be ruled out. To report these events on abacavir hypersensitivity, a registry has been established (1-800-270-0425). Immune reconstitution syndrome: Patients may develop immune reconstitution syndrome resulting in the occurrence of an inflammatory response to an indolent or residual opportunistic infection; further evaluation and treatment may be required. Lactic acidosis/hepatomegaly: [U.S Boxed Warning]: Lactic acidosis and severe hepatomegaly with steatosis have been reported with nucleoside analogues, including fatal cases; use with caution in patients with risk factors for liver disease (risk may be increased with female gender, obesity, pregnancy or prolonged exposure) and suspend treatment in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or hepatotoxicity (transaminase elevation may/may not accompany hepatomegaly and steatosis).
Disease-related concerns: Hepatic impairment: Use with caution in patients with mild hepatic dysfunction (contraindicated in moderate-to-severe dysfunction). HIV: Appropriate use: Abacavir should always be used as a component of a multidrug regimen.
Special populations: Pediatrics: Safety and efficacy have not been established in children <3 months of age.
RESTRICTIONS — An FDA-approved medication guide and warning card (summarizing symptoms of hypersensitivity) must be distributed when dispensing an outpatient prescription (new or refill) where this medication is to be used without direct supervision of a healthcare provider. Medication guides are available at http://www.fda.gov/cder/Offices/ODS/medication_guides.htm.
DRUG INTERACTIONS Ganciclovir, valganciclovir: May increase the adverse/toxic effects of nucleoside reverse transcriptase inhibitors.
Ribavirin: Concomitant use of ribavirin and nucleoside analogues may increase the risk of developing hepatic decompensation or other signs of mitochondrial toxicity, including pancreatitis or lactic acidosis.
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Ethanol may increase the risk of toxicity.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — It is not known if abacavir crosses the human placenta. No increased risk of overall birth defects has been observed following 1st trimester exposure according to data collected by the antiretroviral pregnancy registry. Cases of lactic acidosis/hepatic steatosis syndrome have been reported in pregnant women receiving nucleoside analogues. It is not known if pregnancy itself potentiates this known side effect; however, pregnant women may be at increased risk of lactic acidosis and liver damage. Hepatic enzymes and electrolytes should be monitored frequently during the 3rd trimester of pregnancy in women receiving nucleoside analogues. Dose adjustment is not needed for pregnancy. The Perinatal HIV Guidelines Working Group considers abacavir to be an alternative NRTI in dual nucleoside combination regimens. Health professionals are encouraged to contact the antiretroviral pregnancy registry to monitor outcomes of pregnant women exposed to antiretroviral medications (1-800-258-4263 or www.APRegistry.com).
LACTATION — Excretion in breast milk unknown/contraindicated
BREAST-FEEDING CONSIDERATIONS — HIV-infected mothers are discouraged from breast-feeding to decrease potential transmission of HIV.
DIETARY CONSIDERATIONS — May be taken with or without food.
PRICING — (data from drugstore.com)Solution (Ziagen) 20 mg/mL (240): $113.54
Tablets (Ziagen) 300 mg (60): $466.91
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Treatment should be symptom-directed and supportive. Benefit of dialysis is unknown.
CANADIAN BRAND NAMES — Ziagen®
INTERNATIONAL BRAND NAMES — Abamune (IN); Filabac (AR); Zepril (AR); Ziagen (AN, AT, AU, BB, BE, BG, BM, BS, BZ, CA, CH, CL, CO, CR, CZ, DE, DK, DO, ES, FI, FR, GB, GR, GT, GY, HK, HN, HU, IE, IL, IT, JM, KR, NI, NL, NO, NZ, PA, PE, PL, PT, RU, SE, SG, SR, SV, TR, TT, TW, VE); Ziagenavir (AR, BR, MX, TH, UY)
MECHANISM OF ACTION — Nucleoside reverse transcriptase inhibitor. Abacavir is a guanosine analogue which is phosphorylated to carbovir triphosphate which interferes with HIV viral RNA-dependent DNA polymerase resulting in inhibition of viral replication.
PHARMACODYNAMICS / KINETICS Absorption: Rapid and extensive absorption
Distribution: Vd: 0.86 L/kg
Protein binding: 50%
Metabolism: Hepatic via alcohol dehydrogenase and glucuronyl transferase to inactive carboxylate and glucuronide metabolites
Bioavailability: 83%
Half-life elimination: 1.5 hours
Time to peak: 0.7-1.7 hours
Excretion: Primarily urine (as metabolites, 1.2% as unchanged drug); feces (16% total dose)
PATIENT INFORMATION — If you experience any of the following: Fever, skin rash, fatigue, nausea, vomiting, diarrhea, abdominal pain, contact your prescriber immediately. This drug is not a cure for HIV infection, nor will it reduce the risk of transmission to others. You will need frequent blood tests to adjust dosage for maximum therapeutic effect. Take as directed; do not discontinue (even if feeling better). You may experience headache or muscle pain or weakness. If you are instructed to stop the medication, do not take this medication in the future. Do not restart without specific instructions by your prescriber.