Abacavir, lamivudine, and zidovudine: Drug information

(For additional information see "Abacavir, lamivudine, and zidovudine: Patient drug information" and see "Abacavir, lamivudine, and zidovudine: Pediatric drug information")
U.S. BRAND NAMES — Trizivir®
PHARMACOLOGIC CATEGORY Antiretroviral Agent, Reverse Transcriptase Inhibitor (Nucleoside)
DOSING: ADULTS — HIV treatment: Oral: 1 tablet twice daily. Note: Not recommended for patients <40 kg.
DOSING: PEDIATRIC — HIV treatment: Adolescents: Refer to adult dosing (not recommended for patients <40 kg).
(For additional information see "Abacavir, lamivudine, and zidovudine: Pediatric drug information")
DOSING: ELDERLY — Use with caution.
DOSING: RENAL IMPAIRMENT — Clcr 50 mL/minute: Avoid use.
DOSING: HEPATIC IMPAIRMENT — Use contraindicated.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet: Trizivir®: Abacavir 300 mg, lamivudine 150 mg, and zidovudine 300 mg
DOSAGE FORMS: CONCISE Tablet: Trizivir®: Abacavir 300 mg, lamivudine 150 mg, and zidovudine 300 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Administer without regard to food or water.
USE — Treatment of HIV infection (either alone or in combination with other antiretroviral agents) in patients whose regimen would otherwise contain the components of Trizivir®
ADVERSE REACTIONS SIGNIFICANT — Fatal hypersensitivity reactions have occurred in patients taking abacavir (in Trizivir®). If Trizivir® is to be restarted following an interruption in therapy, first evaluate the patient for previously unsuspected symptoms of hypersensitivity. Do not restart if hypersensitivity is suspected or if hypersensitivity cannot be ruled out.
The following information is based on CNA3005 study data concerning effects noted in patients receiving abacavir, lamivudine, and zidovudine. See individual agents for additional information.
>10%: Central nervous system: Headache (13%), malaise (12%), fatigue (12%) Gastrointestinal: Nausea (19%)
1% to 10%: Central nervous system: Fever/chills (6%), depression (6%), anxiety (5%) Dermatologic: Rash (5%) Endocrine & metabolic: Triglycerides increased (2% grade 3-4) Gastrointestinal: Nausea and vomiting (10%), diarrhea (7%), amylase increased (2%) Hematologic: Neutropenia (5%) Hepatic: ALT increased (6%) Neuromuscular & skeletal: CPK increased (7%) Otic: Ear infection (5%) Respiratory: Nose/throat infection (5%) Miscellaneous: Hypersensitivity (2% to 9% based on abacavir component), viral infection (5%)
Other (frequency unknown): Pancreatitis, GGT increased, fat redistribution, immune reconstitution syndrome
CONTRAINDICATIONS — Hypersensitivity to abacavir, lamivudine, zidovudine, or any component of the formulation; hepatic impairment. Do not rechallenge patients who have experienced hypersensitivity to abacavir.
WARNINGS / PRECAUTIONS Box warnings: Chronic hepatitis B: See "Disease-related concerns" below. Hematologic toxicity: See "Concerns related to adverse effects" below. HIV: Appropriate use: See "Disease-related concerns" below. Hypersensitivity reactions: See "Concerns related to adverse effects" below. Lactic acidosis/hepatomegaly: See "Concerns related to adverse effects" below. Myopathy: 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). Hematologic toxicity: [U.S. Boxed Warning]: Zidovudine has been associated with hematologic toxicities (eg, neutropenia, anemia); use with caution in patients with bone marrow compromise. Hypersensitivity reactions: [U.S. Boxed Warning]: Fatal hypersensitivity reactions have occurred in patients taking abacavir (in Trizivir®). Patients exhibiting symptoms of fever, skin rash, fatigue, respiratory symptoms (eg, pharyngitis, dyspnea, cough) and/or GI symptoms (eg, abdominal pain, nausea, vomiting, diarrhea) should discontinue therapy immediately and call for medical attention. Trizivir® should be permanently discontinued if hypersensitivity cannot be ruled out, even when other diagnoses are possible. Trizivir® 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 (eg, 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 Trizivir® is to be restarted following an interruption in therapy, first evaluate the patient for previously unsuspected symptoms of hypersensitivity. Do not restart if hypersensitivity is suspected or cannot be ruled out. To report these events on Trizivir® 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). Myopathy: [U.S. Boxed Warning]: Prolonged use of zidovudine has been associated with symptomatic myopathy and myositis.
Disease-related concerns: Chronic hepatitis B: [U.S. Boxed Warning]: Exacerbation of hepatitis B has been reported with discontinuation of lamivudine in coinfected HIV/HBV patients; monitor hepatic function closely for several months after discontinuing Trizivir® in coinfected patients. HIV: Appropriate use: [U.S. Boxed Warning]: This combination should only be used as part of a multidrug regimen for which the individual components are indicated. Renal impairment: Trizivir®, as a fixed-dose combination tablet, should not be used in patients with Clcr 50 mL/minute.
Concurrent drug therapy issues: Interferon alfa: Use with caution in combination with interferon alfa with or without ribavirin in HIV/HBV coinfected patients; monitor closely for hepatic decompensation, anemia, or neutropenia; dose reduction or discontinuation of interferon and/or ribavirin may be required if toxicity evident.
Special populations: Adults <40 kg: Trizivir®, as a fixed-dose combination tablet, should not be used in patients <40 kg or those requiring dosage adjustment. Pediatrics: Trizivir®, as a fixed-dose combination tablet, should not be used in children.
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 — See individual agents.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — See individual agents.
LACTATION — See individual agents.
BREAST-FEEDING CONSIDERATIONS — See individual agents.
DIETARY CONSIDERATIONS — May be taken without regard to food or water.
PRICING — (data from drugstore.com)Tablets (Trizivir) 300-150-300 mg (60): $1154.51
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms of overdose with zidovudine include nausea, vomiting, headache, dizziness, drowsiness, lethargy, confusion, and hematologic changes. Myocardial degeneration has been documented in animals during long-term high-dose toxicology studies; clinical relevance is unknown. Treatment is symptom-directed and supportive. Peritoneal dialysis and hemodialysis have little to no effect on the removal of the components of Trizivir®.
MECHANISM OF ACTION — The combination of abacavir, lamivudine, and zidovudine is believed to act synergistically to inhibit reverse transcriptase via DNA chain termination after incorporation of the nucleoside analogue as well as to delay the emergence of mutations conferring resistance.
PHARMACODYNAMICS / KINETICS — Bioavailability studies of Trizivir® show no difference in AUC or Cmax when compared to abacavir, lamivudine, and zidovudine given together as individual agents. See individual agents.