ABACAVIR AND LAMIVUDINE
Clinical safety rating: safe
Fixed-dose combination of two nucleoside reverse transcriptase inhibitors (NRTIs) for the treatment of HIV-1 infection. Abacavir is a carbocyclic nucleoside analogue and lamivudine is a cytidine analogue, both acting to inhibit viral reverse transcriptase.
Abacavir is a carbocyclic synthetic nucleoside analogue. Intracellularly, it is phosphorylated to carbovir triphosphate, an analogue of deoxyguanosine-5'-triphosphate (dGTP). Carbovir triphosphate inhibits the activity of HIV-1 reverse transcriptase (RT) by competing with the natural substrate dGTP and by incorporating into viral DNA, causing chain termination. Lamivudine is a synthetic nucleoside analogue. Intracellularly, it is phosphorylated to lamivudine triphosphate, which inhibits HIV-1 RT via DNA chain termination after incorporation into viral DNA. Both drugs are nucleoside reverse transcriptase inhibitors (NRTIs).
| Metabolism | Abacavir is primarily metabolized by alcohol dehydrogenase and glucuronyl transferase to form the 5'-carboxylic acid and 5'-glucuronide metabolites. Approximately 2% of abacavir is metabolized by CYP450 enzymes (CYP3A4, CYP2D6). Lamivudine undergoes limited metabolism; about 5.6% is metabolized to the trans-sulfoxide metabolite. Lamivudine is not significantly metabolized by CYP450 enzymes. |
| Excretion | Abacavir: 83% renal (primarily as metabolites via alcohol dehydrogenase and glucuronidation), 16% fecal. Lamivudine: ~70% renal as unchanged drug via active tubular secretion. |
| Half-life | Abacavir: ~1.5 h; Lamivudine: 5–7 h in adults, prolonged to ~9 h in children. Clinically, twice-daily dosing maintains therapeutic concentrations. |
| Protein binding | Abacavir: ~50% bound to plasma proteins. Lamivudine: <36% bound (primarily albumin). |
| Volume of Distribution | Abacavir: 0.86 L/kg (extensive extravascular distribution). Lamivudine: 1.3 L/kg (distributes into CSF and tissues). |
| Bioavailability | Abacavir: 83% (oral). Lamivudine: 86% (oral), decreased by ~30% with food. |
| Onset of Action | Oral: Antiviral effect begins within hours of first dose; maximal suppression typically achieved by 4 weeks. |
| Duration of Action | Oral: Dosing every 12 h; sustained viral suppression with adherence. Missed doses may lead to rapid viral rebound. |
One tablet (600 mg abacavir/300 mg lamivudine) orally once daily.
| Dosage form | TABLET |
| Renal impairment | CrCl ≥50 mL/min: no adjustment; CrCl <50 mL/min: fixed-dose combination contraindicated; use individual components with dose adjustment (lamivudine dose reduction). |
| Liver impairment | Mild hepatic impairment (Child-Pugh A): no adjustment; moderate or severe (Child-Pugh B or C): contraindicated (due to abacavir). |
| Pediatric use | Approved for children ≥3 months and ≥6 kg; weight-based dosing: abacavir 8 mg/kg twice daily (max 600 mg) and lamivudine 4 mg/kg twice daily (max 150 mg). Fixed-dose tablets available for children weighing ≥14 kg. |
| Geriatric use | No specific adjustments; monitor renal function and hematology due to age-related decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Use during pregnancy only if potential benefit justifies risk. Available data from the Antiretroviral Pregnancy Registry show no increased risk of birth defects. Monitor for hepatic decompensation in women co-infected with HBV.
| FDA category | Human |
| Placental transfer | Both abacavir and lamivudine cross the placenta in humans, with cord blood concentrations similar to maternal plasma. |
| Breastfeeding | Both drugs excreted in breast milk. M/P ratio not established. Potential for infant toxicity. Contraindicated in breastfeeding due to risk of HIV transmission and adverse effects. |
■ FDA Black Box Warning
Serious and sometimes fatal hypersensitivity reactions have been associated with abacavir. Hypersensitivity reactions are characterized by fever, rash, and constitutional symptoms. Abacavir should be discontinued immediately if hypersensitivity is suspected. Do not restart abacavir or any abacavir-containing product after a hypersensitivity reaction because more severe symptoms, including life-threatening hypotension and death, can occur within hours. Screening for the HLA-B*5701 allele is recommended prior to abacavir use; abacavir should not be used in patients who test positive for HLA-B*5701.
| Common Effects | nausea, headache, fatigue, insomnia, diarrhea, fever, rash |
| Serious Effects | Hypersensitivity reaction (abacavir: fever, rash, malaise, GI/respiratory symptoms, anaphylaxis); lactic acidosis; severe hepatomegaly with steatosis; pancreatitis; exacerbation of hepatitis B; hepatotoxicity; myocardial infarction (possible association with abacavir). |
["Presence of HLA-B*5701 allele","Prior hypersensitivity reaction to abacavir or lamivudine","Severe hepatic impairment (Child-Pugh class C)"]
| Precautions |
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| Teratogenic Risk | No evidence of teratogenicity in first trimester. Animal studies show no fetal harm. Inadequate human data for second and third trimesters; risk cannot be excluded. |
| Fetal Monitoring | Monitor LFTs, CBC, serum amylase, and HIV viral load monthly. Assess for hypersensitivity reaction. Fetal ultrasound for anomalies if exposure occurs in first trimester. |
| Fertility Effects | No impairment of fertility observed in animal studies. Human data lacking; no known effect on reproductive function. |
| ["Hypersensitivity reactions (see black box warning)","Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with NRTIs","Exacerbation of hepatitis B after discontinuation of lamivudine in patients co-infected with HBV; monitor hepatic function","Immune reconstitution syndrome including autoimmune disorders","Myocardial infarction risk: Some studies suggest increased risk with abacavir","Pancreatitis (especially in children) has been observed with lamivudine","Use with caution in patients with hepatic impairment (Child-Pugh class B or C) due to increased abacavir concentrations"] |
| Food/Dietary | No significant food interactions. Take with or without food. Avoid alcohol due to potential hepatotoxicity. |
| Clinical Pearls | Abacavir/lamivudine is a fixed-dose combination NRTI for HIV-1. Screen for HLA-B*5701 before abacavir initiation; if positive, contraindicated due to hypersensitivity risk. Dose adjustment required for CrCl <50 mL/min; avoid if CrCl <30 mL/min. Monitor for lactic acidosis and hepatomegaly with steatosis. Abacavir associated with increased cardiovascular risk; use caution in patients with high baseline risk. Lamivudine has activity against HBV; monitor for HBV flare upon discontinuation in co-infected patients. |
| Patient Advice | Take exactly as prescribed, with or without food. · Do not miss doses; if missed, take as soon as remembered unless close to next dose. · Report any rash, fever, or flu-like symptoms immediately (possible abacavir hypersensitivity). · This drug does not cure HIV or prevent transmission; use barrier protection. · Tell your doctor if you have liver disease, kidney disease, or heart disease. · Avoid alcohol as it may increase risk of liver problems. · Store at room temperature away from moisture and heat. |