ABACAVIR; LAMIVUDINE
Clinical safety rating: safe
Abacavir/lamivudine is a fixed-dose combination of two nucleoside reverse transcriptase inhibitors (NRTIs) used for the treatment of HIV-1 infection in adults and children. It is often co-formulated with other antiretrovirals as part of combination antiretroviral therapy.
Abacavir is a carbocyclic synthetic nucleoside analogue (guanosine analogue) that is phosphorylated intracellularly to carbovir triphosphate, which competes with deoxyguanosine triphosphate for incorporation into viral DNA by HIV reverse transcriptase, leading to chain termination. Lamivudine is a synthetic nucleoside analogue (cytosine analogue) that is phosphorylated intracellularly to lamivudine triphosphate, which competes with deoxycytidine triphosphate for incorporation into viral DNA by HIV reverse transcriptase, causing chain termination.
| Metabolism | Abacavir is metabolized primarily by alcohol dehydrogenase and glucuronyl transferase (UGT1A1, UGT2B7) to form carboxylate and glucuronide metabolites. Lamivudine is not significantly metabolized; it is predominantly eliminated unchanged in the urine via glomerular filtration and active tubular secretion (involving OCT2 and MATE transporters). |
| Excretion | Abacavir: 83% renal (1.2% unchanged, rest as metabolites), 16% fecal. Lamivudine: ~70% renal (mostly unchanged via tubular secretion), ~5% fecal. |
| Half-life | Abacavir: 1.5 hr (single dose) to 2 hr (steady state), clinically short requiring twice-daily dosing. Lamivudine: 5-7 hr (adults), extended in renal impairment (up to 20 hr with CrCl <50 mL/min). |
| Protein binding | Abacavir: ~50% bound to plasma proteins (albumin, alpha-1-acid glycoprotein). Lamivudine: <36% bound to albumin. |
| Volume of Distribution | Abacavir: 0.86 ± 0.15 L/kg; indicates extensive extravascular distribution (CNS, genital tract). Lamivudine: 1.3 ± 0.4 L/kg; distributes into CSF (ratio 0.16) and mucosa. |
| Bioavailability | Oral: Abacavir ~83% (with/without food). Lamivudine ~86% (reduced by ~30% with food; administer without regard to food per label). No parenteral forms. |
| Onset of Action | Oral: Abacavir inhibits HIV RT within 1 hr post-dose; Lamivudine requires intracellular triphosphorylation, maximal antiviral activity within 2-4 hr. Clinical antiviral effect measurable after 1-2 weeks. |
| Duration of Action | Oral: Antiviral effect persists for dosing interval (12 hr) but requires consistent levels to prevent resistance. Intracellular half-life of active triphosphates: abacavir ~12 hr, lamivudine ~15 hr. |
One tablet (abacavir 600 mg/lamivudine 300 mg) orally once daily with or without food. Can be used in combination with other antiretrovirals.
| Dosage form | TABLET |
| Renal impairment | Not recommended for patients with CrCl <50 mL/min due to lamivudine accumulation. No dose adjustment for abacavir alone, but the fixed-dose combination is contraindicated in renal impairment (CrCl <30 mL/min). For CrCl 30-49 mL/min, use individual components with lamivudine dose reduction (150 mg once daily). |
| Liver impairment | Abacavir is contraindicated in Child-Pugh Class B or C hepatic impairment. Lamivudine may require dose reduction in severe hepatic impairment (Child-Pugh C) due to decreased clearance. For mild impairment (Child-Pugh A), no adjustment necessary. |
| Pediatric use | Approved for children ≥3 months and weighing ≥6 kg. Dosing based on weight: for combination tablet, only for patients weighing ≥25 kg; otherwise use individual liquid formulations. Weight-based dosing: abacavir 8 mg/kg twice daily (max 300 mg) and lamivudine 4 mg/kg twice daily (max 150 mg) or as per age-appropriate guidelines. |
| Geriatric use | No specific dose adjustment for age; use caution due to age-related renal decline and monitor renal function. Consider using individual components if renal function is impaired. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Abacavir/lamivudine is generally avoided during pregnancy unless the benefit outweighs the risk; limited data in pregnancy. Antiretroviral Pregnancy Registry data do not show an increased risk of major birth defects overall, but abacavir has been associated with a possible small increased risk of cleft lip/palate in some studies, though not confirmed. Use only if clearly needed.
| FDA category | Human |
| Placental transfer | Abacavir and lamivudine both cross the placenta. Lamivudine reaches cord blood levels similar to maternal levels; abacavir also achieves significant placental transfer. |
| Breastfeeding |
■ FDA Black Box Warning
Serious and sometimes fatal hypersensitivity reactions have been associated with abacavir. Patients who carry the HLA-B*5701 allele are at increased risk. Discontinue abacavir immediately if hypersensitivity is suspected, regardless of HLA-B*5701 status. Never restart abacavir after a hypersensitivity reaction because more severe symptoms, including life-threatening hypotension and death, can occur.
| Common Effects | Nausea, Headache, Fatigue, Diarrhea, Insomnia, Cough, Rash, Fever |
| Serious Effects | Hypersensitivity reaction (abacavir)Lactic acidosis with hepatic steatosisSevere hepatomegalyPancreatitis (especially in children on lamivudine)Exacerbation of hepatitis B (if lamivudine used alone or discontinued)Mitochondrial toxicity (peripheral neuropathy, myopathy) |
History of hypersensitivity to abacavir or lamivudine; presence of HLA-B*5701 allele (contraindicated for abacavir); moderate to severe hepatic impairment (Child-Pugh B or C) for abacavir; caution in renal impairment (adjust lamivudine dose).
| Precautions | Hypersensitivity reactions (may be fatal); HLA-B*5701 screening required before initiation; hepatic toxicity/lactic acidosis; pancreatitis; immune reconstitution syndrome; exacerbation of hepatitis B (lamivudine component); monitoring of hepatic function, pancreatic enzymes, and lactic acid levels; renal impairment (dose adjustment for lamivudine); drug interactions (e.g., methadone, sorbitol). |
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| Both drugs are excreted into human breast milk. Abacavir milk-to-plasma ratio is approximately 1.0; lamivudine M/P ratio is approximately 0.6. Limited data suggest low infant exposure. Alternatives exist; in settings where formula is available, breastfeeding is not recommended due to risk of HIV transmission. If mother is HIV-positive, breastfeeding is contraindicated regardless of therapy. |
| Teratogenic Risk | Abacavir and lamivudine cross the placenta. No increased risk of major birth defects has been observed in first trimester exposure based on Antiretroviral Pregnancy Registry data. Second and third trimester exposure is not associated with teratogenicity. Potential risk of mitochondrial toxicity in infants with in utero exposure, but clinical significance is unclear. |
| Fetal Monitoring | Monitor maternal CD4 count, HIV viral load, and complete blood count. Assess liver function tests due to abacavir hypersensitivity reaction risk (especially in HLAB*5701 positive patients). Fetal ultrasound for growth and anatomy as per standard prenatal care. Neonatal monitoring for anemia and neutropenia if used near term. |
| Fertility Effects | Abacavir and lamivudine have no known negative effects on male or female fertility. No impairment in fertility observed in animal studies. HIV infection itself may impair fertility; effective antiretroviral therapy may improve fertility outcomes. |
| Food/Dietary | No significant food interactions. Alcohol should be avoided or limited due to potential hepatotoxicity. |
| Clinical Pearls | Abacavir/lamivudine is a fixed-dose combination NRTI used for HIV-1 infection. Screen for HLA-B*5701 prior to abacavir initiation; if positive, abacavir is contraindicated due to risk of hypersensitivity reaction. Monitor for lactic acidosis and hepatomegaly with steatosis, especially in women and obese patients. Dose adjustment needed for CrCl <50 mL/min; avoid in ESRD. Administer once daily without regard to food. Assess renal function before starting and periodically. |
| Patient Advice | Take one tablet daily at the same time to maintain steady drug levels. · Do not miss doses as it may lead to drug resistance; if missed, take as soon as remembered unless close to next dose. · Report any rash, fever, fatigue, gastrointestinal symptoms, or respiratory symptoms immediately as these may indicate abacavir hypersensitivity. · Abacavir/lamivudine does not cure HIV or prevent transmission; use barrier protection and avoid sharing needles. · May be taken with or without food; no specific food restrictions. · Avoid alcohol as it may increase risk of liver toxicity. · Inform your doctor of all medications, including over-the-counter and herbal products. · Store at room temperature away from moisture and heat. |