ABACAVIR SULFATE AND LAMIVUDINE
Clinical safety rating: safe
Abacavir sulfate and lamivudine is a fixed-dose combination of two nucleoside reverse transcriptase inhibitors (NRTIs) used for the treatment of HIV-1 infection. It is administered in combination with other antiretroviral agents to suppress viral replication and improve immune function.
Abacavir is a carbocyclic synthetic nucleoside analog of guanosine; it is phosphorylated intracellularly to carbovir triphosphate, which inhibits HIV-1 reverse transcriptase by competing with the natural substrate dGTP and by incorporating into viral DNA, causing chain termination. Lamivudine is a synthetic nucleoside analogue of cytidine; it is phosphorylated intracellularly to lamivudine triphosphate, which inhibits HIV-1 reverse transcriptase via competitive inhibition and chain termination.
| Metabolism | Abacavir is primarily metabolized by alcohol dehydrogenase and glucuronyl transferase to form the 5'-carboxylic acid and glucuronide metabolites, which are excreted in urine and feces. Lamivudine is predominantly cleared by renal excretion of unchanged drug via glomerular filtration and active tubular secretion; hepatic metabolism accounts for a minor pathway (trans-sulfoxidation). |
| Excretion | Renal: abacavir ~83% as metabolites (<2% unchanged), lamivudine ~70% unchanged; biliary/fecal: minimal. |
| Half-life | Abacavir: ~1.5 h; Lamivudine: ~5-7 h (adults), prolongation in renal impairment. |
| Protein binding | Abacavir: ~50% (albumin); Lamivudine: <36% (albumin, α1-acid glycoprotein). |
| Volume of Distribution | Abacavir: ~0.86 L/kg; Lamivudine: ~1.3 L/kg; distribution into CSF and tissues. |
| Bioavailability | Oral: Abacavir ~83%; Lamivudine ~86-100% (capsule/tablet); solution: ~92%. |
| Onset of Action | Oral: antiretroviral effect begins within hours; clinical suppression of HIV RNA detectable within 2-4 weeks. |
| Duration of Action | Abacavir: ~12 h (requires twice-daily dosing); Lamivudine: ~24 h (once-daily adequate). |
One tablet (600 mg abacavir/300 mg lamivudine) once daily orally, or with food, in combination with other antiretroviral agents.
| Dosage form | TABLET |
| Renal impairment | Contraindicated in patients with CrCl <30 mL/min. For CrCl 30-49 mL/min: reduce lamivudine dose (e.g., using individual components). No dose adjustment for abacavir alone, but the fixed-dose combination is not recommended due to lamivudine component. |
| Liver impairment | Abacavir is contraindicated in patients with moderate to severe hepatic impairment (Child-Pugh B or C). Lamivudine requires no adjustment in mild hepatic impairment; limited data for severe impairment. |
| Pediatric use | Approved for children ≥3 months and weighing ≥6 kg. Dosing based on weight (tablets or oral solution): e.g., for weight 25-40 kg: 600 mg abacavir/300 mg lamivudine once daily or weight-adjusted twice-daily doses of individual components. |
| Geriatric use | Limited data; monitor renal function due to age-related decline in CrCl, and adjust lamivudine if necessary. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Abacavir and lamivudine are both FDA Pregnancy Category C. Use during pregnancy only if potential benefit justifies potential risk. No adequate and well-controlled studies in pregnant women. Antiretroviral Pregnancy Registry data for abacavir do not suggest a major teratogenic risk; lamivudine also shows no increased birth defects in registry. However, cases of lactic acidosis and hepatotoxicity have been reported in pregnant women receiving NRTIs. Recommend using in pregnancy only if clearly needed and with close monitoring.
| FDA category | Human |
| Placental transfer | Abacavir crosses the placenta, and concentrations in cord blood are similar to maternal blood. Lamivudine also crosses extensively, achieving levels in cord blood that approximate maternal levels. |
■ FDA Black Box Warning
Hypersensitivity reactions (including fatalities) have occurred with abacavir-containing products. Patients who carry the HLA-B*5701 allele are at increased risk. Serious hypersensitivity reactions are characterized by fever, rash, fatigue, gastrointestinal symptoms, and respiratory symptoms. Abacavir should be discontinued immediately and never restarted if hypersensitivity is suspected, even if other diagnoses are possible, unless the HLA-B*5701 allele is absent and the reaction is clearly not abacavir-related.
| Common Effects | Nausea, Headache, Fatigue, Diarrhea, Insomnia, Rash, Fever |
| Serious Effects | Hypersensitivity reaction (anaphylaxis, Stevens-Johnson syndrome); lactic acidosis; hepatotoxicity (including hepatic steatosis); pancreatitis; myocardial infarction (abacavir potential association); immune reconstitution syndrome. |
["Hypersensitivity to abacavir, lamivudine, or any component of the formulation","HLA-B*5701 positive patients (contraindicated for abacavir-containing products)","Moderate to severe hepatic impairment (Child-Pugh class B or C) (for abacavir)","Caution with severe renal impairment (CrCl <30 mL/min) as fixed-dose combination not recommended"]
Loading safety data…
| Breastfeeding | Abacavir and lamivudine are excreted in human breast milk. M/P ratio: Abacavir 0.85; lamivudine 1.0-2.0. Infant exposure estimated at <5% of maternal weight-adjusted dose. WHO recommends breastfeeding while on antiretroviral therapy with undetectable viral load. Theoretical risk of mitochondrial toxicity in infants requires caution. |
| Teratogenic Risk | Abacavir sulfate and lamivudine combination: No increased risk of birth defects based on prospective pregnancy registries (Antiretroviral Pregnancy Registry). First trimester: No evidence of teratogenicity. Second and third trimesters: No fetal toxicity reported. Exposures throughout gestation not associated with major malformations. |
| Fetal Monitoring | Maternal: HIV viral load, CD4 count, liver function tests, complete blood count, and renal function every 1-3 months. Fetal: Ultrasound for growth and anatomy (standard). Monitor for hypersensitivity reaction (abacavir) with HLA-B*5701 testing before therapy. |
| Fertility Effects | No known adverse effects on human fertility. Studies in animals at high doses showed no impairment of fertility. May restore ovulation in HIV-infected women due to improved health. |
| Precautions |
| ["Hypersensitivity reactions associated with abacavir","Hepatic decompensation and lactic acidosis/hepatomegaly with steatosis reported with nucleoside analogues","Exacerbation of hepatitis B after lamivudine discontinuation in patients co-infected with HBV and HIV","Immune reconstitution syndrome","Increased risk of myocardial infarction with abacavir use (controversial)","Pancreatitis, especially in children or those with risk factors","Fat redistribution and accumulation","Monitoring of liver function tests, amylase, and lactic acid levels"] |
| Food/Dietary | No significant food interactions; can be taken with or without food. |
| Clinical Pearls | Abacavir is associated with a hypersensitivity reaction (HSR) in HLA-B*5701-positive patients; screen before initiation. Lamivudine has activity against both HIV-1 and HBV, but may cause HBV flare upon discontinuation in co-infected patients. Monitor for immune reconstitution syndrome. Dosage adjustment required for renal impairment (lamivudine component). |
| Patient Advice | Take exactly as prescribed, with or without food. · Do not stop taking without consulting your doctor; stopping lamivudine can worsen hepatitis B. · Seek immediate medical help if you experience fever, rash, nausea, vomiting, abdominal pain, fatigue, or difficulty breathing (signs of hypersensitivity reaction). · Inform all healthcare providers that you are taking this medication, especially if you need a new prescription. · Store at room temperature, away from moisture and heat. |