ABACAVIR SULFATE; LAMIVUDINE
Clinical safety rating: safe
Abacavir sulfate and lamivudine are nucleoside reverse transcriptase inhibitors (NRTIs) used in combination with other antiretrovirals for the treatment of HIV-1 infection. They are available as a fixed-dose combination tablet (e.g., Epzicom).
Abacavir is a nucleoside reverse transcriptase inhibitor (NRTI) that, after intracellular phosphorylation to carbovir triphosphate, competes with natural deoxyguanosine triphosphate for incorporation into viral DNA, causing chain termination. Lamivudine is an NRTI that, after phosphorylation to lamivudine triphosphate, inhibits HIV-1 reverse transcriptase via incorporation into viral DNA, resulting in chain termination.
| Metabolism | Abacavir is primarily metabolized by alcohol dehydrogenase and glucuronyl transferase to form 5'-carboxylic acid and glucuronide metabolites; also a minor substrate of CYP450 (not major). Lamivudine is phosphorylated intracellularly to its active triphosphate and undergoes limited hepatic metabolism; mostly excreted unchanged in urine via renal organic cation transporters. |
| Excretion | Renal: Abacavir ~83% (metabolites), Lamivudine ~70% (unchanged). Fecal: Abacavir ~16%, Lamivudine minimal. Biliary: negligible. |
| Half-life | Abacavir: 1.5 h; Lamivudine: 5-7 h (intracellular 10-15 h). Clinical context: Both support twice-daily dosing; lamivudine's longer intracellular half-life allows once-daily dosing. |
| Protein binding | Abacavir: ~50% (albumin). Lamivudine: <36% (albumin). |
| Volume of Distribution | Abacavir: 0.86 L/kg. Lamivudine: 1.3 L/kg. Clinical meaning: Extensive distribution into total body water, including CNS and genital tract; lamivudine achieves higher intracellular concentrations in PBMCs. |
| Bioavailability | Abacavir: 83% oral. Lamivudine: 86% oral. Both well absorbed; food does not affect bioavailability. |
| Onset of Action | Oral: Antiviral effect begins within 1-2 weeks of therapy; maximal HIV RNA suppression by 4-8 weeks. |
| Duration of Action | Abacavir: 12 h (dosing interval). Lamivudine: 12-24 h (dosing interval). Continuous dosing required to maintain viral suppression; resistance develops if discontinued. |
| Molecular Weight | Abacavir sulfate: 670.77 Da; Lamivudine: 229.26 Da |
One tablet (abacavir 600 mg/lamivudine 300 mg) once daily, in combination with other antiretrovirals.
| Dosage form | TABLET |
| Renal impairment | For patients with CrCl <50 mL/min, the combination tablet is not recommended; individual component dosing is required. Lamivudine dose reduction needed: CrCl 30-49 mL/min: 150 mg once daily; CrCl 15-29 mL/min: 150 mg first dose then 100 mg daily; CrCl 5-14 mL/min: 150 mg first then 50 mg daily; CrCl <5 mL/min: 50 mg first then 25 mg daily. Abacavir: no adjustment required but caution with severe impairment. |
| Liver impairment | Abacavir is contraindicated in moderate to severe hepatic impairment (Child-Pugh B or C); no dose adjustment for mild. Lamivudine: no adjustment needed for mild-moderate; insufficient data for severe. |
| Pediatric use | For children weighing ≥25 kg, same once-daily dose may be used; for lower weights, individual components are recommended. FDA-approved for children ≥3 months. |
| Geriatric use | Age-related renal function decline may require adjustment; monitoring recommended. |
| 1st trimester | Safe. Use only if clearly needed. No increased risk of major birth defects in humans. |
| 2nd trimester | Safe. No evidence of fetal harm in clinical studies. |
| 3rd trimester | Safe. Monitor for lactic acidosis and hepatic steatosis, though risk is low. |
Clinical note
Pregnancy: Antiretroviral therapy is recommended for HIV-infected pregnant women to prevent vertical transmission. Abacavir/lamivudine is a preferred NRTI backbone in pregnancy, with extensive safety data.
| FDA category | Human |
| Placental transfer | Abacavir and lamivudine cross the placenta with cord blood concentrations similar to maternal plasma. |
| Breastfeeding |
■ FDA Black Box Warning
Hypersensitivity reactions (serious and sometimes fatal) have been associated with abacavir. Patients who carry the HLA-B*5701 allele are at high risk. Therapy should not be restarted in patients who have experienced a hypersensitivity reaction; rechallenge can cause life-threatening hypotension and death.
| Common Effects | Nausea, Headache, Fatigue, Diarrhea, Insomnia, Cough, Rash |
| Serious Effects | Abacavir hypersensitivity reaction (fever, rash, GI symptoms, respiratory distress); lactic acidosis with hepatic steatosis; severe hepatomegaly; pancreatitis; myocardial infarction risk (controversial). |
Hypersensitivity reaction to abacavir (e.g., positive HLA-B*5701 status)Severe hepatic impairmentConcurrent use with products containing emtricitabine or lamivudine
| Precautions | Hypersensitivity reactions (HLA-B*5701 screening required before initiation; discontinue permanently if hypersensitivity suspected); lactic acidosis and severe hepatomegaly with steatosis (including fatal cases); pancreatitis (especially in children); immune reconstitution syndrome; hepatotoxicity; risk of myocardial infarction (abacavir may be associated); monitoring of serum lactate, hepatic enzymes, and clinical status. |
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| Both components are excreted into human breast milk at low concentrations. Theoretical risk of viral resistance in the infant. In areas with low infant HIV infection risk, benefits of breastfeeding may outweigh risks; otherwise, formula feeding is recommended. |
| Lactation Rating | L3: Moderately Safe |
| Teratogenic Risk | Abacavir sulfate and lamivudine are classified as FDA Pregnancy Category C. In animal studies, abacavir showed embryotoxicity and increased fetal malformations at doses 35 times human exposure; lamivudine showed no teratogenicity at 130 times human exposure. Human data from the Antiretroviral Pregnancy Registry show no increased risk of major birth defects overall (first trimester exposure prevalence 3.0% vs background 2.7%). However, cases of neural tube defects have been reported with abacavir in early pregnancy. First trimester: potential risk of major malformations; second/third trimester: no specific trimester risks, but monitor for mitochondrial toxicity and lactic acidosis. |
| Fetal Monitoring | Monitor maternal HIV viral load and CD4 count every 3-4 weeks; perform fetal ultrasound for neural tube defects if exposed in first trimester; assess for signs of lactic acidosis/hepatic steatosis (maternal symptoms: nausea, abdominal pain, dyspnea); monitor infant for HIV infection, hematologic toxicity, and growth parameters postpartum. |
| Fertility Effects | No significant adverse effects on fertility have been reported in preclinical or human studies. Abacavir and lamivudine do not impair sperm parameters or ovulation in animal models. No specific human fertility impairment data, but HIV itself can affect fertility. |
| Food/Dietary | No significant food interactions; can be taken with or without food. Alcohol is not restricted but may increase risk of liver toxicity; avoid excessive alcohol consumption. |
| Clinical Pearls | Abacavir is associated with a potentially fatal hypersensitivity reaction (HSR) in HLA-B*5701-positive individuals; test for HLA-B*5701 prior to initiation and never rechallenge if HSR is suspected. Lamivudine is active against hepatitis B (HBV) but at lower doses; abrupt discontinuation may cause severe HBV flares. Monitor for lactic acidosis and hepatomegaly with steatosis (nucleoside analogue toxicity). |
| Patient Advice | Take exactly as prescribed; do not skip doses to prevent resistance. · Report any rash, fever, nausea, vomiting, abdominal pain, or extreme tiredness immediately—these may be signs of a serious allergic reaction. · Abacavir hypersensitivity can be fatal; if you have had an allergic reaction, never take abacavir again. · Inform all healthcare providers you are taking this medication, especially before starting new treatments. · Do not stop lamivudine without doctor advice; sudden stop can worsen hepatitis B. · Use if you have HIV; this combination is not a cure and can still transmit HIV. |