LAMIVUDINE; ZIDOVUDINE; ABACAVIR
Clinical safety rating: safe
Other bone marrow suppressants may have additive effects Can cause severe myelosuppression and myopathy.
Lamivudine, zidovudine, and abacavir are nucleoside reverse transcriptase inhibitors (NRTIs). They are phosphorylated intracellularly to active metabolites that compete with natural nucleotides for incorporation into viral DNA, causing chain termination and inhibition of HIV reverse transcriptase.
| Metabolism | Lamivudine: predominantly renal excretion as unchanged drug; minor hepatic metabolism. Zidovudine: hepatic glucuronidation (UGT2B7); renal excretion. Abacavir: hepatic alcohol dehydrogenase and glucuronidation (UGT2B7); renal excretion. |
| Excretion | Lamivudine: ~70% excreted unchanged in urine via glomerular filtration and active tubular secretion; Zidovudine: ~75% excreted as metabolites (primarily 5'-glucuronide) in urine, with <20% unchanged; Abacavir: ~83% excreted as metabolites in urine (via alcohol dehydrogenase and glucuronidation) and ~16% in feces; Total renal elimination accounts for >80% of clearance for all three components. |
| Half-life | Lamivudine: 5-7 hours (single dose), prolonged to ~11 hours in renal impairment; Zidovudine: 1.1 hours (terminal), increased to 1.4 hours in hepatic impairment; Abacavir: 1.5 hours (terminal), slightly prolonged in hepatic impairment; Clinical context: Dosing interval of 12 hours requires therapeutic drug monitoring in renal/hepatic dysfunction. |
| Protein binding | Lamivudine: <36% bound primarily to albumin; Zidovudine: 34-38% bound to albumin; Abacavir: ~50% bound to albumin (low affinity); Total binding: <50% for all, minimal drug interactions at binding sites. |
| Volume of Distribution | Lamivudine: 1.3 L/kg (total body water); Zidovudine: 1.6 L/kg (higher in CSF, ratio 0.6); Abacavir: 0.86 L/kg (extensively distributed into tissues including CSF); Clinical meaning: Indicates good penetration into cerebrospinal fluid and lymphoid tissues. |
| Bioavailability | Lamivudine: 86-88% (oral); Zidovudine: 60-70% (oral, reduced by food); Abacavir: 83% (oral, no food effect); All three dose as oral tablets with fixed combination; no parenteral formulations for this combination. |
| Onset of Action | Oral: Lamivudine: 1-2 hours (peak plasma concentration); Zidovudine: 0.5-1.5 hours; Abacavir: 0.5-2 hours; Clinical antiviral effect observed within 2-4 weeks (based on viral load reduction). |
| Duration of Action | Lamivudine: 12 hours (dosing interval) with sustained intracellular triphosphate half-life of 18-22 hours; Zidovudine: 4-8 hours; Abacavir: 12 hours (dosing interval) with intracellular carbovir triphosphate half-life of 12-21 hours; Combination therapy dosed every 12 hours; duration limited by resistance if adherence poor. |
| Molecular Weight | 678.7 |
One tablet (300 mg abacavir, 150 mg lamivudine, 300 mg zidovudine) orally twice daily.
| Dosage form | TABLET |
| Renal impairment | Not recommended for CrCl <50 mL/min. For CrCl 30-49 mL/min: Consider separate components with zidovudine dose adjustment (e.g., 300 mg once daily). CrCl <30 mL/min: Contraindicated fixed-dose combination. |
| Liver impairment | Child-Pugh A: Use with caution; no specific dose adjustment defined. Child-Pugh B or C: Contraindicated due to abacavir and zidovudine metabolism. |
| Pediatric use | Weight-based: For children ≥25 kg, same as adult dose. For <25 kg, use individual components: abacavir 8 mg/kg twice daily (max 300 mg), lamivudine 4 mg/kg twice daily (max 150 mg), zidovudine 160 mg/m² twice daily (max 300 mg). |
| Geriatric use | Monitor renal function and hematologic parameters; dose adjustment based on renal function; increased risk of anemia and neutropenia. |
| 1st trimester | Limited human data; animal studies show no evidence of teratogenicity. Use only if benefit outweighs risk. |
| 2nd trimester | No increased risk of major birth defects reported; monitor for hematologic toxicity in mother. |
| 3rd trimester | Safe for use in prevention of mother-to-child transmission; zidovudine component reduces perinatal transmission. |
Clinical note
Other bone marrow suppressants may have additive effects Can cause severe myelosuppression and myopathy.
| FDA category | Human |
| Placental transfer | All three drugs cross the placenta with cord blood concentrations similar to maternal plasma (lamivudine and zidovudine have extensive transfer; abacavir moderately). |
| Breastfeeding |
■ FDA Black Box Warning
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases; exacerbation of hepatitis B (lamivudine component) upon discontinuation; hypersensitivity reactions (abacavir component), which may be fatal; hematologic toxicity (zidovudine component), including neutropenia and anemia.
| Common Effects | Anemia |
| Serious Effects |
History of hypersensitivity reaction to abacavir (including HLA-B*5701 positive status)Severe hepatic impairmentNeonates less than 4 weeks of ageConcomitant use with other zidovudine- or lamivudine-containing products
| Precautions | Hepatic toxicity, lactic acidosis, pancreatitis, bone marrow suppression (zidovudine), hypersensitivity to abacavir (screen for HLA-B*5701 allele prior to use), immune reconstitution syndrome, fat redistribution, myocardial infarction risk (abacavir), mitochondrial toxicity (neonates). |
| Food/Dietary |
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| All three drugs are excreted into human breast milk. In mothers on antiretroviral therapy, breastfeeding is generally avoided in settings where formula is available and acceptable to reduce potential infant exposure and risk of resistance. |
| Lactation Rating | L4 (Possibly Hazardous) |
| Teratogenic Risk | First trimester: Lamivudine, zidovudine, and abacavir are not associated with increased risk of major malformations based on human data from the Antiretroviral Pregnancy Registry. Zidovudine crosses placenta; lamivudine and abacavir also cross. Second and third trimesters: Continued use recommended to prevent perinatal transmission; no known fetal toxicity. Excluding prematurity and low birth weight possibly associated with antiretroviral therapy, no specific trimester risks identified. |
| Fetal Monitoring | Maternal: Complete blood count (CBC), liver function tests, renal function, CD4 count, HIV viral load; monitor for mitochondrial toxicity in infants exposed in utero. Fetal/neonatal: Monitor for anemia, neutropenia, and hyperlactatemia (zidovudine). No specific fetal monitoring beyond standard ultrasound; non-stress test if indicated. |
| Fertility Effects | No clinically significant effects on fertility in humans. In animal studies, no impairment of fertility observed with lamivudine, zidovudine, or abacavir. |
| No significant food interactions. Take with or without food. |
| Clinical Pearls | Triple antiretroviral combination of two NRTIs (lamivudine, abacavir) and one NNRTI (zidovudine). Note: Abacavir requires HLA-B*5701 screening before initiation to avoid hypersensitivity reaction. Zidovudine can cause macrocytic anemia and neutropenia, monitor CBC. Lamivudine has minimal CYP interactions. This fixed-dose combination is not recommended for use with other NRTIs or when a PI-based regimen is preferred. |
| Patient Advice | Take this medication exactly as prescribed, with or without food. · Do not miss doses; if you miss a dose, take it as soon as you remember, but do not double the next dose. · Get tested for HLA-B*5701 before starting abacavir to avoid a severe allergic reaction. · Report any rash, fever, or other signs of hypersensitivity immediately. · This drug does not cure HIV; it helps control the virus and reduces transmission risk. · Regular blood tests are required to monitor for side effects like anemia and neutropenia. · Avoid breastfeeding; HIV can be transmitted through breast milk. |