EPZICOM
Clinical safety rating: caution
Comprehensive clinical and safety monograph for EPZICOM (EPZICOM).
EPZICOM is a combination of abacavir and lamivudine, both nucleoside reverse transcriptase inhibitors (NRTIs). Abacavir is a guanosine analogue that is phosphorylated to carbovir triphosphate, which competes with dGTP for incorporation into viral DNA and causes chain termination. Lamivudine is a cytidine analogue that is phosphorylated to lamivudine triphosphate, which inhibits HIV-1 reverse transcriptase via DNA chain termination.
| Metabolism | Abacavir is metabolized primarily by alcohol dehydrogenase and glucuronyl transferase; lamivudine is eliminated renally as unchanged drug and undergoes limited hepatic metabolism (5-10%). |
| Excretion | Abacavir: 83% as metabolites in urine, 16% in feces; Lamivudine: 71% unchanged in urine within 24 hours, 5-10% as trans-sulfoxide metabolite in urine; Biliary excretion minimal. |
| Half-life | Abacavir: 1.54 ± 0.63 hours (terminal), Lamivudine: 13-19 hours (terminal); effective half-life of abacavir 1.5 hours, lamivudine 12-15 hours at steady state. |
| Protein binding | Abacavir: ~49% to human plasma proteins, independent of concentration; Lamivudine: <36% to plasma albumin (in vitro). |
| Volume of Distribution | Abacavir: 0.86 ± 0.15 L/kg; Lamivudine: 1.3 ± 0.4 L/kg; extensive distribution into extravascular spaces including CNS (CSF-to-plasma ratio 0.5-1.0 for abacavir, 0.1-0.2 for lamivudine). |
| Bioavailability | Abacavir: 83% (oral); Lamivudine: 88% (oral); food delays absorption but does not reduce extent. |
| Onset of Action | Oral: Onset of antiviral effect within hours, maximal suppression achieved within 4-8 weeks of therapy. |
| Duration of Action | Dosing interval 12 hours; continuous suppression requires twice-daily dosing; viral rebound occurs within days to weeks if discontinued. |
| Molecular Weight | 670.6 |
One tablet (600 mg abacavir/300 mg lamivudine) orally once daily.
| Dosage form | TABLET |
| Renal impairment | Not recommended for creatinine clearance <50 mL/min. |
| Liver impairment | Contraindicated in Child-Pugh class A, B, or C (abacavir component contraindicated in hepatic impairment). |
| Pediatric use | For patients weighing ≥25 kg: one tablet orally once daily. For <25 kg, use individual components. Not recommended for <3 months of age. |
| Geriatric use | Select dose with caution due to age-related renal function decline; monitor creatinine clearance. |
| 1st trimester | Contains abacavir and lamivudine. Both are FDA Pregnancy Category C. Data from the Antiretroviral Pregnancy Registry show no increased risk of birth defects. Use only if benefit outweighs risk. |
| 2nd trimester | Continue if indicated. No known fetal toxicity; monitor for maternal toxicity such as lactic acidosis. |
| 3rd trimester | Considered safe; recommended as part of combination therapy to prevent perinatal transmission of HIV. |
Clinical note
Comprehensive clinical and safety monograph for EPZICOM (EPZICOM).
| Placental transfer | Both components cross the placenta; abacavir exhibits moderate transfer (cord blood levels ~30-50% maternal), lamivudine exhibits extensive transfer (cord blood levels similar to maternal). |
| Breastfeeding | Both abacavir and lamivudine are excreted into human milk. In HIV-infected women, breastfeeding is not recommended due to risk of HIV transmission. In HBV-infected women, benefits may outweigh risks; consult specialist. |
■ FDA Black Box Warning
Abacavir: Hypersensitivity reactions (can be fatal) and lactic acidosis with severe hepatomegaly and steatosis.
| Serious Effects |
Hypersensitivity to abacavir (carries HLA-B*5701 allele positive status)Hypersensitivity to lamivudine or any componentModerate to severe hepatic impairment
| Precautions | Hypersensitivity reaction to abacavir (fatal reactions reported); screen for HLA-B*5701 allele prior to initiation. Lactic acidosis and hepatomegaly with steatosis. Risk of immune reconstitution syndrome. Exacerbation of hepatitis B in co-infected patients upon discontinuation. Pancreatitis and peripheral neuropathy reported. |
| Food/Dietary | No significant food interactions. Can be taken with or without food. Avoid alcohol, as it may increase liver toxicity risk (especially in hepatitis B co-infection). |
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| Lactation Rating | L4 (Possibly Hazardous) - generally avoid due to HIV transmission risk. |
| Teratogenic Risk | EPZICOM (abacavir/lamivudine) is classified as FDA Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. In animal studies, abacavir showed no evidence of teratogenicity at doses up to 35 times the human exposure, but lamivudine was associated with early embryo lethality in rabbits at doses similar to human exposure. Use only if potential benefit justifies risk. The Antiretroviral Pregnancy Registry reports no increased risk of major birth defects overall for abacavir or lamivudine based on sufficient first trimester exposures. |
| Fetal Monitoring | Monitor HIV viral load and CD4 count throughout pregnancy. Assess liver function, renal function, and complete blood counts regularly. Monitor for hypersensitivity reactions to abacavir (especially if HLA-B*5701 positive). Perform fetal ultrasound for growth and development as per standard obstetrical care. |
| Fertility Effects | No specific data on fertility impairment in humans. In animal studies, there were no adverse effects on fertility with abacavir or lamivudine at exposures up to 35 times (abacavir) or 200 times (lamivudine) the human dose. |
| Clinical Pearls | EPZICOM is a fixed-dose combination of abacavir and lamivudine. Prior to initiation, screen for HLA-B*5701 allele; if positive, do not use due to risk of abacavir hypersensitivity reaction. Monitor for signs of hypersensitivity (fever, rash, respiratory symptoms) especially within first 6 weeks. Avoid if creatinine clearance <50 mL/min; dose adjustment may be needed. Can be taken with or without food. |
| Patient Advice | Get tested for the HLA-B*5701 gene before starting; if positive, you must not take this drug. · Seek immediate medical help if you develop fever, rash, nausea, vomiting, fatigue, or respiratory symptoms, especially in the first few weeks. · Do not stop or restart without your doctor's advice; stopping and restarting may increase risk of severe allergic reaction. · Take exactly as prescribed; do not miss doses, as this can lead to resistance. · Store at room temperature, away from moisture and heat. · Inform your doctor of any other medications, including over-the-counter and herbal products. · This drug does not cure HIV or prevent transmission; use barrier protection. |