TRIZIVIR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TRIZIVIR (TRIZIVIR).
Trizivir contains abacavir, lamivudine, and zidovudine, all nucleoside reverse transcriptase inhibitors (NRTIs). Abacavir and lamivudine are cytidine analogs, zidovudine is a thymidine analog. They inhibit HIV-1 reverse transcriptase by competing with natural substrates and causing DNA chain termination.
| Metabolism | Abacavir is metabolized primarily by alcohol dehydrogenase and glucuronyl transferase; lamivudine is minimally metabolized (5-10%) by endogenous metabolism; zidovudine is metabolized by glucuronidation via UGT2B7 to an inactive glucuronide metabolite. |
| Excretion | Renal elimination via glomerular filtration and active tubular secretion: abacavir 82% unchanged, lamivudine 71% unchanged, zidovudine 14% unchanged plus 74% as glucuronide metabolite. Total urinary recovery: abacavir 83%, lamivudine ~71%, zidovudine ~88% (14% unchanged, 74% as 5'-glucuronide). Fecal <2% each. |
| Half-life | Abacavir: 1.45 ± 0.33 h; lamivudine: 5-7 h (prolonged in renal impairment); zidovudine: 0.5-1 h (active metabolite zidovudine triphosphate: 3-4 h). Clinically: twice-daily dosing maintains intracellular triphosphate levels. |
| Protein binding | Abacavir ~50%, lamivudine <36%, zidovudine <38% (primarily to albumin). |
| Volume of Distribution | Abacavir: 0.86 ± 0.15 L/kg (moderate penetration into CSF, ratio ~0.3); lamivudine: 1.3 L/kg (extensive total body water); zidovudine: 1.6 L/kg (wide distribution, CSF:plasma ratio 0.6). |
| Bioavailability | Oral: abacavir 83%, lamivudine 86-88%, zidovudine 64% (first-pass metabolism). |
| Onset of Action | Oral: inhibition of viral replication begins within hours; maximal antiviral effect achieved within 2-4 weeks of continuous therapy. |
| Duration of Action | Dosing interval 12 h; intracellular half-lives: abacavir triphosphate 20.6 h, lamivudine triphosphate 18-22 h, zidovudine triphosphate 3-4 h. Clinical viral suppression persists with regular dosing. |
| Molecular Weight | Abacavir: 286.33 Da; Lamivudine: 229.26 Da; Zidovudine: 267.24 Da |
One tablet (abacavir 600 mg, lamivudine 300 mg) orally once daily.
| Dosage form | TABLET |
| Renal impairment | Contraindicated if CrCl <30 mL/min. For CrCl 30-49 mL/min: not recommended due to fixed-dose combination; use individual components. No adjustment needed for CrCl ≥50 mL/min. |
| Liver impairment | Contraindicated in Child-Pugh class B or C. No studies in mild impairment; use with caution. |
| Pediatric use | Not recommended for patients weighing <25 kg. For ≥25 kg: one tablet (abacavir 600 mg, lamivudine 300 mg) orally once daily. |
| Geriatric use | No specific dose adjustment; monitor renal function and adjust components individually if needed. |
| 1st trimester | Use only if benefit outweighs risk. Based on data with individual components, abacavir and lamivudine are associated with low risk of malformations, but zidovudine has a well-established safety record in pregnancy. There is no evidence of increased risk for major birth defects from cohort studies. |
| 2nd trimester | May be used if indicated. No specific trimester-related safety concerns beyond those for general pregnancy. Monitor for maternal HIV viral load and liver function. |
| 3rd trimester | May be used. Consider potential neonatal anemia and neutropenia due to zidovudine component; hematologic monitoring of infant recommended. |
Clinical note
Comprehensive clinical and safety monograph for TRIZIVIR (TRIZIVIR).
| Placental transfer | All three components (abacavir, lamivudine, zidovudine) cross the placenta. Zidovudine and lamivudine achieve cord blood concentrations similar to maternal levels; abacavir also crosses but with slightly lower ratios. |
| Breastfeeding |
■ FDA Black Box Warning
Hypersensitivity reactions to abacavir (can be fatal), lactic acidosis and severe hepatomegaly with steatosis (including fatal cases) with zidovudine, and exacerbation of hepatitis B virus (HBV) infection upon discontinuation of lamivudine.
| Serious Effects |
Hypersensitivity to abacavir, lamivudine, zidovudine, or any excipientPatients with known moderate or severe hepatic impairment (Child-Pugh class B or C)Low body weight (< 40 kg) due to risk of dose formula inadequacySevere neutropenia (absolute neutrophil count < 0.75 x 10^9/L) or severe anemia (hemoglobin < 7.5 g/dL or 4.65 mmol/L)
| Precautions | Hypersensitivity reactions to abacavir (screen for HLA-B*5701 allele prior to initiation), lactic acidosis/hepatomegaly with steatosis (especially in women, obesity, and prolonged NRTI use), exacerbation of hepatitis B after lamivudine discontinuation, hematologic toxicity (severe anemia, neutropenia) with zidovudine, pancreatitis, lipoatrophy, and immune reconstitution syndrome. |
| Food/Dietary | No significant food interactions. May be taken with or without food. |
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| Breastfeeding is not recommended in HIV-infected women due to risk of HIV transmission via breast milk. In settings where replacement feeding is not acceptable, feasible, affordable, sustainable, or safe, exclusive breastfeeding for the first 6 months may be considered, but guidelines strongly advise against if alternative feeding is available. |
| Lactation Rating | Avoid (due to HIV transmission risk, not drug toxicity) |
| Teratogenic Risk | TriZIVIR (abacavir/lamivudine/zidovudine) is classified as FDA Pregnancy Category C. First trimester: Data from the Antiretroviral Pregnancy Registry do not show an increased risk of major birth defects compared to the background rate; however, zidovudine has been associated with mitochondrial toxicity in utero. Second and third trimesters: No specific teratogenic risk identified. Zidovudine use may cause transient hematologic effects (anemia, neutropenia) in neonates. Overall, the benefits of preventing perinatal HIV transmission outweigh theoretical risks. |
| Fetal Monitoring | Monitor complete blood count (CBC) and differential every 2-4 weeks during pregnancy due to zidovudine-associated anemia and neutropenia. Assess liver function tests and lactate levels (risk of lactic acidosis/hepatic steatosis). Perform HIV viral load and CD4 count every 1-3 months. Obtain fetal ultrasound for anomaly detection if exposure in first trimester. Monitor neonatal CBC at birth. |
| Fertility Effects | No known adverse effects on fertility in animal studies; human data are limited. Abacavir, lamivudine, and zidovudine are not associated with impaired fertility in clinical use. However, underlying HIV disease may affect fertility. |
| Clinical Pearls | TRIZIVIR is a fixed-dose combination of abacavir, lamivudine, and zidovudine. It should be used with caution in patients with hepatic impairment due to zidovudine metabolism. Screen for HLA-B*5701 allele before abacavir use to avoid hypersensitivity reaction. Monitor for hematologic toxicity (neutropenia, anemia) associated with zidovudine. Not recommended as a first-line regimen due to higher toxicity and lower efficacy compared to modern antiretrovirals. Avoid in patients with creatinine clearance <50 mL/min due to lamivudine and zidovudine dose adjustments required. |
| Patient Advice | Take exactly as prescribed, with or without food. Do not miss doses. · Report any signs of hypersensitivity (fever, rash, malaise, nausea) immediately; do not restart abacavir if hypersensitivity suspected. · Regular blood tests are required to monitor blood cell counts and liver function. · Avoid alcohol as it may worsen liver toxicity when taken with zidovudine. · This drug does not cure HIV or prevent transmission; use barrier protection. |