Abacavir + Lamivudine + Zidovudine

Indications

Abacavir + Lamivudine + Zidovudine is used for: Acquired immunodeficiency syndrome (AIDS), HIV infection

Adult Dose

Adults and Adolescents >12 years: Recommended Dose: 1 tablet twice daily. This should not be administered to adolescents and adults who weigh <40 kg because it is a fixed-dose tablet, therefore the dose cannot be reduced. <12 years or <40 kg: Not recommended Hepatic Impairment: This drugs is contraindicated for use in hepatically impaired patients.

Child Dose

Renal Dose

Renal Impairment: Dosage reduction of lamivudine or zidovudine may be necessary in renally impaired patients. It is therefore recommended that separate preparations of abacavir, lamivudine and zidovudine should be administered to patients with reduced renal function (CrCl <50 mL/min).

Administration

Administration: Can be taken with or without food.

Contra Indications

Hypersensitivity. Hepatic impairment, abnormally low neutrophil counts (<0.75 x 10 9/L) or abnormally low Hb levels (<7.5 g/dL or 4.65 mmol/L). Patient <40 kg, CrCl <50 mL/min.

Precautions

Use of abacavir in patients known to carry HLA B*5701 allele is not recommended. Screening should be performed before initiating treatment or prior to reinitiation in patients w/ unknown HLA B*5701 status who have previously tolerated abacavir. Hypersensitivity reaction. Risk of lactic acidosis & hepatomegaly w/ steatosis in patients (esp obese women w/ hepatomegaly), pancreatitis, hepatitis or other known risk factors for hepatic disease. Due to haematological AR, monitor haematological parameters during treatment esp in patients w/ poor bone marrow reserve or advanced HIV disease. Discontinue immediately if pancreatitis is suspected. Co-infection w/ HBV or HCV. Immune reconstitution syndrome, opportunistic infections, transmission of infection, MI. Elderly. Pregnancy & lactation. Lactation: Not recommended; excreted in breast milk; HIV+ women shouldn't nurse anyway.

Pregnancy-Lactation

Pregnancy Available data from the APR show no difference in the overall risk of birth defects for abacavir, lamivudine, or zidovudine compared with background rate for birth defects of 2.7% in the Metropolitan Atlanta Congenital Defects Program (MACDP) reference population Hyperlactatemia, which may be due to mitochondrial dysfunction, reported in infants with in utero exposure to zidovudine-containing products; causal relationship between these events and exposure to zidovudine-containing products in utero or peri-partum not established Lactation The Centers for Disease Control and Prevention recommend that HIV-1-infected mothers in the United States not breastfeed their infants to avoid risking postnatal transmission of HIV-1 infection; abacavir, lamivudine and zidovudine are present in human milk; there is no information on effects of abacavir, lamivudine and zidovudine on breastfed infant or effects of drug on milk production; because of potential for (1) HIV-1 transmission (in HIV-negative infants), (2) developing viral resistance (in HIV-positive infants), and (3) serious adverse reactions in breastfed infant, similar to those seen in adults; instruct mothers not to breastfeed if they are beind treated with the drug combination

Interactions

Abacavir: Alcohol may cause decreased elimination of abacavir. Lactic acidosis with nucleoside analogues concomitantly. Decreased serum concentrations of methadone. Zidovudine: acyclovir and valacyclovir may increase CNS depression. Increased risk of haematologic toxicity with ganciclovir, valganciclovir, dapsone, doxorubicin, vincristine and vinblastine. Doxorubicin may reduce phophorylation; fluconazole may increase levels/effects; increased risk of hepatic decompensation or haematologic toxicities with interferon-? and ribavirin (also increases risk of pancreatitis and lactic acidosis). Methadone may increase effects/levels. Increased risk of myalgia, malaise and/or fever, maculopapular rash and effects/levels with probenecid. Stavudine may decrease antiviral activity; valproic acid may increase plasma levels (AUC increased by 80%). Lamivudine: Increased risk of hepatic decompensation or haematologic toxicities with interferon-? and ribavirin (also increases risk of mitochondrial toxicity, pancreatitis and lactic acidosis). Ganciclovir and valganciclovir may increase effects and toxicity; sulfamethoxazole/trimethoprim may increase AUC and decrease clearance (increasing levels and effects).

Adverse Effects

Side effects of Abacavir + Lamivudine + Zidovudine : >10% Nausea, Headache, Fatigue, Malaise, Vomiting 1-10% Rash, Fever/chills, Anxiety, Depression, Increased triglyceride levels, Diarrhea, Increased amylase, Neutropenia, Increased ALT, Increased CPK, Ear infection, Nose/throat infection, Viral infection Frequency Not Defined Immune reconstitution syndrome, GGT increased, Fat redistribution, Pancreatitis

Mechanism of Action

Abacavir, lamivudine and zidovudine are all nucleoside reverse transcriptase inhibitors. Converted to their respective active triphosphate form, they act synergistically to reduce viral resistance and inhibit reverse transcriptase via DNA chain termination.