Abacavir + Lamivudine + Zidovudine

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

Oral Tablet 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

Oral Tablet HIV Infection Indicated in combination with other antiretrovirals or alone for the treatment of human immunodeficiency virus type 1 (HIV-1) infection who weigh at least 40 kg <40 kg: Not recommended >40 kg: 1 tablet PO twice daily.

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). Renal impairment CrCl <50 mL/min: Fixed dose tablet cannot be dose adjusted

Administration: Can be taken with or without food.

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.

Hypersensitivity reactions • Severe and sometimes fatal hypersensitivity reaction, with multiple organ involvement, have occurred • Reintroduction of abacavir or any other abacavir-containing product, even in patients who have no identified history or unrecognized symptoms of hypersensitivity to abacavir therapy, can result (within hours) in serious or fatal hypersensitivity reactions • Patients who carry the HLA-B*5701 allele are at a higher risk of a hypersensitivity reaction to abacavir; although, hypersensitivity reactions have occurred in patients who do not carry the HLA-B*5701 allele • Contraindicated with history of prior hypersensitivity reaction to abacavir and in patients who are HLA-B*5701-positive • All patients should be screened for the HLA-B*5701 allele before initiating or reinitiating abacavir, unless patients have a previously documented HLA-B*5701 allele assessment • If hypersensitivity is suspected, discontinue abacavir immediately, regardless of HLA-B*5701 status and even when other diagnoses are possible Exacerbations of hepatitis B • Severe acute exacerbations of hepatitis B reported in patients who are coinfected with hepatitis B virus (HBV) and human immunodeficiency virus (HIV-1) and have discontinued lamivudine • Monitor hepatic function closely in these patients and, if appropriate, initiate antihepatitis B treatment Hematologic toxicity • Hematologic toxicity, including neutropenia and anemia, has been associated with the use of zidovudine Myopathy • Symptomatic myopathy associated with prolonged use of zidovudine Lactic acidosis and severe hepatomegaly with steatosis • Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues, including abacavir, lamivudine, and zidovudine • Suspend treatment if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occur Monitoring Parameter All patients should be screened for the HLA-B*5701 allele before initiating or reinitiating abacavir Monitor hepatic function closely in these patients and, if appropriate, initiate antihepatitis B treatment. Use caution when treating in combination with interferon alfa with or without ribavirin in HIV/HBV; monitor for hepatic decompensation, neutropenia, or anemia.

Pregnancy Abacavir Based on prospective reports to APR of exposures to abacavir during pregnancy resulting in live births (including over 1,300 exposed in the first trimester and over 1,300 exposed in the second/third trimester), there was no difference between overall risk of birth defects for abacavir compared with the background birth defect rate of 2.7% in the U.S. reference population of the MACDP The prevalence of defects in live births was 3.2% (95% CI: 2.3% to 4.3%) following first-trimester exposure to abacavir-containing regimens and 2.9% (95% CI: 2.1% to 4.0%) following second/third-trimester exposure to abacavir-containing regimens. Lamivudine Based on prospective reports to APR of exposures to lamivudine during pregnancy resulting in live births (including over 5,300 exposed in first trimester and over 7,400 exposed in second/third trimester), there was no difference between overall risk of birth defects for lamivudine compared with background birth defect rate of 2.7% in U.S. reference population of MACDP The prevalence of birth defects in live births was 3.1% (95% CI: 2.7% to 3.6%) following first-trimester exposure to lamivudine-containing regimens and 2.9% (95% CI: 2.5%, 3.3%) following second/third-trimester exposure to lamivudine- containing regimens. Zidovudine Based on prospective reports to the APR of exposures during pregnancy resulting in live births (including over 4,200 exposed in the first trimester and over 9,700 exposed in the second/third trimester), there was no difference between the overall risk of birth defects for zidovudine compared with the background birth defect rate of 2.7% in a U.S. reference population of the MACDP. 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 being treated with the drug combination.

Methadone: An increased methadone dose may be required in a small number of patients. Sorbitol: Coadministration of lamivudine and sorbitol may decrease lamivudine concentrations; when possible, avoid chronic coadministration. Agents antagonistic with zidovudine: Concomitant use should be avoided. Hematologic/bone marrow suppressive/cytotoxic agents: May increase the hematologic toxicity of zidovudine. 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-alfa 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-alfa 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). Contraindicated (2) • elvitegravir/cobicistat/emtricitabine/tenofovir DF • emtricitabine Serious - Use Alternative (14) • atidarsagene autotemcel • betibeglogene autotemcel • cabotegravir • cidofovir • elivaldogene autotemcel • elivaldogene autotemcel • clozapine • deferiprone • elivaldogene autotemcel • ganciclovir • lovotibeglogene autotemcel • ribavirin • sorbitol • valganciclovir

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

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.