Abacavir + Dolutegravir + Lamivudine

Abacavir + Dolutegravir + Lamivudine is used for: Human immunodeficiency virus type 1 (HIV-1) infection

HIV Infection Indicated for human immunodeficiency virus type 1 (HIV-1) infection in patients weighing >40 kg 1 tablet (600mg/50mg/300mg) PO once daily

HIV-1 Infection Indicated for treatment of HIV-1 infection in children aged 3 months weighing at least 6 kg <6 kg: Safety and efficacy not established Do not interchange (Tablet for oral use) and (Tablet for oral suspension) on a mg-per-mg basis (Tablet for oral suspension): Weight 6 to <25 kg (Tablet for oral use): Weight at least 25 kg (Tablet for oral suspension) Contains 60mg/5mg/30mg per tablet; dissolve in 20 mL of drinking water before administration 6 to <10 kg: 3 tablets (180 mg abacavir, 15 mg dolutegravir, and 90 mg lamivudine) PO qDay 10 to <14 kg: 4 tablets (240mg/20mg/120mg) PO qDay 14 to <20 kg: 5 tablets (300mg/25mg/150mg) PO qDay 20 to <25 kg: 6 tablets (360mg/30mg/180mg) PO qDay Not recommended in patients weighing >25 kg (Tablet for oral use) >25 kg: 1 tablet (600mg/50mg/300mg) PO qDay

Renal impairment CrCl >50 mL/min: No dosage adjustment is required CrCl <50 mL/min: Not recommended; fixed-dose tablet cannot be dose-adjusted

Oral administration Take with or without food

Presence of HLA-B*5701 allele Previous hypersensitivity reaction to abacavir, dolutegravir, or lamivudine Coadministration with dofetilide Moderate or severe hepatic impairment

Use in patients with underlying hepatitis B or C may be associated with increased risk for worsening or development of elevated hepatic transaminase; monitor LFTs Hepatic toxicity, including elevated serum liver biochemistries, hepatitis, and acute liver failure reported without pre-existing hepatic disease or other identifiable risk factors; drug-induced liver injury leading to liver transplant reported; monitoring for hepatotoxicity recommended Hepatic decompensation, some fatal, has occurred in HIV-1/hepatitis C virus (HCV) coinfected patients receiving combination antiretroviral therapy (ART) and interferon alfa with or without ribavirin; discontinue as medically appropriate and consider dose reduction or discontinuation of interferon alfa, ribavirin, or both Posttreatment exacerbation of hepatitis reported in patients coinfected with hepatitis B infection Immune reconstitution syndrome may occur; patients may develop an inflammatory response to indolent or residual opportunistic infections (eg, Mycobacterium avium infection, cytomegalovirus infection, Pneumocystis jirovecii pneumonia [PCP] infection, or tuberculosis) Administration is not recommended in patients receiving other products containing abacavir or lamivudine Abacavir use was correlated with an increased risk of myocardial infarction (MI) based on a prospective, observational, epidemiological trial, but not in a meta-analysis of 26 randomized trials; caution with risks for coronary heart disease and minimizing modifiable risk factors, including smoking, hypertension, and hyperlipidemia Monitoring Parameter Test for hepatitis B virus infection Pregnancy testing recommended before in females of childbearing potential

Pregnancy Insufficient data related to abacavir/dolutegravir/lamivudine use during pregnancy to inform a drug associated risk of birth defects and miscarriage In animal reproduction studies, no evidence of adverse developmental outcomes was observed with dolutegravir; during organogenesis in rat and rabbit and a rat pre/postnatal developmental study, systemic exposures (AUC) to dolutegravir were less than (rabbits) and ~50 times (rats) the exposure in humans at recommended human dose (RHD) Oral administration of abacavir to pregnant rats during organogenesis resulted in fetal malformations and other embryonic and fetal toxicities at exposures 35 times the human exposure (AUC) at the RHD; no adverse developmental effects were observed following oral administration of abacavir to pregnant rabbits during organogenesis at exposures ~9 times the human exposure (AUC) at the RHD Oral administration of lamivudine to pregnant rabbits during organogenesis resulted in embryo lethality at a human exposure (AUC) similar to the RHD; no adverse development effects were observed with oral administration of lamivudine to pregnant rats during organogenesis at plasma concentrations (Cmax) 35 times RHD Potential risk of neural tube birth defects Serious cases of neural tube birth defects involving the brain, spine, and spinal cord reported in babies born to women treated with dolutegravir Preliminary results from an ongoing observational study in Botswana found women who had received dolutegravir at the time of becoming pregnant or early in the first trimester appear to be at higher risk for these defects; to date, in this observational study there are no reported cases of babies born with neural tube defects to women starting dolutegravir later in pregnancy Recommendations Patients should not discontinue dolutegravir without consulting a healthcare professional because stopping your medicine can cause the HIV infection to worsen Pregnant women stopping dolutegravir-containing regimen without switching to alternative HIV medicines could cause the amount of virus to increase and spread HIV to your baby Patients taking a dolutegravir-containing regimen at the time of becoming pregnant and during the first trimester of pregnancy, there is a potential risk of neural tube defects; neural tube defects happen early in pregnancy, before many women even know they are pregnant Inform women of childbearing age about the potential risk of neural tube defects when a dolutegravir-containing regimen is used at the time of conception and early in pregnancy; women of childbearing age should consult their healthcare providers about other non-dolutegravir-containing antiretroviral medicine Healthcare providers should weigh the benefits and the risks of dolutegravir when prescribing antiretroviral medicines to women of childbearing age; consider alternative antiretroviral medicines; discuss the relative risks and benefits of appropriate alternative antiretroviral therapies Women of childbearing age who decide to take a dolutegravir-containing regimen should consistently use effective birth control (contraception) while on HIV treatment; women should discuss their healthcare professionals about an effective birth control method to use while taking a dolutegravir-containing regimen Perform pregnancy testing before initiating a dolutegravir-containing regimen in women of childbearing age to exclude pregnancy Lactation The Centers for Disease Control and Prevention does not recommend HIV-1-infected mothers in the United States breastfeed their infants to avoid the risk of postnatal transmission of HIV-1 infection Abacavir and lamivudine are present in human milk When administered to lactating rats, dolutegravir was present in milk There is no information on the effects of abacavir/dolutegravir/lamivudine or its components on the breastfed infant or the effects of the drug on milk production; because of the potential for HIV-1 transmission in HIV-negative infants, developing viral resistance (in HIV-positive infants), and serious adverse reactions in a breastfed infant, instruct mothers not to breastfeed

Coadministration of Abacavir + Dolutegravir + Lamivudine with other drugs can alter the concentration of other drugs and other drugs may alter the concentrations of Abacavir + Dolutegravir + Lamivudine. The potential drug-drug interactions must be considered prior to and during therapy. Contraindicated (2) • dofetilide • elvitegravir/cobicistat/emtricitabine/tenofovir DF Serious - Use Alternative (29) • aluminum hydroxide/magnesium carbonate • atidarsagene autotemcel • betibeglogene autotemcel • cabotegravir • carbamazepine • elivaldogene autotemcel • efavirenz • elivaldogene autotemcel • etravirine • fosamprenavir • fosphenytoin • ganciclovir • lovotibeglogene autotemcel • lovotibeglogene autotemcel • magnesium citrate • magnesium gluconate • magnesium oxide • nevirapine • oxcarbazepine • phenobarbital • phenytoin • Prussian blue • St John's Wort • ribavirin • sorbitol • sucralfate • tafenoquine • tipranavir • trilaciclib

Side effects of Abacavir + Dolutegravir + Lamivudine : 1-10% Lipase (4-9%) Hyperglycemia (2-7%) Creatinine kinase (4-5%) Insomnia (3%) Decreased neutrophils (2-3%) Increased AST (<1 to 3%) Headache (2%) Fatigue (2%) Increased ALT (<1 to 2%) Depression (1%) <1% Abnormal dreams Dizziness Nausea Diarrhea Rash

Abacavir: Nucleoside reverse transcriptase inhibitor (NRTI); guanosine analog that inhibits HIV-1 reverse transcriptase by competing with dGTP as substrate, which, in turn, inhibits viral replication Dolutegravir: Integrase strand transfer inhibitor (INSTI); inhibits catalytic activity of HIV-1 integrase, an HIV encoded enzyme required for viral replication Lamivudine: NRTI; following phosphorylation, inhibits HIV reverse transcriptase by viral DNA chain termination; cytosine analog