Triumeq - Drug Monograph

Introduction

Triumeq is a fixed-dose combination antiretroviral medication used for the treatment of human immunodeficiency virus type 1 (HIV-1) infection. It contains three active ingredients: dolutegravir (an integrase strand transfer inhibitor), abacavir (a nucleoside reverse transcriptase inhibitor), and lamivudine (a nucleoside reverse transcriptase inhibitor). This single-tablet regimen simplifies HIV treatment by combining three effective antiretroviral agents into one daily dose.

Mechanism of Action

Triumeq exerts its antiviral effect through three distinct mechanisms:

• Dolutegravir: Inhibits HIV integrase, preventing the integration of viral DNA into the host genome
• Abacavir: A guanosine analog that inhibits HIV reverse transcriptase by competing with natural nucleoside substrates and incorporating into viral DNA to cause chain termination
• Lamivudine: A cytosine analog that inhibits HIV reverse transcriptase through similar mechanisms as abacavir

The combination provides synergistic antiviral activity against HIV-1 by targeting multiple stages of the viral replication cycle.

Indications

Triumeq is indicated for:

• Treatment of HIV-1 infection in adults and pediatric patients weighing at least 40 kg
• As a complete regimen or in combination with other antiretroviral agents
• Not recommended for patients with HIV-1 harboring certain resistance mutations to its components

Dosage and Administration

• Renal impairment: Not recommended if CrCl <50 mL/min
• Hepatic impairment: Use with caution in patients with hepatic impairment
• Pediatric patients: Only for those weighing ≥40 kg using same adult dose
• Elderly patients: No dosage adjustment required, but consider age-related comorbidities

• Screening for HLA-B*5701 allele must be performed before initiation
• Patients should be assessed for hepatitis B virus coinfection
• Tablets should be swallowed whole, not chewed or crushed

Pharmacokinetics

• Dolutegravir: Protein binding ~99%
• Abacavir: Protein binding ~50%
• Lamivudine: Protein binding <36%
• All components distribute well into cerebrospinal fluid

• Dolutegravir: Primarily metabolized via UGT1A1 with minor CYP3A involvement
• Abacavir: Metabolized by alcohol dehydrogenase and glucuronyl transferase
• Lamivudine: Minimal metabolism

• Dolutegravir: Half-life ~14 hours, primarily fecal elimination
• Abacavir: Half-life ~1.5 hours, primarily renal elimination
• Lamivudine: Half-life ~5-7 hours, primarily renal elimination

Contraindications

• Patients who test positive for HLA-B*5701 allele
• Patients with previously demonstrated hypersensitivity to any component
• Patients with hepatic impairment
• Moderate to severe renal impairment (CrCl <50 mL/min)
• Co-administration with dofetilide

Warnings and Precautions

• Hypersensitivity reactions (associated with abacavir)
• Lactic acidosis and severe hepatomegaly with steatosis
• Exacerbations of hepatitis B

• Immune reconstitution syndrome
• Fat redistribution
• Cardiovascular risk
• Myocardial infarction risk (associated with abacavir)
• Hepatic toxicity
• Depression and suicidal ideation (associated with integrase inhibitors)

Drug Interactions

• Metformin: Dolutegravir may increase metformin exposure
• Antacids: Separate administration by 2 hours
• Cation-containing products: Separate administration by 2 hours
• Efavirenz, nevirapine, tipranavir/ritonavir: May decrease dolutegravir concentrations
• Oxcarbazepine, phenytoin, phenobarbital: May decrease dolutegravir concentrations

• Dofetilide (contraindicated)
• Other products containing abacavir or lamivudine

Adverse Effects

• Insomnia
• Headache
• Fatigue
• Nausea
• Diarrhea

• Hypersensitivity reactions
• Lactic acidosis
• Hepatic steatosis
• Hepatotoxicity
• Immune reconstitution syndrome
• Myocardial infarction
• Depression and suicidal ideation

Monitoring Parameters

• HLA-B*5701 screening
• Hepatitis B serology
• HIV viral load and CD4 count
• Renal function (serum creatinine, CrCl)
• Liver function tests
• Lipid panel
• Blood glucose

• HIV viral load and CD4 count (every 3-6 months)
• Liver function tests (regularly)
• Renal function (regularly)
• Signs and symptoms of hypersensitivity
• Cardiovascular risk factors
• Mental health status

Patient Education

• Take exactly as prescribed, one tablet daily
• Do not miss doses to maintain viral suppression
• Recognize symptoms of hypersensitivity reaction (fever, rash, nausea, vomiting, abdominal pain, fatigue, respiratory symptoms)
• Seek immediate medical attention if hypersensitivity symptoms occur
• Inform all healthcare providers about Triumeq use
• Use effective contraception as Triumeq may interact with hormonal contraceptives
• Regular follow-up appointments are essential
• Do not breastfeed while taking Triumeq
• Report any new symptoms or side effects promptly
• Understand that Triumeq controls but does not cure HIV infection

References

1. Triumeq [package insert]. Research Triangle Park, NC: ViiV Healthcare; 2022. 2. Saag MS, Gandhi RT, Hoy JF, et al. Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2020 Recommendations of the International Antiviral Society-USA Panel. JAMA. 2020;324(16):1651-1669. 3. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV. Department of Health and Human Services. 4. Walmsley SL, Antela A, Clumeck N, et al. Dolutegravir plus abacavir-lamivudine for the treatment of HIV-1 infection. N Engl J Med. 2013;369(19):1807-1818. 5. Clotet B, Feinberg J, van Lunzen J, et al. Once-daily dolutegravir versus darunavir plus ritonavir in antiretroviral-naive adults with HIV-1 infection (FLAMINGO): 48 week results from a randomised open-label study. Lancet. 2014;383(9936):2222-2231.