Abacavir, Dolutegravir, And Lamivudine

Introduction Overview

Generic Name

abacavir, dolutegravir, and lamivudine

Brand Name

Triumeq; Triumeq PD

Dosage Form

Triumeq film-coated tablet for oral use contains 600 mg abacavir, 50 mg dolutegravir, and 300 mg lamivudine. Triumeq PD tablets for oral suspension contain 60 mg abacavir, 5 mg dolutegravir, and 30 mg lamivudine per tablet.

Drug Class

Antiretroviral fixed-dose combination: two nucleoside reverse transcriptase inhibitors (abacavir and lamivudine) plus one integrase strand transfer inhibitor (dolutegravir).

Pharmacokinetics

Absorption:
All three components are absorbed after oral administration. Abacavir and lamivudine are rapidly absorbed. Dolutegravir reaches peak plasma concentrations about 2 to 3 hours after a dose, and steady state is reached in about 5 days with once-daily dosing. Triumeq and Triumeq PD may be taken with or without food, but food can help when dolutegravir is taken near calcium or iron supplements.

Distribution:
Abacavir distributes widely and is about 50% bound to plasma proteins. Dolutegravir is highly protein bound, greater than 98.9%, and has an apparent volume of distribution of about 17.4 L after 50 mg once daily. Lamivudine has low plasma protein binding and distributes into body fluids, including some penetration into cerebrospinal fluid.

Metabolism:
Abacavir is primarily metabolized by alcohol dehydrogenase and glucuronyl transferase. Dolutegravir is mainly metabolized by UGT1A1, with a smaller contribution from CYP3A. Lamivudine is minimally metabolized.

Elimination:
Abacavir has a short plasma half-life of about 1.5 hours, but its intracellular active metabolite supports antiviral activity. Dolutegravir has an apparent terminal half-life of about 14 hours. Lamivudine is eliminated mostly unchanged in urine, so clinically important renal impairment can make this fixed-dose combination unsuitable because the lamivudine dose cannot be adjusted separately.

Dosage Forms

Available dosage forms:
- Triumeq tablet: 600 mg abacavir, 50 mg dolutegravir, and 300 mg lamivudine.
- Triumeq PD tablet for oral suspension: 60 mg abacavir, 5 mg dolutegravir, and 30 mg lamivudine.

Adult dosage:
- Adults: one Triumeq tablet by mouth once daily, with or without food.
- Do not use Triumeq PD in adults because it is designed for pediatric weight-based dosing.

Pediatric dosage by body weight:
- 6 kg to less than 10 kg: three Triumeq PD tablets once daily.
- 10 kg to less than 14 kg: four Triumeq PD tablets once daily.
- 14 kg to less than 20 kg: five Triumeq PD tablets once daily.
- 20 kg to less than 25 kg: six Triumeq PD tablets once daily.
- 25 kg or more: one Triumeq tablet once daily; Triumeq PD is not recommended.

Administration details:
Triumeq tablets should be swallowed whole and should not be chewed, cut, or crushed. Triumeq PD tablets must be fully dispersed in drinking water and administered within 30 minutes. Triumeq tablets and Triumeq PD tablets must not be substituted milligram-for-milligram because the dolutegravir exposure differs between the formulations.

Mechanism Of Action

This medicine treats HIV-1 infection by blocking two different steps in the HIV life cycle.

Abacavir and lamivudine are nucleoside reverse transcriptase inhibitors. Inside cells, they are converted to active triphosphate forms. These active forms compete with natural nucleotides during viral DNA synthesis. When they are inserted into viral DNA, the chain cannot continue properly, so reverse transcription is interrupted.

Dolutegravir is an integrase strand transfer inhibitor. HIV integrase normally inserts viral DNA into the host cell genome. Dolutegravir binds the integrase active site and blocks strand transfer, preventing the viral DNA from becoming a stable part of the host cell DNA.

For students, the simple model is: two drugs block "RNA to DNA," and one drug blocks "viral DNA into human DNA." Combining these steps helps suppress viral replication and reduces the chance of resistance when the virus is susceptible and the patient takes therapy consistently.

Pharmacological Actions

Suppresses HIV-1 replication through combined reverse transcriptase and integrase inhibition.
Reduces plasma HIV RNA when the virus is susceptible to all three components.
Helps preserve or improve CD4 cell counts by reducing ongoing viral replication.
Provides once-daily treatment without a pharmacokinetic booster such as ritonavir or cobicistat.
Has a high resistance barrier from dolutegravir compared with older first-generation integrase inhibitors.
Requires HLA-B*5701 screening because abacavir hypersensitivity can be serious or fatal.
Does not provide a complete hepatitis B treatment backbone because lamivudine alone can select HBV resistance; HBV coinfection requires special planning.

Therapeutic Or Clinical Uses

Treatment of HIV-1 infection in adults.
Treatment of HIV-1 infection in pediatric patients weighing at least 6 kg, using the correct formulation for body weight.
Use only in patients who do not have the HLA-B*5701 allele.
Use only when there is no known or suspected resistance to abacavir, dolutegravir, or lamivudine.
May be used as an initial or switch regimen in selected patients, but current U.S. adult HIV guidelines place dolutegravir/abacavir/lamivudine among other initial regimens for certain clinical scenarios rather than a preferred regimen for most people.
May be useful when a single-tablet, once-daily regimen is desired and abacavir is appropriate after reviewing cardiovascular risk, HLA-B*5701 status, hepatitis B status, renal function, liver function, and resistance history.

Side Or Adverse Effects

Headache, insomnia, fatigue, nausea, diarrhea, abdominal discomfort, or reduced appetite.
Abacavir hypersensitivity reaction, often involving fever, rash, gastrointestinal symptoms, malaise, fatigue, achiness, or respiratory symptoms.
Serious hypersensitivity can progress to hypotension, respiratory failure, organ failure, or death if the drug is continued or restarted.
Hepatotoxicity, including elevated liver enzymes, hepatitis, or rare severe liver injury.
Lactic acidosis and severe hepatomegaly with steatosis, a rare but serious NRTI-associated toxicity.
Immune reconstitution inflammatory syndrome after starting antiretroviral therapy.
Weight gain has been reported with integrase inhibitor-based antiretroviral therapy, including dolutegravir-containing regimens.
Possible increased myocardial infarction risk with abacavir has been reported in some observational studies, although evidence for causality is inconsistent.
Severe acute exacerbation of hepatitis B can occur after stopping lamivudine-containing therapy in people with HIV and HBV coinfection.

Precautions

Screen for HLA-B*5701 before starting therapy. Do not use if the test is positive.
Never restart abacavir, Triumeq, or any abacavir-containing product after a suspected abacavir hypersensitivity reaction.
Test for hepatitis B before starting antiretroviral therapy. If HBV coinfection is present, use an HIV regimen that also fully treats HBV or add appropriate HBV therapy.
Assess renal function. Triumeq and Triumeq PD are not recommended when creatinine clearance is less than 30 mL/min because lamivudine dose adjustment cannot be made in the fixed-dose tablet.
Assess liver function. Triumeq and Triumeq PD are contraindicated in moderate or severe hepatic impairment and are not recommended in mild hepatic impairment because abacavir dose adjustment cannot be made.
Review cardiovascular risk factors before choosing abacavir-containing therapy and reduce modifiable risks such as smoking, hypertension, diabetes, and hyperlipidemia.
Review resistance history and baseline genotype results when selecting therapy.
Use pregnancy guidance from HIV specialists or perinatal HIV guidelines. A pregnancy exposure registry is available for patients exposed during pregnancy.
Teach patients to recognize hypersensitivity symptoms and to seek urgent medical care if they occur.

Warnings

Boxed warning: serious and sometimes fatal hypersensitivity reactions can occur with abacavir-containing products. HLA-B*5701-positive patients are at much higher risk.
Boxed warning: severe acute exacerbations of hepatitis B have been reported after discontinuation of lamivudine in patients coinfected with HIV-1 and HBV.
Stop therapy immediately if abacavir hypersensitivity is suspected. Restarting abacavir after hypersensitivity can cause a more severe reaction within hours.
Coadministration with dofetilide is contraindicated because dolutegravir can increase dofetilide concentrations and cause serious or life-threatening events.
Monitor for hepatotoxicity, especially in patients with hepatitis B, hepatitis C, or other liver disease.
Monitor for lactic acidosis and severe hepatomegaly with steatosis if symptoms such as persistent nausea, vomiting, abdominal pain, unusual fatigue, rapid breathing, or weakness occur.
Triumeq and Triumeq PD are not approved for HIV pre-exposure prophylaxis.

Contraindication

Presence of the HLA-B*5701 allele.
Prior hypersensitivity reaction to abacavir, dolutegravir, or lamivudine.
Concomitant use with dofetilide.
Moderate or severe hepatic impairment.

Not recommended is different from contraindicated: Triumeq PD is not recommended in adults or in patients weighing 25 kg or more, and Triumeq/Triumeq PD are not recommended when creatinine clearance is less than 30 mL/min or in mild hepatic impairment because this fixed-dose product cannot be adjusted component by component.

Drug Interactions

Dofetilide: contraindicated because dolutegravir may increase dofetilide exposure.
Efavirenz, fosamprenavir/ritonavir, tipranavir/ritonavir, carbamazepine, and rifampin can lower dolutegravir concentrations. Additional dolutegravir dosing is recommended when these combinations are used.
Aluminum- or magnesium-containing antacids, sucralfate, buffered medicines, and other polyvalent cation products can reduce dolutegravir absorption. Separate dosing according to label instructions.
Calcium or iron supplements can reduce dolutegravir absorption if taken fasting. They may be taken with Triumeq if taken with food, or separated when fasting.
Metformin exposure can increase with dolutegravir; metformin dose adjustment and glucose monitoring may be needed.
Sorbitol-containing medicines can reduce lamivudine exposure and should be avoided when possible.
Do not combine with other products containing abacavir, lamivudine, emtricitabine, or dolutegravir unless specifically directed by an HIV specialist.
St. John's wort and other strong enzyme inducers may reduce antiretroviral exposure and should be reviewed carefully before use.

Preparations Of The Drug

Triumeq tablets: purple, oval, film-coated tablets containing abacavir sulfate equivalent to 600 mg abacavir, dolutegravir sodium equivalent to 50 mg dolutegravir, and 300 mg lamivudine.
Triumeq PD tablets for oral suspension: yellow, strawberry cream flavored, film-coated tablets containing abacavir sulfate equivalent to 60 mg abacavir, dolutegravir sodium equivalent to 5 mg dolutegravir, and 30 mg lamivudine.
Triumeq PD tablets are dispersed in 15 mL of drinking water for a 3-tablet dose or 20 mL for a 4-, 5-, or 6-tablet dose, then administered within 30 minutes.
Store tablets in the original bottle, tightly closed, and protect from moisture. Keep the desiccant in the bottle and do not remove it.
Prescription only; treatment should be managed by clinicians experienced in HIV care.

Student Key Points

Triumeq combines ABC + DTG + 3TC: two NRTIs plus one INSTI.
Always remember HLA-B*5701 before abacavir. Positive test means do not use.
Abacavir hypersensitivity is a permanent stop rule: do not rechallenge.
HBV status matters because lamivudine alone is not enough HBV therapy and stopping can trigger HBV flare.
Triumeq and Triumeq PD are not interchangeable milligram-for-milligram.
The regimen is useful in selected patients, but it is no longer listed by U.S. adult guidelines as a preferred initial regimen for most people.