Dosing and uses of Triumeq (abacavir/dolutegravir/lamivudine)
Adult dosage forms and strengths
abacavir/dolutegravir/lamivudine
tablet
- 600mg/50mg/300mg
HIV Infection
1 tablet PO qDay
Dosage modifications
If coadministered with efavirenz, fosamprenavir/ritonavir, tipranavir/ritonavir, or rifampin: Take an additional dolutegravir (as single-entity) 50-mg tablet, separated by 12 hr from abacavir/dolutegravir/lamivudine dose
Moderate-to-severe hepatic impairment: Contraindicated
Dosing Considerations
Not recommended alone for use in patients with current or past history of resistance to any components of Triumeq
Not recommended alone in patients with resistance-associated integrase substitutions or clinically suspected INSTI resistance because the dose of dolutegravir in Triumeq is insufficient in these populations
Before initiating treatment with abacavir-containing products, screening for the presence of a genetic marker, the HLA-B*5701 allele, should be performed in any HIV-infected patient, irrespective of racial origin
Products containing abacavir should not be used in patients known to carry the HLA-B*5701 allele; these patients are at high risk for hypersensitivity reactions
Administration
May take with or without food
Bottle contains desiccant packet should not be removed
Pediatric dosage forms and strengths
<18 years: Safety and efficacy not established
Triumeq (abacavir/dolutegravir/lamivudine) adverse (side) effects
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
Warnings
Black box warnings
HLA‑B*5701 allele and hypersensitivity
- Serious and sometimes fatal hypersensitivity reactions have been associated with abacavir-containing products
- Hypersensitivity to abacavir is a multiorgan clinical syndrome
- Patients who carry the HLA‑B*5701 allele are at high risk for experiencing a hypersensitivity reaction to abacavir
- Discontinue as soon as a hypersensitivity reaction is suspected; regardless of HLA-B*5701 status, permanently discontinue Triumeq if hypersensitivity cannot be ruled out, even when other diagnoses are possible
- Following a hypersensitivity reaction to abacavir, NEVER restart abacavir-containing products
Lactic acidosis and hepatomegaly
- Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues; discontinue therapy if clinical or laboratory findings suggest lactic acidosis or pronounced hepatotoxicity
Hepatitis B exacerbation
- Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with hepatitis B virus (HBV) and HIV-1 and have discontinued lamivudine, a component of Triumeq
- Monitor hepatic function closely in these patients and, if appropriate, initiate antihepatitis B treatment
Contraindications
Presence of HLA-B*5701 allele
Previous hypersensitivity reaction to abacavir, dolutegravir, or lamivudine
Coadministration with dofetilide
Moderate or severe hepatic impairment
Cautions
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 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
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)
Redistribution/accumulation of body fat reported with combination ART therapy
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
Pregnancy and lactation
Pregnancy category: C
Lactation: Breastfeeding is not recommended due to the potential for HIV transmission
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Triumeq (abacavir/dolutegravir/lamivudine)
Mechanism of action
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
Absorption
Peak plasma concentration
- Abacavir: 4.26 mcg/mL
- Dolutegravir: 3.67 mcg/mL
- Lamivudine: 2.04 mcg/mL
Peak plasma time
- Dolutegravir: 2-3 hr
AUC
- Abacavir: 11.95 mcg•hr/mL
- Dolutegravir: 53.6 mcg•hr/mL
- Lamivudine: 8.87 mcg•hr/mL
Distribution
Protein bound
- Abacavir: 50%
- Dolutegravir: ≥98.9%
- Lamivudine: Low
Vd
- Dolutegravir: 17.4 L
Metabolism
Abacavir: Primarily metabolized by alcohol dehydrogenase to form the 5′-carboxylic acid and glucuronyl transferase to form the 5′-glucuronide
Dolutegravir: Primarily metabolized via UGT1A1 with some contribution from CYP3A
Lamivudine: Negligible
Elimination
Half-life
- Abacavir: 1.54 hr
- Dolutegravir: 14 hr
- Lamivudine: 5-7 hr
Total body clearance
- Abacavir: 0.8 L/hr/kg
- Dolutegravir: 1 L/hr
- Lamivudine: 398.5 mL/min
Excretion
- Dolutegravir: 53% feces (unchanged); 31% urine
- Lamivudine: 70% urine (unchanged)
Pharmacogenomics
Patients who carry the HLA-B*5701 allele are at high risk for experiencing a hypersensitivity reaction to abacavir
Prior to initiating therapy with abacavir, screen for the HLA-B*5701 allele
For HLA-B*5701-positive patients, treatment with an abacavir-containing regimen is contraindicated
