Triumeq by ViiV Healthcare

Specialty Pharmacy Times, March/April 2015, Volume 6, Issue 2

The FDA approved Triumeq (abacavir, dolutegravir, and lamivudine) tablets for the treatment of HIV-1 infection in patients without the HLA-B*5701 allele.

The FDA approved Triumeq (abacavir, dolutegravir, and lamivudine) tablets for the treatment of HIV-1 infection in patients without the HLA-B*5701 allele.

On August 22, 2014, ViiV Healthcare announced FDA approval of Triumeq (abacavir, dolutegravir, and lamivudine) tablets, an oral combination treatment for the management of HIV-1 infection in patients without the HLA-B*5701 allele. Triumeq carries a black box warning for hypersensitivity reactions, lactic acidosis, severe hepatomegaly, and hepatitis B exacerbations.1,2

Because Triumeq contains abacavir, any patient initiating treatment with Triumeq must be screened for the HLA-B*5701 allele, which is associated with severe hypersensitivity reactions to abacavir. Contraindications to the use of Triumeq include presence of the HLA-B*5701 allele; any previous hypersensitivity reaction to abacavir, dolutegravir, or lamivudine; moderate or severe hepatic impairment; and use in any patient who is also taking the antiarrhythmic medication dofetilide.2

Mechanism of Action

Triumeq is a fixed-dose combination of the integrase strand transfer inhibitor dolutegravir and the nonnucleoside reverse transcriptase inhibitors abacavir and lamivudine. Together, these 3 medications form a complete regimen for the management of HIV-1 infection.2,3

Dosage and Administration

Triumeq is a tablet containing 50 mg of dolutegravir, 600 mg of abacavir, and 300 mg of lamivudine. Triumeq can be taken either with or without food and unlike other regimens for HIV-1, no boosting agent is required.2,3

Pharmacology and Pharmacokinetics

The 3 components of Triumeq have different pharmacokinetic properties. Abacavir has an elimination half-life of 1.5 hours, dolutegravir has a half-life of 14 hours, and lamivudine has a half-life ranging from 5 to 7 hours. Although exposure to lamivudine is unaffected, exposure to abacavir may be slightly lower and exposure to dolutegravir slightly higher in patients taking Triumeq with a high-fat meal—but not to a clinically significant degree.2

Clinical Trials

The phase 3, 414-patient SINGLE study was a randomized, double-blind, active-control trial of treatment-naïve, HLA-B*5701-negative, HIV-1—infected adults comparing once-daily dolutegravir/abacavir/lamivudine (in the form of Tivicay [dolutegravir] plus Epzicom [abacavir/lamivudine]) with once-daily efavirenz/tenofovir/emtricitabine (Atripla). After 96 weeks, 80% of patients taking Tivicay plus Epzicom achieved HIV-1 RNA levels of less than 50 copies/mL compared with 72% of patients taking Atripla, which was a statistically significant difference (P = .006). Over the course of the trial, 3% of patients taking Tivicay plus Epzicom discontinued treatment due to adverse events (AEs) compared with 12% of patients of patients taking Atripla.2,4

A single-dose, randomized, 2-part, open-label, crossover study of 66 healthy adults confirmed the bioequivalence of Tivicay plus Epzicom as 2 separate tablets and Triumeq, which combines the ingredients of the 2 tablets into a single tablet. Both with and without food, treatment with Triumeq was bioequivalent to the combination of Tivicay plus Epzicom, confirming that the results of the SINGLE study apply to patients taking Triumeq.2,5

Warnings and Precautions

Use of Triumeq with efavirenz, fosamprenavir/ritonavir, tipranavir/ritonavir, or rifampin may reduce exposure to dolutegravir. Patients using any of these treatments may require an additional dose of dolutegravir 12 hours after administration of Triumeq to compensate for the drug interaction.

Inorganic antacids and supplements containing calcium or iron can all lower concentrations of dolutegravir. As a result, patients should take Triumeq at least 2 hours before or 6 hours after a dose of inorganic antacids or vitamins containing calcium or iron. Patients with type 2 diabetes mellitus taking metformin may require reductions in the dosage of metformin due to increased metformin exposure in patients taking Triumeq. In addition, because oxcarbazepine and nevirapine may alter levels of dolutegravir, these medications should be avoided by patients taking Triumeq.2

Patients coinfected with hepatitis B or hepatitis C who are taking Triumeq for HIV-1 infection may be at increased risk for elevations of liver enzymes and hepatic decompensation. In these patients, regular monitoring of serum transaminase levels is recommended. Even more intensive monitoring may be necessary in patients taking interferons for hepatitis C due to the risk of interferon-related hepatotoxicity.2

Immune reconstitution syndrome, fat redistribution, and myocardial infarction are potential AEs with Triumeq. The most common AEs with Triumeq included insomnia, headache, and fatigue, each of which occurred in at least 2% of patients. Triumeq is a Pregnancy Category C medication. For a complete discussion of potential drug interactions and AEs with Triumeq, please consult the product package insert.2 SPT

References

  • ViiV Healthcare receives FDA approval for Triumeq [news release]. London, UK: ViiV Healthcare. www.viivhealthcare.com/media/press-releases/2014/august/viiv-healthcare-receives-fda-approval-for-triumeq.aspx. Accessed March 2015.
  • Triumeq (abacavir, dolutegravir, and lamivudine) tablets [package insert]. Research Triangle Park, NC: Viiv Healthcare; 2014.
  • Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. US Department of Health and Human Services. http://aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf. Updated November 13, 2014. Accessed March 2015.
  • Walmsley S, Berenguer J, Khuong-Josses M, et al. Dolutegravir regimen statistically superior to efavirenz/tenofovir/emtricitabine: 96-week results from the SINGLE study (ING114467). Poster presented at: 21st Conference on Retroviruses and Opportunistic Infections; March 3-6, 2014; Boston, MA. Poster 543.
  • Weller S, Chen S, Borland J, et al. Bioequivalence of a dolutegravir, abacavir, and lamivudine fixed-dose combination tablet and the effect of food. J Acquir Immune Defic Syndr. 2014;66(4):393-398.

About the Author

Michael R. Page, PharmD, RPh, earned his PharmD from the Ernest Mario School of Pharmacy at Rutgers University. He has worked as a community pharmacist at CVS Pharmacy and is currently clinical editor in clinical and scientific affairs at Pharmacy Times.