Pharmacological Class:
HIV-1 integrase strand transfer inhibitor (INSTI).

Active Ingredient(s):
Dolutegravir 50mg; tablets.

Company
ViiV Healthcare
Indication(s):
In combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and children ≥12 years and ≥40kg.

Pharmacology:
Dolutegravir inhibits HIV-1 integrase by binding to the integrase active site and blocking the strand transfer step of retroviral deoxyribonucleic acid (DNA) integration which is essential for the HIV replication cycle.

Clinical Trials:
The efficacy of Tivicay was based on analyses of data from two trials, SPRING-2 and SINGLE, in treatment-naïve, HIV-1-infected subjects (n=1,641); one trial, SAILING, in treatment-experienced, INSTI-naïve HIV-1-infected subjects (n=715); and from VIKING-3 trial in INSTI-­experienced ­HIV-1-infected subjects (n=183) with virological failure and current or historical evidence of raltegravir and/or elvitegravir resistance.

In the SPRING-2 trial, once-daily Tivicay versus twice-daily raltegravir in 822 HIV-infected, treatment-naïve patients, both in combination with a fixed-dose dual-NRTI treatment were eva luated. At week 48, the proportion of subjects who were virologically suppressed (HIV-1 RNA <50 copies/mL) was 88% for the regimen containing Tivicay and 86% for the regimen containing raltegravir, meeting the 10% non-inferiority criteria.

In the SINGLE trial, once-daily Tivicay plus fixed-dose Epzicom versus the fixed-dose Atripla regimen in 833 HIV-infected, treatment-naïve patients were eva luated. At 48 weeks, the proportion of subjects who were virologically suppressed (HIV-1 RNA <50 copies/mL) was 88% for Tivicay regimen and 81% for Atripla which was statistically significant.

For more information on clinical trials, see full labeling.

Legal Classification:
Rx

Adults:
≥12 years and ≥40kg: treatment-naïve or treatment-experienced INSTI-naïve: 50mg once daily. Treatment-naïve or treatment-experienced INSTI-naïve with concomitant potent UGT1A/CYP3A inducers (eg, efavirenz, fosamprenavir/ritonavir, tipranavir/ritonavir, or rifampin): 50mg twice daily. INSTI-experienced with certain INSTI-associated resistance substitutions or clinically suspected INSTI resistance: 50mg twice daily.

Children:
<12 years or <40kg, or INSTI-experienced with documented or clinically suspected resistance to other INSTIs (raltegravir, elvitegravir): not established.

Contraindication(s):
Concomitant dofetilide.

Warnings/Precautions:
Discontinue if hypersensitivity reactions develop. Increased risk for worsening/development of elevated transaminases in patients with hepatitis B or C; monitor LFTs prior to starting and during therapy. Severe hepatic impairment: not recommended. INSTI-experienced patients (with certain INSTI-associated resistance substitutions or clinically suspected INSTI resistance) with severe renal impairment: decrease in dolutegravir concentrations may result in loss of efficacy and development of resistance. Pregnancy (Category B). Nursing mothers: not recommended.

Interaction(s)
May be affected by drugs that induce or inhibit UGT1A1, UGT1A3, UGT1A9, BCRP, and P-gp enzymes or transporters. Avoid concomitant nevirapine, oxcarbazepine, phenytoin, phenobarbital, carbamazepine, St. John’s wort. Avoid etravirine unless coadministered with atazanavir/ritonavir, darunavir/ritonavir, or lopinavir/ritonavir. Concomitant efavirenz, fosamprenavir/ritonavir, tipranavir/ritonavir, or rifampin: adjust dose to 50mg twice daily. Concomitant cation-containing antacids, laxatives, sucralfate, oral iron/calcium supplements, and buffered drugs: give dolutegravir 2 hours before or 6 hours after. Concomitant metformin; monitor closely and adjust metformin dose if necessary.

Adverse Reaction(s)
Insomnia, headache; immune reconstitution syndrome, lab abnormalities.

How Supplied:
Tabs—30

LAST UPDATED:
8/30/2013