Dolutegravir

TIVICAY and TIVICAY PD are indicated in combination with other antiretroviral agents for the treatment of HIV ‑ 1 infection in adults (treatment-naïve or -experienced) and in pediatric patients (treatment-naïve or -experienced but integrase strand transfer inhibitor [INSTI]-naïve) weighing at least 2 kg. TIVICAY is indicated in combination with rilpivirine as a complete regimen for the treatment of HIV-1 infection in adults to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies/mL) on a stable antiretroviral regimen for at least 6 months with no history of treatment failure or known substitutions associated with resistance to either antiretroviral agent.

Dolutegravir is an HIV-1 antiretroviral agent.

• May be taken without regard to food. UGT = uridine diphosphate glucuronosyltransferase, CYP = cytochrome P450. a Rilpivirine dose is 25 mg once daily for those switching to dolutegravir plus rilpivirine. b Alternative combinations that do not include metabolic inducers should be considered where possible. Adult Population Recommended Dose Treatment-naïve or treatment-experienced INSTI-naïve or virologically suppressed (HIV-1 RNA <50 copies per mL) adults switching to dolutegravir plus rilpivirine a 50 mg once daily Treatment-naïve or treatment-experienced INSTI-naïve when coadministered with certain UGT1A or CYP3A inducers 50 mg twice daily INSTI-experienced with certain INSTI-associated resistance substitutions or clinically suspected INSTI resistance b 50 mg twice daily Pediatric Patients: Treatment-naïve or treatment-experienced INSTI-naïve patients weighing at least 2 kg.

TIVICAY and TIVICAY PD are contraindicated in patients: • with previous hypersensitivity reaction to dolutegravir. • receiving dofetilide due to the potential for increased dofetilide plasma concentrations and the risk for serious and/or life-threatening events. • Previous hypersensitivity reaction to dolutegravir. • Coadministration with dofetilide.

• Hypersensitivity reactions characterized by rash, constitutional findings, and sometimes organ dysfunction, including liver injury, have been reported. Discontinue TIVICAY or TIVICAY PD and other suspect agents immediately if signs or symptoms of hypersensitivity reactions develop, as a delay in stopping treatment may result in a life-threatening reaction. • Hepatotoxicity has been reported in patients receiving dolutegravir-containing regimens. Patients with underlying hepatitis B or C may be at increased risk for worsening or development of transaminase elevations. Monitoring for hepatotoxicity is recommended. • Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy. • TIVICAY tablets and TIVICAY PD tablets for oral suspension are not substitutable.

The following serious adverse drug reactions are discussed in other sections of the labeling: • Hypersensitivity reactions. • Hepatotoxicity. • Immune Reconstitution Syndrome. The most common adverse reactions of moderate to severe intensity and incidence at least 2% (in those receiving TIVICAY in any one adult trial) are insomnia, fatigue, and headache.

• Refer to the full prescribing information for important drug interactions with TIVICAY or TIVICAY PD. • Drugs that are metabolic inducers may decrease the plasma concentrations of dolutegravir. • TIVICAY or TIVICAY PD should be taken 2 hours before or 6 hours after taking cation-containing antacids or laxatives, sucralfate, oral supplements containing iron or calcium, or buffered medications. When taken with food, TIVICAY and supplements containing calcium or iron can be taken at the same time.

Store TIVICAY tablets at 25°C (77°F), excursions permitted 15° to 30°C (59° to 86°F). Store TIVICAY PD tablets for oral suspension below 30°C (86°F). Store and dispense the 10-mg tablets in the original package, protect from moisture, and keep the bottle tightly closed. Store and dispense the 5-mg tablets in the original bottle, protect from moisture, and keep the bottle tightly closed.