Overview
11 DESCRIPTION TIVICAY contains dolutegravir, as dolutegravir sodium, an HIV INSTI. The chemical name of dolutegravir sodium is sodium (4 R ,12a S )-9-{[(2,4-difluorophenyl)methyl]carbamoyl}-4-methyl-6,8-dioxo-3,4,6,8,12,12a-hexahydro-2 H -pyrido[1',2':4,5]pyrazino[2,1- b ][1,3]oxazin-7-olate. The empirical formula is C 20 H 18 F 2 N 3 NaO 5, and the molecular weight is 441.36 g/mol.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Dolutegravir is an HIV-1 antiretroviral agent [see Microbiology ( 12.4 )]. 12.2 Pharmacodynamics Effects on Electrocardiogram In a randomized, placebo-controlled, cross-over trial, 42 healthy subjects received single-dose oral administrations of placebo, dolutegravir 250-mg suspension (exposures approximately 3–fold of the 50-mg once-daily dose at steady state), and moxifloxacin 400 mg (active control) in random sequence. After baseline and placebo adjustment, the maximum mean QTc change based on Fridericia correction method (QTcF) for dolutegravir was 2.4 msec (1-sided 95% upper CI: 4.9 msec). TIVICAY did not prolong the QTc interval over 24 hours postdose.
Indications
- 1 INDICATIONS AND USAGE 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) aged at least 4 weeks and weighing at least 3 kg [see Microbiology ( 12.4 )]. 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...
Common Doses
- 25 mg
- 50 mg
- 5 mg
- 15 mg
Dosage
2 DOSAGE AND ADMINISTRATION May be taken without regard to food. ( 2.2 , 2.6) 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
Contraindications
- 4 CONTRAINDICATIONS TIVICAY and TIVICAY PD are contraindicated in patients: with previous hypersensitivity reaction to dolutegravir [see Warnings and Precautions ( 5.1 )]. receiving dofetilide due to the potential for increased dofetilide plasma concentrations and the risk for serious and/or life-threatening events [see Drug Interactions ( 7 )] . Previous hypersensitivity reaction to dolutegravir. ( 4 ) Coadministration with dofetilide. ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following serious adverse drug reactions are discussed in other sections of the labeling: Hypersensitivity reactions [see Warnings and Precautions ( 5.1 )] . Hepatotoxicity [see Warnings and Precautions ( 5.2 )]. Immune Reconstitution Syndrome [see Warnings and Precautions ( 5.4 )] . 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. ( 6.
Interactions
- 7 DRUG INTERACTIONS Refer to the full prescribing information for important drug interactions with TIVICAY or TIVICAY PD. ( 4 , 7 ) Drugs that are metabolic inducers may decrease the plasma concentrations of dolutegravir. ( 7.2 , 7.3 ) 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. ( 7.3 ) 7.