Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)
USE IN SPECIFIC POPULATIONS
- The safety, virologic, and immunologic responses in subjects who received TIVICAY were evaluated in 46 treatment-experienced, INSTI-naïve, HIV-1–infected subjects aged 6 to less than 18 years in an open-label, multicenter, dose-finding clinical trial, IMPAACT P1093. Frequency, type, and severity of adverse drug reactions among the 46 pediatric subjects were comparable to those observed in adults. In 17 subjects weighing at least 30 kg, pharmacokinetic parameters of dolutegravir were comparable to adults receiving 50 mg once daily.
- Safety and efficacy of TIVICAY have not been established in pediatric patients weighing less than 30 kg or in any pediatric patients who are INSTI-experienced.
PATIENT COUNSELING INFORMATION
Addition of the following sections:
- Advise patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to TIVICAY during pregnancy.
- Instruct women with HIV-1 infection not to breastfeed because HIV-1 can be passed to the baby in the breast milk.
- Instruct patients that if they miss a dose of TIVICAY, to take it as soon as they remember. Advise patients not to double their next dose or take more than the prescribed dose.
- Instruct patients to store the TIVICAY 10-mg tablets in the original package, keep the bottle tightly closed, and protect from moisture. Do not remove desiccant.
PATIENT PACKAGE INSERT
- Extensive changes to this section; please refer to label.
Effect of Dolutegravir on the Pharmacokinetics of Other Agents
Clinical Trials Experience
- Week 144 safety and efficacy data from Phase III study ING114467 (SINGLE) in antiretroviral therapy (ART)-naïve subjects.
- Week 96 safety and efficacy data from Phase III study ING114915 (FLAMINGO) in ART-naïve subjects.
- in vitro, dolutegravir was not a substrate of OATP1B1 or OATP1B3.
- If TIVICAY is used with carbamazepine adjust dose of TIVICAY to 50 mg twice daily in treatment-naïve or treatment-experienced, INSTI-naïve patients. Use alternative treatment that does not include carbamazepine where possible for INSTI-experienced patients with certain INSTI-associated resistance substitutions or clinically suspected INSTI resistance.
- When TIVICAY is used with metformin, limit the total daily dose of metformin to 1,000 mg either when starting metformin or TIVICAY. When stopping TIVICAY, the metformin dose may require an adjustment. Monitoring of blood glucose when initiating concomitant use and after withdrawal of TIVICAY is recommended.
*Section 6.1 updated to provide information regarding:
- Week 96 results from Phase 3 trials ING113086 (SPRING-2) and ING114467 (SINGLE) and Week 48 results from Phase 3 trial ING114915 (FLAMINGO) in antiretroviral (ARV) treatment-naïve subjects
- Week 48 clinical results from Phase 3 trial ING111762 (SAILING) in ARV-treatment experienced, INSTI-naïve subjects
- Week 48 results from trial ING112574 (VIKING-3), in treatment-experienced, INSTI experienced subjects
- Boceprevir drug-drug interaction trial, ING115697
7 DRUG INTERACTIONS
7.1 Effect of Dolutegravir on the Pharmacokinetics of Other Agents
- The effect of dolutegravir on renal transporters updated
7.3 Established and Other Potentially Significant Drug Interactions
- Table 5 edited...Oral calcium or iron supplements, including multivitamins containing calcium or iron