CLINICAL TRIALS INVOLVING TIVICAY

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IMPORTANT SAFETY INFORMATION

Contraindications

• Do not use TIVICAY or TIVICAY PD in patients with previous hypersensitivity reaction to dolutegravir
• Do not use TIVICAY or TIVICAY PD in patients receiving dofetilide

Warnings and precautions

Hypersensitivity Reactions:

• Hypersensitivity reactions have been reported with dolutegravir and were characterized by rash, constitutional findings, and sometimes organ dysfunction, including liver injury
• Discontinue dolutegravir immediately if signs or symptoms of hypersensitivity reaction develop, as a delay in stopping treatment may result in a life-threatening reaction. Clinical status, including liver aminotransferases, should be monitored and appropriate therapy initiated

Hepatotoxicity:

• Hepatic adverse events have been reported, including cases of hepatic toxicity (elevated serum liver biochemistries, hepatitis, and acute liver failure) in patients receiving a dolutegravir-containing regimen without pre-existing hepatic disease or other identifiable risk factors
• Patients with underlying hepatitis B or C or marked elevations in transaminases prior to treatment may be at increased risk for worsening or development of transaminase elevations with use of dolutegravir. In some cases, the elevations in transaminases were consistent with immune reconstitution syndrome or hepatitis B reactivation, particularly in the setting where anti-hepatitis therapy was withdrawn
• Monitoring for hepatotoxicity is recommended

Embryo-Fetal Toxicity:

• Assess the risks and benefits of TIVICAY and TIVICAY PD and discuss with the patient to determine if an alternative treatment should be considered at the time of conception through the first trimester of pregnancy due to the risk of neural tube defects
• Pregnancy testing is recommended before use of TIVICAY or TIVICAY PD. Adolescents and adults of childbearing potential should be counseled on the consistent use of effective contraception

Adverse Reactions or Loss of Virologic Response Due to Drug Interactions with concomitant use of dolutegravir and other drugs may occur (see Contraindications and Drug Interactions)

Immune Reconstitution Syndrome, including the occurrence of autoimmune disorders with variable time to onset, has been reported with the use of dolutegravir

Different Formulations Are Not Interchangeable:
TIVICAY and TIVICAY PD are not bioequivalent and are not interchangeable on a milligram-per-milligram basis. If a patient switches from one formulation to the other, the dose must be adjusted

Adverse reactions

The most common adverse reactions (incidence ≥2%, Grades 2-4) in treatment-naïve adults receiving TIVICAY in a combination regimen were insomnia (3%), headache (2%), and fatigue (2%)

 

Drug interactions

• Consult the full Prescribing Information for more information on potentially significant drug interactions
• Drugs that induce or inhibit UGT1A1 and/or CYP3A may affect plasma concentrations of dolutegravir
• Administer TIVICAY or TIVICAY PD 2 hours before or 6 hours after taking antacids, polyvalent cation-containing products or laxatives, sucralfate, oral supplements containing iron or calcium, or buffered medications. Alternatively, TIVICAY and supplements containing calcium or iron can be taken with food

Use in specific populations

• Pregnancy: There are insufficient human data on the use of dolutegravir during pregnancy to definitively assess a drug-associated risk for birth defects and miscarriage. An Antiretroviral Pregnancy Registry has been established. Advise adolescents and adults of childbearing potential of the potential risk of neural tube defects. Assess the risks and benefits of continuing TIVICAY and TIVICAY PD and discuss with the patient to determine if an alternative treatment should be considered at the time of conception through the first trimester of pregnancy or if pregnancy is confirmed in the first trimester
• Lactation: Breastfeeding is not recommended due to the potential for HIV-1 transmission, developing viral resistance in HIV-positive infants, and adverse reactions in a breastfed infant
• Females and Males of Reproductive Potential: Pregnancy testing is recommended before initiation of TIVICAY or TIVICAY PD. Counsel adolescents and adults of childbearing potential taking TIVICAY or TIVICAY PD on the consistent use of effective contraception

Please see full Prescribing Information for TIVICAY and TIVICAY PD.