TIVICAY and TIVICAY PD are indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus type 1 (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.

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 per 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.

Perform pregnancy testing before initiation of dolutegravir in adolescents and adults of childbearing potential.

Do not interchange TIVICAY tablets and TIVICAY PD tablets for oral suspension on a milligram-per milligram basis due to differing pharmacokinetic profiles.

Do not use TIVICAY tablets in patients weighing 3 to 14 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

Hypersensitivity reactions have been reported and were characterized by rash, constitutional findings, and sometimes organ dysfunction, including liver injury.

Hepatic adverse events have been reported in patients receiving a dolutegravir-containing regimen. Patients with underlying hepatitis B or C may be at increased risk for worsening or development of transaminase elevations with use of TIVICAY or TIVICAY PD.

Cases of hepatic toxicity, including elevated serum liver biochemistries, hepatitis, and acute liver failure have been reported in patients receiving a dolutegravir-containing regimen without pre-existing hepatic disease or other identifiable risk factors.

Caution is warranted for INSTI-experienced patients (with certain INSTI-associated resistance substitutions or clinically suspected INSTI resistance. With severe renal impairment, as the decrease in dolutegravir concentrations may result in loss of therapeutic effect and development of resistance to TIVICAY, TIVICAY PD, or other co-administered antiretroviral agents.

Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including TIVICAY or TIVICAY PD. During the initial phase of combination antiretroviral treatment, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia [PCP], or tuberculosis), which may necessitate further evaluation and treatment.

Autoimmune disorders (such as Graves’ disease, polymyositis, and Guillain-Barré syndrome) have also been reported to occur in the setting of immune reconstitution; however, the time to onset is more variable and can occur many months after initiation of treatment.

Use of TIVICAY or TIVICAY PD with etravirine without co-administration of atazanavir/ritonavir, darunavir/ritonavir, or lopinavir/ritonavir is not recommended.

If used with Efavirenz adjust dose of TIVICAY to twice daily for treatment-naïve and treatment- experienced, INSTI-naïve adult patients. In pediatric patients, increase the weight-based dose of TIVICAY or TIVICAY PD to twice daily. Use alternative combinations that do not include metabolic inducers where possible for INSTI-experienced patients with certain INSTI-associated resistance substitutions or clinically suspected INSTI resistance.

Avoid co-administration with nevirapine because there are insufficient data to make dosing recommendations.

Use with Fosamprenavir/ritonavira or Tipranavir/ritonavira adjust dose of TIVICAY to twice daily for treatment-naïve and treatment-experienced, INSTI-naïve adult patients. In pediatric patients, increase the weight-based dose of TIVICAY or TIVICAY PD to twice daily.  Use alternative combinations that do not include metabolic inducers where possible for INSTI-experienced patients with certain INSTI-associated resistance substitutions or clinically suspected INSTI resistance.

Co-administration with  Dofetilid is contraindicated with TIVICAY or TIVICAY PD.

If used with Carbamazepine adjust dose of TIVICAY to twice daily in treatment-naïve or treatment-experienced, INSTI-naïve adult patients. In pediatric patients, increase the weight-based dose of TIVICAY or TIVICAY PD to twice daily.  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.

Avoid co-administration of Oxcarbazepine, Phenytoin, Phenobarbital, or St. John’s wort with TIVICAY or TIVICAY PD because there are insufficient data to make dosing recommendations.

In medications containing polyvalent cations (e.g., Mg or Al): Cation-containing antacids or laxatives Sucralfate Buffered medications, administer TIVICAY or TIVICAY PD 2 hours before or 6 hours after taking medications containing polyvalent cations.

When taken with food, TIVICAY and supplements or multivitamins containing calcium or iron can be taken at the same time. Under fasting conditions, TIVICAY or TIVICAY PD should be taken 2 hours before or 6 hours after taking supplements containing calcium or iron.

Elevated levels of dalfampridine increase the risk of seizures. The potential benefits of taking dalfampridine concurrently with TIVICAY or TIVICAY PD should be considered against the risk of seizures in these patients.

If taken with Rifampin adjust dose of TIVICAY to twice daily for treatment-naïve and treatment-experienced, INSTI-naïve adult patients. In pediatric patients, increase the weight-based dose of TIVICAY or TIVICAY PD to twice daily. Use alternatives to rifampin where possible for INSTI-experienced patients with certain INSTI-associated resistance substitutions or clinically suspected INSTI resistance.

An observational study showed an association between TIVICAY and an increased risk of neural tube defects when TIVICAY was administered at the time of conception and in early pregnancy. As there is limited understanding of reported types of neural tube defects associated with dolutegravir use and because the date of conception may not be determined with precision, an alternative treatment to TIVICAY should be considered at the time of conception through the first trimester of pregnancy.

Dolutegravir may be considered during the second and third trimesters of pregnancy if the expected benefit justifies the potential risk to the pregnant woman and the fetus.

The Centers for Disease Control and Prevention recommends that HIV-1–infected mothers in the
United States not breastfeed their infants to avoid risking postnatal transmission of HIV-1 infection.

It is not known whether dolutegravir is present in human breast milk, affects human milk production, or has effects on the breastfed infant. When administered to lactating rats, dolutegravir was present in milk.

Because of the potential for (1) HIV-1 transmission (in HIV-negative infants), (2) developing viral resistance (in HIV-positive infants), and (3) adverse reactions in a breastfed infant similar to those seen in adults, instruct mothers not to breastfeed if they are receiving dolutegravir.

GoToSource

• Use in patient under 4 weeks of age. GoToSource

• Monotherapy. GoToSource

Liver injury and worsening or flares of hepatitis. GoToSource

Increases in serum creatinine (signifies impaired kidney function or kidney disease). GoToSource

Hypersensitivity reactions including epidermal necrolysis and drug rash with eosinophilia and systemic symptoms. GoToSource

Immune reconstitution inflammatory syndrome (clinical worsening of a known condition or the appearance of a new condition after initiating antiretroviral therapy). GoToSource

Insomnia and weight gain. GoToSource

Lawsuits filed for birth defects.