For HIV-1. See Full Indication.

RISKS AND SIDE EFFECTS OF TIVICAY AND TIVICAY PD

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reconstitution syndrome or hepatitis B reactivation, particularly in the setting where anti-hepatitis therapy was withdrawn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

TREATMENT-NAÏVE STUDIES

ADVERSE DRUG REACTIONS

SINGLE

SPRING-2

FLAMINGO

STUDY 1490

Grades 2 to 4 treatment-emergent ADRs
(≥2% frequency in either treatment arm)1,2

Grade 1 insomnia rates
7% and 4% in patients receiving TIVICAY and efavirenz/TDF/FTC, respectively
These events were not treatment limiting 

*Includes pooled terms: rash, rash generalized, rash macular, rash maculopapular, rash pruritic, and drug eruption.

Grades 2 to 4 treatment-emergent ADRs2,3*

Grade 1 insomnia rates
1% or <1% in patients receiving TIVICAY and raltegravir, respectively
These events were not treatment limiting 

*From table 3 of the full PI for TIVICAY.

†Includes pooled terms: rash, rash generalized, rash macular, rash maculopapular, rash pruritic, and drug eruption.

Grades 2 to 4 treatment-emergent ADRs
(≥2% frequency in either treatment arm)2

Grade 1 insomnia rates2
1% and 2% in patients receiving TIVICAY and darunavir/ritonavir, respectively
These events were not treatment limiting 

*Includes pooled terms: rash, rash generalized, rash macular, rash maculopapular, rash pruritic, and drug eruption.

Adverse reactions (all Grades)
(≥2% frequency in either treatment arm) through 96 weeks5,6

DISCONTINUATIONS DUE TO AEs

Proportion of patients who discontinued due to
AEs in treatment-naïve trials1-5

Treatment-Experienced Study

ADVERSE DRUG REACTIONS

SAILING—Grades 2 to 4 treatment-emergent
adverse drug reactions (≥2% frequency) through 48 weeks2,7

The only treatment-emergent adverse drug reaction of moderate to severe intensity with at least 2% frequency in either treatment group was diarrhea: 2% (6 of 354) in patients receiving TIVICAY 50 mg once daily + BR‡ and 1% (5 of 361) in patients receiving
RAL 400 mg twice daily + BR‡

DISCONTINUATIONS DUE TO AEs
THROUGH 48 WEEKS

Proportion of patients who discontinued due to AEs
in a treatment-experienced, INSTI-naïve trial7

‡BR was investigator-selected and consisted of up to 2 agents, including at least 1 fully active agent. Most common BRs: darunavir/r + TDF, lopinavir/r + TDF, darunavir/r + etravirine, lopinavir/r, atazanavir/r + TDF, darunavir/r + maraviroc.

 

3TC=lamivudine; ABC=abacavir; ADR=adverse drug reaction; AE=adverse event; BIC=bictegravir; BR=background regimen; DTG=dolutegravir; FTC=emtricitabine; INSTI=integrase strand transfer inhibitor; PI=prescribing information; r=ritonavir; RAL=raltegravir; TAF=tenofovir alafenamide; TDF=tenofovir disoproxil fumarate.

References: 1. Walmsley S, Baumgarten A, Berenguer J, et al. Dolutegravir plus abacavir/lamivudine for the treatment of HIV-1 infection in antiretroviral therapy-naive patients: week 96 and week 144 results from the SINGLE randomized clinical trial. J Acquir Immune Defic Syndr. 2015;70(5):515-519. 2. Data on file, ViiV Healthcare. 3. Raffi F, Jaeger H, Quiros-Roldan E, et al; on behalf of the SPRING-2 Study Group. Once-daily dolutegravir versus twice-daily raltegravir in antiretroviral-naive adults with HIV-1 infection (SPRING-2 study): 96 week results from a randomised, double-blind, non-inferiority trial. Lancet Infect Dis. 2013;13(11):927-935. 4. Molina J-M, Clotet B, van Lunzen J, et al. Once-daily dolutegravir versus darunavir plus ritonavir for treatment-naive adults with HIV-1 infection (FLAMINGO): 96 week results from a randomized, open-label, phase 3b study. Lancet HIV. 2015;2(4):e127-e136. 5. Stellbrink H-J, Arribas JR, Stephens JL, et al. Co-formulated bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir with emtricitabine and tenofovir alafenamide for initial treatment of HIV-1 infection: week 96 results from a randomised, double-blind, multicentre, phase 3, non-inferiority trial. Lancet HIV. 2019;6(6):e364-e372. 6. BIKTARVY [package insert]. Foster City, CA: Gilead Sciences, Inc; 2018. 7. Cahn P, Pozniak AL, Mingrone H, et al; on behalf of the extended SAILING Study Team. Dolutegravir versus raltegravir in antiretroviral-experienced, integrase-inhibitor-naive adults with HIV: week 48 results from the randomised, double-blind, non-inferiority SAILING study. Lancet. 2013;382(9893):700-708.

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