TIVICAY- dolutegravir sodium tablet, film coated
REMEDYREPACK INC.
1 INDICATIONS AND USAGE
TIVICAY � is indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults and pediatric patients weighing at least 30 kg.
Limitations of Use:
Use of TIVICAY in integrase strand transfer inhibitor (INSTI)-experienced patients should be guided by the number and type of baseline INSTI substitutions. The efficacy of TIVICAY 50 mg twice daily is reduced in patients with an INSTI-resistance Q148 substitution plus 2 or more additional INSTI-resistance substitutions, including T66A, L74I/M, E138A/K/T, G140S/A/C, Y143R/C/H, E157Q, G163S/E/K/Q, or G193E/R [see Microbiology (12.4)].
2 DOSAGE AND ADMINISTRATION
2.1 Adults
TIVICAY tablets may be taken with or without food.TIVICAY tablets may be taken with or without food.
DOSAGE FORMS AND STRENGTHS
Tablets:
10 mg: Each tablet contains 10 mg of dolutegravir (as dolutegravir sodium). Tablets are white, round, film-coated, biconvex tablets debossed with "SV 572" on one side and "10" on the other side.
25 mg: Each tablet contains 25 mg of dolutegravir (as dolutegravir sodium). Tablets are pale yellow, round, film-coated, biconvex tablets debossed with "SV 572" on one side and "25" on the other side.
50 mg: Each tablet contains 50 mg of dolutegravir (as dolutegravir sodium). Tablets are yellow, round, film-coated, biconvex tablets debossed with "SV 572" on one side and "50" on the other side.
4 CONTRAINDICATIONS
TIVICAY is 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.
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 per mol.
Dolutegravir sodium is a white to light yellow powder and is slightly soluble in water.
Each film-coated tablet of TIVICAY for oral administration contains 10.5, 26.3, or 52.6 mg of dolutegravir sodium, which is equivalent to 10, 25, or 50 mg dolutegravir free acid, respectively, and the following inactive ingredients: D-mannitol, microcrystalline cellulose, povidone K29/32, sodium starch glycolate, and sodium stearyl fumarate. The tablet film‑coating contains the inactive ingredients iron oxide yellow (25-mg and 50-mg tablets only), macrogol/PEG, polyvinyl alcohol-part hydrolyzed, talc, and titanium dioxide.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Dolutegravir is an HIV-1 antiviral agent.
Microbiology
Mechanism of Action
Dolutegravir inhibits HIV integrase by binding to the integrase active site and blocking the strand transfer step of retroviral deoxyribonucleic acid (DNA) integration which is essential for the HIV replication cycle. Strand transfer biochemical assays using purified HIV-1 integrase and pre-processed substrate DNA resulted in IC 50 values of 2.7 nM and 12.6 nM.
HOW SUPPLIED/STORAGE AND HANDLING
TIVICAY tablets, 10 mg, are white, round, film-coated, biconvex tablets debossed with "SV 572" on one side and "10" on the other side. Bottle of 30 tablets with child-resistant closure and containing a desiccant. NDC 49702-226-13.
Store and dispense the 10-mg tablets in the original package, protect from moisture, and keep the bottle tightly closed. Do not remove desiccant.
TIVICAY tablets, 25 mg, are pale yellow, round, film-coated, biconvex tablets debossed with "SV 572" on one side and "25" on the other side. Bottle of 30 tablets with child-resistant closure. NDC 49702-227-13.
TIVICAY tablets, 50 mg, are yellow, round, film-coated, biconvex tablets debossed with "SV 572" on one side and "50" on the other side. Bottle of 30 tablets with child-resistant closure. NDC 49702-228-13.
Store at 25 � C (77 � F); excursions permitted 15 � to 30 � C (59 � to 86 � F) [See USP Controlled Room Temperature].
17 PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Patient Information).
Drug Interactions
TIVICAY is contraindicated with dofetilide because interactions between these drugs can result in potentially life-threatening adverse events [see Contraindications (4)].
Hypersensitivity Reactions
Advise patients to immediately contact their healthcare provider if they develop rash. Instruct patients to immediately stop taking TIVICAY and other suspect agents, and seek medical attention if they develop a rash associated with any of the following symptoms, as it may be a sign of a more serious reaction such as severe hypersensitivity: fever; generally ill feeling; extreme tiredness; muscle or joint aches; blisters or peeling of the skin; oral blisters or lesions; eye inflammation; facial swelling; swelling of the eyes, lips, tongue, or mouth; breathing difficulty; and/or signs and symptoms of liver problems (e.g., yellowing of the skin or whites of the eyes, dark or tea-colored urine, pale-colored stools or bowel movements, nausea, vomiting, loss of appetite, or pain, aching, or sensitivity on the right side below the ribs) [see Warnings and Precautions (5.1)].
Effects on Serum Liver Biochemistries in Patients with Hepatitis B or C Co-infection
Advise patients that it is recommended to have laboratory testing before and during therapy as patients with underlying hepatitis B or C may be at increased risk for worsening or development of transaminase elevations with use of TIVICAY [see Warnings and Precautions (5.2)].
Fat Redistribution
Inform patients that redistribution or accumulation of body fat may occur in patients receiving antiretroviral therapy and that the cause and long‑term health effects of these conditions are not known at this time [see Warnings and Precautions (5.3)].
Immune Reconstitution Syndrome
Advise patients to inform their healthcare provider immediately of any signs or symptoms of infection as inflammation from previous infection may occur soon after combination antiretroviral therapy, including when TIVICAY is started [see Warnings and Precautions (5.4)].
Pregnancy Registry
Advise patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to TIVICAY during pregnancy [see Use in Specific Populations (8.1)].
Lactation
Instruct women with HIV-1 infection not to breastfeed because HIV-1 can be passed to the baby in the breast milk [see Use in Specific Populations (8.2)].
Missed Dosage
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 [see Dosage and Administration (2)].
Storage
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 [see How Supplied/Storage and Handling (16)].
TIVICAY and EPZICOM are registered trademarks of the ViiV Healthcare group of companies.
The other brands listed are trademarks of their respective owners and are not trademarks of the ViiV Healthcare group of companies. The makers of these brands are not affiliated with and do not endorse the ViiV Healthcare group of companies or its products.
Manufactured for:
ViiV Healthcare
Research Triangle Park, NC 27709
