TIVICAY® (dolutegravir) Tablets for Oral Use

TIVICAY contains dolutegravir, as dolutegravir sodium, an HIV INSTI. The chemical name of dolutegravir sodium is sodium (4R,12aS)-9-{[(2,4-difluorophenyl)methyl]carbamoyl}-4-methyl-6,8-dioxo-3,4,6,8,12,12a-hexahydro-2H-pyrido[1',2':4,5]pyrazino[2,1-b][1,3]oxazin-7-olate. The empirical formula is C20H18F2N3NaO5 and the molecular weight is 441.36 g/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 52.6 mg of dolutegravir sodium, which is equivalent to 50 mg dolutegravir free acid, 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, macrogol/PEG, polyvinyl alcohol-part hydrolyzed, talc, and titanium dioxide.

The following should be considered prior to initiating TIVICAY:
Poor virologic response was observed in subjects treated with TIVICAY 50 mg twice daily with an INSTI-resistance Q148 substitution plus 2 or more additional INSTI-resistance substitutions including L74I/M, E138A/D/K/T, G140A/S, Y143H/R, E157Q, G163E/K/Q/R/S, or G193E/R.

1.  Hypersensitivity reactions characterized by rash, constitutional findings, and sometimes organ dysfunction, including liver injury, have been reported. Discontinue TIVICAY and other suspect agents immediately if signs or symptoms of hypersensitivity reactions develop, as a delay in stopping treatment may result in a life-threatening reaction. TIVICAY should not be used in patients who have experienced a previous hypersensitivity reaction to TIVICAY.
2. Patients with underlying hepatitis B or C may be at increased risk for worsening or development of transaminase elevations with use of TIVICAY. Appropriate laboratory testing prior to initiating therapy and monitoring for hepatotoxicity during therapy with TIVICAY is recommended in patients with underlying hepatic disease such as hepatitis B or C.
3. Redistribution/accumulation of body fat and immune reconstitution syndrome have been reported in patients treated with combination antiretroviral therapy.

To report SUSPECTED ADVERSE REACTIONS, contact ViiV Healthcare at 1-877-844-8872 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

---------------
DRUG INTERACTIONS:
Drugs that are metabolic inducers may decrease the plasma concentrations of dolutegravir.

TIVICAY should be taken 2 hours before or 6 hours after taking cation-containing antacids or laxatives, sucralfate, oral iron supplements, oral calcium supplements, or buffered medications.

---------------
USE IN SPECIFIC POPULATIONS:
Pregnancy: TIVICAY should be used during pregnancy only if the potential benefit justifies the potential risk.

Nursing mothers: Breastfeeding is not recommended due to the potential for HIV transmission.

Pediatric patients: Safety and efficacy of TIVICAY have not been established in pediatric patients younger than 12 years or weighing less than 40 kg, or in pediatric patients who are INSTI-experienced with documented or clinically suspected resistance to other INSTIs (raltegravir, elvitegravir).

See PACKAGE INSERT for PATIENT COUNSELING INFORMATION and Medication Guide.

-----------
Adult Population:
Recommended Dose:

1] Treatment-naïve or treatment-experienced INSTI-naïve:
50 mg once daily

2] Treatment-naïve or treatment-experienced INSTI-naïve when coadministered with the following potent UGT1A/CYP3A inducers: efavirenz, fosamprenavir/ritonavir, tipranavir/ritonavir, or rifampin:
50 mg twice daily

3] INSTI-experienced with certain INSTI-associated resistance substitutions or clinically suspected INSTI resistance:
50 mg twice daily.
Alternative combinations that do not include metabolic inducers should be considered where possible.

-----------
Pediatric Patients: (Treatment-naïve or treatment-experienced, INSTI-naïve, aged 12 years and older, and weighing at least 40 kg).

1] The recommended dose is TIVICAY 50 mg once daily.

2] If efavirenz, fosamprenavir/ritonavir, tipranavir/ritonavir, or rifampin are coadministered, then the dose is TIVICAY 50 mg twice daily.

Manufactured for:
ViiV Healthcare
Research Triangle Park, NC 27709

by:
GlaxoSmithKline
Research Triangle Park, NC 27709
August 2013

TVC:1PIL
©2013, ViiV Healthcare. All rights reserved.
TIVICAY and LEXIVA are registered trademarks of ViiV Healthcare.

PRINCIPAL DISPLAY PANEL
NDC 49702-228-13
Tivicay®
(dolutegravir)

Tablets
50 mg
30 Tablets
Rx Only

Each film-coated tablet contains dolutegravir sodium equivalent to 50 mg of dolutegravir.

Store at controlled room temperature of 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) (see USP).