ecting renal glomerular function [seeClinical Pharmacology (12.2)].
Increases in serum creatinine occurred within the first 4 weeksof treatment in both arms and remained stable through 48 weeks. A mean change from baselineof 0.116mg/dL and 0.154 mg/dL was observed after 48 weeks of treatment with TIVICAY plusEPIVIR and TIVICAY plus TRUVADA, respectively. These changes are not considered to be
clinically relevant.
6.2 Postmarketing Experience
The following adverse reactions have been identified during postmarketing experience inpatients receiving a dolutegravir- or lamivudine-containing regimen. Because postmarketingreactions are reported voluntarily from a population of uncertain size, it is not always possible toreliably estimate their frequency or establish a causal relationship to drug exposure.
Body as a Whole
Redistribution/accumulation of body fat.
Endocrine and Metabolic
Hyperglycemia.
General
Weakness.
Hemic and Lymphatic
Anemia (including pure red cell aplasia and severe anemias progressing on therapy).
Hepatic and Pancreatic
Lactic acidosis and hepatic steatosis [see Warnings and Precautions (5.5)], pancreatitis,posttreatment exacerbations of HBV [see Warnings and Precautions (5.1)].
Hepatobiliary DisordersAcute liver failure, hepatotoxicity.
Hypersensitivity
Anaphylaxis, urticaria.
Investigations
Weight increased.
Musculoskeletal
Arthralgia, CPK elevation, muscle weakness, myalgia, rhabdomyolysis.
Nervous System
Paresthesia, peripheral neuropathy.
Skin
Alopecia.
7 DRUG INTERACTIONS
7.1 Coadministration with Other Antiretroviral Drugs
DOVATO is a complete regimen for the treatment of HIV-1 infection; therefore,coadministration with other antiretroviral drugs for the treatment of HIV-1 infection is notrecommended [see Indications and Usage (1)]. Information regarding potential drug-druginteractions with other antiretroviral drugs is not provided [see Contraindications (4), Warningsand Precautions (5.6), Clinical Pharmacology (12.3)].
7.2 Potential for DOVATO to Affect Other Drugs
Dolutegravir, a component of DOVATO, inhibits the renal organic cation transporters (OCT)2and multidrug and toxin extrusion transporter (MATE)1; thus, it may increase plasmaconcentrations of drugs eliminated via OCT2 or MATE1 such as dofetilide and metformin [seeContraindications (4), Drug Interactions (7.4), Clinical Pharmacology (12.3)].
7.3 Potential for Other Drugs to Affect the Components of DOVATODolutegravir is metabolized by uridine diphosphate (UDP)-glucuronosyl transferase (UGT)1A1
with some contribution from cytochrome P450 (CYP)3A. Dolutegravir is also a substrate ofUGT1A3, UGT1A9, breast cancer resistance protein (BCRP), and P-glycoprotein (P-gp) in vitro.
Drugs that induce those enzymes and transporters may decrease dolutegravir plasmaconcentrations and reduce the therapeutic effect of DOVATO [see Drug Interactions (7.4),Clinical Pharmacology (12.3)]. Coadministration of DOVATO and other drugs that inhibit theseenzymes may increase dolutegravir plasma concentrations.
Coadministration of dolutegravir with polyvalent cation-containing products may lead todecreased absorption of dolutegravir [see Drug Interactions (7.4), Clinical Pharmacology(12.3)].
7.4 Established and Other Potentially Significant Drug Interactions
No drug interaction studi |
