Product Information
Registration Status: ActiveTIVICAY TABLET 50MG is approved to be sold in Singapore with effective from 2014-07-31. It is marketed by GLAXOSMITHKLINE PTE LTD, with the registration number of SIN14579P.
This product contains Dolutegravir 50mg in the form of TABLET, FILM-COATED. It is approved for ORAL use.
This product is manufactured by GLAXO OPERATIONS UK LTD (TRADING AS GLAXO WELLCOME OPERATIONS) in UNITED KINGDOM, andGlaxoSmithKline Pharmaceuticals S.A. in POLAND.
It is a Prescription Only Medicine that can only be obtained from a doctor or a dentist, or a pharmacist with a prescription from a Singapore-registered doctor or dentist.
Description
Dolutegravir is a HIV-1 intergrase inhibitor that blocks the strand transfer step of the integration of the viral genome into the host cell (INSTI).[A7514] The effect of this drug has no homology in human host cells which gives it an excellent tolerability and minimal toxicity.[A31342] Dolutegravir was developed by ViiV Healthcare and FDA approved on August 12, 2013.[L1035] On November 21, 2017, dolutegravir, in combination with rilpivirine, was approved as part of the first complete treatment regimen with only two drugs for the treatment of adults with HIV-1 named Juluca.[L1031]
Indication
Dolutegravir is indicated in combination with other antiretroviral agents for the treatment of patients with HIV-1 infection that comply with the characteristics of being adults or children aged 12 years and older and present at least a weight of 40 kg.[A7520] The FDA combination therapy approval of dolutegravir and rilpivirine is indicated for adults with HIV-1 infections whose virus is currently suppressed (< 50 copies/ml) on a stable regimen for at least six months, without history of treatment failure and no known substitutions associated to resistance to any of the two components of the therapy.[L1031]
Mechanism of Action
Dolutegravir is an HIV-1 antiviral agent. It inhibits HIV integrase by binding to the active site and blocking the strand transfer step of retroviral DNA integration in the host cell. The strand transfer step is essential in the HIV replication cycle and results in the inhibition of viral activity. Dolutegravir has a mean EC50 value of 0.5 nM (0.21 ng/mL) to 2.1 nM (0.85 ng/mL) in peripheral blood mononuclear cells (PBMCs) and MT-4 cells.[A7517]
Pharmacokinetics
- Absorption
- When 50 mg of dolutegravir once daily was orally administered to HIV-1 infected adults, the AUC, Cmax, and Cmin is 53.6 mcg h/mL, 3.67 mcg/mL, and 1.11 mcg/mL, respectively. The peak plasma concentration was observed 2 to 3 hours post-dose. Steady state is achieved within approximately 5 days with average accumulation ratios for AUC, Cmax, and C24h ranging from 1.2 to 1.5. When 50 mg once daily is given to pediatric patients (12 to < 18 years and weighing ≥40 kg) the Cmax, AUC, and C24 is 3.49 mcg/mL, 46 mcg.h/mL, and 0.90 mcg/mL respectively.[A7514]
- Distribution
- The administration of a dose of 50 mg of dolutegravir presents an apparent volume of distribution of 17.4 L. The median dolutegravir concentration in CSF was 18 ng/mL after 2 weeks of treatment.[A7514]
- Metabolism
- Dolutegravir is highly metabolized through three main pathways and it forms no long-lived metabolites. The first pathway is defined by the glucuronidation by UGT1A1, the second pathway by carbon oxidation by CYP3A4 and the third pathway is what appears to be a sequential oxidative defluorination and glutathione conjugation. The main metabolite found in blood plasma is the ether glucuronide form (M2) and its chemical properties disrupt its ability to bind metal ions, therefore, it is inactive.[A31344]
- Elimination
Clearance
The apparent clearance rate of dultegravir is 1.0 L/h.[FDA label]
Toxicity
There was no significant increases in drug-related neoplasms or in genotoxic effects or in mating or fertility effects.[A31345]
Active Ingredient/Synonyms
Dolutegravir | Dolutegravir |
Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.