Dovato

— THERAPEUTIC CATEGORIES —
  • Viral infections

Dovato Generic Name & Formulations

General Description

Dolutegravir 50mg, lamivudine 300mg; tabs.

Pharmacological Class

HIV-1 integrase strand transfer inhibitor (INSTI) + nucleoside analog reverse transcriptase inhibitors (NRTIs).

How Supplied

Tabs—30; Blister pack—30

Manufacturer

Generic Availability

NO

Mechanism of Action

Dolutegravir inhibits HIV integrase by binding to the integrase active site and blocking the strand transfer step of retroviral DNA integration which is essential for the HIV replication cycle. Lamivudine is converted to its active metabolite, lamivudine triphosphate, which inhibits reverse transcriptase via DNA chain termination after incorporation of the nucleotide analogue.

Dovato Indications

Indications

As a complete regimen for the treatment of HIV-1 infection in patients with no antiretroviral treatment history or to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable antiretroviral regimen with no history of treatment failure and no known substitutions associated with resistance to the individual components of Dovato.

Dovato Dosage and Administration

Adult

Test for HBV infection prior to initiation. Take with or without food. ≥12yrs (≥25kg): 1 tab daily. Concomitant carbamazepine, rifampin: give additional dolutegravir 50mg separated by 12hrs from Dovato. 

Children

<12yrs (<25kg): not established.

Dovato Contraindications

Contraindications

Concomitant dofetilide.

Dovato Boxed Warnings

Boxed Warning

Patients co-infected with HBV and HIV-1: Emergence of lamivudine-resistant HBV and exacerbations of HBV.

Dovato Warnings/Precautions

Warnings/Precautions

Emergence of lamivudine-resistant HBV variants associated with lamivudine-containing antiretroviral regimens. Discontinuation of lamivudine-containing products and possibly Dovato may be associated with severe acute exacerbations of hepatitis B. Closely monitor patients co-infected with HBV and HIV for several months after stopping treatment; if appropriate, anti-HBV therapy may be warranted (esp. in advanced liver disease or cirrhosis). Discontinue immediately if hypersensitivity reactions develop. Increased risk for worsening/development of elevated transaminases in patients with underlying hepatitis B or C; monitor for hepatotoxicity. Suspend if lactic acidosis or pronounced hepatotoxicity (eg, hepatomegaly, steatosis) occurs. Renal impairment (CrCl <30mL/min): not recommended; if lamivudine dose reduction is required, use individual components; (CrCl 30–49mL/min): monitor for hematologic toxicities; may need dose adjustment. Severe hepatic impairment: not recommended. Elderly. Embryo-fetal toxicity: increased risk of neural tube defects (consider alternative treatment at time of conception through 1st trimester or if pregnancy is confirmed). Advise individuals of reproductive potential to use effective contraception. Pregnancy: exclude status prior to initiation. Nursing mothers: not recommended.

Dovato Pharmacokinetics

Absorption

Median time to maximum concentration: 2.5 hours (dolutegravir); 1 hour (lamivudine).

Distribution

Plasma protein bound: ~99% (dolutegravir); 36% (lamivudine).

Metabolism

Dolutegravir: UGT1A1 (primary), CYP3A4 (minor). Lamivudine: not significantly metabolized.

Elimination

Dolutegravir: renal (31%), fecal (64%). Lamivudine: renal (~70%). Half-life: ~14 hours (dolutegravir); 13–19hrs (lamivudine).

Dovato Interactions

Interactions

See Contraindications. Concomitant other antiretrovirals: not recommended. Dolutegravir may be affected by drugs that induce or inhibit UGT1A1, CYP3A, UGT1A3, UGT1A9, BCRP, and P-gp enzymes or transporters. May potentiate drugs eliminated via OCT2 or MATE1 (eg, dofetilide, dalfampridine, metformin). Avoid concomitant oxcarbazepine, phenytoin, phenobarbital, St. John’s wort. Antagonized by carbamazepine, rifampin; see Adult dose. Avoid concomitant sorbitol-containing products. Concomitant cation-containing antacids, laxatives, sucralfate, buffered drugs, or oral iron/calcium supplements (also can give together with a meal): give Dovato 2hrs before or 6hrs after.

Dovato Adverse Reactions

Adverse Reactions

Headache, nausea, diarrhea, insomnia, fatigue, anxiety; hypersensitivity reactions, hepatotoxicity, immune reconstitution syndrome.

Dovato Clinical Trials

See Literature

Dovato Note

Notes

To enroll pregnant patients exposed to Dovato in the Antiretroviral Pregnancy Registry (APR), call (800) 258-4263.

Dovato Patient Counseling

See Literature