Dosage & administration
By using PrescriberAI, you agree to the AI Terms of Use.
Dovato prescribing information
All patients with HIV-1 should be tested for the presence of HBV prior to or when initiating DOVATO.
Safety and efficacy of lamivudine have not been established for treatment of chronic HBV in subjects dually infected with HIV-1 and HBV. Emergence of HBV variants associated with resistance to lamivudine has been reported in HIV‑1–infected subjects who have received lamivudine‑containing antiretroviral regimens in the presence of concurrent infection with HBV. If a decision is made to administer DOVATO to patients co-infected with HIV-1 and HBV, additional treatment should be considered for appropriate treatment of chronic HBV; otherwise, consider an alternative regimen.
Severe acute exacerbations of HBV have been reported in patients who are co-infected with HIV-1 and HBV and have discontinued products containing lamivudine, and may occur with discontinuation of DOVATO. Patients who are co-infected with HIV-1 and HBV who discontinue DOVATO should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment with DOVATO. If appropriate, initiation of anti-HBV therapy may be warranted, especially in patients with advanced liver disease or cirrhosis, since posttreatment exacerbation of hepatitis may lead to hepatic decompensation and liver failure.
DOVATO is indicated as a complete regimen for the treatment of HIV-1 infection in adults and adolescents 12 years of age and older and weighing at least 25 kg with no antiretroviral treatment history or to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA less than 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.
• Prior to or when initiating DOVATO, test patients for hepatitis B virus (HBV) infection. ()2.1 Testing Prior to or When Initiating Treatment with DOVATOPrior to or when initiating DOVATO, test patients for HBV infection
[see Warnings and Precautions ].• One tablet taken orally once daily with or without food. ()2.2 Recommended DosageDOVATO is a fixed-dose combination product containing 50 mg of dolutegravir and 300 mg of lamivudine. The recommended dosage regimen of DOVATO in adults and adolescents 12 years of age and older and weighing at least 25 kg is one tablet taken orally once daily with or without food
[see Clinical Pharmacology ].• The dolutegravir dose (50 mg) in DOVATO is insufficient when coadministered with carbamazepine or rifampin. If DOVATO is coadministered with carbamazepine or rifampin, take one tablet of DOVATO once daily, followed by an additional dolutegravir 50-mg tablet, approximately 12 hours from the dose of DOVATO. ()2.3 Recommended Dosage with Certain Coadministered DrugsThe dolutegravir dose (50 mg) in DOVATO is insufficient when coadministered with drugs listed in Table 1that may decrease dolutegravir concentrations; the following dolutegravir dosage regimen is recommended.
Table 1. Dosing Recommendations for DOVATO with Coadministered Drugs Coadministered DrugDosing RecommendationCarbamazepine, rifampin
An additional dolutegravir 50-mg tablet, separated by 12 hours from DOVATO, should be taken.
DOVATO tablets are oval, biconvex, white, film-coated tablets, debossed with “SV 137” on one face. Each tablet contains 50 mg of dolutegravir and 300 mg of lamivudine.
• Renal impairment: DOVATO is not recommended in patients with creatinine clearance less than 30 mL/min. ()8.6 Renal ImpairmentDOVATO is not recommended for patients with creatinine clearance <30 mL/min because DOVATO is a fixed-dose combination, and the dosage of the individual components cannot be adjusted. If a dose reduction of lamivudine, a component of DOVATO, is required for patients with creatinine clearance <30 mL/min, then the individual components should be used.
Patients with a creatinine clearance between 30 and 49 mL/min receiving DOVATO may experience a 1.6- to 3.3-fold higher lamivudine exposure (AUC) than patients with a creatinine clearance ≥50 mL/min. There are no safety data from randomized, controlled trials comparing DOVATO to the individual components in patients with a creatinine clearance between 30 and 49 mL/min who received dose-adjusted lamivudine. In the original lamivudine registrational trials in combination with zidovudine, higher lamivudine exposures were associated with higher rates of hematologic toxicities (neutropenia and anemia), although discontinuations due to neutropenia or anemia each occurred in <1% of subjects. Patients with a sustained creatinine clearance between 30 and 49 mL/min who receive DOVATO should be monitored for hematologic toxicities. If new or worsening neutropenia or anemia develop, dose adjustment of lamivudine, per lamivudine prescribing information, is recommended. If lamivudine dose adjustment is indicated, DOVATO should be discontinued, and the individual components should be used to construct the treatment regimen.
• Hepatic impairment: DOVATO is not recommended in patients with severe hepatic impairment (Child-Pugh Score C). ()8.7 Hepatic ImpairmentNo dosage adjustment of DOVATO is necessary in patients with mild or moderate hepatic impairment (Child-Pugh Score A or B). Dolutegravir has not been studied in patients with severe hepatic impairment (Child-Pugh Score C); therefore, DOVATO is not recommended for patients with severe hepatic impairment.
DOVATO is contraindicated in patients:
• with prior hypersensitivity reaction to dolutegravir or lamivudine[see Warnings and Precautions (.)]5.2 Hypersensitivity ReactionsHypersensitivity reactions have been reported with the use of dolutegravir, a component of DOVATO, and were characterized by rash, constitutional findings, and sometimes organ dysfunction, including liver injury. These events were reported in <1% of subjects receiving dolutegravir in Phase 3 clinical trials.
Discontinue DOVATO immediately if signs or symptoms of hypersensitivity reactions develop (including, but not limited to, severe rash or rash accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters or peeling of the skin, oral blisters or lesions, conjunctivitis, facial edema, hepatitis, eosinophilia, angioedema, difficulty breathing). Clinical status, including liver aminotransferases, should be monitored and appropriate therapy initiated. Delay in stopping treatment with DOVATO or other suspect agents after the onset of hypersensitivity may result in a life-threatening reaction
[see Contraindications ].• receiving dofetilide due to the potential for increased dofetilide plasma concentrations and the risk for serious and/or life-threatening events[see Drug Interactions (.)]7.2 Potential for DOVATO to Affect Other DrugsDolutegravir, a component of DOVATO, inhibits the renal organic cation transporters (OCT)2 and multidrug and toxin extrusion transporter (MATE)1; thus, it may increase plasma concentrations of drugs eliminated via OCT2 or MATE1 such as dofetilide, dalfampridine, and metformin
[see Contraindications , Drug Interactions , Clinical Pharmacology ].