Dovato Lamivudine and Dolutegravir Tablets

1. Indications and Usage
Treatment of HIV-1 Infection:
Indicated as a complete regimen for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults and pediatric patients weighing at least 25 kg.
Specific Patient Populations:
1. For patients with no antiretroviral treatment history.
2. To replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA < 50 copies/mL) on a stable regimen, with no history of treatment failure, and no known substitutions associated with resistance to the individual components.
2. Dosage and Administration
Recommended Dosage:
Adults and Adolescents (≥12 years and ≥25 kg): One tablet (50 mg dolutegravir and 300 mg lamivudine) orally once daily.
Administration Instructions:
Can be taken with or without food.
Swallow the tablet whole; do not chew or crush.
Missed Dose:
If a dose is missed and it is more than 4 hours before the next scheduled dose, take the dose as soon as possible and resume the normal schedule.
If the next scheduled dose is due in less than 4 hours, skip the missed dose and resume the normal schedule. Do not take a double dose.
3. Mechanism of Action
Fixed-Dose Combination:
Dolutegravir: An HIV-1 integrase strand transfer inhibitor (INSTI). It binds to the integrase active site and blocks the strand transfer step of retroviral DNA integration, which is essential for the HIV replication cycle.
Lamivudine: A nucleoside analog reverse transcriptase inhibitor (NRTI). Its active metabolite (lamivudine triphosphate) inhibits HIV-1 reverse transcriptase via DNA chain termination after incorporation into the viral DNA.
Physiological Effect:
The combination inhibits HIV replication by targeting two different steps in the viral life cycle (reverse transcription and integration).
4. Safety and Warnings
Hepatitis B Virus (HBV) Reactivation:
Severe acute exacerbations of hepatitis B have been reported in patients coinfected with HIV-1 and HBV who have discontinued lamivudine. Test all patients for HBV infection before or during initiation of this product. Monitor hepatic function closely for several months after stopping treatment.
Hypersensitivity Reactions:
Hypersensitivity reactions have been reported with dolutegravir, characterized by rash, constitutional findings, and sometimes organ dysfunction (including liver injury). Discontinue immediately if signs or symptoms develop.
Lactic Acidosis and Severe Hepatomegaly with Steatosis:
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues.
Immune Reconstitution Syndrome:
May occur shortly after initiation of antiretroviral therapy.
5. Adverse Reactions
Most Common:
Headache, nausea, diarrhea, insomnia, fatigue, and anxiety.
Laboratory Abnormalities:
Increases in serum creatinine (due to inhibition of renal tubular creatinine transport, not reflecting a change in glomerular filtration rate), and elevated hepatic enzymes.
6. Drug Interactions
Polyvalent Cation-Containing Products:
(e.g., Antacids containing magnesium or aluminum; Calcium or Iron supplements). Separate dosing by at least 2 hours before or 6 hours after taking this product. If taken with food, calcium or iron supplements can be taken at the same time.
CYP3A and UGT1A1 Inducers:
(e.g., Rifampin, carbamazepine, phenytoin, St. John’s wort). These drugs may significantly decrease dolutegravir plasma concentrations. Concomitant use requires dosage adjustments (often adding a separate dose of dolutegravir) or is not recommended.
Dofetilide:
Contraindicated due to the potential for increased dofetilide plasma concentrations and serious or life-threatening events.
Metformin:
Concomitant use may increase metformin plasma concentrations. Consider dose adjustment of metformin when starting or stopping dolutegravir.
7. Pharmaceutical Information
Chemical Name:
Dolutegravir Sodium: Sodium (4R,12aS)-9-[(2,4-difluorophenyl)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
Lamivudine: 4-Amino-1-[(2R,5S)-2-(hydroxymethyl)-1,3-oxathiolan-5-yl]pyrimidin-2(1H)-one
Molecular Formula:
Dolutegravir Sodium: C20H18F2N3NaO5
Lamivudine: C8H11N3O3S
Storage:
Store at or below 30°C (86°F).