Delstrigo Doravirine Lamivudine and Tenofovir Disoproxil Fumarate Tablets

1. Indications and Usage
HIV-1 Infection:
Indicated for the treatment of HIV-1 infection in adults and pediatric patients weighing at least 35 kg with no prior antiretroviral treatment history.
2. Dosage and Administration
Route of Administration:
For Oral Use ONLY.
Recommended Dosage:
Dose: One tablet once daily.
Administration: Can be taken with or without food.
Special Populations:
Renal Impairment: Not recommended for patients with creatinine clearance (CrCl) < 50 mL/min.
Hepatic Impairment: No dosage adjustment is necessary for patients with mild to moderate hepatic impairment. Safety and efficacy have not been established in patients with severe hepatic impairment.
3. Mechanism of Action
Combination Mechanism:
Doravirine (DOR): A non-nucleoside reverse transcriptase inhibitor (NNRTI) that binds to a specific pocket on the HIV-1 reverse transcriptase enzyme, inhibiting its activity and preventing viral RNA from being converted into DNA.
Lamivudine (3TC): A nucleoside reverse transcriptase inhibitor (NRTI) that acts as a chain terminator.
Tenofovir Disoproxil Fumarate (TDF): A nucleotide reverse transcriptase inhibitor (NRTI) that also acts as a chain terminator.
4. Safety and Warnings
Hepatitis B Reactivation:
Patients coinfected with HBV and HIV-1 should not interrupt therapy with this product. Discontinuation may lead to severe acute exacerbations of hepatitis B.
Immune Reconstitution Syndrome:
May occur in patients with advanced HIV, allowing for the unmasking of opportunistic infections.
Renal Impairment:
TDF is associated with renal toxicity (proximal tubulopathy). Monitoring of renal function is recommended before and during therapy.
Decreases in Bone Mineral Density:
TDF can cause decreases in bone mineral density (BMD). Monitoring is recommended for patients with a history of pathologic fracture or other risk factors for osteoporosis.
5. Adverse Reactions
Most Common:
Gastrointestinal: Nausea, diarrhea, vomiting.
Neurologic: Dizziness, headache.
Dermatologic: Rash.
Laboratory Abnormalities:
Increased creatine kinase, increased ALT/AST, decreased phosphate.
6. Drug Interactions
Metabolic Pathway (CYP3A4):
Doravirine is a substrate and a weak inducer of CYP3A.
Strong Inducers:
Do not co-administer with strong CYP3A inducers (e.g., Rifampin, Carbamazepine, Phenobarbital, St. John’s Wort) as they significantly decrease Doravirine exposure, leading to potential treatment failure.
Acid Reducers:
Doravirine solubility decreases as pH increases. Proton Pump Inhibitors (PPIs) should be avoided. H2-receptor antagonists can be administered with specific timing constraints.
7. Pharmaceutical Information
Chemical Composition:
Active Ingredients: Doravirine (100 mg), Lamivudine (300 mg), Tenofovir Disoproxil Fumarate (300 mg).
Appearance: White to off-white, capsule-shaped film-coated tablets.
Storage: Store at 25°C (77°F); excursions permitted to 15°C–30°C (59°F–86°F).