A residual risk of sexual transmission of HIV-1 cannot be excluded and precautions should be taken in accordance with national guidelines. Use with CYP3A inducers may reduce the exposure of doravirine. Autoimmune disorders and immune reactivation syndrome have been reported in patients treated with combination antiretroviral therapy which may require investigation and treatment. Contains lactose monohydrate. DELSTRIGO: Post-treatment exacerbation of HBV (including hepatic decompensation and liver failure) have been reported in patients co-infected with HIV-1 and HBV following discontinuation of lamivudine or tenofovir disproxil. Monitor patients co-infected with HIV-1 and HBV after discontinuation of DELSTRIGO and if appropriate, initiate anti-HBV therapy. Renal impairment, including acute renal failure and Fanconi syndrome have been reported with tenofovir disoproxil. Assess estimated CrCl prior to initiation and during therapy. In patients at risk of renal dysfunction, serum phosphorus, urine glucose, and urine protein should also be assessed. Discontinue therapy if estimated CrCl declines below 50 mL/min. Avoid with concurrent or recent use of nephrotoxic medicinal products (e.g. high-dose or multiple NSAIDs). Evaluation of renal function is recommended for persistent or worsening bone pain, pain in extremities, fractures, and/or muscular pain or weakness. Assessment of bone mineral density should be considered for patients who have a history of pathologic bone fracture or other risk factors for osteoporosis or bone loss. Hypophosphatemia and osteomalacia secondary to proximal renal tubulopathy should be considered in patients at risk of renal dysfunction who present with persistent or worsening bone or muscle symptoms. Doravirine/lamivudine/tenofovir disoproxil must not be co-administered with other medicinal products containing lamivudine, tenofovir disoproxil, or tenofovir alafenamide or with adefovir dipivoxil. Doravirine/lamivudine/tenofovir disoproxil should not be administered with doravirine unless needed for dose adjustment (e.g. co-administered with rifabutin).
Drug interactions: Refer to SmPC for full information on drug interactions. PIFELTRO and DELSTRIGO: Doravirine is metabolized primarily by CYP3A. Do not co-administer with strong CYP3A enzyme inducers. If co-administration with rifabutin or other moderate CYP3A inducers cannot be avoided, increase doravirine dose to 100 mg twice daily (taken 12 hours apart). Use with caution when co-administering doravirine with medicinal products that are sensitive CYP3A substrates that have a narrow therapeutic window (e.g., midazolam, tacrolimus and sirolimus). DELSTRIGO: Do not administer with other antiretroviral medicinal products. Co-administration of doravirine/lamivudine/tenofovir disoproxil with medicinal products that reduce renal function or compete for active tubular secretion may increase serum concentrations of lamivudine. Co-administration of doravirine/lamivudine/tenofovir disoproxil with medicinal products that reduce renal function or compete for active tubular secretion via OAT1, OAT3 or MRP4 may increase serum concentrations of tenofovir. Avoid with concurrent or recent use of nephrotoxic medicinal products.
Pregnancy and Lactation: PIFELTRO and DELSTRIGO: Avoid use during pregnancy. An Antiretroviral Pregnancy Registry has been established. Breastfeeding is not recommended.

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 of the SmPC.

Co-administration with medicinal products that are strong cytochrome P450 CYP3A enzyme inducers is contraindicated as significant decreases in doravirine plasma concentrations are expected to occur, which may decrease the effectiveness of PIFELTRO (see sections 4.4 and 4.5 in the SmPC). These medicinal products include, but are not limited, to the following:

• Carbamazepine, oxcarbazepine, phenobarbital, phenytoin
• Rifampicin, rifapentine
• St. John’s wort (Hypericum perforatum)
• Mitotane
• Enzalutamide
• Lumacaftor