Doravirineinteractions

Because DELSTRIGO is a complete regimen, co-administration with other antiretroviral medications for treatment of HIV-1 infection is not recommended. Consult the full prescribing information prior to and during treatment for important potential drug-drug interactions.

7.1 Concomitant

Use with Other Antiretroviral Medications Because DELSTRIGO is a complete regimen for the treatment of HIV-1 infection, co-administration with other antiretroviral medications for treatment of HIV-1 infection is not recommended. Information regarding potential drug-drug interactions with other antiretroviral medications is not provided.

7.2 Effect of

Other Drugs on DELSTRIGO Co-administration of DELSTRIGO with a CYP3A inducer decreases doravirine plasma concentrations, which may reduce DELSTRIGO efficacy. Co-administration of DELSTRIGO and drugs that are inhibitors of CYP3A may result in increased plasma concentrations of doravirine. Table 6 shows the significant drug interactions with the components of DELSTRIGO. The drug interactions described are based on studies conducted with either DELSTRIGO or the components of DELSTRIGO as individual agents.

Table 6: Drug Interactions with DELSTRIGO This table is not all-inclusive Concomitant Drug Class: Drug Name Effect on Concentration Clinical Comment ↑ = increase, ↓ = decrease All other drug-drug interactions shown are anticipated based on the known metabolic and elimination pathways. Androgen Receptors enzalutamide ↓ doravirine Co-administration is contraindicated with enzalutamide. At least a 4-week cessation period is recommended prior to initiation of DELSTRIGO. Anticonvulsants carbamazepine oxcarbazepine phenobarbital phenytoin ↓ doravirine Co-administration is contraindicated with these anticonvulsants. At least a 4-week cessation period is recommended prior to initiation of DELSTRIGO. Antimycobacterials rifampin The interaction between doravirine and the concomitant drug was evaluated in a clinical study. rifapentine ↓ doravirine Co-administration is contraindicated with rifampin or rifapentine. At least a 4-week cessation period is recommended prior to initiation of DELSTRIGO. rifabutin ↓ doravirine If DELSTRIGO is co-administered with rifabutin, one tablet of doravirine (PIFELTRO) should be taken approximately 12 hours after the dose of DELSTRIGO. Cytotoxic Agents mitotane ↓ doravirine Co-administration is contraindicated with mitotane. At least a 4-week cessation period is recommended prior to initiation of DELSTRIGO. Hepatitis C Antiviral Agents ledipasvir/sofosbuvir sofosbuvir/velpatasvir ↑ tenofovir Monitor for adverse reactions associated with TDF. Herbal Products St. John's wort ↓ doravirine Co-administration is contraindicated with St. John's wort. At least a 4-week cessation period is recommended prior to initiation of DELSTRIGO. Other Agents sorbitol ↓ lamivudine Co-administration of single doses of lamivudine and sorbitol resulted in a sorbitol dose-dependent reduction in lamivudine exposures. When possible, avoid use of sorbitol-containing medicines with lamivudine-containing medicines. Co-administration of DELSTRIGO with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of lamivudine, tenofovir, and/or other renally eliminated drugs. Some examples of drugs that are eliminated by active tubular secretion include, but are not limited to, acyclovir, cidofovir, ganciclovir, valacyclovir, valganciclovir, aminoglycosides (e.g., gentamicin), and high-dose or multiple NSAIDs. No clinically significant changes in concentration were observed for doravirine when co-administered with the following agents: TDF, lamivudine, elbasvir and grazoprevir, ledipasvir and sofosbuvir, ritonavir, ketoconazole, aluminum hydroxide/magnesium hydroxide/simethicone containing antacid, pantoprazole, or methadone. No clinically significant changes in concentration were observed for tenofovir when co-administered with tacrolimus or entecavir.

7.3 Effect of DELSTRIGO on

Other Drugs No clinically significant changes in concentration were observed for the following agents when co-administered with doravirine: lamivudine, TDF, elbasvir and grazoprevir, ledipasvir and sofosbuvir, atorvastatin, an oral contraceptive containing ethinyl estradiol and levonorgestrel, metformin, methadone, or midazolam. No clinically significant drug interactions have been observed between TDF and the following medications: entecavir, methadone, oral contraceptives, sofosbuvir, or tacrolimus in studies conducted in healthy participants. Lamivudine is not significantly metabolized by CYP enzymes nor does it inhibit or induce this enzyme system; therefore, it is unlikely that clinically significant drug interactions will occur through these pathways.