Effect of Rifapentine on Other Medicinal Products: Effect on medicinal products metabolized by CYP3A4 and CYP2C8/9: Rifapentine is an inducer of CYP3A4 and CYP2C8/9. Therefore, rifapentine may increase the metabolism of other coadministered drugs that are metabolized by these enzymes.
Appropriate monitoring and dosage adjustment may be necessary if drugs metabolized by CYP 3A4 or CYP 2C8/9 are coadministered with Priftin.
Induction of enzyme activities by rifapentine occurred after the first dose of rifapentine. Enzyme activities returned to baseline levels in general 14 days after discontinuing rifapentine.
Examples of such substances include: Antiretroviral drugs: Protease inhibitors: Indinavir, darunavir, lopinavir, saquinavir, ritonavir.
Non Nucleoside Reverse Transcriptase Inhibitors: Rilpirivine, delaviridine.
Nucleoside Reverse Transcriptase Inhibitor: zidovudine.
Antifungals: Itraconazole, ketoconazole, voriconazole.
Narcotics analgesics: Methadone, alfentanil, buprenorphine.
Antiarrythmic: Dronedarone, quinidine.
Hypoglycemic agents: Repaglinide, tolbutamide.
Calcium channel blockers: Felodipine, nicardipine, diltiazem, verapamil, nifedipine.
Alpha/Beta Adrenergic Antagonists: Propranolol.
Ergot alkaloids derivates: Ergotamine, dihydroergotamine.
Oral anti-Vit K anticoagulant: Warfarin.
Hormonal contraceptives: Oral, transdermal, and implant.
Immunosuppressants: cyclosporine, tacrolimus, sirolimus, voclosporin.
Effect of rifapentine on transporter substrates: In vitro, rifapentine has been shown to inhibit and to induce P-gp which could modify plasma exposure of digoxin (P-gp substrate) (see Pharmacology: Pharmacokinetics under Actions).
Because of narrow therapeutic index of digoxin, appropriate monitoring and dose adjustment of digoxin may be necessary in case of co-administration with rifapentine.
Effect of rifapentine on Antiretroviral drugs: Protease Inhibitors and certain Reverse Transcriptase Inhibitors: Concomitant use of rifapentine with Protease Inhibitors and certain Reverse Transcriptase Inhibitors, metabolized by CYP3A4 or CYP2C8/9, may cause a significant decrease in plasma concentrations and loss of therapeutic effect of these drugs.
Fixed dose combination of Efavirenz, Emtricitabine and Tenofovir: Once-weekly co-administration of 900 mg Priftin with the antiretroviral fixed dose combination of efavirenz 600 mg, emtricitabine 200 mg and tenofovir disoproxyl fumarate 300 mg in HIV- infected patients did not result in any substantial change in steady state exposures of efavirenz, emtricitabine, and tenofovir. No clinically significant change in CD4 cell counts or viral loads were noted.
No need for dose adjustment of fixed dose combination of Efavirenz, Emtricitabine and Tenofovir, if coadministered with Priftin 900 mg once-weekly.
Raltegravir: Once-weekly co-administration of 900 mg Priftin with raltegravir resulted in a 71% mean increase in raltegravir AUC0-12, and an 89% increase in Cmax. The increased raltegravir exposure was safe and tolerable. No need for dose adjustment of raltegravir, if coadministered with Priftin 900 mg once-weekly.
Hormonal contraceptives: Priftin may reduce the effectiveness of hormonal contraceptives. Women taking oral contraceptions, transdermal patch, or other systemic hormonal contraceptives who need Priftin therapy should discuss with their physician regarding the use of an additional non-hormonal means of contraception or the change of their contraceptive pill.
Effect of Other Drugs on Rifapentine: Potential drug interaction with CYP450 inducer/inhibitor drugs, as well as with transporters inhibitor/inducer drugs are not expected (see Pharmacology: Pharmacokinetics under Actions).
Since rifapentine is highly bound to albumin, drug displacement interactions with NSAIDs, sulfonylureas, and oral anticoagulants may also occur.
Interferences with Laboratory and Diagnostic Test: Therapeutic concentrations of rifampin have been shown to inhibit standard microbiological assays for serum folate and Vitamin B12. Similar interferences should be considered for rifapentine. Therefore, alternative assay methods should be considered.