Rifabutin

Concomitant administration reduces atovaquone concentrations. Concomitant use with atovaquone oral suspension is not recommended.

Rifabutin reduces atovaquone concentrations; concomitant use is not recommended.

Concomitant administration reduces atovaquone concentrations. Concomitant use with atovaquone oral suspension is not recommended.

Voriconazole 400 mg twice a day for 7 days (maintenance dose) 300 mg once a day for 7 days Healthy male subjects (12) ↑ AUC by 331%, ↑ C max by 195% ↑ AUC by ~100%, ↑ C max by ~100% g CONTRAINDICATED ANTI-PCP (Pneumocystis carinii pneumonia) Dapsone 50 mg once a day 300 mg once a day HIV infected patients (16) ND ↓ AUC by 27 -40% Sulfamethoxazole-Trimethoprim 800/160 mg 300 mg once a day HIV infected patients (12) ↓ AUC by 15-20% ANTI-MAC (Mycobacterium avium intracellulare complex) Azithromycin 500 mg once a day for 1 day, then 250 mg once a day for 9 days 300 mg once a day Healthy subjects (6) Clarithromycin 500 mg twice a day 300 mg once a day HIV infected patients (12) ↑ AUC by 75% ↓ AUC by 50% Monitor for rifabutin associated adverse events.

Rifabutin reduces bictegravir AUC by 38% and Cmin by 56%. Co-administration with Biktarvy is not recommended due to decreased tenofovir alafenamide and bictegravir.

Co-administration of rifabutin with cabotegravir/rilpivirine prolonged-release injectable suspension is contraindicated Ritonavir 500 mg twice a day for 10 days 150 mg once a day for 16 days Healthy subjects (5) ↑ AUC by 300%, ↑ C max by 150% ND Reduce rifabutin dose by at least 75% (to a maximum 150 mg every other day or three times per week) when given with lopinavir/ritonavir combination.

This effect may reduce the efficacy of standard doses of such drugs, which include itraconazole, clarithromycin, and saquinavir. Therefore, carefully monitor for rifabutin associated adverse events in those patients also receiving CYP3A inhibitors, which include fluconazole and clarithromycin. Voriconazole 400 mg twice a day for 7 days (maintenance dose) 300 mg once a day for 7 days Healthy male subjects (12) ↑ AUC by 331%, ↑ C max by 195% ↑ AUC by ~100%, ↑ C max by ~100% g CONTRAINDICATED ANTI-PCP (Pneumocystis carinii pneumonia) Dapsone 50 mg once a day 300 mg once a day HIV infected patients (16) ND ↓ AUC by 27 -40% Sulfamethoxazole-Trimethoprim 800/160 mg 300 mg once a day HIV infected patients (12) ↓ AUC by 15-20% ANTI-MAC (Mycobacterium avium intracellulare complex) Azithromycin 500 mg once a day for 1 day, then 250 mg once a day for 9 days 300 mg once a day Healthy subjects (6) Clarithromycin 500 mg twice a day 300 mg once a day HIV infected patients (12) ↑ AUC by 75% ↓ AUC by 50% Monitor for rifabutin associated adverse events.

Delavirdine increases rifabutin AUC by 230% and Cmax by 128%, while rifabutin reduces delavirdine concentrations by 80%. Interaction is contraindicated.

Co-administration is contraindicated based on FDA labeling.

Delavirdine 400 mg three times a day 300 mg once a day HIV infected patients (7) ↑ AUC by 230%, ↑ C max by 128% ↓ AUC by 80%, ↓ C max by 75%, ↓ C min by 17% CONTRAINDICATED Didanosine 167 or 250 mg twice a day for 12 days 300 or 600 mg once a day for 12 days HIV infected patients (11) Dolutegravir 50 mg daily for 14 days 300 mg daily for 14 days Healthy adult subjects ND No significant change in dolutegravir pharmacokinetic s at steady state.

Strong CYP3A inducer expected to decrease elexacaftor, tezacaftor, and ivacaftor exposures, reducing TRIKAFTA efficacy.

Strong CYP3A4 inducer. Should not be coadministered with everolimus.

Strong CYP3A4 inducer; co-administration with everolimus is not recommended.

Strong CYP3A4 inducer substantially reduces exposure to irinotecan and SN-38. Do not administer unless no therapeutic alternatives exist.

Lopinavir/ ritonavir 400/100 mg twice a day for 20 days 150 mg once a day for 10 days Healthy subjects (14) ↑ AUC by 203% c ↓ C max by 112% Reduce rifabutin dose by at least 75% (to a maximum 150 mg every other day or three times per week) when given with lopinavir/ritonavir combination. Co-administration of rifabutin with cabotegravir/rilpivirine prolonged-release injectable suspension is contraindicated Ritonavir 500 mg twice a day for 10 days 150 mg once a day for 16 days Healthy subjects (5) ↑ AUC by 300%, ↑ C max by 150% ND Reduce rifabutin dose by at least 75% (to a maximum 150 mg every other day or three times per week) when given with lopinavir/ritonavir combination.

Avoid coadministration of rifabutin with posaconazole unless the benefit outweighs the risks.

CYP3A inducer. Do not use with ranolazine extended-release tablets.

Strong CYP3A4/P-gp inducer that decreases sirolimus concentrations. Avoid concomitant use; consider alternative agents.

Voriconazole 400 mg twice a day for 7 days (maintenance dose) 300 mg once a day for 7 days Healthy male subjects (12) ↑ AUC by 331%, ↑ C max by 195% ↑ AUC by ~100%, ↑ C max by ~100% g CONTRAINDICATED ANTI-PCP (Pneumocystis carinii pneumonia) Dapsone 50 mg once a day 300 mg once a day HIV infected patients (16) ND ↓ AUC by 27 -40% Sulfamethoxazole-Trimethoprim 800/160 mg 300 mg once a day HIV infected patients (12) ↓ AUC by 15-20% ANTI-MAC (Mycobacterium avium intracellulare complex) Azithromycin 500 mg once a day for 1 day, then 250 mg once a day for 9 days 300 mg once a day Healthy subjects (6) Clarithromycin 500 mg twice a day 300 mg once a day HIV infected patients (12) ↑ AUC by 75% ↓ AUC by 50% Monitor for rifabutin associated adverse events.

Voriconazole 400 mg twice a day for 7 days (maintenance dose) 300 mg once a day for 7 days Healthy male subjects (12) ↑ AUC by 331%, ↑ C max by 195% ↑ AUC by ~100%, ↑ C max by ~100% g CONTRAINDICATED ANTI-PCP (Pneumocystis carinii pneumonia) Dapsone 50 mg once a day 300 mg once a day HIV infected patients (16) ND ↓ AUC by 27 -40% Sulfamethoxazole-Trimethoprim 800/160 mg 300 mg once a day HIV infected patients (12) ↓ AUC by 15-20% ANTI-MAC (Mycobacterium avium intracellulare complex) Azithromycin 500 mg once a day for 1 day, then 250 mg once a day for 9 days 300 mg once a day Healthy subjects (6) Clarithromycin 500 mg twice a day 300 mg once a day HIV infected patients (12) ↑ AUC by 75% ↓ AUC by 50% Monitor for rifabutin associated adverse events. Time Curve; C max -Maximum serum concentration; C min - Minimum serum concentration a compared to rifabutin 300 mg once a day alone b compared to historical control (fosamprenavir/ritonavir 700/100 mg twice a day) c also taking zidovudine 500 mg once a day d compared to rifabutin 150 mg once a day alone e compared to rifabutin 300 mg once a day alone f data from a case report g compared to voriconazole 200 mg twice a day alone Other drugs The structurally similar drug, rifampin, is known to reduce the plasma concentrations of a number of other drugs (see prescribing information for rifampin).

Decreases tenofovir alafenamide concentrations. Coadministration is not recommended.

Co-administration significantly increases rifabutin AUC by 193% and Cmax by 119%. Reduce rifabutin dose by at least 50% and monitor closely for adverse reactions.

Atazanavir/ritonavir increases rifabutin concentrations significantly. Reduce rifabutin dose to 150 mg every other day or 3 times weekly and increase monitoring.

Strong CYP3A4/5 inducer reduces axitinib plasma exposure. Co-administration should be avoided.

Darunavir/ritonavir increases rifabutin and metabolite concentrations significantly. Reduce rifabutin dose to 150 mg every other day or 3 times weekly and monitor closely.

Co-administration decreases doravirine plasma concentrations. Increase PIFELTRO dosage to one tablet twice daily when co-administered with rifabutin.

Co-administration decreases doravirine plasma concentrations. If co-administered, one tablet of doravirine should be taken approximately 12 hours after the dose of DELSTRIGO.

Decreases TAF concentration. Coadministration with DESCOVY is not recommended.

CYP3A4 inducer decreases erlotinib exposure. Increase erlotinib dosage if co-administration is unavoidable.

CYP3A4 inducer decreases erlotinib exposure. Increase erlotinib dosage if co-administration is unavoidable.

Fosamprenavir/ritonavir increases rifabutin AUC by 35% and Cmax by 36%. Reduce rifabutin dose by at least 75% (maximum 150 mg every other day or three times per week).

Indinavir increases rifabutin AUC by 173% and Cmax by 134%; rifabutin reduces indinavir AUC by 34% and Cmax by 25%. Dose adjustment needed.

Itraconazole increases rifabutin concentrations. Not recommended 2 weeks before, during, and 2 weeks after itraconazole treatment.

Strong CYP3A inducer. Co-administration not recommended.

Potent CYP3A4 enzyme inducer that may decrease ketoconazole bioavailability and reduce antifungal efficacy. Coadministration not recommended.

Increases metabolism of contraceptive steroids, reducing contraceptive effectiveness and potentially resulting in unintended pregnancy or unscheduled bleeding.

Strong CYP3A inducer reduces the bioavailability and efficacy of nifedipine; careful consideration needed if co-administered.

May decrease plasma concentrations of COCs and potentially diminish effectiveness or increase breakthrough bleeding.

Avoid coadministration unless benefit outweighs risks. Rifabutin may decrease posaconazole plasma concentrations.

Ritonavir increases rifabutin and desacetyl-rifabutin concentrations. Dose adjustment of rifabutin and increased monitoring for adverse reactions warranted.

May decrease tacrolimus whole blood trough concentrations and increase risk of rejection. Increase tacrolimus dose and monitor concentrations.

Strong CYP3A inducer may decrease tacrolimus concentrations and increase risk of rejection. Increase tacrolimus dose and monitor concentrations.

Strong CYP3A inducer. Co-administration not recommended due to reduced SYMDEKO efficacy.

Strong CYP3A4 inducer that decreases toremifene steady-state concentration and should be avoided.

Strong CYP3A4 inducer. Avoid chronic co-administration or increase COMETRIQ dosage if unavoidable.

Induces CYP3A4 and may decrease plasma concentrations of desogestrel and ethinyl estradiol, potentially diminishing contraceptive effectiveness and increasing breakthrough bleeding.

May decrease systemic concentrations of hormonal contraceptives and diminish effectiveness or increase breakthrough bleeding.

Induces CYP3A activity, increasing efavirenz clearance and lowering plasma concentrations.

Induces CYP3A activity, increasing efavirenz clearance and lowering plasma concentrations.

Induction of CYP3A activity by rifabutin may increase clearance of efavirenz resulting in lowered plasma concentrations.

CYP3A4 inducer that may reduce plasma concentrations of estrogens, possibly decreasing therapeutic effects and altering uterine bleeding profile.

May decrease plasma concentrations of etonogestrel and diminish contraceptive effectiveness or increase breakthrough bleeding.

CYP3A4 enzyme inducer that may decrease plasma concentrations of etonogestrel and ethinyl estradiol, potentially diminishing contraceptive effectiveness or increasing breakthrough bleeding.

Induces CYP3A4, may decrease plasma concentrations of CHCs and potentially diminish effectiveness or increase breakthrough bleeding.

CYP3A4 inducer; concomitant use may decrease flibanserin exposure and therapeutic effect.

Therefore, carefully monitor for rifabutin associated adverse events in those patients also receiving CYP3A inhibitors, which include fluconazole and clarithromycin. ANTIFUNGALS Fluconazole 200 mg once a day for 2 weeks 300 mg once a day for 2 weeks HIV infected patients (12) ↑ AUC by 82%, ↑ C max by 88% Monitor for rifabutin associated adverse events.

CYP3A4 inducer may decrease serum hydrocortisone concentrations and increase risk of adrenal crisis; may require dose increase.

Rifabutin induces CYP3A4 and may decrease plasma concentrations of COCs, potentially diminishing contraceptive effectiveness or increasing breakthrough bleeding.

Induces CYP3A4, may decrease plasma concentrations of COCs and diminish effectiveness or increase breakthrough bleeding.

Moderate CYP3A4 inducer that decreases maribavir concentrations. A dose adjustment of LIVTENCITY is recommended when coadministered.

Enzyme inducer that may decrease plasma concentrations of CHCs and potentially diminish effectiveness or increase breakthrough bleeding.

May decrease systemic concentrations of norethindrone and potentially diminish contraceptive effectiveness or increase breakthrough bleeding.

Enzyme inducer that may decrease plasma concentrations of COCs and potentially diminish contraceptive effectiveness or increase breakthrough bleeding.

May decrease plasma concentrations of COCs and diminish contraceptive effectiveness or increase breakthrough bleeding.

Enzyme inducer that may decrease plasma concentrations of norethindrone and ethinyl estradiol, potentially diminishing contraceptive effectiveness or increasing breakthrough bleeding.

May decrease plasma concentrations and efficacy of contraceptive; may increase breakthrough bleeding.

Concomitant use may decrease rilpivirine plasma concentrations. Dose adjustment or monitoring may be recommended.

Concomitant use may cause decrease in rilpivirine plasma concentrations. Rilpivirine dose should be increased from 25 mg once daily to 50 mg once daily during coadministration.

Rifabutin induces CYP3A enzymes and may reduce plasma concentrations of saquinavir, potentially reducing its efficacy.

Metabolic enzyme inducer that may decrease systemic concentrations of estrogen and/or progestin, potentially diminishing contraceptive effectiveness.

No significant alterations in pharmacokinetic parameters of rifabutin when megestrol acetate is administered with it, though effects of rifabutin on megestrol acetate pharmacokinetics were not studied.

Elvitegravir/ Cobicistat 150/50 mg daily 300 mg daily or 150 mg every other day Healthy subjects (12) No significant change in rifabutin pharmacokinetics. 6.3-fold ↑in AUC, 4.8-fold ↑ C max of 25-O-desacetyl-rifabutin No change in elvitegravir except 67% ↓ C trough of elvitegravir No change in cobicistat exposure. Co-administration of rifabutin with elvitegravir/ cobicistat is not recommended due to an expected decrease in elvitegravir exposure.

Nelfinavir 1250 mg twice a day for 7-8 days 150 mg once a day for 8 days HIV infected patients (11) ↑ AUC by 83%, e ↑ C max by 19% Reduce rifabutin dose by 50% (to 150 mg once a day) and increase the nelfinavir dose to 1250 mg twice a day.

ANTI-HCV DRUGS Sofosbuvir 400 mg on day 1 and day 21 300 mg daily on day 10 to day 29 Healthy subjects (20) ND 36% ↓ in C max and 24% ↓ AUC Co-administration of rifabutin with sofosbuvir (alone or in combination) is not recommended.

Bictegravir 75 mg once a day 300 mg once a day (fasted) Healthy subjects ND ↓ AUC 38% ↓ C min 56% ↓ C max 20% Co-administration of rifabutin with Biktarvy (bictegravir/ emtricitabine/tenofovir alafenamide) is not recommended due to an expected decrease in tenofovir alafenamide in addition to the reported reduction in bictegravir. Rilpivirine 25 mg once a day 300 mg once a day Healthy subjects (18) ND ↓ AUC by 42% ↓ C min by 48% ↓ C max by 31% Co-administration of rifabutin with Odefsey (rilpivirine/ tenofovir alafenamide/ emtricitabine) is not recommended, due to an expected decrease in tenofovir alafenamide in addition to the reported reduction in rilpivirine.

Tipranavir/ ritonavir 500/200 twice a day for 15 doses 150 mg single dose Healthy subjects (20) ↑ AUC by 190%, ↑ C max by 70% Reduce rifabutin dose by at least 75% (to a maximum 150 mg every other day or three times per week) when given with tipranavir/ritonavir combination.