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.
Source: FDA drug label - rifabutin
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.
Source: FDA drug label - rifabutin
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.
Source: FDA drug label - rifabutin
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.
Source: FDA drug label - rifabutin
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.
Source: FDA drug label - rifabutin
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).
Source: FDA drug label - rifabutin
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.
Source: FDA drug label - rifabutin
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.
Source: FDA drug label - rifabutin
Table 2 Rifabutin Interaction Studies Co-administered drug Dosing regimen of co-administered drug Dosing regimen of rifabutin Study population (n) Effect on rifabutin Effect on co-administered drug Recommendation ANTIRETROVIRALS Amprenavir 1200 mg twice a day for 10 days 300 mg once a day for 10 days Healthy male subjects (6) ↑ AUC by 193%, ↑ C max by 119% Reduce rifabutin dose by at least 50%. Fosamprenavir/ ritonavir 700 mg twice a day plus ritonavir 100 mg twice a day for 2 weeks 150 mg every other day for 2 weeks Healthy subjects (15) ↔ AUC a ↓ C max by 15% ↑ AUC by 35% b , ↑ C max by 36%, ↑ C min by 36%, Reduce rifabutin dose by at least 75% (to a maximum 150 mg every other day or three times per week) when given with fosamprenavir/ritonavir combination. 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).
Source: FDA drug label - rifabutin
Atazanavir/ Ritonavir 300/100 mg once daily 150 mg twice weekly Healthy adult subjects 48% ↑ in AUC, 149% ↑ C max of rifabutin.
Source: FDA drug label - rifabutin
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.
Source: FDA drug label - rifabutin
Darunavir/ Ritonavir 600/100 mg twice a day for 12 days 150 mg every other day for 12 days Healthy HIV negative adults No significant change in rifabutin pharmacokinetics. 881% ↑in AUC, 377% ↑ C max of 25-O-desacetyl-rifabutin 57% ↑in AUC, 42% ↑ C max of darunavir.
Source: FDA drug label - rifabutin
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.
Source: FDA drug label - rifabutin
Fosamprenavir/ ritonavir 700 mg twice a day plus ritonavir 100 mg twice a day for 2 weeks 150 mg every other day for 2 weeks Healthy subjects (15) ↔ AUC a ↓ C max by 15% ↑ AUC by 35% b , ↑ C max by 36%, ↑ C min by 36%, Reduce rifabutin dose by at least 75% (to a maximum 150 mg every other day or three times per week) when given with fosamprenavir/ritonavir combination. 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).
Source: FDA drug label - rifabutin
Indinavir 800 mg three times a day for 10 days 300 mg once a day for 10 days Healthy subjects (10) ↑ AUC by 173%, ↑ C max by 134% ↓ AUC by 34%, ↓ C max by 25%, ↓ C min by 39% Reduce rifabutin dose by 50%, and increase indinavir dose from 800 mg to 1000 mg three times a day.
Source: FDA drug label - rifabutin
This effect may reduce the efficacy of standard doses of such drugs, which include itraconazole, clarithromycin, and saquinavir. Itraconazole 200 mg once a day 300 mg once a day HIV Infected patients (6) ↑ f ↓ AUC by 70%, ↓ C max by 75%, If co-administration of these two drugs cannot be avoided, patients should be monitored for adverse events associated with rifabutin administration, and lack of itraconazole efficacy. In a separate study, one case of uveitis was associated with increased serum rifabutin levels following co-administration of rifabutin (300 mg once a day) with itraconazole (600-900 mg once a day).
Source: FDA drug label - rifabutin
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% also taking zidovudine 500 mg once a day ↓ 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. 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.
Source: FDA drug label - rifabutin
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.
Source: FDA drug label - rifabutin
Posaconazole 200 mg once a day for 10 days 300 mg once a day for 17 days Healthy subjects (8) ↑ AUC by 72%, ↑ C max by 31% ↓ AUC by 49%, ↓ C max by 43% If co-administration of these two drugs cannot be avoided, patients should be monitored for adverse events associated with rifabutin administration, and lack of posaconazole efficacy.
Source: FDA drug label - rifabutin
Atazanavir/ Ritonavir 300/100 mg once daily 150 mg twice weekly Healthy adult subjects 48% ↑ in AUC, 149% ↑ C max of rifabutin. Darunavir/ Ritonavir 600/100 mg twice a day for 12 days 150 mg every other day for 12 days Healthy HIV negative adults No significant change in rifabutin pharmacokinetics. 66% ↑in AUC,68% ↑ C max of ritonavir.
Source: FDA drug label - rifabutin
This effect may reduce the efficacy of standard doses of such drugs, which include itraconazole, clarithromycin, and saquinavir. Saquinavir/ ritonavir 1000/100 mg twice a day for 14 or 22 days 150 mg every 3 days for 21-22 days Healthy subjects ↑ AUC by 53% d ↑ C max by 88% (n=11) ↓ AUC by 13%, ↓ C max by 15%, (n=19) Reduce rifabutin dose by at least 75% (to a maximum 150 mg every other day or three times per week) when given with saquinavir/ritonavir combination.
Source: FDA drug label - rifabutin
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.
Source: FDA drug label - rifabutin
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.
Source: FDA drug label - rifabutin
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.
Source: FDA drug label - rifabutin