Rifabutin (Page 3 of 5)

Drug Interactions

Effect of Rifabutin on the Pharmacokinetics of Other Drugs

Rifabutin induces CYP3A enzymes and therefore may reduce the plasma concentrations of drugs metabolized by those enzymes. This effect may reduce the efficacy of standard doses of such drugs, which include itraconazole, clarithromycin, and saquinavir.

Effect of Other Drugs on Rifabutin Pharmacokinetics

Some drugs that inhibit CYP3A may significantly increase the plasma concentration of rifabutin. Therefore, carefully monitor for rifabutin associated adverse events in those patients also receiving CYP3A inhibitors, which include fluconazole and clarithromycin. In some cases, the dosage of rifabutin may need to be reduced when it is coadministered with CYP3A inhibitors.

Table 2 summarizes the results and magnitude of the pertinent drug interactions assessed with rifabutin. The clinical relevance of these interactions and subsequent dose modifications should be judged in light of the population studied, severity of the disease, patient’s drug profile, and the likely impact on the risk/benefit ratio.

Table 2: Rifabutin Interaction Studies

↑ indicates increase; ↓ indicates decrease; ↔ indicates no significant change

ND -No Data

AUC -Area under the Concentration vs. Time Curve; Cmax -Maximum serum concentration; Cmin –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

Coadministered drug Dosing regimen of coadministered drug Dosing regimen of rifabutin Study population (n) Effect on rifabutin Effect on coadministered 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%, ↑ Cmax by 119% Reduce rifabutin dose by at least 50%. Monitor closely for adverse reactions.
Bictegravir 75 mg once a day 300 mg once a day (fasted) Healthy subjects ND ↓ AUC by 38, ↓Cmin by 56%, ↓Cmax by 20% Co-administration of Rifabutin with Biktarvy (bictegravir/ emtricitabin/ tenofovir alafenamide) is not recommended due to an expected decrease in tenofovir alafenamide in addition to the reported reduction in bictegravir. Refer to Biktarvy prescribing information for additional information
Delavirdine 400 mg three times a day 300 mg once a day HIV-infected patients (7) ↑ AUC by 230%, ↑ Cmax by 128% ↓ AUC by 80%, ↓ Cmax by 75%, ↓ Cmin 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)
Doravirine 100 mg single dose 300 mg once a day for 16 days Healthy subjects (12) ND ↓ 50% in AUC, ↓ 68% in C24 ↔ in Cmax If concomitant use is necessary, increase the doravirine dosage as instructed in doravirine-containing product prescribing information.
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) ↔ AUCa ↓ Cmax by 15% ↑ AUC by 35%b , ↑ Cmax by 36%, ↑ Cmin 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.
Indinavir 800 mg three times a day for 10 days 300 mg once a day for 10 days Healthy subjects (10) ↑ AUC by 173%, ↑ Cmax by 134% ↓ AUC by 34%, ↓ Cmax by 25%, ↓ Cmin by 39% Reduce rifabutin dose by 50%, and increase indinavir dose from 800 mg to 1000 mg three times.
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 ↓ Cmax 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. Monitor closely for adverse reactions. Reduce rifabutin dosage further, as needed.
Saquinavir/ ritonavir 1000/100 mg twice a day for 14 or 22 days 150 mg every 3 days for 21 to 22 days Healthy subjects ↑ AUC by 53% d ↑ Cmax by 88% (n=11) ↓ AUC by 13%, ↓ Cmax 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. Monitor closely for adverse reactions.
Rilpivirine 25 mg once a day 300 mg once a day Healthy subjects (18) ND ↓ AUC by 42%, ↓ Cmin by 48%, ↓ Cmax 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. Refer to Odefsey prescribing information for additional information.
Ritonavir 500 mg twice a day for 10 days 150 mg once a day for 16 days Healthy subjects (5) ↑ AUC by 300%, ↑ Cmax 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. Monitor closely for adverse reactions. Reduce rifabutin dosage further, as needed.
Tipranavir/ ritonavir 500/200 twice a day for 15 doses 150 mg single dose Healthy subjects (20) ↑ AUC by 190%, ↑ Cmax 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. Monitor closely for adverse reactions. Reduce rifabutin dosage further, as needed.
Nelfinavir 1250 mg twice a day for 7 to 8 days 150 mg once a day for 8 days HIV-infected patients (11) ↑ AUC by 83%,e ↑ Cmax by 19% Reduce rifabutin dose by 50% (to 150 mg once a day) and increase the nelfinavir dose to 1250 mg twice a day
Zidovudine 100 or 200 mg every four hours 300 or 450 mg once a day HIV-infected patients (16) ↓ AUC by 32%, ↓ Cmax by 48% Because zidovudine levels remained within the therapeutic range during coadministration of rifabutin, dosage adjustments are not necessary.
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%, ↑ Cmax by 88% Monitor for rifabutin associated adverse events. Reduce rifabutin dose or suspend rifabutin use if toxicity is suspected.
Posaconazole 200 mg once a day for 10 days 300 mg once a day for 17 days Healthy subjects (8) ↑ AUC by 72%, ↑ Cmax by 31% ↓ AUC by 49%, ↓ Cmax 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.
Itraconazole 200 mg once a day 300 mg once a day HIV-Infected patients (6) f ↓ AUC by 70%, ↓ Cmax 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 to 900 mg once a day).
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%, ↑ Cmax by 195% ↑ AUC by ~100%, ↑ Cmax 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 to 40%
Sulfamethoxazole-Trimethoprim 800/160 mg 300 mg once a day HIV-infected patients (12) ↓ AUC by 15 to 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. Reduce dose or suspend use of rifabutin if toxicity is suspected. Alternative treatment for clarithromycin should be considered when treating patients receiving rifabutin
ANTI-TB (Tuberculosis)
Ethambutol 1200 mg 300 mg once a day for 7 days Healthy subjects (10) ND
Isoniazid 300 mg 300 mg once a day for 7 days Healthy subjects (6) ND
OTHER
Methadone 20 to 100 mg once a day 300 mg once a day for 13 days HIV-infected patients (24) ND
Ethinylestradiol (EE)/ Norethindrone (NE) 35 mg EE / 1 mg NE X 21 days 300 mg once a day for 10 days Healthy female subjects (22) ND EE: ↓ AUC by 35%, ↓ Cmax by 20% NE: ↓ AUC by 46% Patients should be advised to use additional or alternative methods of contraception.
Theophylline 5 mg/kg 300 mg for 14 days Healthy subjects (11) ND

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). Although a weaker enzyme inducer than rifampin, rifabutin may be expected to have some effect on those drugs as well.

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