A complete medication review with assessment for potential drug interactions and need for dose adjustments of concomitant medications is recommended for all patients at initiation of TB treatment. Any adjustments of doses of these medications should be reconsidered within 2 weeks of stopping TB treatment.217–219
There are several freely available online drug interaction resources that we suggest can be helpful to guide this assessment:
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Medscape (https://reference.medscape.com/drug-interactionchecker)
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University of Liverpool HIV Drug Interactions (https://www.hiv-druginteractions.org/checker)
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HIV/HCV Drug Therapy Guide from Toronto (https://hivclinic.ca/wp-content/plugins/php/app.php)
Rifampin is a well-documented potent inducer of hepatic and intestinal cytochrome P450 (CYP) enzymes, as well as the P-glycoprotein (P-gp) transport system. The onset of induction effects is gradual, with maximal effects on metabolizing enzymes and drug transporters by about two weeks. Induction can last for up to 4 weeks after stopping rifampin.220
Rifabutin is a less potent inducer of CYP P450 then rifampin. However, unlike rifampin, rifabutin is also a substrate of CYP3A4 and, therefore, can participate in bi-directional interactions, meaning that the metabolism of rifabutin can be altered by other drugs.68,221
Rifapentine, when dosed weekly, exerts less induction of CYP P450 then does rifampin. However, when rifapentine is dosed daily, it appears to have an even greater inductive effect than standard-dosed rifampin.222 Rifapentine is not a substrate for CYP3A.
Isoniazid is primarily metabolized via N-acetylation and is an inhibitor of several CYP450 isoenzymes. Isoniazid may inhibit the metabolism of concomitant agents, including some antiepileptics or benzodiazepines.223,224
The absorption of quinolones is significantly affected when administered at the same time as antacids and minerals containing multivalent cations, such as aluminum, magnesium or iron. Separating administration times by at least 2 hours is recommended.21
EMB and PZA have a low risk of drug-drug interactions.
Good practice statement
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Drug-drug interactions and altered pharmacokinetics of TB drugs are frequently encountered in people with HIV co-infection, organ transplantation, medical co-morbidities, liver disease, renal dysfunction, and advanced age. Consultation with an experienced pharmacist is recommended when treating TB in these populations.
Table 2. Common drug-drug interactions with Rifamycins (Last updated Dec 2021).
Drugs/Drug Classes Impacted | Potential Mitigation Strategy |
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Anticoagulants Warfarin Apixaban, dabigatran, edoxaban, rivaroxaban |
Continue warfarin with frequent INR monitoring while on rifampin and for 4 weeks after stopping rifampin. Alternatively, could change to LMWH injection. 225 , 226 Avoid use of direct-acting oral anticoagulants with rifampin. Rifabutin may be used with dabigatran. 227–231 |
Anticonvulsants carbamazepine, phenytoin, lamotrigine | Consult with neurologist to discuss the possibility of using alternative anti-epileptic agent. Levetiracetam is a preferred anticonvulsant when taking rifamycins as there are no clinically relevant interactions. Alternatively, therapeutic drug monitoring of these anti-epileptic agents with subsequent dose adjustment is required. 232–235 |
Antidiabetics agents | More frequent blood glucose monitoring recommended. Potential for decrease in drug concentration of most oral antidiabetic agents in patients on rifamycins and potential for increased blood glucose levels. Dose adjustment of antidiabetic agents may be required, 236–243 No significant interaction with metformin or insulin. 243 |
Antifungals Azoles (itraconazole, fluconazole, posaconazole, voriconazole, isavuconazole) |
Subtherapeutic azole concentrations may occur when used with any of the rifamycins. 244–248 |
Antihypertensives | Increased BP monitoring recommended with most antihypertensives. Rifampin has a strong interaction with calcium channel blockers and clinicians may be required to increase dose of the calcium channel blocker or change/add an alternate antihypertensive agent (consult provider). Rifabutin has a less potent interaction as compared to rifampin. 249–252 |
Antiretroviral agents | See Text and Table 1. |
Corticosteroids dexamethasone, methylprednisolone, prednisone | Monitor clinical response. May require increase in dose of corticosteroids. 253–255 |
Immunosuppressive agents cyclosporine, tacrolimus | Rifabutin use is preferred over rifampin to minimize impact on concentrations of calcineurin inhibitors and to reduce the risk of allograft rejection. Monitor calcineurin inhibitor concentrations and adjust dose as required. 256–260 |
Levothyroxine | Continue both agents but monitor TSH monthly. May require increase in dose of levothyroxine with rifamycins. Monitor TSH after stopping rifamycins. 261–263 |
Opiate agonist therapy methadone, buprenorphine/naloxone (Suboxone) | Methadone and buprenorphine serum concentrations decrease substantially with rifampin and precipitation of withdrawal symptoms is frequent. May need preemptive OAT regimen dosage adjustment in addition to close monitoring. Discuss OAT with provider. 204 , 264 , 265 Rifabutin has much less impact on methadone and buprenorphine serum concentrations and is not associated with withdrawal symptoms. 205 , 206 |
Oral hormonal contraceptive ethinyl estradiol, norethindrone, etc | Add a barrier method of contraception when taking a rifamycin with oral hormonal contraceptives. 266 |
Abbreviations: INR, international normalized ratio; LMWH, Low molecular weight heparin; BP, blood pressure; TSH, thyroid-stimulating hormone; OAT, opiate agonist therapy.
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