Rifampin

Explanation

Omeprazole is metabolised by CYP2C19 and CYP3A4; rifampicin induces these enzymes and can reduce its concentrations by more than 50%, decreasing gastric acid suppression (relevant in ulcer, severe GORD or stress prophylaxis). Monitor the clinical response and consider increasing the omeprazole dose or preferring a less affected PPI (e.g. pantoprazole) during the combination.

Explanation

The interaction is bidirectional: rifampicin induces CYP3A4 and markedly reduces ketoconazole concentrations (loss of antifungal effect), while ketoconazole inhibits CYP3A4 and can raise rifampicin levels, with risk of hepatotoxicity. The combination should be avoided; if unavoidable, monitor the antifungal response and liver function, considering antifungal alternatives not dependent on CYP3A4 (e.g. amphotericin B, echinocandins).

Explanation

Rifampicin induces CYP2C9 and CYP3A4, pathways of fluconazole metabolism, and can reduce its concentrations by about 25–50% and shorten the half-life; the antifungal effect may be compromised in severe infections. Monitor the clinical response and consider increasing the fluconazole dose during the combination, monitoring liver function.

Explanation

Itraconazole is metabolised by CYP3A4; rifampicin, a potent inducer, can reduce its concentrations and those of the active metabolite (hydroxy-itraconazole) to undetectable levels, with complete loss of antifungal effect. The combination is practically contraindicated; if unavoidable, consider an alternative antifungal (amphotericin B, echinocandins) or monitor itraconazole levels if available.

Explanation

Rifampicin increases linezolid clearance and reduces its exposure by about 30%, even though linezolid is not significantly CYP-metabolised; the clinical relevance is debated, but the failure risk is higher in severe infections (e.g. endocarditis, resistant staphylococcal pneumonia). Monitor the clinical response and consider an alternative (e.g. vancomycin, daptomycin) when the combination is discouraged by the context.

Explanation

Praziquantel undergoes extensive CYP3A4 first-pass metabolism; rifampicin, a potent inducer, markedly reduces its concentrations and compromises efficacy against schistosomiasis, taeniasis and other parasitoses — a classically label-documented interaction. Avoid the coadministration; if unavoidable, treat the parasitosis after completing the rifampicin regimen or choose an alternative therapy.

Explanation

Prednisolone is metabolised by CYP3A4; rifampicin induces this enzyme and can reduce its concentrations by 30–50%, attenuating the anti-inflammatory/immunosuppressive effect (relevant in autoimmune diseases, transplantation and respiratory diseases). Monitor the clinical response and consider increasing the prednisolone dose during the combination, reducing it after rifampicin discontinuation.

Explanation

Rifampicin is a potent inducer of CYP3A4 and P-glycoprotein and can reduce amiodarone (and active metabolite) concentrations by more than 50%, with loss of antiarrhythmic control. The effect persists for weeks after rifampicin discontinuation given the very long amiodarone half-life (up to 60 days). Avoid the combination when possible; if unavoidable, monitor the rhythm, consider adjusting (often increasing) the amiodarone dose and monitor the ECG.

Explanation

Rifampicin is a potent inducer of CYP3A4 and can reduce carbamazepine concentrations by more than 50%, with risk of seizure relapse; the effect develops over days to weeks and persists after rifampicin discontinuation. Both are hepatotoxic, with an additive risk. Monitor carbamazepine plasma levels and increase the dose as needed during and after antituberculosis treatment, monitoring transaminases.

Explanation

Rifampicin is a potent inducer of CYP3A4, the main pathway of atorvastatin metabolism; with chronic use it substantially reduces its concentrations and compromises lipid control. Monitor the lipid profile and increase the atorvastatin dose as needed, or prefer a statin less dependent on CYP3A4 (e.g. pravastatin, rosuvastatin) during rifampicin treatment.

Explanation

Rifampicin induces the hepatic enzymes that metabolise doxycycline and can reduce its half-life and concentrations by about 50%, compromising the treatment of brucellosis, rickettsioses and other zoonoses (a classically documented combination). Avoid the association; if unavoidable, consider doubling the doxycycline dose (with monitoring) or choosing an alternative regimen.

Explanation

Bedaquiline is metabolised by CYP3A4 and rifampicin, a potent inducer, can reduce its concentrations by more than 50%, compromising multidrug-resistant tuberculosis treatment. The bedaquiline label advises against combination with potent CYP3A4 inducers. The coadministration should be avoided; if needed, consider alternative regimens and monitor the clinical and microbiological response.

Explanation

Sildenafil is metabolised by CYP3A4; rifampicin induces this enzyme and can markedly reduce its concentrations, decreasing the effect in erectile dysfunction or pulmonary hypertension. Monitor the response and consider increasing the sildenafil dose (within approved limits) during the combination, or prefer an alternative less dependent on CYP3A4.

Explanation

Voriconazole is metabolised by CYP2C19 and CYP3A4; rifampicin, a potent inducer of both pathways, can reduce its concentrations to nearly undetectable values, with loss of antifungal effect. The combination is practically contraindicated; if unavoidable, consider another antifungal (liposomal amphotericin B, echinocandins) and monitor voriconazole levels if available.

Explanation

Explanation

Rifampicin is a potent CYP3A4 inducer and reduced tadalafil exposure (AUC) by 88%. Other inducers (phenobarbital, phenytoin, carbamazepine) are expected to act similarly. Tadalafil efficacy may be compromised.

Explanation

Vardenafil is predominantly metabolised by CYP3A4; rifampicin, a potent inducer of this enzyme, reduces plasma concentrations and may compromise efficacy.

Explanation

The approved tamoxifen label (DailyMed) documents that rifampicin, a CYP3A4 inducer, reduces tamoxifen AUC and Cmax by 86% and 55%, respectively — a loss of exposure that may compromise antitumour efficacy. The EMC-UK SmPC reinforces caution with CYP3A4 inducers. This combination arises mainly in tuberculosis or antibiotic prophylaxis; management should be multidisciplinary.

Explanation

Pioglitazone is mainly metabolised by CYP2C8; rifampicin, a potent inducer of this isoenzyme, reduces pioglitazone AUC by about 54% (EMC-UK SmPC). The reduced exposure can compromise glycaemic control. This combination occurs in patients with tuberculosis and diabetes.

Explanation

The levonorgestrel over-the-counter label (DailyMed) explicitly instructs asking a doctor or pharmacist before use if taking efavirenz or rifampicin (tuberculosis treatment) or seizure medicines, as these can reduce the effectiveness of levonorgestrel. Rifampicin induces CYP3A4 and accelerates progestogen elimination. In patients with tuberculosis, hormonal emergency contraception is unreliable — the copper IUD is the alternative.

Explanation

The approved estradiol label (DailyMed) cites rifampicin among the CYP3A4 inducers that reduce plasma oestrogen concentrations, with possible decreased therapeutic effect and changes in the bleeding pattern. In patients taking rifampicin (e.g. tuberculosis), hormone replacement therapy may be insufficient and hormonal contraceptive effectiveness is compromised.

Explanation

Rifampicin is one of the most potent inducers of CYP2C9 and CYP3A4, the enzymes that metabolise warfarin. The induction accelerates warfarin elimination and markedly reduces the INR, with thromboembolism risk; studies show reductions of more than 50% in warfarin exposure. Some patients need the warfarin dose doubled or even tripled, with frequent INR monitoring, and the dose must be re-adjusted in the 1–2 weeks after rifampicin is stopped, because the inducing effect fades gradually and the INR can then rise. This interaction is particularly relevant in tuberculosis treatment in anticoagulated patients.

Explanation

Rifampicin is a potent P-glycoprotein inducer: it increases transporter expression and accelerates digoxin elimination, reducing its plasma concentrations. The effect can decrease digoxin efficacy (loss of rate control in atrial fibrillation or of heart failure control), sometimes requiring a dose increase. The interaction is particularly relevant in tuberculosis treatment in cardiac patients. Monitor digoxin levels when rifampicin is started and stopped, adjust the digoxin dose as needed and re-evaluate after discontinuation (levels may rise when the inducing effect fades).

Explanation

Rifampicin is a potent CYP1A2 and CYP3A4 inducer, potentially reducing theophylline concentrations by 30-50% and compromising bronchodilator control. QUADRO 2 of Annex 7 records this interaction in the rifampicin section. The reduced effect may appear within days and persist for weeks after stopping rifampicin. Asthmatic or COPD patients may worsen clinically and require substantial theophylline dose increases; when rifampicin is stopped, the opposite risk (toxicity) applies. Monitor theophylline levels when available and respiratory function; warn the patient about worsening bronchospasm.

Explanation

Rifampicin induces CYP2C9 and CYP3A4, accelerating phenytoin metabolism and reducing its plasma concentrations and antiepileptic effect. QUADRO 2 of Annex 7 records this interaction in the phenytoin section. The fall in levels can lead to loss of seizure control within days to weeks; when rifampicin is stopped, phenytoin levels rise and toxicity may appear. The risk is higher in patients with well-controlled epilepsy starting antituberculosis therapy. Monitor phenytoin levels and seizure control; adjust the phenytoin dose when starting, adjusting or stopping rifampicin.

Explanation

Rifampicin induces CYP3A4 and P-glycoprotein, accelerating glibenclamide metabolism and efflux and reducing its concentrations and hypoglycaemic effect. QUADRO 2 of Annex 7 records this interaction in the rifampicin section. In diabetic patients on glibenclamide, glucose may rise within days and require a dose increase or a change of antidiabetic; when rifampicin is stopped, the opposite effect (hypoglycaemia) may occur. Monitor glucose frequently and adjust therapy; consider other antidiabetics with less interaction when possible.

Explanation

Ticagrelor is metabolised by CYP3A4 and rifampicin is a potent inducer of this enzyme, potentially drastically reducing the antiplatelet concentrations and compromising cardiovascular protection. QUADRO 2 of Annex 7 records this interaction in the ticagrelor section. The loss of antiplatelet efficacy is clinically relevant in patients with acute coronary syndrome or recent stent, increasing thrombotic risk. The combination should be avoided; if rifampicin is essential (e.g. tuberculosis), consider increasing the ticagrelor dose or using an alternative antiplatelet not dependent on CYP3A4 (e.g. prasugrel or clopidogrel according to profile). Monitor for ischaemic events.

Explanation

Medroxyprogesterone is metabolised mainly by hydroxylation via CYP3A4 ("Medroxyprogesterone acetate is metabolized in-vitro primarily by hydroxylation via the CYP3A4"), and the Prontuário documents "Rifampicin: reduction of effect". Rifampicin, a potent CYP3A4 inducer, accelerates progestogen metabolism and reduces its exposure, which may compromise hormonal control of breast or endometrial cancer. The consequence is possible loss of therapeutic efficacy during concomitant use. Monitor clinical response to hormonal therapy and consider a therapeutic alternative or adjustment when the combination is unavoidable (e.g., concomitant tuberculosis treatment). Level monitoring is not routine — the criterion is clinical.

Explanation

Like other progestogens, megestrol is metabolised by hydroxylation via CYP3A4, and the Prontuário records for the class "Rifampicin: reduction of effect". Rifampicin, a potent CYP3A4 inducer, reduces exposure to megestrol and may compromise the palliative hormonal effect in breast or endometrial cancer (and the orexigenic effect in cachexia). The combination is particularly relevant in oncology patients receiving tuberculosis treatment. Monitor clinical response (oncological control and nutritional status) and consider an alternative or adjustment when the combination is unavoidable.

Explanation

Explanation

The Prontuário Terapêutico documents the montelukast interaction with rifampicin (5.1.3.2). Rifampicin is a potent CYP3A4 inducer and accelerates montelukast metabolism, potentially significantly reducing its concentrations and compromising asthma control — relevant in the asthmatic patient treated for tuberculosis. The practical guidance is to monitor asthma control (symptoms, reliever use, PEF) during the combination and consider montelukast dose adjustment or a therapeutic alternative if control is lost. The interaction is moderate, but rifampicin enzyme induction is marked, so vigilance should be active during the tuberculosis regimen.

Explanation

Rifampicin induces hepatic enzymes (CYP3A4, CYP2C8) that metabolise clofazimine, potentially reducing its levels. Although clofazimine has an extremely long half-life (70 days) due to tissue accumulation, rifampicin enzyme induction may significantly reduce this accumulation over time. In MDR-TB regimens combining rifampicin and clofazimine (regimen B), monitor clinical response and skin discoloration (visual indicator of accumulation).

Explanation