Predicting Interactions between Rifampin and Antihypertensive Drugs Using the Biopharmaceutics Drug Disposition Classification System

Abstract

Study Objective Lack of blood pressure control is often seen in hypertensive patients concomitantly taking antituberculosis medications due to the complex drug‐drug interactions between rifampin and antihypertensive drugs. Therefore, it is of clinical importance to understand the underlying mechanisms of these interactions to help formulate recommendations on the use of antihypertensive drugs in patients taking these medications concomitantly. Our objective was to assess the reliability of the Biopharmaceutics Drug Disposition Classification System (BDDCS) to predict potential interactions between rifampin and antihypertensive drugs and thus provide recommendations on the choice of antihypertensive drugs in patients receiving rifampin. Design Evidence‐based in vitro and in vivo predictions of drug‐drug interactions. Measurements and Main Results We systematically evaluated interactions between rifampin and antihypertensive drugs using the theory of the BDDCS, taking into consideration the role of drug transporters and metabolic enzymes involved in these interactions. We provide recommendations on the selection of antihypertensive drugs for patients with tuberculosis. Antihypertensive drugs approved by the U.S. Food and Drug Administration and the China National Medical Products Administration were included in this study. The drugs were classified into four categories under the BDDCS classification. Detailed information on cytochrome P450 (CYP) enzymes and drug transporters for each antihypertensive drug was searched in PubMed and other electronic databases. This information was combined with the effects of rifampin on CYP enzymes and drug transporters, and the direction and relative extent of the potential interactions between rifampin and antihypertensive drugs were predicted. Recommendations were then made using the theory of BDDCS. A thorough systematic literature review was performed, and data from all published human studies and case reports were summarized for the validation of our predictions. Interventional and observational studies published in PubMed and two Chinese databases (CNKI and WanFang) through December 16, 2019, were included, and data were extracted for validation of the predictions. Using the BDDCS theory, class 3 active drugs were predicted to exhibit minimal interactions with rifampin. On reviewing case reports and pre‐post studies, the predictions we made were found to be reliable. When antituberculosis medications that include rifampin are started in patients with hypertension, it is recommended that the use of calcium channel blockers and classes 1 and 2 β‐blockers be avoided. Angiotensin‐converting enzyme inhibitors, olmesartan, class 3 β‐blockers, spironolactone, and hydrochlorothiazide would be preferable because clinically relevant interactions would not be expected. Conclusion Application of the BDDCS to predict interactions between rifampin and antihypertensive drugs for patients with both tuberculosis and hypertension was found to be reliable. It should be noted, however, that bas...

Interactive effect of oral anti-hyperglycaemic or anti–hypertensive drugs on the inhibitory and bactericidal activity of first line anti-TB drugs against M. tuberculosis

“…Recommendations based on case study reviews, suggested that, in patients with hypertension when anti-tuberculosis treatment which include rifampicin is started, the use of calcium channel blockers and classes 1 and 2 β-blockers should be avoided. In such patients, use of, Angiotensin-converting enzyme inhibitors (e.g., Ramipril ), Valsartan (Angiotensin II antagonists) and diuretics (like hydrochlorothiazide) should be preferred, as clinically relevant interactions are not expected with these classes of drugs and are shown to be effective [ 51 , 52 ]. Anti-HT drug, Verapamil has been shown to play an important role in the treatment of TB patients in two ways, (i) by transforming non-killing macrophages in to bactericidal, and (ii) improving the therapeutic efficacy of anti-TB drugs by restoring their activity by acting as efflux pump inhibitor.…”

Prediction of potential drug interactions between repurposed COVID-19 and antitubercular drugs: an integrational approach of drug information software and computational techniques data

“…Therefore, co-administration with rifampin, an inducer of all the above transporters, may increase valsartan exposure. 124 Concurrent use of atorvastatin and rifampin may result in decreased atorvastatin concentration when administered separately after rifampin or increased atorvastatin exposure when administered simultaneously with rifampin which is due to induction of CYP3A4 metabolism of atorvastatin by rifampin and inhibition of organic anion-transporting polypeptide (OATP1B1)-mediated atorvastatin hepatic reuptake by rifampin, respectively. 125 , 126 Concurrent use of fluvastatin and rifampin may result in decreased fluvastatin effectiveness.…”

Cardiopatía coronaria isquémica y tuberculosis: una sindemia inadvertida.Revisión de la literatura y propuesta de manejo

“…los IECA no parecen verse afectados por la rifampicina ya que no son metabolizados por CYP (49) . Cabe mencionar que se ha visto una reducción del AUC del metabolito activo del enalapril (enalaprilato) en un 31%, aunque no están del todo claro y no parecen ser secundarias a esta interacción farmacológica (49) .…”

“…los IECA no parecen verse afectados por la rifampicina ya que no son metabolizados por CYP (49) . Cabe mencionar que se ha visto una reducción del AUC del metabolito activo del enalapril (enalaprilato) en un 31%, aunque no están del todo claro y no parecen ser secundarias a esta interacción farmacológica (49) . De los ARA II, losartán es un sustrato conocido de CYP por lo que se ha observado una reducción del AUC y debería desestimarse como terapia inicial, mientras que para candesartan y valsartan la interacción es poco conocida pero se ha sugerido un aumento de su AUC aunque no es del todo claro (49) .…”