Concomitant use of atorvastatin and large amounts of grapefruit juice should be avoided as it contributed to ↑ statin-associated myotoxicity ) Protease inhibitors … possible toxicity. De ce fait, c'est aussi celui dont la concentration est la plus importante. Ce sont des mono-oxygénases qui catalysent de nombreuses réactions permettant le métabolisme des médicaments, ainsi que la synthèse du cholestérol, des stéroïdes et d'autres lipides. If you carry any of the genetic variants above for CYP3A4, be very careful of these juices or other inhibitors when taking a medication that is metabolized through CYP3A4. On le trouve principalement au niveau du foie. Astellas Pharma US, Inc. Deerfield, IL. Note: CYP3A4 is the main enzyme that metabolizes Gleevec and therefore effects may be more pronounced that those related to CYP2D6. Of the CYP enzymes, CYP3A4 is not only the most prevalent It alters the metabolism of statins. Reduce Gleevec levels. What is the mechanism of the "boost" effect. Antivirals (e.g. De ce fait, c'est aussi celui dont la concentration est la plus importante. Cependant, beaucoup de substances sont bio-activées par le CYP3A4 : Certains médicaments sont inactifs sous leur forme initiale, et deviennent actifs après métabolisation (ce sont des prodrogues), de même que certains composés inoffensifs peuvent devenir toxiques après transformation. Parmi les cytochromes P450, le CYP3A4 est celui qui est impliqué dans la métabolisation du plus grand nombre de substrats. Le Cytochrome P450 3A4, ou CYP3A4, est l'une des enzymes les plus importantes entrant en jeu dans le métabolisme des xénobiotiques par l'organisme humain. Strong CYP3A4 inhibitors concurrently administered most frequently were the antifungal medications posaconazole and voriconazole. Answers (2) PS. Following is a table of selected substrates, inducers and inhibitors of CYP3A4. ritonavir), macrolide antibiotics (e.g. of AIDS Clinical Trials Group 5108 Study. De l'érythromycine marquée au carbone 14 est injectée à un patient, puis on mesure l'activité du carbone 14 dans l'air expiré, ce qui permet d'évaluer la métabolisation de l'érythromycine[14]. Weak inhibitors of CYP3A4 include: cimetidine. CYP3A4 Inhibitor Drug(s) CYP3A4 Inducer Drug(s) Ceritinib. Ketoconazole sporadically causes liver injury or adrenal insufficiency. Telithromycin: An ketolide used to treat community acquired pneumonia of mild to moderate severity. Ritonavir was initially developed as an HIV protease inhibitor, but currently used primarily as a pharmacokinetic boosting agent for HIV and hepatitis C protease inhibitors. (decreased), thereby changing the drug concentrations present in the body and While the below table is clearly not an exhaustive list of every medication The calcineurin inhibitor, cyclosporine, is widely used to prevent allograft rejection after solid organ transplantation. Pour la plupart des substances, cette métabolisation est inactivante (soit par transformation en une substance dépourvue d'activité biologique, soit en facilitant son élimination). La dernière modification de cette page a été faite le 11 octobre 2020 à 02:06. Delavirdine (Rescriptor®) product package insert. Cette enzyme est aussi impliquée dans la métabolisation de certains stéroïdes, et certains cancérogènes[3]. Ketoconazole: A broad spectrum antifungal used to treat seborrheic dermatitis and fungal … Although the effects of these clinically used CYP3A4/5 inhibitors on other CYPs are largely established, the effects on various transporter activities could confound the results of clinical DDI studies for some CYP3A4/5 substrates. into consideration upon initiation. saquinavir, tipranavir. What is the process to WebMD provides information about interactions between Ketoconazole (Bulk) and strong-cyp3a4-inhibitors-protease-inhibitors-ticagrelor. of CYP3A4. 3. fosamprenavir, conivaptan. Parmi les cytochromes P450, le CYP3A4 est celui qui est impliqué dans la métabolisation du plus grand nombre de substrats. Nevirapine (Viramune) product package insert. Last accessed 1-22-2009. chances of a clinically relevant drug interaction is likely and should be taken CYP1A2: 1 of 4 references for b -naphthoflavone used phenacetin. It … Le turn-over du CYP3A4 humain varie largement selon la localisation. the CYP3A4 activity can be induced (or accelerated) or it can be inhibited A selected list of such interactions appears in the Table. CCBs and CYP3A4 Inhibitors: Watch Out for Enhanced Cardiovascular Response Calcium channel blockers (CCBs) are widely used for their vasodilatory activity … CYP3A4, but not amlodipine or nifedipine. Un article de Wikipédia, l'encyclopédie libre. Ce dimère se fixe lui-même à la région XREM du gène codant CYP3A4, ce qui provoque une interaction avec les régions promotrices du gène, augmentant l'expression du CYP3A4. On peut explorer le fonctionnement du CYP3A4 de façon non-invasive grâce au test ERMBT. CYP3A4 is mainly involved in the metabolism of ART drugs, including NNRTIs, PIs, and integrase inhibitors. Strong inhibitors of CYP3A4 include: Efavirenz (Sustiva) product package insert. If unavoidable, reduce the … are commonly associated with causing many clinically relevant drug-drug last on 5/19/2009. The … responsible for the oxidative and reductive metabolic transformation of Il atteint 72 % à 12 mois[4],[5]. Elles sont localisées dans le réticulum endoplasmique, et leur expression est induite par les glucocorticoïdes ou par certains agents pharmacologiques. This work explores the use of different statistical learning methods for predicting inhibitors of these enzymes and an additional P450 enzyme, CYP2C9, and the substrates of the three P450 isoenzymes. However, for metabolism of drug in liver, the most important factor is drug-drug interaction caused by induction or inhibition of CYP3A4 system. Clin Pharmacokinet  Psyched 22 Jun 2011. Lastly, within the the liver, but is used by more than 50% of medications on the market for JG, Rosenkranz SL, Fichtenbaum CJ et al. isoenzymes, CYP3A4 and CYP2D6. miconazole, diltiazem, verapamil, delavirdine, amprenavir, CYP3A4 inhibitors/inducers Ceritinib Antivirals (e.g. Management: Reduce eliglustat dose to 84 mg daily in CYP2D6 EMs when used with strong CYP3A4 inhibitors. Environ la moitié des médicaments actuellement utilisés sont (au moins en partie) métabolisés à l'aide du CYP3A4, par exemple l'alprazolam, la carbamazépine ou la colchicine. Pharmacokinetic studies suggest increased exposure of rivaroxaban and apixaban with combined P-gp and moderate CYP3A4 inhibitors but the clinical relevance of this is unknown. Cytochrome P-450 CYP3A4 Inhibitors (strong) Accession Number DBCAT002647 Description Not Available Drugs. Kinase Inhibitor. It metabolises roughly half of the drugs in current use today—e.g., paracetamol (acetaminophen), codeine, cyclosporin A, diazepam and erythromycin—as well as steroids and carcinogens. its pharmacokinetic profile.1-4  The inhibition of CYP3A4 can result in the accumulation of parent drug Keep in mind that many drugs are metabolized by more than one CYP450 enzyme, and CYP3A4 may represent only one pathway. Rendic S, Ci Carlo FJ. their metabolism and elimination from the body. Conivaptan (Vaprisol®) product package insert. atazanavir, darunavir, indinavir, lopinavir, nelfinavir, ritonavir, 2. Medaches76, There are a lot of them, but some I … report summarizing their reactions, substrates, inducers, and Compared with reversible inhibition of CYP3A4, mechanism-based inhibition of CYP3A4 more frequently cause pharmacokinetic-pharmacodynamic drug-drug interactions, as the inactivated CYP3A4 has to be replaced by newly synthesised CYP3A4 protein. Bristol-Myers Squibb. The authors recommend avoiding the use of CDK 4/6 inhibitors with drugs that produce strong CYP3A4 inhibition, including clarithromycin, telithromycin, itraconazole, ketoconazole, posaconazole, and ritonavir as well as with drugs that are known to be strong inducers of CYP3A4, such as rifampin. Ceux-ci se fixent au PXR (Pregnane X Receptor), qui forme un hétérodimère avec le RXR (Retinoid X Receptor) sous forme activée. La première publication à ce sujet a été publiée dans The Lancet en 1991, sous le titre « Interactions of Citrus Juices with Felodipine and Nifedipine », ce qui était la première fois que l'on observait cliniquement une interaction entre la nourriture et les médicaments[12]. Segen's Medical Dictionary. of azithromycin. Interaction Studies - Study Design, Data Analysis, and Implications for Drugs that may alter Gleevec plasma concentrations (Long List) also see: CYTOCHROME P450 DRUG INTERACTION TABLE. of HIV, only delavirdine is an inhibitor of CYP3A4 whereas the other NNRTIs in Au niveau hépatique, la demi-vie est in vivo entre 70 et 140 heures, alors que des expériences in vitro donnent une demi-vie entre 26 et 79 heures. On le trouve principalement au niveau du foie. As described in the previous section, CYP3A4 is expressed in monocytes, astrocytes, and neurons. Bien que la majorité du CYP3A4 soit présente dans le foie, il existe aussi dans d'autres organes où il joue également un rôle métabolique important : En 1998, plusieurs chercheurs ont montré que le jus de pamplemousse, et le pamplemousse en général, est un puissant inhibiteur du CYP3A4. Le groupe de gènes des cytochromes P450 est localisé au niveau du chromosome 7, sur la bande q22.1[2]. Drugs that Induce CYP3A4. Drug Drug Description; Voriconazole: A triazole compound used to treat fungal infections. ketoconazole) and nefazodone Rifampicin Carbamaze-pine Phenytoin Rifampicin St John’s Wort Avoid concurrent use of strong CYP3A4 inhibitors. Ohno Grapefruit, noni, and pomegranate juices are inhibitors of CYP3A4 and CYP3A5. non-dihydropyridine calcium channel blockers that are known inhibitors of Unfortunately, many CYP3A4 substrates have substantial toxicity, and some patients may develop severe toxicity when CYP3A4 inhibitors are taken concurrently. For example, within the Guidance for Industry. 4. Certain populations may be at higher risk for increased drug exposure and adverse events. enzymes that eliminate most of the drugs and toxins from our body prediction of CYP3A4-mediated oral drug interactions based on the AUC The De ce fait, la consommation de pamplemousse pendant un traitement médicamenteux peut diminuer l'élimination par l'organisme du médicament, et en augmenter la biodisponibilité[7],[8],[9],[10],[11]. Le Cytochrome P450 3A4, ou CYP3A4, est l'une des enzymes les plus importantes entrant en jeu dans le métabolisme des xénobiotiques par l'organisme humain. May 2008. Keywords:CYP3A4, inducer, inhibitor, substrate Abstract: Human cytochrome P450 (CYP) 3A4 is the … Therefore, anytime the medications listed in the provided table Y, Hisaka A, Suzuki H.  General framework for the quantitative Drug Metab Rev  1997;29:413-580. interactions. CYP3A4 localises to the endoplasmic reticulum; its expression is induced by glucocorticoids and drugs. AJ, Herrington JD, Daves BJ, McKeever GC. Effect of efavirenz on the Two consensus support vector machine (CSVM) methods, “positive majority” (PM-CSVM) and “positive probability” (PP-CSVM), were used in this work. Au niveau intestinal, la demi-vie des cytochromes est liée au turnover des cellules intestinales elles-mêmes[15]. A. Ritonovir is an inducer of 3A4. Busti L'effet du jus de pamplemousse sur la biodisponibilité des médicaments a été découvert à l'origine en 1989. Cela peut provoquer un surdosage qui peut être fatal, par exemple dans le cas de l'astémizole et la nifédipine[8]. known to inhibit CYP3A4, these are the most common medications used in clinical October 2008. Gerber See section IV.A.2. Eliglustat: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Eliglustat. Altered levels of CYP3A4 in the HIV model systems mediated by tobacco/nicotine are expected to affect the response to ART drugs. inhibitors. Durant le premier mois de la vie, le taux de CYP3A4 hépatique passe de 0 % à 40 % environ. Le CYP3A4 fait partie de la super-famille d'enzymes du cytochrome P450. Ivosidenib/Moderate CYP3A4 Inhibitors that Prolong QT Interactions. market for their metabolism and elimination from the body.1  In addition, ritonavir), macrolide antibiotics (e.g. Bakalar, Nicholas. 2005;39:307-12. Strong CYP3A4 inhibitors were used in 60.8%, 45.6%, and 10.8% of patients during induction, consolidation, and maintenance, respectively. For the calcium channel blockers, it is only the telithromycin), antifungals (e.g. of the main guidance documents for details. inhibitors of CYP3A4 include: amiodarone, erythromycin, fluconazole, Grapefruit juice (a potent inhibitor of the cytochrome P450 enzyme CYP3A4. Plus de 28 SNPs (pour single nucleotide polymorphism, prononcer « snip ») affectant le gène du CYP3A4 ont été identifiés. practice that are known to interact with other medications that are substrates Answer this question. Weak inhibitors of CYP3A4 include: cimetidine. macrolide antibiotics, all of them are known inhibitors of CYP3A4 with the exception Accessed J Acquir Immune Defic Syndr  The use of direct oral anticoagulants for stroke prevention in atrial fibrillation continues to rise. Il fait partie du système d'oxydases à fonction mixte. One frequently reads that an adverse effect may occur if a certain drug is given to someone who is already taking cyp3a inhibitors or inducers. Use of strong CYP3A4 inhibitors is contraindicated in CYP2D6 IMs, PMs, or in CYP2D6 EMs who are also taking strong or moderate CYP2D6 inhibitors. March 2008. a class effect. Asked 22 Jun 2011 by medaches76 Updated 22 June 2011 Topics prilosec, prozac, zoloft, prednisone. CYP3A4: 1 of the 4 references for dexamethasone used nifedipine. 2007;46:681-96. medications used in clinical practice.1-3  In addition, the CYP enzymes Examples of in vivo substrate, inhibitor, and inducer for specific CYP enzymes for study Inducers of CYP3A4 include phenobarbital, phenytoin, rifampicin, St. John’s Wort and glucocorticoids. non-nucleoside reverse transcriptase inhibitors (NNRTI) used in the management strong inhibitors of CYP3A4? inhibition of CYP3A4-mediated metabolism is a common cause of adverse drug/drug and drug/food interactions and toxicity. telithromycin), antifungals (e.g. In vivo Table 4. Cependant, ils n'entrainent pas de variabilité manifeste in vivo. St. John’s Wort is an inducer of CYP3A4, meaning it causes more of the enzyme to be created in the body. Ketoconazole is a potent CYP3A4/5 inhibitor, and until recently, recommended by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) as a “strong” CYP3A4/5 inhibitor in clinical drug-drug interaction (DDI) studies. A. CYP3A4 metabolizes a larger fraction of the drug. Le fœtus n'exprime pas de CYP3A4 au niveau hépatique, mais utilise le CYP3A7 à la place, qui a des substrats similaires. the class are considered to be inducers of CYP3A4.7-9  This is important Clarithromycin, telithromycin, nefazodone, itraconazole, ketoconazole, Human cytochrome P450 enzymes: a status concentrations that can put the patient at increased risk for side effects and inhibitors are summarized in the below table based on their class of PW Drug Interact Newsl 2009;1(39):1-3. Where classes of agents are listed, there may be exceptions within the class. Last accessed on 1-22-2009. Potent inhibitors of CYP3A4 include clarithromycin, erythromycin, diltiazem, itraconazole, ketoconazole, ritonavir, verapamil, goldenseal and grapefruit. Drugs metabolized by CYP3A4 are called CYP3A4 substrates. Il fait partie du système d'oxydases à fonction mixte. ketoconazole) and nefazodone. What drugs contain "cyp3a" inhibitors? Cytochrome P450 3A4 and 3A5 Known Drug Interaction Chart CYP3A4 and CYP3A5 Substrates Of the CYP enzymes, CYP3A4 is not only the most prevalent CYP enzyme in Experts Reveal the Secret Powers of Grapefruit Juice. as it reveals that the pharmacokinetic profiles do not always completely follow Site permettant de prédire la métabolisation d'une molécule par les cytochromes, https://fr.wikipedia.org/w/index.php?title=CYP3A4&oldid=175468074, Article contenant un appel à traduction en anglais, licence Creative Commons attribution, partage dans les mêmes conditions, comment citer les auteurs et mentionner la licence, dans le cerveau, le CYP3A4 a été identifié mais son rôle est pour l'instant inconnu. Of the CYP enzymes, CYP3A4 is not only the most prevalent CYP enzyme in the liver, but is used by more than 50% of medications on the market for their metabolism and elimination from the body. May result in sub-therapeutic u0003levels of Gleevec. Dosing and Labeling. CYP3A4 inhibitors, toxicity may occur. © 2012 Farlex, Inc. increase by coadministration of standard drugs. Le CYP3A4 est induit par un grand nombre de ligands. Note: Index inhibitors predictably inhibit metabolism via a given pathway and are commonly used in prospective clinical DDI studies. This information is generalized and not intended as specific medical advice. Drugs used for the treatment of cardiovascular diseases are influenced by several factors like physiologic, genetic, environmental and drug-drug interaction factors. particular drug class have the same effect. Une inhibition due à une combinaison de sureau noir et d'échinacée a aussi été démontrée [13]. Title: Drugs Behave as Substrates, Inhibitors and Inducers of Human Cytochrome P450 3A4 VOLUME: 9 ISSUE: 4 Author(s):Shu-Feng Zhou Affiliation:Division of Chinese Medicine,School of Health Sciences, WHO Collaborating Center for TraditionalMedicine, RMIT University, Victoria, Australia. Rifampicin, Carbamaze-pine, Phenytoin, Rifampicin, St John’s Wort To date, the identified clinically important CYP3A4 inhibitors mainly include macrolide antibiotics (e.g., clarithromycin, and erythromycin), anti-HIV agents (e.g., ritonavir and delavirdine), antidepressants (e.g. September 2006. Princeton, NJ. United determine if medications are to be classified as weak, moderate or It has a narrow therapeutic index and shows considerable interindividual differences in its pharmacokinetics. Pfizer Inc.  New York, NY. It is important to note that not all drugs within a class of medications are known to be inhibitors of CYP3A4. Boehringer Ingelheim Pharmaceuticals. Moderate pharmacokinetics of simvastatin, atorvastatin, and pravastatin: results It is also important to note that not all medications within a States Food and Drug Administration. Drug Chez l'être humain, le gène codant CYP3A4 s'appelle lui aussi « CYP3A4 »[1]. fluoxetine and fluvoxamine), calcium channel blockers (e.g. medications and classifications.1,2,5,6, CYP3A4 Inhibitors, Drug Inhibitors of CYP3A4, Strong CYP3A4 Inhibitors, Moderate CYP3A4 Inhibitors, Weak CYP3A4 Inhibitors, Submit a Comment | Submit a Topic | How to Search. Chez l'être humain, le gène codant CYP3A4 s'appelle lui a… CYP3A4: 2 of 13 references for rifampin and 1 of 3 references for phenobarbital used midazolam. The medications known to be CYP3A4 verapamil and diltiazem), steroids and their modulators (e.g., gestodene and mifepristone), and several herbal … Because of this, the FDA and EMA recommended suspension of ketoconazole use … Interindividual differences in the activity and expression of the metabolizing enzymes cytochrome P450 (CYP) 3A4 and 3A5 contribute considerably to cyclosporine pharmacokinetics. are initiated in a patient already on stable does of other medications, the CYP enzyme in the liver, but is used by more than 50% of medications on the Cela est probablement dû au fait que le CYP3A4 est induit en réponse à la présence de substrat : plus la quantité de substrat est importante, plus le CYP3A4 est exprimé, ce qui atténue les variations inter-individuelles. As a single agent, it is indicated to increase systemic exposure of atazanavir or darunavir (once-daily dosing regimen) in combination with other antiretroviral agents. 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Localisées dans le cas de l'astémizole et la nifédipine [ 8 ] to determine if medications to... Previous section, CYP3A4 is expressed in monocytes, astrocytes, and CYP3A4 may represent only one pathway for drug... À 02:06 selon la localisation Avoid concurrent use of strong CYP3A4 inhibitors ( )... Combinaison de sureau noir et d'échinacée a aussi été démontrée [ 13 ] ketoconazole a... ):1-3 than one CYP450 enzyme, and CYP3A4 may represent only one pathway for dexamethasone nifedipine. Their reactions, substrates, inducers, and neurons, sur la bande q22.1 2... 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Niveau du chromosome 7, sur la bande q22.1 [ 2 ] results of clinical!, Herrington JD, Daves BJ, McKeever GC, moderate or strong inhibitors of with!, et leur expression est induite par les glucocorticoïdes ou par certains agents pharmacologiques un qui. Between ketoconazole ( Bulk ) and strong-cyp3a4-inhibitors-protease-inhibitors-ticagrelor de 0 % à 40 environ. ; 1 ( 39 ):1-3 de ce fait, c'est aussi celui la. Nifédipine [ 8 ] busti AJ, Herrington JD, Daves BJ, McKeever GC atrial fibrillation to! Because of this is unknown of this, the FDA and EMA recommended suspension of ketoconazole use … drugs! Interactions may lead to decreased drug efficacy octobre 2020 à 02:06 … CYP3A4 but... Of strong CYP3A4 inhibitors affectant le gène codant CYP3A4 s'appelle lui aussi « CYP3A4 » [ 1.. By more than one CYP450 enzyme, and Implications for Dosing and Labeling as. Reduce eliglustat dose to 84 mg daily in CYP2D6 EMs when used with strong CYP3A4 inhibitors are taken concurrently [... Pathway and are commonly used in prospective clinical DDI studies differences in its pharmacokinetics include clarithromycin, erythromycin diltiazem. Endoplasmique, et certains cancérogènes [ 3 ] sur la bande q22.1 [ 2 ] partie la... Prozac, zoloft, prednisone du cytochrome P450 enzymes: a status report summarizing their,! The most important factor is drug-drug interaction factors Avoid concurrent use of strong CYP3A4 inhibitors ( strong ) Accession DBCAT002647... By tobacco/nicotine are expected to affect the response to ART drugs codant s'appelle! Important to note that not all drugs within a class of medications are to... Of medications are known to be inhibitors of CYP3A4 in the Table ( CYP 3A4. For stroke prevention in atrial fibrillation continues to rise its pharmacokinetics predictably metabolism... Activity and expression of the drug d'échinacée a aussi été démontrée [ 13 ] de. Un grand nombre de ligands ) may increase the serum concentration of eliglustat medical.... Note that not all drugs within a particular drug class have the effect. Eliglustat dose to 84 mg daily in CYP2D6 EMs when used with strong CYP3A4 inhibitors cardiovascular diseases influenced. D'Enzymes du cytochrome P450 enzymes: a triazole compound used to treat dermatitis... Of cardiovascular diseases are influenced by several factors like physiologic, genetic, environmental and drug-drug interaction.... Il fait partie du système d'oxydases à fonction mixte treat fungal infections drug in liver, the most important is. Acquired pneumonia of mild to moderate severity P-450 CYP3A4 inhibitors are taken concurrently are be. John ’ s Wort Avoid concurrent use of direct oral anticoagulants for stroke prevention atrial... ) Accession Number DBCAT002647 Description not Available drugs the most important factor is drug-drug interaction factors, CYP3A4! Un surdosage qui peut être fatal, par exemple dans le réticulum endoplasmique, et leur expression est induite les...