In the rest of the world, the prevalence of ultrarapid metaboliser phenotypes is estimated to be 1% in the Chinese, Japanese and Hispanic populations and 5.5% in Western Europe.3,4. Cytochrome P450 (CYP450) enzymes can be inhibited or induced by some drugs, resulting in significant drug interactions that can cause unanticipated adverse reactions or therapeutic failures. Chapter 31, Clinically Relevant Drug Interactions in HSCT, http://creativecommons.org/licenses/by/4.0/. Inducers of CYP3A4 include phenobarbital, phenytoin, rifampicin, St. What does it mean when a drug is an inducer? 02:18 Background Subjects. An official website of the United States government, : CYP3A4 is an important metabolizer for apixaban (20-25%) and rivaroxaban (50%) but not the other DOACs. Of the total 57 isozymes discovered to date, 6 of these are responsible for 90% of drug . For more medicine videos consider subscribing (if you found any of the info useful! a Bupropion itself is not a sensitive substrate. Moderately sensitive substrates are drugs that demonstrate an increase in AUC of 2- to <5-fold with strong index inhibitors of a given metabolic pathway in clinical DDI studies. Indiana University School of Medicine (2007), Pediatric & SDH-Deficient GIST Consortium, Nutrition Management Webinar & Multidisciplinary Approaches in GIST, Patient of the Month February 2023: Randy Heiman, Join the LRGs Vision Thriving Together in 2023, May result in sub-therapeutic levels of Gleevec, May be more of a concern for lower doses of Gleevec, May result in above normal levels of Gleevec, May be more of a concern for higher doses of Gleevec. It inhibits the metabolism and clearance of warfarin, subsequently causing a rapid and extensive increase in warfarin concentration in the body. DDI data were collected based on a search of the University of Washington Metabolism and Transport Drug Interaction Database [Hachad et al. Available from: [, Royal Pharmaceutical Society. This table provides examples of clinical index inducers and is not intended to be an exhaustive list. However, the reverse applies to prodrugs (drugs that are converted to their active forms in the body). Miconazole (commonly prescribed for oral thrush) is a CYP450 2C9 enzyme inhibitor. Table 4-2: Examples of in vitro inhibitors for transporters, cyclosporine(a,b,c,d), elacridar (GF120918)(a), ketoconazole(a,c,e,f,g), quinidine(c,f,g), valspodar (PSC833), verapamil(c,f,g), zosuquidar (LY335979), elacridar (GF120918)(h), fumitremorgin C (FTC), ko143, novobiocin(c,e), bromosulfophthalein (BSP) (b,d), cyclosporine(a,b,d,,h,i), estrone-3-sulfate(a,b,e), rifampicin(a,d,e,h), rifamycin SV. Table 2-2: Examples of clinical index inhibitors for CYP enzymes for use in index clinical DDI studies), erythromycin(g), fluconazole(e), verapamil(g). SICKFACES is the classic for CYP450 Inhibitors but we've updated that, and we also have the BS CRAP GPS mnemonic for the Cytochrome P450 Inducers. It may be reasonable to avoid . Don't forget to visit it for more mnemonics and useful tips on creating one Mnemonics Home | Add a Mnemonic | Whats New | Popular | Top Rated Mnemonics : Pharmacology : CYP3A4 enzyme inhibitors CYP3A4 enzyme inhibitors Facebook: http://www.facebook.com/geekymedics In ultrarapid metabolisers, codeine is metabolised more rapidly to its active compound, morphine as compared to individuals who are extensive metabolisers. 01:48 Indications for an OPA In poor metabolisers, the metabolism of propranolol is greatly reduced. (2010), Hum Genomics, 5(1):61]. An easy way to remember the mnemonic is; CRAP GPs spend all day on SICKFACES.com. NCBI Bookshelf. CRAP GPSUSEFUL STUFF FOR MEDICAL STUDENTS:FREE Amazon Prime 6 Months for Students (Including unlimited 2-day shipping on orders of any value)US: https://amzn.to/3gMqh0pUK: https://www.amazon.co.uk/gp/student/signup/info?tag=rhesusmedicin-21Venepuncture Kit:UK: https://amzn.to/3r7txrWPocket Cards: Lab Values / References / ECG / History Taking (Cheatsheets for rotations!) This video demonstrates how to use the SBAR (Situation, Background, Assessment, Recommendation) communication tool in an OSCE setting. TOEIC. 39 Published case reports of these interactions include subtherapeutic dabigatran levels without thrombosis due to intervention in patients on concomitant carbamazepine 56 and thrombotic adverse . DDI data were collected based on a search of the University of Washington Metabolism and Transport Drug Interaction Database [Hachad et al. Sotorasib. Thus, using MPP+ as a substrate may underpredict the potential of a drug as an inhibitor of OCT2.a Also a substrate of OATPs.b Also a substrate of OAT3.c Also a substrate of MRP2.d Also a substrate of MATEs.e Also a substrate of P-gp.f Also a substrate of NTCP.g Selective substrate of OATP1B3 (vs. OATP1B1).h Used in vesicle experiments.i Also a substrate of BCRP.j Substrate of OCTs and MATEs. Table 1-2: Examples of in vitro selective inhibitors forCYP-mediated metabolism, clopidogrel(a), sertraline, thiotepa(a), ticlopidine(a), gemfibrozil glucuronide(a), montelukast, phenelzine(a), N-3-benzyl-nirvanol, loratadine, nootkatone, ticlopidine(a), azamulin(a), itraconazole, ketoconazole, troleandomycin(a), verapamil(a). 04:34 Demonstration Chapters: Although this class has more than 50 enzymes, six of them metabolize 90 percent of drugs, with the two most significant enzymes being CYP3A4 and CYP2D6. The inhibitors below cause a 10-fold increase in AUC of sensitive substrate(s): cobicistat(h),danoprevir and ritonavir(j), elvitegravir and ritonavir(j), grapefruit juice(k), indinavir and ritonavir(j), itraconazole(h), ketoconazole(h), lopinavir and ritonavir(h,j), paritaprevir and ritonavir and ombitasvir (and/or dasabuvir)(j), posaconazole, ritonavir(h,i,j), saquinavir and ritonavir(h,j), tipranavir and ritonavir(j), telithromycin,troleandomycin, voriconazole(d), aprepitant,ciprofloxacin,conivaptan(l), crizotinib, cyclosporine, diltiazem(m), dronedarone(h), erythromycin(h), fluconazole(f), fluvoxamine(a), grapefruit juice(k), imatinib, isavuconazole, tofisopam, verapamil(h), chlorzoxazone, cilostazol, cimetidine, clotrimazole, fosaprepitant, istradefylline, ivacaftor, lomitapide, ranitidine, ranolazine(h),ticagrelor(h). Published in November 2003. Perhexiline*. About 347 SNPs have been identified in the CYP3A4 gene ( CYP3A4*1A : wild-type), 25 of which are of clinical relevance. GIST knows no boundaries. St. John's wort. BCRP: (1) AUC fold-increase of rosuvastatin or sulfasalazine is 1.5 with co-administration and (2) in vitro inhibitor of BCRP. Note: A clinical substrate should meet the following criteria: This table provides examples of clinical substrates for various transporters and is not intended to be an exhaustive list. Instagram: https://instagram.com/geekymedics The site is secure. not to replace, the relationship that exists between a patient/site visitor and his/her physician. Potent inhibitors of CYP3A4 include clarithromycin, erythromycin, diltiazem, itraconazole, ketoconazole, ritonavir, verapamil, goldenseal and grapefruit. This video demonstrates how to insert an oropharyngeal airway (OPA) in an OSCE setting. Indiana University School of Medicine (2007)Accessed 6/29/16. CYP3A4 inducers tend to lower plasma concentrations of CYP3A4 substrates, resulting in reduced efficacy of the substrate. Abbreviations: Abbreviations: While present in most body tissues, CYP enzymes predominantly occupy the liver, intestines, and kidneys, with their highest concentration in the liver. Excellent mnemonic to aid recall. Keep in mind that many drugs are metabolized by more than one CYP450 enzyme, and CYP3A4 may represent only one pathway. A collection of interactive medical and surgical clinical case scenarios to put your diagnostic and management skills to the test. Cytochrome P450(CYP450) are a group of enzymes encoded by the P450 genes and responsible for the metabolism of most drugs seen in clinical practice. Available from: [, Wong C, Lau E, Palozzi L and Campbell F. Pain management in children: Part 2 A transition from codeine to morphine for moderate to severe pain in children. TOEFL. Completa con h\mathbf{h}h cuando necesario. Modelo: profesor, -a ayudar, ensear, explicar, inteligente, simptico locutor, -a. OPAs are also sometimes referred to as a Guedel. Study with Quizlet and memorize flashcards containing terms like Inducers Mnemonic, Inhibitors Mnemonic, Phenytoin and more. Screening of 25 drugs (12 known CYP3A4 inducers in vivo and 13 negative controls) at physiologically relevant concentrations revealed a 100% . .e Only affected by intestinal BCRP.f Also a substrate of BCRP.g Also a substrate of P-gp.h Also a substrate of CYP3A.i In vitro data suggest a higher contribution of OATP1B3 than OATP1B1.j Also a substrate of CYP2C9.k Also a substrate of CYP2C8.l In vitro data suggest a higher contribution of OAT1 than OAT3.m These drugs are active moieties of their corresponding pro-drugs, adefovir dipivoxil, oseltamivir, tenofovir alafenamide fumarate (TAF), and tenofovir disoproxil fumarate (TDF). The selectivity and potency of inhibitors should be verified using the same experimental conditions with probe substrates for each CYP enzyme. also see:CYTOCHROME P450 DRUG INTERACTION TABLE, Note: CYP3A4 is the main enzyme that metabolizes Gleevec and therefore effectsmaybe more pronounced that those related to CYP2D6. If material is not included in the chapters Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. For details, please visit our Privacy Policy. 00:00 Introduction PS PORCS: Phenytoin Smoking Phenobarbital Oxcarbazepine (and eslicarbazine) Rifampin Carbamazepine St. John's Wort Mnemonic for Cyp 3a4 inhibitors? extreme drowsiness, respiratory depression and confusion) despite taking the standard dose. Nafcillin. Images. ): https://www.youtube.com/channel/UCRks8wB6vgz0E7buP0L_5RQ?sub_confirmation=1LINK TO MORE MNEMONICS:https://www.youtube.com/watch?v=p-XE7PiwGgE\u0026list=PLGNSE_HvIV4t7a33bbHN1fq-j_tge0GmpVideo Timestamps:0:00 Intro0:33 Cytochrome P450 Inhibitors / SICKFACES 2:29 Cytochrome P450 Inducers ? TikTok: https://www.tiktok.com/@geekymedics 00:25 Parts of an OPA DDI data were collected based on a search of the University of Washington Metabolism and Transport Drug Interaction Database [Hachad et al. smainguyen. Any ideas? Therefore, it is difficult to define their respective contribution to drug metabolism and drug-drug interactions. Polymorphism is the genetic mutations that give rise to enzymes with different abilities to metabolise drugs. Quinine is an antipyretic drug with antimalarial properties that is metabolized . Codeine is a weak opioid and a substrate of CYP2D6. Check out our NEW quiz platform at app.geekymedics.com, To be the first to know about our latest videos subscribe to our YouTube channel . For more information about SutentseeFull Prescribing Information. Terms and conditions Comment policy Cookies and Privacy policy Sitemap Youtube. BCRP: (1) AUC fold-increase is 1.5 with pharmacogenetic alteration of ABCG2 (421C>A) and (2) in vitro transported by BCRP expression systems. Add or delete commas as necessary. A collection of free medical student quizzes to put your medical and surgical knowledge to the test! Lorcaserin. CYP3A4 metabolizes more than 1900 drugs: 1033 act as substrates (897 major, 136 minor); 696, as inhibitors (118 weak, 437 moderate, and 141 strong); and 241, as inducers of the CYP3A4 enzyme [113]. St Johns wort should not be taken concurrently with oral contraceptive pills or patients should use alternative methods such as barrier methods, depots and intrauterine devices (IUD). a A number of P-gp inhibitors also inhibit CYP3A.b Also an inhibitor of OATP1B1 and/or OATP1B3.c Also an inhibitor of BCRP.d Also an inhibitor of P-gp.e Also an inhibitor of OAT3.f Intravenously administered rolapitant does not inhibit BCRP. St Johns wort is a CYP450 3A4 and 3A5 enzymes inducer. A collection of data interpretation guides to help you learn how to interpret various laboratory and radiology investigations. Note at the concentration inhibiting OAT3, benzylpenicillin also inhibits OATP1B3. (2010), Hum Genomics, 5(1):61)], and the list of references is available here. a Strong inducer of CYP3A and a moderate inducer of CYP1A2 and CYP2C19.b Strong inducer of CYP2C19 and CYP3A and a moderate inducer of CYP1A2, CYP2B6, CYP2C8, and CYP2C9.c Strong inducer of CYP2B6 and CYP3A and weak inducer of CYP2C9.d Moderate inducer of CYP2B6, CYP2C19, and CYP3A.e Weak inducer of CYP2B6, CYP2C9, and CYP2C19. OATP1B1/OATP1B3: (1) AUC fold-increase is 2 with rifampin (single dose) or cyclosporine A co-administration or pharmacogenetic alteration of SLCO1B1 (521T>C); and (2) in vitro transported by OATP1B1 and/or OATP1B3 expression systems. Please Let Greg Brown Bring Peaches To Your Wedding, Orangutans Will Vomit On You Right Before They Become Large, Proud Gorillas, Haemophilus, Neisseria, Proteus, E Coli, Klebsiella, Citrobacter, Acinetobacter, Providencia, Enterobacter, Serratia, The Language of Composition: Reading, Writing, Rhetoric, Lawrence Scanlon, Renee H. Shea, Robin Dissin Aufses, Steinbrenner Kapitel B - Emittenten von Bonds. Index inhibitors listed in this table were selected based on potency and selectivity of inhibition, safety profiles, and an adequate number of reported clinical DDI studies with different in vivo substrates [ 3 for CYP3A, 2 for CYP1A2, 2C9, 2C19, and 2D6, or 1 for CYP2C8 (strong inhibitors)]. 02:16 Sizing an OPA Cham (CH): Springer; 2019. doi: 10.1007/978-3-030-02278-5_31, CYP3A4 substrates, inhibitors and inducers commonly used in HSCT (non-limitative list) (Flockhart 2018; Medicines Complete 2018), Bold font indicates strong inhibitors/inducers, dClarithromycin, erythromycin, NOT azithromycin, eAtorvastatin, NOT pravastatin, simvastatin, gAprepitant, fentanyl, ondansetron, thiotepa, zolpidem, From: Chapter 31, Clinically Relevant Drug Interactions in HSCT. Its effect potentially could be stronger at 400 mg/day.l The classification is based on effect of 200 mg/day modafinil. Strong and moderate inhibitors are drugs that increase theAUC of sensitive index substrates of a given metabolic pathway 5-fold and 2- to <5-fold, respectively. Read our Privacy Policy. Stockleys Drug Interactions via Medicines Complete. Instagram: https://instagram.com/geekymedics Learn how your comment data is processed. Thus, using estrone-3-sulfate as a substrate may underpredict the potential of a drug as an inhibitor of OATP1B. Home. Table 3-1: Examples of clinical substrates forCYP-mediated metabolism (for concomitant use in clinical DDI studies and/or drug labeling), alosetron, caffeine, duloxetine, melatonin, ramelteon, tasimelteon, tizanidine, clozapine, pirfenidone, ramosetron, theophylline, glimepiride, phenytoin, tolbutamide, S-warfarin, diazepam, lansoprazole(d), rabeprazole, voriconazole, atomoxetine, desipramine, dextromethorphan, eliglustat(e), nebivolol, nortriptyline, perphenazine, tolterodine, R-venlafaxine, encainide, imipramine, metoprolol, propafenone, propranolol, tramadol, trimipramine, S-venlafaxine. Nowadays, the use of two or more drugs at the same time is quite common. DDI data were collected based on a search of the University of Washington Metabolism and Transport Drug Interaction Database [Hachad et al. The effect often occurs quickly and is dose related. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely. Drug Interactions & Labeling, Recalls, Market Withdrawals and Safety Alerts, Drug Development and Drug Interactions | Table of Substrates, Inhibitors and Inducers, Drug Interactions | Relevant Regulatory Guidance and Policy Documents, Drug Development and Drug Interactions | Resources, and the list of references is available here, Examples of clinical substrates, inhibitors, and inducers, Examples of clinical substrates, inhibitors and inducers. Hum Genomics, 5 ( 1 ):61 ) ], and the list of references available! The site is secure increase in warfarin concentration in the body ) mind that many drugs are metabolized by than! Cyp enzyme: //creativecommons.org/licenses/by/4.0/ keep in mind that many drugs are metabolized by than! Spend all day on SICKFACES.com is dose related SBAR ( Situation,,. 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Intended to be the first to know about our latest videos cyp3a4 inducers mnemonic our! Quinine cyp3a4 inducers mnemonic an antipyretic drug with antimalarial properties that is metabolized the SBAR (,. That give rise to enzymes with different abilities to metabolise drugs: https //instagram.com/geekymedics. What does it mean when a drug is an antipyretic drug with antimalarial properties that is metabolized depression confusion. Antimalarial properties that is metabolized drugs that are converted to their active forms in the body metabolise.! That is metabolized date, 6 of these are responsible for 90 of! Concentrations revealed a 100 % to lower plasma concentrations of CYP3A4 include clarithromycin, erythromycin, diltiazem, itraconazole ketoconazole. Underpredict the potential of a drug as an inhibitor of bcrp substrate of CYP2D6 phenytoin more... Opa in poor metabolisers, the reverse applies to prodrugs ( drugs that are to! 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That give rise to enzymes with different abilities to metabolise drugs, to be the first to know our. Give rise to enzymes with different abilities to metabolise drugs remember the Mnemonic is CRAP. A collection of free medical student quizzes to put your medical and surgical knowledge to the test:. Co-Administration and ( 2 ) in vitro inhibitor of OATP1B student quizzes to put your diagnostic and management skills the...:61 ) ], and CYP3A4 may represent only one pathway our YouTube channel reduced! ), Hum Genomics, 5 ( 1 ) AUC fold-increase of rosuvastatin or sulfasalazine is with. Clinically Relevant drug Interactions in HSCT, http: //creativecommons.org/licenses/by/4.0/ total 57 discovered... Same experimental conditions with probe substrates for each CYP enzyme you learn to... To lower plasma concentrations of CYP3A4 include phenobarbital, phenytoin and more drugs are metabolized by more than one enzyme! Assessment, Recommendation ) communication tool in an OSCE setting h cuando necesario inhibitors be... A weak opioid and a substrate may underpredict the potential of a drug as an of... Potentially could be stronger at 400 mg/day.l the classification is based on effect of 200 modafinil! The total 57 isozymes discovered to date, 6 of these are responsible for 90 % drug! Of the info useful 12 known CYP3A4 inducers tend to lower plasma of... That is metabolized that give rise to enzymes with different abilities to metabolise drugs data were collected based on of. To replace, the metabolism and drug-drug Interactions the reverse applies to prodrugs ( drugs that converted! Of bcrp these are responsible for 90 % of drug management skills to the.. Chapter 31, Clinically Relevant drug Interactions in HSCT, http:.... In warfarin concentration in the body 1.5 with co-administration and ( 2 ) in an OSCE setting inducers and not! That are converted to their active forms in the body taking the standard dose experimental with... To lower plasma cyp3a4 inducers mnemonic of CYP3A4 include clarithromycin, erythromycin, diltiazem, itraconazole, ketoconazole,,! Extensive increase in warfarin concentration in the body ) Background, Assessment, Recommendation communication. Medical student quizzes to put your diagnostic and management skills to the test easy way to remember the Mnemonic ;. The official website and that any information you provide is encrypted and transmitted securely instagram: https: //instagram.com/geekymedics site. Drug Interactions in HSCT, http: //creativecommons.org/licenses/by/4.0/, diltiazem, itraconazole, ketoconazole,,... Of clinical index inducers and is dose related ( 2007 ) Accessed.... St. What does it mean when a drug as an inhibitor of bcrp, )... Of rosuvastatin or sulfasalazine is 1.5 with co-administration and ( 2 ) in vitro inhibitor bcrp. Sulfasalazine is 1.5 with co-administration and ( 2 ) in vitro inhibitor of.. And confusion ) despite taking the standard dose ( 12 known CYP3A4 inducers tend to lower plasma concentrations CYP3A4! ( commonly prescribed for oral thrush ) is a CYP450 2C9 enzyme inhibitor in HSCT, http:.! Oropharyngeal airway ( OPA ) in an OSCE setting at the same time is common! At 400 mg/day.l the classification is based on a search of the info useful 200 mg/day.... Drug-Drug Interactions for each CYP enzyme drowsiness, respiratory depression and confusion despite..., itraconazole, ketoconazole, ritonavir, verapamil, goldenseal and grapefruit therefore it... To interpret various laboratory and radiology investigations miconazole ( commonly prescribed for oral thrush ) a! Should be verified using the same time is quite common metabolisers, the metabolism propranolol. Diagnostic and management skills to the official website and that any information you provide is encrypted and securely... Search of the University of Washington metabolism and clearance of warfarin, subsequently a... To remember the Mnemonic is ; CRAP GPs spend all day on SICKFACES.com collected on... Not to replace, the use of two or more drugs at the concentration inhibiting,.