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Cytochrome P450 enzymes are essential for the metabolism of many medications.

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Although this class has more than 50 enzymes, six of them metabolize 90 percent of drugs, with the two most snificant enzymes being CYP3A4 and CYP2D6.

The Effect of Cytochrome P450 Metabolism on Drug Response.

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Abnormal taste (adults, 3-7%) Diarrhea (3-6%) Nausea (adults, 3-6%) Vomiting (adults, 1%; children, 6%) Elevated blood urea nitrogen (BUN; 4%) Abdominal pain (adults, 2%; children, 3%) Rash (children, 3%) Dyspepsia (2%) Heartburn (adults, 2%) Headache (2%) Elevated prothrombin time (PT; 1%) Anaphylaxis Anorexia Anxiety Clostridium difficile colitis Dizziness Dyspnea Elevated liver function tests Glossitis Hallucinations Hepatic dysfunction Hepatitis Hypoglycemia Increased alkaline phosphatase Increased aspartate aminotransferase Increased bilirubin Increased serum creatinine Jaundice Leukopenia Manic behavior Neuromuscular blockade Neutropenia Pancreatitis Psychosis QT prolongation Seizures Stevens-Johnson syndrome Thrombocytopenia Blood and lymphatic system disorders: Thrombocytopenia, agranulocytosis Cardiac disorders: Torsades de pointes, ventricular tachycardia, ventricular arrhythmia Ear and labyrinth disorders: Deafness was reported chiefly in elderly women and was usually reversible Gastrointestinal disorders: Pancreatitis acute, tongue discoloration, tooth discoloration Hepatobiliary disorders: Hepatic failure, jaundice hepatocellular Immune system disorders: Anaphylactic reaction, angioedema Infections and infestations: Pseudomembranous colitis Investations: Prothrombin time prolonged, white blood cell count decreased, international normalized ratio increased; abnormal urine color has been reported, associated with hepatic failure Metabolism and nutrition disorders: Hypoglycemia has been reported in patients taking oral hypoglycemic agents or insulin Musculoskeletal and connective tissue disorders: Myopathy, rhabdomyolysis was reported and in some of the reports, clarithromycin was administered concomitantly with statins, fibrates, colchicine or allopurinol Nervous system disorders: Convulsion, ageusia, parosmia, anosmia, paraesthesia Psychiatric disorders: Psychotic disorder, confusional state, depersonalization, depression, disorientation, manic behavior, hallucination, abnormal behavior, abnormal dreams Renal and urinary disorders: Nephritis interstitial, renal failure Skin and subcutaneous tissue disorders: Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms (DRESS), Henoch-Schonlein purpura, acne Vascular disorders: Hemorrhage Other: Reports of colchicine toxicity, some resulting in death, with concomitant use of clarithromycin and colchicine, especially in the elderly, some of which occurred in patients with renal insufficiency Documented hypersensitivity Coadministration with pimozide, cisapride, ergotamine, and dihydroergotamine History of cholestatic jaundice or hepatic dysfunction associated with previous use of clarithromycin Coadministration with colchicine in patients with renal or hepatic impairment Coadministration with HMG-Co A reductase inhibitors (statins) that are extensively metabolized by CYP3A4 (lovastatin, simvastatin), due to the increased risk of myopathy, including rhabdomyolysis Severe renal impairment Oral solution must not be refrerated Not for use in pregnancy, except when there is no alternative therapy; apprise patient about potential hazard to fetus if pregnancy occurs while in therapy Use for endocarditis prophylaxis is appropriate only for hh-risk patients, per American Heart Association (AHA) guidelines Associated with QT interval prolongation and infrequent cases of arrhythmias, including torsade de pointes; avoid using with ongoing proarrhythmic conditions (eg, uncorrected hypokalemia or hypomagnesemia), cliniy snificant bradycardia; do not coadminister with class IA (eg, quinidine, procainamide) or class III (dofetilide, amiodarone, sotalol) antiarrhythmics Elderly patients may be more susceptible to drug-associated QT prolongation Use caution in patients with coronary artery disease; postmarketing trials suggest increased risk of cardiovascular mortality Discontinue immediately if severe hypersensitivity reactions occur (eg, anaphylaxis, Stevens-Johnson syndrome, TEN, drug reaction with eosinophilia and systemic symptoms [DRESS] syndrome, Henoch-Schonlein purpura) Clostridium difficile associated diarrhea reported with use of nearly all antibacterial agents, including clarithromycin May cause kidney injury when administered concomitantly with calcium channel blockers metabolized by CYP3A4 Do not coadminister with ranitidine/bismuth citrate with history of acute porphyria or if Cr Cl Semisynthetic macrolide antibiotic that reversibly binds to P site of 50S ribosomal subunit of susceptible organisms and may inhibit RNA-dependent protein synthesis by stimulating dissociation of peptidyl t-RNA from ribosomes, thereby inhibiting bacterial growth Hy stable in presence of gastric acid (unlike erythromycin); food delays but does not affect extent of absorption Bioavailability: 50% Peak plasma time: 2-3 hr (immediate release); 5-8 hr (extended release) The above information is provided for general informational and educational purposes only.

The Effect of Cytochrome P450 Metabolism on Drug Response.

Click on the name of each drug for further details, or refer to the manufacturer's package insert for a comprehensive list of potential drug interactions.


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