Phenytoin Calcium-channel blockers

Procainamide, quinidine, quinine, disopyramide, phenytoin, and (i-adrenergic blockers, calcium channel blockers... 

Drugs that may affect repaglinide include CYP 450 inhibitors (eg, clarithromycin, erythromycin, ketoconazole, miconazole), CYP 450 inducers (eg, barbiturates, carbamazepine, rifampin), beta blockers, calcium channel blockers, chloramphenicol, corticosteroids, coumarins, estrogens, gemfibrozil, isoniazid, itraconazole, levonorgestrel and ethinyl estradiol, MAOIs, nicotinic acid, NSAIDs, oral contraceptives, phenothiazines, phenytoin, probenecid, salicylates, simvastatin, sulfonamides, sympathomimetics, thiazides and other diuretics, and thyroid products. 

Drugs affected by voriconazole include the following benzodiazepines, calcium channel blockers, cisapride, coumarin anticoagulants, cyclosporine, ergot alkaloids, HMG-CoA reductase inhibitors, NNRTIs, phenytoin, protease inhibitors, pimozide, proton pump inhibitors, quinidine, prednisolone, rifabutin, sirolimus, sulfonylureas, tacrolimus, vinca alkaloids. 

Drugs that may affect tacrolimus include nephrotoxic agents (aminoglycosides, amphotericin B, cisplatin, cyclosporine), antifungals, bromocriptine, calcium channel blockers, cimetidine, clarithromycin, danazol, diltiazem, erythromycin, methylprednisolone, metoclopramide, carbamazepine, phenobarbital, phenytoin, rifamycins, cisapride, chloramphenicol, metronidazole, nefazodone, omeprazole, protease inhibitors, macrolide antibiotics, fosphenytoin, and St. John s wort. 

Drugs that may affect cyclosporine include allopurinol, amiodarone, androgens (eg, danazol, methyltestosterone), anticonvulsants (eg, carbamazepine, phenobarbital, phenytoin), azole antifungals (eg, fluconazole, ketoconazole), beta-blockers, bosentan, bromocriptine, calcium channel blockers, colchicine, oral contraceptives, corticosteroids, fluoroquinolones (eg, ciprofloxacin), foscarnet, HMG-CoA reductase inhibitors, imipenem-cilastatin, macrolide antibiotics, methotrexate, metoclopramide, nafcillin, nefazodone, orlistat, potassium-sparing diuretics, probucol, rifamycins (rifampin, rifabutin), serotonin reuptake inhibitors (SSRIs eg, fluoxetine, sertraline),... 

Phenytoin [NE] Increased metabolism of calcium channel blockers. 

Thiazides and other diuretics Corticosteroids Phenothiazines Thyroid products Estrogens Oral contraceptives Phenytoin Nicotinic acid Sympathomimetics Calcium channel blockers Isoniazid Miconazole... 

Drugs that tend to produce hyperglycemia (thiazide and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blockers, isoniazid)... 

CALCIUM CHANNEL BLOCKERS PHENYTOIN 1. Phenytoin levels are t by diltiazem and possibly nifedipine and isradipine 2.1 plasma concentrations of diltiazem, felodipine, nisoldipine, verapamil and possibly nimodipine 1. Postulated to be due to inhibition of CYP3A4-mediated metabolism of phenytoin. Diltiazem is also known to inhibit intestinal P-gp, which may t the bioavailability of phenytoin 2. Phenytoin induces CYP3A4, which metabolizes calcium channel blockers 1. Monitor phenytoin levels when initiating calcium channel blockers, particularly diltiazem and verapamil 2. Monitor PR and BP closely watch for t BP when starting phenytoin in patients already on calcium channel blockers... 

Gingival hyperplasia, similar to that seen with phenytoin and ciclosporin, is a rare but well-recognized adverse effect of nifedipine (88). It has also been reported in patients taking felodipine (89,90), nitrendipine (SEDA-16, 200), and verapamil (91), suggesting that this adverse effect is a class effect. Only one case of gingival hyperplasia related to calcium channel blockers was reported to the Norwegian Adverse Drug Reaction Committee up to 1991, despite their widespread use (92). However,... 

Current concepts of resuscitation after local anesthetic cardiotoxicity have been reviewed (17). Vasopressin may be a logical vasopressor in the setting of hypotension, rather than adrenaline, in view of the dysrhythmogenic potential of the latter. Amiodarone is probably of use in the treatment of dysrhythmias. Calcium channel blockers, phenytoin, and bretyllium should be avoided. In terms of new modes of therapy targeted at the specific action of local anesthetics, lipid infusions, propofol, and insulin/ glucose/potassium infusions may all have a role, but further research is necessary. 

Bahls FH, Ozuna J, Ritchie DE. Interactions between calcium channel blockers and the anticonvulsants carbamaze-pine and phenytoin. Neurology 1991 41(5) 740-2. 

Clinically important, potentially hazardous interactions with acetazolamide, aminoglycosides, anticholinesterases, bambuterol, calcium channel blockers, chloroquine, chlorpromazine, clindamycin, d-pencillamine, ecothiophate iodine, enflurane, furosemide, halothane, hexomethonium, isoflurane, ketamine, lidocaine, lincomycin, lithium salts, magnesium salts, mannitol, MAO inhibitors, organophosphates, pancuronium, phenytoin, polymyxins, procainamide, quinidine, sevoflurane, spectinomycin, tetracyclines... 

CYP3A4 alprazolam, calcium channel blockers, cisapride, clarithromycin, cyclosporin A, erythromycin, HIV protease inhibitors, lidocaine, midazolam, simvastatin, terfenadine carbamazepine, dexamethsone, phenobarbital, phenytoin, rifampicin, St John s wort cimetidine, erythromycin, grapefruit juice, HIV protease inhibitors, itraconazole, ketoconazole... 

A4 Barbiturates, carbamazepine, corticosteroids, efavirenz, phenytoin, rifampin, troglitazone Antiarrhythmics, antidepressants, azole antifungals, benzc iazepines, calcium channel blockers, cyclosporine, delavirdine, doxorubicin, efavirenz, erythromycin, estrogens, HIV protease inhibitors, nefazodone, paclitaxel, proton pump inhibitors, HMG-CoA reductase inhibitors, rifabutin, rifampin, sildenafil, SSRIs, tamoxifen, trazodone, vinca anticancer agents... 

Induction of hepatic metabolism 2. Inhibition of phenytoin metabolism (parecoxib - CYP2C9 calcium channel blockers -CYP3A4 mianserin -unknown) 3. Uncertain amiodarone inhibits CYP2C9, which plays a role in phenytoin metabolism and inhibits Intestinal P-gp, which may t bioavailability of phenytoin. Theophylline i absorption of phenytoin... 

A. Cimetidine, and to a lesser extent ranitidine, reduces hepatic clearance and prolongs the elimination half-life of several dmgs as a result of inhibition of cytochrome P-450 activity and reduction of hepatic blood flow. Examples of drugs affected include phenytoin, theophylline, phenobatbital, cyclosporine, morphine, lidocaine, calcium channel blockers, tricyclic antidepressants, and warfarin. 

Diltiazem may inhibit the metabolism of phenytoin. In contrast, the antiepileptics are well recognised as enzyme inducers, which can increase the metabolism of the calcium-channel blockers by the liver, resulting in a very rapid loss from the body. 

Information about the effects of calcium-channel blockers on phenytoin is limited, but what is known indicates that if diltiazem is given with phenytoin, the dosage of phenytoin may possibly need to be reduced to avoid toxicity. The case report of phenytoin toxicity with nifedipine is isolated, and of unknown importance. Phenytoin markedly reduces felodipine, verapamil and possibly nifedipine levels. Although not all calcium-channel blockers have been studied, most would be expected to interact with phenytoin similarly, as they are metabolised by the same isoenzymes (see Calcium-channel blockers , (p.860)). A considerable increase in the dosage of any calcium-channel blocker will probably be needed in the presence of phenytoin. Note that the manufacturers of nimodipine and nisoldipine contraindieate the eoneurrent use of phenytoin because of the possibility of a large reduction in their levels. 

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