Felodipine Phenytoin

Gingival hyperplasia Antiepileptics (phenytoin), immunosuppressant drugs, calcium channel antagonists (felodipin, amlodipin, nifedipin)... 

Itraconazole Alfentanil, alprazolam, astemizole, atorvastatin, buspirone, cisapride, cyclosporine, delavirdine, diazepam, digoxin, felodipine, indinavir, loratadine, lovastatin, midazolam, nisoldipine, phenytoin, quinidine, ritonavir, saquinavir, sildenafil, simvastatin, sirolimus, tacrolimus, triazolam, verapamil, warfarin... 

Phenobarbital Enhances phasic GABAa receptor responses reduces excitatory synaptic responses Nearly complete absorption not significantly bound to plasma proteins peak concentrations in Vi to 4 h no active metabolites tjy2 varies from 75 to 125 h Generalized tonic-clonic seizures, partial seizures, myoclonic seizures, generalized seizures, neonatal seizures, status epilepticus Toxicity Sedation, cognitive issues, ataxia, hyperactivity Interactions Valproate, carbamazepine, felbamate, phenytoin, cyclosporine, felodipine, lamotrigine, nifedipine, nimodipine, steroids, theophylline, verapamil, others... 

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,... 

Clinically important, potentially hazardous interactions with abacavir, atorvastatin, bepridil, bupropion, carbamazepine, clarithromycin, cyclosporine, dexamethasone, digoxin, felodipine, fluticasone propionate, fosamprenavir, itraconazole, ketoconazole, lovastatin, methadone, midazolam, nicardipine, nifedipine, phenobarbital, phenytoin, rifabutin, simvastatin, sirolimus, St John s wort, systemic lidocaine, tacrolimus, tenofovir, trazodone, vinblastine, vincristine, voriconazole, warfarin, zidovudine... 

CYP2C8 <5 1-2 Disopyramide Amiodarone Clozapine Diclofenac Fluvastatin Nicardipine Paclitaxel Retinoic acid Rosiglitazone Torsemide Repaglinide Amiodarone Celecoxib Felodipine Nicardipine Fluoxetine Ketoconazole Ritonavir Indinavir Troglitazone Zafirlukast Retinoic acid Clotrimazole Phenobarbital Dexamethasone Gemfibrozil Rifampin Phenytoin Ritonavir... 

After taking felodipine 10 mg daily for 4 days, 10 epileptics (ineluding 4 taking carbamazepine alone and 3 taking carbamazepine with phenytoin) had markedly reduced plasma felodipine levels (peak levels of 1.6 nanomol/L compared with 8.9 nanomol/L in 12 control subjects). The felodipine bioavailability was reduced to 6.6%. A study in 8 subjects found that the AUC of felodipine was reduced by only 28% by oxcar-bazepine 600 to 900 mg daily for a week. ... 

The plasma levels of felodipine and nisoldipine are very markedly reduced by phenytoin (either alone or with carbamazepine). Case reports surest that nimodipine and verapamil levels may be reduced by phenytoin, and that phenytoin levels may be raised by nifedipine. 

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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