Phenytoin fluvoxamine

Phenytoin serum levels can be increased in some patients by fluoxetine and toxicity may occur. There are also isolated reports of phenytoin toxicity in patients taking fluvoxamine. Phenytoin and sertraline do not normally interact, but two patients have shown increased serum phenytoin levels. Sertraline and possibly paroxetine levels may be reduced by phenytoin. Note that SSRIs should be avoided in unstable epilepsy and used with care in other epileptics. 

Quetiapine 3A4 2D6, 2C9 Carbamazepine and phenytoin topiramate prednisolone. Fluvoxamine fluoxetine sertraline (high dose) CYP3A4 substrates grapefruit juice. 

Acenocoumarol, amiodarone, celecoxib, coumadin, dexamethasone, diclofenac, etoposide, fluconazole, fluoxetine, fluvas-tatin, fluvoxamine, ghmepiride, ghpizide, glyburide, ibuprofen, irbesartan, isoniazid, losartan, midazolam, phenylbutazone, phenytoin, rifampin, teniposide, tenoxicam, thiotepa, tolbutamide, torsemide, vitamin D, warfarin... 

Theophylline is a narrow therapeutic index drug with significant difference in bioavailability following oral administration. The half-life of the drug is increased by heart failure, cirrhosis and viral infections, in elderly patients, and by certain drugs, such as cimetidine, ciprofloxacin, oral contraceptives and fluvoxamine. The half-life is decreased in smokers, chronic alcoholism, and by certain drugs, such as phenytoin, rifampicin and carbamazepine. 

Others Acetaminophen, amiodarone, carbamazepine, delavirdine, efavirenz, nevirapine, quinidine, repaglinide, sildenafil, tadalafil, trazodone, vardenafil Amiodarone, amprenavir, atazanavir, ciprofloxacin, cisapride, clarithromycin, diltiozem, erythromycin, fluconazole, fluvoxamine, grapefruit juice (in high ingestion), indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, norfloxacin, ritonavir, telithromycin, troleandomycin, verapamil, voriconazole Carbamazepine, efavirenz, glucocorticoids, macrolide antibiotics, nevirapine, phenytoin, phenobarbital, rifabutin, rifapentine, rifampin, St. John s wort... 

Most benzodiazepines undergo oxidative metabolism in the liver that may be enhanced by enzyme inducers (e.g. carbamazepine, phenytoin) or slowed by inhibitors (sodium valproate, fluoxetine, fluvoxamine). Oxazepam, lorazepam and temazepam are directly conjugated and are not subject to these interactions. 

Clozapine is metabolized by hepatic CYP 1A2 and, to a lesser degree, CYP 3A3/4 therefore, the drug is subject to changes in serum concentration when combined with medications that inhibit or induce these enzymes. Serum clozapine levels increase with coadministration of fluvoxamine or erythromycin and decrease with coadministration of phenobarbital or phenytoin and with cigarette smoking (Byerly and DeVane 1996). These pharmacokinetic interactions are particularly important because of the dose-dependent risk of seizures. 

C19 TCAs, citalopram (partly), warfarin, tolbutamide, phenytoin, diazepam Fluoxetine, fluvoxamine, sertraline, imipramine, ketoconozole, omeprazole Rifampin... 

Interactions are similar to those of opioid analgesics. Methadone has interactions with enzyme inducers. Withdrawal symptoms of methadone are observed upon concurrent administration with phenobarbitone, phenytoin, and rifampicin. Methadone toxicity increases if administered with cimetidine and fluvoxamine. 

Fluvoxamine inhibits CYP2C9 and CYP2C19, the enzymes responsible for the metabolism of phenytoin. 

A 45-year-old woman taking phenytoin 300 mg/day had a plasma phenytoin concentration of 66 pmol/1 (29). When she became depressed fluvoxamine 50 mg/day was added. A month later her depressive symptoms had improved, but she was ataxic and the plasma phenytoin concentration was 196 pmol/1. The fluvoxamine was withdrawn and the phenytoin dose reduced to 150 mg/day. Her plasma phenytoin concentration fell to 99 pmol/1, with resolution of the ataxia. 

In 14 healthy volunteers fluvoxamine (150-300 mg/day for 5 days) significantly reduced the clearance of tolbutamide (30). This suggests that fluvoxamine should be used with caution when it is co-administered with drugs that are substrates for CYP2C9, such as tolbutamide, phenytoin, and warfarin. 

Mamiya K, Kojima K, Yukawa E, Higuchi S, Ieiri I, Ninomiya H, Tashiro N. Phenytoin intoxication induced by fluvoxamine. Ther Drug Monit 2001 23(l) 75-7. 

Avoid use of astemizole with fluvoxamine use alternate antihistamine Decrease dose of benzodiazepines Decrease dose of theophylline by approximately 1/3 avoid caffeine intake Monitor INR decrease dose of warfarin if necessary Monitor phenytoin increased dose may be necessary... 

Fluvoxamine Carbamazepine Diazepam Phenytoin Risk of toxicity of the affected drugs with carbamazepine, interaction inconsistent Inhibition of metabolism of the object drugs... 

Clinically important, potentially hazardous interactions with ciprofloxacin, fluvoxamine, lisinopril, phenytoin, rofecoxib... 

CYP2C9 20 10 Celecoxib Diclofenac Fluoxetine Fluvastatin Ibuprofen Irbesarten Naproxen Amitriptyline Phenytoin Tolbutamide Torsemide S-warfarin Rosiglitazone Amiodarone Fluconazole Fluvoxamine Fluvastatin Isoniazid Sertraline Sulfaphenazole Trimethoprin Zafirlukast Rifampin Clotrimazole Carbamazepine Hyperforin Phenobarbital Ritonavir... 

CYP2C19 <5 5 Amitriptyline S-mephenytoin Omeprazole Phenytoin Phenobarbital Propranolol Diazepam Fluoxetine Fluvoxamine Ketoconazole Omeprazole Ticlopidine Topiramate Carbamazepine Rifampin... 

Also analyzed acebutolol, acepromazine, acetaminophen, acetazolamide, acetophenazine, albuterol, amitriptyline, amobarbital, amoxapine, antipsrrine, atenolol, atropine, azata-dine, baclofen, benzocaine, bromocriptine, brompheniramine, brotizolam, bupivacaine, buspirone, butabarbital, butalbital, caffeine, carbamazepine, cetirizine, chlorqyclizine, chlordiazepoxide, chlormezanone, chloroquine, chlorpheniramine, chlorpromazine, chlorpropamide, chlorprothixene, chlorthalidone, chlorzoxazone, cimetidine, cisapride, clomipramine, clonazepam, clonidine, clozapine, cocaine, codeine, colchicine, qyclizine, (yclo-benzaprine, dantrolene, desipramine, diazepam, diclofenac, diflunisal, diltiazem, diphenhydramine, diphenidol, dipheno late, dipyridamole, disopyramide, dobutamine, doxapram, doxepin, droperidol, encainide, ethidium bromide, ethopropazine, fenoprofen, fentanyl, flavoxate, fluoxetine, fluphenazine, flurazepam, flurbiprofen, fluvoxamine, fii-rosemide, glutethimide, glyburide, guaifenesin, haloperidol, homatropine, hydralazine, hydrochlorothiazide, hydrocodone, hydromorphone, hydro g chloroquine, hydroxyzine, ibuprofen, imipramine, indomethacin, ketoconazole, ketoprofen, ketorolac, labetalol, le-vorphanol, lidocaine, loratadine, lorazepam, lovastatin, loxapine, mazindol, mefenamic acid, meperidine, mephenytoin, mepivacaine, mesoridazine, metaproterenol, methadone, methdilazine, methocarbamol, methotrexate, methotrimeprazine, methoxamine, methyl-dopa, methylphenidate, metoclopramide, metolazone, metoprolol, metronidazole, midazolam, moclobemide, morphine, nadolol, nalbuphine, naloxone, naphazoline, naproxen, nifedipine, nizatidine, norepinephrine, nortriptyline, oxazepam, oxycodone, oxymetazo-line, paroxetine, pemoline, pentazocine, pentobarbital, pentoxifylline, perphenazine, pheniramine, phenobarbital, phenol, phenolphthalein, phentolamine, phenylbutazone, phenyltoloxamine, phenytoin, pimozide, pindolol, piroxicam, pramoxine, prazepam, prazosin, probenecid, procainamide, procaine, prochlorperazine, procyclidine, promazine, promethazine, propafenone, propantheline, propiomazine, propofol, propranolol, protriptyline, quazepam, quinidine, quinine, racemethorphan, ranitidine, remoxipride, risperidone, salicylic acid, scopolamine, secobarbital, sertraline, sotalol, spironolactone, sulfinpyrazone, sulindac, temazepam, terbutaline, terfenadine, tetracaine, theophylline, thiethyl-perazine, thiopental, thioridazine, thiothixene, timolol, tocainide, tolbutamide, tolmetin, trazodone, triamterene, triazolam, trifluoperazine, triflupromazine, trimeprazine, trimethoprim, trimipramine, verapamil, warfarin, xylometazoline, yohimbine, zopiclone... 

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