Fluvoxamine Smoking

Clozapine 1A2 3A3/4, 2D6, 2C19 Fluvoxamine, ciprofloxacin, paroxetine Cigarette smoking... 

Effects of smoking Smokers had a 25% increase in the metabolism of fluvoxamine compared with nonsmokers. 

Smoking cessation, with or without nicotine substitutes, may alter response to concomitant medication in ex-smokers. Smoking may affect alcohol, benzodiazepines, beta-adrenergic blockers, caffeine, clozapine, fluvoxamine, olanzapine, tacrine, theophylline, clorazepate, lidocaine (oral), estradiol, flecanide, imipramine, heparin, insulin, mexiletine, opioids, propranolol, catecholamines, and cortisol. 

Substrates Inhibitors Inducers CYP1A2 Acetaminophen, caffeine, clozapine, imipramine, theophylline, propranolol Most fluoroquinolone antibiotics, fluvoxamine, cimetidine Tobacco smoking, charcoal-broiled foods, cruciferous vegetables, omeprazole... 

CYP1A2 Theophylline, unipramine Omeprazole, tobacco smoke Fluvoxamine, furafyUine... 

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. 

Clozapine is principally metabolized to N -desmethylclozapine (norclozapine). It is also metabolized to and n-oxide, other hydroxyl metabolites, and a protein-reactive metabolite. The n-oxide can be converted back to clozapine. The enzyme responsible for the metabolism of clozapine to norclozapine is the cytochrome P450 1A2 enzyme (325). This is consistent with a study showing that caffeine, a marker for 1A2, is cleared in relationship to the conversion of clozapine to norclozapine ( 326). Discontinuation of coffee intake can decrease the clozapine plasma levels by more than 50%, and increasing caffeine intake can produce a reemergence of the side effects (e.g., drowsiness, excess salivation). Additionally, smoking, which induces 1A2, lowers clozapine plasma levels. Fluvoxamine, an inhibitor of 1A2, dramatically increases plasma levels, and on occasion, adverse effects are seen ( 327). This phenomenon can lead to clozapine intoxication in patients on high doses of fluvoxamine. 

A2 Acetaminophen, antipyrine, caffeine, clomipramine, phenacetin, tacrine, tamoxifen, theophylline, warfarin Smoking, charcoal-broiled foods, cruciferous vegetables, omeprazole Galangin, furafylline, fluvoxamine... 

Fluvoxamine under steady-state conditions increases the systemic availability of olanzapine and inhibits the metabolism of clozapine, as shown in 21 male non-smoking Chinese volunteers (mean age 27 years) (277). This could be related to the different metabolic pathways and secretion rates of the two drugs it would be advisable to reduce the dosage of olanzapine and to extend the dosing interval of clozapine when they are combined with fluvoxamine. 

CANNABIS FLUVOXAMINE 1 levels, with risk of therapeutic failure Induction of CYP1 A2-mediated metabolism by any form of smoking. Foods (e.g. broccoli, cabbage, Brussels sprouts, chargrilled meat) also induce this isoenzyme Watch for poor response to fluvoxamine conversely, watch for toxic effects if a previously heavy cannabis user stops smoking... 

Dose may need to be lowered if given with CYP4501A2 inhibitors (e.g., fluvoxamine) raised if given in conjunction with CYP450 1A2 inducers (e.g., cigarette smoke, carbamazepine)... 

Based on current information, inhibitors of CYP 1A2 have the greatest potential for causing interactions with olanzapine. Examples include cimetidine, fluvoxamine, and fluoroquinolone antibiotics (e.g., ciprofloxacin) to varying degrees. To date, however, no serious inhibition interactions have been reported with olanzapine, which may be a result of olanzapine s wide therapeutic index. Carbamazepine has been reported to increase olanzapine elimination by as much as 50%. Cigarette smoking is a potent inducer of CYP 1A2, and one would expect lower mean olanzapine serum concentrations in smokers compared to nonsmokers. 

CYP1A2 caffeine, imipramine, paracetamol, theophylline cigarette smoke, omeprazole cimetidine, ciprofloxacin, enoxacin, fluvoxamine... 

Cimetidine, fluoroquinolone antibiotics such as ciprofloxacin and the selective serotonin-reuptake inhibitor (SSRI) fluvoxamine inhibit the metabolism of theophylline, whereas, the its metabolism can be induced by smoking or by the ingestion of char-broiled meats. 

Smoking does not appear to alter citalopram pharmacokinetics, and has onfy modest effects on fluvoxamine pharmacokinetics. 

Spigset O, Carleboig L, Hedenmalm K, Dahlqvist R. Effect of cigarette smoking on fluvoxamine pharmacokinetics in humans. Chn Pharmacol Ther (1995) 58,399-403. 

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