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Fazaclo (Clozapine) - Drug Interactions, Contraindications, Overdosage, etc



Potential for Other Drugs to Affect FAZACLO

Clozapine is a substrate for many cytochrome P450 isozymes, in particular CYP1A2, CYP3A4, and CYP2D6. Use caution when administering FAZACLO concomitantly with drugs that are inducers or inhibitors of these enzymes.

CYP1A2 Inhibitors

Concomitant use of FAZACLO and CYP1A2 inhibitors can increase plasma levels of clozapine, potentially resulting in adverse reactions. Reduce the FAZACLO dose to one third of the original dose when FAZACLO is coadministered with strong CYP1A2 inhibitors (e.g., fluvoxamine, ciprofloxacin, or enoxacin). The FAZACLO dose should be increased to the original dose when coadministration of strong CYP1A2 inhibitors is discontinued [see Dosage and Administration, Clinical Pharmacology].

Moderate or weak CYP1A2 inhibitors include oral contraceptives and caffeine. Monitor patients closely when FAZACLO is coadministered with these inhibitors. Consider reducing the FAZACLO dosage if necessary [see Dosage and Administration].

CYP2D6 and CYP3A4 Inhibitors

Concomitant treatment with FAZACLO and CYP2D6 or CYP3A4 inhibitors (e.g., cimetidine, escitalopram, erythromycin, paroxetine, bupropion, fluoxetine, quinidine, duloxetine, terbinafine, or sertraline) can increase FAZACLO levels and lead to adverse reactions [see Clinical Pharmacology]. Use caution and monitor patients closely when using such inhibitors. Consider reducing the FAZACLO dose [see Dosage and Administration].

CYP1A2 and CYP3A4 Inducers

Concomitant treatment with drugs that induce CYP1A2 or CYP3A4 can decrease the plasma concentration of clozapine, resulting in decreased effectiveness of FAZACLO. Tobacco smoke is a moderate inducer of CYP1A2. Strong CYP3A4 inducers include carbamazepine, phenytoin, St. John’s wort, and rifampin. It may be necessary to increase the FAZACLO dose if used concomitantly with inducers of these enzymes. However, concomitant use of FAZACLO and strong CYP3A4 inducers is not recommended [see Dosage and Administration].

Consider reducing the FAZACLO dosage when discontinuing coadministered enzyme inducers, because discontinuation of inducers can result in increased clozapine plasma levels and an increased risk of adverse reactions [see Dosage and Administration].

Drugs that Cause QT Interval Prolongation

Use caution when administering concomitant medications that prolong the QT interval or inhibit the metabolism of FAZACLO. Drugs that cause QT prolongation include: specific antipsychotics (e.g., ziprasidone, iloperidone, chlorpromazine, thioridazine, mesoridazine, droperidol, and pimozide), specific antibiotics (e.g., erythromycin, gatifloxacin, moxifloxacin, sparfloxacin), Class 1A antiarrhythmics (e.g., quinidine, procainamide) or Class III antiarrhythmics (e.g., amiodarone, sotalol), and others (e.g., pentamidine, levomethadyl acetate, methadone, halofantrine, mefloquine, dolasetron mesylate, probucol or tacrolimus) [see Warnings and Precautions].

Potential for FAZACLO to Affect Other Drugs

Concomitant use of FAZACLO with other drugs metabolized by CYP2D6 can increase levels of these CYP2D6 substrates. Use caution when coadministering FAZACLO with other drugs that are metabolized by CYP2D6. It may be necessary to use lower doses of such drugs than usually prescribed. Such drugs include specific antidepressants, phenothiazines, carbamazepine, and Type 1C antiarrhythmics (e.g., propafenone, flecainide, and encainide).


Overdosage Experience

The most commonly reported signs and symptoms associated with FAZACLO overdose are: sedation, delirium, coma, tachycardia, hypotension, respiratory depression or failure; and hypersalivation. There are reports of aspiration pneumonia, cardiac arrhythmias, and seizure. Fatal overdoses have been reported with clozapine, generally at doses above 2500 mg. There have also been reports of patients recovering from overdoses well in excess of 4 g.

Management of Overdosage

For the most up-to-date information on the management of FAZACLO overdosage, contact a certified Regional Poison Control Center (1-800-222-1222). Telephone numbers of certified Regional Poison Control Centers are listed in the Physicians’ Desk Reference ®, a registered trademark of Thomson PDR. Establish and maintain an airway; ensure adequate oxygenation and ventilation. Monitor cardiac status and vital signs. Use general symptomatic and supportive measures. There are no specific antidotes for FAZACLO.

In managing overdosage, consider the possibility of multiple-drug involvement.


4.1 History of Clozapine-induced Agranulocytosis or Severe Granulocytopenia

FAZACLO is contraindicated in patients with a history of clozapine-induced agranulocytosis or severe granulocytopenia [see Warnings and Precautions].

4.2 Hypersensitivity

FAZACLO is contraindicated in patients with a history of hypersensitivity to clozapine (e.g., photosensitivity, vasculitis, erythema multiforme, or Stevens-Johnson Syndrome) or any other component of FAZACLO [see Adverse Reactions].

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