Drug Interactions between clozapine and Dolophine

MONITOR CLOSELY: Clozapine has the potential to prolong QT interval of the electrocardiogram. Theoretically, coadministration with other agents that can cause QT prolongation may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. Clozapine treatment alone has been associated with ventricular arrhythmia, torsade de pointes, cardiac arrest, and sudden death. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia, hypocalcemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s). Certain QT-prolonging agents (e.g., neuroleptics; phenothiazines; tricyclic antidepressants; some antihistamines, antispasmodics, and skeletal muscle relaxants) may also have additive parasympatholytic and central nervous system-depressant effects with clozapine. Excessive parasympatholytic effects can result in paralytic ileus, hyperthermia, mydriasis, blurred vision, tachycardia, urinary retention, psychosis, and seizures.

MANAGEMENT: Caution is recommended if clozapine is used in combination with other drugs that can prolong the QT interval. Serum electrolytes, including potassium, magnesium and calcium, should be measured at baseline and periodically during treatment, and any abnormalities corrected prior to initiating clozapine. Routine ECG assessment may detect QTc prolongation, but is not always effective in preventing arrhythmias. Clozapine treatment should be discontinued if the QTc interval exceeds 500 msec. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope. Additional precaution is required when using QT-prolonging agents with anticholinergic properties, particularly in the elderly and those with underlying organic brain disease. Patients should be advised to notify their physician if they experience potential symptoms of anticholinergic intoxication such as abdominal pain, fever, heat intolerance, blurred vision, confusion, and/or hallucinations. Dosage adjustments may be necessary if excessive adverse effects develop. Ambulatory patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them.

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