Drug Interactions between Etrafon Forte and Propoven

MONITOR: Coadministration of a phenothiazine with a tricyclic antidepressant (TCA) may result in elevated plasma concentrations of one or both drugs as well as additive adverse effects. Most phenothiazines and TCAs have been found to undergo metabolism by CYP450 2D6, thus competitive inhibition of the enzyme may occur when more than one of these agents are administered. Although these drugs have been used together clinically, the possibility of increased risk of serious adverse effects such as central nervous system depression, tardive dyskinesia, hypotension, and prolongation of the QT interval should be considered, as many of these agents alone can and have produced these effects. In addition, excessive anticholinergic effects may occur in combination use, which can result in paralytic ileus, hyperthermia, heat stroke, and the anticholinergic intoxication syndrome. Peripheral symptoms of anticholinergic intoxication commonly include mydriasis, blurred vision, flushed face, fever, dry skin and mucous membranes, tachycardia, urinary retention, and constipation. Central symptoms may include memory loss, disorientation, incoherence, hallucinations, psychosis, delirium, hyperactivity, twitching or jerking movements, stereotypy, and seizures.

MANAGEMENT: Concurrent use of phenothiazines and TCAs should be approached with caution, particularly in the elderly and those with underlying organic brain disease, who tend to be more sensitive to the central anticholinergic effects of these drugs and in whom toxicity symptoms may be easily overlooked. Patients should be advised to notify their physician promptly if they experience potential symptoms of anticholinergic intoxication (e.g., abdominal pain, fever, heat intolerance, blurred vision, confusion, hallucinations) or cardiovascular toxicity (e.g., dizziness, palpitations, arrhythmias, syncope). Ambulatory patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them. A dosage reduction in one or both drugs may be necessary if excessive adverse effects develop.

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MONITOR: The concomitant use of general anesthetics with tricyclic antidepressants may increase the risk of hypotension and cardiac arrhythmias. The presence of pancuronium may increase the risk of tachyarrhythmias. Enflurane may also increase the risk of seizures when given to patients who have been taking tricyclic antidepressants.

MANAGEMENT: Close monitoring is recommended when these drugs are used together.

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MONITOR: Treatment with propofol may lead to prolongation of the QT interval; however, the extent of prolongation and its clinical impact is difficult to determine. A retrospective single-center cohort study in patients treated at the Mayo clinic over 17 years (n=628,784) concluded that torsade de pointes (TdP) after propofol administration occurred at an annual incidence of 1.93 per million; however, it was often associated with other risk factors, including concomitant QT-prolonging medications, low serum potassium levels (<3.5 mmol/L), and low serum magnesium levels (<1.8 mg/dL). Other studies have reported that propofol has no effect or that it decreases the QTc interval and may offset QTc prolongation due to other coadministered anesthetic medications. Theoretically, concurrent use of two or more drugs that can cause QT interval prolongation may result in additive effects and increased risk of ventricular arrhythmias including TdP and sudden death. The risk of an individual agent or a combination of these 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). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drugs. Data from formal QT/QTc studies on propofol are lacking.

MANAGEMENT: Caution and clinical monitoring is recommended if propofol is used concomitantly with other agents associated with QT interval prolongation. 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.

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