Drug interactions between Adapin and citalopram

doxepin ↔ citalopram

Applies to:Adapin (doxepin) and citalopram

MONITOR CLOSELY: Concomitant use of agents with serotonergic activity including selective serotonin reuptake inhibitors and tricyclic or tetracyclic antidepressants may potentiate the risk of serotonin syndrome, which is a rare but serious and potentially fatal condition thought to result from hyperstimulation of brainstem 5-HT1A and 2A receptors. Symptoms of the serotonin syndrome may include mental status changes such as irritability, altered consciousness, confusion, hallucination, and coma; autonomic dysfunction such as tachycardia, hyperthermia, diaphoresis, shivering, blood pressure lability, and mydriasis; neuromuscular abnormalities such as hyperreflexia, myoclonus, tremor, rigidity, and ataxia; and gastrointestinal symptoms such as abdominal cramping, nausea, vomiting, and diarrhea.

MANAGEMENT: In general, the concomitant use of multiple serotonergic agents should be avoided if possible, or otherwise approached with caution if potential benefit is deemed to outweigh the risk. Patients should be closely monitored for symptoms of the serotonin syndrome during treatment. Particular caution is advised when increasing the dosages of these agents. If serotonin syndrome develops or is suspected during the course of therapy, all serotonergic agents should be discontinued immediately and supportive care rendered as necessary. Moderately ill patients may also benefit from the administration of a serotonin antagonist (e.g., cyproheptadine, chlorpromazine). Severe cases should be managed under consultation with a toxicologist and may require sedation, neuromuscular paralysis, intubation, and mechanical ventilation in addition to the other measures.

ADJUST DOSE: Citalopram can cause dose-dependent prolongation of the QT interval. Theoretically, coadministration with other agents that can prolong the QT interval including tricyclic or tetracyclic antidepressants may result in additive effects and increased risk of ventricular arrhythmias such as torsade de pointes and sudden death. In a randomized, double-blind, crossover, escalating multiple-dose study consisting of 119 healthy subjects, the maximum mean increase in corrected QT interval from placebo was 8.5 msec for citalopram 20 mg and 18.5 msec for citalopram 60 mg. Based on the established exposure-response relationship, prolongation of the corrected QT interval was estimated to be 12.6 ms for citalopram 40 mg. Cases of QT interval prolongation and torsade de pointes have been reported during postmarketing use. 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). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

MANAGEMENT: Given the risk of dose-dependent QT prolongation, citalopram should not be administered at dosages greater than 40 mg/day. Studies have not shown a benefit in the treatment of depression at dosages above 40 mg/day. Hypokalemia and hypomagnesemia should be corrected prior to initiation of citalopram treatment and periodically monitored. ECG monitoring is recommended with concomitant medications that have demonstrated prolongation of the QT interval and/or underlying risk factors such as heart failure or bradyarrhythmia. Patients should be advised to seek medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, palpitations, irregular heartbeat, shortness of breath, or syncope.