Drug Interactions between atomoxetine and oliceridine

MONITOR: Serotonin syndrome has been reported following the concomitant use of atomoxetine with other serotonergic medicinal products. The use of agents with serotonergic activity (such as selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs), tetracyclic antidepressants, tricyclic antidepressants, 5-HT1 receptor agonists (triptans), ergot alkaloids, lithium, St. John's wort, phenylpiperidine opioids, dextromethorphan, and tryptophan, among others) may potentiate the risk of serotonin syndrome, a rare but serious and potentially fatal condition. Symptoms of 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.

MONITOR: Atomoxetine can cause dose-related prolongation of the QT interval. There is the potential for an increased risk of QTc interval (QT interval corrected for heart rate) prolongation when atomoxetine is administered with other QT prolonging drugs (e.g., neuroleptics, class IA and III antiarrhythmics, moxifloxacin, erythromycin, methadone, mefloquine, tricyclic antidepressants, lithium or cisapride) and drugs that cause electrolyte imbalance (e.g., thiazide diuretics). In a study of 120 healthy male CYP450 2D6 poor metabolizers receiving atomoxetine (20 mg and 60 mg twice daily for 7 days), no large QTc changes were observed (i.e., >60 msec increase or QTc >480 msec); however, there were slight increases in the QTc interval with increased atomoxetine concentrations. 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 including, but not limited to cardiac disease, uncontrolled hypothyroidism, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation may vary depending on the dosage(s) and specific drug(s) involved.

MANAGEMENT: If coadministration of atomoxetine with other agents that both prolong the QT interval and possess or enhance serotonergic activity is required, some authorities advise patients should have more frequent electrocardiograms (ECGs) than normally recommended, and be monitored closely for, and counseled about the signs and symptoms of serotonin syndrome (e.g., altered mental status, hypertension, restlessness, myoclonus, hyperthermia, hyperreflexia, diaphoresis, shivering, and tremor), as well as prolonged QT interval (irregular heartbeat, dizziness, lightheadedness, fainting), especially during initiation and dose escalations. Due to variability and occasionally prolonged half-lives of these coadministered agents, consulting individual product labeling for specific guidance is advised.