Drug Interactions between Adzenys ER and Mepergan Fortis

ADJUST DOSE: The central nervous system and respiratory depressant effects of meperidine may be potentiated by concomitant use of other agents with CNS depressant effects. An increased risk of serious adverse reactions such as respiratory depression, hypotension, profound sedation, syncope, coma, and even death should be considered, particularly in elderly or debilitated patients.

MANAGEMENT: Caution and dosage adjustments are advisable when meperidine is used in combination with other narcotic analgesics, general anesthetics, phenothiazines, sedative-hypnotics, tranquilizers, tricyclic antidepressants, or other CNS depressants such as alcohol. A lower dosage of meperidine should be considered initially, then titrated carefully according to pain level and clinical response. Meperidine dosage reductions of 25% to 50% have been recommended for patients receiving phenothiazines and other tranquilizers. Patients should be advised to avoid rising abruptly from a sitting or recumbent position, and to notify their physician if they experience dizziness, lightheadedness, orthostasis, syncope, tachycardia, or excessive CNS effects that interfere with their normal activities. Patients should also avoid driving or operating hazardous machinery until they know how these medications affect them.

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MONITOR: Coadministration of amphetamines and amphetamine-like drugs with other agents that also increase serotonin levels or effects, may increase the risk of serotonin syndrome. The exact mechanism by which serotonin levels are increased differs depending on the specific medication(s) involved. Serotonin syndrome is believed to result from the hyperstimulation of postsynaptic 5-HT receptors and while postsynaptic 5-HT1A and 5-HT2A receptors are usually implicated, it is more likely that no single receptor is solely responsible. Clinical data are limited. Serotonin syndrome involving amphetamines has most frequently been reported with the use of MDMA, or ecstasy, an amphetamine derivative with enhanced serotonergic activity over classical amphetamines, which tend to be more dopaminergic. However, case reports of serotonin syndrome involving amphetamines and amphetamine-like drugs have been documented with concomitant use of other serotonergic substances (e.g., selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, monoamine oxidase inhibitors). Abuse and/or overdose may increase the risk of experiencing this adverse effect.

MANAGEMENT: Caution is recommended when amphetamines and amphetamine-like drugs are used with other agents that also increase serotonin levels or effects. Initiating patients with lower doses and ensuring close clinical monitoring for signs and symptoms of serotonin syndrome (e.g., altered mental status, hypertension, restlessness, myoclonus, hyperthermia, hyperreflexia, diaphoresis, shivering, tremor) is advised. Particular caution is recommended 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 treatment rendered as indicated.

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GENERALLY AVOID: Phenothiazines may antagonize the pharmacologic effects of amphetamine, amphetamine derivatives, and other centrally-acting sympathomimetic agents (i.e., CNS stimulants). Conversely, these agents may diminish the neuroleptic efficacy of phenothiazines. The exact mechanism of interaction is unknown but may involve opposing effects on dopaminergic activity. Several clinical studies have demonstrated the reduction or lack of effect of amphetamines on weight loss in obese psychiatric patients treated with chlorpromazine and other neuroleptic agents. In one of these studies, dextroamphetamine also had no effect on sleep patterns. As for the reverse interaction, it is uncertain whether CNS stimulants actually antagonize the neuroleptic effect of phenothiazines, since CNS stimulants alone have been reported to cause or aggravate preexisting psychotic symptoms. Finally, it is conceivable that, because of their sympathomimetic effects, CNS stimulants may also potentiate the arrhythmogenicity of phenothiazines. A case of fatal ventricular arrhythmia was reported in a patient treated chronically with thioridazine who ingested a single capsule containing phenylpropanolamine 50 mg and chlorpheniramine 4 mg. However, a causal relationship was not established.

MANAGEMENT: Amphetamine, amphetamine derivatives, and other CNS stimulants should generally not be used, particularly for weight reduction, in patients treated with phenothiazines.

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