Drug Interactions between Meprozine and mesoridazine

GENERALLY AVOID: Concomitant use of opioids with central nervous system (CNS) depressants (e.g., benzodiazepines, sedatives/hypnotics, anxiolytics, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol) may result in profound sedation, respiratory depression, coma, and death. The risk of hypotension may also be increased with some CNS depressants (e.g., alcohol, benzodiazepines, antipsychotics).

MANAGEMENT: The use of opioids in conjunction with benzodiazepines or other CNS depressants should generally be avoided unless alternative treatment options are inadequate. If coadministration is necessary, the dosage and duration of each drug should be limited to the minimum required to achieve desired clinical effect, with cautious titration and dosage adjustments when needed. Patients should be monitored closely for signs and symptoms of respiratory depression and sedation, and advised to avoid driving or operating hazardous machinery until they know how these medications affect them. Cough medications containing opioids (e.g., codeine, hydrocodone) should not be prescribed to patients using benzodiazepines or other CNS depressants including alcohol. For patients who have been receiving extended therapy with both an opioid and a benzodiazepine or antipsychotic and require discontinuation of either medication, a gradual tapering of dose is advised, since abrupt withdrawal may lead to withdrawal symptoms.

MONITOR CLOSELY: Concomitant use of some antipsychotics with other agents that can reduce gastrointestinal motility, such as opioids, may increase the risk of ileus and constipation. Certain antipsychotic agents, including phenothiazines, thioxanthenes, clozapine, olanzapine and quetiapine, can cause gastrointestinal adverse effects in association with their anticholinergic activity. Potential complications may include paralytic ileus, intestinal obstruction, fecal impaction, megacolon, and intestinal ischemia or infarction, particularly with agents that have potent anticholinergic effects such as clozapine and quetiapine.

MANAGEMENT: Close monitoring of bowel function is recommended during concomitant use of opioids with antipsychotic agents that exhibit anticholinergic effects, particularly in the elderly. Delayed diagnosis and treatment of constipation may increase the risk of severe complications, which can result in hospitalization, surgery, and death. Patients should be advised to maintain adequate hydration, physical activity and fiber intake, and to report any changes in the frequency or character of bowel movements as well as signs and symptoms of potential complications of ileus such as nausea, vomiting, abdominal distension, and abdominal pain. If constipation or gastrointestinal hypomotility is identified, monitor closely and treat promptly with appropriate laxatives to prevent severe complications. Consider prophylactic laxatives in high risk patients, such as those with a history of constipation, colonic disease, or lower abdominal surgery.

CONTRAINDICATED: Mesoridazine can cause dose-related prolongation of the QT interval. Theoretically, coadministration with other agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. Mesoridazine overdosage has been associated with ventricular arrhythmias and 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). The extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s). In addition, certain agents with anticholinergic properties (e.g., sedating antihistamines; antispasmodics; neuroleptics; phenothiazines; skeletal muscle relaxants; tricyclic antidepressants; disopyramide) may have additive parasympatholytic and central nervous system-depressant effects when used in combination with mesoridazine. Excessive parasympatholytic effects may include paralytic ileus, hyperthermia, mydriasis, blurred vision, tachycardia, urinary retention, psychosis, and seizures.

MANAGEMENT: Coadministration of mesoridazine with other drugs that can prolong the QT interval is considered contraindicated.

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.