Drug Interactions between darifenacin and Meprozine

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.

MONITOR: Coadministration of opioids with anticholinergic agents may result in additive central nervous system (CNS), gastrointestinal, and genitourinary effects. The risk and/or severity of adverse effects such as sedation, dizziness, confusion, cognitive and psychomotor impairment, dry mouth, constipation, and urinary retention may increase. Severe constipation may lead to paralytic ileus in some cases.

MANAGEMENT: Caution and close monitoring of central nervous system, gastrointestinal, and genitourinary adverse effects are recommended when opioids are used with anticholinergic agents. Ambulatory patients should be counseled to avoid hazardous activities requiring mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

MONITOR: Coadministration with darifenacin may increase the plasma concentrations of drugs that are metabolized by CYP450 2D6, including many psychotherapeutic drugs such as tricyclic antidepressants, phenothiazines, and other neuroleptics. The mechanism is decreased clearance due to inhibition of the CYP450 2D6 isoenzyme by darifenacin. According to the product labeling, darifenacin (30 mg once daily) increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of imipramine by 57% and 70%, respectively. These changes were accompanied by a 3.6-fold increase in the mean Cmax and AUC of desipramine, the active metabolite of imipramine. Pharmacodynamically, anticholinergic effects may also increase when darifenacin is used in combination with these drugs. Excessive parasympatholytic effects may result in mydriasis, blurred vision, flushed face, dry skin and mucous membranes, tachycardia, urinary retention, constipation, paralytic ileus, hyperthermia, and heat stroke.

MANAGEMENT: Caution is advised if darifenacin must be used concomitantly with tricyclic antidepressants, phenothiazines, or other neuroleptics. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate whenever darifenacin is added to or withdrawn from therapy. Clinicians should also be alerted to the potential for additive anticholinergic effects during concomitant administration. Patients should be advised to notify their physician promptly if they experience potential symptoms of anticholinergic intoxication such as abdominal pain, fever, heat intolerance, blurred vision, confusion, and/or hallucinations.