Drug Interactions between Denzapine and DHC Plus

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.

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Caffeine may increase clozapine serum concentrations and exacerbate psychotic symptoms. The mechanism is unknown but may be related to competition for the same metabolic pathway. No specific intervention is necessary; however, if an interaction is suspected it is recommended that caffeine intake be avoided.

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