Drug Interactions between aspirin / carisoprodol / codeine and desmopressin

GENERALLY AVOID: Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants (e.g., nonbenzodiazepine 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, phenothiazines).

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 and require discontinuation of either medication, a gradual tapering of dose is advised, since abrupt withdrawal may lead to withdrawal symptoms. Severe cases of benzodiazepine withdrawal, primarily in patients who have received excessive doses over a prolonged period, may result in numbness and tingling of extremities, hypersensitivity to light and noise, hallucinations, and epileptic seizures.

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MONITOR: Coadministration with opiates may increase the plasma concentrations and pharmacologic effects of oral desmopressin. The risk of water intoxication and/or hyponatremia may be increased. In 18 healthy subjects, loperamide 4 mg given at 24 hours, 12 hours, and 1 hour before a single 400 mcg oral dose of desmopressin increased the peak plasma concentration (Cmax) of desmopressin by 2.3-fold and its systemic exposure (AUC) by 3.1-fold. Pretreatment with loperamide also increased the median time to reach peak desmopressin concentration (Tmax) from 1.3 to 2 hours, but did not affect the terminal elimination half-life. Although not investigated, other opiates may interact similarly with desmopressin by slowing gastrointestinal motility. In addition, some opiate analgesics such as fentanyl, meperidine, morphine, oxycodone, and tramadol have been associated with reports of hyponatremia, sometimes secondary to the syndrome of inappropriate antidiuretic hormone secretion (SIADH). These effects may be additive with those of desmopressin and probably stem from agonist action on morphinic receptors, resulting in increased release of antidiuretic hormone.

MANAGEMENT: Caution is recommended if desmopressin is used in combination with opiates. Serum electrolytes, especially sodium, as well as BUN and creatinine should be monitored regularly. Patients should be advised to seek immediate medical attention if they develop early signs and symptoms of water intoxication or hyponatremia such as anorexia, nausea, vomiting, drowsiness, lethargy, weakness, listlessness, headache, confusion, difficulty concentrating, memory impairment, anuria, and weight gain. Early treatment may help prevent progression to seizure, coma, respiratory arrest, and death.

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Limited data have shown that desmopressin (DDAVP) can significantly reduce aspirin-induced increases in bleeding times. The DDAVP effect on bleeding time correlates closely with increases in the plasma concentration of von Willebrand factor. The clinical consequences of this interaction are not known.

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