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Drug Interactions between desmopressin and Morphine Sulfate IR

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

morphine desmopressin

Applies to: Morphine Sulfate IR (morphine) and desmopressin

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.

References

  1. Appel WC "Possible roles of normeperidine and hyponatremia in a postoperative death." Can Med Assoc J 137 (1987): 912-3
  2. "Product Information. MS Contin (morphine)." Purdue Frederick Company PROD (2002):
  3. "Product Information. DDAVP (desmopressin)." Rhone Poulenc Rorer PROD (2001):
  4. "Product Information. Stimate (desmopressin)." Forest Pharmaceuticals PROD (2001):
  5. "Product Information. OxyContin (oxycodone)." Purdue Frederick Company PROD (2001):
  6. Callreus T, Lundahl J, Hoglund P, Bengtsson P "Changes in gastrointestinal motility influence the absorption of desmopressin." Eur J Clin Pharmacol 55 (1999): 305-9
  7. Kokko H, Hall PD, Afrin LB "Fentanyl-associated syndrome of inappropriate antidiuretic hormone secretion." Pharmacotherapy 22 (2002): 1188-92
  8. Canadian Pharmacists Association "e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink" (2006):
  9. Sarret D, Le Berre JP, Zemraoui N "Tramadol-induced hyponatremia." Am J Kidney Dis 52 (2008): 1026; author reply 1027
View all 9 references

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Drug and food interactions

Major

morphine food

Applies to: Morphine Sulfate IR (morphine)

GENERALLY AVOID: Alcohol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics including morphine and diamorphine. Concomitant use may result in additive CNS depression and impairment of judgment, thinking, and psychomotor skills. In more severe cases, hypotension, respiratory depression, profound sedation, coma, or even death may occur.

GENERALLY AVOID: Consumption of alcohol while taking some sustained-release formulations of morphine may cause rapid release of the drug, resulting in high systemic levels of morphine that may be potentially lethal. Alcohol apparently can disrupt the release mechanism of some sustained-release formulations. The interaction was observed in in vitro studies using a 24-hour morphine formulation (Avinza 30 mg capsule, available in the U.S. from Ligand Pharmaceuticals). When the capsule was mixed with 900 mL of buffer solutions containing ethanol 20% and 40%, the dose of morphine that was released was alcohol concentration-dependent, leading to a more rapid release of morphine. Although the clinical relevance of this finding is unknown, 'dose-dumping' into the bloodstream is conceivable.

MANAGEMENT: Until more information is available, patients taking sustained-release formulations of morphine should not consume alcohol or use medications that contain alcohol. In general, potent narcotics such as morphine or diamorphine should not be combined with alcohol.

References

  1. "Product Information. Avinza (morphine)." Ligand Pharmaceuticals (2005):
  2. Ghalie R "Dear Health Care Professional. http://www.fda.gov/medwatch/safety/2005/AVINZA_DHCP_Letter_Oct2005.pdf" (2005):
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  4. Cerner Multum, Inc. "Canadian Product Information." O 0 (2015):
View all 4 references

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Minor

desmopressin food

Applies to: desmopressin

Food may decrease the rate and extent of absorption of desmopressin following oral administration. In 16 healthy, nonsmoking volunteers, administration of a single 400 mcg oral dose of desmopressin concomitantly with a standardized meal (27% fat) resulted in a 52% decrease in the peak plasma concentration (Cmax) of desmopressin and a 43% decrease in systemic exposure (AUC) compared to administration in the fasting state. The Cmax and AUC were still reduced by 46% and 41%, respectively, when desmopressin was administered 1.5 hours after eating. Both feeding regimens prolonged the time to reach peak plasma concentration (Tmax) from 1 hour to 1.5 hours. However, the pharmacodynamic effects of desmopressin were not affected as assessed by urine volume and osmolality for at least 4 hours postdose. The degree of antidiuresis was similar in the absence of food and when the drug was taken with or 1.5 hours after eating. These findings would suggest a fairly minor clinical impact of the interaction in most patients, especially since oral desmopressin is intended for administration at bedtime. Nevertheless, the possibility of food effects should be considered before increasing the dose whenever a diminution of effect is noted. A significant interaction is not expected to occur with the sublingual formulation, since absorption occurs primarily in the oral mucosa, pharynx, and esophagus.

References

  1. "Product Information. DDAVP (desmopressin)." Rhone Poulenc Rorer PROD (2001):
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  3. Canadian Pharmacists Association "e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink" (2006):

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

See also

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

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