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Drug Interactions between Darvon-N and Syndros

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

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Interactions between your drugs

Major

propoxyphene droNABinol

Applies to: Darvon-N (propoxyphene) and Syndros (dronabinol)

MONITOR CLOSELY: Sedatives, tranquilizers, muscle relaxants, antidepressants, and other central nervous system (CNS) depressants may have additive CNS- and/or respiratory-depressant effects with propoxyphene. Misuse of propoxyphene, either alone or in combination with other CNS depressants, has been a major cause of drug-related deaths, particularly in patients with a history of emotional disturbances, suicidal ideation, or alcohol and drug abuse. In a large Canadian study, propoxyphene use was also associated with a 60% increased risk of hip fracture in the elderly, and the risk was further increased by concomitant use of psychotropic agents (sedatives, antidepressants, neuroleptics), presumably due to additive psychomotor impairment. Therefore, these drugs may constitute a dangerous combination in certain susceptible populations. Pharmacokinetically, propoxyphene is an inhibitor of CYP450 2D6 and may increase the plasma concentrations of many psychotropic agents that are metabolized by the isoenzyme such as phenothiazines, haloperidol, risperidone, phenobarbital, and some tricyclic antidepressants and serotonin reuptake inhibitors.

MANAGEMENT: Caution is advised if propoxyphene is used with sedatives, tranquilizers, muscle relaxants, antidepressants, and other CNS depressants, particularly in the elderly and in patients with a history of emotional disturbances, suicidal ideation, or alcohol and drug abuse. Dosage reductions may be appropriate. Patients should be monitored for potentially excessive or prolonged CNS and respiratory depression and other CNS adverse effects. Patients should be warned not to exceed recommended dosages, to avoid alcohol, and to avoid activities requiring mental alertness until they know how these agents affect them.

References

  1. Abernethy DR, Greenblatt DJ, Morse DS, Shader RI "Interaction of propoxyphene with diazepam, alprazolam and lorazepam." Br J Clin Pharmacol 19 (1985): 51-7
  2. Hansen BS, Dam M, Brandt J, et al. "Influence of dextropropoxyphene on steady state serum levels and protein binding of three anti-epileptic drugs in man." Acta Neurol Scand 61 (1980): 357-67
  3. Abernethy DR, Greenblatt DJ, Steel K, Shader RI "Impairment of hepatic drug oxidation by propoxyphene." Ann Intern Med 97 (1982): 223-4
  4. Peterson GR, Covault HP, Hostetler RM "Acute inhibition of microsomal drug metabolism by propoxphene in narcotic tolerant/dependent mice." Life Sci 22 (1978): 2087-96
  5. Shorr RI, Griffin MR, Daugherty JR, Ray WA "Opioid analgesics and the risk of hip fracture in the elderly: codeine and propoxyphene." J Gerontol 47 (1992): m111-5
  6. Puckett WH Jr, Visconti JA "Orphenadrine and propoxyphene." N Engl J Med 283 (1970): 544
  7. Pearson RE, Salter FJ "Drug interaction? Orphenadrine with propoxyphene." N Engl J Med 282 (1970): 1215
  8. "Product Information. Darvon (propoxyphene)." Lilly, Eli and Company PROD (2001):
View all 8 references

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Drug and food interactions

Major

propoxyphene food

Applies to: Darvon-N (propoxyphene)

GENERALLY AVOID: Alcohol may have additive CNS- and/or respiratory-depressant effects with propoxyphene. Misuse of propoxyphene, either alone or in combination with other CNS depressants, has been a major cause of drug-related deaths, particularly in patients with a history of emotional disturbances, suicidal ideation, or alcohol and drug abuse.

MANAGEMENT: The use of alcohol during propoxyphene therapy should be avoided. Patients should be warned not to exceed the recommended dosage of propoxyphene and to avoid activities requiring mental alertness until they know how these agents affect them.

References

  1. "Product Information. Darvon (propoxyphene)." Lilly, Eli and Company PROD (2001):

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Moderate

droNABinol food

Applies to: Syndros (dronabinol)

GENERALLY AVOID: Alcohol may potentiate some of the effects of CNS-active and/or CNS-toxic agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

GENERALLY AVOID: Grapefruit and/or grapefruit juice may increase the plasma concentrations and effects of drugs that are substrates of the CYP450 3A4 isoenzyme. The proposed mechanism is inhibition of CYP450 3A4 mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. Because pharmacokinetic interactions involving grapefruit juice are often subject to a high degree of interpatient variability, the extent to which a given patient may be affected is difficult to predict.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit the consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete 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. It may be advisable for patients to avoid consumption of grapefruit, grapefruit juice, or supplements that contain grapefruit during treatment with drugs that undergo metabolism by CYP450 3A4. Orange juice is not expected to interact with these drugs.

References

  1. Bailey DG, Arnold JMO, Spence JD "Grapefruit juice and drugs - how significant is the interaction." Clin Pharmacokinet 26 (1994): 91-8
  2. Yamreudeewong W, Henann NE, Fazio A, Lower DL, Cassidy TG "Drug-food interactions in clinical practice." J Fam Pract 40 (1995): 376-84
  3. "Grapefruit juice interactions with drugs." Med Lett Drugs Ther 37 (1995): 73-4
  4. Hukkinen SK, Varhe A, Olkkola KT, Neuvonen PJ "Plasma concentrations of triazolam are increased by concomitant ingestion of grapefruit juice." Clin Pharmacol Ther 58 (1995): 127-31
  5. Ozdemir M, Aktan Y, Boydag BS, Cingi MI, Musmul A "Interaction between grapefruit juice and diazepam in humans." Eur J Drug Metab Pharmacokinet 23 (1998): 55-9
  6. Bailey DG, Malcolm J, Arnold O, Spence JD "Grapefruit juice-drug interactions." Br J Clin Pharmacol 46 (1998): 101-10
  7. Garg SK, Kumar N, Bhargava VK, Prabhakar SK "Effect of grapefruit juice on carbamazepine bioavailability in patients with epilepsy." Clin Pharmacol Ther 64 (1998): 286-8
  8. Lee AJ, Chan WK, Harralson AF, Buffum J, Bui BCC "The effects of grapefruit juice on sertraline metabolism: An in vitro and in vivo study." Clin Ther 21 (1999): 1890-9
  9. Dresser GK, Spence JD, Bailey DG "Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition." Clin Pharmacokinet 38 (2000): 41-57
  10. Gunston GD, Mehta U "Potentially serious drug interactions with grapefruit juice." S Afr Med J 90 (2000): 41
  11. Flanagan D "Understanding the grapefruit-drug interaction." Gen Dent 53 (2005): 282-5; quiz 286
  12. "Product Information. Syndros (dronabinol)." Insys Therapeutics Inc (2017):
  13. "Product Information. Dronabinol (dronabinol)." Watson Pharmaceuticals (2017):
View all 13 references

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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.

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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

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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