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Drug Interactions between Darvon Compound-65 and Uritact-EC

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

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Interactions between your drugs

Major

propoxyphene methylene blue

Applies to: Darvon Compound-65 (aspirin / caffeine / propoxyphene) and Uritact-EC (hyoscyamine / methenamine / methylene blue / phenyl salicylate)

CONTRAINDICATED: Coadministration of monoamine oxidase inhibitors (MAOIs) with certain opioids has been associated with rare reports of severe and fatal adverse reactions. There appear to be two types of interaction, an excitatory and a depressive one. Symptoms of the excitatory reaction may include agitation, headache, diaphoresis, hyperpyrexia, flushing, shivering, myoclonus, rigidity, tremor, diarrhea, hypertension, tachycardia, seizures, and coma. Death has occurred in some cases. The exact mechanism of interaction is unknown, but may involve excessive serotonergic activity in the central nervous system (i.e., serotonin syndrome). The interaction is unpredictable and has been reported primarily with meperidine or fentanyl and various MAOIs including phenelzine, tranylcypromine, linezolid, moclobemide, and selegiline. Fatal hyperpyrexia and hypertension have also been observed in animal studies with meperidine and phenelzine or furazolidone. In contrast, symptoms of the depressive reaction probably stem from potentiation of CNS effects by MAOIs and include respiratory depression, cyanosis, hypotension, and coma.

MANAGEMENT: Meperidine and fentanyl should not be used with MAOIs or other agents that possess MAOI activity (e.g., furazolidone, linezolid, methylene blue, procarbazine). Some manufacturers of MAOIs also contraindicate the concomitant use of propoxyphene and methadone due to their possible serotonergic effects. At least 14 days should elapse between discontinuation of MAOI therapy and initiation of treatment with these opioids. Although morphine may also have significant CNS interactions with MAOIs, it is generally considered a safer alternative in patients treated with MAOIs who require a narcotic analgesic. A sensitivity test should be performed in which repeated, small, incremental doses of morphine are administered over the course of several hours while overall clinical status and vital signs are carefully monitored.

References

  1. Browne B, Linter S (1987) "Monoamine oxidase inhibitors and narcotic analgesics: a critical review of the implications for treatment." Br J Psychiatry, 151, p. 210-2
  2. Zornberg GL, Bodkin JA, Cohen BM (1991) "Severe adverse interaction between pethidine and selegiline." Lancet, 337, p. 246
  3. Pettinger WA, Soyangco FG, Oates JA (1968) "Inhibition of monoamine oxidase in man by furazolidone." Clin Pharmacol Ther, 9, p. 442-7
  4. Schulz R, Antonin KH, Hoffmann E, et al. (1989) "Tyramine kinetics and pressor sensitivity during monoamine oxidase inhibition by selegiline." Clin Pharmacol Ther, 46, p. 528-36
  5. Evans-Prosser CD (1968) "The use of pethidine and morphine in the presence of monoamine oxidase inhibitors." Br J Anaesth, 40, p. 279-82
  6. Goldberg LI (1964) "Monoamine oxidase inhibitors: adverse reactions and possible mechanisms." JAMA, 190, p. 456-62
  7. Vigran IM (1964) "Dangerous potentiation of meperidine hydrochloride by pargyline hydrochloride." JAMA, 187, p. 953-4
  8. Nierenberg DW, Semprebon M (1993) "The central nervous system serotonin syndrome." Clin Pharmacol Ther, 53, p. 84-8
  9. (2002) "Product Information. Demerol (meperidine)." Sanofi Winthrop Pharmaceuticals
  10. Sternbach H (1991) "The serotonin syndrome." Am J Psychiatry, 148, p. 705-13
  11. Starr C (1991) "Interaction between pethidine and selegiline." Lancet, 337, p. 554
  12. Youssef MS, Wilkinson PA (1988) "Epidural fentanyl and monoamine oxidase inhibitors." Anaesthesia, 43, p. 210-2
  13. Noble WH, Baker A (1992) "MAO inhibitors and coronary artery surgery: a patient death." Can J Anaesth, 39, p. 1061-6
  14. (2001) "Product Information. Eldepryl (selegiline)." Somerset Pharmaceuticals Inc
  15. Insler SR, Kraenzler EJ, Licina MG, Savage RM, Starr NJ (1994) "Cardiac surgery in a patient taking monoamine oxidase inhibitors - an adverse fentanyl reaction." Anesth Analg, 78, p. 593-7
  16. Garbutt JC (1987) "Potentiation of propoxyphene by phenelzine." Am J Psychiatry, 144, p. 251-2
  17. Zornberg GL, Hegarty JD (1993) "Adverse interaction between propoxyphene and phenelzine." Am J Psychiatry, 150, p. 1270-1
  18. "Product Information. Duragesic Transdermal System (fentanyl)." Janssen Pharmaceutica, Titusville, NJ.
  19. Limbird LE eds., Gilman AG, Hardman JG (1995) "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: McGraw-Hill
  20. (2001) "Product Information. Matulane (procarbazine)." Roche Laboratories
  21. De Vita VT, Hahn MA, Oliverio VT (1965) "Monoamine oxidase inhibition by a new carcinostatic agent, n-isopropyl-a-(2-methylhydrazino)-p-toluamide (MIH). (30590)." Proc Soc Exp Biol Med, 120, p. 561-5
  22. Michaels I, Serrins M, Shier NQ, Barash PG (1984) "Anesthesia for cardiac surgery in patients receiving monoamine oxidase inhibitors." Anesth Analg, 63, p. 1041-4
  23. Mills KC (1997) "Serotonin syndrome: A clinical update." Crit Care Clin, 13, p. 763
  24. (2001) "Product Information. Furoxone (furazolidone)." Roberts Pharmaceutical Corporation
  25. (2001) "Product Information. Actiq (fentanyl)." Abbott Pharmaceutical
  26. Chan BSH, Graudins A, Whyte IM, Dawson AH, Braitberg G, Duggin GG (1998) "Serotonin syndrome resulting from drug interactions." Med J Aust, 169, p. 523-5
  27. (2001) "Product Information. Nardil (phenelzine)." Parke-Davis
  28. (2001) "Product Information. Parnate (tranylcypromine)." SmithKline Beecham
  29. Weiner AL (1999) "Meperidine as a potential cause of serotonin syndrome in the emergency department." Acad Emerg Med, 6, p. 156-8
  30. Upton R, Graff A, Williamson E, et al. (1997) "American Herbal Pharmacopoeia and Therapeutic Compendium. Monograph printed in Herbalgram." Herbalgram, 40, 1-38(monograph)
  31. (2001) "Product Information. Marplan (isocarboxazid)." Roche Laboratories
  32. (2022) "Product Information. Meperidine Hydrochloride (meperidine)." Astra-Zeneca Pharmaceuticals
  33. Martin TG (1996) "Serotonin syndrome." Ann Emerg Med, 28, p. 520-6
  34. Gillman PK (1995) "Possible serotonin syndrome with moclobemide and pethidine." Med J Aust, 162, p. 554
  35. Gillman PK (2005) "Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity." Br J Anaesth
  36. (2006) "Product Information. Azilect (rasagiline)." Teva Pharmaceuticals USA
  37. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  38. Das PK, Warkentin DI, Hewko R, Forrest DL (2008) "Serotonin syndrome after concomitant treatment with linezolid and meperidine." Clin Infect Dis, 46, p. 264-5
  39. Cerner Multum, Inc. "Australian Product Information."
  40. (2012) "Product Information. Methylene Blue (methylene blue)." American Regent Laboratories Inc
View all 40 references

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Moderate

propoxyphene hyoscyamine

Applies to: Darvon Compound-65 (aspirin / caffeine / propoxyphene) and Uritact-EC (hyoscyamine / methenamine / methylene blue / phenyl salicylate)

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.

References

  1. (2002) "Product Information. Demerol (meperidine)." Sanofi Winthrop Pharmaceuticals
  2. (2002) "Product Information. Dolophine (methadone)." Lilly, Eli and Company
  3. (2001) "Product Information. Tylenol with Codeine (acetaminophen-codeine)." Janssen Pharmaceuticals
  4. "Product Information. Duragesic Transdermal System (fentanyl)." Janssen Pharmaceutica, Titusville, NJ.
  5. (2001) "Product Information. Ultram (tramadol)." McNeil Pharmaceutical
  6. (2001) "Product Information. OxyContin (oxycodone)." Purdue Frederick Company
  7. (2001) "Product Information. Kadian (morphine)." Astra-Zeneca Pharmaceuticals
  8. (2004) "Product Information. DepoDur (morphine liposomal)." Endo Laboratories LLC
  9. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  10. (2006) "Product Information. Opana (oxymorphone)." Endo Laboratories LLC
  11. (2009) "Product Information. Nucynta (tapentadol)." PriCara Pharmaceuticals
  12. (2010) "Product Information. Exalgo (hydromorphone)." Covidien
  13. (2016) "Product Information. Belbuca (buprenorphine)." Endo Pharmaceuticals Solutions Inc
  14. (2017) "Product Information. Alfentanil Hydrochloride (alfentanil)." Akorn Inc
  15. (2017) "Product Information. SUFentanil Citrate (sufentanil)." Akorn Inc
  16. (2017) "Product Information. Lortab (acetaminophen-hydrocodone)." Akorn Inc
  17. (2017) "Product Information. Levorphanol Tartrate (levorphanol)." Sentynl Therapeutics
  18. (2018) "Product Information. Naloxone HCl-Pentazocine HCl (naloxone-pentazocine)." Actavis U.S. (Amide Pharmaceutical Inc)
  19. (2018) "Product Information. Apadaz (acetaminophen-benzhydrocodone)." KemPharm, Inc
View all 19 references

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Moderate

aspirin phenyl salicylate

Applies to: Darvon Compound-65 (aspirin / caffeine / propoxyphene) and Uritact-EC (hyoscyamine / methenamine / methylene blue / phenyl salicylate)

GENERALLY AVOID: Concomitant use of more than one salicylate at a time may increase the potential for gastrointestinal adverse effects (e.g., inflammation, pain, bleeding, ulceration) and bruising or bleeding.

MANAGEMENT: Concomitant use of more than one salicylate at a time should generally be avoided. Patients treated with a salicylate should be advised to take it with food and to immediately report signs and symptoms of GI ulceration and bleeding such as severe abdominal pain, dizziness, lightheadedness, and the appearance of black, tarry stools.

References

  1. (2001) "Product Information. Pepto-Bismol (bismuth subsalicylate)." Procter and Gamble Pharmaceuticals
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics."

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Minor

aspirin caffeine

Applies to: Darvon Compound-65 (aspirin / caffeine / propoxyphene) and Darvon Compound-65 (aspirin / caffeine / propoxyphene)

One study has reported that coadministration of caffeine and aspirin lead to a 25% increase in the rate of appearance and 17% increase in maximum concentration of salicylate in the plasma. A significantly higher area under the plasma concentration time curve of salicylate was also reported when both drugs were administered together. The exact mechanism of this interaction has not been specified. Physicians and patients should be aware that coadministration of aspirin and caffeine may lead to higher salicylate levels faster.

References

  1. Yoovathaworn KC, Sriwatanakul K, Thithapandha A (1986) "Influence of caffeine on aspirin pharmacokinetics." Eur J Drug Metab Pharmacokinet, 11, p. 71-6

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Drug and food interactions

Major

propoxyphene food

Applies to: Darvon Compound-65 (aspirin / caffeine / 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. (2001) "Product Information. Darvon (propoxyphene)." Lilly, Eli and Company

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Moderate

aspirin food

Applies to: Darvon Compound-65 (aspirin / caffeine / propoxyphene)

GENERALLY AVOID: The concurrent use of aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) and ethanol may lead to gastrointestinal (GI) blood loss. The mechanism may be due to a combined local effect as well as inhibition of prostaglandins leading to decreased integrity of the GI lining.

MANAGEMENT: Patients should be counseled on this potential interaction and advised to refrain from alcohol consumption while taking aspirin or NSAIDs.

References

  1. (2002) "Product Information. Motrin (ibuprofen)." Pharmacia and Upjohn

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Moderate

hyoscyamine food

Applies to: Uritact-EC (hyoscyamine / methenamine / methylene blue / phenyl salicylate)

GENERALLY AVOID: Use of anticholinergic agents with alcohol may result in sufficient impairment of attention so as to render driving and operating machinery more hazardous. In addition, the potential for abuse may be increased with the combination. The mechanism of interaction is not established but may involve additive depressant effects on the central nervous system. No effect of oral propantheline or atropine on blood alcohol levels was observed in healthy volunteers when administered before ingestion of a standard ethanol load. However, one study found impairment of attention in subjects given atropine 0.5 mg or glycopyrrolate 1 mg in combination with alcohol.

MANAGEMENT: Alcohol should generally be avoided during therapy with anticholinergic agents. Patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them.

References

  1. Linnoila M (1973) "Drug effects on psychomotor skills related to driving: interaction of atropine, glycopyrrhonium and alcohol." Eur J Clin Pharmacol, 6, p. 107-12

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Minor

caffeine food

Applies to: Darvon Compound-65 (aspirin / caffeine / propoxyphene)

The effect of grapefruit juice on the pharmacologic activity of caffeine is controversial. One report suggests that grapefruit juice increases the effect of caffeine. The proposed mechanism is inhibition of cytochrome P-450 metabolism of caffeine. However, a well-conducted pharmacokinetic/pharmacodynamic study did not demonstrate this effect. The clinical significance of this potential interaction is unknown.

References

  1. (1995) "Grapefruit juice interactions with drugs." Med Lett Drugs Ther, 37, p. 73-4
  2. Maish WA, Hampton EM, Whitsett TL, Shepard JD, Lovallo WR (1996) "Influence of grapefruit juice on caffeine pharmacokinetics and pharmacodynamics." Pharmacotherapy, 16, p. 1046-52

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Minor

aspirin food

Applies to: Darvon Compound-65 (aspirin / caffeine / propoxyphene)

One study has reported that coadministration of caffeine and aspirin lead to a 25% increase in the rate of appearance and 17% increase in maximum concentration of salicylate in the plasma. A significantly higher area under the plasma concentration time curve of salicylate was also reported when both drugs were administered together. The exact mechanism of this interaction has not been specified. Physicians and patients should be aware that coadministration of aspirin and caffeine may lead to higher salicylate levels faster.

References

  1. Yoovathaworn KC, Sriwatanakul K, Thithapandha A (1986) "Influence of caffeine on aspirin pharmacokinetics." Eur J Drug Metab Pharmacokinet, 11, p. 71-6

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Therapeutic duplication warnings

Therapeutic duplication is the use of more than one medicine from the same drug category or therapeutic class to treat the same condition. This can be intentional in cases where drugs with similar actions are used together for demonstrated therapeutic benefit. It can also be unintentional in cases where a patient has been treated by more than one doctor, or had prescriptions filled at more than one pharmacy, and can have potentially adverse consequences.

Duplication

Nonsteroidal anti-inflammatories

Therapeutic duplication

The recommended maximum number of medicines in the 'nonsteroidal anti-inflammatories' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'nonsteroidal anti-inflammatories' category:

  • Darvon Compound-65 (aspirin/caffeine/propoxyphene)
  • Uritact-EC (hyoscyamine/methenamine/methylene blue/phenyl salicylate)

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.

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

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

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