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Drug Interactions between bupivacaine / fentanyl and Uritact-EC

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

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Interactions between your drugs

Major

fentaNYL methylene blue

Applies to: bupivacaine / fentanyl 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 "Monoamine oxidase inhibitors and narcotic analgesics: a critical review of the implications for treatment." Br J Psychiatry 151 (1987): 210-2
  2. Zornberg GL, Bodkin JA, Cohen BM "Severe adverse interaction between pethidine and selegiline." Lancet 337 (1991): 246
  3. Pettinger WA, Soyangco FG, Oates JA "Inhibition of monoamine oxidase in man by furazolidone." Clin Pharmacol Ther 9 (1968): 442-7
  4. Schulz R, Antonin KH, Hoffmann E, et al. "Tyramine kinetics and pressor sensitivity during monoamine oxidase inhibition by selegiline." Clin Pharmacol Ther 46 (1989): 528-36
  5. Evans-Prosser CD "The use of pethidine and morphine in the presence of monoamine oxidase inhibitors." Br J Anaesth 40 (1968): 279-82
  6. Goldberg LI "Monoamine oxidase inhibitors: adverse reactions and possible mechanisms." JAMA 190 (1964): 456-62
  7. Vigran IM "Dangerous potentiation of meperidine hydrochloride by pargyline hydrochloride." JAMA 187 (1964): 953-4
  8. Nierenberg DW, Semprebon M "The central nervous system serotonin syndrome." Clin Pharmacol Ther 53 (1993): 84-8
  9. "Product Information. Demerol (meperidine)." Sanofi Winthrop Pharmaceuticals PROD (2002):
  10. Sternbach H "The serotonin syndrome." Am J Psychiatry 148 (1991): 705-13
  11. Starr C "Interaction between pethidine and selegiline." Lancet 337 (1991): 554
  12. Youssef MS, Wilkinson PA "Epidural fentanyl and monoamine oxidase inhibitors." Anaesthesia 43 (1988): 210-2
  13. Noble WH, Baker A "MAO inhibitors and coronary artery surgery: a patient death." Can J Anaesth 39 (1992): 1061-6
  14. "Product Information. Eldepryl (selegiline)." Somerset Pharmaceuticals Inc PROD (2001):
  15. Insler SR, Kraenzler EJ, Licina MG, Savage RM, Starr NJ "Cardiac surgery in a patient taking monoamine oxidase inhibitors - an adverse fentanyl reaction." Anesth Analg 78 (1994): 593-7
  16. Garbutt JC "Potentiation of propoxyphene by phenelzine." Am J Psychiatry 144 (1987): 251-2
  17. Zornberg GL, Hegarty JD "Adverse interaction between propoxyphene and phenelzine." Am J Psychiatry 150 (1993): 1270-1
  18. "Product Information. Duragesic Transdermal System (fentanyl)." Janssen Pharmaceutica, Titusville, NJ.
  19. Limbird LE eds., Gilman AG, Hardman JG "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: McGraw-Hill (1995):
  20. "Product Information. Matulane (procarbazine)." Roche Laboratories PROD (2001):
  21. De Vita VT, Hahn MA, Oliverio VT "Monoamine oxidase inhibition by a new carcinostatic agent, n-isopropyl-a-(2-methylhydrazino)-p-toluamide (MIH). (30590)." Proc Soc Exp Biol Med 120 (1965): 561-5
  22. Michaels I, Serrins M, Shier NQ, Barash PG "Anesthesia for cardiac surgery in patients receiving monoamine oxidase inhibitors." Anesth Analg 63 (1984): 1041-4
  23. Mills KC "Serotonin syndrome: A clinical update." Crit Care Clin 13 (1997): 763
  24. "Product Information. Furoxone (furazolidone)." Roberts Pharmaceutical Corporation PROD (2001):
  25. "Product Information. Actiq (fentanyl)." Abbott Pharmaceutical PROD (2001):
  26. Chan BSH, Graudins A, Whyte IM, Dawson AH, Braitberg G, Duggin GG "Serotonin syndrome resulting from drug interactions." Med J Aust 169 (1998): 523-5
  27. "Product Information. Nardil (phenelzine)." Parke-Davis PROD (2001):
  28. "Product Information. Parnate (tranylcypromine)." SmithKline Beecham PROD (2001):
  29. Weiner AL "Meperidine as a potential cause of serotonin syndrome in the emergency department." Acad Emerg Med 6 (1999): 156-8
  30. Upton R, Graff A, Williamson E, et al. "American Herbal Pharmacopoeia and Therapeutic Compendium. Monograph printed in Herbalgram." Herbalgram 40 (1997): 1-38(monograph)
  31. "Product Information. Marplan (isocarboxazid)." Roche Laboratories PROD (2001):
  32. "Product Information. Meperidine Hydrochloride (meperidine)." Astra-Zeneca Pharmaceuticals (2022):
  33. Martin TG "Serotonin syndrome." Ann Emerg Med 28 (1996): 520-6
  34. Gillman PK "Possible serotonin syndrome with moclobemide and pethidine." Med J Aust 162 (1995): 554
  35. Gillman PK "Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity." Br J Anaesth (2005):
  36. "Product Information. Azilect (rasagiline)." Teva Pharmaceuticals USA (2006):
  37. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  38. Das PK, Warkentin DI, Hewko R, Forrest DL "Serotonin syndrome after concomitant treatment with linezolid and meperidine." Clin Infect Dis 46 (2008): 264-5
  39. Cerner Multum, Inc. "Australian Product Information." O 0
  40. "Product Information. Methylene Blue (methylene blue)." American Regent Laboratories Inc (2012):
View all 40 references

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Moderate

fentaNYL hyoscyamine

Applies to: bupivacaine / fentanyl 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. "Product Information. Demerol (meperidine)." Sanofi Winthrop Pharmaceuticals PROD (2002):
  2. "Product Information. Dolophine (methadone)." Lilly, Eli and Company PROD (2002):
  3. "Product Information. Tylenol with Codeine (acetaminophen-codeine)." Janssen Pharmaceuticals PROD (2001):
  4. "Product Information. Duragesic Transdermal System (fentanyl)." Janssen Pharmaceutica, Titusville, NJ.
  5. "Product Information. Ultram (tramadol)." McNeil Pharmaceutical PROD (2001):
  6. "Product Information. OxyContin (oxycodone)." Purdue Frederick Company PROD (2001):
  7. "Product Information. Kadian (morphine)." Astra-Zeneca Pharmaceuticals PROD (2001):
  8. "Product Information. DepoDur (morphine liposomal)." Endo Laboratories LLC (2004):
  9. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  10. "Product Information. Opana (oxymorphone)." Endo Laboratories LLC (2006):
  11. "Product Information. Nucynta (tapentadol)." PriCara Pharmaceuticals (2009):
  12. "Product Information. Exalgo (hydromorphone)." Covidien (2010):
  13. "Product Information. Belbuca (buprenorphine)." Endo Pharmaceuticals Solutions Inc (2016):
  14. "Product Information. Alfentanil Hydrochloride (alfentanil)." Akorn Inc (2017):
  15. "Product Information. SUFentanil Citrate (sufentanil)." Akorn Inc (2017):
  16. "Product Information. Lortab (acetaminophen-hydrocodone)." Akorn Inc (2017):
  17. "Product Information. Levorphanol Tartrate (levorphanol)." Sentynl Therapeutics (2017):
  18. "Product Information. Naloxone HCl-Pentazocine HCl (naloxone-pentazocine)." Actavis U.S. (Amide Pharmaceutical Inc) (2018):
  19. "Product Information. Apadaz (acetaminophen-benzhydrocodone)." KemPharm, Inc (2018):
View all 19 references

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Drug and food interactions

Major

fentaNYL food

Applies to: bupivacaine / fentanyl

GENERALLY AVOID: Alcohol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics including fentanyl. 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 grapefruit juice during treatment with oral transmucosal formulations of fentanyl may result in increased plasma concentrations of fentanyl, which is primarily metabolized by CYP450 3A4 isoenzyme in the liver and intestine. Certain compounds present in grapefruit are known to inhibit CYP450 3A4 and may increase the bioavailability of swallowed fentanyl (reportedly up to 75% of a dose) and/or decrease its systemic clearance. The clinical significance is unknown. In 12 healthy volunteers, consumption of 250 mL regular-strength grapefruit juice the night before and 100 mL double-strength grapefruit juice one hour before administration of oral transmucosal fentanyl citrate (600 or 800 mcg lozenge) did not significantly affect fentanyl pharmacokinetics, overall extent of fentanyl-induced miosis (miosis AUC), or subjective self-assessment of various clinical effects compared to control. However, pharmacokinetic alterations associated with interactions involving grapefruit juice are often subject to a high degree of interpatient variability. The possibility of significant interaction in some patients should be considered.

MANAGEMENT: Patients should not consume alcoholic beverages or use drug products that contain alcohol during treatment with fentanyl. Any history of alcohol or illicit drug use should be considered when prescribing fentanyl, and therapy initiated at a lower dosage if necessary. Patients should be closely monitored for signs and symptoms of sedation, respiratory depression, and hypotension. Due to a high degree of interpatient variability with respect to grapefruit juice interactions, patients treated with fentanyl should preferably avoid the consumption of grapefruit and grapefruit juice. In addition, patients receiving transdermal formulations of fentanyl should be cautioned that drug interactions and drug effects may be observed for a prolonged period beyond removal of the patch, as significant amounts of fentanyl are absorbed from the skin for 17 hours or more after the patch is removed.

References

  1. "Product Information. Duragesic Transdermal System (fentanyl)." Janssen Pharmaceutica, Titusville, NJ.
  2. "Product Information. Actiq (fentanyl)." Abbott Pharmaceutical PROD (2001):
  3. Kharasch ED, Whittington D, Hoffer C "Influence of Hepatic and Intestinal Cytochrome P4503A Activity on the Acute Disposition and Effects of Oral Transmucosal Fentanyl Citrate." Anesthesiology 101 (2004): 729-737
  4. Tateishi T, Krivoruk Y, Ueng YF, Wood AJ, Guengerich FP, Wood M "Identification of human cytochrome P-450 3A4 as the enzyme responsible for fentanyl and sufentanil N-dealkylation." Anesth Analg 82 (1996): 167-72
  5. Labroo RB, Paine MF, Thummel KE, Kharasch ED "Fentanyl metabolism by human hepatic and intestinal cytochrome P450 3A4: implicaitons for interindividual variability in disposition, efficacy, and drug interactions." Drug Metab Dispos 25 (1997): 1072-80
View all 5 references

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

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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.

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