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Drug Interactions between Azilect and MHP-A

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

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Interactions between your drugs

Major

methylene blue rasagiline

Applies to: MHP-A (hyoscyamine / methenamine / methylene blue / phenyl salicylate) and Azilect (rasagiline)

CONTRAINDICATED: Coadministration of methylene blue with serotonergic agents may potentiate the risk of serotonin syndrome, which is a rare but serious and potentially fatal condition thought to result from hyperstimulation of brainstem 5-HT1A and 2A receptors. Current research suggests that methylene blue has structural properties similar to monoamine oxidase inhibitors (MAOIs). As such, it may enhance serotonergic effects by inhibiting serotonin metabolism. Symptoms of the serotonin syndrome may include mental status changes such as irritability, altered consciousness, confusion, hallucination, and coma; autonomic dysfunction such as tachycardia, hyperthermia, diaphoresis, shivering, blood pressure lability, and mydriasis; neuromuscular abnormalities such as hyperreflexia, myoclonus, tremor, rigidity, and ataxia; and gastrointestinal symptoms such as abdominal cramping, nausea, vomiting, and diarrhea. Serotonin syndrome has been reported when methylene blue was administered intravenously at dosages ranging from 1 to 8 mg/kg to patients exposed to drugs that interfere with serotonin reuptake. Several cases required admission to the intensive care unit. The risk of administering methylene blue intravenously at dosages less than 1 mg/kg or by non-intravenous routes (e.g., orally or by local injection) is unclear, although the potential for interaction with serotonergic agents should be considered.

MANAGEMENT: Serotonergic agents should not be used in patients receiving methylene blue intravenously. Most serotonergic psychiatric drugs should be stopped 1 to 2 weeks (i.e., 4 to 5 half-lives) prior to treatment with methylene blue if possible, while others such as fluoxetine may require discontinuation up to 5 weeks in advance due to its prolonged half-life. Treatment with serotonergic medications may be resumed 24 hours after the last dose of methylene blue. In patients receiving methylene blue who require urgent treatment of a psychiatric condition, other interventions including hospitalization should be considered. Conversely, when urgent treatment with methylene blue is required (e.g., methemoglobinemia, ifosfamide-induced encephalopathy, cyanide poisoning) in patients receiving serotonergic agents, the benefit of methylene blue treatment should be weighed against the risk of serotonin toxicity. If a decision is made to use methylene blue, the serotonergic drug must be immediately stopped, and the patient closely monitored for emergent symptoms of CNS toxicity for two weeks (five weeks if fluoxetine was taken; three weeks if vortioxetine was taken) or until 24 hours after the last dose of methylene blue, whichever comes first. Patients and/or their caregivers should be advised to seek medical attention if potential symptoms of serotonin syndrome develop.

References

  1. Boyer EW, Shannon M "The serotonin syndrome." N Engl J Med 352 (2005): 1112-20
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  3. Ng BK, Cameron AJ, Liang R, Rahman H "[Serotonin syndrome following methylene blue infusion during parathyroidectomy: a case report and literature review]" Can J Anaesth 55 (2008): 36-41
  4. Gillman PK "Methylene blue is a potent monoamine oxidase inhibitor." Can J Anaesth 55 (2008): 311-2; author reply 312
  5. Khavandi A, Whitaker J, Gonna H "Serotonin toxicity precipitated by concomitant use of citalopram and methylene blue." Med J Aust 189 (2008): 534-5
  6. Ng BK, Cameron AJ "The role of methylene blue in serotonin syndrome: a systematic review." Psychosomatics 51 (2010): 194-200
  7. Heritier Barras AC, Walder B, Seeck M "Serotonin syndrome following Methylene Blue infusion: a rare complication of antidepressant therapy." J Neurol Neurosurg Psychiatry 81 (2010): 1412-3
  8. Gillman PK "Methylene blue and serotonin toxicity: definite causal link." Psychosomatics 51 (2010): 448-9
  9. Health Canada "Association of serotonin toxicity with methylene blue injectable in combination with serotonin reuptake inhibitors. http://www.hc-sc.gc.ca/dhp-mps/alt_formats/pdf/medeff/advisories-avis/prof/2011/methylene_blue-bleu_nth-aah-eng.pdf" (2011):
  10. FDA. U.S. Food and Drug Administration "FDA Drug Safety Communication: serious CNS reactions possible when methylene blue is given to patients taking certain psychiatric medications. http://www.fda.gov/Drugs/DrugSafety/ucm263190.htm" (2011):
View all 10 references

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Drug and food interactions

Moderate

rasagiline food

Applies to: Azilect (rasagiline)

GENERALLY AVOID: Foods that contain large amounts of tyramine may precipitate a hypertensive crisis in patients treated with monoamine oxidase (MAO) inhibitors. The mechanism involves inhibition of MAO-A, the enzyme responsible for metabolizing exogenous amines such as tyramine in the gut and preventing them from being absorbed intact. Once absorbed, tyramine is metabolized to octopamine, a substance that is believed to displace norepinephrine from storage granules. Although rasagiline is a selective inhibitor of MAO-B at the recommended dosages of 0.5 or 1 mg/day, selectivity is not absolute and may diminish with increasing dosage. There were no cases of hypertensive crisis in the clinical development program associated with rasagiline treatment at 1 mg/day, in which most patients did not follow dietary tyramine restriction. However, rare cases of hypertensive crisis have been reported during the postmarketing period in patients who ingested unknown amounts of tyramine-rich foods while taking recommended dosages of rasagiline or selegiline, another MAO-B inhibitor.

Rasagiline peak plasma concentration (Cmax) and systemic exposure (AUC ) are decreased by approximately 60% and 20%, respectively, during coadministration with a high-fat meal. The time to peak concentration (Tmax) is not affected by food.

MANAGEMENT: Dietary restriction is not ordinarily required during rasagiline treatment with respect to most foods and beverages that may contain tyramine such as air-dried and fermented meats or fish, aged cheeses, most soybean products, yeast extracts, red wine, beer, and sauerkraut. However, certain foods like some of the aged cheeses (e.g., Boursault, Liederkrantz, Mycella, Stilton) may contain very high amounts of tyramine and could potentially cause a hypertensive reaction in patients taking rasagiline even at recommended dosages due to increased sensitivity to tyramine. Patients should be advised to avoid ingesting very high levels of tyramine (e.g., greater than 150 mg), and to promptly seek medical attention if they experience potential signs and symptoms of a hypertensive crisis such as severe headache, visual disturbances, confusion, stupor or coma, seizures, chest pain, unexplained nausea or vomiting, and stroke-like symptoms. Rasagiline should not be used at dosages exceeding 1 mg/day (0.5 mg/day for patients with mild hepatic impairment or concomitant use of ciprofloxacin or other CYP450 1A2 inhibitors), as it can increase the risk of hypertensive crisis and other adverse reactions associated with nonselective inhibition of MAO. Rasagiline can be administered with or without food.

References

  1. Goldberg LI "Monoamine oxidase inhibitors: adverse reactions and possible mechanisms." JAMA 190 (1964): 456-62
  2. Nuessle WF, Norman FC, Miller HE "Pickled herring and tranylcypromine reaction." JAMA 192 (1965): 142-3
  3. Sweet RA, Liebowitz MR, Holt CS, Heimberg RG "Potential interactions between monoamine oxidase inhibitors and prescribed dietary supplements." J Clin Psychopharmacol 11 (1991): 331-2
  4. McGrath PJ, Stewart JW, Quitkin FM "A possible L-deprenyl induced hypertensive reaction." J Clin Psychopharmacol 9 (1989): 310-1
  5. Lefebvre H, Noblet C, Morre N, Wolf LM "Pseudo-phaeochromocytoma after multiple drug interactions involving the selective monoamine oxidase inhibitor selegiline." Clin Endocrinol (Oxf) 42 (1995): 95-8
  6. Zetin M, Plon L, DeAntonio M "MAOI reaction with powdered protein dietary supplement." J Clin Psychiatry 48 (1987): 499
  7. Domino EF, Selden EM "Red wine and reactions." J Clin Psychopharmacol 4 (1984): 173-4
  8. Tailor SA, Shulman KI, Walker SE, Moss J, Gardner D "Hypertensive episode associated with phenelzine and tap beer--a reanalysis of the role of pressor amines in beer." J Clin Psychopharmacol 14 (1994): 5-14
  9. Pohl R, Balon R, Berchou R "Reaction to chicken nuggets in a patient taking an MAOI." Am J Psychiatry 145 (1988): 651
  10. Ito D, Amano T, Sato H, Fukuuchi Y "Paroxysmal hypertensive crises induced by selegiline in a patient with Parkinson's disease." J Neurol 248 (2001): 533-4
  11. "Product Information. Azilect (rasagiline)." Teva Pharmaceuticals USA (2006):
View all 11 references

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Moderate

hyoscyamine food

Applies to: MHP-A (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.

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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