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Drug Interactions between Azilect and selegiline

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

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Interactions between your drugs

Major

selegiline rasagiline

Applies to: selegiline and Azilect (rasagiline)

CONTRAINDICATED: Coadministration of a selective monoamine oxidase B (MAO-B) inhibitor with other MAO inhibitors, selective or nonselective, may increase the risk of a hypertensive crisis. Although selective inhibitors of MAO-B presumably have minimal effect on intestinal and hepatic MAO-A that catabolizes exogenous amines like tyramine, the selectivity may not be absolute even at recommended doses and may diminish with increasing doses. Rare cases of hypertensive reactions associated with ingestion of tyramine-containing foods have been reported in patients taking the recommended daily dose of selegiline. There have also been postmarketing reports of patients who experienced significantly elevated blood pressure, including very rare cases of hypertensive crisis, after ingestion of unknown amounts of tyramine-rich foods while taking recommended doses of rasagiline, despite results from multiple tyramine challenge studies demonstrating selectivity for MAO-B at recommended doses. The combination of a selective MAO-B inhibitor and a nonselective MAO inhibitor can also cause hypotensive reactions including orthostasis. Hypotension, sometimes sudden in onset, has been reported with rasagiline and selegiline, particularly when used with levodopa and during the first two months of treatment.

CONTRAINDICATED: Coadministration of a selective MAO-B inhibitor with other MAO inhibitors may increase 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. 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.

MANAGEMENT: Concurrent use of selective MAO-B inhibitors with other MAO inhibitors is considered contraindicated. At least 14 days should elapse between discontinuation of a nonselective MAO inhibitor and initiation of treatment with a selective MAO inhibitor, and vice versa. The recommended dosages of selective MAO-B inhibitors should not be exceeded, as it can increase the risk of nonselective MAO inhibition and precipitation of a hypertensive crisis.

References

  1. McGrath PJ, Stewart JW, Quitkin FM "A possible L-deprenyl induced hypertensive reaction." J Clin Psychopharmacol 9 (1989): 310-1
  2. "Product Information. Eldepryl (selegiline)." Somerset Pharmaceuticals Inc PROD (2001):
  3. 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
  4. 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
  5. "Product Information. Emsam (selegiline)." Bristol-Myers Squibb (2006):
  6. "Product Information. Azilect (rasagiline)." Teva Pharmaceuticals USA (2006):
  7. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  8. "Product Information. Xadago (safinamide)." US WorldMeds LLC (2017):
View all 8 references

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Drug and food interactions

Major

selegiline food

Applies to: selegiline

GENERALLY AVOID: Foods that contain large amounts of tyramine may precipitate a hypertensive crisis in patients treated with monoamine oxidase inhibitors (MAOIs). The mechanism is 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 selegiline is considered a selective inhibitor of MAO-B, the selectivity may not be absolute even at recommended dosages. Rare cases of hypertensive reactions associated with ingestion of tyramine-containing foods have been reported in patients taking the recommended daily oral dose of selegiline. Data for transdermal selegiline indicate that the 6 mg/24 hour dosage may be given safely without dietary restrictions. However, limited data are available for higher dosages.

MANAGEMENT: Patients treated with oral selegiline and transdermal selegiline (greater than 6 mg/24 hour) should preferably avoid consumption of products that contain large amounts of amines and protein foods in which aging or breakdown of protein is used to increase flavor. These foods include cheese (particularly strong, aged or processed cheeses), sour cream, wine (particularly red wine), champagne, beer, pickled herring, anchovies, caviar, shrimp paste, liver (particularly chicken liver), dry sausage, salamis, figs, raisins, bananas, avocados, chocolate, soy sauce, bean curd, sauerkraut, yogurt, papaya products, meat tenderizers, fava bean pods, protein extracts, yeast extracts, and dietary supplements. Caffeine may also precipitate hypertensive crisis so its intake should be minimized as well. At least 14 days should elapse following discontinuation of selegiline therapy before these foods may be consumed. Specially designed reference materials and dietary consultation are recommended so that an appropriate and safe diet can be planned. Patients should also be advised to promptly seek medical attention if they experience potential signs and symptoms of a hypertensive crisis such as severe headache, visual disturbances, difficulty thinking, stupor or coma, seizures, chest pain, unexplained nausea or vomiting, and stroke-like symptoms. The recommended dosages of selegiline should not be exceeded, as it can increase the risk of nonselective MAO inhibition and a hypertensive crisis.

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. "Product Information. Eldepryl (selegiline)." Somerset Pharmaceuticals Inc PROD (2001):
  6. 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
  7. Zetin M, Plon L, DeAntonio M "MAOI reaction with powdered protein dietary supplement." J Clin Psychiatry 48 (1987): 499
  8. Domino EF, Selden EM "Red wine and reactions." J Clin Psychopharmacol 4 (1984): 173-4
  9. 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
  10. Pohl R, Balon R, Berchou R "Reaction to chicken nuggets in a patient taking an MAOI." Am J Psychiatry 145 (1988): 651
  11. 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
  12. "Product Information. Emsam (selegiline)." Bristol-Myers Squibb (2006):
View all 12 references

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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

selegiline food

Applies to: selegiline

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

MANAGEMENT: Patients receiving CNS-active agents should be advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled against driving, operating machinery, or engaging in potentially 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. Warrington SJ, Ankier SI, Turner P "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology 15 (1986): 31-7
  2. Gilman AG, eds., Nies AS, Rall TW, Taylor P "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc. (1990):
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  4. "Product Information. Fycompa (perampanel)." Eisai Inc (2012):
  5. "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc (2015):
View all 5 references

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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

Mao inhibitors for parkinsonism

Therapeutic duplication

The recommended maximum number of medicines in the 'MAO inhibitors for parkinsonism' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'MAO inhibitors for parkinsonism' category:

  • Azilect (rasagiline)
  • selegiline

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.


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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.