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Drug Interactions between fenfluramine and safinamide

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

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Major

fenfluramine safinamide

Applies to: fenfluramine and safinamide

CONTRAINDICATED: By inhibiting serotonin metabolism, monoamine oxidase inhibitors (MAOIs) may potentiate the pharmacologic activity of serotonergic agents such as serotonin reuptake inhibitors, 5-HT1 receptor agonists, ergot alkaloids, buspirone, dextromethorphan, and most antidepressants. The result may be an increased 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, hallucinations, 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: In general, serotonergic agents should not be used concurrently with MAOIs or other agents that possess MAOI activity (e.g., furazolidone, methylene blue, procarbazine). At least 14 days should elapse between discontinuation of MAOI therapy and initiation of treatment with serotonergic agents. A washout period of 5 to 14 days is usually recommended when switching from another antidepressant to an MAOI; however, the individual product labeling should be consulted.

References

  1. Pettinger WA, Soyangco FG, Oates JA (1968) "Inhibition of monoamine oxidase in man by furazolidone." Clin Pharmacol Ther, 9, p. 442-7
  2. 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
  3. Sternbach H (1988) "Danger of MAOI therapy after fluoxetine withdrawal." Lancet, 2, p. 850-1
  4. Sovner R, Wolfe J (1988) "Interaction between dextromethorphan and monoamine oxidase inhibitor therapy with isocarboxazid ." N Engl J Med, 319, p. 1671
  5. Bem JL, Peck R (1992) "Dextromethorphan. An overview of safety issues." Drug Saf, 7, p. 190-9
  6. Nierenberg DW, Semprebon M (1993) "The central nervous system serotonin syndrome." Clin Pharmacol Ther, 53, p. 84-8
  7. Graham PM, Potter JM, Paterson J (1982) "Combination monoamine oxidase inhibitor/tricyclic antidepressants interaction." Lancet, 2, p. 440
  8. Spiker DG, Pugh DD (1976) "Combining tricyclic and monoamine oxidase inhibitor antidepressants." Arch Gen Psychiatry, 33, p. 828-30
  9. White K, Pistole T, Boyd JL (1980) "Combined monoamine oxidase inhibitor-tricyclic antidepressant treatment: a pilot study." Am J Psychiatry, 137, p. 1422-5
  10. White K, Simpson G (1981) "Combined MAOI-tricyclic antidepressant treatment: a reevaluation." J Clin Psychopharmacol, 1, p. 264-82
  11. Rivers N, Horner B (1970) "Possible lethal reaction between nardil and dextromethorphan." Can Med Assoc J, 103, p. 85
  12. (2002) "Product Information. D.H.E. 45 (dihydroergotamine)." Sandoz Pharmaceuticals Corporation
  13. Sternbach H (1991) "The serotonin syndrome." Am J Psychiatry, 148, p. 705-13
  14. Feighner JP, Boyer WF, Tyler DL, Neborsky RJ (1990) "Adverse consequences of fluoxetine-MAOI combination therapy." J Clin Psychiatry, 51, p. 222-5
  15. Graham PM, Ilett KF (1988) "Danger of MAOI therapy after fluoxetine withdrawal." Lancet, 2, p. 1255-6
  16. Bhatara VS, Bandettini FC (1993) "Possible interaction between sertraline and tranylcypromine." Clin Pharm, 12, p. 222-5
  17. Suchowersky O, deVries JD (1990) "Interaction of fluoxetine and selegiline." Can J Psychiatry, 35, p. 571-2
  18. (2001) "Product Information. Effexor (venlafaxine)." Wyeth-Ayerst Laboratories
  19. Brannan SK, Talley BJ, Bowden CL (1994) "Sertraline and isocarboxazid cause a serotonin syndrome." J Clin Psychopharmacol, 14, p. 144-5
  20. Graber MA, Hoehns TB, Perry PJ (1994) "Sertraline-phenelzine drug interaction: a serotonin syndrome reaction." Ann Pharmacother, 28, p. 732-5
  21. Cetaruk EW, Aaron CK (1994) "Hazards of nonprescription medications." Emerg Med Clin North Am, 12, p. 483-510
  22. Diamond S (1995) "The use of sumatriptan in patients on monoamine oxidase inhibitors." Neurology, 45, p. 1039-40
  23. Phillips SD, Ringo P (1995) "Phenelzine and venlafaxine interaction." Am J Psychiatry, 152, p. 1400-1
  24. Klysner R, Larsen JK, Sorensen P, Hyllested M, Pedersen BD (1995) "Toxic interaction of venlafaxine and isocarboxazide." Lancet, 346, p. 1298-9
  25. Darcy PF, Griffin JP (1995) "Interactions with drugs used in the treatment of depressive illness." Adverse Drug React Toxicol Rev, 14, p. 211-31
  26. Heisler MA, Guidry JR, Arnecke B (1996) "Serotonin syndrome induced by administration of venlafaxine and phenelzine." Ann Pharmacother, 30, p. 84
  27. 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
  28. Fischer P (1995) "Serotonin syndrome in the elderly after antidepressive monotherapy." J Clin Psychopharmacol, 15, p. 440-2
  29. Corkeron MA (1995) "Serotonin syndrome - a potentially fatal complication of antidepressant therapy." Med J Aust, 163, p. 481-2
  30. Thomas JM, Rubin EH (1984) "Case report of a toxic reaction from a combination of tryptophan and phenelzine." Am J Psychiatry, 141, p. 281-3
  31. Pope HG Jr, Jonas JM, Hudson JI, Kafka MP (1985) "Toxic reactions to the combination of monoamine oxidase inhibitors and tryptophan." Am J Psychiatry, 142, p. 491-2
  32. Alvine G, Black DW, Tsuang D (1990) "Case of delirium secondary to phenelzine/L-tryptophan combination." J Clin Psychiatry, 51, p. 311
  33. Staufenberg EF, Tantam D (1989) "Malignant hyperpyrexia syndrome in combined treatment." Br J Psychiatry, 154, p. 577-8
  34. Levy AB, Bucher P, Votolato N (1985) "Myoclonus, hyperreflexia and diaphoresis in patients on phenelzine- tryptophan combination treatment." Can J Psychiatry, 30, p. 434-6
  35. Beasley CM Jr, Masica DN, Heiligenstein JH, Wheadon DE, Zerbe RL (1993) "Possible monoamine oxidase inhibitor-serotonin uptake inhibitor interaction: fluoxetine clinical data and preclinical findings." J Clin Psychopharmacol, 13, p. 312-20
  36. Mills KC (1997) "Serotonin syndrome: A clinical update." Crit Care Clin, 13, p. 763
  37. Gardner DM, Lynd LD (1998) "Sumatriptan contraindications and the serotonin syndrome." Ann Pharmacother, 32, p. 33-8
  38. Mathew NT, Tietjen GE, Lucker C (1996) "Serotonin syndrome complicating migraine pharmacotherapy." Cephalalgia, 16, p. 323-7
  39. Weiner LA, Smythe M, Cisek J (1998) "Serotonin syndrome secondary to phenelzine-venlafaxine interaction." Pharmacotherapy, 18, p. 399-403
  40. Diamond S, Pepper BJ, Diamond ML, Freitag FG, Urban GJ, Erdemoglu AK (1998) "Serotonin syndrome induced by transitioning from phenelzine to venlafaxine: four patient reports." Neurology, 51, p. 274-6
  41. 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
  42. Brubacher JR, Hoffman RS, Lurin MJ (1996) "Serotonin syndrome from venlafaxine-tranylcypromine interaction." Vet Hum Toxicol, 38, p. 358-61
  43. Miller LG (1998) "Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions." Arch Intern Med, 158, p. 2200-11
  44. Martin TG (1996) "Serotonin syndrome." Ann Emerg Med, 28, p. 520-6
  45. Jacob JE, Wagner ML, Sage JI (2003) "Safety of selegiline with cold medications." Ann Pharmacother, 37, p. 438-41
  46. (2004) "Product Information. Cymbalta (duloxetine)." Lilly, Eli and Company
  47. (2005) "Product Information. Manerix (moclobemide)." Hoffmann-La Roche Limited
  48. Gillman PK (2005) "Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity." Br J Anaesth
  49. Bodner RA, Lynch T, Lewis L, Kahn D (1995) "Serotonin syndrome." Neurology, 45, p. 219-23
  50. Jimenez-Genchi A (2006) "Immediate switching from moclobemide to duloxetine may induce serotonin syndrome." J Clin Psychiatry, 67, p. 1821-1822
  51. (2008) "Product Information. Pristiq (desvenlafaxine)." Wyeth Laboratories
  52. (2009) "Product Information. Savella (milnacipran)." Forest Pharmaceuticals
  53. (2011) "Product Information. Viibryd (vilazodone)." Trovis Pharmaceuticals LLC
  54. (2013) "Product Information. Fetzima (levomilnacipran)." Forest Pharmaceuticals
View all 54 references

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Drug and food interactions

Moderate

fenfluramine food

Applies to: fenfluramine

GENERALLY AVOID: Alcohol may potentiate the central nervous system and cardiovascular effects of centrally-acting appetite suppressants. In one study, concurrent administration of methamphetamine (30 mg intravenously) and ethanol (1 gm/kg orally over 30 minutes) increased heart rate by 24 beats/minute compared to methamphetamine alone. This increases cardiac work and myocardial oxygen consumption, which may lead to more adverse cardiovascular effects than either agent alone. Subjective effects of ethanol were diminished in the eight study subjects, but those of methamphetamine were not affected. The pharmacokinetics of methamphetamine were also unaffected except for a decrease in the apparent volume of distribution at steady state.

MANAGEMENT: Concomitant use of centrally-acting appetite suppressants and alcohol should be avoided if possible, especially in patients with a history of cardiovascular disease. Patients should be counselled 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.

References

  1. Mendelson J, Jones RT, Upton R, Jacob P 3rd (1995) "Methamphetamine and ethanol interactions in humans." Clin Pharmacol Ther, 57, p. 559-68
  2. (2001) "Product Information. Didrex (benzphetamine)." Pharmacia and Upjohn
  3. (2012) "Product Information. Suprenza (phentermine)." Akrimax Pharmaceuticals

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Moderate

safinamide food

Applies to: safinamide

GENERALLY AVOID: Foods that contain large amounts of tyramine may precipitate a hypertensive crisis in patients treated with safinamide. The proposed mechanism involves potentiation of the tyramine pressor effect due to inhibition of monoamine oxidase (MAO) by safinamide. Monoamine oxidase in the gastrointestinal tract and liver, primarily type A (MAO-A), is the enzyme responsible for metabolizing exogenous amines such as tyramine 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 causing a rise in blood pressure. In vitro, safinamide inhibits MAO-B with greater than 1000-fold selectivity over MAO-A, and neither safinamide nor its major metabolites inhibit MAO-A at clinically relevant concentrations. Results from an oral tyramine challenge study also suggest that safinamide is a selective inhibitor of MAO-B at the recommended dosages of 50 or 100 mg/day. However, this selectivity is not absolute and may diminish in a dose-related manner above the maximum recommended daily dosage. In clinical trials, the incidence of hypertension was 7% and 5% for safinamide 50 mg and 100 mg, respectively, versus 4% for placebo. There were no reported cases of hypertensive crisis.

Administration of safinamide following intake of a high-fat, high-caloric breakfast resulted in a slight delay in the absorption of safinamide, but had no effects on safinamide peak plasma concentration (Cmax) and systemic exposure (AUC) compared to administration under fasted conditions.

MANAGEMENT: Dietary restriction is not ordinarily required during safinamide treatment with respect to most foods and beverages that contain tyramine, which usually include aged, fermented, cured, smoked, or pickled foods (e.g., air-dried and fermented meats or fish, aged cheeses, most soybean products, yeast extracts, red wine, beer, sauerkraut). However, certain foods like some of the aged cheeses (e.g., Boursault, Liederkrantz, Mycella, Stilton) and pickled herring may contain very high amounts of tyramine and could potentially cause a hypertensive reaction in patients taking safinamide, even at recommended dosages, due to increased sensitivity to tyramine. Patients should be advised to avoid the intake of 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, seizures, chest pain, unexplained nausea or vomiting, and stroke-like symptoms. Blood pressure should be regularly monitored and managed accordingly. Medication adjustment may be necessary if blood pressure elevations are sustained or not adequately controlled. Safinamide should not be used at dosages exceeding 100 mg/day, or 50 mg/day in patients with moderate hepatic impairment (Child-Pugh B, 7-9), as it may increase the risk of hypertensive crisis and other adverse reactions associated with nonselective inhibition of MAO. Safinamide can be administered with or without food.

References

  1. (2023) "Product Information. Xadago (safinamide)." US WorldMeds LLC
  2. (2020) "Product Information. Onstryv (safinamide)." Valeo Pharma
  3. (2022) "Product Information. Xadago (safinamide)." Seqirus Pty Ltd
  4. (2021) "Product Information. Xadago (safinamide)." Zambon UK Ltd
View all 4 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.

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