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Drug Interactions between 5-hydroxytryptophan / melatonin / pyridoxine and levomilnacipran

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

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Interactions between your drugs

Major

5-hydroxytryptophan levomilnacipran

Applies to: 5-hydroxytryptophan / melatonin / pyridoxine and levomilnacipran

GENERALLY AVOID: Concomitant use of agents with serotonergic activity such as serotonin reuptake inhibitors and tryptophan 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 5-HT2A 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, the concomitant use of tryptophan and agents with serotonergic activity such as serotonin reuptake inhibitors should be avoided. If concomitant use is considered clinically necessary, caution and close monitoring for signs and symptoms of serotonin syndrome is recommended, particularly at treatment initiation and during any dosage increases. Patients should be instructed to seek immediate medical attention if they develop any signs or symptoms of serotonin syndrome. The product labeling for each serotonergic medication as well as any relevant guidelines should also be consulted for specific recommendations.

References (17)
  1. (2001) "Product Information. Zoloft (sertraline)." Roerig Division
  2. (2001) "Product Information. Prozac (fluoxetine)." Dista Products Company
  3. (2001) "Product Information. Effexor (venlafaxine)." Wyeth-Ayerst Laboratories
  4. (2001) "Product Information. Paxil (paroxetine)." GlaxoSmithKline
  5. (2001) "Product Information. Luvox (fluvoxamine)." Solvay Pharmaceuticals Inc
  6. (2001) "Product Information. Celexa (citalopram)." Forest Pharmaceuticals
  7. (2004) "Product Information. Cymbalta (duloxetine)." Lilly, Eli and Company
  8. (2008) "Product Information. Pristiq (desvenlafaxine)." Wyeth Laboratories
  9. (2009) "Product Information. Savella (milnacipran)." Forest Pharmaceuticals
  10. (2009) "Product Information. Nucynta (tapentadol)." PriCara Pharmaceuticals
  11. (2011) "Product Information. Viibryd (vilazodone)." Trovis Pharmaceuticals LLC
  12. (2013) "Product Information. Fetzima (levomilnacipran)." Forest Pharmaceuticals
  13. (2013) "Product Information. Brintellix (vortioxetine)." Takeda Pharmaceuticals America
  14. (2023) "Product Information. Escitalopram (Apo) (escitalopram)." Arrotex Pharmaceuticals Pty Ltd
  15. (2024) "Product Information. Escitalopram (escitalopram)." Milpharm Ltd
  16. (2024) "Product Information. Escitalopram Oxalate (escitalopram)." Aurobindo Pharma USA Inc
  17. (2024) "Product Information. ACH-Escitalopram (escitalopram)." Accord Healthcare

Drug and food interactions

Moderate

melatonin food

Applies to: 5-hydroxytryptophan / melatonin / pyridoxine

MONITOR: Oral caffeine may significantly increase the bioavailability of melatonin. The proposed mechanism is inhibition of CYP450 1A2 first-pass metabolism. After administration of melatonin 6 mg and caffeine 200 mg orally (approximately equivalent to 1 large cup of coffee) to 12 healthy subjects, the mean peak plasma concentration (Cmax) of melatonin increased by 137% and the area under the concentration-time curve (AUC) increased by 120%. The metabolic inhibition was greater in nonsmokers (n=6) than in smokers (n=6). The greatest effect was seen in subjects with the *1F/*1F genotype (n=7), whose melatonin Cmax increased by 202%. The half-life did not change significantly. The clinical significance of this interaction is unknown.

According to some authorities, alcohol may reduce the effect of melatonin on sleep. The mechanism of this interaction is not fully understood.

In addition, CYP450 1A2 inducers like cigarette smoking may reduce exogenous melatonin plasma levels. In a small clinical trial (n=8), habitual smokers had their melatonin plasma levels measured two times, each after a single oral dose of 25 mg of melatonin. They had smoked prior to the first measurement but had not smoked for 7 days prior to the second. Cigarette smoking significantly reduced melatonin plasma exposure (AUC) as compared to melatonin levels after 7 days of smoking abstinence (7.34 +/- 1.85 versus 21.07 +/- 7.28 nmol/L*h, respectively).

MANAGEMENT: Caution and monitoring are recommended if melatonin is used with inhibitors of CYP450 1A2 like caffeine or inducers of CYP450 1A2 like cigarette smoking. Consumption of alcohol should be avoided when taking melatonin.

References (3)
  1. Hartter S, Nordmark A, Rose DM, Bertilsson L, Tybring G, Laine K (2003) "Effects of caffeine intake on the pharmacokinetics of melatonin, a probe drug for CYP1A2 activity." Br J Clin Pharmacol, 56, p. 679-682
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  3. Ursing C, Bahr CV, Brismar K, Rojdmark S (2005) "Influence of cigarette smoking on melatonin levels in man" Eur J Clin Pharmacol, 61, p. 197-201
Moderate

levomilnacipran food

Applies to: levomilnacipran

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

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled 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 (4)
  1. Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
  2. Gilman AG, eds., Nies AS, Rall TW, Taylor P (1990) "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc.
  3. (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
  4. (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc

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

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

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