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

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

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Interactions between your drugs

Moderate

carbidopa 5-hydroxytryptophan

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

GENERALLY AVOID: Coadministration with carbidopa may potentiate the pharmacologic effects of 5-hydroxytryptophan (5-HTP), which is converted to 5-hydroxytryptamine (5-HT), or serotonin, in vivo. Carbidopa inhibits the peripheral metabolism of 5-HTP, and this effect has been exploited in the treatment of certain neurological disorders such as postanoxic myoclonus to enhance the amount of 5-HTP that reaches the central nervous system. However, higher CNS levels of serotonin may also potentiate the risk of serotonin syndrome, which is a rare but potentially fatal condition thought to result from hyperstimulation of brainstem 5HT1A receptors. Pharmacodynamically, the combination has been associated with a scleroderma-like skin condition in several case reports. The mechanism is unknown.

MANAGEMENT: In general, 5-hydroxytryptophan should not be given with carbidopa. If the combination is used, close monitoring is recommended for signs and symptoms of excessive serotonergic activity such as CNS irritability, altered consciousness, confusion, myoclonus, ataxia, abdominal cramping, hyperpyrexia, shivering, pupillary dilation, diaphoresis, hypertension, and tachycardia.

References (4)
  1. Magnussen I, Van Woert MH (1982) "Human pharmacokinetics of long term 5-hydroxytryptophan combined with decarboxylase inhibitors." Eur J Clin Pharmacol, 23, p. 81-6
  2. Sternberg EM, Van Woert MH, Young SN, Magnussen I, Baker H, Gauthier S, Osterland CK (1980) "Development of a scleroderma-like illness during therapy with L-5- hydroxytryptophan and carbidopa." N Engl J Med, 303, p. 782-7
  3. Klepser T, Nisly N (2000) "5-Hydroxytryptophan (5-HTP) for treatment of depression." Alternative Medicine Alert, 3, p. 121-4
  4. Limbird LE, Gilman AG, eds., Hardman JG (2001) "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: McGraw-Hill

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

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.

Further information

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