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Drug Interactions between melatonin and propoxyphene

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

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Interactions between your drugs

Major

propoxyphene melatonin

Applies to: propoxyphene and melatonin

MONITOR CLOSELY: Sedatives, tranquilizers, muscle relaxants, antidepressants, and other central nervous system (CNS) depressants may have additive CNS- and/or respiratory-depressant effects with propoxyphene. Misuse of propoxyphene, either alone or in combination with other CNS depressants, has been a major cause of drug-related deaths, particularly in patients with a history of emotional disturbances, suicidal ideation, or alcohol and drug abuse. In a large Canadian study, propoxyphene use was also associated with a 60% increased risk of hip fracture in the elderly, and the risk was further increased by concomitant use of psychotropic agents (sedatives, antidepressants, neuroleptics), presumably due to additive psychomotor impairment. Therefore, these drugs may constitute a dangerous combination in certain susceptible populations. Pharmacokinetically, propoxyphene is an inhibitor of CYP450 2D6 and may increase the plasma concentrations of many psychotropic agents that are metabolized by the isoenzyme such as phenothiazines, haloperidol, risperidone, phenobarbital, and some tricyclic antidepressants and serotonin reuptake inhibitors.

MANAGEMENT: Caution is advised if propoxyphene is used with sedatives, tranquilizers, muscle relaxants, antidepressants, and other CNS depressants, particularly in the elderly and in patients with a history of emotional disturbances, suicidal ideation, or alcohol and drug abuse. Dosage reductions may be appropriate. Patients should be monitored for potentially excessive or prolonged CNS and respiratory depression and other CNS adverse effects. Patients should be warned not to exceed recommended dosages, to avoid alcohol, and to avoid activities requiring mental alertness until they know how these agents affect them.

References (8)
  1. Abernethy DR, Greenblatt DJ, Morse DS, Shader RI (1985) "Interaction of propoxyphene with diazepam, alprazolam and lorazepam." Br J Clin Pharmacol, 19, p. 51-7
  2. Hansen BS, Dam M, Brandt J, et al. (1980) "Influence of dextropropoxyphene on steady state serum levels and protein binding of three anti-epileptic drugs in man." Acta Neurol Scand, 61, p. 357-67
  3. Abernethy DR, Greenblatt DJ, Steel K, Shader RI (1982) "Impairment of hepatic drug oxidation by propoxyphene." Ann Intern Med, 97, p. 223-4
  4. Peterson GR, Covault HP, Hostetler RM (1978) "Acute inhibition of microsomal drug metabolism by propoxphene in narcotic tolerant/dependent mice." Life Sci, 22, p. 2087-96
  5. Shorr RI, Griffin MR, Daugherty JR, Ray WA (1992) "Opioid analgesics and the risk of hip fracture in the elderly: codeine and propoxyphene." J Gerontol, 47, m111-5
  6. Puckett WH Jr, Visconti JA (1970) "Orphenadrine and propoxyphene." N Engl J Med, 283, p. 544
  7. Pearson RE, Salter FJ (1970) "Drug interaction? Orphenadrine with propoxyphene." N Engl J Med, 282, p. 1215
  8. (2001) "Product Information. Darvon (propoxyphene)." Lilly, Eli and Company

Drug and food interactions

Major

propoxyphene food

Applies to: propoxyphene

GENERALLY AVOID: Alcohol may have additive CNS- and/or respiratory-depressant effects with propoxyphene. Misuse of propoxyphene, either alone or in combination with other CNS depressants, has been a major cause of drug-related deaths, particularly in patients with a history of emotional disturbances, suicidal ideation, or alcohol and drug abuse.

MANAGEMENT: The use of alcohol during propoxyphene therapy should be avoided. Patients should be warned not to exceed the recommended dosage of propoxyphene and to avoid activities requiring mental alertness until they know how these agents affect them.

References (1)
  1. (2001) "Product Information. Darvon (propoxyphene)." Lilly, Eli and Company
Moderate

melatonin food

Applies to: melatonin

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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