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Drug Interactions between PMB and propoxyphene

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

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Interactions between your drugs

Major

meprobamate propoxyphene

Applies to: PMB (conjugated estrogens / meprobamate) and propoxyphene

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

meprobamate food

Applies to: PMB (conjugated estrogens / meprobamate)

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
Minor

conjugated estrogens food

Applies to: PMB (conjugated estrogens / meprobamate)

Coadministration with grapefruit juice may increase the bioavailability of oral estrogens. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits. In a small, randomized, crossover study, the administration of ethinyl estradiol with grapefruit juice (compared to herbal tea) increased peak plasma drug concentration (Cmax) by 37% and area under the concentration-time curve (AUC) by 28%. Based on these findings, grapefruit juice is unlikely to affect the overall safety profile of ethinyl estradiol. However, as with other drug interactions involving grapefruit juice, the pharmacokinetic alterations are subject to a high degree of interpatient variability. Also, the effect on other estrogens has not been studied.

References (2)
  1. Weber A, Jager R, Borner A, et al. (1996) "Can grapefruit juice influence ethinyl estradiol bioavailability?" Contraception, 53, p. 41-7
  2. Schubert W, Eriksson U, Edgar B, Cullberg G, Hedner T (1995) "Flavonoids in grapefruit juice inhibit the in vitro hepatic metabolism of 17B-estradiol." Eur J Drug Metab Pharmacokinet, 20, p. 219-24

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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