Skip to main content

Drug Interactions between clomipramine and propoxyphene

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

Edit list (add/remove drugs)

Interactions between your drugs

Major

propoxyphene clomiPRAMINE

Applies to: propoxyphene and clomipramine

MONITOR CLOSELY: Concomitant use of propoxyphene and tricyclic and tetracyclic antidepressants (TCAs) may result in additive central nervous system (CNS) depressant effects. 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 including antidepressants, presumably due to additive psychomotor impairment. Therefore, these drugs may constitute a dangerous combination in certain susceptible populations. Pharmacokinetically, propoxyphene is a CYP450 2D6 inhibitor and may increase the plasma concentrations of TCAs such as clomipramine, desipramine, doxepin, maprotiline, and nortriptyline that are primarily metabolized by the isoenzyme. In one case report, doxepin serum concentrations doubled in an 89-year-old patient following the addition of propoxyphene, resulting in lethargy. A retrospective study also found that the plasma concentration/dose ratio of nortriptyline was nearly 40% higher in patients treated concomitantly with propoxyphene than in patients treated with nortriptyline alone.

MANAGEMENT: Caution is advised if propoxyphene is prescribed with TCAs, particularly in the elderly and in patients with a history of emotional disturbances, suicidal ideation, or alcohol and drug abuse. Serum TCA levels should be monitored more closely following the addition or withdrawal of propoxyphene, and the TCA dosage adjusted as necessary. Patients should be warned not to exceed recommended dosages of either drug, to avoid alcohol, and to notify their physician if they experience symptoms of toxicity such as lethargy, excessive sedation, dizziness, syncope, seizures, and/or irregular heartbeat. In addition, they should avoid activities requiring mental alertness until they know how these agents affect them.

References (5)
  1. Abernethy DR, Greenblatt DJ, Steel K, Shader RI (1982) "Impairment of hepatic drug oxidation by propoxyphene." Ann Intern Med, 97, p. 223-4
  2. Tofanetti O, Albiero L, Galatulas I, Genovese E (1977) "Enhancement of propoxyphene-induced analgesia by doxepin." Psychopharmacology (Berl), 51, p. 213-5
  3. Jerling M, Bertilsson L, Sjoqvist F (1994) "The use of therapeutic drug monitoring data to document kinetic drug interactions: an example with amitriptyline and nortriptyline." Ther Drug Monit, 16, p. 1-2
  4. 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
  5. (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

clomiPRAMINE food

Applies to: clomipramine

MONITOR: Limited data suggest that the administration of clomipramine with grapefruit juice or cranberry juice may significantly increase plasma drug concentrations of clomipramine. Clomipramine is initially demethylated by CYP450 1A2, 3A3 and 3A4 before undergoing further metabolism to 8-hydroxyclomipramine. The increase in clomipramine bioavailability may stem from inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. The precise mechanism by which cranberry juice exerts its effects is unknown, but may involve inhibition of CYP450 isoenzymes. This interaction has occasionally been exploited in attempts to improve symptomatic control of obsessive compulsive disorder.

MANAGEMENT: Patients receiving clomipramine therapy who ingest cranberry juice, grapefruits, or grapefruit juice should be monitored for adverse effects and undue fluctuations in plasma drug levels.

References (4)
  1. Oesterheld J, Kallepalli BR (1997) "Grapefruit juice and clomipramine: shifting metabolitic ratios." J Clin Psychopharmacol, 17, p. 62-3
  2. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR (2000) "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther, 68, p. 468-77
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  4. Cerner Multum, Inc. "Australian Product Information."
Moderate

clomiPRAMINE food

Applies to: clomipramine

GENERALLY AVOID: The combination of ethanol and a tricyclic antidepressant may result in additive impairment of motor skills, especially driving skills. Also, one study has suggested that clomipramine metabolism is significantly impaired for several weeks or more following discontinuation of chronic alcohol consumption.

MANAGEMENT: Patients should be warned of this interaction and advised to limit their ethanol intake while taking tricyclic antidepressants. Monitoring for TCA toxicity (CNS depression, excessive anticholinergic effects, hypotension, arrhythmias) is recommended during alcohol withdrawal.

References (3)
  1. Seppala T, Linnoila M, Elonen E, Mattila MJ, Makl M (1975) "Effect of tricyclic antidepressants and alcohol on psychomotor skills related to driving." Clin Pharmacol Ther, 17, p. 515-22
  2. Berlin I, Cournot A, Zimmer R, et al. (1990) "Evaluation and comparison of the interaction between alcohol and moclobemide or clomipramine in healthy subjects." Psychopharmacology (Berl), 100, p. 40-5
  3. Balant-Gorgia AE, Gay M, Gex-Fabry M, Balant LP (1992) "Persistent impairment of clomipramine demethylation in recently detoxified alcoholic patients." Ther Drug Monit, 14, p. 119-24

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.

See also

Report options

Loading...
QR code containing a link to this page

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.

Medical Disclaimer