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Drug Interactions between mibefradil and PC-CAP

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

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Interactions between your drugs

Moderate

propoxyphene mibefradil

Applies to: PC-CAP (aspirin / caffeine / propoxyphene) and mibefradil

MONITOR: Based on in vitro inhibition data, coadministration with mibefradil may increase the plasma concentrations of drugs that are substrates of CYP450 2D6 and/or 3A4. The mechanism is decreased clearance due to inhibition of these isoenzymes by mibefradil.

MANAGEMENT: Caution is advised when mibefradil is used concomitantly with drugs that undergo metabolism by CYP450 2D6 and/or 3A4, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever mibefradil is added to or withdrawn from therapy.

References

  1. "Product Information. Posicor (mibefradil)." Roche Laboratories PROD (2001):
  2. Varis T, Backman JT, Kivisto KT, Neuvonen PJ "Diltiazem and mibefradil increase the plasma concentrations and greatly enhance the adrenal-suppressant effect of oral methylprednisolone." Clin Pharmacol Ther 67 (2000): 215-21

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Minor

aspirin caffeine

Applies to: PC-CAP (aspirin / caffeine / propoxyphene) and PC-CAP (aspirin / caffeine / propoxyphene)

One study has reported that coadministration of caffeine and aspirin lead to a 25% increase in the rate of appearance and 17% increase in maximum concentration of salicylate in the plasma. A significantly higher area under the plasma concentration time curve of salicylate was also reported when both drugs were administered together. The exact mechanism of this interaction has not been specified. Physicians and patients should be aware that coadministration of aspirin and caffeine may lead to higher salicylate levels faster.

References

  1. Yoovathaworn KC, Sriwatanakul K, Thithapandha A "Influence of caffeine on aspirin pharmacokinetics." Eur J Drug Metab Pharmacokinet 11 (1986): 71-6

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Minor

caffeine mibefradil

Applies to: PC-CAP (aspirin / caffeine / propoxyphene) and mibefradil

In vitro studies indicate that mibefradil inhibits the metabolism of drugs that are substrates of the CYP450 1A2 microsomal pathway. This may result in elevated plasma concentrations of these drugs. The manufacturer reports no pharmacokinetic interaction was observed when theophylline, a known substrate of CYP450 1A2, was studied with mibefradil. However, until specific information is available, observation for altered clinical and laboratory effects is recommended if these agents must be used with mibefradil.

References

  1. "Product Information. Posicor (mibefradil)." Roche Laboratories PROD (2001):
  2. Thijssen HH, Flin ois JP, Beaune PH "Cytochrome P4502C9 is the principal catalyst of racemic acenocoumarol hydroxylation reactions in human liver microsomes." Drug Metab Dispos 28 (2000): 1284-90

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Drug and food interactions

Major

propoxyphene food

Applies to: PC-CAP (aspirin / caffeine / 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. "Product Information. Darvon (propoxyphene)." Lilly, Eli and Company PROD (2001):

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Moderate

aspirin food

Applies to: PC-CAP (aspirin / caffeine / propoxyphene)

GENERALLY AVOID: The concurrent use of aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) and ethanol may lead to gastrointestinal (GI) blood loss. The mechanism may be due to a combined local effect as well as inhibition of prostaglandins leading to decreased integrity of the GI lining.

MANAGEMENT: Patients should be counseled on this potential interaction and advised to refrain from alcohol consumption while taking aspirin or NSAIDs.

References

  1. "Product Information. Motrin (ibuprofen)." Pharmacia and Upjohn PROD (2002):

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Minor

caffeine food

Applies to: PC-CAP (aspirin / caffeine / propoxyphene)

The effect of grapefruit juice on the pharmacologic activity of caffeine is controversial. One report suggests that grapefruit juice increases the effect of caffeine. The proposed mechanism is inhibition of cytochrome P-450 metabolism of caffeine. However, a well-conducted pharmacokinetic/pharmacodynamic study did not demonstrate this effect. The clinical significance of this potential interaction is unknown.

References

  1. "Grapefruit juice interactions with drugs." Med Lett Drugs Ther 37 (1995): 73-4
  2. Maish WA, Hampton EM, Whitsett TL, Shepard JD, Lovallo WR "Influence of grapefruit juice on caffeine pharmacokinetics and pharmacodynamics." Pharmacotherapy 16 (1996): 1046-52

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Minor

aspirin food

Applies to: PC-CAP (aspirin / caffeine / propoxyphene)

One study has reported that coadministration of caffeine and aspirin lead to a 25% increase in the rate of appearance and 17% increase in maximum concentration of salicylate in the plasma. A significantly higher area under the plasma concentration time curve of salicylate was also reported when both drugs were administered together. The exact mechanism of this interaction has not been specified. Physicians and patients should be aware that coadministration of aspirin and caffeine may lead to higher salicylate levels faster.

References

  1. Yoovathaworn KC, Sriwatanakul K, Thithapandha A "Influence of caffeine on aspirin pharmacokinetics." Eur J Drug Metab Pharmacokinet 11 (1986): 71-6

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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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