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Drug Interactions between PC-CAP and siponimod

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

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Interactions between your drugs

Major

propoxyphene siponimod

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

GENERALLY AVOID: Due to its significant bradycardic effects, the risk of QT prolongation and torsade de pointes arrhythmia may be increased during initiation of siponimod treatment in patients receiving drugs that prolong the QT interval. Siponimod can cause a decrease in heart rate during initiation of therapy that is apparent within an hour of the first dose, and the day 1 decline is maximal at approximately 3 to 4 hours. The maximal decrease in heart rate from baseline was seen between day 5 and 6. After day 6, heart rate starts increasing and reaches placebo levels within 10 days after treatment initiation. The highest daily postdose-dose decrease in absolute hourly mean heart rate is observed on day 1, with a decrease of 5 to 6 bpm. Following day 1, decreases in heart rate are less pronounced. Heart rates below 40 bpm were rarely observed. In controlled clinical trials, bradycardia (including sinus bradycardia and decreased heart rate) occurred in 6% of siponimod-treated patients compared to 3% of patients receiving placebo. Initiation of siponimod treatment has also resulted in transient AV conduction delays. First-degree AV block (prolonged PR interval on ECG) occurred in 5.1% of siponimod-treated patients and 1.9% of patients receiving placebo. Second-degree AV blocks, usually Mobitz type I (Wenckebach), have been observed at the time of siponimod initiation in less than 1.7% of patients. Bradycardia and conduction abnormalities were usually transient and asymptomatic, and resolved within the first 24 hours, but they occasionally required treatment with atropine. In a study evaluating the effect on QT interval of siponimod 2 or 10 mg at steady-state, siponimod treatment resulted in maximum prolongations of the QTc of 7.8 and 7.2 msec, respectively, with upper bounds of the 90% confidence interval of 9.93 and 9.72 msec, respectively. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

MANAGEMENT: Siponimod has not been studied in patients receiving drugs that can prolong the QT interval. Because bradycardia and AV block are recognized risk factors for QT prolongation and torsade de pointes arrhythmia, treatment with siponimod should generally not be initiated in patients who are concurrently treated with QT prolonging drugs with known arrhythmogenic properties. Advice from a cardiologist should be sought if treatment with siponimod is considered in patients on concurrent therapy with QT prolonging drugs with a known risk of torsades de pointes or drugs that slow heart rate or AV conduction.

References (2)
  1. Cerner Multum, Inc. "Australian Product Information."
  2. (2019) "Product Information. Mayzent (siponimod)." Novartis Pharmaceuticals
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)
  1. Yoovathaworn KC, Sriwatanakul K, Thithapandha A (1986) "Influence of caffeine on aspirin pharmacokinetics." Eur J Drug Metab Pharmacokinet, 11, p. 71-6

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)
  1. (2001) "Product Information. Darvon (propoxyphene)." Lilly, Eli and Company
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)
  1. (2002) "Product Information. Motrin (ibuprofen)." Pharmacia and Upjohn
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 (2)
  1. (1995) "Grapefruit juice interactions with drugs." Med Lett Drugs Ther, 37, p. 73-4
  2. Maish WA, Hampton EM, Whitsett TL, Shepard JD, Lovallo WR (1996) "Influence of grapefruit juice on caffeine pharmacokinetics and pharmacodynamics." Pharmacotherapy, 16, p. 1046-52
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)
  1. Yoovathaworn KC, Sriwatanakul K, Thithapandha A (1986) "Influence of caffeine on aspirin pharmacokinetics." Eur J Drug Metab Pharmacokinet, 11, p. 71-6

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.


Report options

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.