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Drug Interactions between gepirone and procainamide

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

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Interactions between your drugs

Major

procainamide gepirone

Applies to: procainamide and gepirone

GENERALLY AVOID: Class IA (e.g., disopyramide, quinidine, procainamide) and class III (e.g., amiodarone, dofetilide, sotalol) antiarrhythmic agents can cause dose-related prolongation of the QT interval. Theoretically, coadministration with other agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. 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: Coadministration of class IA or class III antiarrhythmic agents with other drugs that can prolong the QT interval should preferably be avoided unless benefits are anticipated to outweigh the risks. Caution and clinical monitoring are recommended if concomitant use is required. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.

References

  1. (2002) "Product Information. Cordarone (amiodarone)." Wyeth-Ayerst Laboratories
  2. (2002) "Product Information. Vascor (bepridil)." McNeil Pharmaceutical
  3. (2001) "Product Information. Procan SR (procainamide)." Parke-Davis
  4. "Product Information. Quiniglute (quinidine)." Berlex, Richmond, CA.
  5. (2001) "Product Information. Betapace (sotalol)." Berlex Laboratories
  6. (2001) "Product Information. Norpace (disopyramide)." Searle
  7. Trujillo TC, Nolan PE (2000) "Antiarrhythmic agents - Drug interactions of clinical significance." Drug Safety, 23, p. 509-32
  8. Yamreudeewong W, DeBisschop M, Martin L, Lower D (2003) "Potentially Significant Drug Interactions of Class III Antiarrhythmic Drugs." Drug Saf, 26, p. 421-38
  9. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  10. Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
  11. Cerner Multum, Inc. "Australian Product Information."
  12. EMA. European Medicines Agency. European Union (2013) EMA - List of medicines under additional monitoring. http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/document_listing/document_listing_000366.jsp&mid=WC0b01ac058067c852
  13. Maxa JL, Hebeler RF, Adeeko MA (2006) "Torsades de pointes following concurrent amiodarone and levofloxacin therapy." Proc (Bayl Univ Med Cent), 19, p. 345-6
View all 13 references

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Drug and food interactions

Moderate

gepirone food

Applies to: gepirone

GENERALLY AVOID: Grapefruit and/or grapefruit juice may increase the plasma concentrations and effects of gepirone. The proposed mechanism is inhibition of CYP450 3A4 mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice, but has been reported for other CYP450 3A4 inhibitors. For example, when subjects who were at steady state on the strong CYP450 3A4 inhibitor ketoconazole (200 mg twice daily) received a single dose of gepirone (36.3 mg), the maximum plasma concentration (Cmax) and systemic exposure (AUC) of gepirone increased by approximately 5-fold. Similarly, when subjects who were at steady state on the moderate CYP450 3A4 inhibitor verapamil (80 mg three times daily) received a single dose of gepirone (18.2 mg), the maximum plasma concentration (Cmax) and systemic exposure (AUC) of gepirone increased by approximately 2.6-fold. In general, the effects of grapefruit products are concentration-, dose-, and preparation-dependent and can vary widely among both brands and individual patients. Some preparations have demonstrated strong CYP450 3A4 inhibition, while others have demonstrated moderate inhibition.

ADJUST DOSING INTERVAL: Food enhances the bioavailability of gepirone and its major active metabolites (3'-OH-gepirone and 1-PP). The magnitude of the effect is dependent on the fat content of the meal, but the systemic exposure of gepirone and its major metabolites was consistently higher under fed conditions as compared to the fasted state. The peak plasma concentration (Cmax) of gepirone after intake of a low-fat (about 200 calorie) breakfast was 27% higher, after a medium-fat (about 500 calorie) breakfast was 55% higher, and after a high-fat (about 850 calorie) breakfast was 62% higher than the Cmax achieved in the fasted state. Likewise, the systemic exposure (AUC) of gepirone was about 14% higher after a low-fat breakfast, 22% higher after a medium-fat breakfast, and 32% to 37% higher after a high-fat breakfast when compared to the AUC achieved in the fasted state. The effect of varying amounts of fat on the AUC and Cmax of 3'-OH-gepirone and 1-PP were similar to that of gepirone.

MANAGEMENT: Coadministration of gepirone with grapefruit products should be avoided. If grapefruit juice is consumed, monitoring for adverse effects (e.g., QT prolongation, serotonin syndrome, dizziness, nausea, insomnia, abdominal pain, and/or dyspepsia) should be considered. Gepirone should be taken orally with food at the approximately the same time each day. Tablets should be swallowed whole.

References

  1. (2023) "Product Information. Exxua (gepirone)." Mission Pharmacal Company, 1
  2. FDA. U.S. Food and Drug Administration (2024) Grapefruit juice and some drugs don't mix. https://www.fda.gov/consumers/consumer-updates/grapefruit-juice-and-some-drugs-dont-mix
  3. Chen M, Zhou S, Fabriaga E, Zhang P, Zhou Q (2024) Food-drug interactions precipitated by fruit juices other than grapefruit juice: an update review. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326888/
  4. Kiani J, Imam SZ (2024) Medicinal importance of grapefruit juice and its interaction with various drugs. https://nutritionj.biomedcentral.com/articles/10.1186/1475-2891-6-33
View all 4 references

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Minor

procainamide food

Applies to: procainamide

Ethanol may increase the acetylation of procainamide. Subtherapeutic plasma levels of procainamide may result in some patients. Because the acetylated metabolite of procainamide also possesses antiarrhythmic properties, the clinical effects are unclear.

References

  1. Olsen H, Morland J (1982) "Ethanol-induced increase in procainamide acetylation in man." Br J Clin Pharmacol, 13, p. 203-8

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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.

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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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