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Drug Interactions between gepirone and histrelin

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

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Interactions between your drugs

Moderate

histrelin gepirone

Applies to: histrelin and gepirone

Consumer information for this interaction is not currently available.

GENERALLY AVOID: Long-term androgen deprivation therapy (ADT) can prolong the QT interval. Coadministration of ADT with other agents that may prolong the QT interval could also result in additive effects and an increased risk of ventricular arrhythmias including torsade de pointes and sudden death. The risk may be increased in patients with certain underlying risk factors like congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). Studies in young men have shown that endogenous serum testosterone levels are inversely associated with QTc (QT interval corrected for heart rate) duration. Clinical trials in men with low serum testosterone levels have reported testosterone administration being associated with a shortening of QTc. Likewise, studies using ADT have shown that it may prolong the QT interval; however, this effect may vary by drug, dose, or even each drug class that can be used to reduce testosterone levels. A clinical study comparing abarelix to a luteinizing hormone-releasing hormone agonist plus nonsteroidal antiandrogen therapy found that both therapies prolonged the mean Fridericia-corrected QT interval (QTcF) by more than 10 msec from baseline. Approximately 20% of patients in both groups had either changes from baseline QTc of >30 msec or end-of-treatment QTc values >450 msec. Similarly, a study comparing degarelix to leuprolide found that approximately 20% of patients on each drug had QT/QTc intervals >450 msec after 1 year of treatment. From baseline to end of study, the median change in QTcF was 12.3 msec for degarelix and 16.7 msec for leuprolide. Some drugs used to lower testosterone levels may also have other side effects that can predispose a patient to QT prolongation and torsade de pointes. For example, inhibitors of 17 alpha-hydroxylase/C17,20-lyase (CYP17) like abiraterone may cause hypokalemia as a result of increased mineralocorticoid levels. Clinical data on ADT prolonging the QT interval in women and children are lacking.

MANAGEMENT: The benefits of androgen deprivation therapy (ADT) should be carefully assessed against the potential risk in patients receiving other drugs known to prolong the QT interval. Electrolyte abnormalities should be corrected prior to initiating therapy, and monitoring of electrocardiograms and electrolytes may be advisable. The manufacturer's labeling as well as current clinical guidelines should be consulted for monitoring recommendations.

References

  1. "Product Information. Lupron (leuprolide)." TAP Pharmaceuticals Inc PROD (2002):
  2. "Product Information. Zoladex (goserelin)." Astra-Zeneca Pharmaceuticals PROD (2001):
  3. "Product Information. Trelstar (triptorelin)." Pharmacia and Upjohn PROD (2001):
  4. "Product Information. Eligard (leuprolide)." Sanofi Winthrop Pharmaceuticals (2002):
  5. "Product Information. Plenaxis (abarelix)." Praecis Pharmaceuticals Inc (2003):
  6. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  7. "Product Information. Vantas (histrelin)." Endo Pharmaceuticals (formally Indevus Pharmaceuticals Inc) (2010):
  8. "Product Information. Firmagon (degarelix)." Ferring Pharmaceuticals Inc (2013):
  9. Krishna KB, Fuqua JS, rogol ad, et al. "Use of gonadotropin-releasing hormone analogs in children: update by an international consortium." Horm Res Paediatr 91 (2019): 357-72
  10. Lazzerini PE, Bertolozzi I, Acampa M, et al. "Androgen deprivation therapy for prostatic cancer in patients with torsades de pointes. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239032/" (2023):
  11. Gagliano-Juca T, Travison TG, kantoff pw, et al. "Androgen deprivation therapy is associated with prolongation of QTc interval in men with prostate cancer." J Endocr Soc 2 (2018): 485-96
  12. Gheorghe GS, Hodorogea AS, Ciobanu A, Nanea IT, Gheorghe ACD "Androgen deprivation therapy, hypogonadism and cardiovascular toxicity in men with advanced prostate cancer." Curr Oncol 28 (2021): 3331-46
  13. "Product Information. Firmagon (degarelix)." Ferring Pharmaceuticals Pty Ltd (2023):
  14. "Product Information. Firmagon (degarelix)." Ferring Pharmaceuticals Inc (2020):
View all 14 references

Drug and food interactions

Moderate

gepirone food

Applies to: gepirone

Consumer information for this interaction is not currently available.

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

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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