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Drug Interactions between histrelin and propafenone

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

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Interactions between your drugs

Moderate

propafenone histrelin

Applies to: propafenone and histrelin

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

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Drug and food interactions

Moderate

propafenone food

Applies to: propafenone

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of propafenone. 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. In over 90% of patients, propafenone is rapidly and extensively converted to 2 active metabolites: 5-hydroxypropafenone via CYP450 2D6 and N-depropylpropafenone (norpropafenone) via CYP450 3A4 and 1A2. In less than 10% of patients (approximately 6% of Caucasians in the U.S. population), however, metabolism of propafenone is slower because the 5-hydroxy metabolite is not formed, or minimally formed, due to a genetic deficiency in CYP450 2D6. In these poor metabolizers of CYP450 2D6, clearance of propafenone via the CYP450 3A4 and 1A2 metabolic pathways becomes more important, and inhibition of these pathways may substantially increase systemic exposure to propafenone. Likewise, patients taking concomitant inhibitors of CYP450 2D6 and 3A4 may experience similar pharmacokinetic effects. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Increased systemic exposure to propafenone may result in proarrhythmic events and exaggerated beta-adrenergic blocking activity.

MANAGEMENT: It may be advisable for patients to avoid the consumption of grapefruit, grapefruit juice, or supplements that contain grapefruit during treatment with propafenone.

References

  1. Botsch S, Gautier JC, Beaune P, Eichelbaum M, Kroemer HK "Identification and characterization of the cytochrome P450 enzymes involved in N-dealkylation of propafenone: molecular base for interaction potential and variable disposition of active metabolites." Mol Pharmacol 43 (1993): 120-6
  2. "Product Information. Rythmol SR (propafenone)." GlaxoSmithKline (2011):
  3. "Product Information. Apo-Propafenone (propafenone)." Apotex Incorporated (2023):
  4. "Product Information. Propafenone (propafenone)." Accord-UK Ltd (2022):
View all 4 references

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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

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