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Drug Interactions between leuprolide / norethindrone and Pitressin

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

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Interactions between your drugs

Moderate

vasopressin leuprolide

Applies to: Pitressin (vasopressin) and leuprolide / norethindrone

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

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Drug and food interactions

Moderate

vasopressin food

Applies to: Pitressin (vasopressin)

MONITOR: Alcohol may decrease the antidiuretic effect of vasopressin. Clinical studies found that plasma vasopressin levels often decrease during alcohol consumption and increase upon cessation of consumption. In addition, alcoholics were found to have a more pronounced decrease in plasma vasopressin levels when drinking and suppressed vasopressin levels even during alcohol withdrawal as compared to non-alcoholic individuals. The mechanism of this interaction is not fully understood.

MANAGEMENT: Patients should be advised to abstain from alcohol during vasopressin treatment. Hemodynamic monitoring is suggested for patients known to drink alcohol while receiving vasopressin.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. Cerner Multum, Inc. "Australian Product Information."
  3. (2017) "Product Information. Vasostrict (vasopressin)." Par Pharmaceutical Inc
  4. Taivainen H, Laitinen K, Tahtela R, Kilanmaa K, Valimaki MJ (1995) "Role of plasma vasopressin in changes of water balance accompanying acute alcohol intoxication." Alcohol Clin Exp Res, 19, p. 759-62
  5. Collins GB, Brosnihan KB, Zuti RA, Messina M, Gupta MK (1992) "Neuroendocrine, fluid balance, and thirst responses to alcohol in alcoholics." Alcohol Clin Exp Res, 16, p. 228-32
  6. Hirschl MM, Derfler K, Bieglmayer C, et al. (1994) "Hormonal derangements in patients with severe alcohol intoxication." Alcohol Clin Exp Res, 18, p. 761-6
  7. Harper KM, Knapp DJ, Criswell HE, Breese GR (2018) "Vasopressin and alcohol: A multifaceted relationship." Psychopharmacology (Berl), 235, p. 3363-79
View all 7 references

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Moderate

norethindrone food

Applies to: leuprolide / norethindrone

MONITOR: Grapefruit juice may increase the plasma concentrations of orally administered drugs that are substrates of the CYP450 3A4 isoenzyme. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Because grapefruit juice inhibits primarily intestinal rather than hepatic CYP450 3A4, the magnitude of interaction is greatest for those drugs that undergo significant presystemic metabolism by CYP450 3A4 (i.e., drugs with low oral bioavailability). 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. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.

MANAGEMENT: Patients who regularly consume grapefruit or grapefruit juice should be monitored for adverse effects and altered plasma concentrations of drugs that undergo significant presystemic metabolism by CYP450 3A4. Grapefruit and grapefruit juice should be avoided if an interaction is suspected. Orange juice is not expected to interact with these drugs.

References

  1. Edgar B, Bailey D, Bergstrand R, et al. (1992) "Acute effects of drinking grapefruit juice on the pharmacokinetics and dynamics on felodipine and its potential clinical relevance." Eur J Clin Pharmacol, 42, p. 313-7
  2. Jonkman JH, Sollie FA, Sauter R, Steinijans VW (1991) "The influence of caffeine on the steady-state pharmacokinetics of theophylline." Clin Pharmacol Ther, 49, p. 248-55
  3. Bailey DG, Arnold JM, Munoz C, Spence JD (1993) "Grapefruit juice--felodipine interaction: mechanism, predictability, and effect of naringin." Clin Pharmacol Ther, 53, p. 637-42
  4. Bailey DG, Arnold JMO, Spence JD (1994) "Grapefruit juice and drugs - how significant is the interaction." Clin Pharmacokinet, 26, p. 91-8
  5. Sigusch H, Hippius M, Henschel L, Kaufmann K, Hoffmann A (1994) "Influence of grapefruit juice on the pharmacokinetics of a slow release nifedipine formulation." Pharmazie, 49, p. 522-4
  6. Bailey DG, Arnold JM, Strong HA, Munoz C, Spence JD (1993) "Effect of grapefruit juice and naringin on nisoldipine pharmacokinetics." Clin Pharmacol Ther, 54, p. 589-94
  7. Yamreudeewong W, Henann NE, Fazio A, Lower DL, Cassidy TG (1995) "Drug-food interactions in clinical practice." J Fam Pract, 40, p. 376-84
  8. (1995) "Grapefruit juice interactions with drugs." Med Lett Drugs Ther, 37, p. 73-4
  9. Hukkinen SK, Varhe A, Olkkola KT, Neuvonen PJ (1995) "Plasma concentrations of triazolam are increased by concomitant ingestion of grapefruit juice." Clin Pharmacol Ther, 58, p. 127-31
  10. Min DI, Ku YM, Geraets DR, Lee HC (1996) "Effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of quinidine in healthy volunteers." J Clin Pharmacol, 36, p. 469-76
  11. Majeed A, Kareem A (1996) "Effect of grapefruit juice on cyclosporine pharmacokinetics." Pediatr Nephrol, 10, p. 395
  12. Clifford CP, Adams DA, Murray S, Taylor GW, Wilkins MR, Boobis AR, Davies DS (1996) "Pharmacokinetic and cardiac effects of terfenadine after inhibition of its metabolism by grapefruit juice." Br J Clin Pharmacol, 42, p662
  13. Josefsson M, Zackrisson AL, Ahlner J (1996) "Effect of grapefruit juice on the pharmacokinetics of amlodipine in healthy volunteers." Eur J Clin Pharmacol, 51, p. 189-93
  14. Kantola T, Kivisto KT, Neuvonen PJ (1998) "Grapefruit juice greatly increases serum concentrations of lovastatin and lovastatin acid." Clin Pharmacol Ther, 63, p. 397-402
  15. Ozdemir M, Aktan Y, Boydag BS, Cingi MI, Musmul A (1998) "Interaction between grapefruit juice and diazepam in humans." Eur J Drug Metab Pharmacokinet, 23, p. 55-9
  16. Bailey DG, Malcolm J, Arnold O, Spence JD (1998) "Grapefruit juice-drug interactions." Br J Clin Pharmacol, 46, p. 101-10
  17. Bailey DG, Kreeft JH, Munoz C, Freeman DJ, Bend JR (1998) "Grapefruit juice felodipine interaction: Effect of naringin and 6',7'-dihydroxybergamottin in humans." Clin Pharmacol Ther, 64, p. 248-56
  18. Garg SK, Kumar N, Bhargava VK, Prabhakar SK (1998) "Effect of grapefruit juice on carbamazepine bioavailability in patients with epilepsy." Clin Pharmacol Ther, 64, p. 286-8
  19. Lilja JJ, Kivisto KT, Neuvonen PJ (1998) "Grapefruit juice-simvastatin interaction: Effect on serum concentrations of simvastatin, simvastatin acid, and HMG-CoA reductase inhibitors." Clin Pharmacol Ther, 64, p. 477-83
  20. Fuhr U, Maier-Bruggemann A, Blume H, et al. (1998) "Grapefruit juice increases oral nimodipine bioavailability." Int J Clin Pharmacol Ther, 36, p. 126-32
  21. Lilja JJ, Kivisto KT, Neuvonen PJ (1999) "Grapefruit juice increases serum concentrations of atorvastatin and has no effect on pravastatin." Clin Pharmacol Ther, 66, p. 118-27
  22. Eagling VA, Profit L, Back DJ (1999) "Inhibition of the CYP3A4-mediated metabolism and P-glycoprotein-mediated transport of the HIV-I protease inhibitor saquinavir by grapefruit juice components." Br J Clin Pharmacol, 48, p. 543-52
  23. Damkier P, Hansen LL, Brosen K (1999) "Effect of diclofenac, disulfiram, itraconazole, grapefruit juice and erythromycin on the pharmacokinetics of quinidine." Br J Clin Pharmacol, 48, p. 829-38
  24. Lee AJ, Chan WK, Harralson AF, Buffum J, Bui BCC (1999) "The effects of grapefruit juice on sertraline metabolism: An in vitro and in vivo study." Clin Ther, 21, p. 1890-9
  25. Dresser GK, Spence JD, Bailey DG (2000) "Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition." Clin Pharmacokinet, 38, p. 41-57
  26. Gunston GD, Mehta U (2000) "Potentially serious drug interactions with grapefruit juice." S Afr Med J, 90, p. 41
  27. Takanaga H, Ohnishi A, Maatsuo H, et al. (2000) "Pharmacokinetic analysis of felodipine-grapefruit juice interaction based on an irreversible enzyme inhibition model." Br J Clin Pharmacol, 49, p. 49-58
  28. Libersa CC, Brique SA, Motte KB, et al. (2000) "Dramatic inhibition of amiodarone metabolism induced by grapefruit juice." Br J Clin Pharmacol, 49, p. 373-8
  29. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR (2000) "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther, 68, p. 468-77
  30. Zaidenstein R, Soback S, Gips M, Avni B, Dishi V, Weissgarten Y, Golik A, Scapa E (2001) "Effect of grapefruit juice on the pharmacokinetics of losartan and its active metabolite E3174 in healthy volunteers." Ther Drug Monit, 23, p. 369-73
  31. Sato J, Nakata H, Owada E, Kikuta T, Umetsu M, Ito K (1993) "Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects." Eur J Clin Pharmacol, 44, p. 295-8
  32. Flanagan D (2005) "Understanding the grapefruit-drug interaction." Gen Dent, 53, 282-5; quiz 286
View all 32 references

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Minor

norethindrone food

Applies to: leuprolide / norethindrone

The central nervous system effects and blood levels of ethanol may be increased in patients taking oral contraceptives, although data are lacking and reports are contradictory. The mechanism may be due to enzyme inhibition. Consider counseling women about this interaction which is unpredictable.

References

  1. Hobbes J, Boutagy J, Shenfield GM (1985) "Interactions between ethanol and oral contraceptive steroids." Clin Pharmacol Ther, 38, p. 371-80

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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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