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Drug Interactions between Nexplanon and st. john's wort

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

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Interactions between your drugs

Major

St. John's wort etonogestrel

Applies to: st. john's wort and Nexplanon (etonogestrel)

ADDITIONAL CONTRACEPTION RECOMMENDED: Coadministration with St. John's wort may reduce the efficacy of contraceptive hormones. The exact mechanism of interaction is unknown but may involve reduced absorption as well as accelerated clearance of the hormones due to induction of intestinal P-glycoprotein drug efflux transporter and intestinal/hepatic CYP450 3A4 metabolism by constituents of St. John's wort. There have been case reports of menstrual breakthrough bleeding following the addition of St. John's wort in patients receiving long-term oral contraceptives, and cases of unplanned pregnancies have also been reported. Between 2000 and 2014, the British Medicines and Healthcare Products Regulatory Agency (MHRA) has received 19 reports of suspected interactions; 15 of which resulted in unintended pregnancies and four resulted in breakthrough bleeding. Clinical trials in healthy female volunteers also demonstrated a higher incidence of breakthrough bleeding during coadministration of low-dose oral contraceptives with St. John's wort compared to administration of the contraceptives alone. However, neither ovarian activity nor endogenous hormone concentrations were affected. St. John's wort also seems to affect the pharmacokinetics of some progestins, probably due to induction of their clearance.

MANAGEMENT: In general, patients should consult a healthcare provider before taking any herbal or alternative medicine. Women using hormonal contraceptives should be advised of the risk of breakthrough bleeding and unintended pregnancy during concomitant therapy with St. John's wort. Alternative or additional methods of birth control should be used during and for at least two weeks after short-term and 4 weeks after long-term (greater than 4 weeks) St. John's wort therapy. If a combination oral contraceptive pill is used, a regimen containing at least 50 mcg of ethinyl estradiol per day or equivalent should be selected. Although breakthrough bleeding is not necessarily indicative of low ethinyl estradiol serum levels or increased risk of ovulation, some clinicians suggest that women who experience breakthrough bleeding during enzyme-inducing therapy may be prescribed an increased dose of ethinyl estradiol above 50 mcg daily by combining more than one formulation of contraceptive pill if necessary. For emergency contraception in patients who have used an hepatic enzyme inducer in the past 4 weeks, a non-hormonal emergency contraceptive (e.g., copper intrauterine device) is considered preferable. If this is not possible, some authorities recommend that the usual dose of levonorgestrel (1.5 mg) should be doubled to 3 mg and taken as a single dose as soon as possible (within 72 hours of unprotected sexual intercourse). However, there are no data on efficacy, compliance, or side effects of this regimen. For women with the etonogestrel subdermal implant, the addition of a barrier method is recommended during concomitant use and for 28 days after discontinuation of hepatic enzyme inducing drugs. It is recommended to remove the implant and to prescribe a nonhormonal method in women who require long-term treatment with hepatic enzyme inducing drugs. No precautions or recommendations are available for women using hormone-releasing intrauterine systems, but a significant interaction with these systems is thought to be unlikely due to their local action. Injectable progestin-only contraceptives are also thought to be unaffected by enzyme-inducing drugs.

References

  1. Ernst E "Second thoughts about safety of St John's wort." Lancet 354 (1999): 2014-6
  2. Fugh-Berman A "Herb-drug interactions." Lancet 355 (2000): 134-8
  3. Jobst KA, McIntyre M, St George D, Whitelegg M "Safety of St John's wort (Hypericum perforatum)." Lancet 355 (2000): 575
  4. De Smet PA, Touw DJ "Safety of St John's wort (Hypericum perforatum)." Lancet 355 (2000): 575-6
  5. Yue QY, Berquist C, Gerden B "Safety of St John's wort (Hypericum perforatum)." Lancet 355 (2000): 576-7
  6. Roby CA, Anderson GD, Kantor E, Dryer DA, Burstein AH "St John's Wort: Effect on CYP3A4 activity." Clin Pharmacol Ther 67 (2000): 451-7
  7. Durr D, Stieger B, KullakUblick GA, Rentsch KM, Steinert HC, Meier PJ, Fattinger K "St John's Wort induces intestinal P-glycoprotein/MDR1 and intestinal and hepatic CYP3A4." Clin Pharmacol Ther 68 (2000): 598-604
  8. Izzo AA, Ernst E "Interactions between herbal medicines and prescribed drugs: a systematic review." Drugs 61 (2001): 2163-75
  9. Henderson L, Yue QY, Bergquist C, Gerden B, Arlett P "St John's wort (Hypericum perforatum): drug interactions and clinical outcomes." Br J Clin Pharmacol 54 (2002): 349-56
  10. "Unwanted pregnancy on self-medication with St John's wort despite hormonal contraception." Br J Clin Pharmacol 55 (2003): 112-113
  11. Pfrunder A, Schiesser M, Gerber S, Haschke M, Bitzer J, Drewe J "Interaction of St John's wort with low-dose oral contraceptive therapy: a randomized controlled trial." Br J Clin Pharmacol 56 (2003): 683-90
  12. Hall SD, Wang Z, Huang SM, et al. "The interaction between St John's wort and an oral contraceptive." Clin Pharmacol Ther 74 (2003): 525-35
  13. Gorski JC, Hamman MA, Wang Z, Vasvada N, Huang S, Hall SD "The effect of St. John's wort on the efficacy of oral contraception." Clin Pharmacol Ther 71 (2002): P25
  14. Schwarz UI, Buschel B, Kirch W "Failure of oral contraceptives because of St. John's wort." Eur J Clin Pharmacol 57 (2001): A25
  15. "FFPRHC Guidance (April 2005). Drug interactions with hormonal contraception." J Fam Plann Reprod Health Care 31 (2005): 139-51
  16. Schwarz UI, Buschel B, Kirch W "Unwanted pregnancy on self-medication with St John's wort despite hormonal contraception." Br J Clin Pharmacol 55 (2003): 112-3
  17. Murphy PA, Kern SE, Stanczyk FZ, Westhoff CL "Interaction of St. John's Wort with oral contraceptives: effects on the pharmacokinetics of norethindrone and ethinyl estradiol, ovarian activity and breakthrough bleeding." Contraception 71 (2005): 402-8
  18. MHRA. Medicines and Healthcare Regulatory Agency. "St John's wort: interaction with hormonal contraceptives, including implants--reduced contraceptive effect. http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON392869" (2014):
  19. Faculty of Sexual & Reproductive Healthcare "FSRH Clinical Guidance: Drug Interactions with Hormonal Contraception. file:///C:/Users/df033684/Downloads/ceuguidancedruginteractionshormonal.pdf" (2016):
View all 19 references

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Drug and food interactions

Moderate

St. John's wort food

Applies to: st. john's wort

GENERALLY AVOID: An isolated case report suggests that foods containing large amounts of tyramine may precipitate a hypertensive crisis in patients treated with St. John's wort. The mechanism of interaction is unknown, as St. John's wort is not thought to possess monoamine oxidase (MAO) inhibiting activity at concentrations achieved in vivo. The case patient was a 41-year-old man who had been taking St. John's wort for seven days prior to presentation at the emergency room with confusion and disorientation. The patient recalled last eating aged cheese and having a glass of red wine approximately 10 hours prior to admission. No other cause of delirium or hypertension could be identified. In addition, alcohol may potentiate some of the pharmacologic effects of St. John's wort. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Until further information is available, patients treated with St. John's wort should consider avoiding consumption of protein foods in which aging or breakdown of protein is used to increase flavor. These foods include cheese (particularly strong, aged or processed cheeses), sour cream, wine (particularly red wine), champagne, beer, pickled herring, anchovies, caviar, shrimp paste, liver (particularly chicken liver), dry sausage, figs, raisins, bananas, avocados, chocolate, soy sauce, bean curd, yogurt, papaya products, meat tenderizers, fava beans, protein extracts, and dietary supplements. Caffeine may also precipitate hypertensive crisis so its intake should be minimized as well. Patients should also be advised to avoid or limit consumption of alcohol.

References

  1. Patel S, Robinson R, Burk M "Hypertensive crisis associated with St. John's Wort." Am J Med 112 (2002): 507-8

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Moderate

etonogestrel food

Applies to: Nexplanon (etonogestrel)

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

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