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Drug Interactions between ethinyl estradiol / ethynodiol and Fasigyn

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

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Interactions between your drugs

Moderate

ethinyl estradiol tinidazole

Applies to: ethinyl estradiol / ethynodiol and Fasigyn (tinidazole)

MONITOR: The effectiveness of estrogen-containing medications may be impaired by concomitant treatment with antimicrobial agents. During metabolism, the estrogen component is conjugated, resulting in sulfation or glucuronidation of the original estrogenic steroid. The conjugates reach the intestine by way of the bile duct where hydrolytic enzymes of intestinal bacteria break down the conjugates into free, active estrogenic hormone. The active hormone is then available for enterohepatic cycling, which helps to maintain estrogen levels. It is important to note that the progestin component of a combined hormonal product does not undergo this process. It has been suggested that broad-spectrum antibiotics may reduce the effectiveness of estrogen-containing contraceptives because of their potential to reduce the number of intestinal bacteria and thus interfere with enterohepatic cycling of estrogen. Most of the research regarding this possible interaction has been done with oral contraceptives, but all estrogens appear to undergo enterohepatic recirculation so theoretically this interaction is a possibility with estrogen containing medications that are being used for alternative purposes. However, the risk appears to be small, and supportive data are primarily limited to anecdotal evidence from case reports and findings from uncontrolled or poorly controlled studies. Most antimicrobials, with the exception of enzyme inducing medications like the rifamycins and possibly griseofulvin, have not been shown to significantly increase the clearance of oral contraceptive estrogens. It is possible that a small number of women may be more sensitive to the effects of antimicrobials on estrogen disposition in vivo, but risk factors or genetic predispositions have yet to be identified.

MANAGEMENT: If a person is using estrogen for a purpose other than contraception, it is important to note that there is a theoretical possibility of lower levels of systemic estrogen available during treatment with an antibiotic due to interference with enterohepatic cycling. These patients should be counseled to report any changes in efficacy of the hormonal product to their healthcare provider. In the case of contraception specifically, the Centers for Disease Control and Prevention do not consider most broad-spectrum antibiotics to significantly interfere with the effectiveness of combined hormonal contraception. However, the manufacturers of certain combined hormonal contraceptives and/or certain antibiotics do recommend using a back-up method of birth control for varying amounts of time; therefore, consulting the product labeling of each medication involved is advised. Some illnesses, as well as some antibiotics, may cause nausea, vomiting, and/or diarrhea. If the patient vomits within a few hours of taking an oral contraceptive pill, consult the product labeling for instructions on what to do in the event of a missed pill. Some authorities recommend a back-up method of birth control if an individual has persistent vomiting or diarrhea.

References

  1. Friedman CI, Huneke AL, Kim MH, Powell J "The effect of ampicillin on oral contraceptive effectiveness." Obstet Gynecol 55 (1980): 33-7
  2. Back DJ, Breckenridge AM, MacIver M, et al. "The effects of ampicillin on oral contraceptive steroids in women." Br J Clin Pharmacol 14 (1982): 43-8
  3. Neely JL, Abate M, Swinker M, D'Angio R "The effect of doxycycline on serum levels of ethinyl estradiol, norethindrone, and endogenous progesterone." Obstet Gynecol 77 (1991): 416-20
  4. Joshi JV, Joshi UM, Sankholi GM, et al. "A study of interaction of low-dose combination oral contraceptive with ampicillin and metronidazole." Contraception 22 (1980): 643-52
  5. Baciewicz AM "Oral contraceptive drug interactions." Ther Drug Monit 7 (1985): 26-35
  6. Bint AJ, Burtt I "Adverse antibiotic drug interactions." Drugs 20 (1980): 57-68
  7. Dossetor J "Drug interactions with oral contraceptives." Br Med J 4 (1975): 467-8
  8. DeSano EA, Hurley SC "Possible interactions of antihistamines and antibiotics with oral contraceptive effectiveness." Fertil Steril 37 (1982): 853-4
  9. Szoka PR, Edgren RA "Drug interactions with oral contraceptives: compilation and analysis of an adverse experience report database." Fertil Steril 49(5 Suppl) (1988): s31-8
  10. Barnett ML "Inhibition of oral contraceptive effectiveness by concurrent antibiotic administration." J Periodontol 56 (1985): 18-20
  11. "Product Information. Declomycin (demeclocycline)." Lederle Laboratories PROD (2001):
  12. London BM, Lookingbill DP "Frequency of pregnancy in acne patients taking oral antibiotics and oral contraceptives." Arch Dermatol 130 (1994): 392-3
  13. Bacon JF, Shenfield GM "Pregnancy attributable to interaction between tetracycline and oral contraceptives." Br Med J 280 (1980): 293
  14. Fazio A "Oral contraceptive drug interactions: important considerations." South Med J 84 (1991): 997-1002
  15. Back DJ, Orme ML "Pharmacokinetic drug interactions with oral contraceptives." Clin Pharmacokinet 18 (1990): 472-84
  16. Back DJ, Tjia J, Martin C, Millar E, Mant T, Morrison P, Orme M "The lack of interaction between temafloxacin and combined oral contraceptive steroids." Contraception 43 (1991): 317-23
  17. Orme ML, Back DJ "Interactions between oral contraceptive steroids and broad-spectrum antibiotics." Clin Exp Dermatol 11 (1986): 327-31
  18. Wermeling DP, Chandler MH, Sides GD, Collins D, Muse KN "Dirithromycin increases ethinyl estradiol clearance without allowing ovulation." Obstet Gynecol 86 (1995): 78-84
  19. Silber TJ "Apparent oral contraceptive failure associated with antibiotic administration." J Adolesc Health Care 4 (1983): 287-9
  20. Bollen M "Use of antibiotics when taking the oral contraceptive pill." Aust Fam Physician 24 (1995): 928-9
  21. Kleier DJ, Tucker JE "Oral contraceptive failure secondary to dentally prescribed drugs: fact or fiction?" J Colo Dent Assoc 66 (1987): 5-6
  22. Back DJ, Breckenridge AM, Crawford FE, MacIver M, Orne ML, Rowe PH "Interindividual variation and drug interactions with hormonal steroid contraceptives." Drugs 21 (1981): 46-61
  23. Helms SE, Bredle DL, Zajic J, Jarjoura D, Brodell RT, Krishnarao I "Oral contraceptive failure rates and oral antibiotics." J Am Acad Dermatol 36 (1997): 705-10
  24. Weisberg E "Interactions between oral contraceptives and antifungals antibacterials - Is contraceptive failure the result?." Clin Pharmacokinet 36 (1999): 309-13
  25. Burroughs KE, Chambliss ML "Antibiotics and oral contraceptive failure." Arch Fam 9 (2000): 81-2
  26. Weaver K, Glasier A "Interaction between broad-spectrum antibiotics and the combined oral contraceptive pill: a literature review." Contraception 59 (1999): 71-8
  27. King VJ "OC failure rates and oral antibiotics." J Fam Pract 45 (1997): 104-5
  28. Zachariassen RD "Loss of oral contraceptive efficacy by concurrent antibiotic administration." Women Health 22 (1994): 17-26
  29. Dickinson BD, Altman RD, Nielsen NH, Sterling ML "Drug interactions between oral contraceptives and antibiotics." Obstet Gynecol 98(5 Pt 1) (2001): 853-60
  30. Archer JS, Archer DF "Oral contraceptive efficacy and antibiotic interaction: A myth debunked." J Am Acad Dermatol 46 (2002): 917-23
  31. Orme M, Back DJ "Oral contraceptive steroids--pharmacological issues of interest to the prescribing physician." Adv Contracept 7 (1991): 325-31
  32. DeRossi SS, Hersh EV "Antibiotics and oral contraceptives." Dent Clin North Am 46 (2002): 653-64
  33. "FFPRHC Guidance (April 2005). Drug interactions with hormonal contraception." J Fam Plann Reprod Health Care 31 (2005): 139-51
  34. Bauer KL, Wolf D, Patel M, Vinson DC "Clinical inquiries. Do antibiotics interfere with the efficacy of oral contraceptives?" J Fam Pract 54 (2005): 1079-80
  35. Back DJ, Grimmer SF, Orme ML, Proudlove D, Mann RD, Breckenridge AM "Evaluation of Committee on Safety of Medicines yellow card reports on oral contraceptive-drug interactions with anticonvulsants and antibiotics." Br J Clin Pharmacol 25 (1988): 527-32
  36. "Product Information. Arikayce (amikacin liposome)." Insmed Incorporated (2018):
  37. "Product Information. Nextstellis (drospirenone-estetrol)." Mayne Pharma (2021):
  38. "Product Information. Nextstellis (drospirenone-estetrol)." Mayne Pharma International Pty Ltd v 2.0 (2022):
  39. Curtis KM, Tepper NK, Jatlaoui TC, et al. "U.S. medical eligibility criteria (US MEC) for contraceptive use. https://www.cdc.gov/reproductivehealth/contraception/mmwr/mec/index.html" (2023):
  40. Faculty of Sexual & Reproductive Healthcare "FSRH CEU response to study: analysis of reports of unintended pregnancies associated with the combined use of non-enzyme inducing antibiotics and hormonal contraceptives - february 2021 https://www.fsrh.org/standards-and-guidance/documents/fsrh-ceu-respo" (2023):
  41. Faculty of Sexual & Reproductive Healthcare "FSRH CEU guidance: drug interactions with hormonal contraception (may 2022) https://www.fsrh.org/standards-and-guidance/documents/ceu-clinical-guidance-drug-interactions-with-hormonal/" (2023):
  42. Simmons KB, Haddad LB, Nanda K, Curtis KM "Drug interactions between non-rifamycin antibiotics and hormonal contraception: a systemic review." Am J Obstet Gynecol 218 (2018): 88-97.e14
  43. Zhanel GG, Siemens S, Slayter K, Mandell L "Antibiotic and oral contraceptive drug interactions: is there a need for concern?" Can J Infect Dis 10 (1999): 429-33
  44. Black A, Francoeur D, Rowe T, et al. "SOGC clinical practice guidelines canadian contraception consensus https://www.jogc.com/article/S1701-2163(16)30260-2/pdf" (2023):
  45. Allen K "Contraception - common issues and practical suggestions." Aust Fam Physician 41 (2012): 770-2
View all 45 references

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Drug and food interactions

Moderate

tinidazole food

Applies to: Fasigyn (tinidazole)

GENERALLY AVOID: Use of alcohol or products containing alcohol during nitroimidazole therapy may result in a disulfiram-like reaction in some patients. There have been a few case reports involving metronidazole, although data overall are not convincing. The presumed mechanism is inhibition of aldehyde dehydrogenase (ALDH) by metronidazole in a manner similar to disulfiram. Following ingestion of alcohol, inhibition of ALDH results in increased concentrations of acetaldehyde, the accumulation of which can produce an unpleasant physiologic response referred to as the 'disulfiram reaction'. Symptoms include flushing, throbbing in head and neck, throbbing headache, respiratory difficulty, nausea, vomiting, sweating, thirst, chest pain, palpitation, dyspnea, hyperventilation, tachycardia, hypotension, syncope, weakness, vertigo, blurred vision, and confusion. Severe reactions may result in respiratory depression, cardiovascular collapse, arrhythmia, myocardial infarction, acute congestive heart failure, unconsciousness, convulsions, and death. However, some investigators have questioned the disulfiram-like properties of metronidazole. One study found neither elevations in blood acetaldehyde nor objective or subjective signs of a disulfiram-like reaction to ethanol in six subjects treated with metronidazole (200 mg three times a day for 5 days) compared to six subjects who received placebo.

MANAGEMENT: Because clear evidence is lacking concerning the safety of ethanol use during nitroimidazole therapy, patients should be apprised of the potential for interaction and instructed to avoid alcoholic beverages and products containing alcohol or propylene glycol while using oral, intravenous, or vaginal preparations of a nitroimidazole. Alcoholic beverages should not be consumed for up to 3 days after completion of systemic nitroimidazole therapy.

References

  1. Giannini AJ, DeFrance DT "Metronidazole and alcohol: potential for combinative abuse." J Toxicol Clin Toxicol 20 (1983): 509-15
  2. Alexander I "Alcohol-antabuse syndrome in patients receiving metronidazole during gynaecological treatment." Br J Clin Pract 39 (1985): 292-3
  3. Harries DP, Teale KF, Sunderland G "Metronidazole and alcohol: potential problems." Scott Med J 35 (1990): 179-80
  4. Edwards DL, Fink PC, Van Dyke PO "Disulfiram-like reaction associated with intravenous trimethoprim-sulfamethoxazole and metronidazole." Clin Pharm 5 (1986): 999-1000
  5. "Product Information. Flagyl (metronidazole)." Searle PROD (2002):
  6. Williams CS, Woodcock KR "Do ethanol and metronidazole interact to produce a disulfiram-like reaction?." Ann Pharmacother 34 (2000): 255-7
  7. Visapaa JP, Tillonen JS, Kaihovaara PS, Salaspuro MP "Lack of disulfiram-like reaction with metronidazole and ethanol." Ann Pharmacother 36 (2002): 971-4
  8. Krulewitch CJ "An unexpected adverse drug effect." J Midwifery Womens Health 48 (2003): 67-8
  9. "Product Information. Tindamax (tinidazole)." Presutti Laboratories Inc (2004):
View all 9 references

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Minor

ethinyl estradiol food

Applies to: ethinyl estradiol / ethynodiol

Coadministration with grapefruit juice may increase the bioavailability of oral estrogens. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits. In a small, randomized, crossover study, the administration of ethinyl estradiol with grapefruit juice (compared to herbal tea) increased peak plasma drug concentration (Cmax) by 37% and area under the concentration-time curve (AUC) by 28%. Based on these findings, grapefruit juice is unlikely to affect the overall safety profile of ethinyl estradiol. However, as with other drug interactions involving grapefruit juice, the pharmacokinetic alterations are subject to a high degree of interpatient variability. Also, the effect on other estrogens has not been studied.

References

  1. Weber A, Jager R, Borner A, et al. "Can grapefruit juice influence ethinyl estradiol bioavailability?" Contraception 53 (1996): 41-7
  2. Schubert W, Eriksson U, Edgar B, Cullberg G, Hedner T "Flavonoids in grapefruit juice inhibit the in vitro hepatic metabolism of 17B-estradiol." Eur J Drug Metab Pharmacokinet 20 (1995): 219-24

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Minor

ethinyl estradiol food

Applies to: ethinyl estradiol / ethynodiol

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 "Interactions between ethanol and oral contraceptive steroids." Clin Pharmacol Ther 38 (1985): 371-80

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Minor

ethynodiol food

Applies to: ethinyl estradiol / ethynodiol

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 "Interactions between ethanol and oral contraceptive steroids." Clin Pharmacol Ther 38 (1985): 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.

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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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