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Drug Interactions between Amabelz and sulfamethoxazole

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

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Moderate

sulfamethoxazole estradiol

Applies to: sulfamethoxazole and Amabelz (estradiol / norethindrone)

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

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  3. Neely JL, Abate M, Swinker M, D'Angio R (1991) "The effect of doxycycline on serum levels of ethinyl estradiol, norethindrone, and endogenous progesterone." Obstet Gynecol, 77, p. 416-20
  4. Joshi JV, Joshi UM, Sankholi GM, et al. (1980) "A study of interaction of low-dose combination oral contraceptive with ampicillin and metronidazole." Contraception, 22, p. 643-52
  5. Baciewicz AM (1985) "Oral contraceptive drug interactions." Ther Drug Monit, 7, p. 26-35
  6. Bint AJ, Burtt I (1980) "Adverse antibiotic drug interactions." Drugs, 20, p. 57-68
  7. Dossetor J (1975) "Drug interactions with oral contraceptives." Br Med J, 4, p. 467-8
  8. DeSano EA, Hurley SC (1982) "Possible interactions of antihistamines and antibiotics with oral contraceptive effectiveness." Fertil Steril, 37, p. 853-4
  9. Szoka PR, Edgren RA (1988) "Drug interactions with oral contraceptives: compilation and analysis of an adverse experience report database." Fertil Steril, 49(5 Suppl), s31-8
  10. Barnett ML (1985) "Inhibition of oral contraceptive effectiveness by concurrent antibiotic administration." J Periodontol, 56, p. 18-20
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  13. Bacon JF, Shenfield GM (1980) "Pregnancy attributable to interaction between tetracycline and oral contraceptives." Br Med J, 280, p. 293
  14. Fazio A (1991) "Oral contraceptive drug interactions: important considerations." South Med J, 84, p. 997-1002
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  16. Back DJ, Tjia J, Martin C, Millar E, Mant T, Morrison P, Orme M (1991) "The lack of interaction between temafloxacin and combined oral contraceptive steroids." Contraception, 43, p. 317-23
  17. Orme ML, Back DJ (1986) "Interactions between oral contraceptive steroids and broad-spectrum antibiotics." Clin Exp Dermatol, 11, p. 327-31
  18. Wermeling DP, Chandler MH, Sides GD, Collins D, Muse KN (1995) "Dirithromycin increases ethinyl estradiol clearance without allowing ovulation." Obstet Gynecol, 86, p. 78-84
  19. Silber TJ (1983) "Apparent oral contraceptive failure associated with antibiotic administration." J Adolesc Health Care, 4, p. 287-9
  20. Bollen M (1995) "Use of antibiotics when taking the oral contraceptive pill." Aust Fam Physician, 24, p. 928-9
  21. Kleier DJ, Tucker JE (1987) "Oral contraceptive failure secondary to dentally prescribed drugs: fact or fiction?" J Colo Dent Assoc, 66, p. 5-6
  22. Back DJ, Breckenridge AM, Crawford FE, MacIver M, Orne ML, Rowe PH (1981) "Interindividual variation and drug interactions with hormonal steroid contraceptives." Drugs, 21, p. 46-61
  23. Helms SE, Bredle DL, Zajic J, Jarjoura D, Brodell RT, Krishnarao I (1997) "Oral contraceptive failure rates and oral antibiotics." J Am Acad Dermatol, 36, p. 705-10
  24. Weisberg E (1999) "Interactions between oral contraceptives and antifungals antibacterials - Is contraceptive failure the result?." Clin Pharmacokinet, 36, p. 309-13
  25. Burroughs KE, Chambliss ML (2000) "Antibiotics and oral contraceptive failure." Arch Fam, 9, p. 81-2
  26. Weaver K, Glasier A (1999) "Interaction between broad-spectrum antibiotics and the combined oral contraceptive pill: a literature review." Contraception, 59, p. 71-8
  27. King VJ (1997) "OC failure rates and oral antibiotics." J Fam Pract, 45, p. 104-5
  28. Zachariassen RD (1994) "Loss of oral contraceptive efficacy by concurrent antibiotic administration." Women Health, 22, p. 17-26
  29. Dickinson BD, Altman RD, Nielsen NH, Sterling ML (2001) "Drug interactions between oral contraceptives and antibiotics." Obstet Gynecol, 98(5 Pt 1), p. 853-60
  30. Archer JS, Archer DF (2002) "Oral contraceptive efficacy and antibiotic interaction: A myth debunked." J Am Acad Dermatol, 46, p. 917-23
  31. Orme M, Back DJ (1991) "Oral contraceptive steroids--pharmacological issues of interest to the prescribing physician." Adv Contracept, 7, p. 325-31
  32. DeRossi SS, Hersh EV (2002) "Antibiotics and oral contraceptives." Dent Clin North Am, 46, p. 653-64
  33. (2005) "FFPRHC Guidance (April 2005). Drug interactions with hormonal contraception." J Fam Plann Reprod Health Care, 31, p. 139-51
  34. Bauer KL, Wolf D, Patel M, Vinson DC (2005) "Clinical inquiries. Do antibiotics interfere with the efficacy of oral contraceptives?" J Fam Pract, 54, p. 1079-80
  35. Back DJ, Grimmer SF, Orme ML, Proudlove D, Mann RD, Breckenridge AM (1988) "Evaluation of Committee on Safety of Medicines yellow card reports on oral contraceptive-drug interactions with anticonvulsants and antibiotics." Br J Clin Pharmacol, 25, p. 527-32
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  39. Curtis KM, Tepper NK, Jatlaoui TC, et al. (2023) U.S. medical eligibility criteria (US MEC) for contraceptive use. https://www.cdc.gov/reproductivehealth/contraception/mmwr/mec/index.html
  40. Faculty of Sexual & Reproductive Healthcare (2023) 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
  41. Faculty of Sexual & Reproductive Healthcare (2023) 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/
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  45. Allen K (2012) "Contraception - common issues and practical suggestions." Aust Fam Physician, 41, p. 770-2
View all 45 references

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Drug and food interactions

Moderate

norethindrone food

Applies to: Amabelz (estradiol / 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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Moderate

sulfamethoxazole food

Applies to: sulfamethoxazole

MONITOR: Two cases have been reported in which patients on sulfamethoxazole-trimethoprim therapy, after consuming beer, reported flushing, heart palpitations, dyspnea, headache, and nausea (disulfiram - alcohol type reactions). First-generation sulfonylureas have been reported to cause facial flushing when administered with alcohol by inhibiting acetaldehyde dehydrogenase and subsequently causing acetaldehyde accumulation. Since sulfamethoxazole is chemically related to first-generation sulfonylureas, a disulfiram-like reaction with products containing sulfamethoxazole is theoretically possible. However, pharmacokinetic/pharmacodynamic data are lacking and in addition, the two reported cases cannot be clearly attributed to the concomitant use of sulfamethoxazole-trimethoprim and alcohol.

MANAGEMENT: Patients should be alerted to the potential for this interaction and although the risk for this interaction is minimal, caution is recommended while taking sulfamethoxazole-trimethoprim concomitantly with alcohol.

References

  1. Heelon MW, White M (1998) "Disulfiram-cotrimoxazole reaction." Pharmacotherapy, 18, p. 869-70
  2. Mergenhagen KA, Wattengel BA, Skelly MK, Clark CM, Russo TA (2020) "Fact versus fiction: a review of the evidence behind alcohol and antibiotic interactions." Antimicrob Agents Chemother, 64, e02167-19

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Minor

estradiol food

Applies to: Amabelz (estradiol / norethindrone)

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

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Minor

norethindrone food

Applies to: Amabelz (estradiol / 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.

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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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