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Drug Interactions between amoxicillin / clarithromycin / omeprazole and Gynodiol

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

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Interactions between your drugs

Major

clarithromycin estradiol

Applies to: amoxicillin / clarithromycin / omeprazole and Gynodiol (estradiol)

MONITOR CLOSELY: Coadministration of clarithromycin, telithromycin, or troleandomycin may increase the plasma concentrations of drugs that are substrates of the CYP450 3A4 isoenzyme, by reducing their clearance, as these antibiotics are potent inhibitors of this isoenzyme. Many estrogen and progestin type medications are CYP450 3A4 substrates. These medications are used for a variety of purposes including, but not limited to, contraception, acne treatment, hormone replacement therapy, and appetite stimulation. When telithromycin was co-administered with oral contraceptives containing ethinyl estradiol and levonorgestrel, studies showed that the systemic concentration (AUC) of ethinyl estradiol did not change and the AUC of levonorgestrel increased by 50%. The study showed that telithromycin did not interfere with the anti-ovulatory effect of oral contraceptives containing ethinyl estradiol and levonorgestrel.

MANAGEMENT: Caution is advised if clarithromycin, telithromycin, or troleandomycin must be used concurrently with medications that undergo metabolism by CYP450 3A4. Patients should be monitored for increased adverse effects from the hormonal treatment if it must be co-administered with one of these antibiotics. Some serious side effects associated with hormonal treatment include, but are not limited to, cardiovascular disease (e.g., venous thromboembolism, myocardial infarction, and stroke); breast cancer; loss of bone mineral density; changes in mood; cholestatic jaundice; and dementia. Some of these side effects are affected by other factors such as medication dosage, concurrent medications, age, smoking status, and other disease states. If concurrent therapy with any of these antibiotics is necessary, please refer to the product labeling for more specific adverse effects to monitor for and counsel the patient and/or the patient's caregiver on the risks and benefits of concurrent therapy.

MONITOR CLOSELY: Estrogenic steroids, but not progestins, undergo enterohepatic cycling. It is possible that antimicrobials may interfere with the enterohepatic recirculation of estrogens by decreasing bacteria in the gastrointestinal tract that are responsible for regenerating parent estrogen molecules following first-pass metabolism. Most of the research regarding this possible interaction has been done with oral contraceptives; however, 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. 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, except for enzyme inducing medications like the rifamycins and possibly griseofulvin, have not been shown to significantly increase the clearance of estrogens present in combined hormonal contraceptives. 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. 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):
  2. 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):
  3. 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):
  4. 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
  5. 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
  6. 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):
  7. Allen K "Contraception - common issues and practical suggestions." Aust Fam Physician 41 (2012): 770-2
  8. "Product Information. Ketek (telithromycin)." Physicians Total Care (2010):
  9. "Product Information. Ketek (telithromycin)." Aventis Pharmaceuticals (2009):
  10. "Product Information. Ketek (telithromycine)." SANOFI BELGIUM (2011):
  11. "Product Information. Clarithromycin (clarithromycin)." Alembic Pharmaceuticals (2023):
  12. "Product Information. Clarithromycin ER (clarithromycin)." Actavis U.S. (Purepac Pharmaceutical Company) (2020):
  13. "Product Information. Act Clarithromycin XL (clarithromycin)." Actavis Pharma Company (2020):
  14. "Product Information. Biaxin BID (clarithromycin)." BGP Pharma Inc (2021):
  15. "Product Information. CLARITHROMYcin (Noumed) (cLARITHROMYcin)." Blooming Health Pty Ltd (2021):
  16. "Product Information. Klacid (cLARITHROMYcin)." Mylan Health Pty Ltd (2022):
  17. "Product Information. Klaricid IV (clarithromycin)." Viatris UK Healthcare Ltd (2022):
  18. "Product Information. Clarithromycin (clarithromycin)." Ranbaxy (UK) Ltd (2023):
  19. "Product Information. Clarithromycin (clarithromycin)." Milpharm Ltd (2023):
  20. "Product Information. Mycifor XL (clarithromycin)." Forum Products Ltd (2015):
  21. FDA. United States Food and Drug Administration "Drug development and drug interactions: table of substrates, inhibitors and inducers. https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers" (2023):
View all 21 references

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Moderate

amoxicillin estradiol

Applies to: amoxicillin / clarithromycin / omeprazole and Gynodiol (estradiol)

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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Minor

amoxicillin clarithromycin

Applies to: amoxicillin / clarithromycin / omeprazole and amoxicillin / clarithromycin / omeprazole

Although some in vitro data indicate synergism between macrolide antibiotics and penicillins, other in vitro data indicate antagonism. When these drugs are given together, neither has predictable therapeutic efficacy. Data are available for erythromycin, although theoretically this interaction could occur with any macrolide. Except for monitoring of the effectiveness of antibiotic therapy, no special precautions appear to be necessary.

References

  1. Strom J "Penicillin and erythromycin singly and in combination in scarlatina therapy and the interference between them." Antibiot Chemother 11 (1961): 694-7
  2. Cohn JR, Jungkind DL, Baker JS "In vitro antagonism by erythromycin of the bactericidal action of antimicrobial agents against common respiratory pathogens." Antimicrob Agents Chemother 18 (1980): 872-6
  3. Penn RL, Ward TT, Steigbigel RT "Effects of erythromycin in combination with penicillin, ampicillin, or gentamicin on the growth of listeria monocytogenes." Antimicrob Agents Chemother 22 (1982): 289-94

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Minor

clarithromycin omeprazole

Applies to: amoxicillin / clarithromycin / omeprazole and amoxicillin / clarithromycin / omeprazole

Clarithromycin may increase and prolong the omeprazole plasma concentration. The mechanism may be related to clarithromycin inhibition of hepatic cytochrome P450 enzymes responsible for omeprazole metabolism. Coadministration of omeprazole may result in an increase in clarithromycin and 14-(R)-hydroxyclarithromycin plasma concentrations. These increases may be due to the effect of omeprazole on gastric pH.

References

  1. Zhou Q, Yamamoto I, Fukuda T, Ohno M, Sumida A, Azuma J "CYP2C19 genotypes and omeprazole metabolism after single and repeated dosing when combined with clarithromycin." Eur J Clin Pharmacol 55 (1999): 43-7
  2. Gustavson LE, Kaiser JF, Edmonds AL, Locke CS, DeBartolo ML, Schneck DW "Effect of omeprazole on concentrations of clarithromycin in plasma and gastric tissue at steady state." Antimicrob Agents Chemother 39 (1995): 2078-83
  3. Furuta T, Ohashi K, Kobayashi K, Iida I, Yoshida H, Shirai N, Takashima M, Kosuge K, Hanai H, Chiba K, Ishizaki T, Kaneko E "Effects of clarithromycin on the metabolism of omeprazole in relation to CYP2C19 genotype status in humans." Clin Pharmacol Ther 66 (1999): 265-74

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Drug and food interactions

Minor

clarithromycin food

Applies to: amoxicillin / clarithromycin / omeprazole

Grapefruit juice may delay the gastrointestinal absorption of clarithromycin but does not appear to affect the overall extent of absorption or inhibit the metabolism of clarithromycin. The mechanism of interaction is unknown but may be related to competition for intestinal CYP450 3A4 and/or absorptive sites. In an open-label, randomized, crossover study consisting of 12 healthy subjects, coadministration with grapefruit juice increased the time to reach peak plasma concentration (Tmax) of both clarithromycin and 14-hydroxyclarithromycin (the active metabolite) by 80% and 104%, respectively, compared to water. Other pharmacokinetic parameters were not significantly altered. This interaction is unlikely to be of clinical significance.

References

  1. Cheng KL, Nafziger AN, Peloquin CA, Amsden GW "Effect of grapefruit juice on clarithromycin pharmacokinetics." Antimicrob Agents Chemother 42 (1998): 927-9

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Minor

estradiol food

Applies to: Gynodiol (estradiol)

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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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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