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Drug Interactions between Doxy 100 and Kelnor 1/50

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

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Interactions between your drugs

Moderate

doxycycline ethinyl estradiol

Applies to: Doxy 100 (doxycycline) and Kelnor 1 / 50 (ethinyl estradiol / ethynodiol)

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.

ADJUST DOSING INTERVAL: The non-hormonal placebo pills included in some oral contraceptive preparations may contain iron, usually ferrous fumarate. Concomitant administration of these iron pills may significantly decrease the gastrointestinal absorption of antibiotics such as quinolones and tetracyclines. The mechanism is chelation of the antibiotic by the iron cation, forming a complex that is poorly absorbed from the gastrointestinal tract.

MANAGEMENT: In general, quinolone antibiotics should be dosed either 2 to 6 hours before or 4 to 8 hours after iron preparations to minimize the potential for interaction. The administration of tetracycline antibiotics and iron preparations should be separated by at least 2 to 3 hours, although this may not prevent the interaction with all tetracyclines. Some manufacturers advise against the use of iron-containing medications while patients are on tetracycline antibiotics. The antibiotic product labeling should be consulted for more specific information regarding timing of doses and/or avoidance of iron.

References

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  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. Polk RE, Helay DP, Sahai J, Drwal L, Racht E "Effect of ferrous sulfate and multivitamins with zinc on absorption of ciprofloxacin in normal volunteers." Antimicrob Agents Chemother 33 (1989): 1841-4
  4. 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
  5. Neuvonen PJ "Interactions with the absorption of tetracyclines." Drugs 11 (1976): 45-54
  6. Campbell NR, Kara M, Hasinoff BB, Haddara WM, McKay DW "Norfloxacin interaction with antacids and minerals." Br J Clin Pharmacol 33 (1992): 115-6
  7. Akerele JO, Okhamafe AO "Influence of oral co-administered metallic drugs on ofloxacin pharmacokinetics." J Antimicrob Chemother 28 (1991): 87-94
  8. Gothoni G, Neuvonen PJ, Mattila M, Hackman R "Iron-tetracycline interaction: effect of time interval between the drugs." Acta Med Scand 191 (1972): 409-11
  9. Wadworth AN, Goa KL "Lomefloxacin: a review of its antibacterial activity, pharmacokinetic properties and therapeutic use." Drugs 42 (1991): 1018-60
  10. 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
  11. Venho VM, Salonen RO, Mattila MJ "Modification of the pharmacokinetics of doxycycline in man by ferrous sulphate or charcoal." Eur J Clin Pharmacol 14 (1978): 277-80
  12. Baciewicz AM "Oral contraceptive drug interactions." Ther Drug Monit 7 (1985): 26-35
  13. Bint AJ, Burtt I "Adverse antibiotic drug interactions." Drugs 20 (1980): 57-68
  14. Dossetor J "Drug interactions with oral contraceptives." Br Med J 4 (1975): 467-8
  15. DeSano EA, Hurley SC "Possible interactions of antihistamines and antibiotics with oral contraceptive effectiveness." Fertil Steril 37 (1982): 853-4
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  18. Barnett ML "Inhibition of oral contraceptive effectiveness by concurrent antibiotic administration." J Periodontol 56 (1985): 18-20
  19. "Product Information. Declomycin (demeclocycline)." Lederle Laboratories PROD (2001):
  20. Campbell NR, Hasinoff BB "Iron supplements: a common cause of drug interactions." Br J Clin Pharmacol 31 (1991): 251-5
  21. London BM, Lookingbill DP "Frequency of pregnancy in acne patients taking oral antibiotics and oral contraceptives." Arch Dermatol 130 (1994): 392-3
  22. Bacon JF, Shenfield GM "Pregnancy attributable to interaction between tetracycline and oral contraceptives." Br Med J 280 (1980): 293
  23. Fazio A "Oral contraceptive drug interactions: important considerations." South Med J 84 (1991): 997-1002
  24. Back DJ, Orme ML "Pharmacokinetic drug interactions with oral contraceptives." Clin Pharmacokinet 18 (1990): 472-84
  25. 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
  26. Orme ML, Back DJ "Interactions between oral contraceptive steroids and broad-spectrum antibiotics." Clin Exp Dermatol 11 (1986): 327-31
  27. Lehto P, Kivisto KT "Different effects of products containing metal ions on the absorption of lomefloxacin." Clin Pharmacol Ther 56 (1994): 477-82
  28. Wermeling DP, Chandler MH, Sides GD, Collins D, Muse KN "Dirithromycin increases ethinyl estradiol clearance without allowing ovulation." Obstet Gynecol 86 (1995): 78-84
  29. Bateman FJ "Effects of tetracyclines." Br Med J 4 (1970): 802
  30. Neuvonen PJ, Gothoni G, Hackman R, Bjorksten K "Interference of iron with the absorption of tetracyclines in man." Br Med J 4 (1970): 532-4
  31. Greenberger NJ "Absorption of tetracyclines: interference by iron." Ann Intern Med 74 (1971): 792-3
  32. Neuvonen PJ, Penttila O "Effect of oral ferrous sulphate on the half-life of doxycycline in man." Eur J Clin Pharmacol 7 (1974): 361-3
  33. Silber TJ "Apparent oral contraceptive failure associated with antibiotic administration." J Adolesc Health Care 4 (1983): 287-9
  34. Bollen M "Use of antibiotics when taking the oral contraceptive pill." Aust Fam Physician 24 (1995): 928-9
  35. Kleier DJ, Tucker JE "Oral contraceptive failure secondary to dentally prescribed drugs: fact or fiction?" J Colo Dent Assoc 66 (1987): 5-6
  36. "Product Information. Levaquin (levofloxacin)." Ortho McNeil Pharmaceutical PROD (2001):
  37. "Product Information. Raxar (grepafloxacin)." Glaxo Wellcome PROD (2001):
  38. "Product Information. Zagam (sparfloxacin)." Rhone Poulenc Rorer PROD (2001):
  39. "Product Information. Trovan (trovafloxacin)." Pfizer U.S. Pharmaceuticals PROD (2001):
  40. 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
  41. 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
  42. Honig PK, Gillespie BK "Clinical significance of pharmacokinetic drug interactions with over-the-counter (OTC) drugs." Clin Pharmacokinet 35 (1998): 167-71
  43. Weisberg E "Interactions between oral contraceptives and antifungals antibacterials - Is contraceptive failure the result?." Clin Pharmacokinet 36 (1999): 309-13
  44. Burroughs KE, Chambliss ML "Antibiotics and oral contraceptive failure." Arch Fam 9 (2000): 81-2
  45. Weaver K, Glasier A "Interaction between broad-spectrum antibiotics and the combined oral contraceptive pill: a literature review." Contraception 59 (1999): 71-8
  46. King VJ "OC failure rates and oral antibiotics." J Fam Pract 45 (1997): 104-5
  47. Zachariassen RD "Loss of oral contraceptive efficacy by concurrent antibiotic administration." Women Health 22 (1994): 17-26
  48. Dickinson BD, Altman RD, Nielsen NH, Sterling ML "Drug interactions between oral contraceptives and antibiotics." Obstet Gynecol 98(5 Pt 1) (2001): 853-60
  49. Archer JS, Archer DF "Oral contraceptive efficacy and antibiotic interaction: A myth debunked." J Am Acad Dermatol 46 (2002): 917-23
  50. Orme M, Back DJ "Oral contraceptive steroids--pharmacological issues of interest to the prescribing physician." Adv Contracept 7 (1991): 325-31
  51. "Product Information. Factive (gemifloxacin)." *GeneSoft Inc (2003):
  52. DeRossi SS, Hersh EV "Antibiotics and oral contraceptives." Dent Clin North Am 46 (2002): 653-64
  53. "FFPRHC Guidance (April 2005). Drug interactions with hormonal contraception." J Fam Plann Reprod Health Care 31 (2005): 139-51
  54. 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
  55. 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
  56. "Product Information. Seysara (sarecycline)." Allergan Inc (2018):
  57. "Product Information. Nuzyra (omadacycline)." Paratek Pharmaceuticals, Inc. (2018):
  58. 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):
  59. 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):
  60. 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):
  61. 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
  62. 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
  63. 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):
  64. Allen K "Contraception - common issues and practical suggestions." Aust Fam Physician 41 (2012): 770-2
  65. "Product Information. Ciprofloxacin Hydrochloride (ciprofloxacin)." Aurobindo Pharma USA Inc (2021):
  66. "Product Information. Tetracycline Hydrochloride (tetracycline)." Blenheim Pharmaceutical, Inc. (2010):
  67. "Product Information. Doxycycline Monohydrate (doxycycline)." Lupin Pharmaceuticals Inc (2023):
  68. "Product Information. Apo-Doxy (doxycycline)." Apotex Incorporated (2016):
  69. "Product Information. Apo-Doxycycline MR (doxycycline)." Apotex Inc (2021):
  70. "Product Information. Doxycycline Hyclate (doxycycline)." Sovereign Medical Ltd (2021):
  71. "Product Information. Efracea (doxycycline)." Galderma (UK) Ltd (2022):
  72. "Product Information. LevoFLOXacin (levoFLOXacin)." Aurobindo Pharma USA Inc (2020):
  73. "Product Information. Levofloxacin (levofloxacin)." Ipca Laboratories UK Ltd (2021):
  74. "Product Information. Ofloxacin (ofloxacin)." Nivagen Pharmaceuticals (2022):
  75. "Product Information. Ofloxacin (ofloxacin)." Viatris UK Healthcare Ltd (2022):
  76. "Product Information. Ciprofloxacin Extended Release (ciprofloxacin)." Dr. Reddy's Laboratories Inc (2011):
  77. "Product Information. Ciprofloxacin (ciprofloxacin)." Milpharm Ltd (2021):
  78. "Product Information. Moxifloxacin Hydrochloride (moxifloxacin)." Mylan Institutional LLC (2021):
  79. "Product Information. Avelox (moxifloxacin)." Bayer Plc (2020):
  80. Fischer JAJ, Sasai CS, Karakochuk CD "Iron-containing oral contraceptives and their effect on hemoglobin and biomarkers of iron status: a narrative review. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308850/" (2023):
View all 80 references

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Drug and food interactions

Moderate

doxycycline food

Applies to: Doxy 100 (doxycycline)

GENERALLY AVOID: The bioavailability of oral tetracyclines and iron salts may be significantly decreased during concurrent administration. Therapeutic failure may result. The proposed mechanism is chelation of tetracyclines by the iron cation, forming an insoluble complex that is poorly absorbed from the gastrointestinal tract. In ten healthy volunteers, simultaneous oral administration of ferrous sulfate 200 mg and single doses of various tetracyclines (200 mg to 500 mg) resulted in reductions in the serum levels of methacycline and doxycycline by 80% to 90%, oxytetracycline by 50% to 60%, and tetracycline by 40% to 50%. In another study, 300 mg of ferrous sulfate reduced the absorption of tetracycline by 81% and that of minocycline by 77%. Conversely, the absorption of iron has been shown to be decreased by up to 78% in healthy subjects and up to 65% in patients with iron depletion when ferrous sulfate 250 mg was administered with tetracycline 500 mg. Available data suggest that administration of iron 3 hours before or 2 hours after a tetracycline largely prevents the interaction with most tetracyclines except doxycycline. Due to extensive enterohepatic cycling, iron binding may occur with doxycycline even when it is given parenterally. It has also been shown that when iron is administered up to 11 hours after doxycycline, serum concentrations of doxycycline may still be reduced by 20% to 45%.

MANAGEMENT: Coadministration of a tetracycline with any iron-containing product should be avoided if possible. Otherwise, patients should be advised to stagger the times of administration by at least three to four hours, although separating the doses may not prevent the interaction with doxycycline.

References

  1. Neuvonen PJ "Interactions with the absorption of tetracyclines." Drugs 11 (1976): 45-54
  2. Gothoni G, Neuvonen PJ, Mattila M, Hackman R "Iron-tetracycline interaction: effect of time interval between the drugs." Acta Med Scand 191 (1972): 409-11
  3. Venho VM, Salonen RO, Mattila MJ "Modification of the pharmacokinetics of doxycycline in man by ferrous sulphate or charcoal." Eur J Clin Pharmacol 14 (1978): 277-80
  4. "Product Information. Minocin (minocycline)." Lederle Laboratories PROD (2002):
  5. Campbell NR, Hasinoff BB "Iron supplements: a common cause of drug interactions." Br J Clin Pharmacol 31 (1991): 251-5
  6. Bateman FJ "Effects of tetracyclines." Br Med J 4 (1970): 802
  7. Neuvonen PJ, Gothoni G, Hackman R, Bjorksten K "Interference of iron with the absorption of tetracyclines in man." Br Med J 4 (1970): 532-4
  8. Greenberger NJ "Absorption of tetracyclines: interference by iron." Ann Intern Med 74 (1971): 792-3
  9. Neuvonen PJ, Penttila O "Effect of oral ferrous sulphate on the half-life of doxycycline in man." Eur J Clin Pharmacol 7 (1974): 361-3
  10. "Product Information. Seysara (sarecycline)." Allergan Inc (2018):
  11. "Product Information. Nuzyra (omadacycline)." Paratek Pharmaceuticals, Inc. (2018):
View all 11 references

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Minor

ethinyl estradiol food

Applies to: Kelnor 1 / 50 (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

doxycycline food

Applies to: Doxy 100 (doxycycline)

Chronic alcohol consumption may enhance the elimination of doxycycline. The mechanism is induction of hepatic microsomal enzymes by alcohol. In one study, the half-life of doxycycline in six alcoholics was 10.5 hours, compared with 14.7 hours in six control patients. In addition, half the alcoholic patients had serum concentrations below what is generally considered the minimum therapeutic concentration (0.5 mcg/mL) at 12 to 24 hours after the dose. The investigators suggest that twice-a-day dosing may be indicated in these patients, especially if additional inducing drugs are used. The elimination of other tetracyclines probably is not affected by alcohol consumption.

References

  1. Neuvonen PJ, Penttila O, Roos M, Tirkkonen J "Effect of long-term alcohol consumption on the half-life of tetracycline and doxycycline in man." Int J Clin Pharmacol Biopharm 14 (1976): 303-7

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Minor

ethinyl estradiol food

Applies to: Kelnor 1 / 50 (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: Kelnor 1 / 50 (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

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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