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Oral contraceptive efficacy and antibiotic interaction: A myth debunked

      Abstract

      The purpose of this study was to review the pharmacokinetic and clinical literature regarding the efficacy of oral contraceptives when used concomitantly with antibiotic therapy. Relevant literature was identified by searching MEDLINE and EMBASE. Other sources were located by consulting the bibliographies of the material collected from MEDLINE and EMBASE. Pharmacokinetic evidence demonstrates that plasma levels of oral contraceptive steroids are unchanged with the concomitant administration of antibiotics, including ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline. However, reduced steroid levels have been reported in women taking rifampin with oral contraceptives. Clinical reports of contraceptive failure with antibiotic use are retrospective, have multiple potential biases, and are not supported by pharmacokinetic data. Available scientific and pharmacokinetic data do not support the hypothesis that antibiotics (with the exception of rifampin) lower the contraceptive efficacy of oral contraceptives. (J Am Acad Dermatol 2002;46:917-23.)
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      References

        • American College of Obstetricians and Gynecologists
        The use of hormonal contraception in women with coexisting medical conditions.
        ACOG Practice Bulletin. 2000; 18: 1-13
        • Thiboutot D
        • Archer DF
        • Lemay A
        • Washenik K
        • Roberts J
        • Harrison DD.
        A randomized, controlled trial of 20 μg ethinyl estradiol/100 μg levonorgestrel for acne treatment.
        Fertil Steril. 2001; 76: 461-468
        • Lucky AW
        • Henderson TA
        • Olson WH
        • Robisch DM
        • Lebwohl M
        • Swinyer LJ.
        Effectiveness of norgestimate and ethinyl estradiol in treating moderate acne vulgaris.
        J Am Acad Dermatol. 1997; 37: 746-754
        • Redmond GP
        • Olson WH
        • Lippman JS
        • Kafrissen ME
        • Jones TM
        • Jorizzo JL.
        Norgestimate and ethinyl estradiol in the treatment of acne vulgaris: a randomized, placebo-controlled trial.
        Obstet Gynecol. 1997; 89: 615-622
        • Shenfield GM.
        Oral contraceptives. Are drug interactions of clinical significance?.
        Drug Saf. 1993; 9: 21-37
        • Orme ML'E
        • Back DJ.
        Factors affecting the enterohepatic circulation of oral contraceptive steroids.
        Am J Obstet Gynecol. 1990; 163: 2146-2152
        • Hanker JP.
        Gastrointestinal disease and oral contraception.
        Am J Obstet Gynecol. 1990; 163: 2204-2207
        • Back DJ
        • Breckenridge AM
        • Crawford FE
        • MacIver M
        • Orme ML'E
        • Rowe PH
        • et al.
        An investigation of the pharmacokinetics of ethynyl estradiol in women using radioimmunoassay.
        Contraception. 1979; 20: 263-273
        • Back DJ
        • Orme ML'E
        Drug interactions.
        in: Pharmacology of the contraceptive steroids. Raven Press, New York1994: 407-425
        • Orme ML'E
        • Back DJ.
        Interactions between oral contraceptive steroids and broad-spectrum antibiotics.
        Clin Exp Dermatol. 1986; 11: 327-331
        • Kuhl H.
        Pharmacokinetics of oestrogens and progestogens.
        Maturitas. 1990; 12: 171-197
        • Back DJ
        • Bates M
        • Burke MW
        • Breckenridge AM
        • Crawford FE
        • MacIver M
        • et al.
        Plasma Xa inhibitory activities and plasma concentrations of norgestrel and ethinyloestradiol in women on oral contraceptive steroids.
        Br J Clin Pharmacol. 1979; 8: 505-506
        • Shenfield GM
        • Griffin JM.
        Clinical pharmacokinetics of contraceptive steroids. An update.
        Clin Pharmacokinet. 1991; 20: 15-37
        • Murphy AA
        • Zacur HA
        • Charache P
        • Burkman RT.
        The effect of tetracycline on levels of oral contraceptives.
        Am J Obstet Gynecol. 1991; 164: 28-33
        • Back DJ
        • Breckenridge AM
        • Crawford F
        • MacIver M
        • Orme ML'E
        • Park BK
        • et al.
        The effect of rifampicin on norethisterone pharmacokinetics.
        Eur J Clin Pharmacol. 1979; 15: 193-197
        • Back DJ
        • Breckenridge AM
        • Crawford FE
        • Hall JM
        • MacIver M
        • Orme ML'E
        • et al.
        The effect of rifampicin on the pharmacokinetics of ethynylestradiol in women.
        Contraception. 1980; 21: 135-143
        • Barditch-Crovo P
        • Trapnell CB
        • Ette E
        • Zacur HA
        • Coresh J
        • Rocco LE
        • et al.
        The effects of rifampin and rifabutin on the pharmacokinetics and pharmacodynamics of a combination oral contraceptive.
        Clin Pharmacol Ther. 1999; 65: 428-438
        • LeBel M
        • Masson E
        • Guilbert E
        • Colborn D
        • Paquet F
        • Allard S
        • et al.
        Effects of rifabutin and rifampicin on the pharmacokinetics of ethinylestradiol and norethindrone.
        J Clin Pharmacol. 1998; 38: 1042-1050
        • Adlercreutz H
        • Martin F
        • Lehtinen T
        • Tikkanen MJ
        • Pulkkinen MO.
        Effect of ampicillin administration on plasma conjugated and unconjugated estrogen and progesterone levels in pregnancy.
        Am J Obstet Gynecol. 1977; 128: 266-271
        • Dada OA
        • Martins OO.
        Drug effects on the intestinal absorption of estrogens.
        J Steroid Biochem. 1983; 19: 821-825
        • Back DJ
        • Breckenridge AM
        • MacIver M
        • Orme ML'E
        • Rowe PH
        • Staiger C
        • et al.
        The effects of ampicillin oral contraceptive steroids in women.
        Br J Clin Pharmacol. 1982; 14: 43-48
        • Friedman CI
        • Huneke AL
        • Kim MH
        • Powell J.
        The effect of ampicillin on oral contraceptive effectiveness.
        Obstet Gynecol. 1980; 55: 33-37
        • Joshi JV
        • Joshi UM
        • Sankholi GM
        • Krishna U
        • Mandlekar A
        • Chowdhury V
        • et al.
        A study of interaction of low-dose combination oral contraceptive with ampicillin and metronidazole.
        Contraception. 1980; 22: 643-652
        • Maggiolo F
        • Puricelli G
        • Dottorini M
        • Caprioli S
        • Bianchi W
        • Suter F.
        The effect of ciprofloxacin on oral contraceptive steroid treatments.
        Drugs Exp Clin Res. 1991; 17: 451-454
        • Scholten PC
        • Droppert RM
        • Zwinkels MG
        • Moesker HL
        • Nauta JJ
        • Hoepelman IM.
        No interaction between ciprofloxacin and an oral contraceptive.
        Antimicrob Agents Chemother. 1998; 42: 3266-3268
        • Back DJ
        • Tjia C
        • Martin C
        • Miller E
        • Salmon P.
        The interaction between clarithromycin and combined oral contraceptive steroids.
        J Pharm Med. 1991; 2: 81-87
        • 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. 1991; 77: 416-420
        • Csemiczky G
        • Alvendal C
        • Landgren BM.
        Risk for ovulation in women taking a low-dose oral contraceptive (Microgynon) when receiving antibacterial treatment with a fluoroquinolone (ofloxacin).
        Adv Contracept. 1996; 12: 101-109
        • Meyer B
        • Muller F
        • Wessels P
        • Maree J.
        A model to detect interactions between roxithromycin and oral contraceptives.
        Clin Pharmacol Ther. 1990; 47: 671-674
        • Back DJ
        • Tjia J
        • Martin C
        • Millar E
        • Mant T
        • Morrison P
        • et al.
        The lack of interaction between temafloxacin and combined oral contraceptive steroids.
        Contraception. 1991; 43: 317-323
      1. Grimmer SF, Allen WL, Back DJ, Breckenridge AM, Orme ML'E, Tjia J. The effect of cotrimoxazole on oral contraceptive steroids in women. Contraception 983;28:53-9.

        • Leigh DA
        • Reeves DS
        • Simmons K
        • Thomas AL
        • Wilkinson PJ.
        Talampicillin: a new derivative of ampicillin.
        BMJ. 1976; 2: 378-380
        • Wermeling DP
        • Chandler MHH
        • Sides GD
        • Collins D
        • Muse KN.
        Dirithromycin increases ethinyl estradiol clearance without allowing ovulation.
        Obstet Gynecol. 1995; 85: 78-84
        • Sparrow MJ.
        Pill method failures.
        N Z Med J. 1987; 100: 102-105
        • Silber TJ.
        Apparent oral contraceptive failure associated with antibiotic administration.
        J Adolesc Health Care. 1983; 4: 287-289
        • London BM
        • Lookingbill DP.
        Frequency of pregnancy in acne patients taking oral antibiotics and oral contraceptives.
        Arch Dermatol. 1994; 130 ([letter]): 392-393
        • DeSano Jr, EA
        • Hurley SC.
        Possible interactions of antihistamines and antibiotics with oral contraceptive effectiveness.
        Fertil Steril. 1982; 37: 853-854
        • Back DJ
        • Grimmer SF
        • Orme ML'E
        • Proudlove C
        • 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. 1988; 25: 527-532
        • Fraser IS
        • Jansen RPS.
        Why do inadvertent pregnancies occur in oral contraceptive users? Effectiveness of oral contraceptive regimens and interfering factors.
        Contraception. 1983; 27: 531-551
        • Rosenberg MJ
        • Waugh MS
        • Stevens CM.
        Smoking and cycle control among oral contraceptive users.
        Am J Obstet Gynecol. 1996; 174: 628-632
        • Szoka PR
        • Edgren RA.
        Drug interactions with oral contraceptives: compilation and analysis of an adverse experience report database.
        Fertil Steril. 1988; 49: 31S-38S
        • Helms SE
        • Bredle DL
        • Zajic J
        • Jarjoura D
        • Brodell RT
        • Krishnarao I.
        Oral contraceptive failure rates and oral antibiotics.
        J Am Acad Dermatol. 1997; 36: 705-710
        • Stockley I.
        Interactions with oral contraceptives.
        Pharm J. 1976; : 140-143
        • Back DJ
        • Breckenridge AM
        • Challiner M
        • Crawford FE
        • Orme ML'E
        • Rowe PH
        • et al.
        The effect of antibiotics on the enterohepatic circulation of ethinylestradiol and norethisterone in the rat.
        J Steroid Biochem. 1978; 9: 527-531
        • Fotherby K.
        Interactions with oral contraceptives.
        Am J Obstet Gynecol. 1990; 163: 2153-2159
        • LaCasa C.
        California court denies wrongful birth claim.
        J Law Med Ethics. 1996; 24: 273-274