Penicillins Hormonal contraceptives

Drugs That Interfere with Hormonal Contraceptives Concomitant use of HIV-protease inhibitors, griseofulvin, modafinil, penicillins, rifampin, rifabutin, phenytoin, carbamazepine, or certain herbal supplements such as St. John s wort with hormonal contraceptive agents may reduce the effectiveness of the contraception and up to one month after discontinuation of these concomitant therapies. Therefore, women requiring treatment with one or more of these drugs must use two other effective or highly effective methods of contraception or abstain from heterosexual sexual contact while taking thalidomide... 

The introduction of the sulfa drugs was followed by the development of the penicillin antibiotics. Fleming s chance observation of the anti-bacterial action of the penicillin mold in 1928 and the subsequent isolation and identification of its active constituent by Florey and Chain in 1940 marked the beginning of the antibiotics era that still continues today. At roughly the same time, the steroid hormones found their way into medical practice. Cortisone was introduced by the pharmaceutical industry in 1944 as a drug for the treatment of arthritis and rheumatic fever. This was followed by the development of steroid hormones as the active constituents of the contraceptive pill. 

Contraceptive efficacy can be decreased when taken concurrently with drugs that increase the metabolism of hormones (e.g., CYP450 inducers). Similarly, drugs that reduce enterohepatic recycling of COCs (e.g., tetracycline, penicillins) can also reduce efficacy. 

The macrolides such as erythromycin might possibly be expected to suppress the bacteria responsible for the enterohepatic recycling of ethinylestradiol, but good evidence that this is clinically important is scant (see Hormonal contraceptives + Antibacterials Penicillins , p.981). Erythromycin, and to a lesser extent the other macrolides discussed here, also inhibit the cytochrome P450 isoenzyme CYP3A4, which is responsible for the metabolism of the contraceptive steroids. Therefore they might be expected to increase rather than reduce contraceptive efficacy. This would be expected to offset any possible reduced enterohepatic recycling. 

The interaction between metronidazole and combined oral contraceptives is not established, and the whole issue of any interaction with broad-spectrum antibacterials remains very controversial. Bearing in mind the extremely wide use of both metronidazole and combined oral contraceptives, any increased incidence of contraceptive failure above that seen in general usage is clearly very low indeed. The Faculty of Family Planning and Reproductive Health Care (FFPRHC) Clinical Effectiveness Unit has issued guidance on the use of antibacterials with combined hormonal contraceptives. Although they recognise that there is poor evidence for contraceptive failure, they recommend that additional form of contraception, such as condoms, should be used for short courses of antibacterials, see Hormonal contraceptives + Antibacterials Penicillins , p.981, for more detailed information. This applies to both the oral and the patch form of the combined contraceptive. This advice has usually been applied to only broad-spectrum antibacterials that do not induce liver enzymes but the FFPRHC notes that some confusion has occurred over which antibacterials are considered to be broad-spectrum , and thus they recommend that this advice is applied to all antibacterials that do not induce liver enzymes, which would include metronidazole. ... 

The interaetion between combined hormonal eontraceptives and penicillins is inadequately established and controversial. Almost all of the evidence is anecdotal with no controls. The total number of failures is extremely small when viewed against the number of women worldwide using combined hormonal contraceptives (estimated at 70 million in 1996 by WHO ), so most women are apparently not at risk. 

The fluoroquinolones are broad-spectrum antibacterials, and so might be expected to interrupt the enterohepatic recirculation of ethinylestradiol, but the evidence that this is clinically important is scant (for a more detailed discussion of this mechanism see Hormonal contraceptives + Antibacterials Penicillins , p.981). 

The pharmacokinetics of a single 25-mg dose of doxylamine in 13 subjeets and the pharmacokinetics of a single 50-mg dose of diphenhydramine in 10 subjeets were not significantly altered by the use of low-dose eombined oral eontraceptives. Cases of oral contraceptive failure have been attributed to the use of doxylamine, chlorpheniramine, and an unnamed antihistamine, but these antihistamines were all used in con-junetion with penieillins, which would seem to be a more likely cause of contraceptive failure (see Hormonal contraceptives + Antibacterials Penicillins , p.981). The effect of the antihistamines on the pharmacokinetics and pharmacodynamics of contraceptive steroids appear not to have been studi. No particular precautions would seem necessary during concurrent use. 

The reliability of progestogen-only methods of hormonal contraception are not affected by antibacterials that do not induce liver enzymes, such as the penicillins and tetracyclines. 

Note that the mechanism behind the rare cases of failure of combined oral contraceptives seen with various broad-spectrum antibacterials is postulated to be reduced enterohepatic recycling of ethinylestradiol (see Hormonal contraceptives + Antibacterials Penicillins , p.981). Since progestagens are largely metabolised to inactive substances before they are conjugated, they do not undergo enterohepatic recycling of the active substance. 

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