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Pharmacokinetic Drug Interactions with Oral Contraceptives

  • Pharmacokinetic Drug Interactions
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Summary

Oral contraceptive steroids are used by an estimated 60 to 70 million women worldwide. Over the past 20 years there have been both case reports and clinical studies on the topic of drug interactions with these agents. Some of the interactions are of definite therapeutic relevance, whereas others can be discounted as being of no clinical significance. Pharmacological interactions between oral contraceptive steroids and other compounds may be of 2 kinds: (a) drugs may impair the efficacy of oral contraceptive steroids, leading to breakthrough bleeding and pregnancy (in a few cases, the activity of the contraceptive is enhanced); (b) oral contraceptive steroids may interfere with the metabolism of other drugs.

A number of anticonvulsants (phenobarbital, Phenytoin, carbamazepine) are enzymeinducing agents and thereby increase the clearance of the oral contraceptive steroids. Valproic acid has no enzyme-inducing properties, and thus women on this anticonvulsant can rely on their low dose oral contraceptive steroids for contraceptive protection. Researchers are now beginning to unravel the molecular basis of this interaction, with evidence of specific forms of cytochrome P450 (P450IIC and IIIA gene families) being induced by phenobarbital. Rifampicin, the antituberculous drug, also induces a cytochrome P450 which is a product of the P450IIIA gene subfamily. This isozyme is one of the major forms involved in 2-hydroxylation of ethinylestradiol.

Broad spectrum antibiotics have been implicated in causing pill failure; case reports document the interaction, and general practitioners are convinced that it is real. The problem remains that there is still no firm clinical pharmacokinetic evidence which indicates that blood concentrations of oral contraceptive steroids are altered by antibiotics. However, perhaps this should not be a surprise, given that the incidence of the interaction may be very low. It is suggested that an individual at risk will have a low bioavailability of ethinylestradiol, a large enterohepatic recirculation and gut flora particularly susceptible to the antibiotic being used.

Two drugs, ascorbic acid (vitamin C) and paracetamol (acetaminophen), give rise to increased blood concentrations of ethinylestradiol due to competition for sulphation. The interactions could have some significance to women on oral contraceptive steroids who regularly take high doses of either drug. Although on theoretical grounds adsorbents (e.g. magnesium trisilicate, aluminium hydroxide, activated charcoal and kaolin) could be expected to interfere with oral contraceptive efficacy, there is no firm evidence that this is the case. Similarly, there is no evidence that smoking alters the pharmacokinetics of oral contraceptive steroids.

These agents are now well documented as being able to alter the pharmacokinetics of other concomitantly administered drugs. The clearance of a number of benzodiaze-pines undergoing oxidation (chlordiazepoxide, alprazolam, diazepam) and nitro reduction (nitrazepam), theophylline, prednisolone, caffeine and cyclosporin, is reduced in oral contraceptive steroid users. The clearance of some drugs undergoing glucuronidation (temazepam, salicylic acid, paracetamol, morphine, clofibric acid) is apparently increased.

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  1. Department of Pharmacology and Therapeutics, University of Liverpool, P.O. Box 147, Liverpool, L69 3BX, England

    David J. Back & Michael L’E. Orme

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Back, D.J., Orme, M.L. Pharmacokinetic Drug Interactions with Oral Contraceptives. Clin Pharmacokinet 18, 472–484 (1990). https://doi.org/10.2165/00003088-199018060-00004

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