Interactions between oral Yvonne contraceptives and other drugs: a review

Summary

A number of interactions have been reported between oral contraceptive steroids and other drugs. These interactions may lead to impairment of contraceptive efficacy and, in addition, the oral contraceptive steroids can modify the metabolism and pharmacological activity of several drugs.

Loss of cycle control or pregnancy have resulted from simultaneous therapy with oral contraceptives and drugs which are powerful inducers of hepatic microsomal enzymes. These include phenobarbitone, rifampicin, and phenytoin, but occasional reports have implicated other anticonvulsants and barbiturates. By stimulating the formation of enzymes that increase the rate of metabolism of the oral contraceptive, the concentration of steroids in the plasma falls to levels inadequate for the control of conception. Breakthrough bleeding and spotting are common warning signs indicating that additional drug treatment has caused accelerated steroid metabolism. In animals, steroid metabolism has also been increased by treatment with antihistamines, phenylbutazone, orphenadrine and hyoscine.

Apart from enzyme induction, an interaction may occur by competition between an oral contraceptive and another drug for a common metabolising enzyme. An example is quoted in which the dose of a tricyclic antidepressant needed to be reduced in a woman taking an oral contraceptive. In addition, the oral contraceptive might induce the opposite physiological effect from another drug, as with an oral anticoagulant whose dose may have to be increased.

There is a possibility that antibiotic-induced interference with the enterohepatic circulation of steroid metabolites might lead to a decrease in plasma oestrogen levels, and pregnancies have been reported in women treated with ampicillin whilst using oral contraceptives. The displacement of oral contraceptive steroids from their binding sites on plasma proteins and interference with the renal excretion of steroids seem, so far, to be unimportant mechanisms of interaction.

The clinical implications of drug interactions are discussed. Although the number of interaction reports is still very low, it is possible that the advent of contraceptives with a lower hormone content may reveal more interactions than were evident with those containing more than 50 μg. oestrogen.

Key Words::

• Contraceptives
• oral
• drug interactions