Co-cyprindiol is expected to interact with enzyme inducers in asimilar manner to combined oral contraceptives, and therefore risk of contraceptive failure is increased. Like combinedoral contraceptives,there may be rare cases of contraceptive failure with broad-spectrum antibacterials. There is some evidencethat co-cyprindiol also interacts with minocycline to increase facial pigmentation.
Clinical evidence,mechanism, importance and management
Co-cyprindiol is a mixture of anti-androgenic progestogen, cyproterone acetate 2 mg, with ethinylestradiol 35 micrograms. It is used for treatment of acne and moderately severe hirsutism in women who may also wish to use it as an oral contraceptive, and its contraceptive efficacy is expected to be reduced by same hepatic enzyme inducers (see table 1 below’,) that interact with conventional combined oral contraceptives (See reference number 1). The precautions described in this section for combined hormonal contraceptives with various drugs listed in table 1 below,, should therefore be followed, see ‘Hormonal contraceptives + Antiepileptics; Barbiturates or Phenytoin.
Similarly, it is anticipated that use of broad-spectrum antibacterials that do not induce liver enzymes may rarely reduce contraceptive efficacy of co-cyprindiol and Faculty of Family Planning and Reproductive Health Care (FFPRHC) guidance under Hormonal contraceptives + Antibacterials; Penicillins interaction, should be followed. Usually these precautions (additional barrier methods) are considered unnecessary after 3 weeks of concurrent use. However, manufacturer of co-cyprindiol says that when tetracyclines are being taken it is advisable to use additional non-hormonal methods of contraception (except rhythm or temperature methods) since an extremely high degree of contraceptive protection must be provided with co-cyprindiol due to theoretical risk of cyproterone causing feminization of a male foetus. However, they do also note that oral tetracyclines have not actually been shown to reduce contraceptive efficacy of co-cyprindiol. In addition co-cyprindiol may also possibly interact with minocycline to accentuate facial pigmentation (see Tetracyclines; Minocycline + Ethinylestradiol interaction).
The manufacturer also points out that combined oral contraceptives (and presumably combined hormonal contraceptive patch) must not be taken with co-cyprindiol (See reference number 1). To do this would be analogous to doubling ethinylestradiol dose with consequent increased risk of adverse effects. In addition, some of progestogens in combined oral contraceptives have weak androgenic effects, which could oppose benefits of cyproterone.
1. Dianette (Cyproterone/ethinylestradiol). Schering Health Care Ltd. UK Summary of productcharacteristics,June 2007.
| Table 1 Enzyme-inducing drugs shown to reduce the efficacy and/or increase the metabolism of hormonal contraceptives | |
|---|---|
| Group | Drugs |
| Antibacterials | Rifabutin, Rifampicin (Rifampin) |
| Antiepileptics | Barbiturates (e.g. phenobarbital, primidone), Carbamazepine, Phenytoin, Topiramate |
| Antifungals | Griseofulvin |
| Antivirals | Nevirapine, Protease inhibitors (e.g. nelfinavir, ritonavir) |
| Other drugs | Aprepitant, Modafinil, St John’s wort (Hypericum perforatum) |
| Table 2 Enzyme-inducing drugs shown to reduce the efficacy and/or increase the metabolism of hormonal contraceptives | |
|---|---|
| Group | Drugs |
| Antibacterials | Rifabutin, Rifampicin (Rifampin) |
| Antiepileptics | Barbiturates (e.g. phenobarbital, primidone), Carbamazepine, Phenytoin, Topiramate |
| Antifungals | Griseofulvin |
| Antivirals | Nevirapine, Protease inhibitors (e.g. nelfinavir, ritonavir) |
| Other drugs | Aprepitant, Modafinil, St John’s wort (Hypericum perforatum) |