Estradiol Transdermal Patch and Griseofulvin: Interaction Details

a) A case report described pregnancy occurring in a 25-year-old woman receiving griseofulvin and oral contraceptives concurrently. The woman, who had been taking the oral contraceptive (OC), Triphasil(R), for 4 years with no menstrual irregularities, was treated with ultramicrocrystalline griseofulvin 330 mg twice daily while continuing to use oral contraception. Two month after initiation of griseofulvin, her nails were greatly improved but she reported transient headaches. Two months later, the patient was found to be pregnant. Her last menstrual period had occurred 2 months after initiation of griseofulvin. The patient claimed to have taken her OC regularly and did not take any other medications during this period. It was postulated the pregnancy probably resulted from failure of the oral contraceptive due to an interaction between the oral contraceptive and griseofulvin ⁴.

b) A case report described oligomenorrhea and irregular menses in a 32-year-old woman receiving concomitant griseofulvin and oral contraceptive therapy with norethindrone 0.5 and 1 mg plus ethinyl estradiol 0.035 mg (Ortho Novum 7/7/7(R)). The woman, who had two normal pregnancies and subsequent deliveries from 1981 to 1984 and who had been taking the oral contraceptive for the preceding four months with no abnormalities in menstruation, was diagnosed with tinea unguium. She was treated with griseofulvin 250 mg daily for 14 days, then increased to 500 mg daily for the remainder of the 6-month regimen. No other drugs were given. Following griseofulvin therapy initiation, the woman presented with oligomenorrhea and irregular menses. As a result, the patient's gynecologist changed her oral contraceptive to norgestrel 0.5 mg plus ethinyl estradiol 0.05 mg (Ovral-28(R)), providing a 57% increase in the estrogen component. Six months following the oral contraceptive change, the patient reported regular menses with normal menstrual flow ⁵.

c) The Safety of Medicines in the United Kingdom committee and the Netherlands Centre for Monitoring of Adverse Reactions to Drugs received 22 reports of a possible oral contraceptive (OC) and griseofulvin interaction. Among the 22 women using long-term OC who began receiving griseofulvin 0.5 to 1 g/day, 15 women (mean age, 26 years; range, 17 to 42 years; mean griseofulvin dose, 550 mg/day) reported transient intermenstrual bleeding and 5 women (mean age, 33.4 years; range, 17 to 44 years; mean griseofulvin dose, 880 mg/day) reported amenorrhea in the first and second cycles following griseofulvin initiation. In 7 of the intermenstrual bleeding cases and one of the amenorrhea cases, the women were using OCs with less than 50 mcg estrogen. Of the 20 women reporting menstrual irregularities, 14 women received no other drugs during the time of griseofulvin treatment and 3 women used drugs not known to interfere with OCs (ie, miconazole ointment, grass pollen vaccine, tetanus vaccine). In the 3 remaining patients, details of concurrent drug administration were not reported. In 2 patients with intermenstrual bleeding and 2 with amenorrhea, the original reaction recurred upon rechallenge with griseofulvin. Two unintended pregnancies were also reported among the 22 cases. In one case, the patient had been using a high-dose OC for 15 months and griseofulvin 500 mg/day for 2.5 months. One month after starting griseofulvin, she received a 1-week course of cotrimoxazole and became pregnant in that time period. In the second case, conception occurred when a patient was taking an unspecified OC, griseofulvin, and a combination of sulfonamides ⁶.