A 30-year-old mother of 2 children weighing 60 kg was taking combined oral contraceptive pill containing levonorgestrel 0.15 mg + ethinylestradiol 30 μg per day cyclically (3 weeks treatment— 1 week gap). She developed fever with cough and was diagnosed as a case of pulmonary tuberculosis after sputum smear examination. She was put on isoniazid (300 mg) + rifampin (600 mg) + pyrazinamide (1.5 g) + ethambutol (1.0 g) daily for 2 months, followed by isoniazid (600 mg) + rifampin (600 mg) thrice weekly. In the 3rd month, she failed to have the usual withdrawal bleeding during the gap period of contraceptive cycle. After 10 days, her urinary pregnancy test was found to be positive.What could be the reason for failure of the oral contraceptive?
High-Yield Explanation
Rifampin is known to induce the metabolism of contraceptive steroids. Thus, after regular intake of rifampin for more than 2 weeks (needed for enzyme induction) the steady-state blood level of levonorgestrel and ethinylestradiol could have fallen below the threshold for inhibition of ovulation/contraception. As such, fertility was restored and the woman conceived.