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?
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?
💡 Explanation
**Core Concept**
The question tests the interaction between oral contraceptives and antitubercular drugs, specifically the enzyme-inducing effect of rifampicin on the metabolism of ethinylestradiol.
**Why the Correct Answer is Right**
Rifampicin is a potent inducer of the cytochrome P450 enzyme system, which is responsible for the metabolism of ethinylestradiol. By inducing the production of this enzyme, rifampicin increases the metabolism of ethinylestradiol, leading to decreased plasma concentrations and reduced efficacy of the oral contraceptive. This results in the failure of withdrawal bleeding and, ultimately, pregnancy.
**Why Each Wrong Option is Incorrect**
* **Option A:** Isoniazid is not a significant inducer of the cytochrome P450 enzyme system and is not responsible for the failure of the oral contraceptive.
* **Option B:** Pyrazinamide is also not a significant inducer of the cytochrome P450 enzyme system and is not responsible for the failure of the oral contraceptive.
* **Option D:** Ethambutol is not known to interact with the metabolism of ethinylestradiol and is not responsible for the failure of the oral contraceptive.
**Clinical Pearl / High-Yield Fact**
When prescribing oral contraceptives to patients taking rifampicin or other enzyme-inducing antitubercular drugs, consider alternative contraceptive methods or adjust the dose of ethinylestradiol to maintain contraceptive efficacy.
**Correct Answer: C. Rifampicin's enzyme-inducing effect on ethinylestradiol metabolism.**
✓ Correct Answer: A. Rifampicin is enzyme inducer and induced metabolism of contraceptives
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