Summary

Nevirapine significantly reduces ethinylestradiol levels through enzyme induction, potentially leading to contraceptive failure and breakthrough bleeding. This clinically significant interaction requires careful monitoring and alternative contraceptive methods may be necessary.

Introduction

Ethinylestradiol is a synthetic estrogen commonly used in oral contraceptives and hormone replacement therapy. It belongs to the class of synthetic estrogens and works by suppressing ovulation and altering cervical mucus. Nevirapine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) used in the treatment of HIV infection. It belongs to the antiretroviral drug class and works by blocking HIV reverse transcriptase enzyme, preventing viral replication.

Mechanism of Interaction

Nevirapine is a potent inducer of cytochrome P450 enzymes, particularly CYP3A4, which is the primary enzyme responsible for ethinylestradiol metabolism. When nevirapine induces CYP3A4, it significantly increases the metabolic clearance of ethinylestradiol, leading to reduced plasma concentrations and decreased bioavailability. This enzyme induction effect typically develops over 2-4 weeks of nevirapine therapy and can reduce ethinylestradiol levels by up to 20-30%.

Risks and Symptoms

The primary clinical risk of this interaction is contraceptive failure due to reduced ethinylestradiol effectiveness. Women may experience breakthrough bleeding, irregular menstrual cycles, and increased risk of unintended pregnancy. The interaction is considered clinically significant because it can compromise the primary therapeutic goal of hormonal contraception. Additionally, reduced estrogen levels may affect other therapeutic benefits of hormone therapy, such as bone density maintenance in postmenopausal women.

Management and Precautions

Healthcare providers should counsel patients about reduced contraceptive effectiveness when prescribing nevirapine to women using ethinylestradiol-containing contraceptives. Consider alternative contraceptive methods such as barrier methods, intrauterine devices, or depot medroxyprogesterone acetate. If hormonal contraception is preferred, higher-dose formulations (≥35 mcg ethinylestradiol) may be considered, though effectiveness may still be compromised. Regular monitoring for breakthrough bleeding and contraceptive failure is essential. Patients should be advised to use additional barrier contraception, especially during the first few weeks of nevirapine therapy when enzyme induction is developing.

Ethinylestradiol interactions with food and lifestyle

Smoking significantly increases the risk of serious cardiovascular side effects when taking ethinylestradiol, particularly blood clots, stroke, and heart attack. Women over 35 who smoke should not use ethinylestradiol-containing medications. Grapefruit juice may increase ethinylestradiol levels in the blood, potentially increasing the risk of side effects. St. John's wort can decrease the effectiveness of ethinylestradiol by increasing its metabolism, potentially leading to breakthrough bleeding and reduced contraceptive efficacy.