Clomiphene (drug interactions)

DEFINITION: A drug used to enhance female fertility.

INTERACTIONS: N-acetylcysteine, traditional Chinese herbal medicine, ospemifene, benazepril, fluoroestradiol F18, abrocitinib, bexarotene, black cohash, blue cohash, chasteberry, DHEA (Dehydroepiandrosterone), other fertility medications

TRADE NAMES: Clomid, Serophene

N-acetylcysteine

Effect: Possible Helpful Interaction

The supplement N-acetylcysteine (NAC) has shown promise for enhancing the effectiveness of clomiphene. A double-blind study enrolled 150 women with polycystic ovary syndrome for whom clomiphene had not been effective. One-half of the women were given NAC at a dose of 1.2 grams per day, while the other half received a placebo. All participants continued to receive clomiphene. The results showed that the use of NAC significantly improved both ovulation rate and pregnancy rate in patients previously resistant to NAC. Supplementation of NAC during treatment with clomiphene remains a staple in the fertility community due to its ability to improve ovulation and decrease insulin resistance.

Traditional Chinese Herbal Medicine

Effect: Possible Helpful Interaction

Traditional Chinese herbal medicine employs complex combinations of herbs. Several studies conducted in China reported that using such combinations can enhance the effectiveness of clomiphene. None of these studies achieved the minimum standards necessary for scientific validity, and more formal medical studies remained necessary.

Other Interactions

Clomiphene interacts with several other medications, decreasing the effectiveness of each drug. It has been shown to have severe interactions with ospemifene, an estrogen drug used to treat various conditions related to menopause. It has also been proven to interact with benazepril, an ACE inhibitor prescribed to patients with hypertension, and fluoroestradiol F18, a radioactive drug used to diagnose breast cancer during PET scans. Clomiphene interacts with abrocitinib, a treatment for topic dermatitis, and bexarotene, used to treat lymphoma. 

There are several other potential interactions that patients should be cautioned about when taking clomiphene. Black and blue cohosh contain estrogen-like qualities that may interfere with clomiphene. Chasteberry, sometimes used to regulate menstrual cycles, may also interfere with clomiphene. DHEA may interfere with the hormonal balance necessary to achieve ovulation. Patients should also avoid taking additional fertility drugs as this could lead to ovarian hyperstimulation syndrome.

Bibliography

Chao, S. L., L. W. Huang, and H. R. Yen. "Pregnancy in Premature Ovarian Failure After Therapy Using Chinese Herbal Medicine." Chang Gung Medical Journal, vol. 26, 2003, pp. 449-452.

"Clomiphene (Oral Route) Before Using." Mayo Clinic, 1 Feb. 2024, www.mayoclinic.org/drugs-supplements/clomiphene-oral-route/before-using/drg-20063072. Accessed 10 Sept. 2024.

Durbin, Kaci. "Clomiphene: Uses, Dosage, Side Effects." Drugs.com, 26 Jan. 2024, www.drugs.com/clomiphene.html. Accessed 10 Sept. 2024.

Khan, Sarfaroj. "Clomiphene: Side Effects, Uses, Dosage, Interactions, Warnings." RxList, 22 Feb. 2022, www.rxlist.com/clomiphene/generic-drug.htm. Accessed 10 Sept. 2024.

Rizk, A. Y., et al. "N-acetyl-cysteine Is a Novel Adjuvant to Clomiphene Citrate in Clomiphene Citrate-Resistant Patients with Polycystic Ovary Syndrome." Fertility and Sterility, vol. 83, 2005, pp. 367-370.