Enclomiphene Citrate Overdose and Accidental Excess Dose: Recognition, Risks, and Clinical Management

Is there an enclomiphene-specific overdose guideline?

No. Enclomiphene is not FDA-approved, and FDA says no FDA-approved drugs contain enclomiphene as an active ingredient [1]. The nearest overdose section is in the clomiphene citrate label, which covers a different product: clomiphene citrate, a mixture of enclomiphene and zuclomiphene, approved for ovulatory dysfunction in women, not for low testosterone in men [1][2].

What the clomiphene label says after too much

The label says toxic effects accompanying acute overdosage of clomiphene citrate have not been reported [2]. It lists nausea, vomiting, vasomotor flushes, visual blurring, spots or flashes, scotomata, and ovarian enlargement with pelvic or abdominal pain when more than the recommended dose is used during therapy [2]. The acute oral LD50 is 1700 mg/kg in mice and 5750 mg/kg in rats; the toxic dose in humans is not known [2].

Visual symptoms and what the label says

The clomiphene label warns that blurring or other visual symptoms such as spots or flashes may occur and increase in incidence with higher total dose or longer treatment duration [2]. It says the disturbances are usually reversible, but prolonged visual disturbance has been reported, sometimes after stopping, and may be irreversible, especially with increased dosage or duration [2]. The label says patients with any visual symptoms should discontinue treatment and have a complete ophthalmological evaluation carried out promptly [2].

Why enclomiphene is not the same as clomiphene

Clomiphene citrate is a mixture of two geometric isomers, enclomiphene (trans) and zuclomiphene (cis) [1]. Enclomiphene is the more anti-estrogenic, pro-gonadotropic isomer; zuclomiphene is more estrogenic [3]. Oral enclomiphene peaks about 2 to 3 hours after a dose and has a half-life of about 10 hours [1]. The clomiphene label notes that zuclomiphene has a longer half-life and that detectable levels persisted for longer than a month [2]. That longer persistence belongs to the zuclomiphene component of clomiphene, not to pure enclomiphene.

How excess exposure is managed in the label

The clomiphene label's overdose section says appropriate supportive measures should be employed in addition to gastrointestinal decontamination [2]. Compounded enclomiphene products are not FDA-approved and have not been reviewed by FDA for safety, effectiveness or quality [4].