Enclomiphene Citrate Dosing in Hepatic Impairment

Is there a dose of enclomiphene for liver disease?

No. Enclomiphene has no approved dose, so any number offered as a liver-disease dose is an extrapolation, not a measured recommendation [1].

The doses that have been studied went to men with secondary hypogonadism: 6.25, 12.5 and 25 mg once daily for six weeks in a randomized phase 2 study of 48 men [4], and 12.5 mg once daily, up-titrated to 25 mg at week 6 if morning testosterone stayed below 300 ng/dL, in the phase 3 protocols [5].

What the clomiphene label says — and what it covers

Clomiphene citrate (Clomid and generics) is FDA-approved only for ovulatory dysfunction in women who want to become pregnant; the label carries no male indication [2]. Its contraindications list liver disease or a history of liver dysfunction [2], and its postmarketing reactions include increased transaminases and hepatitis [2].

That label covers clomiphene citrate, a mixture of two isomers; it does not establish a liver-disease contraindication for enclomiphene alone [2][1]. Per FDA, the USP monograph gives enclomiphene content of clomiphene as 50 to 70 percent [1].

How enclomiphene is cleared

In human liver microsomes, CYP2D6 was primarily responsible for enclomiphene metabolism; quinidine blocked it completely, and microsomes from one liver with low CYP2D6 activity did not metabolize it at all. Ketoconazole had no significant effect in three of four livers [3]. After an oral dose, enclomiphene peaks at 2 to 3 hours, has a half-life of about 10 hours, and is excreted mainly in feces [1].

Liver disease can change how drugs are handled [6], but the laboratory study above examined enclomiphene in liver microsomes, not in people with liver disease [3].

Safety concerns FDA listed

FDA's 2022 review listed cardiac and thromboembolic events, including pulmonary embolism and deep vein thrombosis in a safety study, raised estradiol, raised PSA, raised hematocrit, and no long-term safety data [1]. The most frequent side effects were headache, hot flushes, nausea and muscle spasm; in one 12-week study headache was reported by 7 of 112 men on 12.5 mg versus 1 of 47 on placebo [7].

Enclomiphene citrate sits on FDA's Category 1 list of bulk substances under evaluation for compounding — an enforcement-discretion policy, not an approval or a finding of safety or effectiveness [8]. HealthRX.com offers enclomiphene by prescription.