Finasteride Dosing in Hepatic Impairment

Does finasteride need a different dose in liver disease?

The Propecia label gives one regimen: 1 mg once daily, with or without meals, with benefit usually needing three months or more of daily use and reversal of effect within 12 months of stopping [1]. Proscar also gives one regimen: 5 mg once daily, with or without meals [2]. Neither dosing section describes a reduced dose, a longer interval or an alternative for liver disease, and neither mentions Child-Pugh class or liver tests [1][2]. Elsewhere, the Proscar label states that the effect of hepatic impairment on finasteride pharmacokinetics has not been studied, and that caution should be exercised in patients with liver function abnormalities as finasteride is metabolized extensively in the liver [2].

What the labels say about how finasteride is handled

Finasteride is extensively metabolized in the liver, mainly by CYP3A4, to two metabolites that retain no more than 20% of the activity of the parent drug [1]. Bioavailability is about 65% and food does not change it, about 90% is bound to plasma proteins, mean terminal half-life is about 5 to 6 hours in men 18 to 60 and about 8 hours in men over 70, and roughly 39% of a dose is excreted in urine as metabolites with 57% in feces [1].

The measurements below come from studies of liver disease and CYP3A4 in general, not from finasteride.

What liver disease does to CYP3A4

A review of hepatic pharmacokinetics describes chronic liver disease as producing variable, non-uniform reductions in drug-metabolizing activity, with different CYP450 enzymes affected to different degrees in cirrhosis; the Child-Pugh score grades severity but gives only rough guidance for dose adjustment because it cannot quantify a patient's elimination capacity [3].

CYP3A activity has been measured in fatty liver disease. Using oral midazolam phenotyping, people with NASH had 2.4-fold higher plasma midazolam levels than controls, plasma 4β-hydroxycholesterol was 51% lower in simple steatosis and 37% lower in NASH, fibrosis was associated with 57% lower 4β-hydroxycholesterol, and hepatic CYP3A4 mRNA in NASH was 69% lower than in control livers [4]. Those measurements describe CYP3A, not finasteride. Cirrhosis can also change plasma protein binding, which affects distribution and elimination [3], and about 90% of finasteride is protein bound [1].

Interactions and other medicines

The label states that no drug interactions of clinical importance have been identified, that finasteride does not appear to affect the cytochrome P450 system, and that antipyrine, digoxin, propranolol, theophylline and warfarin were tested in humans with no clinically meaningful interactions [1]. That section does not discuss CYP3A4 inhibitors or inducers, although CYP3A4 is the main enzyme that metabolizes finasteride [1].