Finasteride and Nicotine Interaction Profile: What Patients and Clinicians Need to Know

Does nicotine change how finasteride is metabolized?

Finasteride is extensively metabolized in the liver, mainly by CYP3A4. Its terminal half-life is about 5 to 6 hours in men aged 18 to 60 and about 8 hours in men over 70, and roughly 39% of a dose leaves in urine as metabolites while 57% leaves in feces [1]. The label's drug interaction section says 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 with no clinically meaningful interactions [1].

Nicotine runs on a different track. It is metabolized mainly in the liver to cotinine (about 15% of a dose in urine) and trans-3-hydroxycotinine (about 45%), and it is a CYP2A6 substrate [4]. Cigarette smoke, separately, induces CYP1A1 and CYP1A2 and possibly CYP2E1 through polycyclic aromatic hydrocarbons in the smoke [6][2]. A review of drug interactions with smoking names caffeine, clozapine, fluvoxamine, olanzapine, tacrine and theophylline as the main CYP1A2 substrates affected [2]. Finasteride's labeled pathway is CYP3A4 [1], which is not the enzyme those smoking interactions run through.

The induction is not a nicotine effect. A review of smoking cessation and prescription drugs states that the effect on hepatic microsomal enzymes is not related to the nicotine component of tobacco and that nicotine replacement will not alter it [3].

One animal study adds a small wrinkle. A single nicotine dose in rats induced CYP1A1 in lung tissue (4.4-fold at 6 hours, 14.7-fold at 12 hours, back to near baseline by 24 hours) but did not significantly change liver CYP1A2 protein or mRNA, and the relevance to people is unknown [8].

Why smoking still matters on this page

Smoking speeds the clearance of some CYP1A2-substrate drugs. Finasteride's label does not list it among the drugs affected, and the smoking literature cited here does not name it as a CYP1A2 substrate [1][2][3]. Caffeine half-life was 3.5 hours in 13 smokers versus 6.0 hours in 13 non-smokers, with clearance of 155 versus 94 mL/kg/h [9]. After 12 heavy smokers (20 or more cigarettes a day) stopped abruptly, caffeine clearance fell 36.1%, from 2.47 to 1.53 mL/min/kg, and the decline in CYP1A2 activity had an apparent half-life of 38.6 hours [10]. A review says dose adjustment is clearly indicated after quitting for warfarin, olanzapine, clozapine and theophylline [3].

Sexual side effects: finasteride's numbers, and smoking's separate signal

Both finasteride and smoking come up around erectile dysfunction, but the data behind each are different in size and design.

For Propecia 1 mg, three 12-month controlled trials enrolled 945 men on finasteride and 934 on placebo. Decreased libido was reported by 1.8% versus 1.3%, erectile dysfunction by 1.3% versus 0.7%, and ejaculation disorder by 1.2% versus 0.7%; 3.8% versus 2.1% reported one or more of these (p=0.04), and the incidence of each fell to 0.3% or lower by year 5 [1]. The label's postmarketing section also lists sexual dysfunction that continued after stopping, including erectile dysfunction, libido disorders, ejaculation disorders and orgasm disorders, and notes that these reports are voluntary and that a causal relationship cannot reliably be established [1].

For Proscar 5 mg, the 4-year PLESS trial followed 1524 men on finasteride and 1516 on placebo aged 45 to 78. In year 1, impotence was 8.1% versus 3.7%, decreased libido 6.4% versus 3.4%, and decreased ejaculate volume 3.7% versus 0.8%; in years 2 to 4, impotence was 5.1% in both groups [5].

For smoking, the clearest data concern cigarettes rather than nicotine alone. In a prospective study of smokers with erectile dysfunction who requested nicotine replacement therapy, erectile function after a year improved in at least 25% of the 118 men who stopped smoking and in none of the 163 men who continued smoking (P=0.009); 2.5% of those who stopped and 6.8% of those who continued got worse, and the severity of dysfunction correlated with pack-years of exposure [11].

So when a man taking finasteride has erectile dysfunction, both his finasteride exposure and his smoking status are part of the picture, and neither one establishes the cause in an individual case [1][11].

Nicotine's cardiovascular effects

Nicotine causes peripheral vasoconstriction, tachycardia and higher blood pressure, and tolerance does not develop to its catecholamine-releasing effects [6]. A review of nicotine's cardiovascular toxicity notes that nicotine may contribute to cardiovascular disease through sympathetic stimulation and systemic catecholamine release, that cigarette smoke contains many other cardiovascular toxins, and that smoking raises blood coagulability while transdermal nicotine does not appear to; the same review says trials of nicotine replacement in stable coronary disease suggest nicotine does not raise cardiovascular risk, and that at worst replacement carries no more risk than smoking [7].

If you quit smoking while taking finasteride

The change that matters after quitting is de-induction of CYP1A2, and it affects the drugs listed above rather than finasteride [3][1]. Nicotine replacement does not prevent that de-induction [3].

The Propecia label lists no smoking-related dose adjustment. It lists 1 mg once daily, with or without food, and says that daily use for three months or more is generally necessary before benefit is observed [1].