Actos (Pioglitazone) and Finasteride Interaction: What Patients and Clinicians Need to Know

Is there an interaction between Actos and finasteride?

The finasteride drug interactions section opens with a flat statement: no drug interactions of clinical importance have been identified, and finasteride does not appear to affect the cytochrome P450-linked drug-metabolizing enzyme system [2]. The drugs it was tested against in people were antipyrine, digoxin, propranolol, theophylline and warfarin, with no clinically meaningful interactions reported [2]. Pioglitazone is not on that list.

The Actos label names three interaction partners [1]:

• Strong CYP2C8 inhibitors such as gemfibrozil raise pioglitazone exposure about threefold; the Actos label sets a maximum of 15 mg daily when they are used together [1]
• CYP2C8 inducers such as rifampin may significantly lower pioglitazone exposure [1]
• Topiramate lowers exposure to pioglitazone and its active metabolites [1]

Finasteride is not among them, and neither label describes a dose adjustment for the pair [1][2].

How each drug is metabolized

Pioglitazone is metabolized mainly by CYP2C8, with CYP3A4 also involved, into the active metabolites M-III and M-IV [1]. Finasteride is metabolized mainly by CYP3A4, into two metabolites with no more than 20% of the activity of the parent drug [2].

Does finasteride affect blood sugar control?

The Actos interaction section does not name finasteride [1]. What each label describes on its own: finasteride blocks conversion of testosterone to dihydrotestosterone (DHT), and a 1 mg tablet suppresses serum DHT by 65% within 24 hours; mean testosterone and estradiol rise by about 15% and stay inside the normal range; finasteride has no affinity for the androgen receptor [2]. Pioglitazone lowers insulin resistance in the periphery and the liver and is not an insulin secretagogue [1].

The Actos label warns about low blood sugar when Actos is combined with insulin or a sulfonylurea [1]. In a 16-week trial adding Actos to insulin, hypoglycemia occurred in 15.4% of patients on 30 mg versus 4.8% on placebo, and edema in 17.6% versus 7.0% [1]. The label says to lower the sulfonylurea dose if hypoglycemia occurs, and to lower insulin by 10% to 25% [1].

What the Actos label says to watch for

The boxed warning on Actos is about congestive heart failure [1]. Thiazolidinediones, including Actos, cause or exacerbate heart failure in some patients, and the label says to monitor for excessive rapid weight gain, shortness of breath and edema after starting and after each dose increase [1]. Starting Actos in someone with established NYHA class III or IV heart failure is contraindicated, and it is not recommended in symptomatic heart failure [1].

Fluid retention is dose-related and most common when Actos is combined with insulin [1]. In PROactive, which followed 5,238 adults with type 2 diabetes and macrovascular disease for a mean of 34.5 months, edema occurred in 26.7% of those on pioglitazone versus 15.3% on placebo, cardiac failure in 8.1% versus 6.1%, and hospitalization for heart failure in 5.7% versus 4.1% [1][4].

The label also calls for liver tests before starting, and it carries a Warnings and Precautions item on bladder tumors with inconsistent human data: bladder cancer was diagnosed in 0.54% of the pioglitazone arm of PROactive versus 0.19% of the placebo arm, but across 13 years of trial plus observational follow-up the rates were the same (HR 1.00, 95% CI 0.59 to 1.72) [1]. Fractures rose in women in PROactive (5.1% versus 2.5%) and not in men (1.7% versus 2.1%) [1]. Macular edema is listed as a postmarketing report [1].

What the finasteride labels say to watch for

Finasteride lowers PSA. The Proscar label reports that 5 mg lowers PSA by about 50% within six months [3]. The Propecia label reports that at 1 mg, mean PSA fell from 0.7 to 0.5 ng/mL at month 12 in men aged 18 to 41 [2]. The label says any confirmed rise from the lowest value while on treatment should be evaluated for prostate cancer, even if the reading is still normal for a man not taking a 5-alpha reductase inhibitor [2].

The labels say 5-alpha reductase inhibitors may increase the risk of high-grade prostate cancer. In a 7-year trial, 18,882 men aged 55 or older were assigned to finasteride 5 mg or placebo. Gleason 8 to 10 cancer was found in 1.8% versus 1.1%, respectively [2][5]. Proscar is not approved to prevent prostate cancer [3].

Sexual adverse effects in the 1 mg trials: decreased libido 1.8% versus 1.3%, erectile dysfunction 1.3% versus 0.7%, ejaculation disorder 1.2% versus 0.7%, with 3.8% versus 2.1% reporting one or more (p=0.04) [2]. The postmarketing section lists sexual dysfunction that continued after stopping and male infertility or poor seminal quality [2].

Finasteride is contraindicated in pregnancy and is not indicated for women. The Propecia label says women who are or may be pregnant should not handle crushed or broken tablets [2].

Which finasteride product is meant?

There are two separate products. Proscar 5 mg, approved 06/19/1992, is for symptomatic benign prostatic hyperplasia [6]. Propecia 1 mg, approved 12/19/1997, is for male pattern hair loss in men only [7]. Propecia finasteride 1 mg is the 1 mg product. The Actos label gives no dose adjustment for finasteride; its 15 mg daily limit applies to strong CYP2C8 inhibitors such as gemfibrozil [1].