Finasteride and Acetaminophen Interaction: What Patients and Clinicians Need to Know

Does finasteride interact with acetaminophen?

The finasteride prescribing information names acetaminophen directly. Section 7.2 of the Propecia (finasteride 1 mg) label states that although specific interaction studies were not performed, finasteride doses of 1 mg or more were used with acetaminophen, aspirin, NSAIDs, ACE inhibitors, alpha-blockers and other medicines in clinical studies without evidence of clinically significant adverse interactions [1]. The Proscar (finasteride 5 mg) label lists the same co-medications for Proscar [2]. Section 7.1 of both labels adds that no drug interactions of clinical importance have been identified and that finasteride does not appear to affect the cytochrome P450-linked drug-metabolizing enzyme system [1][2].

The Tylenol Drug Facts warnings name warfarin, other acetaminophen-containing products and three or more alcoholic drinks a day as the things to watch [3].

How each drug is handled

Finasteride. It is about 65% bioavailable, peaks 1 to 2 hours after a dose, is about 90% protein bound, and is extensively metabolized in the liver, mainly by CYP3A4, into two metabolites with no more than 20% of finasteride's activity. Mean terminal half-life is about 5 to 6 hours [1]. It works as a competitive inhibitor of Type II 5-alpha-reductase, the enzyme that converts testosterone to dihydrotestosterone, and has no affinity for the androgen receptor [1]. Finasteride is used at 1 mg once daily for male pattern hair loss and 5 mg once daily for benign prostatic hyperplasia [1][2].

Acetaminophen. It is metabolized in the liver by glucuronidation, sulfation and CYP2E1 oxidation. CYP2E1 produces a reactive metabolite (NAPQI) that is cleared at normal doses by conjugation with glutathione, and substances that induce or regulate CYP2E1 may change acetaminophen metabolism and its liver toxicity [3]. The finasteride label says finasteride does not appear to affect the cytochrome P450 system, and the Tylenol liver warning is built around total daily dose, other acetaminophen-containing products and regular heavy drinking [1][3].

Where the acetaminophen risk actually sits

The Tylenol labels carry a Liver warning: severe liver damage may occur if an adult takes more than 4,000 mg in 24 hours, takes it with other drugs containing acetaminophen, or has three or more alcoholic drinks every day while using the product. The label also says to ask a doctor before use if you have liver disease [3]. The 4,000 mg figure is a ceiling, not the number printed on the package. Extra Strength 500 mg allows 2 caplets every 6 hours, maximum 6 caplets (3,000 mg) in 24 hours. Regular Strength 325 mg allows a maximum of 10 tablets (3,250 mg). 8 HR Arthritis Pain 650 mg allows 6 caplets (3,900 mg) [3].

Prescription products carry a stronger warning. Intravenous acetaminophen and acetaminophen-opioid combinations such as Percocet and Norco have a boxed hepatotoxicity warning, with most cases involving doses above the daily maximum and often more than one acetaminophen-containing product [3]. In a US multicenter study of 662 patients with acute liver failure, 275 cases (42%) were caused by acetaminophen. The median dose ingested was 24 g. Forty-eight percent of the acetaminophen cases were unintentional, and within that group 38% had taken two or more acetaminophen preparations while 63% had used narcotic-containing products [4].

Alcohol is the modifier worth discussing

The Tylenol labels treat three or more drinks a day as a liver-damage risk, and the IV label lists alcoholism as a caution, describing alcohol's effect on acetaminophen metabolism as complex [3]. Two randomized trials are reassuring within narrow limits. In 201 people entering alcohol detoxification, acetaminophen 1,000 mg four times daily for two days produced a day-4 mean AST of 38.0 U/L versus 37.5 U/L on placebo, with no evidence of liver injury [5]. In people drinking one to three drinks a day, 4 g daily for 10 days raised mean ALT by 8.7 IU/L at day 11, without symptoms or predefined hepatotoxicity [6]. Neither trial tested long courses or heavy ongoing drinking [5][6].

What else the labels flag

The Tylenol label warns against using the product with any other acetaminophen-containing medicine. Rarely, serious skin reactions (AGEP, SJS, TEN) can occur, and the label says to stop at the first rash [3]. The finasteride labels carry separate cautions, including pregnancy and handling of crushed tablets and effects on PSA interpretation, that do not involve acetaminophen [1].

Bottom line

For a man taking finasteride 1 mg or 5 mg daily, the finasteride labels report that acetaminophen was used in clinical studies without evidence of clinically significant adverse interactions [1][2]. The dose printed on the acetaminophen package, the other products in the medicine cabinet and the amount of alcohol in the picture are what the Tylenol labels actually warn about [3].