Cialis and Acetaminophen Interaction: Safety, Risks, and What Your Doctor Wants You to Know

Does Acetaminophen Interact With Cialis?

Cialis is the brand of tadalafil approved for erectile dysfunction, for the signs and symptoms of benign prostatic hyperplasia (BPH), and for the two together [1]. Its drug interactions section covers organic nitrates, alpha-blockers, other antihypertensives, alcohol, CYP3A4 inhibitors such as ketoconazole and ritonavir, CYP3A4 inducers such as rifampin, antacids, and H2 blockers such as nizatidine [1]. Acetaminophen is not among them.

The label does mention acetaminophen in its adverse reactions section, as a treatment for tadalafil-related back pain and myalgia (see below) [1].

Tadalafil is available by prescription only [3]. See the tadalafil page for product information.

Why the Two Drugs Do Not Compete for the Same Enzymes

Tadalafil is metabolized mainly by CYP3A4 [1]. Ketoconazole 400 mg daily raised tadalafil 20 mg exposure (AUC) by 312%, and rifampin 600 mg daily cut tadalafil 10 mg AUC by 88% and peak concentration by 46% [1]. Those are the kinds of drugs that change tadalafil levels.

Acetaminophen is cleared by glucuronidation, sulfation and CYP2E1 oxidation. CYP2E1 produces a reactive metabolite, NAPQI, which is cleared at normal doses by conjugation with glutathione [7].

The Cialis label states that studies showed tadalafil does not inhibit or induce CYP1A2, CYP3A4, CYP2C9, CYP2C19, CYP2D6, or CYP2E1 [1].

Tylenol for a Cialis Headache or Back Pain

In the eight 12-week placebo-controlled trials of Cialis used as needed for ED, headache was the most frequently reported listed adverse reaction: 5% on placebo versus 11% on 10 mg and 15% on 20 mg. Dyspepsia was 1% on placebo versus 8% on 10 mg and 10% on 20 mg; back pain 3% versus 5% and 6%; myalgia 1% versus 4% and 3% [1].

The label adds timing: back pain or myalgia usually began 12 to 24 hours after dosing and typically resolved within 48 hours. When medical treatment was necessary, it says acetaminophen or nonsteroidal anti-inflammatory drugs were generally effective [1]. About 0.5% of men using Cialis as needed stopped treatment because of back pain or myalgia [1]. Among NSAIDs, the label notes that tadalafil did not potentiate the increase in bleeding time caused by aspirin [1].

What the Acetaminophen Label Says to Watch

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, prescription or not, or has 3 or more alcoholic drinks every day while using the product [2]. The labels also carry a before-use warning for liver disease and warn about rare serious skin reactions [2].

The printed maximum on each product is lower than 4,000 mg. Regular Strength 325 mg: 2 tablets every 4 to 6 hours, no more than 10 tablets (3,250 mg) in 24 hours. Extra Strength 500 mg: 2 caplets every 6 hours, no more than 6 caplets (3,000 mg) in 24 hours. 8 HR Arthritis Pain 650 mg: 2 caplets every 8 hours, no more than 6 caplets (3,900 mg) in 24 hours [2]. The labels say not to use it longer than 10 days for pain or 3 days for fever without a doctor [2].

In a US multicenter study of 662 patients with acute liver failure, 275 cases (42%) were attributed to acetaminophen, at a median ingested dose of 24 g; 48% of those cases were unintentional overdoses, and within that group 38% had taken two or more acetaminophen preparations at once and 63% had used narcotic-containing products [4]. Cold and flu products and prescription opioid combinations such as Percocet and Norco also contain acetaminophen [2].

Cialis Dosing When the Liver Is Impaired

Liver disease changes tadalafil dosing. For Cialis used as needed in mild or moderate hepatic impairment (Child-Pugh A or B), the dose should not exceed 10 mg once per day, and once-daily Cialis has not been extensively evaluated in hepatic impairment; use is not recommended in severe impairment (Child-Pugh C) [1].

Alcohol With Both

The Cialis label states that alcohol and tadalafil are both mild vasodilators, and that substantial alcohol (5 units or more) with Cialis can increase orthostatic signs and symptoms, including a higher heart rate, lower standing blood pressure, dizziness, and headache; tadalafil did not change alcohol levels and alcohol did not change tadalafil levels [1].

The acetaminophen label separately names 3 or more alcoholic drinks every day as a liver-damage risk while using the product [2]. Two randomized trials tested acetaminophen at high doses in drinkers. In 201 patients entering alcohol detoxification, acetaminophen 1,000 mg four times daily for 2 days gave 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 1 to 3 drinks a day, 4 g a day 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].