Cialis Dosing in Hepatic Impairment: Evidence-Based Tadalafil Adjustments for Liver Disease

What the Label Allows in Child-Pugh A or B

The hepatic impairment section of the Cialis prescribing information states: 'Mild or moderate (Child Pugh Class A or B): The dose should not exceed 10 mg once per day' [1].

In people without liver disease, as-needed Cialis starts at 10 mg and can be raised to 20 mg or lowered to 5 mg depending on response and tolerability, with a maximum of one dose per day [1]. In Child-Pugh A or B, that 10 mg starting dose is also the ceiling. The daily limit is one dose, and the label says not to split tablets [1]. Cialis can be taken with or without food [1].

For BPH, and for ED with BPH, the usual regimen is 5 mg once daily [1].

What Happens in Child-Pugh C

Severe hepatic impairment is listed as not recommended [1]. No dose is given for this group.

The Cialis label uses Child-Pugh A or B for mild or moderate hepatic impairment and Child-Pugh C for severe impairment [1].

Does Liver Disease Actually Raise Tadalafil Levels?

Tadalafil is metabolized mainly by CYP3A4 [1]. Peak concentration arrives between 30 minutes and 6 hours after an oral dose (median 2 hours), and the mean terminal half-life is 17.5 hours in healthy subjects [1].

Single-dose clinical pharmacology studies were run in healthy subjects and in people with hepatic impairment. In single-dose studies, hepatic impairment had negligible effects on tadalafil exposure, and the authors concluded there was no clinically significant effect of hepatic impairment on tadalafil pharmacokinetics [2]. The most common adverse events across those six studies were headache, back pain and myalgia [2].

Those studies gave single doses. The label's 10 mg ceiling is a standing dosing rule for as-needed use in Child-Pugh A or B [1].

Once-Daily Cialis for ED or BPH

Once-daily Cialis has not been extensively evaluated in people with liver impairment [1]. The once-daily regimens themselves are 2.5 mg for ED, which may be increased to 5 mg, and 5 mg for BPH or ED with BPH [1].

Which Interactions Matter Most?

Strong CYP3A4 inhibitors. Ketoconazole 400 mg daily raised single-dose tadalafil 20 mg exposure (AUC) by 312% and peak concentration by 22%; ketoconazole 200 mg daily raised 10 mg exposure by 107% [1]. With strong CYP3A4 inhibitors such as ketoconazole or ritonavir, the label limits as-needed Cialis to no more than 10 mg every 72 hours, and once-daily Cialis to 2.5 mg [1].

Alpha-blockers. Tadalafil and alpha-blockers both lower blood pressure, and the effect is additive. In healthy volunteers, tadalafil 20 mg with doxazosin 8 mg daily produced a placebo-subtracted mean maximal standing systolic fall of 9.8 mm Hg [1]. For ED, the label says to be stable on the alpha-blocker first and to start tadalafil at the lowest dose; for BPH it does not recommend combining Cialis with an alpha-blocker [1].

Alcohol. Substantial alcohol (5 units or more) with Cialis can increase orthostatic signs and symptoms: higher heart rate, lower standing blood pressure, dizziness and headache. Tadalafil did not change alcohol levels and alcohol did not change tadalafil levels [1].

Nitrates. Any form of organic nitrate is contraindicated with Cialis [1]. In a life-threatening situation where a nitrate is medically necessary, at least 48 hours should pass after the last Cialis dose before a nitrate is considered, and then only under close medical supervision with hemodynamic monitoring [1]. In a 150-man crossover study, standing systolic pressure fell below 85 mm Hg in more men on tadalafil than on placebo up to 24 hours after sublingual nitroglycerin, with no significant difference at 48 hours [3].

Reported side effects

In the eight as-needed ED trials, headache was reported by 11% of men on tadalafil 10 mg versus 5% on placebo, dyspepsia by 8% versus 1%, back pain by 5% versus 3%, myalgia by 4% versus 1%, and flushing by 3% versus 1% [1]. Those rates come from general ED trials rather than from a group with liver disease [1]. Back pain and myalgia usually began 12 to 24 hours after dosing and resolved within 48 hours [1].

An erection lasting more than 4 hours, painful or not, needs emergency care; priapism is a painful erection lasting over 6 hours and can permanently damage erectile tissue [1]. The label also says to stop Cialis and seek medical care for sudden vision loss in one or both eyes, which may be non-arteritic anterior ischemic optic neuropathy [1].

In healthy volunteers, tadalafil 20 mg lowered supine blood pressure by a mean maximal 1.6/0.8 mm Hg compared with placebo [1].

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