Cialis (Tadalafil) in Special Populations: Transplant, HIV, Elderly, and More

Kidney function sets the tightest limits

For as-needed use, the Cialis label starts at 5 mg and caps the dose at 10 mg no more often than every 48 hours when creatinine clearance is 30 to 50 mL/min [1]. Below 30 mL/min, or for anyone on hemodialysis, the maximum is 5 mg no more often than every 72 hours [1]. Once-daily Cialis is not recommended below 30 mL/min or on hemodialysis [1].

Once-daily use for BPH, or for ED with BPH, is handled slightly differently: at a creatinine clearance of 30 to 50 mL/min the label starts at 2.5 mg and allows an increase to 5 mg depending on individual response [1].

The label's once-daily starting dose is 2.5 mg, while Drugs@FDA lists the 2.5 mg Cialis tablet as discontinued, and the label says not to split the tablets [1][2].

Liver function

In mild or moderate hepatic impairment (Child-Pugh A or B) the as-needed dose should not exceed 10 mg once a day [1]. The label states that once-daily Cialis has not been extensively evaluated in hepatic impairment [1]. In severe impairment (Child-Pugh C), Cialis is not recommended [1].

CYP3A4 inhibitors and inducers

Tadalafil is metabolized mainly by CYP3A4 [1]. Ketoconazole 400 mg daily raised exposure (AUC) to a 20 mg tadalafil dose by 312% and peak concentration by 22%; ketoconazole 200 mg daily raised AUC to a 10 mg dose by 107% and peak concentration by 15% [1]. Ritonavir 200 mg twice daily raised AUC to a 20 mg dose by 124% with no change in peak concentration, while 500 to 600 mg twice daily raised AUC by 32% and lowered peak concentration by 30% [1].

For potent CYP3A4 inhibitors the label limits Cialis to no more than 10 mg every 72 hours as needed, and no more than 2.5 mg for once-daily use [1]. Erythromycin, itraconazole and grapefruit juice were not studied with tadalafil, but the label expects them to raise exposure [1]. The label adds that other HIV protease inhibitors would likely increase tadalafil exposure, though they were not studied [1].

In the other direction, rifampin 600 mg daily cut AUC to a 10 mg dose by 88% and peak concentration by 46% [1]. The label calls for no dose adjustment, but says the efficacy of once-daily Cialis may fall by an unknown amount [1]. Carbamazepine, phenytoin and phenobarbital would likely lower exposure too, though they were not studied [1].

Men aged 65 and over

Exposure was about 25% higher in healthy men aged 65 or older than in younger men [1]. The label's dose changes turn on kidney function, liver function and interacting drugs rather than age [1]. Its adverse reactions section notes that diarrhea was reported more frequently in patients 65 and older taking Cialis as needed [1].

Blood pressure is the other consideration. Alpha-blockers and tadalafil are both vasodilators, and their blood pressure effects are additive [1]. For ED, the label says a man should first be stable on the alpha-blocker and should start Cialis at the lowest dose [1]. For BPH, the label does not recommend combining Cialis with an alpha-blocker, because the combination has not been adequately studied for efficacy and because of the risk of blood pressure lowering [1]; it also says that a man taking an alpha-blocker for BPH should stop it at least one day before starting once-daily Cialis for BPH [1].

The size of the effect depends on the alpha-blocker. With doxazosin 8 mg daily, adding tadalafil 20 mg produced a placebo-subtracted maximal standing systolic fall of 9.8 mm Hg (3.6 mm Hg supine) [1]; in a second doxazosin study, 16 of 24 men had a systolic reading below 85 mm Hg or a fall greater than 30 mm Hg after tadalafil, against 6 on placebo [1]. Tamsulosin 0.4 mg produced a standing fall of 1.7 mm Hg with tadalafil 10 mg and 2.3 mm Hg with 20 mg, and alfuzosin 10 mg produced a 4.4 mm Hg standing fall with tadalafil 20 mg [1].

Heart conditions and nitrates

The label says sexual activity itself carries cardiac risk, so ED treatments including Cialis should not be used by men for whom sexual activity is inadvisable because of cardiovascular status [1]. It lists cardiac conditions in which Cialis is not recommended because those patients were not studied: a heart attack within 90 days, unstable angina or angina during intercourse, NYHA class 2 or greater heart failure within 6 months, uncontrolled arrhythmia, blood pressure below 90/50 mm Hg or uncontrolled hypertension, and stroke within 6 months [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]. The label advises caution in left ventricular outflow obstruction such as aortic stenosis and in severely impaired autonomic control of blood pressure [1].

Any organic nitrate, taken regularly or intermittently, is contraindicated with Cialis [1]. The label's one exception is an emergency: if a nitrate is medically necessary in a life-threatening situation, 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, men took tadalafil 20 mg or placebo daily for 7 days and then sublingual nitroglycerin 0.4 mg; standing systolic blood pressure fell below 85 mm Hg in more men on tadalafil at 4, 8 and 24 hours, with no difference at 48, 72 and 96 hours [3]. The label adds that at 48 hours a few more tadalafil men still had greater blood pressure falls [1]. Guanylate cyclase stimulators such as riociguat are also contraindicated [1].

Two smaller label points: five units of alcohol or more with Cialis can increase orthostatic signs and symptoms such as a faster heart rate, lower standing blood pressure, dizziness and headache [1], and common antihypertensives such as amlodipine, ARBs, bendroflumethiazide, enalapril and metoprolol produced small additional blood pressure reductions with tadalafil [1].