Cialis (Tadalafil) Dosing for Older Adults Age 65 and Up

What Changes After 65, and What Does Not

The Cialis label carries one age-specific pharmacokinetic figure: exposure, measured as AUC, is 25% higher in healthy men aged 65 or older than in younger men [1]. The mean terminal half-life in healthy subjects is 17.5 hours [1].

With once-daily Cialis, tadalafil reaches steady levels within 5 days, with exposure about 1.6 times that of a single dose, so daily Cialis gives continuous blood levels rather than a peak and a fade [1]. The label points this out when discussing interactions with nitrates, alpha-blockers, antihypertensives, strong CYP3A4 inhibitors and substantial alcohol [1]. The label does not set a different daily dose based on age alone [1]. The reductions it specifies are tied to kidney function, liver function and interacting drugs, each covered below.

The Starting Doses the Cialis Label Gives

As needed for ED. The recommended starting dose is 10 mg taken before anticipated sexual activity, adjustable to 20 mg or down to 5 mg based on efficacy and tolerability, and not taken more than once a day [1]. Cialis improved erectile function compared with placebo for up to 36 hours after a dose, which is a duration of effect, not a continuous erection [1].

Once daily for ED. The starting dose is 2.5 mg taken at approximately the same time every day, without regard to the timing of sexual activity, and it may be increased to 5 mg based on efficacy and tolerability [1].

BPH, and ED with BPH. The dose is 5 mg once daily at approximately the same time every day [1]. When Cialis is used with finasteride to start BPH treatment, that use is recommended for up to 26 weeks, because the added benefit of Cialis shrinks from 4 weeks to 26 weeks and beyond 26 weeks is unknown [1].

Cialis may be taken with or without food, and the label says not to split the tablets — the entire dose should be taken [1]. HealthRX.com offers tadalafil by prescription.

Kidney Function Sets the Dose Ceiling

The label writes its renal rules in creatinine clearance, not eGFR, so the number that matters is the one from a creatinine clearance calculation [1].

• Creatinine clearance 30 to 50 mL/min, as needed: a starting dose of 5 mg not more than once a day, with a maximum of 10 mg not more than once every 48 hours [1].
• Creatinine clearance below 30 mL/min or hemodialysis, as needed: a maximum of 5 mg not more than once every 72 hours [1].
• Once-daily Cialis for ED below 30 mL/min or on hemodialysis: not recommended [1].
• Once-daily Cialis for BPH or ED with BPH at 30 to 50 mL/min: a starting dose of 2.5 mg, with an increase to 5 mg considered based on response; below 30 mL/min or on hemodialysis, once-daily use is not recommended [1].

In the label, kidney function rather than age sets the dose limits, and kidney disease is common in this age group: an estimated 34% of US adults aged 65 or older have chronic kidney disease, compared with 13% of adults aged 45 to 64 [2].

Liver Function

For mild or moderate hepatic impairment (Child-Pugh class A or B), the as-needed dose should not exceed 10 mg once per day [1]. In severe hepatic impairment (Child-Pugh class C), Cialis is not recommended [1].

Interactions That Change the Dose

Nitrates. Any form of organic nitrate, used regularly or intermittently, is contraindicated with Cialis because tadalafil potentiates the blood-pressure-lowering effect of nitrates [1]. For a life-threatening situation in which a nitrate is medically necessary, the label says 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]. That is an emergency rule, not a spacing schedule. In a crossover study of 150 men given 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 (P<0.05), with no difference at 48, 72 and 96 hours [3].

Alpha-blockers. Both drug types lower blood pressure and the effect is additive [1]. For ED, the label says a man should be stable on the alpha-blocker first and Cialis should be started at the lowest dose [1]. The size of the effect depends on the alpha-blocker: tadalafil 20 mg with doxazosin 8 mg daily produced a placebo-subtracted maximal standing systolic fall of 9.8 mm Hg, and in a second doxazosin study 16 of 24 subjects had a systolic reading below 85 mm Hg or a fall over 30 mm Hg, versus 6 on placebo [1]. With tamsulosin 0.4 mg the standing fall was 1.7 mm Hg with tadalafil 10 mg and 2.3 mm Hg with 20 mg [1]. For BPH, the label does not recommend combining Cialis with an alpha-blocker, because efficacy of the combination has not been adequately studied and because of the blood pressure risk [1].

CYP3A4 inhibitors. Tadalafil is metabolized mainly by CYP3A4 [1]. Ketoconazole 400 mg daily raised tadalafil 20 mg exposure (AUC) by 312%, and ritonavir 200 mg twice daily raised it by 124% [1]. For potent CYP3A4 inhibitors such as ketoconazole or ritonavir, the Cialis label limits as-needed dosing to 10 mg no more than once every 72 hours and once-daily dosing to 2.5 mg [1]. Erythromycin, itraconazole and grapefruit juice were not studied, but the label says they would likely increase tadalafil exposure [1].

Antihypertensives and alcohol. Small additional blood pressure reductions occurred when tadalafil was given with amlodipine, angiotensin II receptor blockers, bendroflumethiazide, enalapril or metoprolol [1]. Substantial alcohol — 5 units or more — with Cialis can increase orthostatic signs and symptoms, including higher heart rate, lower standing blood pressure, dizziness and headache [1]. In healthy volunteers, tadalafil 20 mg lowered supine blood pressure by a mean maximal 1.6/0.8 mm Hg versus placebo [1].

Cardiovascular Status Before the First Dose

The Cialis label says it should not be used when sexual activity is inadvisable because of cardiovascular disease [1]. The label lists groups that were not included in the trials and for whom Cialis is therefore not recommended: a heart attack within 90 days, unstable angina or angina during intercourse, NYHA class 2 or greater heart failure within 6 months, uncontrolled arrhythmias, blood pressure below 90/50 mm Hg or uncontrolled hypertension, and stroke within 6 months [1]. It also advises caution in left ventricular outflow obstruction, such as aortic stenosis, and in severely impaired autonomic control of blood pressure [1]. The Second Princeton Consensus Conference set out a three-tier risk stratification — low, intermediate and high — for sexual activity in men with cardiovascular disease, and reviewed the safety of the three PDE5 inhibitors available at the time, including tadalafil [4].

Side Effects at Label Doses

In eight 12-week placebo-controlled trials of as-needed Cialis for ED, headache occurred in 5% of men on placebo versus 11%, 11% and 15% on 5, 10 and 20 mg; dyspepsia in 1% versus 4%, 8% and 10%; back pain in 3% versus 3%, 5% and 6%; and myalgia in 1% versus 1%, 4% and 3% [1]. Discontinuation for adverse events was 3.1% on 10 or 20 mg versus 1.4% on placebo [1]. Back pain and myalgia generally began 12 to 24 hours after dosing and typically resolved within 48 hours [1].

In the once-daily ED trials, headache was 5% on placebo versus 3% at 2.5 mg and 6% at 5 mg, and dyspepsia 2% versus 4% and 5% [1]. In the three 12-week BPH and ED/BPH trials (placebo 576 men, tadalafil 581), headache was 2.3% versus 4.1%, dyspepsia 0.2% versus 2.4%, and dizziness 0.5% versus 1.0% [1]. The label also notes that in the as-needed ED trials, diarrhea was reported more frequently in patients 65 and older treated with Cialis [1].

The label says to seek emergency treatment for an erection lasting more than 4 hours, painful or not [1]. It says to stop Cialis and seek medical care for sudden loss of vision in one or both eyes, which may be non-arteritic anterior ischemic optic neuropathy (NAION), and for sudden decrease or loss of hearing [1].

5 mg Daily for BPH

A 12-week trial enrolled men aged 45 or older with BPH symptoms and an IPSS of 13 or higher: tadalafil 5 mg once daily (n=161) versus placebo (n=164) [5]. Total IPSS fell by 5.6 points with tadalafil and 3.6 with placebo (P=0.004), with the improvement apparent at week 1 and significant by week 4; peak urine flow and post-void residual volume did not improve significantly [5].

A pooled analysis of four randomized trials of men aged 45 or older, restricted to sexually active men with both ED and BPH symptoms, found total IPSS changes of −6.0 with tadalafil (n=505) versus −3.6 with placebo (n=521), and IIEF erectile function domain improvements of 6.4 versus 1.4 (P<0.001 for both) [6].

When Cialis and finasteride are started together for BPH, the label recommends using the combination for up to 26 weeks, and says the added benefit of Cialis beyond 26 weeks is unknown [1]. In the trial behind that recommendation, 345 men took tadalafil 5 mg plus finasteride 5 mg and 350 took placebo plus finasteride; IPSS fell by 5.5 points at week 26 with tadalafil and 4.5 with placebo, and the gap between groups narrowed from 1.7 points at week 4 to 1.0 point at week 26 [7].