Cialis (Tadalafil) in Adults 65 and Older: What Geriatric Patients and Their Caregivers Need to Know

Does the tadalafil dose change at 65?

The Cialis label's starting dose for as-needed use is 10 mg before sexual activity, adjustable to 20 mg or down to 5 mg by response and tolerability, with a maximum of one dose a day [1]. Once-daily treatment of ED starts at 2.5 mg and may be raised to 5 mg; for BPH, or for ED with BPH, the dose is 5 mg once daily at about the same time every day [1]. The label states that tadalafil exposure (AUC) is 25% higher in healthy men aged 65 or older than in younger men [1].

The mean terminal half-life is 17.5 hours in healthy subjects, which is why a single as-needed dose improves erectile function compared with placebo for up to 36 hours; sexual stimulation is still required [1]. Steady state is reached within 5 days of once-daily dosing, with exposure about 1.6-fold that of a single dose, so daily tadalafil produces continuous blood levels [1]. The label's interaction warnings for once-daily use refer to this [1].

What kidney function changes

The dose limits the Cialis label spells out for specific populations are tied to creatinine clearance, liver function and CYP3A4 inhibitors [1].

For as-needed use with a creatinine clearance of 30 to 50 mL/min, the label gives a starting dose of 5 mg and a maximum of 10 mg not more than once every 48 hours; below 30 mL/min or on hemodialysis, the maximum is 5 mg not more than once every 72 hours [1]. Once-daily use is not recommended below 30 mL/min [1]. For BPH or ED with BPH and a clearance of 30 to 50 mL/min, the starting dose is 2.5 mg, with 5 mg considered by response [1].

In mild or moderate liver impairment (Child-Pugh A or B), as-needed dosing should not exceed 10 mg once a day; tadalafil is not recommended in severe impairment (Child-Pugh C) [1].

With CYP3A4 inhibitors such as ketoconazole or ritonavir, the label sets a maximum of 10 mg not more often than every 72 hours for as-needed use and 2.5 mg for once-daily use [1].

One practical snag for daily dosing: the label's starting dose for once-daily ED treatment is 2.5 mg, but Drugs@FDA lists the brand Cialis 2.5 mg tablet as discontinued, while generic tadalafil 2.5, 5, 10 and 20 mg tablets are approved under ANDAs [2]. Tadalafil is prescription only, and the label says not to split tablets; the entire dose should be taken [1][2].

Heart risk and nitrates

The Cialis label says ED treatments, including Cialis, should not be used in men for whom sexual activity is inadvisable because of their cardiovascular status [1]. It lists groups that were not included in the clinical trials and for which Cialis is therefore not recommended: myocardial infarction within the last 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]. In healthy volunteers, tadalafil 20 mg lowered supine blood pressure by a mean maximal 1.6/0.8 mm Hg versus placebo [1].

The label treats organic nitrates as contraindicated in any form, used regularly or intermittently, because tadalafil potentiates their blood pressure-lowering effect [1]. In a life-threatening situation where a nitrate is medically necessary, the label says nitrate administration may be considered only after at least 48 hours have elapsed since the last Cialis dose, and then only under close medical supervision with hemodynamic monitoring [1].

In a 150-man crossover study, tadalafil 20 mg was given daily for 7 days and then sublingual nitroglycerin 0.4 mg was given at set intervals; 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]. The interaction was still measurable at 24 hours, and the 48-hour figure is an emergency provision, not a safe-timing guide for routine use [1][3].

Guanylate cyclase stimulators such as riociguat are also contraindicated, because PDE5 inhibitors may potentiate their blood pressure-lowering effect [1].

Blood pressure drugs, alpha-blockers and alcohol

Tadalafil and alpha-blockers are both vasodilators, and the label records the size of the additive effect in healthy volunteers. With doxazosin 8 mg daily, tadalafil 20 mg produced a placebo-subtracted maximal standing systolic fall of 9.8 mm Hg; 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]. The standing fall was 1.7 mm Hg with tamsulosin 0.4 mg and tadalafil 10 mg, 2.3 mm Hg with tadalafil 20 mg, and 4.4 mm Hg with alfuzosin 10 mg and tadalafil 20 mg [1].

For ED, the labeled approach is to use tadalafil only after the man is stable on the alpha-blocker and to begin at the lowest dose; for BPH, the label does not recommend combining Cialis with an alpha-blocker, because the combination's efficacy has not been adequately studied and because of the risk of blood pressure lowering [1].

With antihypertensives such as amlodipine, ARBs, bendroflumethiazide, enalapril and metoprolol, clinical pharmacology studies showed small additional blood pressure reductions compared with placebo [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; tadalafil did not change alcohol levels and alcohol did not change tadalafil levels [1].

Tadalafil for BPH in an older man

Cialis 5 mg once daily is indicated for the signs and symptoms of BPH and for ED with BPH [1]. In a 12-week trial of men aged 45 or older with an IPSS of 13 or higher, tadalafil 5 mg once daily (n=161) lowered total IPSS by 5.6 points versus 3.6 on placebo (n=164; P=0.004), with improvement apparent from week 1 and significant by week 4 [4]. Tadalafil did not significantly improve peak urine flow or post-void residual volume [4].

When Cialis is started together with finasteride for BPH, the label recommends this for up to 26 weeks, because the incremental benefit decreases from week 4 to week 26 and the benefit beyond 26 weeks is unknown [1]. In a randomized double-blind study of 695 men aged 45 or older, IPSS fell by 4.0, 5.2 and 5.5 points at weeks 4, 12 and 26 with tadalafil 5 mg plus finasteride 5 mg (n=345), versus 2.3, 3.8 and 4.5 with placebo plus finasteride (n=350) [5]. The gap between the groups narrowed from 1.7 points at week 4 to 1.0 point at week 26 [5].

Vision, hearing and erections lasting over 4 hours

Sudden vision loss in one or both eyes can be non-arteritic anterior ischemic optic neuropathy (NAION), reported rarely after marketing with all PDE5 inhibitors; the label directs patients to stop Cialis and seek medical care [1]. The label cites an annual incidence of NAION of 2.5 to 11.8 cases per 100,000 in males aged 50 or older, and two observational case-crossover studies that suggested roughly a 2-fold risk, with estimates of 2.15 (95% CI 1.06 to 4.34) and 2.27 (95% CI 0.99 to 5.20) [1]. The label states that neither the postmarketing reports nor these studies establish a causal relationship [1]. Cialis should be used with caution in men with prior NAION or a crowded optic disc, and is not recommended in hereditary retinal disorders such as retinitis pigmentosa [1].

Sudden hearing decrease or loss, sometimes with tinnitus and dizziness, has been reported, and the label directs patients to stop Cialis and seek prompt medical attention; the label also says it cannot tell whether this is directly related to the drug [1].

The label calls for emergency care for an erection lasting more than 4 hours, painful or not; painful erections over 6 hours are priapism and can permanently damage erectile tissue [1]. Caution applies with sickle cell anemia, multiple myeloma, leukemia or penile deformity [1].

Side effects in the trials that included older men

In the three 12-week BPH and ED/BPH trials, mean age was 63 with a range of 44 to 93: headache was reported by 4.1% on tadalafil 5 mg versus 2.3% on placebo, dyspepsia 2.4% versus 0.2%, back pain 2.4% versus 1.4% and dizziness 1.0% versus 0.5%, with discontinuation for adverse events of 3.6% versus 1.6% [1]. In the as-needed ED studies, diarrhea was reported more frequently in patients 65 and older treated with Cialis [1]. Back pain and myalgia generally began 12 to 24 hours after dosing and typically resolved within 48 hours [1].

On efficacy, an integrated analysis of five as-needed trials covered 1,112 men with a mean age of 59 (range 22 to 82); with 20 mg, the erectile function domain of the IIEF improved by a mean 7.9 points, 75% of intercourse attempts were successful, and 81% reported improved erections versus 35% on placebo (all P<0.001) [6].

Other tadalafil products

Adcirca is a different tadalafil product, approved for pulmonary arterial hypertension at 40 mg once daily; Cialis is indicated for erectile dysfunction and benign prostatic hyperplasia [1][7]. Because both contain tadalafil, they should not be taken together, and the Cialis label says combinations with other PDE5 inhibitors or ED treatments have not been studied [1]. Tadalafil is not a testosterone treatment; the labels report no adverse effect of tadalafil 10 or 20 mg on mean testosterone, luteinizing hormone or follicle-stimulating hormone concentrations versus placebo [1].