Restarting Cialis (Tadalafil) After Acute Illness: A Clinical Guide

What the label says that bears on restarting

The Cialis label names cardiovascular conditions in which the drug is not recommended, dose ceilings tied to kidney and liver function, and interaction rules for drugs that change tadalafil exposure [1].

Tadalafil works by slowing the breakdown of cyclic GMP during sexual stimulation, which relaxes penile smooth muscle and increases blood flow; without sexual stimulation it has no effect [1]. The label notes that tadalafil has mild systemic vasodilatory properties that can produce transient blood pressure falls, and that it potentiates the hypotensive effect of nitrates [1]. After an illness, the label restrictions that can apply include cardiovascular status, nitrates, kidney and liver function, and interacting medicines [1].

Sexual activity is the first question, not the dose

The label tells physicians to consider cardiovascular status, since there is a degree of cardiac risk associated with sexual activity, and states that treatments for erectile dysfunction, including Cialis, should not be used in men for whom sexual activity is inadvisable as a result of their underlying cardiovascular status [1]. It also says patients who experience symptoms upon initiation of sexual activity should refrain from further sexual activity and seek immediate medical attention [1].

For scale, in a clinical pharmacology study tadalafil 20 mg lowered supine blood pressure by a mean maximal 1.6/0.8 mm Hg relative to placebo in healthy subjects [1].

The conditions the label says were not studied

The label lists groups that were not included in the clinical safety and efficacy trials and states that Cialis is not recommended for them until further information is available: myocardial infarction within the last 90 days; unstable angina or angina occurring during intercourse; NYHA class 2 or greater heart failure in the last 6 months; uncontrolled arrhythmias, hypotension below 90/50 mm Hg, or uncontrolled hypertension; and stroke within the last 6 months [1]. Separately, the label advises caution in left ventricular outflow obstruction such as aortic stenosis, and in severely impaired autonomic control of blood pressure [1].

Nitrates: the one absolute rule

Any form of organic nitrate, taken regularly or intermittently, is contraindicated with Cialis, and guanylate cyclase stimulators such as riociguat are contraindicated as well [1]. The label's nitrate timing provision is for emergencies: where a nitrate is deemed medically necessary in a life-threatening situation, at least 48 hours should elapse after the last Cialis dose before nitrate administration is considered, and even then only under close medical supervision with hemodynamic monitoring [1].

The time course was measured in a crossover study of 150 men who took tadalafil 20 mg or placebo daily for 7 days and then received sublingual nitroglycerin 0.4 mg [3]. 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 label describes the same pattern: a significant interaction at each time point up to and including 24 hours, not seen at 48 hours by most hemodynamic measures, though a few more tadalafil-treated men had greater blood pressure falls at 48 hours [1].

Drugs started during the illness that change tadalafil levels

Tadalafil is metabolized mainly by CYP3A4, so inhibitors raise exposure and inducers lower it [1]. Ketoconazole 400 mg daily raised tadalafil 20 mg exposure (AUC) by 312% and peak concentration by 22%; ketoconazole 200 mg daily raised tadalafil 10 mg AUC by 107% [1]. Ritonavir 200 mg twice daily raised tadalafil 20 mg AUC by 124%, while higher ritonavir doses (500 or 600 mg twice daily) raised AUC by 32% with a 30% fall in peak concentration [1]. Erythromycin, itraconazole and grapefruit juice were not studied but would likely increase exposure, in the label's words [1].

The label's response to CYP3A4 inhibition is a ceiling rather than a ban: as-needed Cialis no more than 10 mg every 72 hours, and once-daily Cialis no more than 2.5 mg [1]. In the other direction, rifampin 600 mg daily cut tadalafil 10 mg AUC by 88% and peak concentration by 46%; no dose adjustment is required, but the label says the reduced exposure can be anticipated to decrease the efficacy of once-daily Cialis by an amount that is unknown [1].

Alpha-blockers started during the illness

Alpha-blockers and tadalafil are both vasodilators, the effect on blood pressure is additive, and symptomatic hypotension such as fainting can occur [1]. In healthy volunteers, tadalafil 20 mg with doxazosin 8 mg daily produced a placebo-subtracted maximal standing systolic fall of 9.8 mm Hg (3.6 mm Hg supine), 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 after the morning tadalafil dose, against 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, and with alfuzosin 10 mg it was 4.4 mm Hg with tadalafil 20 mg [1].

For erectile dysfunction, the label says to be stable on the alpha-blocker first and to start Cialis at the lowest dose; for BPH it does not recommend combining Cialis with an alpha-blocker, and it says a man already on an alpha-blocker for BPH should stop it at least one day before starting once-daily Cialis for BPH [1].

Kidney and liver function after the illness

The label's kidney limits depend on creatinine clearance. As needed, a clearance of 30 to 50 mL/min means a starting dose of 5 mg and a maximum of 10 mg no more often than every 48 hours; below 30 mL/min or on hemodialysis, the maximum is 5 mg no more often than every 72 hours, and once-daily use is not recommended [1]. Exposure is 25% higher in healthy men aged 65 or older [1].

For as-needed use, the label caps the dose at 10 mg once per day in mild or moderate hepatic impairment classified as Child-Pugh A or B, and does not recommend use in severe impairment classified as Child-Pugh C [1].

As-needed and daily dosing in the label

The label says Cialis as needed for ED starts at 10 mg, may be increased to 20 mg or decreased to 5 mg, and is not to be taken more than once a day [1]. The label says it improved erectile function compared with placebo for up to 36 hours after a dose, which does not mean a continuous erection, since sexual stimulation is still required [1]. Once-daily use for ED starts at 2.5 mg and may increase to 5 mg; for BPH or ED with BPH it is 5 mg at about the same time every day [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 dosing gives continuous blood levels, which the label says to weigh when evaluating interactions [1]. The label says tablets are not to be split [1].

What to watch for after starting again

An erection lasting more than 4 hours, painful or not, needs emergency care; painful erections longer than 6 hours are priapism and can permanently damage erectile tissue, and the label advises caution in sickle cell anemia, multiple myeloma, leukemia, or penile deformity such as Peyronie's disease [1].

The label tells patients to stop Cialis and seek medical attention for sudden loss of vision in one or both eyes, which may be non-arteritic anterior ischemic optic neuropathy, and to stop and seek prompt attention for a sudden decrease or loss of hearing [1]. Two observational case-crossover studies suggested roughly a 2-fold increase in NAION risk (2.15, 95% CI 1.06 to 4.34; and 2.27, 95% CI 0.99 to 5.20), and the label states that neither the postmarketing reports nor these studies substantiate a causal relationship [1].

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

HealthRX.com offers tadalafil by prescription.