Cialis Monitoring Schedule: Labs and Exams You Need on Tadalafil

At a glance

• Before starting / Medical assessment for underlying causes of ED or BPH [1]
• Cardiovascular check / Sexual activity must not be inadvisable for cardiac reasons [1]
• Kidney function / Creatinine clearance 30 to 50 mL/min: as-needed start 5 mg, maximum 10 mg every 48 hours [1]
• Kidney function, lower / Below 30 mL/min or hemodialysis: maximum 5 mg every 72 hours; once daily not recommended [1]
• Liver impairment / Child-Pugh A or B: as-needed maximum 10 mg; Child-Pugh C: not recommended [1]
• Blood pressure / Alpha-blockers, antihypertensives and 5 or more alcohol units can add to blood pressure lowering [1]
• CYP3A4 inhibitors / As-needed maximum 10 mg every 72 hours; once-daily maximum 2.5 mg [1]
• Symptoms to act on / Sudden vision or hearing loss, erection over 4 hours [1]

What the Cialis label asks for before treatment

The first item is a medical assessment, not a lab panel. The label says evaluation of erectile dysfunction and BPH should include an appropriate medical assessment to identify potential underlying causes, as well as treatment options [1].

It also asks for a judgment about the heart. The label states there is a degree of cardiac risk associated with sexual activity, and Cialis should not be used in men for whom sexual activity is inadvisable as a result of their cardiovascular status [1]. The label does not recommend Cialis, because these groups were not studied, in men with a myocardial infarction within the last 90 days, unstable angina or angina occurring during intercourse, NYHA class 2 or greater heart failure within the last 6 months, uncontrolled arrhythmias, hypotension below 90/50 mm Hg or uncontrolled hypertension, or a stroke within the last 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 advises caution in left ventricular outflow obstruction, such as aortic stenosis, and in severely impaired autonomic control of blood pressure [1].

Blood pressure and medicines to review

Much of the label's safety content is about blood pressure and drug interactions. For ED, the label says to be stable on the alpha-blocker first and start Cialis at the lowest dose [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 risk of blood pressure lowering [1].

In a healthy-volunteer study, tadalafil 20 mg plus doxazosin 8 mg daily produced a placebo-subtracted mean maximal standing systolic blood pressure fall of 9.8 mm Hg [1]. In a second doxazosin study, 16 of 24 subjects had a standing systolic reading below 85 mm Hg or a fall over 30 mm Hg after the 8 a.m. tadalafil dose, versus 6 on placebo [1]. With tamsulosin 0.4 mg, the mean maximal standing systolic fall was 1.7 mm Hg with tadalafil 10 mg and 2.3 mm Hg with 20 mg, and no subject taking tamsulosin had a standing systolic reading below 85 mm Hg [2].

Tadalafil is metabolized mainly by CYP3A4 [1]. Ketoconazole 400 mg daily raised tadalafil 20 mg exposure (AUC) by 312% [1]. With potent CYP3A4 inhibitors such as ketoconazole or ritonavir, the Cialis label limits as-needed tadalafil to a maximum of 10 mg every 72 hours and once-daily tadalafil to a maximum of 2.5 mg [1]. Rifampin 600 mg daily cut tadalafil 10 mg AUC by 88%; the label says no dose adjustment is warranted, but the efficacy of once-daily Cialis may fall by an unknown amount [1]. Substantial alcohol, 5 units or more, can increase orthostatic signs and symptoms such as a rise in heart rate, a fall in standing blood pressure, dizziness and headache [1].

Nitrates are contraindicated in any form, regularly or intermittently [1]. In a life-threatening situation where a nitrate is medically necessary, at least 48 hours should elapse 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, the interaction with sublingual nitroglycerin was significant at every time point up to and including 24 hours [3]. The label says it was not seen by most measures at 48 hours, although a few more tadalafil men had larger blood pressure falls [1].

Kidney and liver impairment: what changes the dose

Kidney function and liver impairment can affect the Cialis dose. The label uses creatinine clearance and Child-Pugh class to set limits [1].

For as-needed ED use when creatinine clearance is 30 to 50 mL/min, the Cialis label recommends a starting dose of 5 mg and a maximum of 10 mg no more often than every 48 hours. When creatinine clearance is below 30 mL/min or the person is on hemodialysis, the label sets a maximum of 5 mg no more often than every 72 hours [1]. Once-daily Cialis is not recommended below 30 mL/min [1]. For BPH or ED with BPH when creatinine clearance is 30 to 50 mL/min, the label recommends starting at 2.5 mg and considering 5 mg based on individual response [1].

For liver impairment, the label says as-needed use in Child-Pugh A or B should not exceed 10 mg once per day, and Cialis is not recommended in Child-Pugh C [1].

Symptoms that need attention

The label's eye and hearing warnings are symptom-based. The label says to stop Cialis and seek medical care for a sudden loss of vision in one or both eyes, which could be non-arteritic anterior ischemic optic neuropathy (NAION) [1]. NAION has been reported rarely after marketing with all PDE5 inhibitors. Two observational case-crossover studies suggested about 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), and the label says neither the reports nor these studies substantiate a causal relationship [1]. The Cialis label advises caution for people with a history of NAION and says a crowded optic disc may also increase NAION risk, and it is not recommended in hereditary retinal disorders such as retinitis pigmentosa [1].

The label also says to stop Cialis and seek prompt medical attention for a sudden decrease or loss of hearing, which may come with tinnitus and dizziness [1]. An erection lasting more than 4 hours, painful or not, needs emergency care; painful erections over 6 hours are priapism and can permanently damage erectile tissue [1]. The label advises caution in sickle cell anemia, multiple myeloma, leukemia, and penile deformity such as angulation, cavernosal fibrosis or Peyronie's disease [1].

Common side effects in the label's trials

In the as-needed ED trials, headache occurred in 15% of men on tadalafil 20 mg versus 5% on placebo, dyspepsia in 10% versus 1%, back pain in 6% versus 3%, and myalgia in 3% versus 1% [1]. For once-daily 5 mg in BPH or ED with BPH, headache was 4.1% 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% [1]. Back pain or myalgia usually began 12 to 24 hours after dosing and resolved within 48 hours [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 produces continuous blood levels, and the label says interactions last longer than with sildenafil, whose half-life is about 4 hours [1].

Hormone levels and the BPH work-up

Tadalafil is not a testosterone treatment. The label reports no adverse effect of tadalafil 10 or 20 mg on mean testosterone, luteinizing hormone or follicle-stimulating hormone concentrations versus placebo [1]. For BPH, the label says to consider other urological conditions that may cause similar symptoms before starting treatment [1].

Where tadalafil fits

Cialis is approved for erectile dysfunction, for the signs and symptoms of BPH, and for both together; the 5 mg once-daily dose is the BPH dose, and when Cialis is started with finasteride for BPH the label recommends use for up to 26 weeks [1]. Adcirca is a separate tadalafil product, a 20 mg tablet approved for pulmonary arterial hypertension at a different dose from Cialis [4]. The Cialis label says that combining Cialis with other PDE5 inhibitors or other ED treatments has not been studied [1].

Frequently asked questions

›What does the Cialis label require before starting tadalafil?

An appropriate medical assessment to identify underlying causes of ED or BPH and treatment options, plus a judgment that sexual activity is not inadvisable for cardiovascular reasons. The label does not recommend Cialis, because these groups were not studied, after a heart attack within 90 days, with unstable angina, with NYHA class 2 or greater heart failure within 6 months, with uncontrolled arrhythmia, with blood pressure below 90/50 mm Hg or uncontrolled hypertension, or after a stroke within 6 months [1].

›What are the kidney dose limits for tadalafil?

For as-needed use when creatinine clearance is 30 to 50 mL/min, the Cialis label recommends 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. Once-daily use is not recommended below 30 mL/min. For BPH or ED with BPH at 30 to 50 mL/min, the label recommends starting at 2.5 mg and considering 5 mg [1].

›What liver limits does the Cialis label give?

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

›What blood pressure change does tadalafil cause?

In healthy volunteers, tadalafil 20 mg lowered supine blood pressure by a mean maximal 1.6/0.8 mm Hg versus placebo. Alpha-blockers, antihypertensives and 5 or more alcohol units can add to blood pressure lowering [1].

›What symptoms need urgent care on Cialis?

The label says to stop Cialis and seek medical care for sudden loss of vision in one or both eyes, and to stop and seek prompt medical attention for sudden decrease or loss of hearing. An erection lasting more than 4 hours, painful or not, needs emergency care [1].

›Which medicines change the tadalafil dose?

For potent CYP3A4 inhibitors such as ketoconazole or ritonavir, the label sets the as-needed maximum at 10 mg every 72 hours and the once-daily maximum at 2.5 mg. Nitrates in any form and guanylate cyclase stimulators such as riociguat are contraindicated [1].

References

1. U.S. National Library of Medicine, DailyMed. Cialis (tadalafil) tablets, Lilly prescribing information. Cialis (tadalafil) tablets, Lilly label
2. Kloner RA, Jackson G, Emmick JT, Mitchell MI, Bedding A, Warner MR, et al. Interaction between the phosphodiesterase 5 inhibitor, tadalafil and 2 alpha-blockers, doxazosin and tamsulosin in healthy normotensive men. J Urol. 2004;172(5 Pt 1):1935-40. Interaction between the phosphodiesterase 5 inhibitor, tadalafil and 2 alpha-blockers, doxazosin and tamsulosin in healthy normotensive men
3. Kloner RA, Hutter AM, Emmick JT, Mitchell MI, Denne J, Jackson G. Time course of the interaction between tadalafil and nitrates. J Am Coll Cardiol. 2003;42(10):1855-60. Time course of the interaction between tadalafil and nitrates
4. Drugs@FDA: FDA-Approved Drugs. Drugs@FDA: FDA-Approved Drugs