Penile erection during sexual stimulation is caused by increased penile blood flow resulting from the relaxation of penile arteries and corpus cavernosal smooth muscle. This response is mediated by the release of nitric oxide (NO) from nerve terminals and endothelial cells, which stimulates the synthesis of cGMP in smooth muscle cells. Cyclic GMP causes smooth muscle relaxation and increased blood flow into the corpus cavernosum. The inhibition of phosphodiesterase type 5 (PDE5) enhances erectile function by increasing the amount of cGMP. Tadalafil inhibits PDE5. Because sexual stimulation is required to initiate the local release of nitric oxide, the inhibition of PDE5 by tadalafil has no effect in the absence of sexual stimulation.

The effect of PDE5 inhibition on cGMP concentration in the corpus cavernosum and pulmonary arteries is also observed in the smooth muscle of the prostate, the bladder and their vascular supply. The mechanism for reducing BPH symptoms has not been established.

Studies in vitro have demonstrated that tadalafil is a selective inhibitor of PDE5. PDE5 is found in the smooth muscle of the corpus cavernosum, prostate, and bladder as well as in vascular and visceral smooth muscle, skeletal muscle, urethra, platelets, kidney, lung, cerebellum, heart, liver, testis, seminal vesicle, and pancreas.

In vitro studies have shown that the effect of tadalafil is more potent on PDE5 than on other phosphodiesterases. These studies have shown that tadalafil is >10,000-fold morepotent for PDE5 than for PDE1, PDE2, PDE4, and PDE7 enzymes, which are found in the heart, brain, blood vessels, liver, leukocytes, skeletal muscle, and other organs. Tadalafil is >10,000-fold more potent for PDE5 than for PDE3, an enzyme found in the heart and blood vessels. Additionally, tadalafil is 700-fold more potent for PDE5 than for PDE6, which is found in the retina and is responsible for phototransduction. Tadalafil is >9,000- fold more potent for PDE5 than for PDE8, PDE9, and PDE10. Tadalafil is 14-fold more potent for PDE5 than for PDE11A1 and 40-fold more potent for PDE5 than for PDE11A4, two of the four known forms of PDE11. PDE11 is an enzyme found in human prostate, testes, skeletal muscle and in other tissues (e.g., adrenal cortex). In vitro, tadalafil inhibits human recombinant PDE11A1 and, to a lesser degree, PDE11A4 activities at concentrations within the therapeutic range. The physiological role and clinical consequence of PDE11 inhibition in humans have not been defined.

CIALIS is a phosphodiesterase 5 (PDE5) inhibitor indicated for the treatment of:

• erectile dysfunction (ED) 
• the signs and symptoms of benign prostatic hyperplasia (BPH) 
• ED and the signs and symptoms of BPH (ED/BPH) (

If CIALIS is used with finasteride to initiate BPH treatment, such use is recommended for up to 26 weeks.

CIALIS for use as needed:

• ED: Starting dose: 10 mg as needed prior to sexual activity. Increase to 20 mg or decrease to 5 mg based upon efficacy/tolerability.
• Improves erectile function compared to placebo up to 36 hours post dose. Not to be taken more than once per day.

CIALIS for once daily use:

• ED: 2.5 mg taken once daily, without regard to timing of sexual activity. May increase to 5 mg based upon efficacy and tolerability 
• BPH: 5 mg, taken at approximately the same time every day
• ED and BPH: 5 mg, taken at approximately the same time every day

CIALIS may be taken without regard to food.

Most common adverse reactions (≥2%) include headache, dyspepsia, back pain, myalgia, nasal congestion, flushing, and pain in limb.

• Administration of CIALIS to patients using any form of organic nitrate is contraindicated. CIALIS was shown to potentiate the hypotensive effect of nitrates.
• History of known serious hypersensitivity reaction to CIALIS or ADCIRCA.
• Administration with guanylate cyclase (GC) stimulators, such as riociguat.

• Patients should not use CIALIS if sex is inadvisable due to cardiovascular status (5.1).
• Use of CIALIS with alpha-blockers, antihypertensives or substantial amounts of alcohol (≥5 units) may lead to hypotension (5.6, 5.9).
• CIALIS is not recommended in combination with alpha-blockers for the treatment of BPH because efficacy of the combination has not been adequately studied and because of the risk of blood pressurelowering. Caution is advised when CIALIS is used as a treatment for ED in men taking alpha-blockers.
• Patients should seek emergency treatment if an erection lasts >4 hours. Use CIALIS with caution in patients predisposed to priapism.
• Patients should stop CIALIS and seek medical care if a sudden loss of vision occurs in one or both eyes, which could be a sign of non arteritic anterior ischemic optic neuropathy (NAION). CIALIS should be used with caution, and only when the anticipated benefits outweigh the risks, in patients with a history of NAION. Patients with a "crowded" optic disc may also be at an increased risk of NAION.
• Patients should stop CIALIS and seek prompt medical attention in the event of sudden decrease or loss of hearing.
• Prior to initiating treatment with CIALIS for BPH, consideration should be given to other urological conditions that may cause similar symptoms.