Tadalafil is a phosphodiesterase-5 (PDE5) inhibitor that was approved by the US Food and Drug Administration (FDA) in 2003 to treat erectile dysfunction (ED). The FDA has now expanded the approved indications to include benign prostatic hyperplasia (BPH), either alone or in combination with ED.
The inhibition of PDE5 by tadalafil improves erectile function by increasing the amount of cyclic guanosine monophosphate in the smooth muscle of the corpus cavernosa. This action increases penile blood flow, resulting in penile erection during sexual stimulation. PDE5 inhibition also affects concentration of cyclic guanosine monophosphate in the smooth muscle of the prostate, the bladder, and their vascular supply, but the precise mechanism for reducing BPH symptoms has not been determined.
Study Synopsis and Perspective
The FDA approved tadalafil (Cialis, Eli Lilly) a PE5 inhibitor to also treat the signs and symptoms of BPH as well as a combination of BPH and ED when the conditions coincide.
Men with BPH often experience sudden urges to urinate, difficulty in starting urination, a weak urine stream, and more frequent urination, including at night. In 2 clinical trials, men with BPH who took 5 mg of tadalafil daily experienced a significant improvement in these symptoms compared with men receiving a placebo. A third study showed that men who experienced both ED and BPH and who took 5 mg of tadalafil daily had improvement in both conditions compared with a placebo group.
Scott Monroe, MD, director of the Division of Reproductive and Urologic Products in the FDA's Center for Drug Evaluation and Research, said in a press release that both BPH and ED are common disorders among older men. "Cialis offers these men another treatment option," Dr. Monroe said.
For men with BPH or ED and BPH, dosage of tadalafil is 5 mg, taken at approximately the same time every day, with or without food.
Tadalafil joins a long list of other FDA-approved drugs for BPH symptoms: finasteride (Proscar); dutasteride (Avodart); dusasteride plus tamsulosin (Jalyn); and alpha-blockers terazosin (Hytrin), doxazosin (Cardura), tamsulosin (Flomax), alfuzosin (Uroxatral), and silodosin (Rapaflo).
The agency approved tadalafil for treating ED in 2003.
The FDA advises clinicians that they should not prescribe tadalafil for men taking nitrates such as nitroglycerin because the combination may trigger an unsafe drop in blood pressure. Also, the agency does not recommend combining tadalafil with alpha-blockers for the treatment of BPH because the combination therapy has not been adequately studied, and it comes with a risk of lowering blood pressure.
Warnings and Precautions
Men with limited cardiovascular function precluding sexual activity should not use tadalafil.
Concomitant use of tadalafil with alpha-blockers, antihypertensive drugs, or 5 or more units of alcohol may cause hypotension.
The dose of tadalafil should be adjusted for men taking potent inhibitors of cytochrome P450 3A4 (CYP3A4) such as ketoconazole or ritonavir, which increase exposure to tadalafil. For once-daily use, the dose of tadalafil should not exceed 2.5 mg, and for use as needed for ED, the cumulative dose should not exceed 10 mg every 72 hours.
CYP3A4 inducers such as rifampin reduce exposure to tadalafil.
In men with a history of priapism, tadalafil should be used with caution. If an erection lasts for more than 4 hours, men taking tadalafil should seek emergency treatment.
A sudden loss of vision in 1 or both eyes in men taking tadalafil may be a sign of nonarteritic ischemic optic neuropathy (NAION). These patients should stop the drug and seek medical attention. Patients with a history of NAION should be counseled regarding the increased risk for NAION with use of tadalafil.
Men who experience sudden decrease or loss of hearing while taking tadalafil should stop the drug and seek prompt medical care.
Before prescribing tadalafil for treatment of BPH, clinicians should rule out other urologic conditions with similar symptoms.
The most often reported adverse reactions, occurring in 2% or more of patients taking tadalafil, include headache, dyspepsia, back pain, muscle pain, nasal stuffing, flushing, and limb pain.
Use in Specific Populations
Use of tadalafil is not recommended in patients with severe hepatic impairment, and dosage adjustment may be needed in patients with mild or moderate hepatic impairment.
Once-daily use of tadalafil is not recommended in patients with renal impairment requiring hemodialysis or in patients with a creatinine clearance of less than 30 mL/minute. For use in these patients as needed for ED, the dose should not exceed 5 mg every 72 hours. Dosage adjustment may be needed in patients with a creatinine clearance of 30 to 50 mL/minute.
- The FDA has now approved daily use of tadalafil to treat urinary signs and symptoms in men with BPH. The drug may also be used to treat both BPH and ED when these conditions coexist. For daily use in BPH or BPH/ED, the dosage of tadalafil is 5 mg, taken at approximately the same time every day, with or without food.
- Use of tadalafil with nitrates, alpha-blockers, antihypertensive drugs, or 5 or more units of alcohol may cause hypotension. Men in whom cardiovascular function is too limited to engage in sexual activity should not be given tadalafil. Potent inhibitors of CYP3A4 increase exposure to tadalafil, whereas CYP3A4 inducers such as rifampin reduce exposure to tadalafil. Before prescribing tadalafil for treatment of BPH, clinicians should rule out other urologic conditions causing similar symptoms.
- Patients with severe hepatic impairment should not be prescribed tadalafil. Patients with mild or moderate hepatic impairment may require dosage adjustment. Patients with renal impairment requiring hemodialysis, or patients with a creatinine clearance of less than 30 mL/minute, should not use tadalafil once daily. For as-needed use, the dose should not exceed 5 mg every 72 hours. Patients with a creatinine clearance of 30 to 50 mL/minute may require dosage adjustment.