Download FDA Approvals Tadalafil for benign prostatic hyperplasia

From Medscape Education Clinical Briefs > FDA
Approvals for CME
FDA Approvals: Tadalafil for Benign
Prostatic Hyperplasia
News Author: Robert Lowes
CME Author: Laurie Barclay, MD
Faculty and Disclosures
CME/CE Released: 10/28/2011; Valid for credit through 10/28/2012
CME/CE Information
Clinical Context
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.
More information on tadalafil can be found on the FDA Web site.
Laurie Barclay, MD, contributed to this synopsis.
Clinical Implications



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 asneeded 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.