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Inhaled Drugs for COPD Linked to Urinary Problem

Study Shows Inhaled Anticholinergic Drugs May Increase Risk for Acute Urinary Retention

By Brenda Goodman
WebMD Health News

Reviewed By Laura J. Martin, MD

May 23, 2011 -- Men who take certain kinds of inhaled medications to treat chronic lung disease are more likely to experience a medical emergency called acute urinary retention than those who don't take the drugs, a new study shows.

Acute urinary retention is feeling the pressure, pain, and urgency of a having full bladder without being able to relieve it by urination. If left untreated, urine can back up into the kidneys, causing infections and even organ damage.

The study, of more than a half million older adults with chronic obstructive pulmonary disease (COPD), found that men taking inhaled anticholinergic medications, which are sold under the brand names Atrovent, Combivent, and Spiriva, had about a 40% higher risk of acute urinary retention compared to those who were not taking these kinds of medications.

"The thing is that often people don't associate [the inhaled drugs] with a problem peeing," says study researcher Anne Stephenson, MD, MPH, a pulmonologist at St. Michael's Hospital in Toronto. "Not only does the patient not necessarily make that connection, but I think clinicians don't make the connection because there's a belief, not necessarily rightly, that the drugs aren't systemically absorbed."

The risk was higher in men who had just started on the drugs, those who had enlarged prostates, and those using both short- and long-acting anticholinergic bronchodilators at the same time.

There was no increased risk of urinary retention observed in women.

The study is published in the Archives of Internal Medicine.

"It's impressive," says Elizabeth Kavaler, MD, a urologist at Lenox Hill Hospital in New York City who was not involved in the study. "I thought it was a really well done, complicated study. And it certainly reminds us to be attentive in these situations and for patients to be attentive."

Experts, including the study's authors, are careful to note that the study was only able to show an association between the drugs and the risk of urinary retention but that it couldn't prove that the drugs caused the problem.

However, the fact that the increased risk was seen in those who were newly treated and those on more than one kind of anticholinergic medication makes for a strong case.

"The whole thing makes sense," Kavaler says. "Activation of acetylcholine helps you urinate, so if you block that, it relaxes the bladder. So it makes your bladder lazy."

Industry Perspective

Companies that manufacture anticholinergic inhalers say the risk of urinary retention associated with anticholinergic drugs is known.

"It does not add clinical information that would at all change the risk-benefit profile of Spiriva," says Emily Baier, a spokeswoman for Boehringer Ingelheim, the company that makes Spiriva.

"Urinary retention is a known side effect of anticholinergics and can occur in particular with patients with conditions like BPH [benign prostatic hypertrophy]. This is actually listed in our label," Baier says.

Urinary Retention in COPD Patients

Using a database of more than 565,000 Canadians over age 65 with COPD, researchers identified more nearly 10,000 men and 2,000 women who had at least one episode of acute urinary retention in a six-year period between 2003 and 2009.

People were excluded from the analysis if they'd had radical cystectomy, or surgery to remove the bladder, or if they had a history of acute urinary retention, since having one episode increases the chances for another.

Each person with acute urinary retention was compared to five other people of the same age who had not experienced a problem with urination.

No increased risk was seen in women.

Among men, however, those who were new users, meaning that they had started treatment in the last 30 days, had a 42% increased risk of acute urinary retention compared to those not taking the drugs.

Men who had been on the medications for longer than 30 days had a 36% increased risk of acute urinary retention, while past users of the medications did not have a significantly different risk compared to nonusers.

Men with enlarged prostates who were new users of inhaled anticholinergic drugs had an even greater risk, about 80%, compared to those not taking the medications.

To express the risk a different way, researchers calculated that 514 men with COPD and enlarged prostates would need to take these kinds of inhaled bronchodilators for one man to experience acute urinary retention within 30 days of starting the medication.

After six months of treatment, however, that number drops to one in 263 men.

The highest risk was seen in men who were using both short and long-acting inhalers to ease their breathing. They had nearly three times the risk of acute urinary retention as men who weren't using the medications at all.

"The key is that people recognize that if they're having trouble peeing, it may actually be related to the medications they take, including their puffers," Stephenson tells WebMD.

"They should mention that to the people who are prescribing these medicines."

Weighing Benefits and Risks

Experts say the study highlights the need for greater doctor-patient communication about inhaled medications for COPD.

"There's nothing to suggest that these drugs slow down the disease or make you live longer," says Curt D. Furberg, MD, PhD, professor of public health sciences at the Wake Forest University School of Medicine in North Carolina, who wrote a commentary that accompanies the study. "So it's really symptomatic improvement, but clearly, many patients really value that."

SOURCES:

Stephenson, A. Archives of Internal Medicine, May 24, 2011.

Singh, S. Archives of Internal Medicine, May 24, 2011.

Anne Stephenson, MD, MPH, pulmonologist, department of medicine, Keenan Research Centre, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto.

Elizabeth Kavaler, MD, urologist, Lenox Hill Hospital, New York City.

Emily Baier, spokeswoman, Boehringer Ingelheim.

Curt D. Furberg, MD, PhD, professor of public health sciences, Wake Forest University School of Medicine.

© 2011 WebMD, LLC. All rights reserved.



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