American College of Physicians: Internal Medicine — Doctors for Adults ®

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Strategies to overcome 'steroid phobia'

Tailored dosages and combination therapies can help minimize troubling side effects

From the May ACP Observer, copyright © 2004 by the American College of Physicians.

By Margie Patlak

For decades, inhaled corticosteroids have been the gold standard for controlling persistent asthma. Despite their effectiveness, however, the drugs have been dogged by some very real concerns about complications.

No one knows for sure whether cataracts, glaucoma, brittle bones and skin thinning arise when patients inhale corticosteroids directly into their lungs. But the possibility leaves more than a few physicians wary about prescribing the drugs.

"The nagging suspicion that the complications of inhaled corticosteroids are severe enough to warrant worry has interfered with how clinicians use the medications," noted Frank Leone, MD, a pulmonologist at Thomas Jefferson University in Philadelphia.

It's not just physicians who are concerned. Some experts talk about "steroid phobia" to describe the fear of some patients. That nervousness, they say, factors into physicians' decisions about when and how to prescribe inhaled steroids, and it tempers how well patients comply with the drugs.

"Some patients have a dreaded fear of side effects," said Stanley Szefler, MD, head of pediatric clinical pharmacology at the National Jewish Medical and Research Center in Denver. "They decline the treatment when offered or take it so sparingly that it's not beneficial."

While side effects of inhaled steroids are a very real concern for physicians and patients alike, experts say that physicians must balance those risks against other considerations. In patients with severe asthma, that includes the very real possibility of attacks that can be fatal.

Reviewing the data

Because the debate surrounding the use of inhaled steroids to treat asthma has become so intense, particularly on the part of patients, a group of physicians decided to systematically review the results of more than 100 studies on the complications of using inhaled corticosteroids to treat asthma.

Dr. Szefler co-chaired the panel of experts that conducted the review, which was convened by three groups: the American College of Chest Physicians, the American Academy of Allergy, Asthma and Immunology, and the American College of Allergy, Asthma & Immunology.

When the review was published in the December 2003 issue of Chest, it offered both good and bad news. (An abstract is online.) First, the bad news: There does seem to be a dose-dependent effect on skin thickness and ease of bruising in patients who take inhaled steroids. In addition, some adults experience marked loss of bone mineral density.

Both of these side effects, however, occur mainly after prolonged, high-dose treatment with the drugs. The jury is still out as to whether inhaled corticosteroids cause cataracts or glaucoma in adults. And on the plus side, there's good evidence that inhaled steroids don't permanently stunt the growth of children or give them brittle bones or cataracts.

Perhaps just as important, the review focused mainly on studies of first-generation inhaled steroids such as beclomethasone or triamcinolone. Because these drugs have greater systemic absorption, they tend to have more exaggerated side effects than the newer drugs commonly used today.

And because the review included studies conducted in Europe, where physicians tend to prescribe higher doses of steroids than their U.S. counterparts, the Chest article paints a worst-case scenario.

"We shouldn't overemphasize the potential for side effects because we're just living with the ghosts of the past," said allergist and asthma expert Harold S. Nelson, MD, with the National Jewish Medical and Research Center. Dr. Nelson was part of the expert panel that conducted the Chest review.

Other studies have also found that steroid-sparing regimens, such as the combination of an inhaled corticosteroid with a long-acting beta agonist, can be as effective as higher dose treatments that use only an inhaled steroid. Experts now believe that most patients with persistent asthma can be treated adequately with low-dose inhaled steroids that don't foster the complications seen with high-dose therapy or oral steroids.

Dose-reducing strategies

While the Chest review reassures physicians that the benefits of inhaled corticosteroids outweigh their risks, it doesn't give any guidance on how to minimize those side effects. Experts say, however, that following a handful of basic principles when prescribing the drugs will help keep side effects in check.

First, try to minimize the drugs' side effects by using the lowest dose possible for the shortest period of time. It's relatively easy to tailor the dose of inhaled steroids to patients because the drugs come in such a wide range of dosages. (See "Estimated comparative daily dosages for inhaled corticosteroids.")

Once you find a dosage of inhaled steroids that controls your patient's asthma, try to gradually taper down the dose. The goal is to sufficiently control asthma with the lowest dose possible, which requires frequent monitoring of patients.

"I might use high doses for weeks or months to gain control," said Dr. Szefler, "but I then try to back off and use low or medium doses." And for patients who suffer from seasonal asthma, try limiting their use of inhaled steroids to the times of year that are most troublesome—but check their asthma control during any off periods.

Keeping the dose low is just the first step. There are other strategies you can use to limit the drugs' systemic absorption. For example, tell patients to rinse out their mouth after using their inhalers.

You should also consider the systemic absorption rate of the type of steroid you prescribe. Beclomethasone and triamcinolone, for example, have the greatest systemic absorption, while fluticasone has the least.

In general, the newer the drug, the less it is absorbed systemically. Inhaled steroids now in the pipeline, such as inhaled mometasone, are expected to offer even lower rates of systemic absorption.

"You should view each new inhaled steroid as having been developed and approved primarily because it offered greater safety," said Dr. Nelson. "You need to go with the flow and not stick with some ancient drug."

He acknowledged, however, that the newer drugs are more expensive, which can limit their use for some patients. Some health plans may not cover these drugs because of their high costs.

What if you can't control your patient's asthma with low-dose inhaled corticosteroids? Before you bump up the dose of inhaled steroids, try combining a low-dose inhaled steroid with a long-acting beta agonist.

This is a tried-and-true recommendation in the guidelines for the management of asthma put out by the National Heart, Lung, and Blood Institute. (See "Tips to improve compliance with inhaled steroids." ) By adding a long-acting beta agonist to an inhaled corticosteroid, you can cut the dose of the steroid in half without losing any asthma control.

You can also combine an inhaled steroid with a leukotriene modifier or theophylline. These combinations, however, are less effective than the inhaled steroid-long-acting beta agonist combination.

If none of these options work, you may have to resort to high-dose inhaled corticosteroid therapy. While this approach increases the risk of reduced bone mineral density, cataracts and skin thinning, Dr. Nelson said you probably have no other option.

"Anyone who requires a high enough dose of inhaled steroids to produce bone loss has no choice because their asthma is so severe," he explained.

Tracking side effects

While some patients may require inhaled steroids to control their asthma, you need to keep an eye out for side effects.

"You use inhaled corticosteroids because they're very effective," said Paul E. Epstein, FACP, a pulmonologist at Philadelphia's University of Pennsylvania and Deputy Editor of Annals of Internal Medicine. "That doesn't mean you can turn a blind eye to their potential side effects. You have to be vigilante." Or as Montana pulmonologist Harmon Davis II, FACP, admonished: "Don't wait until they bust a bone."

Most experts recommend screening these patients for loss of bone mineral density and cataracts or glaucoma every one to two years, depending on their risk factors. And while most experts agree that patients taking high doses of steroids should be monitored frequently, there is little agreement on how regularly physicians should screen low-dose patients.

"I wouldn't do frequent bone mineral density scans for patients taking 100 micrograms of fluticasone twice a day, unless they started out with low bone density and I was worried about them dropping below the cutoff point for treatment," said Dr. Nelson. "The patient's genetics, activity level and other risk factors are going to affect their bone density more than 100 micrograms of fluticasone."

Dr. Szefler agreed that patients taking low doses are "relatively safe," but he added that "there are individuals who are more sensitive to the side effects of inhaled corticosteroids." He said he takes baseline bone mineral density measurements of all his patients using high-dose inhaled corticosteroids. He will decide how often to monitor them based on how much bone loss he sees in the baseline as compared to subsequent scans.

Dr. Szefler said he also reviews the diets of his patients on high-dose inhaled corticosteroids for calcium intake. If they are not getting enough calcium, he recommends supplements.

Dr. Nelson said he recommends calcium supplements to all his older patients, whether they have asthma or not. He cited a small study reviewed in the Chest article that found that patients who took calcium supplements experienced no decline in their bone mineral density while taking inhaled corticosteroids. Similar patients who didn't take the supplements developed a nearly 2% decline.

There is less agreement on when to screen patients for cataracts. While some physicians screen patients as often as twice a year for cataracts, some don't see the point.

"If your patient needs steroids to control his asthma, then a slowly developing cataract is just part of the price you pay," Dr. Nelson said. "There's no particular virtue in scrutinizing his lenses every three months to see if he's developing one."

Complications

Even if asthma patients develop significant bone loss, cataracts, skin thinning or glaucoma, most experts are unwavering in their commitment to continue treating them with inhaled corticosteroids.

"We have to be aware of the side effects, but they don't moderate my use of these drugs," explained Dr. Davis, a former Governor for the Montana Chapter. "If a patient develops cataracts, they can be easily repaired. But if he develops a fatal asthma attack, that can't be repaired."

Dr. Nelson agreed. "You don't sacrifice the control of asthma because of any of these side effects," he said. "You put your patients on the lowest dose of steroids that works and then you treat the complications. The good news is that most of the complications are treatable."

Cataracts can be easily removed by ophthamologists, who should also be relied on to screen for and treat any glaucoma that arises. Experts agree that it's important to give patients with significant bone loss bisphosphonates or other drugs to stem that loss.

If patients' asthma isn't too severe and they develop bone loss, cataracts or glaucoma, some experts recommend trying to switch them to another drug, such as a leukotriene modifier, and seeing if it keeps their asthma attacks at bay. "But if they had severe enough asthma, you wouldn't attempt this," noted Dr. Szefler.

There's no treatment for skin thinning and easy bruising other than wearing long sleeves and pants to protect the skin. Although this complication is not particularly harmful, it's a concern for some patients.

"Nobody likes to go around with big black and blue marks," said the University of Pennsylvania's Dr. Epstein, Governor for the Pennsylvania Southeastern Chapter. "It's very distressing to some patients, and they stop taking their inhaled steroids for this reason."

In older women, it may be hard to distinguish the skin thinning and easy bruising that is a natural outcome of aging vs. that which is brought on by their inhaled corticosteroids. "In studies that have been done, being a woman carries a bigger risk for bruising than taking inhaled steroids," noted Dr. Nelson. But the two factors are additive, and steroids can worsen a naturally occurring condition.

In general, when dealing with the complications of inhaled corticosteroids, doctors have to weigh the benefits of the drugs vs. the risks of not using them in individual patients. But the scale often seems to tip in the direction of using the inhaled steroids because they are so effective.

"If you take the inhaled steroids away," Dr. Nelson said, "patients get sick."

Margie Patlak is a freelance science writer in Elkins Park, Pa.

The information included herein should never be used as a substitute for clinical judgment and does not represent an official position of ACP.

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Tips to improve compliance with inhaled steroids

Studies show that between 15% and 20% of asthmatic patients who receive a prescription for inhaled corticosteroids don't use the drugs on a regular basis. Why is there such poor compliance with drugs that can dramatically stem the number of patients' asthma attacks?

Experts say in part, poor compliance is not unique to inhaled steroids. Some patients can't afford the drugs or simply forget to take them.

But experts also refer to the "steroid phobia" that makes many patients afraid of side effects. Some patients also balk at taking an inhaled medication instead of a pill.

Another problem with inhaled corticosteroids is that their effects are subtle and take a while to surface. Patients may feel drugs that don't appear to be working aren't worth the expense and inconvenience.

What can you do to boost compliance? First, reassure patients that the side effects of inhaled corticosteroids are minimal to nonexistent depending on the dose taken.

"Let them vent any concerns they might have about steroids so they don't quietly accept the prescription but leave your office muttering 'I'm not going to take this damn drug,' " said allergist and asthma expert Harold S. Nelson, MD, with the National Jewish Medical and Research Center in Denver. He cited one study that suggested physicians could improve compliance by reassuring patients of the safety of inhaled corticosteroids.

Dr. Nelson also recommended using a drug such as Advair, which combines an inhaled corticosteroid (fluticasone) with a long-acting beta agonist (salmeterol). Because patients see the immediate benefit of the long-acting beta agonist, they may be more inclined to take the combination drug.

"Patients sense this combination drug is doing something," he said. "If they forget to use it for two or three days, they realize they're sick again."

This is in contrast to taking only inhaled corticosteroids, whose onset and offset effects are more subtle. Compliance measured by prescription refills is almost double with the combination compared to the inhaled steroid alone, Dr. Nelson said.

When it comes to compliance, the less patients have to use an inhaler the better, several experts pointed out. Try prescribing inhaled steroids that have to be taken only once or twice a day as opposed to three or four times a day.

Dry powder inhalers are also easier to take than metered dose inhalers. And make sure patients rinse their mouths out after taking the inhaler to reduce any topical effect like oral thrush, and to stem their oral absorption of the drug.

Last but not least, encourage forgetful patients to develop a routine of taking the inhaler at the same time every day. And stress the rewards they will reap by taking their inhaled corticosteroids regularly.

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