Rx CARE

Crohn's disease patients find new relief from old drug

Nearly one individual per 1,000 suffers from the diarrhea, cramping, abdominal pain, fatigue, and weight loss associated with Crohn's disease (CD). The incurable, inflammatory condition of the gastrointestinal tract may affect any section—from mouth to anus; however, CD predominates in the intestine and the colon. Periodic exacerbations and remissions characterize the disease process, and flare-ups may deprive the body of vital fluids, nutrients, minerals, and vitamins.

Treatment of acute exacerbations of CD has traditionally relied on the use of salicylates or corticosteroids. Salicylates, such as sulfasalazine or mesalamine, may be effective in treating mild to moderate exacerbations of CD but are not effective for more severe forms.

In fact, Joseph DiPiro, Pharm.D., director of surgical research at the Medical College of Georgia, said of salicylates for treatment of CD, "A high percentage of people still need a steroid." Prednisone, prednisolone, or intravenous methylprednisolone have been treatments of choice in patients with severe disease or disease that is nonresponsive to salicylates. But the utility of these corticosteroids is limited by potential systemic complications, including avascular necrosis, osteoporosis, cataracts, hypertension, diabetes, suppression of the hypothalamic-pituitary axis, acne, and hirsutism.

Commenting on the lack of both safe and effective options for treating CD, William Sandborn, M.D., professor of medicine, Mayo Medical School, and head of inflammatory bowel disease research at the Mayo Clinic, said, "Salicylates are safe but marginally effective. Steroids are effective but marginally safe." Since CD can be debilitating and has few safe and efficacious pharmacologic options for treatment, new advances are always welcomed by patients and physicians alike.

Out of necessity for new therapeutic agents to treat CD, earlier this year, the Food & Drug Administration gave oral budesonide capsules (Entocort EC, AstraZeneca) priority review and approved the drug in early October. According to Jim Coyne, senior manager of gastrointestinal public affairs at AstraZeneca, Entocort EC is approved to treat mild to moderate CD involving the ileum and/or ascending colon.

In clinical trials involving nearly 1,000 individuals, 48%-69% of patients receiving 9 mg of oral budesonide daily reported clinical improvements in their symptoms within eight weeks of treatment.

Although a corticosteroid, budesonide capsules are reportedly well tolerated. The tolerability is due, at least partially, to the formulation of budesonide, which allows the drug to be released in the intestines. Following release, budesonide undergoes extensive local metabolism, thereby preventing most of the drug from entering systemic circulation. Local release allows the drug to reach its site of action, and local metabolism prevents many systemic side effects that limit the utility of other corticosteroids.

According to Sandborn, at therapeutically equivalent doses, "the frequency of adverse effects is substantially less with budesonide compared with prednisolone, but the efficacy is comparable." Headache, respiratory infection, nausea, and symptoms associated with hypercorticism are among the most common adverse effects reported by patients.

As a result of budesonide's safety and efficacy profile, Sandborn predicted that, in time, oral budesonide "will largely replace salicylates for induction of remission" in CD.

Since budesonide already exists as both a pulmonary turbuhaler and respules (Pulmicort, AstraZeneca) as well as a nasal inhaler (Rhinocort, AstraZeneca), it is conceivable that patients could take a prescribed inhalation formulation for treating asthma or allergies with oral Entocort EC for CD. Since the same medication is marketed under vastly different trade names, patients could be unaware that they are taking the same drug via different routes of administration.

When asked whether taking Entocort EC with Pulmicort or Rhinocort could place patients at increased risk of adverse effects, Coyne responded, "When you look at the product labeling, there are no contraindications to Entocort EC other than known hypersensitivity to budesonide. Budesonide is a medication with a high first-pass metabolism, and the bottom line is that this prevents most of the drug from entering systemic circulation."

Kelly Dowhower Karpa, R.Ph., Ph.D.

The author is a clinical writer in the Philadelphia area.

TIPS TO REMEMBER: Entocort EC

• Patients should take 9 mg (three 3-mg capsules) once daily in the morning.

• Entocort EC is contraindicated in patients with a known hypersensitivity to budesonide.

• Like other glucocorticoids, Entocort EC may reduce the hypothalamic-pituitary-adrenal (HPA) axis response to stress.

• Monitoring of HPA function may be required in patients transferred from systemically acting steroids to Entocort EC.

• Budesonide may increase the risk of infections.

 

Kelly Karpa. Crohn's disease patients find new relief from old drug. Drug Topics 2001;21:16.