naltrexoneCrohnDisease

PIC QUESTION OF THE WEEK: 12/17/07 Q: Why would a physician prescribe naltrexone for a patient with Crohn’s disease?

A: Crohn’s disease is a chronic, inflammatory, granulomatous disease that may affect any part of the gastrointestinal tract. The disease is most prevalent in white females between the ages of 15-25 years and there is a family history of disease in approximately 15% of patients. Crohn’s disease most commonly occurs in the terminal ileum, but may be limited to the colon in 15-20% of cases. Signs and symptoms most often include diarrhea, abdominal pain or tenderness, weight loss, low grade fever, fatigue, pallor, and joint pain. The disease is frequently accompanied by complications such as fistula formation, perforation, toxic megacolon, gallstones, etc. There is a significant increase in the risk of adenocarcinoma in patients with extensive colonic involvement. Crohn’s disease is noted for its frequent periods of remission and exacerbation. Depending on the site, severity, and acute versus chronic nature of the disease, a large number of compounds have been used in its management. These include sulfasalazine, mesalamine, topical and systemic corticosteroids, the tumor necrosis factor (TNF) antagonist infliximab, and immunosuppressive agents such as azathioprine, methotrexate, 6-mercaptopurine, cyclosporine, tacrolimus, probiotics, etc. The antimicrobials metronidazole and ciprofloxacin may also be beneficial, especially in patients with disease complicated by fistulas. Neuropeptides such as the enkephalins and endorphins may play some role in the immune and inflammatory response associated with Crohn’s disease. In addition, there is some evidence that these compounds may influence tissue repair. Low doses of opiate antagonists such as naltrexone appear to increase tissue levels of endorphins and enkephalins. Naltrexone may also reduce TNF production. Naltrexone is currently available as an oral formulation for the treatment of opiate and alcohol dependence. In one small, uncontrolled trial of seventeen patients with active Crohn’s disease, low doses of naltrexone (4.5 mg per day) produced a significant decrease in disease activity and improvement in quality of life. In this twelve-week study, nearly 90% of patients responded to treatment and 70% were considered to achieve remission. Treatment with TNF inhibitors and other immunosuppressive drugs had been discontinued for at least eight weeks prior to the study. Sleep disturbances (primarily insomnia) were reported in 7/17 trial participants. A key point is the need for use of low doses of this opiate antagonist. The 4.5 mg capsules used in the study were made available by a compounding pharmacy. A double-blind, placebo-controlled trial is currently underway to determine what role naltrexone may play in the treatment of Crohn’s disease.

Reference: • Sands, BE. Inflammatory bowel disease: past, present, and future. J Gastroenterol 2007;42:16-25.

• Smith JP, Stock H, Bingaman S, et al. Low-dose naltrexone therapy improves active Crohn’s disease.

Am J Gastroenterol 2007;102:820-8.

Sabrina A. Chirumbolo and Lance R. Olszewski, Pharmacy Clerkship Students The PIC Question of the Week is a publication of the Pharmaceutical Information Center, Mylan School of Pharmacy, Duquesne University, Pittsburgh, PA 15282 (412.396.4600).