Chronic Constipation TREATMENT

Enemas and Suppositories

Enema contents may include tap water or osmotic laxatives. Glycerin and bisacodyl can be administered as a sup-pository, and these measures are often effective. However, their regular use can result in trauma from insertion and can damage the rectal epithelium.

Biofeedback

Biofeedback therapy is used mainly for the treatment of dyssynergic defecation. The goal of biofeedback is to restore a normal pattern of defecation via neuromuscular conditioning.

Newer Agents Tegaserod

(Novartis) is a partial 5-hydroxytryptamine-4 (5-HT4) receptor ago-nist. It increases peristalsis and intestinal secretion, and it inhibits visceral hypersensitiv-ity. Tegaserod is currently approved for the treatment of IBS-C in women and chronic idiopathic constipation in men and women younger than 65 years of age (Table 4 and Figure 4).

FIGURE 4 Efficacy of tegaserod (Zelnorm)

FIGURE 4 Efficacy of tegaserod (Zelnorm). A phase 3 study used tegaserod 6 mg twice daily in male and female patients with chronic constipation who were younger than 65 years of age. Responders showed an increase of more than one complete spontaneous bowel movement per week during weeks one to four and after seven or more days of treatment.

In clinical trials, the most common adverse events observed with tegaserod 6 mg for chronic idiopathic constipation were diarrhea, abdominal pain, and nausea. Reports of intestinal ischemia have also been noted. It is not known whether this effect is causally related to the drug. Recent data suggest that the drug is safe and effective for long-term use in those patients with chronic constipation and constipation-predominant IBS.

Table 4   A Closer Look at Two Treatment Options

Lubiprostone (Amitiza)

Tegaserod (Canadian Zelnorm)

Mechanism of action Local, chloride-channel (CIC-2) activator Systemic 5-HT4 agonist
Dose 24 mcg twice a day 6 mg twice a day (for chronic idiopathic constipation)
Adverse events Nausea, diarrhea, headache Diarrhea, headache, abdominal pain
Pregnancy rating* C B
Indications Chronic idiopathic constipation in • IBS-C in women for 12 weeks
adult men and women, no age limit • Chronic idiopathic constipation in men and women
<65 years of age
WAC/price55 $2.43 $2.70

Lubiprostone

Lubiprostone (Amitiza, Sucampo) was approved in 2006 for the treatment of chronic idiopathic constipation in adult men and women. As a novel functional fatty acid with local activity, it increases intestinal fluid secretion by selectively activating gastrointestinal type-2 chloride channels. Lubipro-stone accelerates small-bowel and colonic transit time and the passage of stools without altering serum electrolyte levels.

Multicenter clinical trials have demonstrated that lubipro­stone provides an improvement in the percentage of patients experiencing spontaneous bowel movements within the first 24 hours after treatment when compared with placebo (Figure 5). In addition, treated patients experienced improvements in constipation-related symptoms, such as straining, abdominal bloating, and discomfort, when compared with patients receiving placebo. Results from these trials were consistent for all ages and both sexes (see Table 4).
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FIGURE 5 Rapid onset of action for lubiprostone

FIGURE 5 Rapid onset of action for lubiprostone. Forty-eight-hour data were obtained from a secondary analysis of a phase 3 trial.

The most common adverse events observed in those receiving lubiprostone were nausea, diarrhea, and headache. Nausea diminished when lubiprostone was administered with food.

The recommended dosage of lubiprostone is 24 mcg, administered twice daily in the form of gelatin capsules. Open-label clinical trials lasting up to 12 months reported that lubiprostone was safe and efficacious in decreasing constipation severity as well as abdominal discomfort and bloat-ing. In addition, lubiprostone has been approved for use in patients over age 65.

Lubiprostone appears to be a safe and viable treatment option for patients with chronic idiopathic constipation. A recent publication and clinical review found that on the basis of the available data and depending on overall cost, lubiprostone is worth considering for inclusion in formularies. Its place in the management of chronic constipation will be determined as it gains wider use and clinical experience.

CONCLUSION

Chronic idiopathic constipation is a symptom-based disorder affecting a significant portion of the American public every year. Women and the elderly are particularly at risk. This disorder also has a noteworthy impact on the economy as well as health and quality of life.

Many patients with constipation try to manage their symptoms with over-the-counter laxatives and lifestyle changes. However, if these steps do not work, new therapies are available that improve the well-being of patients with chronic idiopathic constipation.