Lotronex Side Effects

Lotronex Information

Lotronex Side Effects

Gastrointestinal

Constipation is a frequent and dose-related side effect of treatment with Lotronex. In clinical studies constipation was reported in approximately 29% of IBS patients treated with Lotronex 1 mg twice daily (n = 9,316). This effect was statistically significant compared to placebo (p=0.0001). Eleven percent (11%) of patients treated with Lotronex 1 mg twice daily withdrew from the studies due to constipation. Although the number of IBS patients treated with Lotronex 0.5 mg twice daily is relatively small (n = 243), only 11% of those patients reported constipation and 4% withdrew from clinical studies due to constipation. Among the patients treated with Lotronex 1 mg twice daily who reported constipation, 75% reported a single episode and most reports of constipation (70%) occurred during the first month of treatment with the median time to first report of constipation onset of 8 days. Occurrences of constipation in clinical trials were generally mild to moderate in intensity, transient in nature, and resolved either spontaneously with continued treatment or with an interruption of treatment.

However, serious complications of constipation have been reported in clinical studies and in postmarketing experience. In Studies 1 and 2, 9% of patients treated with Lotronex reported constipation and 4 consecutive days with no bowel movement. Following interruption of treatment, 78% of the affected patients resumed bowel movements within a 2-day period and were able to re-initiate treatment with Lotronex.

Hepatic

A similar incidence in elevation of ALT (>2 fold) was seen in patients receiving Lotronex or placebo (1.0% vs. 1.2%). A single case of hepatitis (elevated ALT, AST, alkaline phosphatase, and bilirubin) without jaundice was reported in a 12-week study. A causal association with Lotronex has not been established.

Long-Term Safety

Patient experience in controlled clinical trials is insufficient to estimate the incidence of ischemic colitis in patients taking Lotronex for longer than 6 months.

Other Events Observed During Clinical Evaluation of Lotronex

During its assessment in clinical trials, multiple and single doses of Lotronex were administered resulting in 11,874 subject-exposures in 86 completed clinical studies. The conditions, dosages, and duration of exposure to Lotronex varied between trials, and the studies included healthy male and female volunteers as well as male and female patients with IBS and other indications.

In the listing that follows, reported adverse events were classified using a standardized coding dictionary. Only those events that an investigator believed were possibly related to alosetron, occurred in at least 2 patients, and occurred at a greater frequency during treatment with

Lotronex than during placebo administration are presented. Serious adverse events occurring in at least 1 patient for which an investigator believed there was reasonable possibility that the event was related to alosetron treatment and which occurred at a greater frequency in Lotronex than placebo-treated patients are also presented.

In the following listing, events are categorized by body system. Within each body system, events are presented in descending order of frequency. The following definitions are used: Infrequent adverse events are those occurring on one or more occasion in 1/100 to 1/1000 patients; Rare adverse events are those occurring on one or more occasion in fewer than 1/1000 patients.

Although the side effects reported occurred during treatment with Lotronex, they were not necessarily caused by it.

Blood and Lymphatic Lotronex side effects

• Rare: Quantitative red cell or hemoglobin defects, hemorrhage, and lymphatic signs and symptoms.

Cardiovascular Lotronex side effects

• Infrequent: Tachyarrhythmias.
• Rare: Arrhythmias, increased blood pressure, and extrasystoles.

Drug Interaction, Overdose, and Trauma:

• Rare: Contusions and hematomas.

Ear, Nose, and Throat Lotronex side effects:

• Rare: Ear, nose, and throat infections; viral ear, nose, and throat infections; and laryngitis.

Endocrine and Metabolic Lotronex side effects:

• Rare: Disorders of calcium and phosphate metabolism, hyperglycemia, hypothalamus/pituitary hypofunction, hypoglycemia, and fluid disturbances.

Eye:

• Rare: Light sensitivity of eyes.

Gastrointestinal Lotronex side effects:

• Infrequent: Hyposalivation, dyspeptic symptoms, gastrointestinal spasms, ischemic colitis, and gastrointestinal lesions.
• Rare: Abnormal tenderness, colitis, gastrointestinal signs and symptoms, proctitis, diverticulitis, positive fecal occult blood, hyperacidity, decreased gastrointestinal motility and ileus, gastrointestinal obstructions, oral symptoms, gastrointestinal intussusception, gastritis, gastroduodenitis, gastroenteritis, and ulcerative colitis.

Hepatobiliary Tract and Pancreas Lotronex side effects:

• Rare: Abnormal bilirubin levels and cholecystitis.

Lower Respiratory Lotronex side effects:

• Infrequent: Breathing disorders.
• Rare: Viral respiratory infections.

Musculoskeletal Lotronex side effects:

• Rare: Muscle pain; muscle stiffness, tightness and rigidity; and bone and skeletal pain.

Neurological Lotronex side effects:

• Infrequent: Hypnagogic effects.
• Rare: Memory effects, tremors, dreams, cognitive function disorders, disturbances of sense of taste, disorders of equilibrium, confusion, sedation, and hypoesthesia.

Non-site Specific Lotronex side effects:

• Infrequent: Malaise and fatigue, cramps, pain, temperature regulation disturbances.
• Rare: General signs and symptoms, non-specific conditions, burning sensations, hot and cold sensations, cold sensations, and fungal infections.

Psychiatry:

• Infrequent: Anxiety.
• Rare: Depressive moods.

Reproduction Lotronex side effects:

• Rare: Sexual function disorders, female reproductive tract bleeding and hemorrhage, reproductive infections, and fungal reproductive infections.

Skin Lotronex side effects:

• Infrequent: Sweating and urticaria.
• Rare: Hair loss and alopecia; acne and folliculitis; disorders of sweat and sebum; allergic skin reaction; eczema; skin infections; dermatitis and dermatosis; and nail disorders.

Urology Lotronex side effects:

• Infrequent: Urinary frequency.
• Rare: Bladder inflammation; polyuria and diuresis; and urinary tract hemorrhage.

Postmarketing Experience

The following events have been identified during use of Lotronex in clinical practice. Because they were reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to Lotronex.

Gastrointestinal

Constipation, ileus, impaction, obstruction, perforation, ulceration, ischemic colitis, small bowel mesenteric ischemia.

Neurological

Headache.

Skin

Rash

Lotronex Information