ADVERSE REACTIONS: Worldwide, controlled clinical trials of nizatidine included over 6,000 patients given nizatidine in studies of varying durations. Placebo-controlled trials in the United States and Canada included over 2,600 patients given nizatidine and over 1,700 given placebo. Among the adverse events in these placebo-controlled trials, anemia (0.2% vs 0%) and urticaria (0.5% vs 0.1%) were significantly more common in the nizatidine group. Incidence in Placebo-Controlled Clinical Trials in the United States and Canada Table 5 lists adverse events that occurred at a frequency of 1% or more among nizatidine-treated patients who participated in placebo-controlled trials. The cited figures provide some basis for estimating the relative contribution of drug and nondrug factors to the side-effect incidence rate in the population studied. Table 4. Incidence of Treatment-Emergent Adverse Events in Placebo-Controlled Clinical Trials in the United States and Canada Percentage of Patients Reporting Event Body System/Adverse Event Events reported by at least 1% of nizatidine-treated patients are included. Nizatidine (N=2,694) Placebo (N=1,729) Body as a Whole Headache 16.6 15.6 Abdominal pain 7.5 12.5 Pain 4.2 3.8 Asthenia 3.1 2.9 Back pain 2.4 2.6 Chest pain 2.3 2.1 Infection 1.7 1.1 Fever 1.6 2.3 Surgical procedure 1.4 1.5 Injury, accident 1.2 0.9 Digestive Diarrhea 7.2 6.9 Nausea 5.4 7.4 Flatulence 4.9 5.4 Vomiting 3.6 5.6 Dyspepsia 3.6 4.4 Constipation 2.5 3.8 Dry mouth 1.4 1.3 Nausea and vomiting 1.2 1.9 Anorexia 1.2 1.6 Gastrointestinal disorder 1.1 1.2 Tooth disorder 1.0 0.8 Musculoskeletal Myalgia 1.7 1.5 Nervous Dizziness 4.6 3.8 Insomnia 2.7 3.4 Abnormal dreams 1.9 1.9 Somnolence 1.9 1.6 Anxiety 1.6 1.4 Nervousness 1.1 0.8 Respiratory Rhinitis 9.8 9.6 Pharyngitis 3.3 3.1 Sinusitis 2.4 2.1 Cough, increased 2.0 2.0 Skin and Appendages Rash 1.9 2.1 Pruritus 1.7 1.3 Special Senses Amblyopia 1.0 0.9 A variety of less common events were also reported; it was not possible to determine whether these were caused by nizatidine. Hepatic Hepatocellular injury, evidenced by elevated liver enzyme tests (SGOT [AST], SGPT [ALT], or alkaline phosphatase), occurred in some patients and was possibly or probably related to nizatidine. In some cases, there was marked elevation of SGOT, SGPT enzymes (greater than 500 IU/L) and, in a single instance, SGPT was greater than 2,000 IU/L. The overall rate of occurrences of elevated liver enzymes and elevations to 3 times the upper limit of normal, however, did not significantly differ from the rate of liver enzyme abnormalities in placebo-treated patients.All abnormalities were reversible after discontinuation of nizatidine. Since market introduction, hepatitis and jaundice have been reported. Rare cases of cholestatic or mixed hepatocellular and cholestatic injury with jaundice have been reported with reversal of the abnormalities after discontinuation of nizatidine. Cardiovascular In clinical pharmacology studies, short episodes of asymptomatic ventricular tachycardia occurred in 2 individuals administered nizatidine and in 3 untreated subjects. CNS Rare cases of reversible mental confusion have been reported. Endocrine Clinical pharmacology studies and controlled clinical trials showed no evidence of antiandrogenic activity due to nizatidine. Impotence and decreased libido were reported with similar frequency by patients who received nizatidine and by those given placebo. Rare reports of gynecomastia occurred. Hematologic Anemia was reported significantly more frequently in nizatidine-than in placebo-treated patients. Fatal thrombocytopenia was reported in a patient who was treated with nizatidine and another H 2 -receptor antagonist. On previous occasions, this patient had experienced thrombocytopenia while taking other drugs. Rare cases of thrombocytopenic purpura have been reported. Integumental Sweating and urticaria were reported significantly more frequently in nizatidine- than in placebo-treated patients. Rash and exfoliative dermatitis were also reported. Vasculitis has been reported rarely. Hypersensitivity As with other H 2 -receptor antagonists, rare cases of anaphylaxis following administration of nizatidine have been reported. Rare episodes of hypersensitivity reactions (eg, bronchospasm, laryngeal edema, rash, and eosinophilia) have been reported. Body as a Whole Serum sickness-like reactions have occurred rarely in conjunction with nizatidine use. Genitourinary Reports of impotence have occurred. Other Hyperuricemia unassociated with gout or nephrolithiasis was reported. Eosinophilia, fever, and nausea related to nizatidine administration have been reported.