Nizatidine

Nizatidine capsules are indicated for up to 8 weeks for the treatment of active duodenal ulcer. In most patients, the ulcer will heal within 4 weeks. Nizatidine capsules are indicated for maintenance therapy for duodenal ulcer patients at a reduced dosage of 150 mg h.s. after healing of an active duodenal ulcer.

The consequences of continuous therapy with nizatidine for longer than 1 year are not known. Nizatidine capsules are indicated for up to 12 weeks for the treatment of endoscopically diagnosed esophagitis, including erosive and ulcerative esophagitis, and associated heartburn due to GERD. Nizatidine capsules are indicated for up to 8 weeks for the treatment of active benign gastric ulcer. Before initiating therapy, care should be taken to exclude the possibility of malignant gastric ulceration.

Active Duodenal Ulcer The recommended oral dosage for adults is 300 mg once daily at bedtime. An alternative dosage regimen is 150 mg twice daily. Maintenance of Healed Duodenal Ulcer The recommended oral dosage for adults is 150 mg once daily at bedtime. Gastroesophageal Reflux Disease The recommended oral dosage in adults for the treatment of erosions, ulcerations, and associated heartburn is 150 mg twice daily.

Active Benign Gastric Ulcer The recommended oral dosage is 300 mg given either as 150 mg twice daily or 300 mg once daily at bedtime. Prior to treatment, care should be taken to exclude the possibility of malignant gastric ulceration. Dosage Adjustment for Patients With Moderate to Severe Renal Insufficiency The dose for patients with renal dysfunction should be reduced as follows: Active Duodenal Ulcer, GERD, and Benign Gastric Ulcer C cr Dose 20-50 mL/min 150 mg daily less than 20 mL/min 150 mg every other day Maintenance Therapy C cr Dose 20-50 mL/min 150 mg every other day less than 20 mL/min 150 mg every 3 days Some elderly patients may have creatinine clearances of less than 50 mL/min, and, based on pharmacokinetic data in patients with renal impairment, the dose for such patients should be reduced accordingly.

The clinical effects of this dosage reduction in patients with renal failure have not been evaluated.

Nizatidine capsules are contraindicated in patients with known hypersensitivity to the drug. Because cross sensitivity in this class of compounds has been observed, H 2 -receptor antagonists, including nizatidine, should not be administered to patients with a history of hypersensitivity to other H 2 -receptor antagonists.

Pregnancy Teratogenic Effects Pregnancy category B Oral reproduction studies in pregnant rats at doses up to 1500 mg/kg/day (9000 mg/m 2 /day, 40.5 times the recommended human dose based on body surface area) and in pregnant rabbits at doses up to 275 mg/kg/day (3245 mg/m 2 /day, 14.6 times the recommended human dose based on body surface area) have revealed no evidence of impaired fertility or harm to the fetus due to nizatidine. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers Studies conducted in lactating women have shown that 0.1% of the administered oral dose of nizatidine is secreted in human milk in proportion to plasma concentrations. Because of the growth depression in pups reared by lactating rats treated with nizatidine, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

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 5. 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

15.6Abdominal

pain 7.5

12.5Pain

4.2

3.8Asthenia

3.1

2.9Back

pain 2.4

2.6Chest

pain 2.3

2.1Infection

1.7

1.1Fever

1.6

2.3Surgical

procedure 1.4

1.5Injury,

accident 1.2

0.9Digestive Diarrhea

7.2

6.9Nausea

5.4

7.4Flatulence

4.9

5.4Vomiting

3.6

5.6Dyspepsia

3.6

4.4Constipation

2.5

3.8Dry

mouth 1.4

1.3Nausea and

vomiting 1.2

1.9Anorexia

1.2

1.6Gastrointestinal

disorder 1.1

1.2Tooth

disorder 1.0

0.8Musculoskeletal Myalgia

1.7

1.5Nervous Dizziness

4.6

3.8Insomnia

2.7

3.4Abnormal

dreams 1.9

1.9Somnolence

1.9

1.6Anxiety

1.6

1.4Nervousness

1.1

0.8Respiratory Rhinitis

9.8

9.6Pharyngitis

3.3

3.1Sinusitis

2.4

2.1Cough,

increased 2.0

2.0Skin and Appendages Rash

1.9

2.1Pruritus

1.7

1.3Special 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.