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Overview
Nizatidine is a histamine H2-receptor antagonist that is FDA approved for the treatment of active duodenal ulcer, esophagitis, active benign gastric ulcer, maintenance therapy for duodenal ulcer patients. Common adverse reactions include Diarrhea, Vomiting, Headache,.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Indications
Nizatidine is indicated for up to 8 weeks for the treatment of active duodenal ulcer. In most patients, the ulcer will heal within 4 weeks.
Nizatidine is 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 is 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 is 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.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Nizatidine in adult patients.
There is limited information regarding FDA-Labeled Use of Nizatidine in pediatric patients.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Nizatidine in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Nizatidine in pediatric patients.
Contraindications
Nizatidine is contraindicated in patients with known hypersensitivity to the drug. Because cross sensitivity in this class of compounds has been observed, H2-receptor antagonists, including nizatidine, should not be administered to patients with a history of hypersensitivity to other H2-receptor antagonists.
Warnings
Precautions
General – 1. Symptomatic response to nizatidine therapy does not preclude the presence of gastric malignancy.
2. Because nizatidine is excreted primarily by the kidney, dosage should be reduced in patients with moderate to severe renal insufficiency (see DOSAGE AND ADMINISTRATION).
3. Pharmacokinetic studies in patients with hepatorenal syndrome have not been done. Part of the dose of nizatidine is metabolized in the liver. In patients with normal renal function and uncomplicated hepatic dysfunction, the disposition of nizatidine is similar to that in normal subjects.
Laboratory Tests – False-positive tests for urobilinogen with Multistix® may occur during therapy with nizatidine.
Adverse Reactions
Clinical Trials Experience
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.
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 anti-androgenic 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 H2-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 H2-receptor antagonists, rare cases of anaphylaxis following administration of nizatidine have been reported. Rare episodes of hypersensitivity reactions (e.g., 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.
Postmarketing Experience
There is limited information regarding Postmarketing Experience of Nizatidine in the drug label.
Drug Interactions
No interactions have been observed between nizatidine and theophylline, chlordiazepoxide, lorazepam, lidocaine, phenytoin, and warfarin. Nizatidine does not inhibit the cytochrome P-450-linked drug-metabolizing enzyme system; therefore, drug interactions mediated by inhibition of hepatic metabolism are not expected to occur. In patients given very high doses (3,900 mg) of aspirin daily, increases in serum salicylate levels were seen when nizatidine, 150 mg b.i.d., was administered concurrently.
Oral reproduction studies in pregnant rats at doses up to 1500 mg/kg/day (9000 mg/m2/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/m2/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.
Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Nizatidine in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Nizatidine during labor and delivery.
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.
Pediatric Use
Safety and effectiveness in pediatric patients have not been established.
Geriatic Use
Of the 955 patients in clinical studies who were treated with nizatidine, 337 (35.3%) were 65 and older. No overall differences in safety or effectiveness were observed between these and younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function
Gender
There is no FDA guidance on the use of Nizatidine with respect to specific gender populations.
Race
There is no FDA guidance on the use of Nizatidine with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Nizatidine in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Nizatidine in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Nizatidine in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Nizatidine in patients who are immunocompromised.
Administration and Monitoring
Administration
Oral
Monitoring
Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function
IV Compatibility
There is limited information regarding IV Compatibility of Nizatidine in the drug label.
Overdosage
Overdoses of nizatidine have been reported rarely. The following is provided to serve as a guide should such an overdose be encountered.
Signs and Symptoms – There is little clinical experience with overdosage of nizatidine in humans. Test animals that received large doses of nizatidine have exhibited cholinergic-type effects, including lacrimation, salivation, emesis, miosis, and diarrhea. Single oral doses of 800 mg/kg in dogs and of 1,200 mg/kg in monkeys were not lethal. Intravenous median lethal doses in the rat and mouse were 301 mg/kg and 232 mg/kg respectively.
Treatment – To obtain up-to-date information about the treatment of overdose, a good resource is your certified Regional Poison Control Center. Telephone numbers of certified poison control centers are listed in the Physicians' Desk Reference (PDR). In managing overdosage, consider the possibility of multiple drug overdoses, interaction among drugs, and unusual drug kinetics in your patient.
If overdosage occurs, use of activated charcoal, emesis, or lavage should be considered along with clinical monitoring and supportive therapy. The ability of hemodialysis to remove nizatidine from the body has not been conclusively demonstrated; however, due to its large volume of distribution, nizatidine is not expected to be efficiently removed from the body by this method.
Pharmacology
There is limited information regarding Nizatidine Pharmacology in the drug label.
There is limited information regarding Pharmacodynamics of Nizatidine in the drug label.
Pharmacokinetics
There is limited information regarding Pharmacokinetics of Nizatidine in the drug label.
Nonclinical Toxicology
Carcinogenesis, Mutagenesis, Impairment of Fertility – A 2-year oral carcinogenicity study in rats with doses as high as 500 mg/kg/day (about 80 times the recommended daily therapeutic dose) showed no evidence of a carcinogenic effect. There was a dose-related increase in the density of enterochromaffin-like (ECL) cells in the gastric oxyntic mucosa. In a 2-year study in mice, there was no evidence of a carcinogenic effect in male mice; although hyperplastic nodules of the liver were increased in the high-dose males as compared with placebo. Female mice given the high dose of nizatidine (2,000 mg/kg/day, about 330 times the human dose) showed marginally statistically significant increases in hepatic carcinoma and hepatic nodular hyperplasia with no numerical increase seen in any of the other dose groups. The rate of hepatic carcinoma in the high-dose animals was within the historical control limits seen for the strain of mice used. The female mice were given a dose larger than the maximum tolerated dose, as indicated by excessive (30%) weight decrement as compared with concurrent controls and evidence of mild liver injury (transaminase elevations). The occurrence of a marginal finding at high dose only in animals given an excessive and somewhat hepatotoxic dose, with no evidence of a carcinogenic effect in rats, male mice, and female mice (given up to 360 mg/kg/day, about 60 times the human dose), and a negative mutagenicity battery are not considered evidence of a carcinogenic potential for nizatidine.
Nizatidine was not mutagenic in a battery of tests performed to evaluate its potential genetic toxicity, including bacterial mutation tests, unscheduled DNA synthesis, sister chromatid exchange, the mouse lymphoma assay, chromosome aberration tests, and a micronucleus test.
In a 2-generation, perinatal and postnatal fertility study in rats, doses of nizatidine up to 650 mg/kg/day produced no adverse effects on the reproductive performance of parental animals or their progeny.
Clinical Studies
There is limited information regarding Clinical Studies of Nizatidine in the drug label.
How Supplied
Storage
There is limited information regarding Nizatidine Storage in the drug label.
Images
Drug Images
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