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Nizatidine Capsules USP Rx only | Nizatidine

05:44 EDT 27th August 2014 | BioPortfolio

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Nizatidine USP is a histamine H-receptor antagonist. Chemically, it is N-[2-[[[2-[(Dimethylamino)methyl]-4-thiazolyl]methyl]thio]ethyl]-N'-methyl-2-nitro-1,1-ethenediamine. The structural formula is represented below:

It is an off-white to buff crystalline solid that is soluble in water. Nizatidine has a bitter taste and mild sulfur-like odor. Nizatidine Capsules USP, for oral administration, contain 150 mg or 300 mg nizatidine and the following inactive ingredients: colloidal silicon dioxide, corn starch, croscarmellose sodium, magnesium stearate and pregelatinized starch. The capsule shells contain: ammonium hydroxide, black iron oxide, gelatin, potassium hydroxide, propylene glycol, shellac, silicon dioxide, sodium lauryl sulfate and titanium dioxide.

The 150 mg capsule shell also contains D&C Yellow No. 10 and FD&C Yellow No. 6.

The 300 mg capsule shell also contains black iron oxide, red iron oxide and yellow iron oxide.

IMAGE nizatidine-figure-01.jpg

Nizatidine is a competitive, reversible inhibitor of histamine at the histamine H-receptors, particularly those in the gastric parietal cells.

In a multicenter, double-blind, comparator-controlled study in Europe, healing rates for patients receiving nizatidine (300 mg h.s. or 150 mg b.i.d.) were equivalent to rates for patients receiving a comparator drug, and statistically superior to historical placebo control rates.

Table 4.
Week Treatment Healing Rate vs. Placebo
p-value*
* P-values are one-sided, obtained by Chi-square test, and not adjusted for multiple comparisons.
4 Niz 300 mg h.s. 52/153 (34%) 0.342
Niz 150 mg b.i.d. 65/151 (43%) 0.022
Placebo 48/151 (32%)
8 Niz 300 mg h.s. 99/153 (65%) 0.011
Niz 150 mg b.i.d. 105/151 (70%) <0.001
Placebo 78/151 (52%)

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.

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

False-positive tests for urobilinogen with Multistix may occur during therapy with nizatidine.

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.

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 highdose 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.

Pregnancy Category B

Oral reproduction studies in pregnant rats at doses up to 1500 mg/kg/day (9000 mg/m/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/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.

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.

Safety and effectiveness in pediatric patients have not been established.

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 (see DOSAGE AND ADMINISTRATION).

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.

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.

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* Nizatidine (N=2,694) Placebo (N=1,729)
*Events reported by at least 1% of nizatidine-treated patients are included.
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

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.

In clinical pharmacology studies, short episodes of asymptomatic ventricular tachycardia occurred in 2 individuals administered nizatidine and in 3 untreated subjects.

Rare cases of reversible mental confusion have been reported.

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.

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-receptor antagonist. On previous occasions, this patient had experienced thrombocytopenia while taking other drugs. Rare cases of thrombocytopenic purpura have been reported.

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.

As with other H-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.

Serum sickness-like reactions have occurred rarely in conjunction with nizatidine use.

Reports of impotence have occurred.

Hyperuricemia unassociated with gout or nephrolithiasis was reported. Eosinophilia, fever, and nausea related to nizatidine administration have been reported.

Overdoses of nizatidine have been reported rarely. The following is provided to serve as a guide should such an overdose be encountered.

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.

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.

The recommended oral dosage for adults is 300 mg once daily at bedtime. An alternative dosage regimen is 150 mg twice daily.

The recommended oral dosage for adults is 150 mg once daily at bedtime.

The recommended oral dosage in adults for the treatment of erosions, ulcerations, and associated heartburn is 150 mg twice daily.

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.

The dose for patients with renal dysfunction should be reduced as follows:

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.

Active Duodenal Ulcer, GERD and Benign Gastric Ulcer
Ccr Dose
20-50 mL/min 150 mg daily
<20 mL/min 150 mg every other day
Maintenance Therapy
Ccr Dose
20-50 mL/min 150 mg every other day
<20 mL/min 150 mg every 3 days

Nizatidine Capsules USP, 150 mg are #2, buff opaque capsules imprinted “WPI” and “3137”.

Nizatidine Capsules USP, 300 mg are #0, light brown opaque capsules imprinted “WPI” and “3138”.

They are supplied by Dispensing Solutions Inc. as follows:

NDC Strength Quantity/Form Color Source NDC
68258-3006-1 300 mg 30 CAPSULE light brown 0591-3138-30

Store at controlled room temperature 20°-25°C (68°-77°F). [See USP.]

Dispense in a tight, light-resistant container as defined in the USP.

This product was Manufactured By:

Watson Laboratories, Inc. Corona, CA 92880 USA

And Relabeled By:

Dispensing Solutions Inc. 3000 West Warner Ave Santa Ana, CA 92704 United States

IMAGE NDC 68258-3006-1.jpg

Manufacturer

Dispensing Solutions Inc.

Active Ingredients

Source

Clinical Trials [7 Associated Clinical Trials listed on BioPortfolio]

Bioequivalence Study of Nizatidine Capsules 300 mg of Dr.Reddy's Laboratories Limited Under Fasting Conditions

This is a bioequivalence study of nizatidine Capsules 300 mg of Dr.Reddy's Laboratories Limited under fasting conditions

Bioequivalence Study of Nizatidine Capsules 300 mg of Dr.Reddy's Laboratories Limited Under Non- Fasting Conditions

The purpose of this study is to compare experimental evaluation of relative bioavailabilities in healthy, human subjects under non-fasting conditions.

Weight Gain Management in Patients With Schizophrenia

Evaluate the efficacy of nizatidine in reducing/limiting weight gain in patients with schizophrenia who have been under treatment with olanzapine for at least two months and evaluate the t...

Safety and Efficacy Study of Axid Use in Infants Suffering From Gastroesophageal Reflux Disease (GERD)

The objective of this study is to evaluate the efficacy, acceptability, and safety of Axid Oral Solution versus placebo in the treatment of gastroesophageal reflux disease (GERD) in infan...

[KJ-INT-002] BE Study

Assess the Safety and the Pharmacokinetic Characteristics of INT-2150 after Oral Administration to Healthy Adult Male Subjects

PubMed Articles [1 Associated PubMed Articles listed on BioPortfolio]

Dispersive Liquid-Liquid Microextraction of Famotidine and Nizatidine from Water Samples.

A new extraction method was developed for isolation of the antihistaminic drugs (histamine H2 receptor antagonists) famotidine (FMT) and nizatidine (NZT) from aqueous samples. A low solvent consumptio...

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