Generic Name: Nizatidine
Class: Histamine H2-Antagonists
VA Class: GA301
Chemical Name: N - [2 - [[[2 - [(dimethylamino)methyl] - 4 - thiazolyl]methyl]thio]ethyl] - N′ - methyl - 2 - nitro - 1,1 - ethenediamine
Molecular Formula: C12H21N5O2S2
CAS Number: 76963-41-2

Introduction

Histamine H2 receptor antagonist.1 2 3 4 5

Uses for Axid

Gastroesophageal Reflux (GERD)

Short-term treatment of symptomatic GERD.1 2 39 40 41 42 43 44

Short-term treatment of esophagitis including erosion or ulcers (endoscopically diagnosed) in patients with GERD.1 2 39 40 41 42 43 44

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Self-medication as initial therapy to achieve acid suppression, control symptoms, and prevent complications of less severe symptomatic GERD.165

Short-term self-medication for relief of heartburn symptoms in adults and adolescents ≥12 years of age.b

Short-term self-medication for prevention of heartburn symptoms associated with acid indigestion and sour stomach brought on by ingestion of certain foods and beverages in adults and children ≥12 years of age.b

Duodenal Ulcer

Short-term treatment of active duodenal ulcer (endoscopically or radiographically confirmed).1 2 4 5 27 28 29 30 31 32 33 34

Maintenance of healing and reduction in recurrence of duodenal ulcer.1 2 4 5 16 35 36

Gastric Ulcer

Short-term treatment of active benign gastric ulcer.1 4 5 28 45 46 47

Axid Dosage and Administration

Administration

Oral Administration

Administer orally1 2 3 4 5 without regard to meals.2 6 12

Antacids may be used as necessary for pain relief.2 5 27 28 29 30 31 32 33 34

Tablet for self-medication should be administered with a glass of water.b

For gastroesophageal reflux, once daily dosage not considered appropriate.165

For duodenal ulcer treatment, the advantage of administration once daily at bedtime (when convenience is important for compliance) over twice-daily administration has not been determined.2

For gastric ulcer treatment in adults, administer in divided doses twice daily or once daily at bedtime.1 45 46 47

Dosage

Pediatric Patients

Erosive Esophagitis or GERD
Oral

Children ≥12 years of age: 150 mg twice daily as oral solution for up to 8 weeks.c

Gastroesophageal Reflux
Self-medication for Heartburn in Adolescents ≥12 years of Age
Oral

75 mg once or twice daily (maximum 150 mg in 24 hours continuously for 2 weeks) or as directed by clinician.b

Self-medication for Prevention of Heartburn In Adolescents ≥12 Years of Age
Oral

75 mg once or twice daily (immediately or up to 1 hour before ingestion of causative food or beverage); maximum 150 mg in 24 hours continuously for 2 weeks or as directed by clinician.b

Adults

Gastroesophageal Reflux
Treatment of Esophagitis
Oral

150 mg twice daily for up to 12 weeks.1 2 40 41 42

300 mg at bedtime also has been used, but is less effective2 9 39 130 and not considered appropriate therapy.165

Self-medication for Heartburn
Oral

75 mg once or twice daily (maximum 150 mg in 24 hours continuously for 2 weeks) or as directed by clinician.b

Self-medication for Prevention of Heartburn
Oral

75 mg once or twice daily (immediately or up to 1 hour before ingestion of causative food or beverage); maximum 150 mg in 24 hours continuously for 2 weeks or as directed by clinician.b

Duodenal Ulcer
Treatment of Active Duodenal Ulcer
Oral

300 mg once daily at bedtime, or 150 mg twice daily.1 2

Healing may occur within 2 weeks in some, and within 4 weeks in most patients;1 2 27 28 29 30 31 32 33 34 some patients may benefit from an additional 4 weeks of therapy.1 2 Occasionally may be necessary to continue full-dose therapy for >6–8 weeks.1 2

Safety and efficacy of continuing full-dose therapy for > 8 weeks have not been established.1 2

Maintenance of Healing of Duodenal Ulcer
Oral

150 mg once daily at bedtime.1 2 35 36

Some clinicians recommend continuing maintenance therapy for at least 1 year.4

Safety and efficacy of continuing maintenance therapy beyond 1 year have not been established.1

Gastric Ulcer
Oral

150 mg twice daily or 300 mg once daily at bedtime for up to 8 weeks.1 45 46 47

Complete healing of gastric ulcers usually occurs within 8 weeks.1 4 5 28 45 46 47

Safety and efficacy for >8 weeks have not been established.1 126

Prescribing Limits

Pediatric Patients

Erosive Esophagitis or GERD
Oral

Maximum 300 mg daily for 8 weeks.c

Gastroesophageal Reflux
Self-Medication For Heartburn in Adolescents ≥12 years of Age
Oral

Maximum 150 mg in 24 hours continuously for 2 weeks.b

Self-medication for Prevention of Heartburn in Adolescents ≥12 years of Age
Oral

Maximum 150 mg in 24 hours continuously for 2 weeks.b

Adults

Gastroesophageal Reflux
Treatment of Esophagitis
Oral

Safety and efficacy for >12 weeks not established.1 2 40 41 42

Self-medication for Heartburn
Oral

Maximum 150 mg in 24 hours continuously for 2 weeks.b

Self-medication for Prevention of Heartburn
Oral

Maximum 150 mg in 24 hours continuously for 2 weeks.b

Duodenal Ulcer
Treatment of Active Duodenal Ulcer
Oral

Safety and efficacy for >8 weeks not established.1 2

Maintenance of Healing of Duodenal Ulcer
Oral

Safety and efficacy for >1 year not established.1

Gastric Ulcer
Short-term treatment of Active Benign Gastric Ulcer
Oral

Safety and efficacy for >8 weeks not established.1 126

Special Populations

Renal Impairment

Modify doses and/or frequency of administration to the degree of renal impairment; clinical efficacy of recommended dosages have not been systematically evaluated.1 2 22

Table 1. Nizatidine Dosage Based on Creatinine Clearance

Creatinine Clearance (mL/minute)

Dosage for Treatment of Esophagitis, Active Duodenal Ulcer, Active Benign Gastric Ulcer1 2 22

Dosage for Maintenance of Healing of Duodenal Ulcer1 2

20–50

150 mg once daily

150 mg once every other day

<20

150 mg once every other day

150 mg once every 3 days

Geriatric Patients

Careful dosage selection recommended due to possible age-related decreases in renal function.1 2 (See Renal Impairment under Cautions.) Monitoring renal function may be useful.a

Cautions for Axid

Contraindications

  • Known hypersensitivity to nizatidine, any ingredient in the formulation, or to other histamine H2 antagonists (i.e., cimetidine, famotidine, ranitidine).1

Warnings/Precautions

General Precautions

Gastric Malignancy

Response to nizatidine does not preclude presence of gastric malignancy.1

Respiratory Effects

Administration of H2-receptor antagonists has been associated with an increased risk for developing certain infections (e.g., community-acquired pneumonia).175

Specific Populations

Pregnancy

Category B.1 10

Self-medication in pregnant women: consult a clinician before using.1

Lactation

Distributed into milk.1 21 Discontinue nursing or the drug.1

Self-medication in nursing women: consult a clinician before using.b

Pediatric Use

Efficacy not established in children <12 years of age.1 126

Safety and efficacy for self-medication not established in children <12 years of age; do not use unless directed by a clinician.b

Geriatric Use

No substantial differences in safety and efficacy in those ≥65 years of age relative to younger adults, and dosage adjustment solely on the basis of age generally is not required.1 2 5

Possibility exists of greater sensitivity in some geriatric individuals.a

Substantially eliminated by the kidneys; because geriatric patients are more likely to have decreased renal function, use caution in dosage selection.a Monitoring of renal function may be useful.a In geriatric patients with renal impairment, modify dose and frequency of administration in response to the degree of renal impairment.1 2 (See Renal Impairment under Dosage and Administration).

Renal Impairment

Use with caution.1 Dosage adjustments necessary based on degree of renal impairment.1 (See Renal Impairment under Dosage and Administration).

Common Adverse Effects

Headache, dizziness.1 2 5 31 33 34 40 41 46 50

Interactions for Axid

Does not inhibit hepatic metabolism of drugs by hepatic CYP isoenzymes.1 14

Specific Drugs and Laboratory Tests

Drug/Food/Lab Test

Interaction

Comment

Alcohol

Potential for changes in blood alcohol concentrations, but conflicting data74 75 76 78 79 80 81 82 83 126 129

Potential for psychomotor impairment controversial,74 75 76 77 78 79 80 but use caution during performance of hazardous tasks requiring mental alertness, physical coordination75 76 79 80 126

Antacids

Slight but clinically unimportant decrease in nizatidine bioavailability1 2 4 5 6 9 12

Used concomitantly as necessary for pain relief2 5 27 28 29 30 31 32 33 34

Multistix test for urobilinogen1

False positive1

Salicylate (high-dose aspirin)

Possible inhibition of salicylate excretion and increased serum salicylate concentrations1 2 5 124

Axid Pharmacokinetics

Absorption

Bioavailability

About 70%.1 2 9 12 16

Onset

Gastric acid inhibition within 30 minutes after IV administration.6 19

Duration

Dose dependent.2 6 19

Nocturnal gastric acid secretion is inhibited for 10–12 hours after a single 300-mg dose.1 2 4 7 8

Inhibition of food-stimulated secretion generally persists for up to 4 hours following a 150- or 300-mg dose.1 2 20

Food

May slightly enhance bioavailability.1 2 4 5 6 9 12

Distribution

Extent

Not fully characterized.4

Nizatidine crosses the placenta5 26 and is distributed into milk.1 21

Plasma Protein Binding

35%, mainly to α1-acid glycoprotein.1 2 3 5 6 15

Elimination

Metabolism

Metabolized in the liver to active N-desmethylnizatidine (60% as active as nizatidine in blocking acid secretion), and inactive nizatidine N-oxide and nizatidine sulfoxide.1 2 5 15 22

Minimal first pass metabolism.1 2

Elimination Route

Excreted principally in urine1 2 3 15 (90%);1 5 6 15 about 60–65% is excreted unchanged,1 2 5 6 22 8% is excreted as N-desmethylnizatidine, 6% as nizatidine sulfoxide, 6% as nizatidine N-oxide, and about 15% as unidentified metabolites.1 2 5 6 15 <6% of a dose is eliminated in feces.1 2 5 6 15

Half-life

1–2 hours.1 2 3 4 5 6 9 12 16 22 23

Special Populations

In patients with renal impairment, half-life averages 2.1 hours when Clcr is 50–75 mL/minute, 4.1 hours when Clcr is 10–49 mL/minute, and ranges from 3.5–11 hours in anuric patients.1 2 3 5 6 22 23

Does not appear to be removed appreciably by hemodialysis.1 22 23

Stability

Storage

Oral

Capsules

Tight, light-resistant containers at 20–25°C (may be exposed to 15–30°C).a

Tablets for Self-medication

Tight, light-resistant containers at 20–25°C.b

Actions

  • Inhibits daytime, nocturnal basal and stimulated gastric acid secretion.1 2 3 5 7 8 19 55 56 57 58

  • Competitively inhibits histamine at parietal cell H2 receptors.1 2 3 5 7 8 19 55 56 57 58

Advice to Patients

  • Importance of patients informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs.

  • Importance of women informing clinician if they are or plan to become pregnant or plan to breast-feed.1 b

  • Importance of following dosage instructions when nizatidine is administered for self-medication, unless otherwise directed by a clinician.b

  • Importance of promptly informing clinician of persistent abdominal pain or difficulty swallowing.b

  • Importance of informing patients of other important precautionary information. (See Cautions).

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Nizatidine

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

150 mg

Axid Pulvules

Reliant, (also promoted by Lilly)

300 mg

Axid Pulvules (with povidone)

Reliant, (also promoted by Lilly)

Solution

15 mg/mL

Axid

Reliant

Tablets

75 mg

Axid AR Acid Reducer

Wyeth

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Axid 15MG/ML Solution (BRAINTREE LAB): 480/$409.84 or 1440/$1,120.25

Axid 150MG Capsules (GLAXO SMITH KLINE): 60/$172.98 or 180/$499.87

Nizatidine 15MG/ML Solution (AMNEAL PHARMACEUTICALS): 473/$272.00 or 1419/$795.98

Nizatidine 150MG Capsules (DR.REDDY'S LABORATORIES): 60/$51.98 or 180/$139.96

Nizatidine 300MG Capsules (MYLAN): 30/$54.00 or 90/$138.97

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions April 1, 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

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2. Eli Lilly and Company. Axid (nizatidine) product information. Indianapolis, IN; 1992. Publication No. 60-NZ-0390-1.

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