DrugindexOnline^{2nd edition}

Pronouncation: (nye-ZA-ti-deen)
Class: Histamine H ₂ antagonist

Trade Names:
Axid
- Solution, oral 15 mg/mL

Trade Names:
Axid AR
- Tablets 75 mg

Trade Names:
Axid Pulvules
- Capsules 150 mg
- Capsules 300 mg

Apo-Nizatidine (Canada)
Novo-Nizatidine (Canada)
PMS-Nizatidine (Canada)

Mechanism of Action

Pharmacology

Reversibly and competitively blocks histamine at H ₂ receptors, particularly those in gastric parietal cells, leading to inhibition of gastric acid secretion.

Pharmacokinetics

Absorption

Absolute bioavailability is more than 70%, C _max is 700 to 1,800 mcg/L (150 mg dose) and 1,400 to 3,600 mcg/L (300 mg dose), and T _max is 0.5 to 3 h. Food increases nizatidine AUC and C _max by approximately 10%.

Distribution

Vd is 0.8 to 1.5 L/kg and the plasma protein binding is about 35%, mainly to alpha-1 acid glycoprotein.

Metabolism

Less than 7% of nizatidine is metabolized as N2-monodesmethylnizatidine (main metabolite). Other metabolites include N2-oxide (less than 5%) and S-oxide (less than 6%).

Elimination

Eliminated in urine (90% excreted; 60% as unchanged) and feces (less than 6%). The t _{1/ 2} is 1 to 2 h, plasma Cl is 40 to 60 L/h, and renal Cl is 500 mL/min.

Special Populations

Renal Function Impairment

Moderate to severe renal function impairment prolongs nizatidine t _{1/ 2} and decreases Cl. Reduce amount and frequency of dose according to severity.

Indications and Usage

Treatment and maintenance of duodenal ulcer, gastroesophageal reflux disease (GERD) (including erosive or ulcerative disease), and benign gastric ulcer; prevention of heartburn, acid indigestion, and sour stomach brought on by consuming food and beverages.

Unlabeled Uses

Prevention of olanzapine-induced weight gain; prevention of NSAID-induced gastroduodenal ulcer, in combination with amoxicillin and clarithromycin for Helicobacter pylori infection.

Contraindications

Hypersensitivity to H ₂ antagonists.

Dosage and Administration

Duodenal Ulcer (Active)
Adults

PO 300 mg at bedtime or 150 mg twice daily for up to 8 wk.

Maintenance

PO 150 mg at bedtime.

Benign Gastric Ulcer (Active)
Adults

PO 300 mg at bedtime or 150 mg twice daily.

Moderate to Severe Renal Function Impairment

Ccr 20 to 50 mL/min: 150 mg daily; maintenance dose 150 mg every other day. Ccr less than 20 mL/min: 150 mg every other day; maintenance dose 150 mg every 3 days.

GERD
Adults

PO 150 mg twice daily.

Children 12 yr of age and older

PO (oral solution) 150 mg twice daily for up to 8 wk (max, 300 mg/day).

Moderate to Severe Renal Function Impairment

Ccr 20 to 50 mL/min: 150 mg daily; maintenance dose 150 mg every other day. Ccr less than 20 mL/min: 150 mg every other day; maintenance dose 150 mg every 3 days.

Acid Reduction
Adults and Children 12 yr of age and older

PO 75 mg with water before eating or up to 1 h before consuming food and beverages that may cause symptoms. Can be used up to twice daily.

Storage/Stability

Oral solution: Store at 59° to 86°F. Protect from light. Capsules and tablets: Store at 68° to 77°F. Protect from light.

Drug Interactions

Aspirin

Increased salicylate levels in patients taking very high doses of aspirin (3.9 g/day).

Ethanol

Peak plasma ethanol levels may be increased.

Ketoconazole

Effects of ketoconazole may be reduced.

Laboratory Test Interactions

False-positive tests for urobilinogen with Multistix may occur.

Adverse Reactions

Cardiovascular

Ventricular tachycardia.

CNS

Headache (17%); dizziness (5%); asthenia, insomnia (3%); abnormal dreams, anxiety, somnolence (2%); nervousness (1%). Children: irritability, pyrexia (greater than 5%).

Dermatologic

Pruritus, rash (2%).

EENT

Rhinitis (10%); pharyngitis (3%); amblyopia (1%). Children: nasal congestion, nasopharyngitis (greater than 5%).

GI

Abdominal pain (8%); diarrhea (7%); dyspepsia, flatulence, nausea (5%); vomiting (4%); constipation (2%); anorexia, dry mouth, GI disorder, nausea and vomiting, tooth disorder (1%). Children: diarrhea, vomiting (greater than 5%).

Hepatic

Elevated liver enzymes.

Hematologic-Lymphatic

Eosinophilia, thrombocytopenia, thrombocytopenic purpura.

Musculoskeletal

Back pain, myalgia (2%).

Respiratory

Increased cough, sinusitis (2%). Children: cough (greater than 5%).

Miscellaneous

Pain (4%); chest pain, fever, infection (2%); accidental injury (1%); anaphylaxis, serum sickness–like reaction.

Precautions

Pregnancy

Category B .

Lactation

Excreted in breast milk.

Children

Safety and efficacy not established (capsules and tablets). Safety and efficacy not established in children younger than 12 yr of age (oral solution).

Renal Function

Decreased Cl may occur in patients with renal function impairment; reduced dosage may be needed.

Hepatic Function

Use drug with caution in patients with hepatic function impairment; decreased Cl may occur. In patients with uncomplicated hepatic function impairment, nizatidine disposition is generally normal.

Hepatocellular injury

Abnormalities appear to be reversible after discontinuation of drug.

Patient Information

• Explain name, dose, action, and potential adverse reactions of drug.
• Obtain patient history, including drug history and any known allergies.
• Advise patient to take medication after breakfast and at bedtime if prescribed twice-daily regimen or at bedtime if prescribed once-daily dosage.
• Caution patient to stay active and to increase fluid and roughage in diet to prevent constipation.
• Instruct patient to take missed dose as soon as possible, and caution not to double doses.
• Advise patient to avoid cigarette smoking, which increases gastric acid secretions and, therefore, decreases effectiveness of nizatidine therapy.
• Instruct patient to report the following symptoms to health care provider: abdominal pain, coffee-ground emesis, extreme fatigue, tarry stools, or weakness.
• Advise women to notify health care provider if pregnant, planning to become pregnant, or breast-feeding.
• Caution patient not to take any prescription or OTC medications, herbal preparations, or dietary supplements unless advised by health care provider.
• Advise patient that follow-up visits may be necessary and to keep appointments.