Nizatidine
Nizatidine is a generic medication for the drug Axid:
Nizatidine medication comes in several different strengths; click on the strength you need to view prices from pharmacies competing to earn your business.
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Nizatidine 150 mg
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Nizatidine 300 mg
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Drug Interactions
Drug-Food Interactions
Nizatidine prepared as an extemporaneous solution in apple juice has a much lower bioavailability than the capsule dosage form.
Drug-Laboratory Interactions
Multistix test for urobilinogen may produce false positive results.
Nizatidine
Drug-Drug Interactions
| Interacting Drug | Effect | Clinical Comment |
|---|---|---|
| ASA | ↑ serum salicylate concentration | With high doses of ASA (3.9 g); possibly due to inhibition of renal salicylate excretion |
| Atazanavir | ↓ Atazanavir plasma concentrations | Separate administration of the two drugs by ≥12 hours. |
| Cefuroxime axetil | ↓ bioavailability of cefuroxime | Separate administration by ≥2 hours. |
| Cyclosporine | May ↑ serum cyclosporine concentrations. | Monitor serum cyclosporine concentration. |
| Gefitinib | ↓ absorption of gefitinib | Clinical implications are unclear. |
| Imidazole antifungal agents | ↓ bioavailability of ketoconazole and itraconazole | Consider using a non-interacting antifungal agent (e.g., fluconazole). |
Overview
Nizatidine does not inhibit cytochrome P450 isozymes. As a result, drug interactions linked to inhibition of hepatic metabolism are not expected. Nizatidine significantly raises gastric pH; thus, it has the potential to modify the pharmacokinetic profile of drugs that are dependent on gastric acidity for dissolution and/or absorption from the gastrointestinal tract.
Dosage and Administration
Nizatidine
Dose in Pediatric Patients
| Indication | Age/ Weight | Usual Dose | Maximum Dose | Duration of Therapy |
|---|---|---|---|---|
| Gastroesophageal reflux | ≥12 years | 150 mg BID | 300 mg/day | 8 weeks |
| <12 years | 5–10 mg/kg/day divided BID | Do not exceed 300 mg daily | 8 weeks |
Recommended Dose and Dosage Adjustment
Administration
Nizatidine may be administered concomitantly with antacids. The effect of food on the pharmacokinetics of nizatidine is not clinically significant.
Nizatidine
Dose in Adult Patients
| Indication | Usual Dose | Duration of Therapy | Clinical Comment |
|---|---|---|---|
| Treatment of duodenal ulcers | 300 mg qhs or 150 mg BID | 4–8 weeks | In most patients, healing occurs within 4 weeks. |
| Maintenance therapy for prevention of duodenal ulcer recurrence | 150 mg qhs | 6–12 months | |
| Treatment of gastric ulcers | 300 mg qhs or 150 mg BID | 8 weeks | |
| Gastroesophageal reflux | 150 mg BID | 12 weeks |
Hepatic Impairment
No dosage adjustment is required in patients with hepatic impairment.
Nizatidine
Dose in Adult Patients with Renal Impairment
| Renal Function | Creatinine Clearance | Dosage Adjustment | |
|---|---|---|---|
| Acute | Maintenance | ||
| Normal | >50 mL/min | 300 mg/day | 150 mg/day |
| Moderate Impairment | 20–50 mL/min | 150 mg/day | 150 mg every other day |
| Severe Impairment | <20 mL/min | 150 mg every other day | 150 mg q3days |
Adverse Reactions
Gastrointestinal
nausea, vomiting, abdominal discomfort, constipation, flatulence, dyspepsia, dry mouth, anorexia (similar incidence to placebo).
Hematologic
anemia (significantly more common in nizatidine than placebo recipients), thrombocytopenic purpura.
Less Common Adverse Drug Reactions (<1%)
Endocrine and Metabolism
impotence and decreased libido (similar incidence to placebo), gynecomastia.
Central Nervous System
reversible mental confusion.
Nizatidine
More Common Adverse Drug Reactions in Clinical Trials (≥1%)a
| Body System | Effect | Clinical Comment |
|---|---|---|
| Body as a whole | Headache, pain, asthenia, chest pain, infection, accident | The incidence of adverse events in recipients of nizatidine and placebo was generally similar. |
| CNS | Dizziness, somnolence anxiety, nervousness | |
| Gastrointestinal | Diarrhea, dry mouth | |
| Respiratory | Rhinitis, pharyngitis, sinusitis | |
| Skin | Pruritus |
Dermatologic
urticaria (significantly more common in nizatidine than placebo recipients), exfoliative dermatitis.
Hepatic
reversible increase in serum AST, ALT and/or alkaline phosphatase, hepatitis, jaundice; reversible cholestatic or mixed cholestatic hepatocellular injury with jaundice.
Cardiovascular
asymptomatic ventricular tachycardia.
Indications and Clinical Use
Pediatrics
Nizatidine has been used in infants aged ≥5 days and children aged <18 years for the treatment of gastroesophageal reflux.
Overdosage
For management of a suspected drug overdose, CPhA recommends that you contact your regional Poison Control Centre. See the eCPS Directories section for a list of Poison Control Centres.
Warnings and Precautions
Special Populations
Gastrointestinal
Nizatidine may mask the symptoms of gastric malignancy.
Respiratory
Acid-suppressive therapy may increase the risk of community-acquired pneumonia.
Pregnant Women
There is limited human data regarding the safety of nizatidine during pregnancy. Reproductive studies in rats and rabbits at doses of up to 1500 mg/kg/day and 275 mg/kg/day, respectively, have revealed no evidence of teratogenecity. A placental perfusion model revealed that about 40% of freely diffusible nizatidine crosses the placenta. In a prospective study of 178 women exposed to histamine H2 antagonists, including nizatidine, during the first trimester of pregnancy there was no increase in major fetal malformations compared with matched controls.
Nursing Women
Less than 0.1% of a 150 mg dose of nizatidine was excreted into the breast milk of 5 lactating women during a 12 hour period.
Action and Clinical Pharmacology
Distribution
Nizatidine is widely distributed into body fluids. Approximately 35% of the drug in the circulation is bound to plasma proteins, primarily α1-acid glycoprotein.
Nizatidine
Summary of Pharmacokinetic Parameters
| Cmax | Duration of Action | Elimination t½ | Clearance | Volume of Distribution |
|---|---|---|---|---|
| 0.5–3 h | 8–12 h | 1–2 h | 40–60 L/h | 0.8–1.5 L/kg |
Special Populations
Absorption
Nizatidine is rapidly absorbed from the gastrointestinal tract with absolute bioavailability of about 70%. Food increases the bioavailability of nizatidine to a small degree. Single oral doses of 150 and 300 mg achieved peak plasma concentrations of 700-1800 and 1400-3600 ng/mL, respectively.
Mechanism of Action
Nizatidine competitively inhibits histamine at the H2 receptor on parietal cells resulting in decreased basal acid secretion and, to a smaller degree, decreased stimulated acid production. The extent and duration of gastric acid suppression is directly correlated with the dose of nizatidine. A 300 mg dose of nizatidine inhibited 90% of nocturnal gastric acid secretion for up to 10 hours and 97% of meal-stimulated secretion for up to 4 hours.
Nizatidine has no anticholinergic properties and has no effect on gastric motility or lower esophageal sphincter pressure.
Excretion
Nizatidine is excreted by the kidneys via glomerular filtration and tubular secretion. Dosage adjustments are required in patients with renal impairment. In patients with creatinine clearance <10 mL/min, the elimination half-life ranged from 3.5 to 11 hours and the plasma clearance was estimated to be 7 to 14 L/h.
Metabolism
About 10 to 35% of the drug is metabolized by the liver to N-desmethylnizatidine, nizatidine N-oxide, and nizatidine sulfoxide. Only N-desmethylnizatidine has H2 receptor blocking activity, which corresponds to about 60% of the parent drug. First pass metabolism is not significant. The remainder of a dose is excreted unchanged in the urine.
Pediatrics
In children with a mean age of 8 years given a single oral dose of nizatidine 5 mg/kg, the apparent terminal elimination rate was virtually identical to that reported in adults. Estimates of nizatidine pharmacokinetic parameters (e.g., Cmax, CL/F, Vss/F) in children were also similar to those in adults administered similar oral doses of the drug.
Contraindications
Patients who are hypersensitive to nizatidine, other H2 receptor antagonists, or to any ingredient in the formulation. Cross-sensitivity between nizatidine and ranitidine has been reported.
