Nizatidine

Nizatidine is a Histamine H2 Antagonist of a drug belonging to a Gastrointestinal Agent.

Nizatidine is an H2 receptor antagonist used to treat GERD and a variety of ulcers.

Nizatidine is Readily absorbed from the GI tract. Bioavailability (exceeds 70%) Time taken to reach peak plasma concentration is approximately 0.5-3 hours. Nizatidine is having a volume of distribution of about 0.8-1.5 L/kg. Plasma protein binding is Approximately 35%. Nizatidine is Metabolized Partly via the hepatic route and converted to nizatidine N-2-oxide, nizatidine S-oxide, and N-2-monodesmethylnizatidine. Nizatidine is mainly excreted via urine (>90%), in part by active tubular secretion, within 12 hours, and approximately 60% as an unchanged drug in faeces (<6%).

Nizatidine shows side effects like Headache, dizziness, drowsiness, constipation, diarrhea, stomach pain, runny nose, sneezing, coughing, and sweating.

Nizatidine is available in the form of Oral tablets, Oral capsules, and Oral solutions.

Nizatidine is available in India, Japan, Singapore, Malaysia, Spain, Canada, US, Australia, China, and Italy.

Nizatidine belongs to the Gastrointestinal agent and acts as a Histamine H2 Antagonist.

Nizatidine competes with histamine for binding at the H2-receptors on the gastric basolateral membrane of parietal cells. Competitive inhibition results in a reduction of basal and nocturnal gastric acid secretions. The drug also decreases the gastric acid response to stimuli such as food, caffeine, insulin, betazole, or pentagastrin.

The Data on the Onset and duration of action of Nizatidine is not clinically established.

The Tmax of Nizatidine is approximately 0.5 to 3 hours

Nizatidine is available in the form of Oral Tablets, Oral capsules, and Oral solutions.

Nizatidine tablet, capsule, and suspension are taken orally, usually twice daily.

Nizatidine is a histamine H2 receptor antagonist with low toxicity that inhibits gastric acid secretion. The drug is used for the treatment of duodenal ulcers

Nizatidine is a Histamine H2 Antagonist of a drug belonging to a Gastrointestinal Agent.

Nizatidine is a histamine H2-receptor antagonist. It blocks histamine H2-receptors on gastric parietal cells resulting in decreased gastric acid secretion, gastric volume, and hydrogen ion concentration.

Nizatidine is approved for use in the following clinical indications

Adult Indication:

• Gastroesophageal reflux disease

Pediatric Indication:

• GERD, treatment

• Esophagitis, treatment

Adult Dose:

• Gastroesophageal reflux disease: Oral: 150 mg twice daily; duration of therapy depends on symptoms.

Pediatric Dose:

• GERD, treatment:

Oral:

Infants and Children ≤11 years: 5 mg/kg/dose twice daily; maximum daily dose: 300 mg/day.

Children ≥12 years and Adolescents: 150 mg twice daily; maximum daily dose: 300 mg/day

• Esophagitis, treatment:

Oral:

Infants ≥6 months and Children ≤11 years: Limited data available: 5 mg/kg/dose twice daily. Dosing was based on a double blind, placebo-controlled trial in 26 pediatric patients (treatment group: n=13; age range: 0.5 to 12 years) with mild to moderate esophagitis.

Children ≥12 years and Adolescents: 150 mg twice daily; maximum daily dose: 300 mg/day.

Nizatidine is available in various strengths as 150 mg; 300 mg; 75 mg; 15 mg/mL.

Nizatidine is available in the form of Oral Tablets, Oral capsules, and Oral solutions.

Dosage Adjustment in Kidney Patient

Active treatment:

CrCl >50 mL/minute: No dosage adjustment is necessary.

CrCl 20 to 50 mL/minute: 150 mg once daily

CrCl <20 mL/minute: 150 mg every other day

Maintenance treatment:

CrCl >50 mL/minute: No dosage adjustment is necessary

CrCl 20 to 50 mL/minute: 150 mg every other day

CrCl <20 mL/minute: 150 mg every 3 days

Alternate recommendations:

GFR >50 mL/minute: Administer 75% to 100% of the normal dose.

GFR 10 to 50 mL/minute: 150 mg every 24 to 48 hours

GFR <10 mL/minute: 150 mg every 48 to 72 hours

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 Axid (nizatidine) , should not be administered to patients with a history of hypersensitivity to other H2-receptor antagonists.

• Vitamin B12 deficiency

Prolonged treatment (≥2 years) may lead to vitamin B12 malabsorption and subsequent vitamin B12 deficiency. The magnitude of the deficiency is dose-related and the association is stronger in females and those younger in age (<30 years); prevalence is decreased after discontinuation of therapy.

• Gastric malignancy

Relief of symptoms does not preclude the presence of gastric malignancy.

• Renal impairment

Use with caution in patients with moderate to severe renal impairment; dosage adjustment is recommended.

• Pediatric

The use of gastric acid inhibitors, including proton pump inhibitors and H2 blockers, has been associated with an increased risk for the development of acute gastroenteritis and community-acquired pneumonia in pediatric patients.

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.

Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women.

Common

• Pruritus, Diarrhea (children and adolescents), vomiting (children and adolescents), Infection, Anxiety, dizziness, irritability (children and adolescents), nervousness, Amblyopia, Cough (children and adolescents), nasal congestion (children and adolescents), nasopharyngitis (children and adolescents), Ventricular tachycardia, Anemia, Seizure.

Rare

• Vasculitis, Diaphoresis, exfoliative dermatitis, skin rash, urticaria, Gynecomastia, hyperuricemia, Nausea, Impotence, Aplastic anemia, eosinophilia, immune thrombocytopenia, Cholestatic jaundice (including mixed hepatocellular), hepatitis, jaundice, Anaphylaxis, hypersensitivity angiitis, hypersensitivity reaction, serum sickness-like reaction, Confusion, Fever.

• Acalabrutinib

Histamine H2 Receptor Antagonists may decrease the serum concentration of Acalabrutinib. Management: Give acalabrutinib capsules 2 hours before a histamine H2 receptor antagonist (H2RA). No action is required if acalabrutinib tablets are coadministered with H2RAs

• Atazanavir

Histamine H2 Receptor Antagonists may decrease the serum concentration of Atazanavir. Management: Specific dose limitations and administration guidelines exist; consult full interaction monograph or atazanavir prescribing information

• Belumosudil

Histamine H2 Receptor Antagonists may decrease the serum concentration of Belumosudil.

• Bosutinib

Histamine H2 Receptor Antagonists may decrease the serum concentration of Bosutinib. Management: Administer histamine H2 receptor antagonists more than 2 hours before or after bosutinib

• Cefditoren

Histamine H2 Receptor Antagonists may decrease the serum concentration of Cefditoren.

Cefpodoxime: Histamine H2 Receptor Antagonists may decrease the serum concentration of Cefpodoxime.

• Cefuroxime

Histamine H2 Receptor Antagonists may decrease the absorption of Cefuroxime. Separate oral doses by at least 2 hours.

• Cysteamine (Systemic)

Histamine H2 Receptor Antagonists may diminish the therapeutic effect of Cysteamine (Systemic).

• Dacomitinib

Histamine H2 Receptor Antagonists may decrease the serum concentration of Dacomitinib. Management: Administer dacomitinib at least 6 hours before or 10 hours after a histamine H2-receptor antagonist (H2RA)

• Dasatinib

Histamine H2 Receptor Antagonists may decrease the absorption of Dasatinib. Management: Antacids (taken 2 hours before or after dasatinib administration) can be used in place of H2-antagonists if some acid-reducing therapy is needed.

• Delavirdine

Histamine H2 Receptor Antagonists may decrease the serum concentration of Delavirdine.

• Enoxacin

Histamine H2 Receptor Antagonists may decrease the absorption of Enoxacin.

Erlotinib: Histamine H2 Receptor Antagonists may decrease the serum concentration of Erlotinib. Management: Avoid H2-antagonists in patients receiving erlotinib when possible. If concomitant treatment cannot be avoided, erlotinib should be dosed once daily, 10 hours after and at least 2 hours before H2-antagonist dosing.

The common side effects of Nizatidine include the following

Common side effects

• Headache, dizziness, drowsiness, constipation, diarrhoea, stomach pain, runny nose, sneezing, coughing, sweating.

Rare side effects

• Skin rash, hives, itching, wheezing, difficulty breathing.

• Pregnancy

Pregnancy Category B

Teratogenic Effects

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.

• 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.

• Geriatric 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.

Symptoms: Lacrimation, salivation, emesis, miosis, and diarrhea.

Management: Symptomatic and supportive treatment. Activated charcoal, emesis, or lavage may reduce absorption.

• Pharmacodynamic

Nizatidine is a competitive, reversible inhibitor of histamine at the histamine H2-receptors, particularly those in the gastric parietal cells. By inhibiting the action of histamine on stomach cells, nizatidine reduces stomach acid production. Nizatidine had no demonstrable antiandrogenic action. Full-dose therapy for the problems treated by nizatidine lasts no longer than 8 weeks. It has been demonstrated that treatment with a reduced dose of nizatidine is effective as maintenance therapy following the healing of active duodenal ulcers.

• Pharmacokinetics

Absorption

Nizatidine is Readily absorbed from the GI tract. Bioavailability (exceeds 70%) Time taken to reach peak plasma concentration is Approximately 0.5-3 hours.

Distribution

Nizatidine is having a volume of distribution of about 0.8-1.5 L/kg. Plasma protein binding is Approximately 35%.

Metabolism and Excretion

Nizatidine is Metabolized Partly via the hepatic route and converted to nizatidine N-2-oxide, nizatidine S-oxide, and N-2-monodesmethylnizatidine. Nizatidine is mainly excreted via urine (>90%), in part by active tubular secretion, within 12 hours, and approximately 60% as unchanged drug in faeces (<6%).

Tomokane Y, Nomura M, Kujime S, Noda Y, Kondo N, Nakaya Y, Ito S. Clinical Study on the Effects of Nizatidine on Gastric Motility and Cardiac Autonomic Function. Arzneimittelforschung. 2004 Aug;54(08):427-35.

Morrissey KM, Stocker SL, Chen EC, Castro RA, Brett CM, Giacomini KM. The effect of nizatidine, a MATE2K selective inhibitor, on the pharmacokinetics and pharmacodynamics of metformin in healthy volunteers. Clinical pharmacokinetics. 2016 Apr;55:495-506.

Futagami S, Shimpuku M, Song JM, Kodaka Y, Yamawaki H, Nagoya H, Shindo T, Kawagoe T, Horie A, Gudis K, Iwakiri K. Nizatidine improves clinical symptoms and gastric emptying in patients with functional dyspepsia accompanied by impaired gastric emptying. Digestion. 2012;86(2):114-21.

• https://www.mims.com/malaysia/drug/info/nizatidine?mtype=generic
• https://go.drugbank.com/drugs/DB00585
• https://www.drugs.com/pregnancy/nizatidine.html
• https://www.rxlist.com/axid-drug.htm#warnings
• https://www.uptodate.com/contents/nizatidine-drug-information?search=nizatidine&source=panel_search_result&selectedTitle=1~35&usage_type=panel&kp_tab=drug_general&display_rank=1
• https://medlineplus.gov/druginfo/meds/a694030.html#:~:text=Nizatidine is used to treat,stomach makes too much acid.
• https://reference.medscape.com/drug/axid-nizatidine-341996