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Nizatidine


General


Pronunciation

(ni ZA ti deen)


Brand Names: U.S.

  • Axid
  • Axid AR [OTC] [DSC]

Indications


Use: Labeled Indications

Duodenal ulcer: Treatment of active duodenal ulcer for up to 8 weeks and maintenance therapy after healing of active ulcer in adults.

Gastric ulcer, benign: Treatment of active benign gastric ulcer for up to 8 " ‰weeks in adults.

Gastroesophageal reflux disease: Treatment of endoscopically diagnosed esophagitis, including erosive and ulcerative esophagitis, and associated heartburn due to gastroesophageal reflux disease (GERD) for up to 12 weeks in adults (capsules and oral solution) and up to 8 weeks in children 12 years and older (oral solution only).


Contraindications


Hypersensitivity to nizatidine, other H2 antagonists, or any component of the formulation.


Dosing and Administration


Dosing: Adult

Duodenal ulcer: Oral:

Treatment: 300 mg once daily at bedtime or 150 mg twice daily for up to 8 weeks

Maintenance of healing: 150 mg once daily at bedtime

Gastric ulcer, benign: Oral: 150 mg twice daily or 300 mg once daily at bedtime for up to 8 weeks

GERD: Oral: 150 mg twice daily for up to 12 weeks

Helicobacter pylorieradication(off-label use): Oral: 150 mg twice daily (in combination with amoxicillin and clarithromycin [or bismuth, metronidazole, and tetracycline]) for 10 to 14 days (ACG [Chey 2007]; Graham 2003; Talley 1998).


Dosing: Geriatric

Use with caution; refer to adult dosing.


Dosing: Pediatric

GERD: Oral:

Children ≥12 years and Adolescents: (oral solution only): 150 mg twice daily for up to 8 weeks (maximum: 300 mg/day)

Infants 6 months to Children 11 years (off-label use): Limited information available: 5 to 10 mg/kg/day in divided doses given twice daily for up to 8 weeks (Simeone 1997)


Dosing: Renal Impairment

Manufacturers labeling:

Adults and Pediatrics:

Active treatment:

CrCl >50 mL/minute: No dosage adjustment 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 necessary

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

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

Alternate recommendations:

Adults (Aronoff 2007):

GFR >50 mL/minute: Administer 75% to 100% of 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

Hemodialysis: 150 mg every 48 to 72 hours

Peritoneal dialysis: 150 mg every 48 to 72 hours


Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturers labeling.


Administration

Administer with or without food.


Storage

Store at 20 ‚ °C to 25 ‚ °C (68 ‚ °F to 77 ‚ °F); excursions permitted to 15 ‚ °C to 30 ‚ °C (59 ‚ °F to 86 ‚ °F).

Nizatidine is stable for 48 hours at room temperature when the contents of a capsule are mixed in Gatorade ‚ ® lemon-lime, Cran-Grape ‚ ® grape-cranberry drink, V8 ‚ ®, or aluminum- and magnesium hydroxide suspension (approximate concentration 2.5 mg/mL) (Lantz 1990)


Dosage Forms/Strengths


Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Capsule, Oral:

Axid: 150 mg [DSC], 300 mg [DSC]

Generic: 150 mg, 300 mg

Solution, Oral:

Axid: 15 mg/mL (480 mL) [contains methylparaben, propylparaben, saccharin sodium; bubble-gum flavor]

Generic: 15 mg/mL (473 mL, 480 mL [DSC])

Tablet, Oral:

Axid AR: 75 mg [DSC]


Extemporaneously Prepared

A 2.5 mg/mL oral solution may be made with capsules and one of three different vehicles (lemon-lime Gatorade ‚ ®, Ocean Spray ‚ ® Cran-Grape ‚ ® juice or V8 ‚ ® 100% vegetable juice). Empty the contents of one 300 mg capsule in a mortar. Add small portions of the chosen vehicle and mix to a uniform paste; mix while adding the vehicle in incremental proportions to almost 120 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 120 mL. Label shake well". Stable for 2 days refrigerated.

Nahata MC, Pai VB, and Hipple TF, Pediatric Drug Formulations, 5th ed, Cincinnati, OH: Harvey Whitney Books Co, 2004.

Drug Interactions

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

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

Cefditoren: H2-Antagonists may decrease the serum concentration of Cefditoren. Management: Concomitant use of cefditoren with H2-antagonists and antacids is not recommended. Consider alternative methods to control acid reflux (eg, diet modification) or alternative antimicrobial therapy if use of H2-antagonists can not be avoided. Consider therapy modification

Cefpodoxime: H2-Antagonists may decrease the absorption of Cefpodoxime. Separate oral doses by at least 2 hours. Monitor therapy

Cefuroxime: H2-Antagonists may decrease the absorption of Cefuroxime. Separate oral doses by at least 2 hours. Monitor therapy

Cysteamine (Systemic): H2-Antagonists may diminish the therapeutic effect of Cysteamine (Systemic). Monitor therapy

Dabrafenib: H2-Antagonists may decrease the serum concentration of Dabrafenib. Monitor therapy

Dasatinib: H2-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. Avoid combination

Delavirdine: H2-Antagonists may decrease the serum concentration of Delavirdine. Management: Chronic therapy with H2-antagonists should be avoided in patients who are being treated with delavirdine. The clinical significance of short-term H2-antagonist therapy with delavirdine is uncertain, but such therapy should be undertaken with caution. Avoid combination

Dexmethylphenidate: H2-Antagonists may increase the absorption of Dexmethylphenidate. Specifically, H2-antagonists may interfere with the normal release of drug from the extended-release capsules (Focalin XR brand), which could result in both increased absorption (early) and decreased delayed absorption. Monitor therapy

Erlotinib: H2-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. Consider therapy modification

Fosamprenavir: H2-Antagonists may decrease the serum concentration of Fosamprenavir. Cimetidine may also inhibit the metabolism of the active metabolite amprenavir, making its effects on fosamprenavir/amprenavir concentrations difficult to predict. Monitor therapy

Gefitinib: H2-Antagonists may decrease the serum concentration of Gefitinib. Management: Administer gefitinib at least 6 hours before or after administration of a histamine H2-antagonist, and closely monitor clinical response to gefitinib. Consider therapy modification

Indinavir: H2-Antagonists may decrease the serum concentration of Indinavir. Monitor therapy

Iron Salts: H2-Antagonists may decrease the absorption of Iron Salts. Exceptions: Ferric Carboxymaltose; Ferric Citrate; Ferric Gluconate; Ferric Hydroxide Polymaltose Complex; Ferric Pyrophosphate Citrate; Ferumoxytol; Iron Dextran Complex; Iron Sucrose. Monitor therapy

Itraconazole: H2-Antagonists may decrease the serum concentration of Itraconazole. Management: When this combination is used, the itraconazole should be administered with a cola beverage (8 ounces). Itraconazole oral suspension may be less sensitive to this interaction. Monitor patient response to itraconazole closely. Consider therapy modification

Ketoconazole (Systemic): H2-Antagonists may decrease the serum concentration of Ketoconazole (Systemic). Management: Administer oral ketoconazole at least 2 hours prior to use of any H2-receptor antagonist. Monitor patients closely for signs of inadequate clinical response to ketoconazole. Consider therapy modification

Ledipasvir: H2-Antagonists may decrease the serum concentration of Ledipasvir. Consider therapy modification

Mesalamine: H2-Antagonists may diminish the therapeutic effect of Mesalamine. Histamine H2-Antagonist-mediated increases in gastrointestinal pH may cause the premature release of mesalamine from specific sustained-release mesalamine products. Management: Consider avoiding concurrent administration of high-dose histamine H2-receptor antagonists with sustained-release mesalamine products. Consider therapy modification

Methylphenidate: H2-Antagonists may increase the absorption of Methylphenidate. Specifically, H2-antagonists may interfere with the normal release of drug from the extended-release capsules (Ritalin LA brand), which could result in both increased absorption (early) and decreased delayed absorption. Monitor therapy

Multivitamins/Minerals (with ADEK, Folate, Iron): H2-Antagonists may decrease the serum concentration of Multivitamins/Minerals (with ADEK, Folate, Iron). Specifically, the absorption of iron may be impaired by H2-antagonists. Monitor therapy

Nelfinavir: H2-Antagonists may decrease the serum concentration of Nelfinavir. Concentrations of the active M8 metabolite may also be reduced. Monitor therapy

Nilotinib: H2-Antagonists may decrease the serum concentration of Nilotinib. Management: The nilotinib dose should be given 10 hours after or 2 hours before the H2 receptor antagonist in order to minimize the risk of a significant interaction. Consider therapy modification

PAZOPanib: H2-Antagonists may decrease the serum concentration of PAZOPanib. Management: Avoid the use of histamine H2-antagonists in combination with pazopanib. Strategies to minimize the expected interaction between these agents (eg, dose separation) have not been investigated. Avoid combination

Posaconazole: H2-Antagonists may decrease the serum concentration of Posaconazole. Management: Avoid concurrent use of oral suspension with H2-antagonists whenever possible. Monitor patients closely for decreased antifungal effects if this combination is used. Delayed-release posaconazole tablets may be less likely to interact. Consider therapy modification

Rilpivirine: H2-Antagonists may decrease the serum concentration of Rilpivirine. Management: Administer histamine H2 receptor antagonists at least 12 hours before or 4 hours after rilpivirine. Consider therapy modification

Risedronate: H2-Antagonists may increase the serum concentration of Risedronate. This applies specifically to delayed-release risedronate. Avoid combination

Saquinavir: H2-Antagonists may increase the serum concentration of Saquinavir. Monitor therapy

Varenicline: H2-Antagonists may increase the serum concentration of Varenicline. Management: Monitor for increased varenicline adverse effects with concomitant use of cimetidine or other H2-antagonists, particularly in patients with severe renal impairment. International product labeling recommendations vary. Consult appropriate labeling. Monitor therapy

Velpatasvir: H2-Antagonists may decrease the serum concentration of Velpatasvir. Monitor therapy


Lab Test Interferences


Test Interactions

False-positive for urobilinogen using Multistix


Adverse Reactions


>10%: Central nervous system: Headache (16%)

1% to 10%:

Central nervous system: Anxiety, dizziness, fever (reported in children), insomnia, irritability (reported in children), somnolence, nervousness

Dermatologic: Pruritus, rash

Gastrointestinal: Abdominal pain, anorexia, constipation, diarrhea, dry mouth, flatulence, heartburn, nausea, vomiting

Respiratory: Reported in children: Cough, nasal congestion, nasopharyngitis

<1% (Limited to important or life-threatening): Alkaline phosphatase increased, ALT increased, anaphylaxis, anemia, AST increased, bronchospasm, confusion, eosinophilia, exfoliative dermatitis, gynecomastia, hepatitis, jaundice, laryngeal edema, serum-sickness like reactions, thrombocytopenia, thrombocytopenic purpura, vasculitis, ventricular tachycardia


Warnings/Precautions


Special Populations: Renal Function Impairment

Moderate to severe renal impairment decreases clearance and prolongs half-life.


Warnings/Precautions

Concerns related to adverse effects:

- 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 (Lam 2013).

Disease-related concerns:

- Gastric malignancy: Relief of symptoms does not preclude the presence of a gastric malignancy.

- Renal impairment: Use with caution in patients with moderate to severe renal impairment; dosage adjustment recommended.

Concurrent drug therapy issues:

- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

- Pediatric: Use of gastric acid inhibitors, including proton pump inhibitors and H2 blockers, has been associated with an increased risk for development of acute gastroenteritis and community-acquired pneumonia in pediatric patients (Canani 2006).


Pregnancy Risk Factor

B


Pregnancy Considerations

Adverse events have not been observed in animal reproduction studies. Nizatidine crosses the placenta (Dicke 1988). Information related to the use of nizatidine in pregnancy is limited; other agents may be preferred (Richter 2005).


Actions


Pharmacology

Competitive inhibition of histamine at H2-receptors of the gastric parietal cells, which inhibits gastric acid secretion, gastric volume, and hydrogen ion concentration are reduced. Does not affect pepsin secretion, pentagastrin-stimulated intrinsic factor secretion, or serum gastrin.


Absorption

>70%


Distribution

Vd: 0.8 to 1.5 L/kg


Metabolism

Partially hepatic; forms metabolites


Excretion

Urine (>90%; ~60% as unchanged drug); feces (<6%)


Time to Peak

Plasma: 0.5 to 3 hours


Half-Life Elimination

1 to 2 hours; prolonged with moderate to severe renal impairment


Protein Binding

35% to alpha-1 acid glycoprotein


Patient and Family Education


Patient Education

- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

- Patient may experience headache or diarrhea. Have patient report immediately to prescriber severe dizziness; passing out; confusion; bruising; bleeding; black, tarry, or bloody stools; or vomiting blood (HCAHPS).

- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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