Nizatidine is an oral H2-receptor antagonist. Nizatidine is indicated for gastroesophageal reflux disease (GERD), short-term and maintenance treatment of duodenal ulcer, and short-term treatment of active benign gastric ulcer. A non-prescription (OTC) product is also available for self-treatment of pyrosis (heart burn), dyspepsia, and sour stomach. Of note, for the symptomatic acute and chronic treatment of GERD, proton pump inhibitors (PPIs) are considered to be more effective than H2-blockers.
NOTE: Globally, as well as in the U.S., some nizatidine products have been recalled from the market since September 2019 because they may contain unacceptable levels of N-nitrosodimethylamine (NDMA), a probable human carcinogen. In April 2020, another H2-receptor antagonist, ranitidine, was withdrawn from the U.S. market after an ongoing investigation of NDMA in ranitidine medications. NDMA has been linked with cancers of the digestive tract, bladder, kidney, and others. The FDA has determined that NDMA in some ranitidine products increases over time and especially when the products are stored at higher than room temperatures, and thus result in consumer exposure to unacceptable levels of this impurity. NDMA has also been found in some nizatidine products. The FDA has required testing of manufactured products. If testing shows NDMA above the acceptable daily intake limit, the manufacturer must inform the FDA and should not release the nizatidine product lot for consumer use. Patients taking prescription nizatidine who wish to stop taking these products should talk to their health care professional about other treatment options. As of April 2020, the FDA's testing has not found NDMA in famotidine, cimetidine, esomeprazole, lansoprazole, or omeprazole.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
-All oral dosage forms: May be administered without regard to meals. Administer with food, water, or milk to minimize gastric irritation. Administer with a full glass of water.
-For non-prescription occasional use for symptom prevention: Administer right before eating or up to 60 minutes before consuming food or beverage that may cause heartburn. Administer with a full glass of water.
Oral Liquid Formulations
-Oral solution: Administer using a calibrated measuring device to assure accurate dosage.
Pain (4.2% vs 3.8%) and accidental injury (1.2% vs 0.9%) were reported more often in patients who received oral nizatidine (n = 2694) compared with patients who received placebo (n = 1729) in clinical trials.
Atrophic gastritis, a precursor for gastric cancer, has been associated with prolonged acid suppression with high dose H2-blockers like nizatidine in patients who are H. pylori positive. A 'test and treat' approach for baseline H. pylori infections is recommended for patients with reflux esophagitis on long term acid suppression therapy. Treatment of baseline infection decreases inflammation and may reverse corpus gastritis.
Headache (16.6% vs 15.6%), dizziness (4.6% vs 3.8%), and drowsiness (1.9% vs 1.6%) were reported more often in patients who received oral nizatidine (n = 2694) compared with placebo (n = 1729) in clinical trials. Mental confusion was reported rarely (< 1%). Irritability was reported in greater than 5% of pediatric patients aged 2-18 years who received oral nizatidine. Additionally, 1 pediatric patient experienced seizures (diagnosed by electroencephalogram) after receiving nizatidine oral solution 2.5 mg/kg PO twice daily for 23 days.
Rhinitis (9.8% vs 9.6%), pharyngitis (3.3% vs 3.1%), and sinusitis (2.4% vs 2.1%) occurred more often in patients who received oral nizatidine (n = 2694) compared with placebo (n = 1729) in clinical trials. Nasopharyngitis, nasal congestion, and cough were reported in greater than 5% of pediatric patients aged 2-18 years who received oral nizatidine.
Infection was reported in 1.7% of patients who received oral nizatidine (n = 2694) compared with 1.1% of patients who received placebo (n = 1729) in clinical trials. Pneumonia has been reported with nizatidine use in post-marketing surveillance.
Diarrhea (7.2% vs 6.9%), xerostomia (1.4% vs 1.3%), and tooth disorder (1% vs 0.8%) occurred more often in patients who received oral nizatidine (n = 2694) compared with placebo (n = 1729) in clinical trials. Diarrhea and vomiting were reported in greater than 5% of pediatric patients aged 2-18 years who received oral nizatidine.
Anxiety (1.8% vs 1.4%) and nervousness (1.1% vs 0.8%) occurred more often in patients who received oral nizatidine (n = 2694) compared with placebo (n = 1729) in clinical trials.
Pruritus was reported in 1.7% of patients who received oral nizatidine (n = 2694) compared with 1.3% of patients who received placebo (n = 1729) in clinical trials. Urticaria was reported significantly more often in nizatidine-treated patients compared with patient who received placebo (0.5% vs 0.1%); sweating was also reported significantly more often with nizatidine therapy. Other dermatologic reactions reported in less than 1% of patients include rash (unspecified) and exfoliative dermatitis. Vasculitis was also reported rarely.
Myalgia was reported in 1.7% of patients who received oral nizatidine (n = 2694) compared with 1.5% of patients who received placebo (n = 1729) in clinical trials.
Amblyopia was reported in 1% of patients who received oral nizatidine (n = 2694) compared with 0.9% of patients who received placebo (n = 1729) in clinical trials.
Chest pain (unspecified) was reported in 2.3% of patients who received oral nizatidine (n = 2694) compared with 2.1% of patients who received placebo (n = 1729) in clinical trials. There were 2 cases of asymptomatic ventricular tachycardia in patients receiving nizatidine in clinical pharmacology studies; however, there were 3 cases of asymptomatic ventricular tachycardia in untreated subjects.
Impotence (erectile dysfunction) has been reported in less than 1% of patients who received nizatidine in clinical trials.
Anemia (0.2% vs 0%) occurred significantly more often in patients who received oral nizatidine (n = 2694) compared with patients who received placebo (n = 1729) in clinical trials. Fatal thrombocytopenia was reported in 1 patient with a history of drug-induced thrombocytopenia who received nizatidine and another H2-receptor antagonist. Thrombocytopenia purpura has also been reported rarely.
Fever was reported in greater than 5% of pediatric patients aged 2-18 years who received oral nizatidine.
Gynecomastia has been reported rarely in patients who received nizatidine in clinical trials.
Hyperuricemia unassociated with gout or nephrolithiasis has been reported in less than 1% of patients who received nizatidine in clinical trials.
Hypersensitivity reactions (e.g., anaphylactoid reactions, bronchospasm, laryngeal edema, and rash) have been reported rarely in patients who received nizatidine in clinical trials. Also, eosinophilia, fever, and nausea have been reported with nizatidine therapy.
Serum sickness like reactions have been reported rarely in patients who received nizatidine.
Reversible hepatocellular injury including elevated hepatic enzymes (e.g., increased AST, ALT, or alkaline phosphatase levels) has been reported in patients who received nizatidine in clinical trials, at a rate similar to patients who received placebo. Hepatitis and jaundice have been reported rarely with nizatidine use in post-marketing surveillance. Additionally, reversible cholestatic (cholestasis) or mixed hepatocellular and cholestatic injury with jaundice have been reported. Mild transaminase concentration elevations (1-2 times the upper limit of normal) occurred in some pediatric patients aged 2-18 years who received oral nizatidine.
Long-term (e.g., generally > 3 years) treatment with acid-suppressing agents can lead to malabsorption of vitamin B12 (cyanocobalamin). One large case-controlled study compared patients with and without an incident diagnosis of vitamin B12 deficiency (n = 25,956 and 184,199, respectively). A correlation was demonstrated between vitamin B12 deficiency and gastric acid-suppression therapy. Patients receiving >= 2 years of a proton pump inhibitor (PPI)(OR, 1.65 [95% CI, 1.58-1.73]) or >= 2 years of a H2-receptor antagonist (OR, 1.25 [95% CI, 1.17-1.34]) were associated with having an increased risk for vitamin B12 deficiency. A dose-dependant relationship was evident, as daily doses > 1.5 PPI pills/day were more strongly associated with vitamin B12 deficiency (OR, 1.95 [95% CI, 1.77-2.15]) compared to daily doses < 0.75 pills/day (OR, 1.63 [95% CI, 1.48-1.78]; p = 0.007 for interaction). The possibility of cyanocobalamin deficiency and pernicious anemia should be considered if clinical symptoms are observed. Neurological manifestations of pernicious anemia can occur in the absence of hematologic changes.
Nizatidine is contraindicated in any patient hypersensitive to the drug or with a history of other H2-blocker hypersensitivity.
Symptomatic response to therapy with famotidine does not preclude the presence of gastric cancer. Patients who have a suboptimal response or early symptomatic relapse after completing therapy should consider evaluation for gastric malignancy. In the patient who is self-medicating with nonprescription (OTC) formulations, the continuation of heartburn, acid indigestion, or dyspepsia beyond 2 weeks signals the need to consult a health care professional for evaluation.
Symptomatic response to therapy with nizatidine does not preclude the presence of H. pylori infection. H2-blockers, as single agents, will not eradicate H. pylori infection, if present.
To avoid accumulation of the drug in individuals with clinically significant renal impairment (i.e., CrCl 50 mL/minute or less) and renal failure, the dosage of nizatidine should be reduced in proportion to the severity of dysfunction.
There are no adequate and well-controlled studies of nizatidine use during pregnancy; however, animal reproduction studies do not suggest a risk for fetal harm and epidemiologic data are available. Reproduction studies in pregnant rats at nizatidine oral doses up to 1,500 mg/kg/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 (14.6 times the recommended human dose based on body surface area) have revealed no evidence of impaired fertility or harm to the fetus. Epidemiological evidence based on the use of H2-blockers during pregnancy does not suggest an increase in fetal malformations compared to the normal population, even with first trimester use. In another study of human data, exposure to H2-blockers was not associated with an increased risk for congenital malformations (adjusted OR 1.03, 95% CI: 0.80, 1.32); also, no such association was found when therapeutic pregnancy terminations were included in the analysis (adjusted OR 1.17, 95% CI: 0.93, 1.46). Exposure to H2-blockers was not associated with perinatal mortality, premature delivery, low birth weight, or low Apgar scores. Guidelines recommend a trial of lifestyle modifications as first-line therapy for heartburn and gastroesophageal reflux disease (GERD) during pregnancy, followed by antacids if lifestyle adjustments are ineffective. For ongoing symptoms, an H2-blocker can be used. Other medications should be reserved for pregnant patients who fail H2-blocker therapy. Due to the relatively smaller amount of data available with nizatidine as compared with other H2-blockers, some experts recommend consideration of an H2-blocker with more data if needed during pregnancy, such as famotidine. Self-medication with H2-blockers (OTC formulations) during pregnancy is not recommended. Pregnant patients should see their health care professional for a proper diagnosis and for treatment recommendations. H2-blockers have been used in limited circumstances at term to prevent acid aspiration during labor; some guidelines recommend an H2-blocker (PO or IV) for all women presenting for cesarean delivery.
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 in animal studies, the prescribing label recommends that a decision be made whether to discontinue breast-feeding or discontinue the drug, taking into account the importance of the drug to the lactating individual. According to guidelines, if heartburn/gastroesophageal reflux (GERD) symptoms persist after delivery, antacids and sucralfate are safe to use during lactation because they are not concentrated in breast milk. H2-blockers are excreted in breast milk, but cimetidine and famotidine are considered safe for use during lactation and may be used if symptoms persist despite antacid use.
No overall differences in safety or effectiveness were observed between geriatric adults vs. younger adults in clinical studies of nizatidine. Nizatidine is substantially excreted by the kidney and dosage reduction may be necessary if renal impairment is present in the geriatric adult; monitoring of renal function may be useful. According to the Beers Criteria, H2-receptor antagonists are considered potentially inappropriate medications (PIMs) in geriatric patients with delirium/high risk of delirium (potential for new-onset or worsening delirium) and should be avoided in this patient population. The Beers panel also recommends dose reduction of H2-antagonists in geriatric adults with a creatinine clearance less than 50 mL/minute due to the potential for mental status changes.
Daily treatment with gastric acid-suppressing medication over a long period of time (e.g., generally more than 3 years) may lead to malabsorption of cyanocobalamin and vitamin B12 deficiency. One large case-controlled study compared patients with and without an incident diagnosis of vitamin B12 deficiency. A correlation was demonstrated between vitamin B12 deficiency and gastric acid-suppression therapy with PPIs or H2-blockers of greater than 2 years duration. A dose-dependent relationship was also evident, as larger daily pill counts were more strongly associated with vitamin B12 deficiency. Consider the possibility of cyanocobalamin deficiency if clinical symptoms are observed.
A laboratory test interference may occur with nizatidine use. False-positive tests for urobilinogen with Multistix test strips may occur during therapy with nizatidine.
For self-medication of pyrosis (heartburn), acid dyspepsia (acid indigestion), or sour stomach:
Oral dosage:
Adults, Adolescents, and Children >= 12 years: To prevent heartburn, take 75 mg PO immediately before or up to 60 minutes before consuming food or beverages that are known to cause symptoms. For treatment, take 75 mg PO once or twice daily. Maximum dosage is 150 mg/day PO. Patients should not take for more than 2 weeks without consulting a physician.
For the treatment of gastroesophageal reflux disease (GERD), including endoscopically diagnosed esophagitis (erosive and ulcerative esophagitis) and GERD-associated pyrosis (heartburn):
Oral dosage (capsules):
Adults: 150 mg PO twice daily for up to 12 weeks.
Children* and Adolescents* 12 to 17 years: 150 mg PO twice daily for up to 8 weeks. Alternatively, 5 mg/kg/dose PO twice daily is recommended by the American Academy of Pediatrics (AAP); however, a maximum dosage is not specified. While nizatidine may be effective in patients with less severe GERD, proton pump inhibitors (PPIs) offer more rapid symptom relief and better healing.
Infants* and Children* 1 to 11 years: 5 mg/kg/dose PO twice daily is recommended by the American Academy of Pediatrics (AAP). Doses of 2.5 to 10 mg/kg/dose PO twice daily have also been reported. In an open-label, multiple-dose, randomized, parallel-group, multicenter study, patients (aged 5 days to 18 years, n = 210) were randomized to receive either of 2 dose levels (2.5 or 5 mg/kg/dose twice daily) for 8 weeks; no clear superiority between doses was observed. In a separate placebo controlled study, patients (aged 6 months to 8 years, n = 24) with mild to moderate reflux esophagitis received 10 mg/kg/dose PO twice daily for 8 weeks or a matching placebo. Nizatidine therapy was associated with statistically significant improvement in symptoms, reduced esophageal acid exposure, and healed esophagitis. While nizatidine may be effective in patients with less severe GERD, proton pump inhibitors (PPIs) offer more rapid symptom relief and better healing.
Oral dosage (15 mg/mL solution):
Adults: 150 mg PO twice daily for up to 12 weeks.
Children and Adolescents 12 to 17 years: 150 mg PO twice daily for up to 8 weeks. Alternatively, 5 mg/kg/dose PO twice daily is recommended by the American Academy of Pediatrics (AAP); however, a maximum dosage is not specified. While nizatidine may be effective in patients with less severe GERD, proton pump inhibitors (PPIs) offer more rapid symptom relief and better healing.
Infants* and Children* 1 to 11 years: 5 mg/kg/dose PO twice daily is recommended by the American Academy of Pediatrics (AAP). Doses of 2.5 to 10 mg/kg/dose PO twice daily have also been reported. In an open-label, multiple-dose, randomized, parallel-group, multicenter study, patients (aged 5 days to 18 years, n = 210) were randomized to receive either of 2 dose levels (2.5 or 5 mg/kg/dose twice daily) for 8 weeks; no clear superiority between doses was observed. In a separate placebo controlled study, patients (aged 6 months to 8 years, n = 24) with mild to moderate reflux esophagitis received 10 mg/kg/dose PO twice daily for 8 weeks or a matching placebo. Nizatidine therapy was associated with statistically significant improvement in symptoms, reduced esophageal acid exposure, and healed esophagitis. While nizatidine may be effective in patients with less severe GERD, proton pump inhibitors (PPIs) offer more rapid symptom relief and better healing.
Neonates*: 2.5 to 5 mg/kg/dose PO twice daily for 8 weeks has been studied for GERD in an open-label, multiple-dose, randomized, parallel-group, multicenter study. Patients (aged 5 days to 18 years, n = 210) were randomized to receive either of 2 dose levels (2.5 or 5 mg/kg/dose twice daily) for 8 weeks; no clear superiority between doses was observed. Neonatal data were not reported separately. While nizatidine may be effective in patients with less severe GERD, proton pump inhibitors (PPIs) offer more rapid symptom relief and better healing.
For the treatment of duodenal ulcer:
-for an active ulcer:
Oral dosage (capsules or 15 mg/mL solution):
Adults: 300 mg PO at bedtime, or 150 mg PO every 12 hours, for 8 weeks. In most patients, ulcers heal within 4 weeks.
-for maintenance therapy after the ulcer has healed:
Oral dosage (capsules or 15 mg/mL solution):
Adults: 150 mg PO at bedtime. Treatment beyond 1 year has not been evaluated.
For the treatment of an active benign gastric ulcer:
Oral dosage (capsules or 15 mg/mL solution):
Adults: 300 mg PO daily, administered once daily at bedtime or as 150 mg every 12 hours, for 8 weeks. Prior to treatment, care should be taken to exclude the possibility of malignant gastric ulceration.
For acid aspiration prophylaxis* prior to anesthesia:
Oral dosage:
Adults: 300 mg PO the night prior to or the morning of surgery, before induction of anesthesia. According to guidelines of the American Society of Anesthesiologists, routine preoperative use is NOT recommended in patients who have no apparent increased risk for pulmonary aspiration. However, some guidelines recommend an H2-receptor antagonist (PO or IV) for all women presenting for cesarean delivery.
For stress gastritis prophylaxis* in critically-ill patients:
Oral dosage (capsules or 15 mg/ml solution):
Adults: 150-300 mg PO once daily.
Maximum Dosage Limits:
-Adults
300 mg/day PO.
-Geriatric
300 mg/day PO.
-Adolescents
300 mg/day PO.
-Children
12 years and older: 300 mg/day PO.
1 to 11 years: 10 to 20 mg/kg/day PO has been studied.
-Infants
6 months and older: 10 to 20 mg/kg/day PO has been studied.
1 to 5 months: 10 mg/kg/day PO has been studied.
-Neonates
10 mg/kg/day PO has been studied.
Patients with Hepatic Impairment Dosing
Specific dosage adjustments have not been recommended. Use with caution in patients with hepatorenal syndrome as formal studies have not been done and part of the dose of nizatidine is metabolized in the liver. For patients with normal renal function and uncomplicated hepatic dysfunction, the disposition of nizatidine is similar to that of normal subjects.
Patients with Renal Impairment Dosing
Adults:
CrCl more than 50 mL/minute: No dosage adjustment needed.
CrCl 20 to 50 mL/minute: For adults treated for active duodenal ulcer, GERD, or benign gastric ulcer, decrease the dose to 150 mg PO once daily; for adults receiving maintenance therapy, decrease to 150 mg PO every other day.
CrCl less than 20 mL/minute: For adults treated for active duodenal ulcer, GERD, or benign gastric ulcer, decrease the dose to 150 mg PO every other day; for adults receiving maintenance therapy, decrease to 150 mg PO once every 3 days.
Pediatric patients 12 years and older:
See adult dosage adjustment recommendations.
Intermittent Hemodialysis
See dosage recommendations for CrCl less than 20 mL/minute. Nizatidine is not expected to be efficiently removed from the body by dialysis.
*non-FDA-approved indication
Acalabrutinib: (Moderate) Separate the administration of acalabrutinib capsules and H2-blockers if these agents are used together; administer acalabrutinib capusles 2 hours before the H2-blocker. Acalabrutinib capsule solubility decreases with increasing pH values; therefore, coadministration may result in decreased acalabrutinib exposure and effectiveness.
Albuterol; Budesonide: (Moderate) Monitor for loss of oral, enteric-coated budesonide efficacy during concomitant nizatidine use. Since the dissolution of oral, enteric-coated budesonide is pH dependent, the release properties and uptake of the drug may be altered when used after H2-blockers.
Amphetamine: (Moderate) Use amphetamine; dextroamphetamine and H2-blockers concomitantly with caution. Gastrointestinal alkalinizing agents may increase exposure to amphetamine; dextroamphetamine and exacerbate its actions.
Amphetamine; Dextroamphetamine Salts: (Moderate) Use amphetamine; dextroamphetamine and H2-blockers concomitantly with caution. Gastrointestinal alkalinizing agents may increase exposure to amphetamine; dextroamphetamine and exacerbate its actions.
Amphetamine; Dextroamphetamine: (Moderate) Use amphetamine; dextroamphetamine and H2-blockers concomitantly with caution. Gastrointestinal alkalinizing agents may increase exposure to amphetamine; dextroamphetamine and exacerbate its actions.
Atazanavir: (Major) Coadministration of H2-blockers with atazanavir reduces serum atazanavir concentrations; however, H2-blockers can be used under specific administration restrictions. Although data are insufficient to recommend atazanavir dosing in children < 40 kg receiving concomitant H2-blockers, the same recommendations regarding timing and maximum doses of concomitant H2-blockers should be followed. In treatment-naive patients >= 40 kg, do not exceed an H2- blocker dose equivalent to famotidine 40 mg twice daily, and give atazanavir 300 mg with ritonavir 100 mg once daily with food. Give atazanavir simultaneously with and/or at least 10 hours after the H2- blocker. If a treatment-naive adult or adolescent (>= 40 kg) cannot tolerate ritonavir, do not exceed an H2- blocker dose equivalent to famotidine 20 mg twice daily, and the atazanavir dose should be increased to 400 mg once daily with food given at least 2 hours before or 10 hours after the H2- blocker. Data are insufficent to recommend atazanavir dosing in children or adolescents < 40 kg not receiving ritonavir boosting. In treatment-naive patients on a cobicistat-boosted regimen, cobicistat and atazanavir may be administered without dosage adjustment if given at the same time or a minimum of 10 hours after dosing of the H2-blocker. The H2-blocker dose should not exceed a dose that is comparable to 40 mg/day of famotidine in treatment-naive patients. In treatment-experienced patients >= 40 kg, do not exceed an H2- blocker dose equivalent to famotidine 20 mg twice daily, and give atazanavir 300 mg with ritonavir 100 mg once daily with food. Give atazanavir simultaneously with and/or at least 10 hours after the H2- blocker. In treatment-experienced patients >= 40 kg receiving H2-antagonists and tenofovir, atazanavir should be dosed 400 mg with ritonavir 100 mg once daily with food. In antiretroviral-experienced patients on a cobicistat-boosted regimen, the dosage of cobicistat with atazanavir needs to be increased if administered with H2-blockers; the recommended dose is cobicistat 150 mg/day with atazanavir 400 mg/day and 20 mg/day or less of famotidine or other comparably dosed H2-blocker. Significant reductions in atazanavir serum concentrations may lead to therapeutic failure and the development of HIV resistance. Closely monitor patients for antiretroviral therapeutic failure and resistance development during treatment with an H2- blocker.
Atazanavir; Cobicistat: (Major) Coadministration of H2-blockers with atazanavir reduces serum atazanavir concentrations; however, H2-blockers can be used under specific administration restrictions. Although data are insufficient to recommend atazanavir dosing in children < 40 kg receiving concomitant H2-blockers, the same recommendations regarding timing and maximum doses of concomitant H2-blockers should be followed. In treatment-naive patients >= 40 kg, do not exceed an H2- blocker dose equivalent to famotidine 40 mg twice daily, and give atazanavir 300 mg with ritonavir 100 mg once daily with food. Give atazanavir simultaneously with and/or at least 10 hours after the H2- blocker. If a treatment-naive adult or adolescent (>= 40 kg) cannot tolerate ritonavir, do not exceed an H2- blocker dose equivalent to famotidine 20 mg twice daily, and the atazanavir dose should be increased to 400 mg once daily with food given at least 2 hours before or 10 hours after the H2- blocker. Data are insufficent to recommend atazanavir dosing in children or adolescents < 40 kg not receiving ritonavir boosting. In treatment-naive patients on a cobicistat-boosted regimen, cobicistat and atazanavir may be administered without dosage adjustment if given at the same time or a minimum of 10 hours after dosing of the H2-blocker. The H2-blocker dose should not exceed a dose that is comparable to 40 mg/day of famotidine in treatment-naive patients. In treatment-experienced patients >= 40 kg, do not exceed an H2- blocker dose equivalent to famotidine 20 mg twice daily, and give atazanavir 300 mg with ritonavir 100 mg once daily with food. Give atazanavir simultaneously with and/or at least 10 hours after the H2- blocker. In treatment-experienced patients >= 40 kg receiving H2-antagonists and tenofovir, atazanavir should be dosed 400 mg with ritonavir 100 mg once daily with food. In antiretroviral-experienced patients on a cobicistat-boosted regimen, the dosage of cobicistat with atazanavir needs to be increased if administered with H2-blockers; the recommended dose is cobicistat 150 mg/day with atazanavir 400 mg/day and 20 mg/day or less of famotidine or other comparably dosed H2-blocker. Significant reductions in atazanavir serum concentrations may lead to therapeutic failure and the development of HIV resistance. Closely monitor patients for antiretroviral therapeutic failure and resistance development during treatment with an H2- blocker.
Bisacodyl: (Minor) The concomitant use of bisacodyl tablets with H2-blockers can cause the enteric coating of the bisacody tablet to dissolve prematurely, leading to possible gastric irritation or dyspepsia. Avoid H2-blockers within 1 hour before or after the bisacodyl dosage.
Bismuth Subsalicylate: (Minor) H2-blockers may increase the systemic absorption of bismuth from bismuth-containing compounds like bismuth subsalicylate.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Minor) H2-blockers may increase the systemic absorption of bismuth from bismuth-containing compounds like bismuth subsalicylate.
Bosutinib: (Moderate) Bosutinib displays pH-dependent aqueous solubility; therefore, concomitant use of bosutinib and H2-blockers may result in decreased plasma exposure of bosutinib. Separate the administration of bosutinib and H2-blockers by more than 2 hours.
Budesonide: (Moderate) Monitor for loss of oral, enteric-coated budesonide efficacy during concomitant nizatidine use. Since the dissolution of oral, enteric-coated budesonide is pH dependent, the release properties and uptake of the drug may be altered when used after H2-blockers.
Budesonide; Formoterol: (Moderate) Monitor for loss of oral, enteric-coated budesonide efficacy during concomitant nizatidine use. Since the dissolution of oral, enteric-coated budesonide is pH dependent, the release properties and uptake of the drug may be altered when used after H2-blockers.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) Monitor for loss of oral, enteric-coated budesonide efficacy during concomitant nizatidine use. Since the dissolution of oral, enteric-coated budesonide is pH dependent, the release properties and uptake of the drug may be altered when used after H2-blockers.
Cabotegravir; Rilpivirine: (Moderate) Coadministration with nizatidine may significantly decrease rilpivirine plasma concentrations, potentially resulting in treatment failure. To decrease the risk of virologic failure, avoid use of nizatidine for at least 12 hours before and at least 4 hours after administering rilpivirine.
Cefpodoxime: (Moderate) H2-blockers should be avoided during treatment with cefpodoxime. Coadministration could result in antibiotic failure. H2-blockers increase gastric pH. Cefpodoxime proxetil requires low gastric pH for dissolution. While the rate of absorption is not affected, coadministration reduces cefpodoxime AUC, peak plasma concentration (by 42%), and extent of absorption (by 32%).
Cefuroxime: (Major) Avoid the concomitant use of H2-blockers and cefuroxime. Drugs that reduce gastric acidity, such as H2-blockers, can interfere with the oral absorption of cefuroxime axetil and may result in reduced antibiotic efficacy.
Cysteamine: (Major) Monitor white blood cell (WBC) cystine concentration closely when administering delayed-release cysteamine (Procysbi) with H2-blockers. Drugs that increase the gastric pH may cause the premature release of cysteamine from delayed-release capsules, leading to an increase in WBC cystine concentration.
Dacomitinib: (Moderate) Administer dacomitinib at least 6 hours before or 10 hours after nizatidine. Taking these medications at the same time may reduce dacomitinib absorption and decrease its efficacy.
Dasatinib: (Major) Do not administer H2-blockers with dasatinib due to the potential for decreased dasatinib exposure and reduced efficacy. Consider using an antacid if acid suppression therapy is needed. Administer the antacid at least 2 hours prior to or 2 hours after the dose of dasatinib. Concurrent use of an H2-blocker reduced the mean Cmax and AUC of dasatinib by 63% and 61%, respectively.
Delavirdine: (Major) Coadministration of delavirdine with H2-blockers results in decreased absorption of delavirdine. Administration of delavirdine and H2-blockers should be separated by at least 1 hour. Chronic use of H2-blockers with delavirdine is not recommended.
Dextroamphetamine: (Moderate) Use amphetamine; dextroamphetamine and H2-blockers concomitantly with caution. Gastrointestinal alkalinizing agents may increase exposure to amphetamine; dextroamphetamine and exacerbate its actions.
Diphenhydramine; Naproxen: (Moderate) Avoid concomitant use of enteric-coated, delayed-release naproxen and H2-blockers due to the gastric pH elevating effects of H2-blockers. Enteric-coated, delayed-release naproxen tablets are designed to dissolve at a pH of 6 or more.
Dolutegravir; Rilpivirine: (Moderate) Coadministration with nizatidine may significantly decrease rilpivirine plasma concentrations, potentially resulting in treatment failure. To decrease the risk of virologic failure, avoid use of nizatidine for at least 12 hours before and at least 4 hours after administering rilpivirine.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Coadministration with nizatidine may significantly decrease rilpivirine plasma concentrations, potentially resulting in treatment failure. To decrease the risk of virologic failure, avoid use of nizatidine for at least 12 hours before and at least 4 hours after administering rilpivirine.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Coadministration with nizatidine may significantly decrease rilpivirine plasma concentrations, potentially resulting in treatment failure. To decrease the risk of virologic failure, avoid use of nizatidine for at least 12 hours before and at least 4 hours after administering rilpivirine.
Erlotinib: (Major) If concomitant use of erlotinib with nizatidine is necessary, erlotinib must be taken 10 hours after the last dose of nizatidine and at least 2 hours before the next dose. Erlotinib displays pH-dependent solubility with decreased solubility at a higher pH; the increased gastric pH resulting from nizatidine therapy may reduce the bioavailability of erlotinib. Increasing the dose of erlotinib without modifying the administration schedule is unlikely to compensate for loss of exposure. Erlotinib exposure was decreased by 33% and the Cmax by 54% when erlotinib was administered 2 hours after a single dose of an H2-antagonist. When administered at least 10 hours after an evening dose of an H2-antagonist and 2 hours before the morning dose, erlotinib exposure was decreased by 15% and Cmax by 17%.
Ferric Maltol: (Minor) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of H2-blockers can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. H2-blockers have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
Fosamprenavir: (Moderate) Monitor for decreased fosamprenavir efficacy if coadministered with H2-blockers. Concurrent use may decrease the plasma concentrations of fosamprenavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance.
Gefitinib: (Major) Avoid coadministration of nizatidine with gefitinib if possible due to decreased exposure to gefitinib, which may lead to reduced efficacy. If concomitant use is unavoidable, take gefitinib 6 hours after the last dose or 6 hours before the next dose of nizatidine. Gefitinib exposure is affected by gastric pH. Coadministration with high doses of an H2-blocker to maintain gastric pH above 5 decreased gefitinib exposure by 47%.
Infigratinib: (Moderate) Separate the administration of infigratinib and H2-receptor antagonists if concomitant use is necessary. Coadministration may decrease infigratinib exposure resulting in decreased efficacy. Administer infigratinib two hours before or ten hours after an H2-receptor antagonist.
Iron Salts: (Minor) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of H2-blockers can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. H2-blockers have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
Iron Salts: (Minor) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of H2-blockers can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. H2-blockers have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
Iron: (Minor) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of H2-blockers can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. H2-blockers have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
Itraconazole: (Moderate) When administering H2-blockers with the 100 mg itraconazole capsule and 200 mg itraconazole tablet formulations, systemic exposure to itraconazole is decreased. Conversely, exposure to itraconazole is increased when H2-blockers are administered with the 65 mg itraconazole capsule. Administer H2-blockers at least 2 hours before or 2 hours after the 100 mg capsule or 200 mg tablet. Monitor for increased itraconazole-related adverse effects if H2-blockers are administered with itraconazole 65 mg capsules.
Ketoconazole: (Major) Avoid use of H2-blockers with ketoconazole. Medications that increase gastric pH may impair ketoconazole absorption.
Ledipasvir; Sofosbuvir: (Major) Solubility of ledipasvir decreases as gastric pH increases; thus, coadministration of ledipasvir; sofosbuvir with H2-blockers may result in lower ledipasvir plasma concentrations. Ledipasvir; sofosbuvir can be administered with H2-blockers if given simultaneously or separated by 12 hours. The H2-blocker dose should not exceed a dose that is comparable to famotidine 40 mg twice daily.
Levoketoconazole: (Major) Avoid use of H2-blockers with ketoconazole. Medications that increase gastric pH may impair ketoconazole absorption.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Minor) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of H2-blockers can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. H2-blockers have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Minor) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of H2-blockers can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. H2-blockers have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
Mefloquine: (Moderate) H2-blockers may increase plasma concentrations of mefloquine. Patients on chronic mefloquine therapy might be at increased risk of adverse reactions, especially patients with a neurological or psychiatric history. In a small study involving 6 healthy subjects and 6 peptic ulcer patients, cimetidine increased the Cmax and AUC of mefloquine. In the study, the pharmacokinetics of mefloquine were determined after receiving a single oral mefloquine 500 mg dose alone and after 3-days of cimetidine 400 mg PO twice daily. In both healthy subjects and peptic ulcer patients, Cmax was increased 42.4% and 20.5%, respectively. The AUC was increased by 37.5% in both groups. Elimination half-life, total clearance, and volume of distribution were not significantly affected. An increase in adverse reactions was not noted.
Naproxen: (Moderate) Avoid concomitant use of enteric-coated, delayed-release naproxen and H2-blockers due to the gastric pH elevating effects of H2-blockers. Enteric-coated, delayed-release naproxen tablets are designed to dissolve at a pH of 6 or more.
Naproxen; Esomeprazole: (Moderate) Avoid concomitant use of enteric-coated, delayed-release naproxen and H2-blockers due to the gastric pH elevating effects of H2-blockers. Enteric-coated, delayed-release naproxen tablets are designed to dissolve at a pH of 6 or more.
Naproxen; Pseudoephedrine: (Moderate) Avoid concomitant use of enteric-coated, delayed-release naproxen and H2-blockers due to the gastric pH elevating effects of H2-blockers. Enteric-coated, delayed-release naproxen tablets are designed to dissolve at a pH of 6 or more.
Neratinib: (Major) Take neratinib at least 2 hours before the next dose of an H2-blocker or 10 hours after the last dose of an H2-blocker due to decreased absorption and systemic exposure of neratinib; the solubility of neratinib decreases with increasing pH of the GI tract. The Cmax and AUC of neratinib were reduced by 57% and 48%, respectively, when administered 2 hours after a daily dose of ranitidine 300 mg. The Cmax and AUC of neratinib were reduced by 44% and 32%, respectively, when administered 2 hours before ranitidine 150 mg twice daily (given approximately 12 hours apart).
Nilotinib: (Moderate) If concomitant use of these agents is necessary, administer the H2-blocker approximately 10 hours before and approximately 2 hours after the nilotinib dose. Nilotinib displays pH-dependent solubility with decreased solubility at a higher pH. The concomitant use of nilotinib and H2-blockers that elevate the gastric pH may reduce the bioavailability of nilotinib. In a study in healthy subjects, there was no significant change in nilotinib pharmacokinetics when a single 400-mg nilotinib dose was given 10 hours after and 2 hours prior to famotidine.
Nirogacestat: (Major) Avoid concomitant use of nirogacestat and H2 receptor blockers. Concurrent use may impair nirogacestat absorption which may decrease nirogacestat exposure and reduce its efficacy. Antacids may be used with nirogacestat but administration should be separated by at least 2 hours.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Minor) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of H2-blockers can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. H2-blockers have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Minor) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of H2-blockers can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. H2-blockers have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
Octreotide: (Moderate) Coadministration of oral octreotide with H2-blockers may require increased doses of octreotide. Coadministration of oral octreotide with drugs that alter the pH of the upper GI tract, including H2-blockers, may alter the absorption of octreotide and lead to a reduction in bioavailability.
Pazopanib: (Major) Avoid coadministration of pazopanib with H2-blockers due to decreased absorption of pazopanib, which may decrease efficacy. If concomitant administration with a gastric acid-reducing agent is unavoidable, consider the use of a short-acting antacid in place of an H2-blocker; separate administration of the short-acting antacid and pazopanib by several hours to avoid a reduction in pazopanib exposure. Concomitant use of pazopanib with a proton pump inhibitor decreased pazopanib exposure (AUC and Cmax) by approximately 40%.
Pexidartinib: (Moderate) Administer pexidartinib 2 hours before or 10 hours after H2-blockers as concurrent administration may reduce pexidartinib exposure. Although the effects of H2-blockers on pexidartinib pharmacokinetics have not been studied, other acid-reducing agents have been shown to decrease pexidartinib exposure by 50%.
Polyethylene Glycol; Electrolytes; Bisacodyl: (Minor) The concomitant use of bisacodyl tablets with H2-blockers can cause the enteric coating of the bisacody tablet to dissolve prematurely, leading to possible gastric irritation or dyspepsia. Avoid H2-blockers within 1 hour before or after the bisacodyl dosage.
Rilpivirine: (Moderate) Coadministration with nizatidine may significantly decrease rilpivirine plasma concentrations, potentially resulting in treatment failure. To decrease the risk of virologic failure, avoid use of nizatidine for at least 12 hours before and at least 4 hours after administering rilpivirine.
Risedronate: (Major) Use of H2-blockers with delayed-release risedronate tablets (Atelvia) is not recommended. Co-administration of drugs that raise stomach pH increases risedronate bioavailability due to faster release of the drug from the enteric coated tablet. This interaction does not apply to risedronate immediate-release tablets.
Secretin: (Major) Discontinue use of H2-blockers at least 2 days before administering secretin. Patients who are receiving H2-blockers at the time of stimulation testing may be hyperresponsive to secretin stimulation, falsely suggesting gastrinoma.
Selpercatinib: (Major) Avoid coadministration of selpercatinib with nizatidine due to the risk of decreased selpercatinib exposure which may reduce its efficacy. If concomitant use is unavoidable, take selpercatinib 2 hours before or 10 hours after administration of nizatidine. Coadministration with acid-reducing agents decreases selpercatinib plasma concentrations; however, no clinically significant differences in the pharmacokinetics of selpercatinib were observed when given under fasting conditions with multiple daily doses of another H2-receptor antagonist given 10 hours prior to and 2 hours after the selpercatinib dose.
Sodium Ferric Gluconate Complex; ferric pyrophosphate citrate: (Minor) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of H2-blockers can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. H2-blockers have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
Sofosbuvir; Velpatasvir: (Major) H2-blockers may be administered simultaneously with or 12 hours apart from velpatasvir. H2-blocker doses should not exceed doses comparable to famotidine 40 mg twice daily. Velpatasvir solubility decreases as pH increases; therefore, drugs that increase gastric pH are expected to decrease the concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Major) H2-blockers may be administered simultaneously with or 12 hours apart from velpatasvir. H2-blocker doses should not exceed doses comparable to famotidine 40 mg twice daily. Velpatasvir solubility decreases as pH increases; therefore, drugs that increase gastric pH are expected to decrease the concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy.
Sonidegib: (Moderate) Based on population PK analysis, the concomitant administration of a histamine-2-receptor antagonist such as nizatidine decreases the geometric mean sonidegib steady-state AUC (0-24 hours) value by 34%.
Sotorasib: (Major) Avoid coadministration of sotorasib and gastric acid-reducing agents, such as H2-receptor antagonists. Coadministration may decrease sotorasib exposure resulting in decreased efficacy. If necessary, sotorasib may be administered 4 hours before or 10 hours after a locally acting antacid. Coadministration with an H2-receptor antagonist decreased sotorasib exposure by 38% under fed conditions.
Sparsentan: (Major) Avoid concurrent use of sparsentan and H2 receptor antagonists due to the risk for decreased sparsentan exposure which may reduce its efficacy. Medications that affect gastric pH may reduce sparsentan absorption.
Sumatriptan; Naproxen: (Moderate) Avoid concomitant use of enteric-coated, delayed-release naproxen and H2-blockers due to the gastric pH elevating effects of H2-blockers. Enteric-coated, delayed-release naproxen tablets are designed to dissolve at a pH of 6 or more.
Thalidomide: (Moderate) Thalidomide and other agents that slow cardiac conduction such as H2-blockers should be used cautiously due to the potential for additive bradycardia.
Nizatidine competitively inhibits the binding of histamine to the H2-receptors on the gastric basolateral membrane of parietal cells, reducing basal and nocturnal gastric acid secretions. The drug also decreases the gastric acid response to stimuli such as food, caffeine, insulin, betazole, or pentagastrin. Nizatidine reduces the total volume of gastric juice, thus indirectly decreasing pepsin secretion. The drug does not appear to alter gastric motility, gastric emptying, esophageal pressures, biliary secretions, or pancreatic secretions. Nizatidine may aid in gastromucosal healing, and it may protect the mucosa from the irritant effects caused by aspirin and nonsteroidal antiinflammatory agents. H2-blockers, as single agents, do not erradicate H. pylori infection.
Nizatidine is administered orally.
The drug is roughly 35% protein-bound. Approximately 7% of an oral dose is metabolized in the liver to N2-monodesmethylnizatidine, which has H2-antagonist activity. Approximately 60% of unchanged drug and its metabolites are excreted in the urine and approximately 6% in the feces. Nizatidine is eliminated by both glomerular filtration and active tubular secretion. The elimination half-life is 1 to 2 hours.
-Route-Specific Pharmacokinetics
Oral Route
The bioavailability of nizatidine is about 95% in patients with normal renal function. The presence of food in the GI tract appears to increase the absorption of nizatidine. The drug distribution is unknown.
-Special Populations
Renal Impairment
The bioavailability of nizatidine is about 75% in patients with renal failure. The elimination half-life is 3.5 to 11 hours in functionally anephric patients.
Pediatrics
Children and Adolescents
Elimination of nizatidine and its metabolite is largely dependent on renal excretion. The pharmacokinetics of nizatidine in pediatric patients older than 1 year are comparable with that observed in adults with normal renal function. In children and adolescents 12 to 18 years of age, the half-life of a 150 mg single dose is 1.2 to 1.3 hours. The pharmacodynamic response to a comparable weight-based dose is equal and potentially greater in children as compared to adults.
Neonates and Infants
Elimination of nizatidine and its metabolite is largely dependent on renal excretion. The elimination of nizatidine and N-desmethylnizatidine are reduced in an age-related manner during the first year of life, consistent with immature renal function during this time of development. Preterm neonates would be expected to have longer half-lives than term neonates, consistent with immaturity of renal function associated with pre-term birth.