Axid

Before taking nizatidine,

• tell your doctor and pharmacist if you are allergic to nizatidine or any other drugs.
• tell your doctor and pharmacist what prescription and nonprescription medications you are taking, especially aspirin or antacids such as Maalox or Mylanta, and vitamins.
• tell your doctor if you have or have ever had kidney or liver disease.
• tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking nizatidine, call your doctor.

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

Overdoses of Axid (nizatidine) have been reported rarely. The following is provided to serve as a guide should such an overdose be encountered.

Signs and Symptoms — There is little clinical experience with over-dosage of Axid (nizatidine) in humans. Test animals that received large doses of nizatidine have exhibited cholinergic-type effects, including lacrimation, salivation, emesis, miosis, and diarrhea. Single oral doses of 800 mg/kg in dogs and of 1,200 mg/kg in monkeys were not lethal. Intravenous median lethal doses in the rat and mouse were 301 mg/kg and 232 mg/kg respectively.

Treatment — To obtain up-to-date information about the treatment of overdose, a good resource is your certified Regional Poison Control Center. Telephone numbers of certified poison control centers are listed in the Physicians' Desk Reference (PDR). In managing overdosage, consider the possibility of multiple drug overdoses, interaction among drugs, and unusual drug kinetics in your patient.

If overdosage occurs, use of activated charcoal, emesis, or lavage should be considered along with clinical monitoring and supportive therapy. The ability of hemodialysis to remove nizatidine from the body has not been conclusively demonstrated; however, due to its large volume of distribution, nizatidine is not expected to be efficiently removed from the body by this method.

>10%

Headache (17%)

1-10%

Abdominal pain

Anxiety

Constipation

Diarrhea

Dizziness

Insomnia

Nausea/vomiting

Pruritus

<1%

Anemia

Increased LFT's

Axid is used to treat duodenal ulcers and stomach ulcers.

This medication may be prescribed for other uses. Please contact your doctor or pharmacist for more information.

Axid is part of the drug class:

• H2 receptor antagonists

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include blurred vision, watery eyes, drooling, nausea, vomiting, or diarrhea.

Administration

Oral Administration

Administer orally1 2 3 4 5 without regard to meals.2 6 12

Antacids may be used as necessary for pain relief.2 5 27 28 29 30 31 32 33 34

Tablet for self-medication should be administered with a glass of water.b

For gastroesophageal reflux, once daily dosage not considered appropriate.165

For duodenal ulcer treatment, the advantage of administration once daily at bedtime (when convenience is important for compliance) over twice-daily administration has not been determined.2

For gastric ulcer treatment in adults, administer in divided doses twice daily or once daily at bedtime.1 45 46 47

Dosage

Pediatric Patients

Children ≥12 years of age: 150 mg twice daily as oral solution for up to 8 weeks.c

75 mg once or twice daily (maximum 150 mg in 24 hours continuously for 2 weeks) or as directed by clinician.b

75 mg once or twice daily (immediately or up to 1 hour before ingestion of causative food or beverage); maximum 150 mg in 24 hours continuously for 2 weeks or as directed by clinician.b

Adults

150 mg twice daily for up to 12 weeks.1 2 40 41 42

300 mg at bedtime also has been used, but is less effective2 9 39 130 and not considered appropriate therapy.165

75 mg once or twice daily (maximum 150 mg in 24 hours continuously for 2 weeks) or as directed by clinician.b

75 mg once or twice daily (immediately or up to 1 hour before ingestion of causative food or beverage); maximum 150 mg in 24 hours continuously for 2 weeks or as directed by clinician.b

300 mg once daily at bedtime, or 150 mg twice daily.1 2

Healing may occur within 2 weeks in some, and within 4 weeks in most patients;1 2 27 28 29 30 31 32 33 34 some patients may benefit from an additional 4 weeks of therapy.1 2 Occasionally may be necessary to continue full-dose therapy for >6–8 weeks.1 2

Safety and efficacy of continuing full-dose therapy for > 8 weeks have not been established.1 2

150 mg once daily at bedtime.1 2 35 36

Some clinicians recommend continuing maintenance therapy for at least 1 year.4

Safety and efficacy of continuing maintenance therapy beyond 1 year have not been established.1

150 mg twice daily or 300 mg once daily at bedtime for up to 8 weeks.1 45 46 47

Complete healing of gastric ulcers usually occurs within 8 weeks.1 4 5 28 45 46 47

Safety and efficacy for >8 weeks have not been established.1 126

Prescribing Limits

Pediatric Patients

Maximum 300 mg daily for 8 weeks.c

Maximum 150 mg in 24 hours continuously for 2 weeks.b

Maximum 150 mg in 24 hours continuously for 2 weeks.b

Adults

Safety and efficacy for >12 weeks not established.1 2 40 41 42

Maximum 150 mg in 24 hours continuously for 2 weeks.b

Maximum 150 mg in 24 hours continuously for 2 weeks.b

Safety and efficacy for >8 weeks not established.1 2

Safety and efficacy for >1 year not established.1

Safety and efficacy for >8 weeks not established.1 126

Special Populations

Renal Impairment

Modify doses and/or frequency of administration to the degree of renal impairment; clinical efficacy of recommended dosages have not been systematically evaluated.1 2 22

Geriatric Patients

Careful dosage selection recommended due to possible age-related decreases in renal function.1 2 (See Renal Impairment under Cautions.) Monitoring renal function may be useful.a

Axid is a competitive, reversible inhibitor of histamine at the histamine H2-receptors, particularly those in the gastric parietal cells.

Antisecretory Activity1. Effects on Acid Secretion: Axid significantly inhibited nocturnal gastric acid secretion for up to 12 hours. Axid also significantly inhibited gastric acid secretion stimulated by food, caffeine, betazole, and pentagastrin (Table 1).

2. Effects on Other Gastrointestinal SecretionsPepsin:
Oral administration of 75 to 300 mg of Axid did not affect pepsin activity in gastric secretions. Total pepsin output was reduced in proportion to the reduced volume of gastric secretions.

Intrinsic Factor: Oral administration of 75 to 300 mg of Axid increased betazole-stimulated secretion of intrinsic factor.

Serum Gastrin Concentration: Axid had no effect on basal serum gastrin concentration. No rebound of gastrin secretion was observed when food was ingested 12 hours after administration of Axid.

3. Other Pharmacologic Actions-

4. PharmacokineticsThe absolute oral bioavailability of nizatidine exceeds 70%. Peak plasma concentrations (700 to 1,800 µg/L for a 150-mg dose and 1,400 to 3,600 µg/L for a 300-mg dose) occur from 0.5 to 3 hours following the dose. A concentration of 1,000 µg/L is equivalent to 3 µmol/L; a dose of 300 mg is equivalent to 905 µmoles. Plasma concentrations 12 hours after administration are less than 10 µg/L. The elimination half-life is 1 to 2 hours, plasma clearance is 40 to 60 L/h, and the volume of distribution is 0.8 to 1.5 L/kg. Because of the short half-life and rapid clearance of nizatidine, accumulation of the drug would not be expected in individuals with normal renal function who take either 300 mg once daily at bedtime or 150 mg twice daily. Axid exhibits dose proportionality over the recommended dose range.

The oral bioavailability of nizatidine is unaffected by concomitant ingestion of the propantheline. Antacids consisting of aluminum and magnesium hydroxides with simethicone decrease the absorption of nizatidine by about 10%. With food, the AUC and Cmax increase by approximately 10%.

In humans, less than 7% of an oral dose is metabolized as N2-monodes-methylnizatidine, an H2-receptor antagonist, which is the principal metabolite excreted in the urine. Other likely metabolites are the N2-oxide (less than 5% of the dose) and the S-oxide (less than 6% of the dose).

More than 90% of an orally administered dose of nizatidine is excreted in the urine within 12 hours. About 60% of an oral dose is excreted as unchanged drug. Renal clearance is about 500 mL/min, which indicates excretion by active tubular secretion. Less than 6% of an administered dose is eliminated in the feces.

Moderate to severe renal impairment significantly prolongs the half-life and decreases the clearance of nizatidine. In individuals who are functionally anephric, the half-life is 3.5 to 11 hours, and the plasma clearance is 7 to 14 L/h. To avoid accumulation of the drug in individuals with clinically significant renal impairment, the amount and/or frequency of doses of Axid should be reduced in proportion to the severity of dysfunction (see Dosage and Administration).

Approximately 35% of nizatidine is bound to plasma protein, mainly to α1-acid glycoprotein. Warfarin, diazepam, acetaminophen, propantheline, phenobarbital, and propranolol did not affect plasma protein binding of nizatidine in vitro.

Clinical Trials1. Active Duodenal Ulcer: In multicenter, double-blind, placebo-controlled studies in the United States, endoscopically diagnosed duodenal ulcers healed more rapidly following administration of Axid, 300 mg h.s. or 150 mg b.i.d., than with placebo (Table 2). Lower doses, such as 100 mg h.s., had slightly lower effectiveness.

*P<0.01 as compared with placebo.†P<0.05 as compared with placebo.

2. Maintenance of Healed Duodenal Ulcer: Treatment with a reduced dose of Axid has been shown to be effective as maintenance therapy following healing of active duodenal ulcers. In multicenter, double-blind, placebo-controlled studies conducted in the United States, 150 mg of Axid taken at bedtime resulted in a significantly lower incidence of duodenal ulcer recurrence in patients treated for up to 1 year (Table 3).

 *P<0.001 as compared with placebo.

3. Gastroesophageal Reflux Disease (GERD): In 2 multi-center, double-blind, placebo-controlled clinical trials performed in the United States and Canada, Axid was more effective than placebo in improving endoscopically diagnosed esophagitis and in healing erosive and ulcerative esophagitis.

In patients with erosive or ulcerative esophagitis, 150 mg b.i.d. of Axid given to 88 patients compared with placebo in 98 patients in Study 1 yielded a higher healing rate at 3 weeks (16% vs 7%) and at 6 weeks (32% vs 16%, P<0.05). Of 99 patients on Axid and 94 patients on placebo, Study 2 at the same dosage yielded similar results at 6 weeks (21% vs 11%, P<0.05) and at 12 weeks (29% vs 13%, P<0.01).

In addition, relief of associated heartburn was greater in patients treated with Axid. Patients treated with Axid consumed fewer antacids than did patients treated with placebo.

4. Active Benign Gastric Ulcer: In a multicenter, double-blind, placebo-controlled study conducted in the United States and Canada, endoscopically diagnosed benign gastric ulcers healed significantly more rapidly following administration of nizatidine than of placebo (Table 4).

In a multicenter, double-blind, comparator-controlled study in Europe, healing rates for patients receiving nizatidine (300 mg h.s. or 150 mg b.i.d.) were equivalent to rates for patients receiving a comparator drug, and statistically superior to historical placebo control rates.

Nizatidine is in a group of drugs called histamine-2 blockers. Nizatidine works by decreasing the amount of acid the stomach produces.

Nizatidine is used to treat ulcers in the stomach and intestines. Nizatidine also treats heartburn and erosive esophagitis caused by gastroesophageal reflux disease (GERD), a condition in which acid backs up from the stomach into the esophagus.

Nizatidine may also be used for purposes not listed in this medication guide.

Your pharmacist can provide more information about nizatidine.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2013 Cerner Multum, Inc. Version: 7.02. Revision date: 12/15/2010.

Your use of the content provided in this service indicates that you have read,understood and agree to the End-User License Agreement,which can be accessed by clicking on this link.

Summary of Use during Lactation

Because of the low levels of nizatidine in breastmilk, amounts ingested by the infant are small and would not be expected to cause any adverse effects in breastfed infants. No special precautions are required. Histamine H2-antagonists with more extensive use might be preferred in newborns.

Drug Levels

Maternal Levels.Three women who had been breastfeeding for 3 to 8 months were given nizatidine 150 mg orally every 12 hours for 5 doses. Milk nizatidine was measured at several times after the first and fifth doses. Peak milk levels of about 1.2 mg/L occurred about 2 hours after the dose. The mothers excreted a combined average of 96 mcg (range 55 to 137 mcg) of nizatidine into breast milk over the 12 hours after the first and last doses which was less than 0.1% of the mothers' total dose. The half-life in milk averaged less than 2 hours.[1]

Infant Levels. Relevant published information was not found as of the revision date.

Effects in Breastfed Infants

Relevant published information was not found as of the revision date.

Effects on Lactation and Breastmilk

Histamine H2-receptor blockade is known to stimulate prolactin secretion.[2] No reports of hyperlproactinemia, galactorrhea or effects on breastfeeding women caused by nizatadine were found as of the revision date. The maternal prolactin level in a mother with established lactation may not affect her ability to breastfeed.

Alternate Drugs to Consider

Cimetidine, Famotidine, Omeprazole, Pantoprazole, Ranitidine, Sucralfate

References

1. Obermeyer BD, Bergstrom RF, Callaghan JT et al. Secretion of nizatidine into human breast milk after single and multiple doses. Clin Pharmacol Ther. 1990;47:724-30. PMID: 1972674

2. Knigge UP. Histaminergic regulation of prolactin secretion. Dan Med Bull. 1990;37:109-24. PMID: 2188799