Nizatidine

Common side effects are:

• constipation,
• diarrhea,
• fatigue,
• headache,
• insomnia,
• muscle pain,
• nausea,
• vomiting,
• dizziness,
• confusion,
• depression, and
• agitation.

Serious but rare side effects include anemia, and a reduction in white blood cells or platelets. Hepatitis also has been reported.

Mechanism of Action

H2-receptor antagonist; blocks H2-receptors of gastric parietal cells, leading to inhibition of gastric secretions

Pharmacokinetics

Half-Life: 2.5-3hr (PO); 2-2.5hr (IV)

Peak Plasma Time: 2-3hr (PO); <15 min (IM)

Absorption: 50% (oral)

Bioavailability: 48-50% (PO); 90-100% (IM)

Protein Bound: 15%

Vd: 0.8-1.5 L/kg

Metabolism: Liver, unlike cimetidine, nizatidine does not inhibit microsomal enzymes

Metabolites: N-desmethylnizatidine (active), nizatidine N-oxide (inactive), nizatidine S-oxide (inactive)

Dialyzable: No

Clearance

• Total Body: 660-1000 mL/min
• Renal: 500 mL/min (Not dialyzable by HD)

Excretion

• Urine: 30% (PO); 70% (IV)
• Feces: <6%

Nizatidine is used to treat ulcers. Nizatidine can also prevent and treat heartburn. Nizatidine belongs to a group of medications called H2 antagonists which help by reducing the amount of acid your stomach produces.

Nizatidine is both an over-the-counter and a prescription medication. The over-the-counter form is used to prevent and treat heartburn. The prescription form is used to treat ulcers.

Prescription nizatadine is available as a capsule and oral liquid form which are normally given 1 to 2 times per day with or without food.

Over the counter nizatadine is available as extended release tablets and is taken once a day for relief. It can also prevent heartburn when taken 60 minutes to right before eating or drinking something that causes you heartburn.

Common side effects of nizatadine include headache, diarrhea, and runny nose.

Nizatidine is part of the drug class:

• H2 receptor antagonists

Nizatidine is a histamine-2 blocker that works by decreasing the amount of acid produced by the stomach.

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.

Usual Adult Dose for Duodenal Ulcer:

Initial: 300 mg orally once a day at bedtime, or alternatively may use 150 mg orally twice a day.
Maintenance: 150 mg orally once a day at bedtime.

Usual Adult Dose for Duodenal Ulcer Prophylaxis:

150 mg orally once a day at bedtime.

Usual Adult Dose for Gastric Ulcer:

300 mg orally once a day at bedtime, or alternatively may use 150 mg orally twice a day.

Usual Adult Dose for Erosive Esophagitis:

150 mg twice daily.

Usual Adult Dose for Gastroesophageal Reflux Disease:

150 mg twice daily.

Usual Adult Dose for Dyspepsia:

75 mg orally once or twice a day, taken right before or up to 60 minutes before eating.

Usual Pediatric Dose for Gastroesophageal Reflux Disease:

Investigational:

Greater than 1 year (n=26): In mild to moderate reflux esophagitis: 10 mg/kg/day divided in two doses for 8 weeks.

Greater than or equal to 4 to 11 years (n=104): 6 mg/kg/day divided in two doses, one dose given at 9 PM the night before surgery, and the other given at 6:30 AM the day of surgery.

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

Antisecretory Activity

Nizatidine significantly inhibited nocturnal gastric acid secretion for up to 12 hours. Nizatidine also significantly inhibited gastric acid secretion stimulated by food, caffeine, betazole, and pentagastrin (Table 1).

Pepsin

Oral administration of 75 mg to 300 mg of Nizatidine 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 mg to 300 mg of Nizatidine increased betazole-stimulated secretion of intrinsic factor.

Serum Gastrin

Nizatidine had no effect on basal serum gastrin concentration. No rebound of gastrin secretion was observed when food was ingested 12 hours after administration of Nizatidine.

Hormones

Nizatidine was not shown to affect the serum concentrations of gonadotropins, prolactin, growth hormone, antidiuretic hormone, cortisol, triiodothyronine, thyroxin, testosterone, 5α-dihydrotestosterone, androstenedione, or estradiol.

Nizatidine had no demonstrable antiandrogenic action.

The absolute oral bioavailability of Nizatidine exceeds 70%. Peak plasma concentrations (700 mcg/L to 1800 mcg/L for a 150 mg dose and 1400 mcg/L to 3600 mcg/L for a 300 mg dose) occur from 0.5 to 3 hours following the dose. A concentration of 1000 mcg/L is equivalent to 3 mcmol/L; a dose of 300 mg is equivalent to 905 mcmoles. Plasma concentrations 12 hours after administration are less than 10 mcg/L. The elimination half-life is 1 to 2 hours, plasma clearance is 40 L/h to 60 L/h, and the volume of distribution is 0.8 L/kg 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. Nizatidine 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-monodesmethylNizatidine, 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 oral 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 L/h 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 Nizatidine 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 Trials

In multicenter, double-blind, placebo-controlled studies in the United States, endoscopically diagnosed duodenal ulcers healed more rapidly following administration of Nizatidine, 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.

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

In 2 multi-center, double-blind, placebo-controlled clinical trials performed in the United States and Canada, Nizatidine 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 Nizatidine 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 less than 0.05). Of 99 patients on Nizatidine and 94 patients on placebo, Study 2 at the same dosage yielded similar results at 6 weeks (21% vs 11%, P less than 0.05) and at 12 weeks (29% vs 13%, P less than 0.01).

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

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.

Overdoses of 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 overdosage of 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 1200 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.

Nizatidine Capsules USP, for oral administration, are available as

150 mg

White opaque body and yellow opaque cap, imprinted “E 150” on the body and cap in black ink and supplied as:

NDC 0185-0150-60 bottles of 60

NDC 0185-0150-05 bottles of 500

300 mg

White opaque body and peach opaque cap, imprinted “E 300” on the body and cap in black ink and supplied as:

NDC 0185-0300-30 bottles of 30

NDC 0185-0300-01 bottles of 100

Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].

Dispense contents in a tight, light-resistant container as defined in the USP with a child-resistant closure, as required.

KEEP TIGHTLY CLOSED.

To report SUSPECTED ADVERSE REACTIONS, contact Sandoz Inc. at 1-800-525-8747 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

All brand names listed are the registered trademarks of their respective owners and are not trademarks of Sandoz Inc.

Manufactured by

Sandoz, Inc.

Princeton, NJ 08540

46192904

Rev. September 2016

MF0150REV09/16

NDC 0185-0150-60

Nizatidine Capsules, USP

150 mg

Rx only

60 Capsules

Sandoz

Manufacturer's 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

Administer with or without food.