Consumer medicine information

Tacidine

Nizatidine

BRAND INFORMATION

Brand name

Tacidine

Active ingredient

Nizatidine

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Tacidine.

What is in this leaflet

This leaflet answers some common questions about TACIDINE. It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking TACIDINE against the benefits they expect it will have for you.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine. You may need to read it again.

What TACIDINE is used for

TACIDINE contains the active ingredient nizatidine.

TACIDINE belongs to a group of medicines called histamine (H2) antagonist or histamine (H2) blockers. These medicines work by reducing the amount of stomach acid produced which in turn reduces the pain and allows the ulcers and/or reflux disease to heal in most people.

Ulcers
TACIDINE is used to treat both gastric ulcers and duodenal ulcers. A gastric ulcer occurs in the stomach. A duodenal ulcer occurs in the duodenum (which is part of your small intestine). The ulcers can be caused in part by too much acid being made in the stomach.

TACIDINE is also used to help stop duodenal ulcers from coming back.

Reflux Disease
TACIDINE is also used to treat reflux oesophagitis or reflux disease. This is caused by "washing back" (reflux) of food and acid from the stomach into the food pipe (also known as the oesophagus).

Reflux causes burning sensation in the chest rising up to the throat (heartburn) and most often occurs after eating or at night.

Ask your doctor if you have any questions about why this medicine has been prescribed for you. Your doctor may have prescribed it for another reason.

TACIDINE is not recommended for use in children, as the safety and effectiveness have not been established.

This medicine is not addictive.

This medicine is available only with a doctor's prescription.

Before you take TACIDINE

When you must not take it

Do not take TACIDINE if you have an allergy to:

  • any medicine containing nizatidine
  • any other histamine (H2) blocking medicine
  • any of the ingredients listed at the end of this leaflet

Some of the symptoms of an allergic reaction may include:

  • shortness of breath
  • wheezing or difficulty breathing
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching or hives on the skin

Do not take this medicine after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering. If it has expired or is damaged, return it to your pharmacist for disposal.

If you are not sure whether you should start taking this medicine, talk to your doctor.

Before you start to take it

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you have or have had any of the following medical conditions:

  • kidney disease
  • liver disease
  • chronic lung disease
  • diabetes
  • a weakened immune system or lowered resistance to infection, sometimes caused by certain diseases or treatments

Tell your doctor if you are pregnant or plan to become pregnant or are breastfeeding. Your doctor can discuss with you the risks and benefits involved.

The active ingredient in TACIDINE passes into breast milk and there is a possibility that your baby may be affected.

Tell your doctor if you plan to have surgery.

If you have not told your doctor about any of the above, tell them before you start taking TACIDINE.

Taking other medicines

Tell your doctor or pharmacist if you are taking any other medicines, including any that you get without a prescription from your pharmacy, supermarket or health food shop.

Some medicines and TACIDINE may interfere with each other. These include:

  • aspirin
  • certain antacids used to treat heartburn and indigestion such as Mylanta and Gelusil

These medicines may be affected by TACIDINE or may affect how well it works. You may need different amounts of your medicines, or you may need to take different medicines.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking this medicine.

How to take TACIDINE

Follow all directions given to you by your doctor or pharmacist carefully. They may differ from the information contained in this leaflet.

If you do not understand the instructions on the pack, ask your doctor or pharmacist for help.

How much to take

The dose varies from person to person:

  • duodenal and stomach ulcers - the recommended dosage is 150 mg twice a day or 300 mg once in the evening
  • to stop duodenal ulcers from coming back - the usual dosage is 150 mg once daily
  • reflux disease - the recommended dosage is 150 mg twice daily

Elderly people and those who have kidney problems may need to take a lower dose.

How to take it

Swallow the capsules whole with a full glass of water.

When to take it

Take your medicine at about the same time each day. Taking it at the same time each day will have the best effect. It will also help you remember when to take it.

TACIDINE can be taken with or without food.

The 150 mg capsule is usually taken twice a day - one capsule in the morning and one capsule in the evening before you go to bed.

The 300 mg capsule is usually taken once a day at bedtime.

How long to take it

Continue taking your medicine for as long as your doctor tells you.

This medicine helps to control your condition but does not cure it. It is important to keep taking your medicine even if you feel well.

If you forget to take it

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to.

Otherwise, take it as soon as you remember, and then go back to taking your medicine as you would normally.

Do not take a double dose to make up for the dose you missed. This may increase the chance of you getting an unwanted side effect.

If you are not sure what to do, ask your doctor or pharmacist.

If you have trouble remembering to take your medicine, ask your pharmacist for some hints.

If you take too much (overdose)

Immediately telephone your doctor or the Poisons Information Centre (telephone 13 11 26) for advice, or go to Accident and Emergency at the nearest hospital, if you think that you or anyone else may have taken too much TACIDINE. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

While you are taking TACIDINE

Things you must do

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are taking TACIDINE.

Tell any other doctors, dentists and pharmacists who treat you that you are taking this medicine.

If you are going to have surgery, including dental surgery, tell the surgeon, anaesthetist or dentist that you are taking this medicine. It may affect other medicines used during surgery.

If you become pregnant while taking this medicine, tell your doctor immediately.

Keep all of your doctor's appointments so that your progress can be checked.

Things you must not do

Do not take TACIDINE to treat any other complaints unless your doctor tells you to.

Do not give your medicine to anyone else, even if they have the same condition as you.

Do not stop taking your medicine or lower the dosage without checking with your doctor.

If you stop taking your medicine too soon then your condition may not have been properly treated.

Things to be careful of

Be careful driving or operating machinery until you know how TACIDINE affects you. This medicine may cause dizziness or light-headedness in some people. If you have any of these symptoms, do not drive, operate machinery or do anything else that could be dangerous.

Things that would be helpful for your condition

Some self-help measures suggested below may help your condition. Talk to your doctor or pharmacist about these measures and for more information.

  • alcohol - your doctor may advise you to limit your alcohol intake
  • aspirin and other medicines used to treat arthritis/period pain/headaches - these medicines may irritate the stomach and may make your condition worse. Your doctor or pharmacist may suggest other medicines you can take
  • caffeine - your doctor may advise you to limit the number of drinks which contain caffeine, such as coffee, tea, cocoa and cola drinks, as the caffeine may irritate your stomach
  • eating habits - eat smaller, more frequent meals. Eat slowly and chew your food carefully. Try not to rush at meal times
  • smoking - your doctor may advise you to stop smoking or at least cut down

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking TACIDINE.

This medicine helps most people with ulcers or reflux disease, but it may have unwanted side effects in a few people. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

Do not be alarmed by the following list of side effects. You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor or pharmacist if you notice any of the following and they worry you:

  • sweating
  • itchy skin rash or hives
  • impotence

The above list includes the more common side effects of your medicine. They are usually mild and short-lived.

Tell your doctor immediately if you notice any of the following:

  • yellowing of the whites of the eyes or skin, also called jaundice
  • dark urine
  • breast enlargement/tenderness
  • symptoms of anaemia, which may include tiredness, dizziness and looking pale
  • bleeding or bruising more easily than normal
  • confusion

The above list includes serious side effects that may require medical attention.

If any of the following happen, tell your doctor immediately or go to Accident and Emergency at the nearest hospital:

  • vomiting blood or food
  • passing black (blood-stained) bowel motions
  • symptoms of a severe allergic reaction which may include skin rash, itching or hives; swelling of the face, lips or tongue which may cause difficulty in swallowing or breathing; wheezing or shortness of breath

The above list includes very serious side effects. You may need urgent medical attention or hospitalisation.

Tell your doctor or pharmacist if you notice anything that is making you feel unwell.

Other side effects not listed above may also occur in some people.

After taking TACIDINE

Storage

Keep your capsules in the pack until it is time to take them. If you take the capsules out of the pack they may not keep well.

Keep your capsules in a cool dry place where the temperature stays below 25°C.

Do not store TACIDINE or any other medicine in the bathroom or near a sink. Do not leave it on a window sill or in the car. Heat and dampness can destroy some medicines.

Keep it where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

If your doctor tells you to stop taking this medicine, or the expiry date has passed, ask your pharmacist what to do with any medicine that is left over.

Product description

What it looks like

TACIDINE capsules are available in 2 strengths:

  • TACIDINE 150 mg strength - hard gelatin capsule where one half of the capsule is pale yellow and has "NZ 150" printed in black. The other half of the capsule is dark yellow and has "G" printed in black
    Each pack contains 60 capsules.
  • TACIDINE 300 mg strength - hard, light brown, gelatin capsule with "NZ 300" printed in black on one half of the capsule and "G" printed in black on the other half
    Each pack contains 30 capsules.

Ingredients

TACIDINE contains either 150 mg or 300 mg of nizatidine as the active ingredient.

The capsule also contains:

  • croscarmellose sodium
  • pregelatinised maize starch
  • purified talc
  • magnesium stearate
  • quinoline yellow CI47005 [E104] (150 mg only)
  • allura red AC CI16035 [E129] (150 mg only)
  • iron oxide red CI77491[E172] (300 mg only)
  • iron oxide yellow CI77492 [E172]
  • titanium dioxide [E171]
  • gelatin
  • black Ink SW-9008/SW-9009

The capsules are gluten free.

Sponsor

Alphapharm Pty Limited
Level 1, 30 The Bond
30-34 Hickson Road
Millers Point NSW 2000
www.mylan.com.au

Australian registration numbers:

TACIDINE 150 mg - AUST R 94204

TACIDINE 300 mg - AUST R 94205

This leaflet was prepared in July 2019.

tacidine_cmi\Jul19/00

Published by MIMS September 2019

BRAND INFORMATION

Brand name

Tacidine

Active ingredient

Nizatidine

Schedule

S4

 

1 Name of Medicine

Nizatidine.

6.7 Physicochemical Properties

Nizatidine is an off-white to buff crystalline solid that is sparingly soluble in water. Pharmacologically, it is a histamine H2-receptor antagonist.
Chemical name: N-[2-[[[2-(dimethylamino) methyl]-4-thiazolyl]- methyl]thio]- ethyl]-N'-methyl-2-nitro-1, 1-ethenediamine.
Molecular formula: C12H21N5O2S2.
Molecular weight: 331.46.

Chemical structure.


CAS number.

76963-41-2.

2 Qualitative and Quantitative Composition

Tacidine capsules contain 150 mg or 300 mg of nizatidine as the active ingredient.
For the full list of excipients, see section 6.1 List of Excipients.

3 Pharmaceutical Form

Tacidine 150 capsules.

Hard gelatin capsule with a pale yellow body and dark yellow cap. The body has "NZ 150" and the cap has "G" printed in black.

Tacidine 300 capsules.

Hard gelatin capsule with a light brown body and cap. The body has "NZ 300" and the cap has "G" printed in black.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

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

Antisecretory activity.

Effects on acid secretion.

Nizatidine significantly inhibits basal and nocturnal gastric acid secretion for up to 12 hours. Nizatidine also significantly inhibits gastric acid secretion stimulated by food, caffeine, betazole and pentagastrin in a dose dependent manner. Rebound hypersecretion of gastric acid may occur after cessation of the drug.

Effects on other gastrointestinal secretions. Pepsin.

Oral administration of 75 to 300 mg of nizatidine does not affect pepsin activity in gastric secretions. Total pepsin output is reduced in proportion to the reduced volume of gastric secretions.

Intrinsic factor.

Intrinsic factor is not decreased in subjects administered nizatidine.

Serum gastrin.

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

Other pharmacologic actions.

Hormones.

Nizatidine was not shown to affect the serum concentrations of gonadotropins, growth hormone, antidiuretic hormone, cortisol, triiodothyronine, thyroxine, testosterone, 5α-dihydrotestosterone, androstenedione or oestradiol. With acute nizatidine administration, transient increases in serum prolactin have been observed in male animals.
Nizatidine had no demonstrable antiandrogenic action.

Clinical trials.

1. Active duodenal ulcer.

In multicentre, double-blind, placebo-controlled studies, endoscopically diagnosed duodenal ulcers healed more rapidly following administration of nizatidine 300 mg at bedtime or 150 mg twice daily than with placebo. Lower doses, such as 100 mg at bedtime, had slightly lower effectiveness.

2. Maintenance of healed duodenal ulcer.

In multicentre, double-blind, comparator-controlled studies, the healing rates following the administration of nizatidine (n = 388) were 81% within 4 weeks and 92% within 8 weeks.
Treatment with a reduced dose of nizatidine has been shown to be effective as maintenance therapy following healing of active duodenal ulcers. In multicentre, double-blind, placebo-controlled studies, 150 mg of nizatidine taken in the evening resulted in a significantly lower incidence of duodenal ulcer recurrence in patients treated for up to 1 year.

3. Benign gastric ulcer.

In multicentre, double-blind, comparator-controlled studies, patients received nizatidine 150 mg twice daily or nizatidine 300 mg in the evening. Healing rates in both dosage groups (66.2% and 65.2%, respectively) were not statistically different. Analysis of symptomatic responses showed that 68-76% of patients were symptom free after 4 weeks therapy.

4. Gastroesophageal reflux disease (reflux oesophagitis).

In multicentre, double-blind, placebo-controlled clinical trials, nizatidine was more effective than placebo in improving endoscopically diagnosed oesophagitis and in healing erosive and ulcerative oesophagitis.
In a study in patients with erosive or ulcerative oesophagitis, nizatidine 150 mg twice daily, compared with placebo, yielded a higher healing rate at 3 weeks (16% vs 7%) and at 6 weeks (32% vs 16%, p < 0.05). In another study, nizatidine 150 mg twice daily compared to placebo treatment, showed a higher healing rate 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 nizatidine. Patients treated with nizatidine consumed fewer antacids than did patients treated with placebo.

5.2 Pharmacokinetic Properties

Absorption.

The onset is half an hour while the duration of action is up to 12 hours. The absolute oral bioavailability of nizatidine exceeds 70%.
The oral bioavailability of nizatidine is unaffected by concomitant ingestion of propantheline. Antacids consisting of aluminium and magnesium hydroxides with simethicone decrease the absorption of nizatidine by about 10%. With food the AUC and Cmax increase by approximately 10%.
Charcoal has also been shown to reduce oral bioavailability of nizatidine. This reduction is in the range of 20 to 25%.

Distribution.

Peak plasma concentrations (700 to 1,800 microgram/L for a 150 mg dose and 1,400 to 3,600 microgram/L for a 300 mg dose) occur from 0.5 to 3 hours following the dose. A concentration of 1,000 microgram/L is equivalent to 3 micromol/L; a dose of 300 mg is equivalent to 905 micromoles. Plasma concentrations 12 hours after administration are less than 10 microgram/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 in the evening or 150 mg twice daily. Nizatidine exhibits dose proportionality over the recommended dose range.
Approximately 35% of nizatidine is bound to plasma protein, mainly to alpha 1-acid glycoprotein. Warfarin, diazepam, paracetamol, propantheline, phenobarbitone and propranolol did not affect plasma protein binding of nizatidine in vitro.

Metabolism.

Less than 7% of an oral dose is metabolised as N2-monodesmethyl-nizatidine, 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).

Excretion.

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 faeces.

Pharmacokinetics in special populations.

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 nizatidine should be reduced in proportion to the severity of dysfunction (see Section 4.2 Dose and Method of Administration).

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

A two-year oral carcinogenicity study in rats with doses as high as 500 mg/kg/day (about 80 times the recommended daily therapeutic dose) showed no evidence of a carcinogenic effect. There was a dose related increase in the density of enterochromaffin-like (ECL) cells in the gastric oxyntic mucosa. In a two-year study in mice, there was no evidence of a carcinogenic effect in male mice, although hyperplastic nodules of the liver were increased in the high dose males as compared to placebo. Female mice given the high dose of nizatidine (2,000 mg/kg/day, about 330 times the human dose) showed marginally statistically significant increases in hepatic carcinoma and hepatic nodular hyperplasia with no numerical increase seen in any of the other dose groups. The rate of hepatic carcinoma in the high dose animals was within the historical control limits seen for the strain of mice used. The female mice were given a dose higher than the maximum tolerated dose, as indicated by excessive (30%) weight decrement as compared with concurrent controls and evidence of mild liver injury (transaminase elevations). The occurrence of a marginal finding at high dose only in animals given an excessive and somewhat hepatotoxic dose, with no evidence of a carcinogenic effect in rats, male mice and female mice (given up to 360 mg/kg/day, about 60 times the human dose), and a negative mutagenicity battery, are not considered evidence of a carcinogenic potential for nizatidine.

Mutagenicity.

Nizatidine was not mutagenic in a battery of tests performed to evaluate its potential genetic toxicity, including bacterial mutation tests, unscheduled DNA synthesis, sister chromatid exchange, mouse lymphoma assay, chromosome aberration tests, and a micronucleus test.

4 Clinical Particulars

4.1 Therapeutic Indications

Tacidine is indicated for up to 8 weeks for the treatment of active duodenal ulcer. In most patients, the ulcer will heal within 4 weeks.
Tacidine is also indicated for maintenance therapy for duodenal ulcer patients, at a reduced dosage of 150 mg at bedtime, after healing of the active duodenal ulcer. Continuous therapy with nizatidine for longer than 1 year has not been studied.
Tacidine is indicated for up to 8 weeks for the treatment of benign gastric ulcer.
Tacidine is indicated for up to 12 weeks for the treatment of oesophagitis, including erosive and ulcerative oesophagitis and associated heartburn due to reflux.

4.3 Contraindications

Nizatidine is contraindicated in patients with known hypersensitivity to the drug, and because cross sensitivity in this class of compounds has been observed, nizatidine should not be administered to patients with a history of hypersensitivity to other H2-receptor antagonists.

4.4 Special Warnings and Precautions for Use

Gastric malignancy.

Symptomatic response to nizatidine therapy does not preclude the presence of gastric malignancy. Prior to treatment, care should be taken to exclude the possibility of malignant gastric ulceration.

Nosocomial pulmonary infections.

There is a possibility of nosocomial pulmonary infections associated with bacterial colonisation of the stomach in patients in intensive care units receiving drugs which suppress acid secretion.

Use in hepatic impairment.

Pharmacokinetic studies in patients with hepato-renal syndrome have not been done. Part of the dose of nizatidine is metabolised in the liver. Nizatidine cannot be recommended in patients with hepatic failure. In patients with normal renal function and uncomplicated hepatic dysfunction, the disposition of nizatidine is similar to that in normal subjects.

Use in renal impairment.

Because nizatidine is excreted primarily by the kidney, dosage should be reduced in patients with moderate to severe renal insufficiency (see Section 4.2 Dose and Method of Administration).

Use in the elderly.

Ulcer healing rates in elderly patients are similar to those in younger age groups. The incidence rates of adverse events and laboratory test abnormalities are also similar to those seen in other age groups. Age alone may not be an important factor in the disposition of nizatidine. Nizatidine is known to be substantially excreted by the kidney, and the toxic reactions to this drug may be greater in patients with impaired renal function. Elderly patients are more likely to have reduced renal function. Care should be taken in the dose selection in this patient group and may be useful to monitor renal function (see Section 4.2 Dose and Method of Administration).
In patients such as the elderly, persons with chronic lung disease, diabetes or the immunocompromised, there may be an increased risk of developing community acquired pneumonia. A large epidemiological study showed an increased risk of developing community acquired pneumonia in current users of H2-receptor antagonists versus those that had stopped treatment, with an observed adjusted relative risk of 1.63 (95% Cl, 1.07-2.48).

Paediatric use.

Safety and effectiveness in children have not been established.

Effects on laboratory tests.

False-positive tests for urobilinogen with Multistix may occur during therapy with nizatidine.

4.5 Interactions with Other Medicines and Other Forms of Interactions

No interactions have been observed between nizatidine and theophylline, chlordiazepoxide, lorazepam, lidocaine (lignocaine), phenytoin, warfarin, aminophylline, diazepam and metoprolol. Nizatidine does not inhibit the cytochrome P-450-linked drug metabolising enzyme system; therefore, drug interactions mediated by inhibition of hepatic metabolism are not expected to occur. However, nizatidine and other histamine H2-receptor antagonists can reduce the gastric absorption of drugs whose absorption is dependent on an acidic gastric pH. In patients given very high doses (3,900 mg) of aspirin daily, increases in serum salicylate levels were seen when nizatidine, 150 mg twice daily, was administered concurrently.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

In a 2-generation perinatal and postnatal fertility study in rats, doses of nizatidine up to 650 mg/kg/day produced no adverse effects on the reproductive performance of parental animals or their progeny.
(Category B3)
Oral reproduction studies in rats at doses up to 1,500 mg/kg and in Dutch Belted rabbits at doses up to 275 mg/kg, revealed no evidence of impaired fertility or teratogenic effect. At doses above 275 mg/kg, treated rabbits had abortions, decreased number of live foetuses and depressed foetal weights. On intravenous administration to pregnant New Zealand white rabbits, nizatidine at 20 mg/kg produced cardiac enlargement, coarctation of the aortic arch and cutaneous oedema in 1 foetus and at 50 mg/kg it produced ventricular anomaly, distended abdomen, spina bifida, hydrocephaly and enlarged heart in 1 foetus.
There are, however, no adequate and well-controlled studies in pregnant women. It is also not known whether nizatidine can cause foetal harm when administered to pregnant women or can affect reproduction capacity.
Nizatidine should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus.
Studies conducted in lactating women have shown that 0.1% of the administered oral dose of nizatidine is secreted in human milk in proportion to plasma concentrations. Because of the growth depression in pups reared by lactating rats treated with nizatidine, a decision should be made whether to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother.

4.8 Adverse Effects (Undesirable Effects)

Nizatidine has been shown to be generally well tolerated. The safety profile is at least as good, if not better, than other H2-receptor antagonists.
Placebo-controlled trials conducted included over 2,600 patients given nizatidine and over 1,700 given placebo. Among the adverse events in the placebo-controlled trials, anaemia (0.2% vs 0%) and urticaria (0.5% vs 0.1%) were significantly more common in the nizatidine group.

Hepatic.

Hepatocellular injury, evidenced by elevated liver enzyme tests (SGOT [AST], SGPT [ALT], or alkaline phosphatase), occurred in some patients and was possibly or probably related to nizatidine. In some cases there was marked elevation of SGOT, SGPT enzymes (greater than 500 IU/L) and in a single instance SGPT was greater than 2,000 IU/L. The overall rate of occurrences of elevated liver enzymes and elevations to 3 times the upper limit of normal, however, did not significantly differ from the rate of liver enzyme abnormalities in placebo treated patients. All abnormalities were reversible after discontinuation of nizatidine.
Rare cases of hepatitis and jaundice and cholestatic or mixed hepato-cellular and cholestatic injury with jaundice have been reported, with reversal of the abnormalities after discontinuation of nizatidine.

Cardiovascular.

In clinical pharmacology studies, short episodes of asymptomatic ventricular tachycardia occurred in 2 individuals administered nizatidine and in 3 untreated subjects.

CNS.

Rare cases of reversible mental confusion have been reported.

Endocrine.

Clinical pharmacology studies and controlled clinical trials showed no evidence of anti-androgenic activity due to nizatidine. Impotence and decreased libido were reported with equal frequency by patients who received nizatidine and by those given placebo. Rare reports of gynaecomastia occurred.

Haematologic.

Anaemia was reported significantly more frequently in nizatidine (0.2%) than in placebo-treated (0%) patients. Fatal thrombocytopenia was reported in a patient who was treated with nizatidine and another H2-receptor antagonist. On previous occasions, this patient had experienced thrombocytopenia while taking other drugs. Rare cases of thrombocytopenic purpura have been reported.

Integumental.

Sweating and urticaria were reported significantly more frequently in nizatidine than in placebo patients. Rash, exfoliative dermatitis and pruritus were also reported.

Hypersensitivity.

As with other H2-receptor antagonists, rare cases of anaphylaxis following administration of nizatidine have been reported. Rare episodes of hypersensitivity reactions (e.g. bronchospasm, laryngeal oedema, rash and eosinophilia) have been reported.

Body as a whole.

Serum sickness-like reactions have occurred rarely (in less than 1/1,000 patients) in conjunction with nizatidine use.

Genitourinary.

Reports of impotence have occurred.

Other.

Hyperuricaemia not associated with gout or nephrolithiasis has been reported. Eosinophilia, fever and nausea related to nizatidine administration have been reported.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.2 Dose and Method of Administration

Active duodenal ulcer.

The recommended oral dosage for adults is 150 mg twice daily or 300 mg once daily in the evening (for up to 8 weeks). In most cases, the ulcer will heal within 4 weeks.

Benign gastric ulcer.

The recommended daily dose is 150 mg twice daily or 300 mg once daily in the evening (for up to 8 weeks). Prior to treatment with nizatidine, care should be taken to exclude the possibility of gastric cancer.

Maintenance therapy.

The recommended oral dosage for adults with duodenal ulcer is 150 mg once daily in the evening for a period not exceeding 12 months. Continuous therapy with nizatidine for longer than 12 months has not been studied.

Gastroesophageal reflux disease.

The recommended oral dosage in adults for the treatment of erosions, ulcerations and associated heartburn is 150 mg twice daily (for up to 12 weeks).

Dosage adjustment for patients with moderate to severe renal insufficiency.

The dose for patients with renal dysfunction should be reduced as follows (see Table 1).
Some elderly patients may have creatinine clearances of less than 50 mL/min and, based on pharmacokinetic data in patients with renal impairment, the dose for such patients should be reduced accordingly. The clinical effects of this dosage reduction in patients with renal failure have not been evaluated.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.9 Overdose

Overdoses with 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 diarrhoea. 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.

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 should be considered along with clinical monitoring and supportive therapy. Renal dialysis for 4 to 6 hours increased plasma clearance.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

7 Medicine Schedule (Poisons Standard)

S4.

6 Pharmaceutical Particulars

6.1 List of Excipients

The capsules also contain the following inactive excipients: croscarmellose sodium, starch-pregelatinised maize, purified talc, magnesium stearate, quinoline yellow CI47005 (150 mg only), allura red AC CI16035 (150 mg only), iron oxide yellow CI77492, iron oxide red CI77491 (300 mg capsule only), titanium dioxide, gelatin and black ink SW-9008 (proprietary ingredient number: 2328)/SW-9009 (proprietary ingredient number: 2343).

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C.

6.5 Nature and Contents of Container

Container type: Blister pack (PVC/Al).
Pack sizes: 30 or 60 capsules.
Some strengths, pack sizes and/or pack types may not be marketed.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking it to your local pharmacy.

Summary Table of Changes