Consumer medicine information

Tazac

Nizatidine

BRAND INFORMATION

Brand name

Tazac

Active ingredient

Nizatidine

Schedule

SUMMARY CMI

TAZAC

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using TAZAC?

TAZAC is used to treat the reflux oesophagitis or reflux disease and ulcers.

TAZAC is also used to stop duodenal ulcers from coming back.

For more information, see Section 1. Why am I using TAZAC? in the full CMI.

2. What should I know before I use TAZAC?

Do not use if you have ever had an allergic reaction to nizatidine, other histamine H₂-receptor antagonists (eg. cimetidine, ranitidine, famotidine) or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I use TAZAC? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with TAZAC and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use TAZAC?

The 150 mg capsule is usually taken in the morning and in the evening before you go to bed.
The 300 mg capsule is usually taken once daily, at bedtime.

More instructions can be found in Section 4. How do I use TAZAC? in the full CMI.

5. What should I know while using TAZAC?

Things you should do	Remind any doctor, dentist or pharmacist you visit that you are using TAZAC. 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 should not do	Do not use this medicine to treat any other conditions unless your doctor tells you to. Do not give it to anyone else, even if they have the same condition as you.
Driving or using machines	Be careful driving or operating machinery until you know how TAZAC affects you. TAZAC may cause dizziness or light-headedness in some patients. Make sure you know how you react before driving a car or operating machinery.
Drinking alcohol	Your doctor may advise you to limit your alcohol intake while you are being treated for your condition.
Looking after your medicine	Keep your tablets in a cool dry place where the temperature stays below 25°C. Keep the tablets in their blister pack until it is time to take them.

For more information, see Section 5. What should I know while using TAZAC? in the full CMI.

6. Are there any side effects?

All medicines have side effects. Sometimes they are serious, most of the time they are not. Common side effects include sweating, itchy skin.

Incidences of abnormal liver function, accompanied by jaundice (yellow skin) have been rarely reported by patients taking TAZAC. This side effect has been reversed when TAZAC is stopped.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

FULL CMI

TAZAC

Active ingredient(s): Nizatidine

Consumer Medicine Information (CMI)

This leaflet provides important information about using TAZAC. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using TAZAC.

Where to find information in this leaflet:

1. Why am I using TAZAC?
2. What should I know before I use TAZAC?
3. What if I am taking other medicines?
4. How do I use TAZAC?
5. What should I know while using TAZAC?
6. Are there any side effects?
7. Product details

1. Why am I using TAZAC?

The name of your medicine is TAZAC. It contains the active ingredient called nizatidine.

TAZAC belongs to a class of medicines called H2-antagonists or H2-blockers. TAZAC works by reducing the amount of acid in your stomach. This helps reduce the pain and allows the ulcer and reflux disease to heal in most people.

TAZAC is used to treat the following conditions:

Reflux oesophagitis or reflux disease. This can be caused by “washing back” (reflux) of food and acid from the stomach into the food pipe. Reflux can cause a burning sensation in the chest rising up to the throat, also known as heartburn.
Ulcers. TAZAC is used to treat peptic ulcers. Depending on the position of the ulcer it is called a gastric or duodenal ulcer. A gastric ulcer occurs in the stomach. A duodenal ulcer occurs in the duodenum which is the tube leading out of the stomach. Ulcers can be caused in part by too much acid being made in the stomach.
TAZAC is also used to stop duodenal ulcers from coming back.

Your doctor may have prescribed TAZAC for another reason. Ask your doctor or pharmacist if you have any questions about why TAZAC has been prescribed for you.

There is no evidence that TAZAC is addictive.

2. What should I know before I use TAZAC?

Warnings

You should tell your doctor if you have any of the following conditions or if you have ever experienced any of these conditions. It is very important that your doctor is aware of these matters when determining whether or not to prescribe TAZAC.

Do not use TAZAC if:

if you have had an allergic reaction to TAZAC, other histamine H2-receptor antagonists (eg. cimetidine, ranitidine, famotidine) or to any of the ingredients listed at the end of this leaflet (see ‘Product Description’). Signs of an allergic reaction include itching of the skin, shortness of breath, faintness and hayfever.
if the packaging is torn or shows signs of tampering.
if the expiry date on the pack has passed. If you take this medicine after the expiry date has passed it may not work as well.

Check with your doctor if you:

if you have kidney or liver disease.
if you have any allergies to any other substances, such as foods, preservatives or dyes.
if you are taking any other medicines including any that you
have bought from a pharmacy, supermarket or health food shop. Some medicines may affect the way other medicines work. Your doctor or pharmacist will be able to tell you what to do when taking TAZAC with other medicines.

Tell your doctor about these things before you take TAZAC.

During treatment, you may be at risk of developing certain side effects. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

Use in children

There is no information on its use in children.

3. What if I am taking other medicines?

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

Some medicines may be affected by TAZAC, or may affect how well it works. Medicines such as ketoconazole and itraconazole used to treat fungal infections may be affected by TAZAC.

Your doctor or pharmacist will be able to tell you what to do when taking TAZAC with other medicines.

4. How do I use TAZAC?

How much to take / use

Your doctor will tell you how much TAZAC you need to take each day depending on your condition.

When to take / use TAZAC

The 150 mg capsule is usually taken in the morning and in the evening before you go to bed. The 300 mg capsule is usually taken once daily, at bedtime.

Both the 150 mg and 300 mg capsules should be swallowed whole with a glass of water or another liquid.

How long to take it for

Your doctor will tell you how long you should continue taking TAZAC capsules. Do not stop taking the capsules just because you feel better. If you stop taking your capsules too early then your condition will not have been properly treated.

If you forget to use TAZAC

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 TAZAC as you would normally.

If you are not sure whether to skip the dose, talk to your doctor or pharmacist.

Do not take a double dose to make up for the dose that you missed.

If you use too much TAZAC

If you think that you have used too much TAZAC, you may need urgent medical attention.

You should immediately:

phone the Poisons Information Centre (by calling 13 11 26), or
contact your doctor, or
go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

You may need urgent medical attention.

5. What should I know while using TAZAC?

Things you should do

Tell your doctor or pharmacist if you start any new medicine while you are taking TAZAC.
If you are taking TAZAC for an ulcer, you should go to your doctor regularly for checkups to make sure that TAZAC has healed your ulcer.

Things you should not do

Do not give TAZAC to anyone else. Your doctor has prescribed it for you and your condition.
Do not take TAZAC to treat any other complaints unless your doctor tells you to.

Driving or using machines

Be careful driving or operating machinery until you know how TAZAC affects you. TAZAC may cause dizziness or light-headedness in some people. Make sure you know how you react to TAZAC before you drive a car or operate any machinery.

Drinking alcohol

Your doctor may advise you to limit your alcohol intake while you are being treated for your condition.

Looking after your medicine

Keep the capsules in their blister pack until it is time to take them.
If you take the tablets out of the box or the blister pack they may not keep well.
Keep your tablets in a cool dry place where the temperature stays below 25°C.

Follow the instructions in the carton on how to take care of your medicine properly.

Store it in a cool dry place away from moisture, heat or sunlight; for example, do not store it:

in the bathroom or near a sink, or
in the car or on window sills.
Heat and dampness can destroy some medicines.

There will be an expiry date (month, year) on your TAZAC container. The medicine should not be taken after this date because it may have lost some of its strength.

Keep it where young children cannot reach it.

A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date.

6. Are there any side effects?

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

Like other medicines, TAZAC may cause some unwanted side effects. These are likely to vary from patient to patient. It is important that you tell your doctor as soon as possible about any unwanted effects.

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

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effects	What to do
Sweating Itchy skin	Speak to your doctor if you have any of these less serious side effects and they worry you. These are the more common side effects of TAZAC. They are usually mild.
abnormal liver function, accompanied by jaundice (yellow skin)	Speak to your doctor if you have any of these rare less serious side effects and they worry you. This side effect has been reversed when TAZAC is stopped.

Serious side effects

Serious side effects	What to do
swelling of the face, tongue or back of the throat which may cause difficulty in swallowing or breathing difficulty breathing chest pain.	Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

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

What TAZAC contains

TAZAC 150 mg

Active ingredient (main ingredient)	Nizatidine
Other ingredients (inactive ingredients)	maize starch pregelatinised maize starch dimeticone 350 magnesium stearate iron oxide yellow titanium dioxide sodium lauryl sulfate gelatin printing Ink OPACODE monogramming ink S-1-17823 BLACK (PI 12108).
Potential allergens	does not contain gluten, lactose, sucrose, tartrazine or any other azo dyes. May contain traces of sulfites.

TAZAC 300 mg

Active ingredient (main ingredient)	Nizatidine
Other ingredients (inactive ingredients)	maize starch pregelatinised maize starch povidone croscarmellose sodium dimeticone 350 purified talc iron oxide yellow Iron oxide red titanium dioxide gelatin printing Ink Tekprint SW-09008 black ink (PI 2328).
Potential allergens	does not contain gluten, lactose, sucrose, tartrazine or any other azo dyes. May contain traces of sulfites.

Do not take this medicine if you are allergic to any of these ingredients.

What TAZAC looks like

TAZAC 150 mg capsules are coloured light and dark yellow with "Lilly 3144" marked on them.

TAZAC 300 mg capsules are coloured light yellow and brown with "Lilly 3145" marked on them.

A box of TAZAC 150 mg contains 60 capsules; a box of TAZAC 300 mg contains 30 capsules.

Australian Registration Numbers:

TAZAC 150 mg - AUST R 284130

TAZAC 300 mg - AUST R 49326

Who distributes TAZAC

Arrotex Pharmaceuticals Pty Ltd
15-17 Chapel Street
Cremorne VIC 3121
Australia
www.arrowpharma.com.au

This leaflet was prepared in July 2024.

Published by MIMS September 2024

BRAND INFORMATION

Brand name

Tazac

Active ingredient

Nizatidine

Schedule

1 Name of Medicine

Nizatidine.

2 Qualitative and Quantitative Composition

Tazac (nizatidine) is a histamine H₂-receptor antagonist.
Each capsule contains for oral administration either 150 mg or 300 mg of nizatidine as the active ingredient.

3 Pharmaceutical Form

150 mg.

Size 2 capsule consisting of a dark yellow cap and a pale yellow body, printed with "N150".

300 mg.

Size 1 capsule consisting of a brown cap and a pale yellow body, printed with "N300".

4 Clinical Particulars

4.1 Therapeutic Indications

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

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.

Benign gastric ulcer.

The recommended daily dose is 150 mg twice daily or 300 mg once daily in the evening. 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.

Gastroesophageal reflux disease.

The recommended oral dosage in adults for the treatment of erosions, ulcerations and associated heartburn is 150 mg twice daily.

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.

4.3 Contraindications

Nizatidine is contraindicated in patients with known hypersensitivity to the drug or excipients 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

General.

1. 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.
2. 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).
3. Pharmacokinetic studies in patients with hepatorenal 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.
4. 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 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. Elderly patients may have reduced 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 histamine H₂-receptor antagonists versus those who 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, lignocaine, phenytoin, warfarin, aminophylline, diazepam and metoprolol. Nizatidine does not inhibit the cytochrome P450 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 b.i.d. was administered concurrently.

Endocrine and metabolism.

The prolonged use of H₂-receptor antagonists may impair the absorption of protein-bound Vitamin B₁₂ and may contribute to the development of cyanocobalamin (vitamin B₁₂) deficiency.

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 nursing or discontinue the drug, taking into account the importance of the drug to the mother.

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.

4.8 Adverse Effects (Undesirable Effects)

Nizatidine has been shown to be generally well tolerated. The safety profile is at least as good as, if not better, than other H₂-receptor antagonists. Worldwide, controlled clinical trials of nizatidine included over 6,000 patients given nizatidine in studies of varying durations. Placebo controlled trials included over 2,600 patients given nizatidine and over 1,700 given placebo. Among the adverse events in these 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 hepatocellular 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 antiandrogenic 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 (0%) treated 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, leucopenia, agranulocytosis, anaemia 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 reactions have occurred rarely (in less than 1/1,000 patients) in conjunction with nizatidine use.

Genitourinary.

Reports of impotence have occurred.

Other.

Hyperuricaemia unassociated with gout or nephrolithiasis has been reported. Eosinophilia, fever and nausea related to nizatidine administration have been reported.
Other reported adverse effects include somnolence, vasculitis, arthralgia, myalgia, headache, pain (including abdominal, chest and back pain), asthenia, diarrhoea, flatulence, vomiting, dyspepsia, constipation, dry mouth, tooth disorder, dizziness, insomnia, abnormal dreams, anxiety, nervousness, rhinitis, pharyngitis, sinusitis, increased cough and amblyopia.

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.

4.9 Overdose

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 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 the 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 has increased plasma clearance.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

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.

1. 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.

2. 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. a. Hormones: nizatidine was not shown to affect the serum concentrations of gonadotropins, growth hormone, antidiuretic hormone, cortisol, triiodothyronine, thyroxine, testosterone, 5-dihydrotestosterone, androstenedione or oestradiol. With acute nizatidine administration, transient increases in serum prolactin have been observed in male animals.
b. 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 h.s. or 150 mg b.i.d.) than with placebo. Lower doses such as 100 mg h.s. 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 B.D. or nizatidine 300 mg nocte. 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 b.i.d., 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 b.i.d. 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

Onset and duration of action: half an hour, lasting up to 12 hours. The absolute oral bioavailability of nizatidine exceeds 70%. 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 1.5 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.
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 C_max 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%.
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).
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.
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).
Approximately 35% of nizatidine is bound to plasma protein, mainly to α₁-acid glycoprotein. Warfarin, diazepam, paracetamol, propantheline, phenobarbital and propranolol did not affect plasma protein binding of nizatidine in vitro.

5.3 Preclinical Safety Data

Genotoxicity.

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.

Carcinogenicity.

A two year oral carcinogenicity study in rats with doses as high as 500 mg/kg/day 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) 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 larger 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), and a negative mutagenicity battery, are not considered evidence of a carcinogenic potential for nizatidine.

6 Pharmaceutical Particulars

6.1 List of Excipients

The 150 mg capsule also contains the following excipients: maize starch, pregelatinised maize starch, dimeticone 350, magnesium stearate, iron oxide yellow, titanium dioxide, sodium lauryl sulfate, gelatin and printing Ink Opacode monogramming ink S-1-17823 Black (PI 12108).
The 300 mg capsule also contains the following excipients: maize starch, pregelatinised maize starch, povidone, croscarmellose sodium, dimeticone 350, purified talc, iron oxide red, iron oxide yellow, titanium dioxide, gelatin and printing Ink Tekprint SW-09008 black ink (PI 2328) or printing Ink ACG PAM BKI004 (PI 139674).

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

Tazac 150 mg capsules are available in blister packs (PVC/Al) of 60 capsules.
Tazac 300 mg capsules are available in blister packs (PVC/Al) of 30 capsules.

6.6 Special Precautions for Disposal

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

6.7 Physicochemical Properties

Nizatidine is an off-white to buff crystalline solid that is sparingly soluble in water.

Chemical structure.

CAS number.

CAS No. of 76963-41-2.

7 Medicine Schedule (Poisons Standard)

Schedule 4 - Prescription only medicine.

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Consumer medicine information

Tazac

Nizatidine

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BRAND INFORMATION

Tazac 150 mg

Tazac 300 mg