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.

SUMMARY CMI

TACIDINE®

Consumer Medicine Information (CMI) summary

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

1. Why am I taking TACIDINE?

TACIDINE contains the active ingredient nizatidine. TACIDINE is used to treat reflux oesophagitis or reflux disease, ulcers and to stop duodenal ulcers from coming back.

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

2. What should I know before I take TACIDINE?

Do not take TACIDINE if you have ever had an allergic reaction to nizatidine, other histamine H2-receptor antagonists (e.g. 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 take TACIDINE? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with TACIDINE 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 take TACIDINE?

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

  • 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 take TACIDINE? in the full CMI.

5. What should I know while taking TACIDINE?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are taking TACIDINE.
  • 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 complaints 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 TACIDINE affects you.
  • TACIDINE 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 capsules in a cool dry place where the temperature stays below 25°C.
  • Keep the capsules in their blister pack until it is time to take them.

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

6. Are there any side effects?

Common side effects: sweating, itchy skin rash or hives, headaches, flatulence, vomiting, diarrhoea or constipation. Serious side effects: yellowing of the whites of the eyes or skin, dark urine, tiredness, dizziness and looking pale or confusion. Very serious side effects: vomiting blood or food, passing black bowel motions or 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. This is not a complete list of all possible side effects.

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

TACIDINE®

Active ingredient: nizatidine

Consumer Medicine Information (CMI)

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

Where to find information in this leaflet:

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

1. Why am I taking TACIDINE?

TACIDINE contains the active ingredient nizatidine.

Nizatidine belongs to a group of medicines called H2-antagonist or H2-blockers. These medicines work 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.

TACIDINE 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 (heartburn), and most often occurs after eating or at night.
  • 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 the tube leading out of the stomach (which is part of your small intestine). Ulcers can be caused in part by too much acid being made in the stomach.
  • TACIDINE is also used to stop duodenal ulcers from coming back.

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

2. What should I know before I take TACIDINE?

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 TACIDINE.

Do not take TACIDINE if:

  • you have ever had an allergic reaction to TACIDINE, any other histamine H2-receptor antagonists (e.g. cimetidine, ranitidine, famotidine) or any of the ingredients listed at the end of this leaflet (see section 7. Product details)
    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.
  • the packaging is torn or shows signs of tampering
  • 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:

  • have any allergies to any other medicines, foods, preservatives or dyes
  • have or have had any of the following medical conditions:
    - kidney or liver disease
    - chronic lung disease
    - diabetes
    - a weakened immune system or lowered resistance to infection, sometimes caused by certain diseases or treatments.
  • plan to have surgery.

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

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. 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.

Your doctor can discuss with you the risks and benefits involved.

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

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

Use in children

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

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 interfere with TACIDINE and affect how it works. These include:

  • aspirin
  • certain antacids used to treat heartburn and indigestion.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect or are affected by TACIDINE.

You may need different amounts of your medicines, or you may need to take different medicines.

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

4. How do I 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

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

Swallow the capsules whole with a full glass of water.

When to take TACIDINE

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

How long to take TACIDINE for

Your doctor will tell you how long you should continue taking TACIDINE capsules.

Do not stop taking the capsules just because you feel better. 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 stop taking your capsules too early then your condition will not have been properly treated.

If you forget to take TACIDINE

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 TACIDINE 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 you missed.

This may increase the chance of you getting an unwanted side effect.

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

If you take too much TACIDINE

If you think that you or anyone else has taken too much TACIDINE, urgent medical attention may be needed.

You should immediately:

  • phone the Poisons Information Centre
    (Australia telephone 13 11 26) for advice, 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.

5. What should I know while taking TACIDINE?

Things you should do

  • Tell your doctor or pharmacist if you start any new medicine while 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 are taking TACIDINE for an ulcer, you should go to your doctor regularly for check-ups to make sure that TACIDINE has healed your ulcer.
  • 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 give TACIDINE to anyone else, even if they have the same condition as you. Your doctor has prescribed it for you and your condition.
  • Do not take TACIDINE to treat any other complaints unless your doctor tells you to.
  • 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.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how TACIDINE affects you.

TACIDINE 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. Make sure you know how you react to TACIDINE before you drive a car or operate any machinery.

Drinking alcohol

Tell your doctor if you drink alcohol.

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

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.

  • 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 mealtimes.
  • Smoking - your doctor may advise you to stop smoking or at least cut down.

Looking after your medicine

  • Keep the capsules in their blister pack until it is time to take them.
    If you take the capsules out of the blister pack they may not keep well.
  • Store 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 or dampness can destroy some medicines.

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 take this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not take this medicine after the expiry date.

6. Are there any side effects?

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

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

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

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 effectsWhat to do
  • sweating
  • itchy skin rash or hives
  • headaches
  • flatulence, vomiting, diarrhoea, constipation
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 TACIDINE. They are usually mild and short-lived.

Serious side effects

Serious side effectsWhat to do
  • yellowing of the whites of the eyes or skin, also called jaundice
  • dark urine
  • symptoms of anaemia, which may include tiredness, dizziness and looking pale
  • confusion
Call your doctor straight away if you notice any of these serious side effects.

Very serious side effects

Very serious side effectsWhat to do
  • 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, tongue or back of throat which may cause difficulty in swallowing or breathing; wheezing or shortness of breath
  • chest pain
Call your doctor straight away or go straight to the Emergency Department at your nearest hospital if you notice any of these very serious side effects.

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

Prolonged use of TACIDINE may impair the absorption of Vitamin B12.

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 TACIDINE contains

Active ingredient
(main ingredient)		nizatidine 150 mg or 300 mg
Other ingredients
(inactive ingredients)
  • colloidal anhydrous silica
  • croscarmellose sodium
  • pregelatinised maize starch
  • purified talc
  • sodium lauryl sufate
  • magnesium stearate
  • quinoline yellow (150 mg only)
  • allura red AC (150 mg only)
  • iron oxide red (300 mg only)
  • iron oxide yellow
  • titanium dioxide
  • gelatin
  • TekPrint SW-9008 Black Ink (ID 2328)
  • TekPrint SW-9009 Black Ink (ID 2343)
Potential allergensphenylalanine

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

What TACIDINE looks like

TACIDINE 150 mg is a 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. (AUST R 94204).

TACIDINE 300 mg is a hard gelatin capsule with a light brown body and cap. The body has "NZ 300" and the cap has "G" printed in black. (AUST R 94205).

TACIDINE 150 mg is available in blister packs of 60 capsules.

TACIDINE 300 mg is available in blister packs of 30 capsules.

Who distributes TACIDINE

Alphapharm Pty Ltd trading as Viatris
Level 1, 30 The Bond
30-34 Hickson Road
Millers Point NSW 2000
www.viatris.com.au
Phone: 1800 274 276

This leaflet was prepared in September 2024.

TACIDINE® is a Viatris company trade mark

TACIDINE_cmi\Sep24/00

Published by MIMS November 2024

BRAND INFORMATION

Brand name

Tacidine

Active ingredient

Nizatidine

Schedule

S4

 

1 Name of Medicine

Nizatidine.

2 Qualitative and Quantitative Composition

Tacidine capsules contain 150 mg or 300 mg of nizatidine as the active ingredient.

Excipients with known effect.

Phenylalanine.
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.

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.

4.2 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.

4.3 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

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, 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.

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 fetuses and depressed fetal 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 fetus and at 50 mg/kg it produced ventricular anomaly, distended abdomen, spina bifida, hydrocephaly and enlarged heart in 1 fetus.
There are, however, no adequate and well-controlled studies in pregnant women. It is also not known whether nizatidine can cause fetal 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 fetus.
 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.

4.7 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, 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 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, 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 not associated 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 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).

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, levothyroxine, testosterone, 5α-dihydrotestosterone, androstenedione, or estradiol. With acute nizatidine administration, transient increases in serum prolactin have been observed in male animals.
Nizatidine had no demonstrable antiandrogenic action.

Clinical trials.

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.

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.

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.

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, phenobarbital, 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.

6 Pharmaceutical Particulars

6.1 List of Excipients

The capsules also contain the following inactive excipients: colloidal anhydrous silica, sodium lauryl sulfate, croscarmellose sodium, pregelatinised maize starch, purified talc, magnesium stearate, quinoline yellow (150 mg only), allura red AC (150 mg only), iron oxide yellow, iron oxide red (300 mg only), titanium dioxide, gelatin, TekPrint SW-9008 Black Ink (ID 2328) and TekPrint SW-9009 Black Ink (ID 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.

Australian register of therapeutic goods (ARTG).

AUST R 94204 - Tacidine nizatidine 150 mg capsule blister pack.
AUST R 94205 - Tacidine nizatidine 300 mg capsule blister pack.

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.

6.7 Physicochemical Properties

Chemical structure.

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.

CAS number.

76963-41-2.

7 Medicine Schedule (Poisons Standard)

S4 (Prescription Only Medicine).

Summary Table of Changes