Consumer medicine information

Magicul

Cimetidine

BRAND INFORMATION

Brand name

Magicul

Active ingredient

Cimetidine

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Magicul.

What is in this leaflet

This leaflet answers some common questions about Magicul.

It does not contain all of the available information. It does not take the place of talking to your doctor or pharmacist.

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

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

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

What Magicul is used for

Magicul is used to:

  • treat stomach and duodenal ulcers (duodenal ulcers occur in the tube leading out of the stomach)
  • prevent stomach and duodenal ulcers from coming back
  • treat gastro-oesophageal reflux disease which is the washing back of food and acid from the stomach up into the food pipe (oesophagus)
  • relieve heartburn and other symptoms of reflux disease
  • treat Zollinger-Ellison syndrome, a rare disorder when the stomach produces very large amounts of acid, much more than in ulcers and reflux disease
  • treat scleroderma oesophagitis, a rare condition in which the food pipe becomes thick and hardened, allowing acid to reflux.

How Magicul works

Magicul belongs to a group of medicines called H2-antagonists or H2-blockers. These medicines work by reducing the amount of acid made by the stomach. This helps to:

  • relieve heartburn, the chest pain or burning sensation rising up the food pipe
  • heal the ulcer and/or reflux disease.

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

Magicul is available only with a doctor's prescription.

There is no evidence that Magicul is addictive.

Before you take Magicul

When you must not take it

Do not take Magicul if you are allergic to medicines containing cimetidine or any of the ingredients listed at the end of this leaflet.

Some of the symptoms of an allergic reaction 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.

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.

Magicul is not recommended for use in children unless advised by your child's doctor, as there have been limited studies of its effects in children of this age group.

Before you start to take it

Tell your doctor if you are allergic to any other medicines, foods, dyes or preservatives.

Tell your doctor if you are pregnant or plan to become pregnant. Your doctor will discuss the risks and benefits of taking Magicul during pregnancy.

Tell your doctor if you are breastfeeding or wish to breastfeed. Magicul passes into breast milk. Your doctor will discuss the risks and benefits of taking Magicul when breastfeeding.

Tell your doctor if you have, any medical conditions, especially the following:

  • liver problems
  • kidney problems
  • lung disease
  • diabetes
  • lowered immunity.

Your doctor may want to take special care if you have any of these conditions.

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

Taking other medicines

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

Some medicines and Magicul interfere with each other. These include:

  • warfarin, a medicine used to prevent blood clots
  • phenytoin, a medicine used to treat epilepsy
  • theophylline, a medicine used to treat asthma
  • metformin, a medicine used to treat diabetes
  • chlormethiazole, a sedating medicine used in alcohol withdrawal and some other conditions
  • medicines used for high blood pressure and some heart conditions
  • medicines used to treat depression or anxiety
  • sleeping tablets
  • medicines used to relieve arthritis or other pain
  • ciclosporin and tacrolimus, medicines used to prevent rejection of transplanted organs
  • atazanavir, a medicine used to treat HIV infection
  • some medicines used to treat fungal infections, such as ketoconazole, itraconazole or posaconazole
  • narcotic analgesics, such as morphine or codeine
  • medicines used to treat cancer.

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

Some antacids may interfere with the absorption of Magicul.

To make sure there is no problem with absorption, you should take Magicul at least one hour before or one hour after taking antacids.

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

How to take Magicul

How much to take

To treat an ulcer or reflux disease, the usual dose is 800 mg a day. This can be taken as 800 mg at bedtime or as 400 mg in the morning and 400 mg at bedtime.

To prevent an ulcer from coming back, the usual dose is 400 mg at bedtime.

For short-term relief of heartburn or other symptoms of reflux disease, the usual dose is 200 mg up to four times a day. The maximum dose is 800 mg a day. Magicul does not provide immediate relief of symptoms.

Your doctor may advise you to take a different dose. This depends on your condition and whether you are taking any other medicines.

Follow all directions given to you by your doctor and pharmacist carefully.

How to take it

Swallow the tablets whole with a glass of water.

Do not crush or chew the tablets. If you crush or chew Magicul tablets, they will not work as well.

When to take it

Take Magicul at about the same time each day. Taking your medicine at the same time each day will give the best effect and help you to remember when to take your medicine.

If your doctor has prescribed divided doses of Magicul, space them evenly apart throughout the day. Magicul can be taken with or without food.

If you are undergoing haemodialysis, Magicul should be taken after dialysis.

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 the missed dose as soon as you remember, and then go back to taking your tablets as you would normally.

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

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

How long to take it for

If you are taking Magicul to heal an ulcer, you will need to take it for 4 to 8 weeks.

If you are taking Magicul to treat reflux disease, you may need to take it for up to 12 weeks.

For short-term relief of heartburn and symptoms of reflux disease, you can take Magicul for up to 2 weeks. If the pain or symptoms are not relieved by Magicul or persist you should see your doctor.

If you are taking Magicul to stop an ulcer from coming back or to treat other conditions, your doctor will tell you how long you need to take the tablets.

Keep taking Magicul for as long as your doctor recommends.

It is very important that you take the full course of Magicul prescribed by your doctor so that your condition is properly treated.

If you take too much (overdose)

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

If you take too much Magicul, you may feel drowsy or confused.

While you are taking Magicul

Things you must do

If you are about to be started on any new medicine, tell your doctor or pharmacist that you are taking Magicul.

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

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

Keep all your doctor's appointments so that your progress can be checked. Your doctor may want you to have tests to make sure that your ulcer or reflux disease is healing.

Things you must not do

Do not stop taking Magicul, or change the dose, without checking with your doctor.

Do not use Magicul to treat any other complaints unless your doctor tells you to.

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

Things to be careful of

Be careful driving or operating machinery until you know how Magicul affects you. Magicul may cause drowsiness or dizziness in some people. If any of these occur, do not drive, operate machinery or do anything else that could be dangerous.

Suggestions that may help your condition

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

  • Alcohol - your doctor may advise you to limit your alcohol intake.
  • Aspirin and many other medicines used to treat arthritis, period pain and 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, because they contain ingredients that 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 Magicul. Like all other medicines, Magicul may have unwanted side effects in some people. Sometimes they are serious, most of the time they are not. You may need medical treatment 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:

  • headache
  • tiredness, drowsiness
  • dizziness
  • muscle aches and pains
  • mild skin rash
  • hair loss
  • diarrhoea, constipation, wind
  • nausea (feeling sick), vomiting
  • in men, enlarged breasts and impotence (these have been reported rarely in patients receiving high doses).

For the most part, these side effects are mild.

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

  • fast, slow or irregular heart beat
  • yellowing of the eyes or skin (jaundice)
  • fever
  • confusion, hallucinations, depression
  • severe upper stomach pain, often with nausea and vomiting
  • unusual bruising or bleeding
  • looking pale, tiredness, being short of breath when exercising
  • signs of frequent infections such as fever, chills, sore throat or mouth ulcers.

These side effects may be serious. You may need urgent medical attention.

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

  • hives or severe skin reactions
  • swelling of the face, mouth, throat or limbs
  • shortness of breath or difficulty breathing.

These reactions may be signs of a severe allergic reaction to Magicul. Allergic reactions are rare.

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.

Some health problems may arise from the condition being treated itself, rather than the treatment. For this reason, contact your doctor immediately if you notice any of the following:

  • pain or indigestion which occurs during treatment with Magicul
  • vomiting
  • passing black or blood-stained motions
  • unexpected weight loss.

After taking Magicul

Storage

Keep Magicul 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.

Keep your tablets in a cool dry place where the temperature stays below 30°C for 200 mg and 800 mg tablets, and below 25°C for 400 mg tablets

Do not store Magicul or any other medicine in the bathroom or near a sink.

Do not leave Magicul in the car or on window sills. Heat and dampness can destroy some medicines.

Disposal

If your doctor tells you to stop taking Magicul, or your tablets have passed their expiry date, ask your pharmacist what to do with any that are left over.

Product description

What it looks like

Magicul comes in 3 strengths of tablets:

  • Magicul 200 - round, pale green, film-coated tablet marked CE2 on one side and a Greek Alpha symbol on the reverse. Each pack contains 120 tablets.
  • Magicul 400 mg - White film coated biconvex tablets embossed "CN 400" on one side with "G" on the reverse. Each pack contains 60 tablets.
  • Magicul 800 - oval, pale green, film-coated tablet marked CE8 on one side and a Greek Alpha symbol on the reverse. Each pack contains 30 tablets.

Ingredients

The active ingredient in Magicul is cimetidine. Each tablet contains 200 mg, 400 mg or 800 mg of cimetidine.

The tablets also contain:

  • maize starch
  • povidone
  • microcrystalline cellulose
  • sodium starch glycollate (Type A)
  • magnesium stearate
  • Opadry Green OY-8830 (ARTG no. 1538) for 200 mg and 800 mg tablets.
  • Opadry White Y-1-7000 E171 (ARTG no. 2731) for 400 mg tablets.

The tablets are gluten free.

Manufacturer

Magicul is supplied in Australia by:

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

Australian registration number:

Magicul 400 - AUST R 213382

This leaflet was prepared in December 2019.

Magicul_cmi\Dec19/00

Published by MIMS March 2020

BRAND INFORMATION

Brand name

Magicul

Active ingredient

Cimetidine

Schedule

S4

 

1 Name of Medicine

Cimetidine.

6.7 Physicochemical Properties

Cimetidine is an odourless white to off-white powder, which is sparingly soluble in water.
Active ingredient: cimetidine.
Chemical name: 2-cyano-1-methyl-3- [2-(5-methylimidazol-4-yl-methylthio)ethyl] guanidine.
Molecular formula: C10H16N6S. Molecular weight: 252.3.

Chemical structure.

The structural formula for cimetidine is:

CAS number.

51481-61-9.

2 Qualitative and Quantitative Composition

Each tablet contains 200 mg, 400 mg or 800 mg of cimetidine as the active ingredient.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Magicul 200.

200 mg tablet: Normal convex, pale green film coated, marked "CE2" on one side, "α" on the reverse.

Magicul 400.

400 mg tablet: White film coated biconvex tablets embossed "CN 400" on one side and blank on reverse.

Magicul 800.

800 mg tablet: Oval, normal convex, pale green film coated, marked "CE8" on one side, "α" on the reverse.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Cimetidine is a histamine H2-receptor antagonist. It was the first available agent that blocked the action of histamine at the histamine H2-receptor site of the parietal cells and does so by competitive inhibition.
Pharmacologically, cimetidine does not exhibit classical anticholinergic effects. Studies have shown that cimetidine inhibits both daytime and nocturnal basal gastric acid secretion. Cimetidine also inhibits gastric acid secretion stimulated by food, histamine, pentagastrin, caffeine and insulin.

Animal pharmacology and toxicology.

Cimetidine has been shown by in vitro studies to be a specific competitive H2-receptor antagonist without significant interaction at catecholamine β-receptors, histamine H1-receptors or muscarinic receptors. Its potency in terms of administered dose and in terms of blood concentrations achieved is very similar in man and in experimental animals. Thus, in all species studied, a blood concentration of about 2 micromol/L is associated with 50% inhibition of maximal acid output.
In chronic toxicity studies in dogs, some animals administered 504 mg/kg showed evidence of liver and kidney damage.
The kinetics of cimetidine and its absorption, metabolism and excretion are essentially similar in man, rat and dog.

Human pharmacology.

Effect on basal (non-stimulated) acid secretion.

In double blind, placebo controlled studies in duodenal ulcer patients, single doses of cimetidine markedly and consistently reduced fasting daytime and nocturnal basal gastric acid secretion in a dose related manner. Degree of inhibition was correlated with blood levels attained, at least 80% inhibition usually being achieved when blood levels exceeded 0.5 mg/L. The time over which such levels were sustained varied among doses, the effect of a 200 mg dose diminishing after 4 to 5 hours and 300 mg after 7 to 8 hours, while 400 mg was still effective after 8 hours. The effect of cimetidine was due largely to significantly reduced acid concentration, but volume of gastric juice was reduced also. Gastric pH levels above 5 were seen regularly when effective blood levels were present, indicating that pepsin will be inactive for many periods during therapy.

Effect on stimulated acid secretion.

Cimetidine was shown to be a potent inhibitor of gastric secretion stimulated by histamine, pentagastrin, insulin, food or caffeine in normal subjects and duodenal ulcer patients. At least 50% inhibition was associated with blood levels of 0.5 mg/L or more, while 80 to 90% inhibition usually occurred at blood levels above 1 mg/L. Timing of the dose relative to a test meal affected blood level patterns and hence pattern of response, the data suggesting that administration with meals provides optimum control of gastric secretion. Studies have shown that doses of 800 mg and 1 g per day will reduce 24 hour intragastric acidity by 70% and 72% respectively.
The effect of cimetidine on pepsin concentration was variable in these studies, but total pepsin output decreased as a result of the decrease in volume of gastric juice. As noted above, any pepsin secreted during periods when the pH is above 5 will be inactive.
Cimetidine significantly inhibited the histamine stimulated rise in intrinsic factor concentration, but did not affect the basal level of intrinsic factor.
In studies where serum gastrin was measured the expected rise in response to stimulants (food, etc.) was observed. In these studies, when gastric pH was controlled in both placebo and cimetidine groups, there was no difference in gastrin levels between the groups. However, when gastric pH was uncontrolled, the gastrin levels of the cimetidine groups were higher. This appears to be due to the higher gastric pH obtained with cimetidine.
Cimetidine has no effect on the rate of gastric emptying or on lower oesophageal sphincter (LOS) pressure.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Pharmacokinetic studies carried out in humans have demonstrated that cimetidine is well absorbed orally. Oral absorption studies carried out using a 200 mg dose have resulted in blood levels averaging 2.8 micromol/L (0.7 mg/L), occurring at times ranging from 45 to 75 minutes after dosing. Up to 34% of the drug was recovered from the urine 2 hours after dosing and after 24 hours 70% of the dose was accounted for.

Distribution.

Cimetidine is approximately 22% bound to human plasma protein.

Excretion.

Intravenous infusion of cimetidine labelled with 3H in doses of 75 to 117 mg resulted in peak blood concentrations of 2 to 4.3 micromol/L (0.5 to 1.1 mg/L). The concentration of cimetidine in the blood declined with a half-life of 123 ± 12 minutes. Radioactivity in the urine confirmed rapid excretion by the kidney (60% in 2.5 hours), 70% being excreted unchanged and up to 19% as the sulphoxide.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

In a 24 month toxicity study conducted in rats, at dose levels of 150, 378 and 950 mg/kg/day (approximately 4 to 24 times the recommended human dose), a statistically significant higher incidence of benign Leydig cell tumours was seen in the drug treated groups compared to controls. These tumours were present in control groups as well as treated groups and the difference became apparent only in aged rats.

4 Clinical Particulars

4.1 Therapeutic Indications

Short-term treatment of proven duodenal ulcer and gastric ulcer.
Maintenance treatment in those patients with recurrence of duodenal ulceration after short-term therapy.
Maintenance treatment for periods of up to one year to reduce the risk of relapse in patients with documented healing of chronic benign gastric ulcer.
Short-term treatment (no more than 12 weeks) of persistent gastro-oesophageal reflux disease.
Short-term treatment of heartburn (up to two weeks) and other symptoms of gastro-oesophageal reflux disease.
Treatment of gastrinoma (Zollinger-Ellison syndrome).
Treatment of scleroderma oesophagus.

4.3 Contraindications

Patients with known hypersensitivity to cimetidine or any other component of Magicul.
Inhibition of the renal cation transport system by cimetidine may result in elevated dofetilide plasma concentrations. This can lead to an increased risk of ventricular arrhythmias, including torsades de pointes. Coadministration of dofetilide and cimetidine is therefore contraindicated (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

4.4 Special Warnings and Precautions for Use

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 who had stopped treatment, with an observed adjusted relative risk of 1.63% (055 CI, 1.07-2.48).
Due to the possible interaction with coumarins, close monitoring of prothrombin time is recommended when cimetidine is concurrently used.
Co-administration of therapeutic agents with a narrow therapeutic index, such as phenytoin or theophylline, may require dosage adjustment when starting or stopping concomitantly administered cimetidine (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Gastric ulcer.

Treatment with a histamine H2-receptor antagonist may mask symptoms associated with carcinoma of the stomach and therefore may delay diagnosis of the condition. The potential delay in diagnosis should be borne in mind in patients of middle age or older with new or recently changed dyspeptic symptoms. Accordingly, where gastric ulcer is suspected, the possibility of malignancy should be excluded before therapy with cimetidine is instituted. It is then important to re-endoscope the patient after 8 to 12 weeks of cimetidine therapy to check that the ulcer has healed.

Gastro-oesophageal reflux disease.

Treatment of persistent gastro-oesophageal reflux disease and associated symptoms of reflux should only be initiated if the condition is unresponsive to conservative reflux measures and simple drug therapies such as antacids. Treatment should be short term (no more than 12 weeks).

Intubated patients receiving mechanical ventilation.

Agents that elevate gastric pH may increase the already present risk of nosocomial pneumonia in intubated patients receiving mechanical ventilation in intensive care units.

Cardiovascular.

In an intravenous study in dogs, at a dosage level of 25 mg/kg, tachycardia and hypotension were observed. At an oral dose of 336 mg/kg tachycardia was produced. Propranolol prevented or reversed the increase in heart rate.

Use in renal impairment.

Dosage should be reduced according to creatinine clearance. For patients undergoing haemodialysis it is recommended that dialysis be carried out just prior to the next scheduled dosage since some drug will be removed by dialysis. Where circumstances require an increase in dosage, increases should be made by increasing the frequency of administration of 200 mg doses.
Cimetidine removal by continuous ambulatory peritoneal dialysis is insignificant and there is no need to adjust the conventional renal failure dosage regimen in these patients.
See Section 4.2 Dose and Method of Administration for specific recommendations for use in these patients.

Use in the elderly.

It should be borne in mind that some elderly patients may have reduced renal function, however, if renal function is normal, no dosage adjustment is necessary.

Paediatric use.

Clinical experience in children is limited. Therefore, cimetidine therapy cannot be recommended for children unless, in the judgement of the physician, anticipated benefits outweigh the potential risks. In limited experience, 20 to 40 mg/kg/day has been administered in divided doses by mouth or intravenously.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Cimetidine has the potential to affect the absorption, metabolism or renal excretion of other drugs which is particularly important when drugs with a narrow therapeutic index are administered concurrently. The altered pharmacokinetics may necessitate dosage adjustment of the affected drug or discontinuation of treatment (see Section 4.4 Special Warnings and Precautions for Use).
Interactions may occur by several mechanisms including:
1. Inhibition of certain cytochrome P450 enzymes (including CYP1A2, CYP2C9, CYP2D6 and CYP3A3/A4, and CYP2C18). Inhibition of these enzymes may result in increased plasma levels of certain drugs including warfarin-type coumarin anticoagulants (e.g. warfarin), tricyclic antidepressants (e.g. amitriptyline), class I antiarrhythmics (e.g. lidocaine (lignocaine), quinidine), calcium channel blockers (e.g. nifedipine, diltiazem), oral sulfonylureas (e.g. glipizide), phenytoin, theophylline and metoprolol.
2. Competition for renal tubular secretion. This may result in increased plasma levels of certain drugs including procainamide, quinidine, metformin, cyclosporine, tacrolimus and dofetilide (see Section 4.3 Contraindications).
3. Alteration of gastric pH. The bioavailability of certain drugs may be affected. This can result in either an increase in absorption (e.g. atazanavir) or a decrease in absorption (e.g. some azole antifungals such as ketoconazole, itraconazole or posaconazole).
4. Unknown mechanisms. Cimetidine may potentiate the myelosuppressive effects (e.g. neutropenia, agranulocytosis) of chemotherapeutic agents such as carmustine, fluorouracil, epirubicin, or therapies such as radiation. Isolated cases of clinically relevant interactions have been documented with narcotic analgesics (e.g. morphine).

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Cimetidine exhibited an antiandrogen effect in both rats and dogs. After 12 months dosing in rats at levels of 150 to 950 mg/kg there was a reduction in prostate size in males of all the dosed groups and also a reduction in the size of the testes and seminal vesicles of the top dosed group. Twelve months dosing in dogs at levels of 41 to 504 mg/kg resulted in a reduction in prostate weights. Cimetidine was found to have no significant effect on fertility studies.
(Category B1)
There has been limited experience to date with the use of cimetidine in pregnant patients. No significant adverse effects have been reported. Reproduction studies performed in rats, mice and rabbits have revealed no evidence of impaired fertility or malformation in the foetus due to cimetidine. However, studies in animals and humans have demonstrated that cimetidine crosses the placental barrier and can cross the blood-brain barrier of neonatal animals. Therefore, cimetidine should only be administered to pregnant patients or women of childbearing potential when, in the judgement of the physician, the anticipated benefits outweigh the potential risks.
 Adequate human data on use in lactation are not available. Cimetidine is excreted in human breast milk and, as a general rule, breastfeeding should not be undertaken while a patient is on the drug.

4.8 Adverse Effects (Undesirable Effects)

Adverse events are listed within body systems and categorised by frequency according to the following definitions: common: frequency ≥ 1/100 patients; uncommon: frequency < 1/100 but ≥ 1/1000 patients; rare: frequency < 1/1000 patients.
In a review of patients in short-term clinical trials, cimetidine was found to be well tolerated.
The following adverse effects were observed during the clinical trial programmes:

Body as a whole.

Common: headache.

Gastrointestinal.

Common: diarrhoea, constipation.

Nervous system.

Common: dizziness, drowsiness, tiredness.

Dermatological.

Common: rash.
Headache and constipation occurred more frequently in placebo treated patients. Overall, the incidence of unwanted adverse effects was comparable between placebo and cimetidine treated groups.
In a review of patients treated with cimetidine in maintenance trials (up to 12 months), the following adverse effects were reported:

Body as a whole.

Common: headache. Rare: fever*, anaphylaxis.

Gastrointestinal.

Common: constipation, diarrhoea, vomiting, nausea, flatulence. Rare: hepatitis*.

Nervous system.

Uncommon: depression. Common: tiredness.

Dermatological.

Common: rash.

Musculoskeletal.

Common: musculoskeletal pain.

Urogenital.

Rare: interstitial nephritis*.

Metabolic/ nutritional.

Rare: pancreatitis*.

Cardiovascular.

Rare: hypersensitivity vasculitis#, sinus bradycardia, tachycardia, heart block.

Haematologic/ lymphatic.

Rare: leucopenia (including agranulocytosis), thrombocytopenia, pancytopenia, aplastic anaemia. A risk/ benefit assessment should be made when concomitant use of cimetidine with drugs known to cause bone marrow depression is contemplated.
*Cleared on withdrawal of drug.
#Usually cleared on withdrawal of drug.
Headache, diarrhoea, dizziness, nausea and vomiting occurred more commonly in placebo treated patients.
Severe skin rash and reversible alopecia have been reported on occasion.
Gynaecomastia and impotence have been reported in some patients receiving high doses. These conditions are usually reversible on discontinuation of cimetidine therapy. The incidence of gynaecomastia and impotence is dependent on dose and duration of treatment. Reversible impotence has been reported particularly in patients receiving high doses (e.g. in Zollinger-Ellison syndrome). However, at regular dosage the incidence is similar to that in the general population.
Galactorrhoea has been reported very rarely.
There have been common reports of myalgia and very rare reports of arthralgia.
Some increases in serum transaminase and small increases in plasma creatinine have been reported and should be borne in mind when treating patients with renal or hepatic insufficiency. The rises in creatinine have occurred in 11% of patients usually during the first week of treatment and have been nonprogressive, returning to pretreatment values either during therapy or one week after therapy ceased. The significance of these changes is unknown.
Confusional states, reversible within a few days of withdrawing cimetidine, have been reported rarely, usually in elderly and/or ill patients, such as those with renal insufficiency or organic brain syndrome.
Hallucination has been reported very rarely.

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

Acute duodenal ulceration.

800 mg at bedtime, or 400 mg morning and at bedtime, or 200 mg three times daily and 400 mg at bedtime.
A single bedtime dose of 800 mg has been shown to be comparable in efficacy to that of a daily dose of 800 mg divided into two administrations (400 mg in the morning and 400 mg at bedtime).
In most cases, healing will occur on this dose within 4 weeks. However, a small number of patients may require an additional period of 2 to 4 weeks therapy. If response is inadequate, the dose may be increased to 400 mg four times a day (with meals and at bedtime).

Maintenance treatment (recurrent duodenal ulceration).

400 mg at bedtime.

Acute gastric ulceration.

(See Section 4.4 Special Warnings and Precautions for Use, Gastric ulcer.) 800 mg at bedtime, or 400 mg morning and at bedtime, or 200 mg three times daily and 400 mg at bedtime.
In most cases, healing will occur on this dose within 4 weeks. However, a small number of patients may require an additional period of 2 to 4 weeks therapy. If response is inadequate, the dose may be increased to 400 mg four times a day (with meals and at bedtime).

Maintenance treatment (chronic benign gastric ulceration).

400 mg at bedtime for periods of up to one year. In chronic benign gastric ulceration, re-evaluation of the patient should be undertaken at regular intervals.

Zollinger-Ellison syndrome (gastrinoma).

200 mg three times a day and 400 mg at bedtime.
Dosage may be increased, as necessary, to 1.6 to 2 g daily.

Gastro-esophageal reflux disease.

800 mg at night or in divided doses for up to 12 weeks.

Short-term treatment of heartburn and symptoms of gastro-oesophageal reflux disease.

200 mg up to four times a day for up to 2 weeks. Dosage should not exceed 800 mg per day.

Scleroderma oesophagus.

Usual dose is 1,200 mg daily in divided doses (see Section 4.2 Dose and Method of Administration, Impaired renal function).

Impaired renal function.

Dosage should be reduced according to creatinine clearance. The following dosages are suggested (see Table 1).
For patients undergoing haemodialysis it is recommended that dialysis be carried out just prior to the next scheduled dosage since some drug will be removed by dialysis. Where circumstances require an increase in dosage, increases should be made by increasing the frequency of administration of 200 mg doses.
Cimetidine removal by continuous ambulatory peritoneal dialysis is insignificant and there is no need to adjust the conventional renal failure dosage regimen in these patients.

Special cases.

In some instances, e.g. draining gastrocutaneous fistula, control of acid secretion may be necessary.

4.7 Effects on Ability to Drive and Use Machines

Symptoms such as dizziness and drowsiness have been noted in connection with cimetidine. If such symptoms appear, the ability to drive and operate machinery may be impaired.

4.9 Overdose

Symptoms.

There have been reports of severe CNS symptoms, e.g. unresponsiveness, following ingestion of cimetidine 20 to 40 g. There have been deaths in adults who were reported to have ingested over 40 g cimetidine orally as a single dose.
In animal toxicity experiments CNS depression, hypotension, tachycardia, liver enzyme elevation and renal abnormalities have been observed.

Treatment.

Administer activated charcoal within one hour of ingestion if possible. Institute supportive therapy for the evolving clinical syndrome. Studies in animals indicate that artificial respiration may be of value.
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 tablets also contain maize starch, povidone, microcrystalline cellulose, sodium starch glycollate (Type A), magnesium stearate, Opadry Green OY-8830 (ARTG no. 1538) for 200 mg and 800 mg tablets, and Opadry White Y-1-7000 E171 (ARTG no. 2731) for 400 mg tablets. The tablets are gluten free.

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

Magicul 200.

Store below 30°C.

Magicul 400.

Store below 25°C.

Magicul 800.

Store below 30°C.

6.5 Nature and Contents of Container

Magicul 200.

Blister pack* (PVC/PVDC/Al) of 20, 30, 40, 120 and 150's; Bottle* (HDPE and PP cap) of 30, 120 and 150's.

Magicul 400.

Blister pack (PVC/PVDC/Al) of 60's.

Magicul 800.

Blister pack* (PVC/PVDC/Al) of 30 and 60's; Bottle* (HDPE and PP cap) of 30 and 60's.
*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