Consumer medicine information

Zoton FasTabs

Lansoprazole

BRAND INFORMATION

Brand name

Zoton FasTabs

Active ingredient

Lansoprazole

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Zoton FasTabs.

What is in this leaflet

This leaflet answers some common questions about Zoton FasTabs. It does not contain all 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 Zoton FasTabs against the benefits this medicine is expected to have.

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

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

What Zoton FasTabs is used for

Peptic Ulcers
Zoton FasTabs is used to treat peptic ulcers in adults. Depending on the position of the ulcer it is either 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.

Too much acid being made in the stomach can cause these ulcers.

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

Reflux Oesophagitis
Zoton FasTabs is used to treat the symptoms of reflux oesophagitis or reflux disease in adults and in children from 6 to 17 years of age. This can be caused by backflow (reflux) of food and acid from the stomach into the food pipe or gullet, also known as the oesophagus.

Reflux can cause a burning sensation in the chest rising up to the throat, also known as heartburn.

Heartburn and stomach pain associated with reflux or peptic ulcer.
Zoton FasTabs is used for the short-term treatment of heartburn and peptic ulcer symptoms in adults.

Peptic Ulcers Associated with Helicobacter Pylori Infection
Most people who have a peptic ulcer also have bacteria called Helicobacter pylori in their stomach. Zoton FasTabs can be taken in conjunction with certain antibiotics to help eradicate Helicobacter pylori and let your peptic ulcer heal. However, it is possible that the antibiotics may not always get rid of Helicobacter pylori.

How Zoton FasTabs works

Zoton FasTabs contains lansoprazole, which is a type of medicine called a proton pump inhibitor (PPI). It works by decreasing the amount of acid the stomach makes, to give relief from the symptoms of excessive acid and allow healing to take place. This does not stop food being digested in the normal way.

Ask your doctor if you have any questions about why Zoton FasTabs has been prescribed for you.

Your doctor may prescribe this medicine for another reason.

There is no evidence that Zoton FasTabs is habit-forming. This medicine is available only with a doctor's prescription.

Before you take Zoton FasTabs

When you must not take it

Do not take Zoton FasTabs if you have an allergy to:

  • Lansoprazole
  • Any medicines containing a proton-pump inhibitor
  • Any of the ingredients listed at the end of this leaflet.

Some of the symptoms of an allergic reaction include:

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

Do not take Zoton FasTabs if you have severe liver disease.

Do not take Zoton FasTabs if you are already taking the medicine atazanavir. Atazanavir is used to treat HIV infection. If it is taken at the same time as Zoton FasTabs, it won't be absorbed properly and will be less effective in treating HIV infection.

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

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

Before you start to take it

You must tell your doctor if:

You have any allergies to any other medicines, foods, dyes or preservatives.

You are pregnant, plan to become pregnant or are breast-feeding.

Your doctor will discuss the possible risks and benefits of taking Zoton FasTabs during pregnancy.

Taking Zoton FasTabs during breast-feeding should be avoided as it is not known if this medicine passes into your breast milk.

You have any other medical conditions, including:

  • Liver or kidney problems
  • Inflammation of the bowel
  • A tumour in the stomach region.

You have problems with digestion, or have an intolerance to:

  • Fructose
  • Glucose
  • Galactose
  • Lactose
  • Sucrose.

If you have not told your doctor about any of the above, tell him or her before you take Zoton FasTabs.

Taking other medicines

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

Some medicines may interfere with Zoton FasTabs. These medicines include:

  • Theophylline used to treat asthma
  • Oral contraceptives
  • Warfarin used to prevent blood clots
  • Carbamazepine and phenytoin used to treat seizures
  • Ketoconazole used to treat fungal infections
  • Digoxin used to treat heart complaints
  • Sucralfate (used to treat gastric ulcers) and antacids (used to treat heartburn and indigestion)
    Zoton FasTabs should be taken at least one hour before taking sucralfate or an antacid.
  • Iron preparations
  • Ampicillin esters used in some antibiotics
  • Tacrolimus used in transplant patients to reduce organ rejection
  • Atazanavir, nelfinavir or other medicines used to treat HIV infection
  • Methotrexate used to treat some cancers.

These medicines may be affected by Zoton FasTabs, or may affect how well it works. You may need different amounts of your medicine, or you may need to take different medicines. Your doctor will advise you.

How to take Zoton FasTabs

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

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

When to take it

Take Zoton FasTabs in the morning before food. Zoton FasTabs works best when taken on an empty stomach.

How much to take

Take one tablet each day, unless your doctor has told you otherwise.

Adults
The dose is usually 30 mg a day. The dose may vary from 15 mg to 30 mg a day depending on your condition.

Children (6 years or older)
For children between 6 to 11 years, the recommended dose depends on the weight of the child.

For children weighing 30 kg or less, the usual dose is 15 mg daily.

For children weighing over 30 kg, the usual dose is one 30 mg tablet daily.

For children between 12 to 17 years, the dose may vary from 15 mg to 30 mg a day depending on the condition.

How to take it

Swallow the tablet whole with a glass of water, or gently suck the tablet, then swallow the granules with your saliva. Do not chew or crush the tablet as this affects how well Zoton FasTabs works.

How long to take it

Keep taking Zoton FasTabs as directed, unless your doctor gives you other instructions.

In most patients, Zoton FasTabs relieves symptoms rapidly and healing is usually complete within 4 weeks. In some patients a further 4 weeks of treatment may be needed for complete healing.

In some cases, your doctor may decide that long-term treatment is needed.

Tell your doctor if any of your symptoms return after stopping long-term treatment.

Zoton FasTabs is recommended only for short-term use (8 to 12 weeks) in children.

For children aged 6-11 years, do not exceed 12 weeks of treatment with Zoton FasTabs.

For children aged 12-17 years, do not exceed 8 weeks of treatment with Zoton FasTabs.

Tell your doctor if your symptoms return. You may need further treatment.

If you forget to take it

If it is almost time for the next dose, skip the missed dose and take the next dose when you are meant to. Otherwise, take it as soon as you remember, and then go back to your normal routine.

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

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

If you take too much (overdose)

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

While you are taking Zoton FasTabs

Things you must do

Take Zoton FasTabs exactly as your doctor has prescribed.

Tell your doctor if you become pregnant while you are taking Zoton FasTabs.

If you are about to start any new medicine, remind your doctor and pharmacist that you are taking Zoton FasTabs.

Things you must not do

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

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

Do not stop taking your medicine or change the dosage without checking with your doctor. If you stop taking it suddenly, your condition may worsen or you may have unwanted side effects.

Things to be careful of

Be careful driving or operating machinery until you know how Zoton FasTabs affects you. Zoton FasTabs generally does not cause any problems with your ability to drive a car or operate machinery. However, as with many other medicines, Zoton FasTabs may cause dizziness in some people. Make sure you know how you react to Zoton FasTabs before you drive a car, operate machinery, or do anything else that could be dangerous if you are dizzy. If you drink alcohol, dizziness may be worse.

Things that may help your condition

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

  • Alcohol
    Your doctor may advise you to limit your alcohol intake.
  • Aspirin and many other medicines used to treat arthritis, period pain or 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 that contain caffeine, such as coffee, tea, cocoa and cola drinks, because they contain ingredients that may irritate the stomach.
  • Eating habits
    Eat smaller, more frequent meals. Eat slowly and chew your food carefully. Try not to rush at meal times. Eat your meals well before bedtime.
  • Smoking
    Your doctor may advise you to stop smoking or at least cut down.
  • Weight
    Your doctor may suggest losing some weight to help your condition.

Side effects

Tell your doctor as soon as possible if you do not feel well while taking Zoton FasTabs.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

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

Ask your doctor or pharmacist any questions you may have.

Tell your doctor if…

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

Stomach or bowel problems such as:

  • Vomiting or nausea
  • Diarrhoea or constipation
  • Stomach pain
  • Indigestion
  • Flatulence or wind.

If you suffer from severe persistent diarrhoea and/or vomiting when taking Zoton FasTabs, tell your doctor.

As natural acid in the stomach helps to kill bacteria, the lowering of acid by acid-reducing medicines such as Zoton FasTabs may cause some people to get certain stomach infections.

Difficulty thinking or working because of:

  • Headache
  • Dizziness
  • Tiredness
  • Joint or muscle aches or pains
  • Generally feeling unwell
  • Feeling confused, depressed or having hallucinations.

Changes to your appearance such as:

  • Skin rashes
  • Hives or itchy skin
  • Hair thinning
  • Breast enlargement and impotence in men with long term use.

Signs of infection such as:

  • Coughs, colds, sore throats or sinuses indicating an upper respiratory tract infection
  • Frequent and painful passing of urine indicating a urinary tract infection
  • Dry or sore mouth or throat.

Changes in your sight, hearing, taste or touch such as:

  • Tingling or numbness of hands and feet
  • Blurred vision
  • Increased sensitivity to sunlight
  • Taste disturbances.

Go to hospital if…

Tell your doctor immediately or go to Accident and Emergency at your nearest hospital if you notice any of the following:

  • Red, itchy blistering spots, especially if it appears in areas of the skin that are exposed to the sun and is accompanied by joint pain
  • Yellowing of the skin or eyes, especially if accompanied by fever, fatigue, loss of appetite, dark coloured urine or light coloured bowel movements
  • Watery and severe diarrhoea
  • Pain in the kidney region
  • Swelling of the face, lips, tongue or throat, which may cause difficulty breathing
  • Swelling of hands, ankles or feet
  • Bruising or bleeding more easily than normal, bleeding under the skin or red or purple flat pinhead spots under the skin
  • Frequent infections such as fever, severe chills, sore throat or mouth ulcers
  • Cramping of the muscles in your hands or feet
  • Irregular heartbeat
  • Fits or seizures.

These are serious to very serious side effects. You may need urgent medical attention. These side effects are rare.

Tell your doctor if you notice anything making you feel unwell when taking, or soon after finishing taking, Zoton FasTabs.

Other side effects not listed above may occur in some patients.

Other problems are more likely to arise from the ulcer itself rather than the treatment.

For this reason, contact your doctor immediately if you notice any of the following:

  • Pain or indigestion occurring during treatment with Zoton FasTabs
  • You begin to vomit blood or food
  • You pass black (blood-stained) motions.

Ask your doctor or pharmacist if you do not understand anything in this list.

After taking Zoton FasTabs

Storage

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

Keep it in a cool dry place where the temperature stays below 25 °C. Do not store it or any other medicines in a bathroom or near a sink. Do not leave it in the car or on windowsills. Heat and 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.

Disposal

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

Product description

What it looks like

Zoton FasTabs 15 mg is available in a blister pack of 28 tablets.

Zoton FasTabs 30 mg is available in a blister pack of 7 or 28 tablets.

Zoton FasTabs 15 mg tablets are white to yellowish white uncoated tablets with orange to dark brown speckles, with "15" marked on one side.

Zoton FasTabs 30 mg tablets are white to yellowish white uncoated tablets with orange to dark brown speckles, with "30" marked on one side.

Ingredients

Zoton FasTabs contain either 15 mg or 30 mg of lansoprazole as the active ingredient.

Zoton FasTabs also contain the inactive ingredients:

  • Lactose monohydrate
  • Microcrystalline cellulose
  • Magnesium carbonate hydrate
  • Low-substituted hyprolose
  • Hyprolose
  • Hypromellose
  • Titanium dioxide
  • Purified talc
  • Mannitol
  • Methacrylic acid - ethyl acrylate copolymer (1:1) 30 percent
  • Polyacrylate dispersion 30 percent
  • Macrogol 8000
  • Citric acid
  • Glyceryl monostearate
  • Polysorbate 80
  • Triethyl citrate
  • Iron oxide yellow (E172)
  • Iron oxide red (E172)
  • Crospovidone
  • Magnesium stearate
  • Strawberry flavour
  • Aspartame.

Zoton FasTabs do not contain gluten, tartrazine or any other azo dyes.

Australian Registration Number
Zoton FasTabs 15 mg tablets: AUST R 153575.

Zoton FasTabs 30 mg tablets: AUST R 153701.

Supplier

Pfizer Australia Pty Ltd
Sydney NSW
Toll Free Number: 1800 675 229.

This leaflet was prepared in September 2019

© Pfizer Australia Pty Ltd 2019.

® Manufactured by and licensed from Takeda Chemical Industries Limited, Osaka Japan. Proprietor of the trademark Zoton FasTabs®.

Published by MIMS November 2019

BRAND INFORMATION

Brand name

Zoton FasTabs

Active ingredient

Lansoprazole

Schedule

S4

 

1 Name of Medicine

Zoton FasTabs (lansoprazole) 15 mg and 30 mg tablets.

6.7 Physicochemical Properties

Non-proprietary name: lansoprazole.
Chemical name: 2[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl] methyl] sulphinyl]-1H-benzimidazole.
Molecular formula: C16H14F3N3O2S.
Molecular weight: MW 369.36.
Lansoprazole is a substituted benzimidazole. It is a white to slightly brownish crystalline, acid-labile powder, slightly soluble in ethanol and almost insoluble in water (0.033 mg/mL), but more soluble at higher pH. It is a chiral compound with one centre (-SO) and is present as a racemic mixture. Lansoprazole melts at 165.8°C with decomposition and has a pKa of 8.8.

Chemical structure.

The structural formula of lansoprazole is shown:

CAS number.

CAS Registry Number: CAS No. 103577-45-3.

2 Qualitative and Quantitative Composition

Zoton FasTabs contain 15 mg or 30 mg of lansoprazole.

Excipients with known effect.

Lactose monohydrate.
For the full list of excipients, see Section 6.1.

3 Pharmaceutical Form

White to yellowish white circular, flat bevelled-edge oro-dispersible tablets speckled with orange to dark brown enteric-coated microgranules, with "15" or "30" debossed on one side of the tablet.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Lansoprazole reduces gastric acid secretions by inhibiting the H+/K+-ATPase (proton pump) of the parietal cells in the gastric mucosa, the terminal phase of acid secretion. The drug is effective in the treatment of acid-related disorders of the upper gastrointestinal tract.
A single dose of 30 mg lansoprazole inhibits stimulated acid secretion by approximately 80%. Basal acid secretion and basal and stimulated secretion volumes are affected to a lesser degree.
After repeated dosing (for 7 days) 90% inhibition of stimulated acid secretion is achieved. Despite its short elimination half-life, lansoprazole has a prolonged pharmacological action, providing effective suppression of gastric acid secretion over 24 hours.
When used in combination with the recommended antibiotics, Zoton is associated with H. pylori eradication rates of up to 90%.

Clinical trials.

Helicobacter pylori.

In clinical trials, the recommended dosage regimens were associated with H. pylori eradication rates of up to 90%. The best eradication rates were obtained with regimens which included clarithromycin. Trials which used Zoton in combination with only one antibiotic resulted in significantly lower eradication rates. Therefore, such regimens are not recommended.

Reflux oesophagitis.

Paediatrics.

In an open-label, U.S. multicentre study, 66 children, 1 to 11 years of age, with GORD were assigned to receive an initial dose of either lansoprazole 15 mg capsules once daily, if the body weight was < 30 kg, or lansoprazole 30 mg capsules once daily, if the body weight was > 30 kg, administered for 8 to 12 weeks. The lansoprazole dose was increased up to 60 mg daily in some children after 2 weeks of treatment. (See Table 3.)
Treatment with lansoprazole also demonstrated significant reduction in frequency and severity of GORD symptoms (p < 0.001).
In a double blind, U.S. multicentre study, 63 patients 12 to 17 years of age with proven GORD were randomised to receive either lansoprazole 15 mg once daily or 30 mg once daily for five days. Subjects in both groups demonstrated improvement in symptoms of reflux disease. A reduction in heartburn severity was shown to be statistically significant for patients treated with either 15 mg or 30 mg lansoprazole. The majority of patients (69% for lansoprazole 15 mg once daily and 74% for lansoprazole 30 mg once daily) reported that their reflux symptoms were better after treatment.

Adults.

In two double-blind, placebo controlled multicentre studies (of 336 patients) examining the efficacy of lansoprazole 15 mg and 30 mg tablets in maintaining healed erosive reflux oesophagitis, lansoprazole was significantly superior to placebo in maintaining endoscopic and symptomatic freedom from disease. The time to median recurrence of either symptoms or endoscopic evidence of disease was less than 1 month for the placebo and greater than 12 months for 15 mg and 30 mg lansoprazole (p ≤ 0.001). There was a slight trend for a better outcome with 30 mg lansoprazole, although this was not statistically significant.
A study in 266 patients, comparing lansoprazole 15 mg and 30 mg daily with ranitidine 300 mg twice daily, found both lansoprazole 15 mg and 30 mg increased the time to relapse and probability of no relapse in comparison to ranitidine. The percentage of patients who relapsed endoscopically during the 12-month maintenance period was 31% in the lansoprazole 15 mg group, 20% in the lansoprazole 30 mg group and 68% in the ranitidine group. The difference between the lansoprazole groups and the ranitidine was apparent from the earliest time point in the study and maintained throughout the 12-month period. Comparison of treatment groups with regard to symptom control showed similar superiority of lansoprazole over ranitidine (p < 0.001 for each comparison).
A study in 882 patients comparing lansoprazole 15 mg and 30 mg daily with omeprazole 20 mg daily showed endoscopic remission rates (after 12 months) of 75% with lansoprazole 15 mg daily, 88% with lansoprazole 30 mg daily and 89% with omeprazole 20 mg daily. The results demonstrate that lansoprazole 30 mg daily achieved significantly better remission rates compared to lansoprazole 15 mg daily and is of equal efficacy to omeprazole 20 mg daily.
The results of the 4 pivotal studies examining the use of lansoprazole in the long-term management of reflux oesophagitis are tabulated in Table 4.

Duodenal ulcer.

In a study comparing lansoprazole 15 mg daily with placebo in 180 patients with endoscopically documented duodenal ulcer, the percentage of patients who remained healed after twelve months was significantly higher with lansoprazole than with placebo. Lansoprazole 15 mg was significantly superior to placebo in preventing endoscopic and symptomatic relapses of disease. (See Table 5.)
The maintenance studies discussed, using lansoprazole 15 mg and 30 mg, did not extend beyond 12 months.

Acid-related dyspepsia.

The efficacy of lansoprazole 15-30 mg daily has been examined in a total of 531 patients, compared with ranitidine (n=171), omeprazole (n=281) and placebo (n=138).
The efficacy of lansoprazole (30 mg mane) was compared to ranitidine (150 mg bd) for the treatment of acid-related dyspepsia in a double-blind, parallel, 4-week study. The results are presented in Table 6.
There was also a significant difference in the usage of "rescue" antacid treatment in the two groups, with 67% of the lansoprazole group taking antacids in the first two weeks of treatment compared with 83% of the ranitidine group (p=0.001).
In patients with symptoms of ulcer-like and reflux-like dyspepsia, lansoprazole 15 mg mane was compared to omeprazole 10 mg mane for a 4-week period in a double-blind, parallel study. In the primary efficacy analyses in the intent to treat population, the study revealed that more patients were free of overall primary symptoms of dyspepsia in the lansoprazole-treated group compared to the omeprazole-treated group (p=0.007 and 0.078 respectively). (See Table 7.)

Non-ulcer dyspepsia.

A randomised, double-blind parallel study 15 mg lansoprazole mane was compared to placebo in 269 patients suffering from non-ulcer dyspepsia. In the intent-to-treat population the healing rate was 81/131 (61.8%) in the lansoprazole group after 2-3 weeks treatment, compared to 61/138 (44.2%) in the placebo group (p=0.005). In the 3-month follow-up period, the recurrence of non-ulcer dyspepsia symptoms was reported by 32/86 (37.2%) patients in the lansoprazole group and by 29/79 (36.7%) in the placebo group (p=1.0). Healing was defined as the percentage of patients with no heartburn or acid regurgitation, as well as no nausea and vomiting and a reduction in the Visual Analogue Scale value of ≤ 20% during the last 5 days of treatment.

5.2 Pharmacokinetic Properties

Adults.

Lansoprazole is well absorbed and exhibits high bioavailability (80-90%) following an oral dose. The bioavailability has been shown to be affected by the presence of food; however, acid inhibition (which is an endpoint for efficacy), as measured from sampling of gastric juice in healthy volunteers, is not significantly affected by food. It was shown in one study that a.m. dosing produced higher mean gastric pH values than p.m. dosing.
Plasma protein binding is high (98%) and is gender and concentration independent. Binding does not change as a result of multiple dosing. The plasma elimination half-life in healthy subjects ranges from 1 to 2 hours following a single dose or multiple doses. Peak plasma levels occur within 1.5 to 2.0 hours after dosing in these subjects.
After IV administration, the volume of distribution is 29 ± 4 L, total clearance is 31 ± 8 L/h and elimination half-life is 0.9 ± 0.44 h.
Following absorption, lansoprazole is extensively metabolised and the metabolites are excreted by both the renal and biliary route. A study with 14C-labelled lansoprazole showed that up to 50% of the label was excreted in the urine, although unchanged drug does not appear to be excreted by this route; unchanged drug is eliminated, however, by biliary excretion.

Paediatric patients 1 to 11 years of age.

The pharmacokinetics of lansoprazole were studied in paediatric patients with gastro-oesophageal reflux disease (GORD) aged 1 to 11 years, with lansoprazole capsule doses of 15 mg once daily for subjects weighing < 30 kg and 30 mg once daily for subjects weighing > 30 kg. Lansoprazole pharmacokinetics in these paediatric patients were similar to those previously observed in healthy adult subjects. The mean Cmax and AUC values were similar between the two dose groups and were not affected by weight or age within each weight-adjusted dose group used in this study.

Paediatric patients 12 to 17 years of age.

In a study of paediatric patients aged 12 to 17 years with GORD, the pharmacokinetics of lansoprazole were shown to be similar to those previously observed in healthy adult subjects. No statistically significant differences were observed between doses for Tmax, t1/2 or natural logarithms of dose normalised Cmax and AUC0-24. None of the selected covariates (body weight, age and gender) had any statistically significant effect on lansoprazole Tmax or the natural logarithms of dose normalised Cmax and AUC0-24.

5.3 Preclinical Safety Data

Carcinogenicity/mutagenicity, impairment of fertility.

In a 2-year carcinogenicity study in rats, oral doses of 5, 15 or 50 mg/kg/day, 5 days per week produced gastric ECL cell hyperplasia and carcinoid tumours in a dose-related manner in both male and female rats. The incidence of these effects was markedly higher in female rats. A "no-effect" dose was not established for female rats. An increased incidence of benign Leydig cell tumours and testicular hyperplasia was also reported at dose levels of 15 mg/kg/day. Two repeat 2-year carcinogenicity studies in rats using doses ranging from 5-150 mg/kg/day, 7 days per week confirmed these findings. The effects of lansoprazole on human male fertility have not been evaluated.
In mice, a 78-week carcinogenicity study was performed at doses of 1.5, 5, 15 and 50 mg/kg/day, 5 days per week. No gastric ECL cell carcinoids were seen. In a repeat carcinogenicity study, mice were dosed with 15, 75, 150 or 300 mg/kg/day, 7 days a week. Terminal studies showed ECL cell hyperplasia, mucosal hyperplasia/hypertrophy and glandular dilatation and vacuolation at all dosages. Carcinoids were found in occasional animals receiving 15, 150 or 300 mg/kg/day.
Hypergastrinaemia secondary to prolonged hypochlorhydria has been postulated to be the mechanism by which ECL cell hyperplasia and gastric carcinoid tumours develop.
Negative results were obtained in gene mutation assays and in an in vivo assay of chromosomal damage. In vitro assays of chromosomal damage showed evidence of chromosomal aberrations, though this may reflect cytotoxicity rather than genotoxic activity.

Juvenile animal studies.

In an 8-week juvenile rat study, changes in male reproductive tissue (testes and epididymis) and heart (cardiac valve thickening) occurred at approximately 6-fold and 11-fold the expected human exposure, respectively, based on AUC (75-fold and 150-fold the expected human exposure based on body surface area). The findings reversed or trended towards reversibility after a 4-week drug-free recovery period.
The relevance of these findings to paediatric patients less than 12 years of age is unknown. The findings in this study are not relevant for patients 12 years of age and above.

4 Clinical Particulars

4.1 Therapeutic Indications

Adults.

1. Healing and long-term management of reflux oesophagitis.
2. Healing and long-term management for patients with duodenal ulcer.
3. Healing of benign gastric ulcer (see Section 4.2).
4. Lansoprazole is also effective in patients with benign peptic lesions that do not respond to H2-receptor antagonists.
5. Eradication of H. pylori from the upper gastrointestinal tract in patients with peptic ulcer or chronic gastritis when used in combination with appropriate antibiotics (see Section 5.1, Clinical trials).
6. Relief of reflux-like and/or ulcer-like symptoms associated with acid-related dyspepsia.

Paediatric patients 6 to 17 years of age.

1. Treatment of gastro-oesophageal reflux disease, including all grades of oesophagitis.
2. Healing of erosive oesophagitis.

4.3 Contraindications

Hypersensitivity to lansoprazole, other proton pump inhibitors (PPIs) or any of the excipients in the tablets.
Severe hepatic impairment.
Lansoprazole should not be co-administered with atazanavir due to a significant reduction in atazanavir exposure.

4.4 Special Warnings and Precautions for Use

As with other anti-ulcer therapies, the possibilities of malignancy should be excluded when a gastric ulcer is suspected, since treatment with lansoprazole may alleviate the symptoms of a malignancy and possibly delay its diagnosis.
Similarly, the possibility of serious underlying disease such as malignancy should be excluded before treatment for dyspepsia commences, particularly in patients of middle age or older who have new or recently changed dyspeptic symptoms.
The granules in Zoton FasTabs are enteric coated. Therefore, the tablets should be sucked slowly and should not be crushed or chewed.

Use with caution in the following circumstances.

Agents that elevate gastric pH may increase the already-present risk of nosocomial pneumonia in intubated ICU patients receiving mechanical ventilation.
When using lansoprazole with antibiotics to eradicate H. pylori, it is recommended that prescribers see the approved product information for the antibiotics selected.
Decreased gastric acidity due to any means, including proton pump inhibitors, increases gastric counts of bacteria normally present in the gastrointestinal tract. Treatment with acid-reducing drugs may lead to a slightly increased risk of gastrointestinal infections such as Salmonella and Campylobacter. Proton pump inhibitor therapy may be associated with an increased risk of Clostridium difficile infection.
Daily treatment with any acid-suppressing medications over a long period of time (e.g. longer than 3 years) may lead to malabsorption of cyanocobalamin (vitamin B12) caused by hypo- or achlorhydria. Cyanocobalamin deficiency should be considered in patients with Zollinger-Ellison syndrome and other pathological hypersecretory conditions requiring long-term treatment, individuals with reduced body stores or risk factors for reduced vitamin B12 absorption (such as the elderly) on long-term therapy or if relevant clinical symptoms are observed.
PPIs, especially if used in high doses and over long durations (> 1 year), may modestly increase the risk of hip, wrist and spine fracture, predominantly in the elderly or in presence of other recognised risk factors. Observational studies suggest that PPIs may increase the overall risk of fracture. Some of this increase may be due to other risk factors. Patients at risk of osteoporosis should receive clinical guidelines and they should have an adequate intake of vitamin D and calcium.

Enterochromaffin-like (ECL) cell effects.

Safety concerns of long-term treatment relate to hypergastrinaemia and possible ECL effects. ECL cell hyperplasia and gastric carcinoid tumour were observed in animal studies.
Human gastric biopsy specimens from patients treated with proton pump inhibitors have not detected ECL cell effects similar to those seen in rats. Gastric biopsies taken in all the long-term maintenance studies have revealed the following.
A slight increase in mean endocrine cell count during 12 months maintenance treatment with lansoprazole 15 or 30 mg, observed in 3 of 4 studies. Cell density averages were slightly higher under 30 mg lansoprazole than under 15 mg lansoprazole once daily. These observations were reversible approximately 3 months after maintenance therapy stopped in two of the studies.
Single cases of changes from normal to simple hyperplasia which persisted in one patient 3 months after discontinuation of treatment.
For antral biopsies a greater mean gastrin-positive cell density and mean serotonin-positive cell density was found for lansoprazole 30 mg compared to lansoprazole 15 mg once daily.
No evidence of carcinoid tumours or visible endocrine cell proliferation was seen in any patient for either fundus or antral biopsies.
(There are currently biopsy data on over 400 patients treated between 9 months and one year and over 230 patients treated for more than one year.)

Retinal atrophy.

In animal studies, retinal atrophy was observed in Sprague Dawley rats dosed orally with lansoprazole. Retinal atrophy has not been found in mice, dogs, monkeys or humans. Mechanistic studies have indicated that the effect is specific to species dependent on hepatic synthesis of the amino acid taurine, which has a protective effect on the retina. Lansoprazole inhibits hepatic synthesis of taurine; however, humans obtain their taurine requirements from the diet.

Impaired hepatic and renal function.

Lansoprazole is metabolised substantially by the liver. The results of clinical trials in adult patients with liver disease indicate that the metabolism of lansoprazole is prolonged in patients with severe hepatic impairment. Consider dose adjustment in patients with severe hepatic impairment. There is no need to alter the dosage in adult patients with impaired renal function.
There is insufficient experience to recommend the use of lansoprazole in paediatric patients with hepatic or renal impairment.

Acute interstitial nephritis.

Acute interstitial nephritis has been observed in patients taking PPIs including lansoprazole. Acute interstitial nephritis may occur at any point during PPI therapy and is generally attributed to an idiopathic hypersensitivity reaction. Discontinue lansoprazole if acute interstitial nephritis develops.

Hypomagnesaemia.

Hypomagnesaemia, symptomatic and asymptomatic, has been reported rarely in patients treated with PPIs for at least three months, in most cases after a year of therapy. Serious adverse events include tetany, arrhythmias, and seizures. In most patients, treatment of hypomagnesaemia required magnesium replacement and discontinuation of the PPI.
For patients expected to be on prolonged treatment or who take PPIs with medications such as digoxin or drugs that may cause hypomagnesaemia (e.g. diuretics), health care professionals may consider monitoring magnesium levels prior to initiation of PPI treatment and periodically during PPI treatment.

Subacute cutaneous lupus erythematosus (SCLE).

Proton pump inhibitors are associated in rare cases with the occurrence of subacute cutaneous lupus erythematosus (SCLE). If lesions occur, especially in sun exposed areas of the skin, and if accompanied by arthralgia, the patient should seek medical help promptly and the healthcare professional should consider stopping the product.

Use in the elderly.

Dosage adjustment is not required in the elderly.

Interference with laboratory tests.

Increased Chromogranin A (CgA) level may interfere with investigations for neuroendocrine tumours. To avoid this interference, proton pump inhibitor treatment should be stopped 14 days before CgA measurements.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Lansoprazole is metabolised in the liver and is a weak inducer of cytochrome P450. Therefore, there is the possibility of interaction with other drugs metabolised via this system, e.g. theophylline, phenytoin, carbamazepine and warfarin. Patients receiving such drugs concomitantly with lansoprazole should be monitored to determine if any dosage adjustment is necessary.
There have been isolated cases of a suspected drug interaction with warfarin, but a definitive relationship to lansoprazole therapy has not been established.
No clinically significant effects on plasma levels of non-steroidal anti-inflammatory drugs, phenytoin (single IV doses only) and diazepam have been found.
Concomitant administration of lansoprazole and tacrolimus may increase whole blood levels of tacrolimus, especially in transplant patients who are intermediate or poor metabolisers of CYP2C19. Inhibitors of CYP2C19 such as fluvoxamine would likely increase the systemic exposure to lansoprazole. Inducers of CYP2C19 would likely decrease the systemic exposure to lansoprazole. The possibility of interaction between lansoprazole and low-dose oral contraceptives cannot be excluded.
Coadministration of lansoprazole with sucralfate delayed absorption and reduced lansoprazole bioavailability by approximately 30%. Similarly, antacids may also reduce the bioavailability of lansoprazole. Therefore, lansoprazole should be taken at least an hour prior to sucralfate or antacid administration.
Lansoprazole causes a profound and long-lasting inhibition of gastric acid secretion; therefore, lansoprazole may interfere with the absorption of drugs where gastric pH is an important determinant of bioavailability (e.g. ketoconazole, ampicillin esters, iron salts, digoxin).
Coadministration of PPIs in healthy subjects and in transplant patients receiving mycophenolate mofetil has been reported to reduce exposure to the active metabolite, mycophenolic acid. This is possibly due to a decrease in mycophenolate mofetil solubility at an increased gastric pH. The clinical relevance of reduced mycophenolic acid exposure on organ rejection has not been established in transplant patients receiving PPIs and mycophenolate mofetil. Use lansoprazole with caution in transplant patients receiving mycophenolate mofetil.
Concomitant use with methotrexate (primarily at high dose), may elevate and prolong serum levels of methotrexate and/or its metabolite, possible leading to methotrexate toxicities. A temporary withdrawal of the PPI may be considered in some patients receiving treatments with high dose methotrexate.
Lansoprazole, and other PPIs, should not be co-administered with HIV protease inhibitors for which absorption is dependent on acidic intragastric pH (e.g. atazanavir and nelfinavir), due to significant reduction in their bioavailability. The decreased systemic concentration of the HIV protease inhibitor may result in a loss of therapeutic effect and the development of HIV resistance.
Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

See Section 5.3.
(Category B3)
Reproductive studies conducted in pregnant rats and rabbits at oral doses up to 300 and 30 mg/kg/day, respectively, did not disclose any evidence of a teratogenic effect. A significant increase in fetal mortality was observed in the rabbit study at doses above 10 mg/kg/day. In rats a slight reduction in litter survival and weights was noted at doses above 100 mg/kg/day.
There are insufficient data to recommend the administration of lansoprazole during pregnancy. Lansoprazole should not be used during pregnancy, unless the benefit clearly outweighs the potential risk to the fetus.
Animal studies indicate that lansoprazole is secreted into breast milk. There is no information on the secretion of lansoprazole into breast milk in humans. The use of lansoprazole during breast feeding should be avoided.

4.8 Adverse Effects (Undesirable Effects)

Zoton is well-tolerated, with adverse events generally being mild and transient.

Nervous system disorders.

Headache, dizziness.
Rarely, paraesthesia and taste disturbances.

Psychiatric disorders.

Depression, confusion and hallucinations.

Gastrointestinal disorders.

Diarrhoea, constipation, abdominal pain, dyspepsia, nausea, vomiting, flatulence, and dry or sore mouth or throat.
Frequency not known: Withdrawal of long-term PPI therapy can lead to aggravation of acid-related symptoms and may result in rebound acid hypersecretion.
Rarely, cases of colitis (macroscopic and microscopic) have been reported. In severe and/or protracted cases of diarrhoea, discontinuation of therapy should be considered. In the majority of cases symptoms resolve on discontinuation of therapy.

Infections and infestations.

Upper respiratory tract infections, urinary tract infections.
As with any broad-spectrum antibiotic treatment, the risk of pseudomembranous colitis should be considered in patients using triple therapy for the eradication of H. pylori.

Hepatobiliary disorders.

Abnormal liver function test values, elevation of aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase, lactate dehydrogenase (LDH) and gamma-glutamyl transpeptidase (γ-GTP).
Rarely, jaundice or hepatitis have been reported. However, routine monitoring of liver function tests is not required.

Skin and subcutaneous tissue disorders.

Skin rashes, urticaria and pruritus. These generally resolve on discontinuation of drug therapy. Serious dermatological reactions are rare but there have been occasional reports of Stevens-Johnson syndrome, toxic epidermal necrolysis and erythematous or bullous rashes including cutaneous lupus erythematosus and erythema multiforme. Cases of hair thinning and photosensitivity have also been reported.

Immune system disorders.

Angioedema, wheezing and, very rarely, anaphylactic reaction.

Renal and urinary disorders.

Cases of interstitial nephritis have been reported which have sometimes resulted in renal failure.

Metabolism and nutrition disorders.

Hypomagnesaemia has been reported rarely.
There have been isolated reports of hyponatraemia, but a definitive relationship to lansoprazole therapy has not been established.

Blood and lymphatic system disorders.

Haematological effects (thrombocytopenia, agranulocytosis, eosinophilia, leucopoenia, neutropenia and pancytopenia) have occurred rarely. Bruising, purpura and petechiae have also been reported.

Musculoskeletal and connective tissue disorders.

Arthralgia, myalgia.

Eye disorders.

Blurred vision.

Ear and labyrinth disorders.

Vertigo.

Respiratory, thoracic and mediastinal disorders.

There have been isolated reports of interstitial pneumonia, but a definitive relationship to lansoprazole therapy has not been established.

Reproductive system and breast disorders.

Gynaecomastia and erectile dysfunction have been reported rarely.

Injury, poisoning and procedural complications.

Fracture of the hip, wrist or spine has been reported.

General disorders and administration site conditions.

Fatigue, malaise, peripheral oedema.
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 https://www.tga.gov.au/reporting-problems.

4.2 Dose and Method of Administration

For oral administration.
Zoton FasTabs are strawberry flavoured and should be placed on the tongue and gently sucked. The tablet rapidly disperses in the mouth, releasing the enteric-coated microgranules, which are swallowed with the patient's saliva. Alternatively, the tablet can be swallowed whole with a drink of water. The tablets must not be chewed.
The tablets should not be crushed or chewed (see Section 4.4). To achieve the optimal acid inhibitory effect, and hence most rapid healing and symptom relief, Zoton 'once daily' should be administered in the morning before food.

Adults.

Reflux oesophagitis.

30 mg lansoprazole once daily for 4 weeks. The majority of patients will be healed after the first course. For patients who have not fully healed within this time, a further 4 weeks treatment using the same dosage regimen is indicated. For long-term management, a maintenance dose of 15 mg or 30 mg once daily can be used dependent upon patient response.

Duodenal ulcer*.

30 mg lansoprazole once daily for 4 weeks. For the prevention of relapse, the recommended maintenance dose is 15 mg once daily.

Gastric ulcer*.

30 mg lansoprazole once daily for 8 weeks.
*Patients whose gastric or duodenal ulcer is not associated with ingestion of non-steroidal anti-inflammatory drugs require treatment with antimicrobial agents in addition to antisecretory drugs whether on first presentation or on recurrence.

Acid-related dyspepsia.

15 mg or 30 mg lansoprazole once daily for 2-4 weeks, depending on the severity and persistence of symptoms. Patients who do not respond after 4 weeks, or who relapse shortly afterwards, should be investigated.

Eradication of H. pylori.

The following combinations have been shown to be effective when used for 7 days: 30 mg lansoprazole twice daily plus two of the following antibiotics: amoxycillin 1 g twice daily, metronidazole 400 mg twice daily and clarithromycin 250 mg twice daily.

Paediatrics.

Paediatric patients 6 to 11 years of age.

In clinical studies, lansoprazole was not administered beyond 12 weeks in 6 to 11 year olds. It is not known if lansoprazole is safe and effective if used longer than the recommended duration. Do not exceed the recommended dose and duration of use in children as outlined in Table 1 (see Section 5.3 for nonclinical data).

Paediatric patients 12 to 17 years of age.

In clinical studies, lansoprazole was not administered beyond 8 weeks in 12 to 17 year olds. It is not known if lansoprazole is safe and effective if used longer than the recommended duration. Do not exceed the recommended dose and duration of use in children as outlined in Table 2.

4.7 Effects on Ability to Drive and Use Machines

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

4.9 Overdose

There is no information on the effect of acute overdosage. In a case of overdose, supportive and symptomatic therapy should be initiated. Doses of up to 180 mg/day for more than a year have been used to treat Zollinger-Ellison syndrome with no serious adverse effects.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

7 Medicine Schedule (Poisons Standard)

S4.

6 Pharmaceutical Particulars

6.1 List of Excipients

The gastro-resistant microgranules contain the excipients: lactose monohydrate, microcrystalline cellulose, magnesium carbonate hydrate, low-substituted hyprolose, hyprolose, hypromellose, titanium dioxide, talc, mannitol, methacrylic acid - ethyl acrylate copolymer (1:1) 30 per cent, polyacrylate dispersion 30 per cent, macrogol 8000, citric acid, glyceryl monostearate, polysorbate 80, triethyl citrate, iron oxide yellow (E172) and iron oxide red (E172).
Other excipients contained in the tablets are crospovidone, magnesium stearate, strawberry flavour and aspartame.

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

Zoton FasTabs should be stored below 25°C.

6.5 Nature and Contents of Container

Supplied in blister packs of 7 or 28 tablets.

6.6 Special Precautions for Disposal

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

Summary Table of Changes