Consumer medicine information

Lanzopran

Lansoprazole

BRAND INFORMATION

Brand name

Lanzopran

Active ingredient

Lansoprazole

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Lanzopran.

What is in this leaflet

This leaflet answers some common questions about LANZOPRAN.

It does not contain all the available information.

It does not take the place of talking to your doctor or pharmacist.

This leaflet was last updated on the date at the end of this leaflet. More recent information may be available. The latest Consumer Medicine Information is available from https://www.ebs.tga.gov.au/ and may contain important information about the medicine and its use of which you should be aware.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking LANZOPRAN against the benefits it is expected to have for you.

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

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

What Lanzopran is used for

The name of your medicine is LANZOPRAN.

LANZOPRAN contains lansoprazole as active ingredient. Lansoprazole belongs to a group of medicines called proton pump inhibitors (PPIs). Lansoprazole works by decreasing the amount of acid the stomach makes, to give relief from the symptoms and allow healing to take place.

Reflux Oesophagitis (inflammation of oesophagus):
LANZOPRAN
is used to treat the symptoms of reflux oesophagitis or reflux disease in adults and in children from 1 to 17 years of age. This can be caused by backflow (reflux) of food and acid from the stomach into the food pipe, also known as the oesophagus. Reflux can cause a burning sensation in the chest rising up to the throat, also known as heart burn.

Peptic Ulcers (Ulcers of stomach or duodenum):
LANZOPRAN is used to treat peptic ulcers in adults. Depending on the position of the ulcer it is called a gastric or duodenal ulcer. A gastric ulcer occurs in the stomach. A duodenal ulcer occurs in the duodenum, which is the tube leading out of the stomach. These can be caused in part by too much acid being made in the stomach. LANZOPRAN is also used to stop duodenal ulcers from coming back.

LANZOPRAN is also used for treatment of infections caused by the bacteria Helicobacter pylori when given in combination with antibiotic therapy.

LANZOPRAN is also used for the treatment of heartburn and acid regurgitation.

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

Before you take Lanzopran

When you must not take it

  • Do not take LANZOPRAN if you are allergic to lansoprazole, any medicines containing a proton-pump inhibitor or any of the ingredients listed at the end of this leaflet.
    Symptoms of an allergic reaction may include skin rash, itchiness or hives, shortness of breath, wheezing or difficulty breathing, swelling of the tongue, lips, face or other parts of the body.
  • Do not take LANZOPRAN if you have severe problems with your liver.
  • Do not take LANZOPRAN after the expiry date printed on the pack.
    If you take it after the expiry date has passed, it may not work as well.
  • Do not take LANZOPRAN if the capsules do not look quite right.
  • Do not take LANZOPRAN if the packaging is torn or shows signs of tampering.

If you are not sure whether you should start taking LANZOPRAN, talk to your doctor or pharmacist.

Before you start to take it

You must tell your doctor if you:

  • Have any allergies to: any medicines, foods, dyes or preservative.
  • Are pregnant or intend to become pregnant: your doctor will discuss the possible risks and benefits of taking LANZOPRAN.
  • Are breast-feeding currently or intend to breast-feed: lactating women should not breast-feed while taking LANZOPRAN.
  • Have or have had any medical conditions including the following:
    - problems with your kidney(s) or liver
    - an abnormal growth (tumour)in stomach.

If you have not told your doctor about any of the above, tell them before you take LANZOPRAN.

Taking other medicines

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

Some medicines may interfere with LANZOPRAN. These include:

  • Theophylline, used to treat asthma
  • Carbamazepine and phenytoin used to treat fits (seizures)
  • Warfarin, used to prevent blood clot
  • Oral contraceptive
  • Sucralfate (use to treat stomach ulcers) and antacids (used to treat heartburn). LANZOPRAN should be taken at least an hour prior sucralfate or antacid administration.
  • Ampicillin esters and clarithromycin antibiotic
  • Ketoconazole used to treat fungal infection
  • Iron salt preparation
  • Digoxin for cardiac complication

These medicines may be affected by LANZOPRAN or they 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 use Lanzopran

Follow all directions given to you by your doctor or pharmacist carefully. This 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 LANZOPRAN in the morning before food.

How much to take

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

Adults
The dose to be taken depends on what your condition is and how long you require treatment. It may vary from 15 mg to 30 mg per day.

Children and Adolescents (1-17 years old)
The recommended dose depends on the weight of the child or adolescent.

For those weighing 30 kg or less, the usual dose is one LANZOPRAN 15 mg capsule daily.

For those weighing over 30 kg, the usual dose is one LANZOPRAN 30 mg capsule daily.

How long to take it

Continue taking the capsules for as long as your doctor tells you. Do not stop taking it unless your doctor tells you to, even if you feel better.

In most patients, lansoprazole relieves symptoms rapidly and healing is usually complete within 4 weeks, although the pain and discomfort caused by the ulcer or reflux may go away well before all the prescribed LANZOPRAN capsules have been finished.

Although lansoprazole heals ulcers very successfully, it may not prevent them from coming back at a later date. Your doctor may want you to keep taking LANZOPRAN long-term to prevent the condition from recurring. However, lansoprazole is only recommended for short-term use (8 to 12 weeks) in children.

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

How to take it

The capsule should be swallowed whole with plenty of water. Do not crush or chew.

If you have difficulty swallowing LANZOPRAN, you can open a capsule and administered as follows:

Sprinkle intact granules on one tablespoon of apple sauce, strained pears, cottage cheese or yoghurt and swallow immediately. The capsules may also be emptied into a small volume of either apple juice, orange juice or tomato juice. Mix briefly and swallowed immediately.

To ensure complete delivery of the dose, the glass should be rinsed with two or more volumes of juice and the contents swallowed immediately.

Do not use other foods or liquids to swallow the granules because they have not been tested for use with LANZOPRAN.

If you have a nasogastric tube in place:
LANZOPRAN may be given by a doctor or nurse by mixing the intact granules from the capsule with 40 mL of apple juice and injecting the mixture through the tube into the stomach. The tube is then flushed with more apple juice to clear it.

If you forget to take it

  • Take your dose as soon as you remember, and then continue to take it as you would normally.
  • If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to.
  • 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 missed more than one dose, or are not sure what to do, check with your doctor or pharmacist.

If you take too much (overdose)

Immediately telephone your doctor or the Poisons Information Centre (Tel. 131126) for advice, or go to Accident & Emergency at your nearest hospital. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

Keep these numbers handy in case of an emergency.

While you are using Lanzopran

Things you must do

Use LANZOPRAN exactly as your doctor has prescribed.

Tell your doctor if you become pregnant while you are taking LANZOPRAN.

Tell all doctors, dentist and pharmacists who are treating you that you are taking LANZOPRAN.

Tell your doctor that you are taking LANZOPRAN before any blood tests. This medicine may interfere with the results of certain tests.

Things you must not do

Do not give LANZOPRAN to anyone else, even if their symptoms seem similar or they have the same condition as you. Your doctor has prescribed it for you and your condition only.

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

Do not stop taking LANZOPRAN, or lower the dosage, even if you are feeling better, 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 LANZOPRAN affects you. LANZOPRAN generally does not cause any problems with your ability to drive a car or operate machinery. However, as with many other medicines, LANZOPRAN may cause dizziness or light-headedness in some people.

Make sure you know how you react to LANZOPRAN before you drive a car, operate machinery, or do anything else that could be dangerous if you are dizzy or light-headed.

If you drink alcohol, dizziness or light-headedness 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 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.
  • Weight - your doctor may suggest losing some weight to help your condition.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are using LANZOPRAN. LANZOPRAN helps most people with ulcers or reflux, but it may have unwanted side effects in some.

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

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

Stomach or bowel problems such as:

  • diarrhoea, constipation
  • indigestion nausea (feeling sick), vomiting (being sick)
  • flatulence or wind
  • abdominal or stomach pain
    Tell your doctor if you suffer from severe persistent diarrhoea and/or vomiting when taking LANZOPRAN. The natural acid in your stomach helps kill bacteria. Taking medicines (such as lansoprazole) that reduce acid may result in stomach infections in some people.

Difficulty in thinking or working due to:

  • headache
  • fatigue ( tiredness)
  • light-headedness, feeling like you may faint
  • generally feeling unwell
  • joint or muscle aches or pain
  • feeling depressed or confused
  • having hallucinations

Changes to appearance such as:

  • thinning hair
  • 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
  • dry or sore mouth or throat
  • frequent and painful passing of urine indicating urinary tract infection

Changes in sight, hearing, taste or touch including:

  • taste disturbances
  • tingling or numbness of hands and feet
  • blurred vision
  • increased sensitivity to sunlight

These are more common side effects of lansoprazole.

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

  • pain in the kidney region
  • bruising or bleeding more easily than usual, 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
  • watery or severe diarrhoea with stomach and bowel problem#
  • yellowing of the skin or eyes, especially if accompanied by fever, fatigue, loss of appetite, dark coloured urine or light coloured bowel movements#
    #These side effects may occur when LANZOPRAN is used in combination with antibiotics for H. pylori infection.
  • symptoms of sunburn such as redness, itching or blistering
  • sudden signs of allergy such as rash, itching, or hives, swelling of the face, lips, tongue or other parts of the body, shortness of breath, wheezing or difficulty breathing

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

Other side effects not listed above may occur in some patients. Tell your doctor if you notice anything that make you feel unwell when you are taking, or soon after you have finished taking, LANZOPRAN.

Ask your doctor or pharmacist if you do not understand anything in this list. Do not be alarmed by this list of possible side effects. You may not experience any of them.

After using Lanzopran

Storage

Keep LANZOPRAN in the original pack until it is time to take them.

If you take the capsules out of the original pack they may not keep well.

Keep LANZOPRAN in a cool, dry place where the temperature is below 25°C.

Do not store LANZOPRAN or any medicine in the bathroom or near a sink. Do not leave medicines in the car or on window sills.

Heat and dampness can destroy some medicines.

Keep LANZOPRAN where children cannot reach it.

A locked cupboard at least one and a half metres (1.5 m) above the ground is a good place to store medicines.

Disposal

If your doctor tells you to stop taking LANZOPRAN, or your medicine has passed its expiry date, ask your pharmacist what to do with any capsules which may be left over.

Product description

What LANZOPRAN looks like

LANZOPRAN 30 mg - Purple cap/lavender body, self-locked hard gelatin capsules of size ‘1’ imprinted with ‘L 30’ on both cap and body, containing white to off-white pellets.

LANZOPRAN 30 mg is available in blister packs of 28 capsules.

Ingredients

LANZOPRAN does not contain gluten and lactose.

Active ingredient:
Each LANZOPRAN contains 30 mg of lansoprazole as active ingredient.

Inactive ingredients:
sugar spheres (sugar, starch), hypromellose, purified talc, titanium dioxide, macrogol 300, colloidal anhydrous silica, methacrylic acid-ethyl acrylate copolymer (1:1) dispersion 30%, OPACODE monogramming ink S-1-277002 black. The capsule shells contain gelatin and titanium dioxide, and the colourants indigo carmine CI73015 and carmoisine CI14720 (30 mg capsule). The capsules are imprinted with OPACODE S-1-277002 black ink.

Australian Registration Numbers

LANZOPRAN 30 mg capsule - AUST R 159343

Sponsor

LANZOPRAN capsules are supplied in Australia by:

Sun Pharma ANZ Pty Ltd
12 Waterloo Road
Macquarie Park, NSW 2113
Email: [email protected] com
Tel no. 1800 726 229

This leaflet was prepared in September 2019.

Published by MIMS November 2019

BRAND INFORMATION

Brand name

Lanzopran

Active ingredient

Lansoprazole

Schedule

S4

 

1 Name of Medicine

Lansoprazole.

6.7 Physicochemical Properties

Lanzopran delayed release capsules contain lansoprazole, which is a substituted benzimidazole. Lansoprazole 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.
Molecular formula: C16H14F3N3O2S.
Chemical name: 2-[[[3-methyl-4- (2,2,2-trifluoroethoxy)-2-pyridyl]methyl] sulphinyl]-1H-benzimidazole.
Molecular weight: 369.36.

Chemical structure.


CAS number.

103577-45-3.

2 Qualitative and Quantitative Composition

Each Lanzopran capsule contains enteric-coated delayed release pellets with 15 mg or 30 mg of lansoprazole.
Contains excipients with known effects: sucrose.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Lanzopran 15 mg capsules.

Yellow cap/yellow body, self-locked hard gelatin capsules of size '3' imprinted with 'L 15' on both cap and body, containing white to off-white pellets.

Lanzopran 30 mg capsules.

Purple cap/lavender body, self-locked hard gelatin capsules of size '1' imprinted with 'L 30' on both cap and body, containing white to off-white pellets.

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, lansoprazole 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 lansoprazole in combination with only one antibiotic resulted in significantly lower eradication rates. Therefore, such regimens are not recommended.

Reflux oesophagitis.

Paediatric and adolescent patients.

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 once daily, if the bodyweight was ≤ 30 kg, or lansoprazole 30 mg once daily, if the bodyweight 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 2.
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 3.

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 4.)
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 5.
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 6.)

Nonulcer dyspepsia.

In a randomised, double blind parallel study, 15 mg lansoprazole mane was compared to placebo in 269 patients suffering from nonulcer 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 nonulcer 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.

Children and adolescents.

1 to 11 years of age.

The pharmacokinetics of lansoprazole were studied in pediatric patients with gastroesophageal reflux disease (GORD) aged 1 to 11 years, with lansoprazole 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.

12 to 17 years of age.

In a study of 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 (bodyweight, age and gender) had any statistically significant effect on lansoprazole Tmax or the natural logarithms of dose normalized Cmax and AUC0-24.

5.3 Preclinical Safety Data

Genotoxicity.

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.

Carcinogenicity.

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.
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.

4 Clinical Particulars

4.1 Therapeutic Indications

Adults.

Lanzopran capsules are indicated for:
Healing and long-term management of reflux oesophagitis.
Healing and long-term management for patients with duodenal ulcer.
Healing of benign gastric ulcer. Patients whose gastric or duodenal ulcer is not associated with ingestion of nonsteroidal anti-inflammatory drugs require treatment with antimicrobial agents in addition to antisecretory drugs whether on first presentation or on recurrence.
Patients with benign peptic lesions that do not respond to H2-receptor antagonists.
Eradication of H. pylori from the upper gastrointestinal tract in patients with peptic ulcer or chronic gastritis when used in combination with appropriate antibiotics.
Relief of reflux-like and/or ulcer-like symptoms associated with acid related dyspepsia.

Paediatric and adolescent patients 1 to 17 years of age.

Lanzopran capsules are indicated for:
Treatment of gastroesophageal reflux disease, including all grades of oesophagitis.
Healing of erosive oesophagitis.

4.3 Contraindications

Hypersensitivity to lansoprazole, other proton pump inhibitors or any of the ingredients.
Severe hepatic impairment.

4.4 Special Warnings and Precautions for Use

As with other antiulcer 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.

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 refer to 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.

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:
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.

Use in hepatic impairment.

Lansoprazole is metabolized 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.
See Section 4.3 Contraindications.

Use in renal impairment.

There is no need to alter the dosage in adult patients with impaired renal function.

Use in the elderly.

Dosage adjustment is not required in the elderly.

Paediatric use.

There is insufficient experience to recommend the use of lansoprazole in paediatric patients with hepatic or renal impairment.
See Section 4.2 Dose and Method of Administration; Section 5.1 Pharmacodynamic Properties, Clinical trials; Section 5.2 Pharmacokinetic Properties.

Effects on 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 nonsteroidal anti-inflammatory drugs phenytoin (single IV doses only) and diazepam have been found.
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, it is theoretically possible that 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).
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.

The effects of lansoprazole on human male fertility have not been evaluated.
(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 foetal 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.
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 breastfeeding should be avoided.

4.8 Adverse Effects (Undesirable Effects)

Lansoprazole is well tolerated, with adverse events generally being mild and transient. The most commonly reported adverse events are headache, dizziness, fatigue and malaise.
Gastrointestinal effects include diarrhoea, constipation, abdominal pain, dyspepsia, nausea, vomiting, flatulence and dry or sore mouth or throat.
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.

Frequency not known.

Withdrawal of long-term PPI therapy can lead to aggravation of acid related symptoms and may result in rebound acid hypersecretion.
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.
Alterations in liver function test values and, rarely, jaundice or hepatitis, have been reported. However, routine monitoring of liver function tests is not required.
Dermatological reactions include 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 erythema multiforme. Cases of hair thinning and photosensitivity have also been reported.
Other hypersensitivity reactions include angioedema, wheezing, and very rarely, anaphylaxis. Cases of interstitial nephritis have been reported which have sometimes resulted in renal failure.
Haematological effects (thrombocytopenia, agranulocytosis, eosinophilia, leucopoenia, neutropenia and pancytopenia) have occurred rarely. Bruising, purpura and petechiae have also been reported.
Other reactions include arthralgia, myalgia, depression, peripheral oedema, upper respiratory tract infections, urinary tract infections and, rarely, paraesthesia, blurred vision, taste disturbances, vertigo, confusion and hallucinations.
There have been isolated reports of interstitial pneumonia and hyponatraemia, but a definitive relationship to lansoprazole therapy has not been established.
Gynaecomastia and impotence have been reported 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

Lanzopran capsules contain 15 or 30 mg of lansoprazole as enteric coated delayed release capsules.
To achieve the optimal acid inhibitory effect, and hence most rapid healing and symptom relief, Lanzopran capsules should be taken in the morning before food. The capsules should be swallowed whole. Do not crush or chew.

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.

Acid related dyspepsia.

Lansoprazole 15 mg or 30 mg 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:
Lansoprazole 30 mg 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/ adolescents.

Short-term treatment (8-12 weeks). In patients aged 1-17 years with gastroesophageal reflux disease, including all grades of oesophagitis, the recommended initial dosage is shown in Table 1.
After 2 weeks, an increase in dose up to 60 mg lansoprazole daily may be beneficial for patients who are not responding satisfactorily.

Instructions for patients who are unable to swallow capsules.

For other patients who have difficulty swallowing lansoprazole capsules, the capsule can be opened and administered as follows:
Open the capsule.
Sprinkle intact granules on one tablespoon of apple sauce, strained pears, cottage cheese or yoghurt.
Swallow immediately.
The capsules may also be emptied into a small volume of either apple juice, orange juice or tomato juice and administered as follows:
Open the capsule.
Sprinkle intact granules into a small volume of apple juice, orange juice or tomato juice. Mix briefly and swallow immediately.
To ensure complete delivery of the dose, the glass should be rinsed with two or more volumes of juice and the contents swallowed immediately.
Use in other foods or liquids has not been studied clinically and is, therefore, not recommended.

Nasogastric tube administration.

For patients with a nasogastric tube in place, Lanzopran capsules can be administered as follows:
Open the capsule.
Mix the intact granules into 40 mL of apple juice (do not use any other liquids).
Inject through the nasogastric tube into the stomach.
Flush with additional apple juice to clear the tube.

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 13 11 26 (Australia).

7 Medicine Schedule (Poisons Standard)

S4.

6 Pharmaceutical Particulars

6.1 List of Excipients

The pellets also contain the inactive ingredients sugar spheres (sugar, starch), hypromellose, purified talc, titanium dioxide, macrogol 300, colloidal anhydrous silica, methacrylic acid-ethyl acrylate copolymer (1:1) dispersion 30%, Opacode monogramming ink S-1-277002 black (proprietary ingredient no. 107581). The capsule shells contain gelatin and titanium dioxide, and the colourants iron oxide yellow CI77492 and quinoline yellow CI47005 (15 mg capsule), or indigo carmine CI73015 and carmoisine CI14720 (30 mg capsule). The capsules are imprinted with Opacode S-1-277002 black ink.

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

The capsules are supplied in cold form blister and strip pack containing 28 or 30 capsules of 15 or 30 mg strength.

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