Consumer medicine information

APO-Lansoprazole Capsules

Lansoprazole

BRAND INFORMATION

Brand name

APO-Lansoprazole

Active ingredient

Lansoprazole

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using APO-Lansoprazole Capsules.

What is in this leaflet

This leaflet answers some common questions about lansoprazole. It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

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

The name of your medicine is APO-Lansoprazole. It contains the active ingredient lansoprazole.

In adults it is used to treat:

  • reflux oesophagitis
  • peptic ulcers
  • Helicobacter pylori infection in patients with peptic ulcer or chronic gastritis
  • reflux-like and/or ulcer-like symptoms associated with acid-related dyspepsia

In children aged 1-17 years of age it is used to treat:

  • gastro-oesophageal reflux disease, including all grades of oesophagitis
  • erosive oesophagitis

Lansoprazole belongs to a group of medicines called proton pump inhibitors (PPIs). It works by decreasing the amount of acid the stomach makes, to give relief from excessive acid and allow healing to take place.

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

There is no evidence that this medicine is addictive.

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

Before you take this medicine

When you must not take it

Do not take this medicine if you have allergy to:

  • lansoprazole or other proton pump inhibitors
  • any of the ingredients listed at the end of this leaflet

Some of the symptoms of an allergic reaction may include:

  • shortness of breath, cough, wheezing or difficulty breathing
  • swelling of the face, lips, tongue, throat or other parts of the body
  • rash, itching or hives on the skin

Do not take this medicine if you have severe liver disease.

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

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

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

Before you start to use it

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you have or have had any of the following medical conditions:

  • kidney or liver problems
  • inflammation of the bowel
  • a tumour in the stomach region
  • osteoporosis
  • low magnesium levels
  • fructose intolerance, glucose galactose malabsorption or sucrose-isomaltase insufficiency.

Do not take this medicine if you are pregnant or plan to become pregnant.

Do not take lansoprazole whilst pregnant until you and your doctor have discussed the risks and benefits involved.

It may affect your developing baby if you take it during pregnancy.

Do not take this medicine if you are breastfeeding or plan to breastfeed.

Do not take lansoprazole whilst breastfeeding until you and your doctor have discussed the risks and benefits involved.

Taking other medicines

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

Some medicines and lansoprazole may interfere with each other. These include:

  • theophylline, used to treat asthma
  • carbamazepine and phenytoin used to treat seizures (fits)
  • warfarin, used to prevent blood clots
  • oral contraceptives
  • sucralfate (used to treat stomach ulcers) and antacids (used to treat heartburn)

Lansoprazole should be taken at least an hour prior to taking sucralfate or an antacid.

  • ampicillin esters, used in some antibiotics
  • ketoconazole, used to treat fungal infections
  • iron preparations
  • digoxin, used to treat heart conditions
  • tacrolimus or mycophenolate used in transplant patients to reduce organ rejection
  • methotrexate, used in rheumatoid arthritis and some cancers to control immune response
  • atazanavir, nelfinavir and others that require an acidic pH to be effective to treat HIV
  • fluvoxamine, used to treat depression and anxiety

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

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

How to take this medicine

Follow all directions given to you by your doctor or pharmacist carefully. Their instructions may be different to the information in this leaflet.

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

How much to take

Your doctor will tell you how much of this medicine you should take. This will depend on your condition and whether you are taking any other medicines.

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

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

If you have difficulty swallowing this medicine, the capsule can be opened and taken as follows:

  • Sprinkle the intact granules on one tablespoon of apple sauce, strained pears, cottage cheese or yoghurt and swallow immediately
  • or sprinkle the intact granules into a small volume of either 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.

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

If you have a nasogastric tube in place, this medicine 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.

When to take it

Take this medicine in the morning before food.

Taking it at the same time each day will have the best effect. It will also help you remember when to take it.

How long to take it for

Continue taking your medicine for as long as your doctor tells you.

If you forget to take it

If it is almost time to take your next dose, skip the dose you missed and take your next dose when you are meant to.

Otherwise, take it as soon as you remember, and then go back to taking your medicine as you would normally.

Do not take a double dose to make up for the dose that you missed. This may increase the chance of you getting an unwanted side effect.

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

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

If you take too much (overdose)

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

While you are taking this medicine

Things you must do

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are taking this medicine.

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

If you are going to have surgery, tell the surgeon or anaesthetist that you are taking this medicine. It may affect other medicines used during surgery.

If you become pregnant or start to breastfeed while taking this medicine, tell your doctor immediately.

If you are about to have any blood tests, tell your doctor that you are taking this medicine. Lansoprazole may interfere with the results of some tests.

Keep all your doctor's appointments so that your progress can be checked. Your doctor may do some tests from time to time to make sure lansoprazole is working and to prevent unwanted side effects.

Things you must not do

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

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

Do not stop taking your medicine or lower 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 when driving or operating machinery until you know how this medicine affects you.

Lansoprazole may cause dizziness in some people.

Side effects

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

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 following lists of side effects. You may not experience any of them.

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

Tell your doctor if you notice any of the following:

Stomach or bowel problems such as:

  • diarrhoea, constipation
  • indigestion
  • nausea (feeling sick), vomiting
  • flatulence or wind
  • abdominal or stomach pain

Tell your doctor if you suffer from severe persistent diarrhoea and/or vomiting when taking lansoprazole.

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

Difficulty in thinking or working due to:

  • headache
  • fatigue (tiredness)
  • dizziness
  • generally feeling unwell
  • joint or muscle aches or pain
  • feeling depressed, confused or having hallucinations

Changes to your appearance such as:

  • thinning hair
  • skin rashes
  • hives or itchy skin
  • breast enlargement and impotence in men (with long-term use)

Signs of infection such as:

  • cough, cold, sore throat or sinus
  • dry or sore mouth or throat
  • frequent and painful passing of urine

Changes in sight, hearing, taste or touch including:

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

Tell your doctor as soon as possible if you notice any of the following:

  • pain or indigestion
  • vomiting blood or food
  • passing black (blood-stained) motions

The above list includes serious side effects that may require medical attention.

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

  • 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 problems
  • yellowing of the skin or eyes, especially if accompanied by fever, fatigue, loss of appetite, dark coloured urine or light-coloured bowel movements
  • 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
  • swelling of the face, lips, tongue or throat, which may cause difficulty breathing
  • swelling of hands, ankles or feet
  • cramping of the muscles in your hands or feet
  • irregular heartbeat
  • fits or seizures
  • hallucinations.

These are very serious side effects and you may need urgent medical attention or hospitalisation.

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

Storage and disposal

Storage

Keep your medicine in its original pack until it is time to take them. If you take your medicine out of the original pack, they may not keep well.

Keep your medicine in a cool, dry place where the temperature will stay below 25°C.

Do not store this medicine or any other medicine in the bathroom or near a sink. Do not leave it on a window sill or in the car. Heat and dampness can destroy some medicines.

Keep it where children cannot reach it. A locked cupboard at least one and a half metres above the ground is a good place to store medicines.

Disposal

If your doctor tells you to stop taking this medicine or the expiry date has passed, ask your pharmacist what to do with any medicine that is left over.

Product description

What APO- Lansoprazole looks like

APO-Lansoprazole 15 mg
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. AUST R 159350. AUST R 159346.

APO-Lansoprazole 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. AUST R 159345. AUST R 159348

APO-Lansoprazole 15 mg and 30 mg are available in blister packs of 28 or 30 capsules.

Ingredients

Each APO-Lansoprazole Enteric Capsules contains 15 mg or 30 mg of lansoprazole as active ingredient.

It also contains the following inactive ingredients:

  • sucrose
  • maize starch
  • purified talc
  • hypromellose
  • titanium dioxide
  • methacrylic acid-ethyl acrylate copolymer (1:1)
  • macrogol 300
  • colloidal anhydrous silica
  • gelatin
  • Opacode S-1-277002 black

The 15 mg enteric capsule also contains the below colourants:

  • iron oxide yellow CI77492
  • quinoline yellow CI47005.

The 30 mg enteric capsule also contains the below colourants:

  • indigo carmine CI73015
  • carmoisine CI14720.

This medicine does not contain gluten and lactose. Contains sugars as sucrose. Contains sulfites.

Sponsor

Apotex Pty Ltd
16 Giffnock Avenue
Macquarie Park NSW 2113

APO and APOTEX are registered trademarks of Apotex Inc.

This leaflet was last updated in:
March 2021

Published by MIMS April 2021

BRAND INFORMATION

Brand name

APO-Lansoprazole

Active ingredient

Lansoprazole

Schedule

S4

 

1 Name of Medicine

Lansoprazole.

2 Qualitative and Quantitative Composition

Each APO-Lansoprazole enteric capsule contains enteric-coated delayed release pellets with 15 mg or 30 mg of lansoprazole.

Excipients with known effect.

Contains sugars as sucrose. Contains sulfites.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

APO-Lansoprazole 15 mg enteric 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.

APO-Lansoprazole 30 mg enteric 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.

4 Clinical Particulars

4.1 Therapeutic Indications

Adults.

APO-Lansoprazole enteric 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 (see Section 5.1 Pharmacodynamic Properties, Clinical trials).
Relief of reflux-like and/or ulcer-like symptoms associated with acid related dyspepsia.

Paediatric and adolescent patients 1 to 17 years of age.

APO-Lansoprazole enteric capsules are indicated for:
Treatment of gastro-oesophageal reflux disease, including all grades of oesophagitis.
Healing of erosive oesophagitis.

4.2 Dose and Method of Administration

To achieve the optimal acid inhibitory effect, and hence most rapid healing and symptom relief, APO-Lansoprazole enteric capsules should be taken in the morning before food. The enteric capsules should be swallowed whole. Do not crush or chew.

Dosage.

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 nonsteroidal anti-inflammatory drugs require treatment with antimicrobial agents in addition to antisecretory drugs whether on first presentation or on recurrence.

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.

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.

Instructions for patients who are unable to swallow capsules.

For other patients who have difficulty swallowing lansoprazole enteric capsules, the enteric capsule can be opened and administered as follows.
1. Open the enteric capsule.
2. Sprinkle intact granules on one tablespoon of apple sauce, strained pears, cottage cheese or yoghurt.
3. Swallow immediately.
The enteric capsules may also be emptied into a small volume of either apple juice, orange juice or tomato juice and administered as follows.
1. Open the enteric capsule.
2. Sprinkle intact granules into a small volume of apple juice, orange juice or tomato juice. Mix briefly and swallow immediately.
3. 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, APO-Lansoprazole enteric capsules can be administered as follows.
1. Open the enteric capsule.
2. Mix the intact granules into 40 mL of apple juice (do not use any other liquids).
3. Inject through the nasogastric tube into the stomach.
4. Flush with additional apple juice to clear the tube.

4.3 Contraindications

Hypersensitivity to lansoprazole, other proton pump inhibitors or any of the excipients in the capsules.
Severe hepatic impairment.
Concomitant use with atazanavir. Lansoprazole should not be coadministered with atazanavir due to a significant reduction in atazanavir exposure.

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. 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.

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. Consider dose adjustment in patients with severe hepatic impairment.
There is insufficient experience to recommend the use of lansoprazole in paediatric patients with hepatic impairment.

Use in renal 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 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 manifestations of hypomagnesaemia such as fatigue, tetany, delirium, convulsions, seizures, dizziness and ventricular arrhythmia can occur but they may begin insidiously and be overlooked. 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), healthcare 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.

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 the elderly.

Dosage adjustment is not required in the elderly.

Paediatric use.

See Section 4.2 Dose and Method of Administration, Paediatrics.
There is insufficient experience to recommend the use of lansoprazole in paediatric patients with hepatic or renal impairment.

Effects on laboratory tests.

Increased Chromogramin 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.
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 coadministered 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.

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.
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 foetus.
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.

4.7 Effects on Ability to Drive and Use Machines

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

4.8 Adverse Effects (Undesirable Effects)

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

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.

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, anaphylaxis.

Renal and urinary disorders.

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

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.

Nervous system disorders.

Headache, dizziness.
Rarely, paraesthesia and taste disturbances.

Psychiatric disorders.

Depression, confusion and hallucinations.

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.

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.

Respiratory, thoracic and mediastinal disorders.

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

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.

General disorders and administration site conditions.

Fatigue, malaise, peripheral oedema.

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 http://www.tga.gov.au/reporting-problems and contact Apotex Medical Information Enquiries/Adverse Drug Reaction Reporting on 1800 195 055.

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).

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.

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 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 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.

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.

Absorption.

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.

Distribution.

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.

Metabolism/excretion.

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 use.

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 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 normalised 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.

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. In a follow-up lansoprazole developmental sensitivity study, juvenile rats younger than postnatal Day 21 (age equivalent to approximately 2 years in humans) were more sensitive to the development of heart valve thickening, with valve thickening occurring at lower exposure (approximately 4-fold the expected human exposure based on AUC) in animals dosed starting at postnatal Day 14 (age equivalent to approximately 1 year in humans). 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.

6 Pharmaceutical Particulars

6.1 List of Excipients

Sugar spheres (sucrose, maize starch), hypromellose, purified talc, titanium dioxide, macrogol 300, colloidal anhydrous silica, methacrylic acid-ethyl acrylate copolymer (1:1) dispersion 30%, gelatin, iron oxide yellow CI77492 (15 mg capsule), quinoline yellow CI47005 (15 mg capsule), indigo carmine CI73015 (30 mg capsule), carmoisine CI14720 (30 mg capsule), 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

APO-Lansoprazole 15 mg enteric capsules.

PA/Al/PVC/Al - polyamide-aluminum foil-polyvinylchloride/aluminum foil AUST R 159350, strip pack AUST R 159346.

APO-Lansoprazole 30 mg enteric capsules.

PA/Al/PVC/Al - polyamide-aluminum foil-polyvinylchloride/aluminum foil AUST R 159345, strip pack AUST R 159348.
The enteric capsules are supplied in cold form blister and strip pack containing 28 or 30 capsules of 15 or 30 mg strength.
Apotex Pty Ltd is the licensee of the registered trade mark APO from the registered proprietor, Apotex Inc.
Not all strengths or pack sizes may be available.

6.6 Special Precautions for Disposal

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

6.7 Physicochemical Properties

APO-Lansoprazole enteric 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.

Chemical structure.


Molecular formula.

C16H14F3N3O2S.

Chemical name.

2 [[[3-methyl-4-(2,2,2-trifluoroethoxy)- 2-pyridyl] methyl] sulphinyl]-1H-benzimidazole.

Molecular weight.

369.36.

CAS number.

103577-45-3.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

Summary Table of Changes