Consumer medicine information

APO-Pantoprazole Heartburn Relief

Pantoprazole

BRAND INFORMATION

Brand name

APO-Pantoprazole Heartburn Relief

Active ingredient

Pantoprazole

Schedule

S3 | S2

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using APO-Pantoprazole Heartburn Relief.

What is in this leaflet

Read this leaflet carefully before taking your medicine.

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

The information in this leaflet was last updated on the date listed on the last page. More recent information on this medicine may be available.

Ask your doctor or pharmacist:

  • if there is anything you do not understand in this leaflet,
  • if you are worried about taking your medicine, or
  • to obtain the most up-to-date information.

You can also download the most up to date leaflet from www.apotex.com.au.

All medicines have risks and benefits.

Pharmaceutical companies cannot give you medical advice or an individual diagnosis.

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

What this medicine is used for

The name of your medicine is APO-Pantoprazole Heartburn Relief Tablets. It contains the active ingredient pantoprazole.

It is used for symptomatic relief of frequent heartburn and stomach acid complaints due gastro-oesophageal reflux disease (GORD).

This can be caused by "washing back" (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 heartburn.

Frequent heartburn is when you have heartburn for two or more days a week. Heartburn that occurs frequently is a typical symptom of gastro-oesophageal reflux disease.

How it works

Pantoprazole belongs to a group of medicines called proton pump inhibitors (PPIs).

Pantoprazole works by decreasing the amount of acid the stomach makes, to give relief from the symptoms.

This medicine will start to suppress acid within a few hours; however it will not give instant symptom relief. You may need to take this medicine for a few days before experiencing the full effect.

There is no evidence that this medicine is addictive.

Use in children

This medicine should not be used in children or adolescents under 18 years of age.

Before you take this medicine

When you must not take it

Do not take this medicine if:

  • You have or have had cirrhosis or severe liver disease.
  • You are taking atazanavir, an anti-viral medicine.
  • You are hypersensitive to, or have had an allergic reaction to, pantoprazole or any of the ingredients listed at the end of this leaflet.
    Symptoms of an allergic reaction may include: cough, shortness of breath, wheezing or difficulty breathing; swelling of the face, lips, tongue, throat or other parts of the body; rash, itching or hives on the skin; fainting; or hay fever-like symptoms.
    If you think you are having an allergic reaction, do not take any more of the medicine and contact your doctor immediately or go to the Accident and Emergency department at the nearest hospital.
  • The expiry date (EXP) printed on the pack has passed.
  • The packaging is torn, shows signs of tampering or it does not look quite right.

Before you start to take it

Before you start taking this medicine, tell your doctor if:

  1. You have allergies to:
  • any other medicines
  • any other substances, such as foods, preservatives or dyes.
  1. You have or have had any medical conditions, especially the following:
  • difficulty swallowing, jaundice, liver problems, anaemia, previous gastric ulcer or gastrointestinal surgery
  • new or recently changed symptoms including persistent vomiting or vomiting of blood, blood in the stools or unexplained weight loss.
  1. You have previously taken heartburn / indigestion medications continuously for 4 or more weeks to control your heartburn.
  2. You are currently being treated for GORD symptoms and require pantoprazole for more than 14 days.
  3. You are due to have an endoscopy (a special test ordered by your doctor).
  4. You are currently pregnant or you plan to become pregnant. Do not take this medicine whilst pregnant until you and your doctor have discussed the risks and benefits involved.
  5. You are currently breastfeeding or you plan to breast-feed. Do not take this medicine whilst breastfeeding until you and your doctor have discussed the risks and benefits involved.
  6. You are planning to have surgery or an anaesthetic.
  7. You are currently receiving or are planning to receive dental treatment.

Taking other medicines

Tell your doctor if you are taking or are planning to take any other medicines. This includes vitamins and supplements that are available from your pharmacy, supermarket or health food shop.

Some medicines may interact with pantoprazole. These include:

  • atazanavir, do not take this at the same time as pantoprazole
  • coumarin anti-coagulants such as phenprocoumon and warfarin
  • ketoconazole, itraconazole, posaconazole, medicines used to treat fungal infection
  • methotrexate, a medicine used to treat arthritis and some types of cancer
  • erlotinab or related medicines used to treat cancer.

If you are taking any of these you may need a different dose or you may need to take different medicines.

Other medicines not listed above may also interact with pantoprazole.

How to take this medicine

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

How much to take

The usual dose is one tablet daily

How to take it

Swallow whole with water. Do not chew or crush tablets.

When to take it

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

It does not matter if you take it before, with or after food.

How long to take it for

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

It should be taken for at least 7 days and up to 14 days. It should not be taken for more than 14 days unless directed by your doctor.

If you forget to take it

If it is almost time to take your next dose, skip the missed dose and take your next dose at the usual time. 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 missed doses. This may increase the chance of you experiencing side effects.

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

If you take too much (overdose)

If you think that you or anyone else may have taken too much of this medicine, immediately telephone your doctor or the Poisons Information Centre (Tel: 13 11 26 in Australia) for advice. Alternatively, go to the Accident and Emergency department at your nearest hospital.

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

Tell your doctor that you are taking this medicine if:

  • you are about to be started on any new medicine
  • you are pregnant or are planning to become pregnant
  • you are breastfeeding or are planning to breast-feed
  • you are about to have any blood tests
  • you are going to have surgery or an anaesthetic or are going into hospital.

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

Tell your doctor if you do not feel better while taking this medicine. Your doctor may recommend further examination.

Tell your doctor if symptoms persist or recur within 2 weeks of completing the course.

Things you must not do

Do not:

  • Give this medicine to anyone else, even if their symptoms seem similar to yours.
  • Take your medicine to treat any other condition unless your doctor or pharmacist tells you to.
  • Stop taking your medicine, or change the dosage, without first checking with your doctor or pharmacist.

Things to be careful of

Be careful when driving or operating machinery until you know how this medicine affects you.

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, 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.

Possible side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking pantoprazole or if you have any questions or concerns.

Do not be alarmed by the following lists of side effects. You may not experience any of them. All medicines can have side effects. Sometimes they are serious but most of the time they are not.

Tell your doctor if you notice any of the following:

  • headache
  • dizziness
  • diarrhoea
  • nausea or vomiting
  • stomach pain
  • excessive gas in the stomach or bowel
  • indigestion
  • constipation
  • dry mouth
  • metallic taste
  • weakness or tiredness
  • increased sweating
  • blurred vision
  • skin problems such as itchiness and rash
  • reflux after stopping the medication suddenly, especially if you have taken it for a while without consulting your doctor.

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

These may be serious side effects and you may need medical attention:

  • unusual tiredness or weakness
  • loss of appetite, feeling generally unwell, fever, itching, yellowing of the skin and eyes, and dark coloured urine
  • skin problems such as itchiness and rash, or swelling, blistering or peeling of the skin
  • frequent infections such as fever, severe chills, sore throat or mouth ulcers
  • chest pain
  • shortness of breath
  • high blood pressure
  • swelling of the legs
  • bleeding or bruising more easily than normal
  • depression, confusion or anxiety.

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

Allergic reactions

If you think you are having an allergic reaction to pantoprazole, do not take any more of this medicine and tell your doctor immediately or go to the Accident and Emergency department at your nearest hospital.

Symptoms of an allergic reaction may include some or all of the following:

  • cough, shortness of breath, wheezing or difficulty breathing
  • swelling of the face, lips, tongue, throat or other parts of the body
  • rash, itching or hives on the skin
  • fainting
  • hay fever-like symptoms.

Storage and disposal

Storage

Keep your medicine in its original packaging until it is time to take it.

If you take your medicine out of its original packaging it may not keep well.

Keep your medicine in a cool dry place where the temperature will stay below 25°C. Protect from light and moisture.

Do not store your 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 this medicine 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 or pharmacist tells you to stop taking this medicine or it has passed its expiry date, your pharmacist can dispose of the remaining medicine safely.

Product description

What APO-Pantoprazole Heartburn Relief Tablets look like

The tablets are available in 20 mg strength. The tablets have an acid-resistant coating called an enteric coating.

The tablets are yellow, oval, biconvex, enteric-coated tablets engraved "APO" on one side, "20" on the other side.

Available in blister packs of 7 and 14 tablets

* Not all pack sizes may be available.

Ingredients

Each tablet contains 20 mg of pantoprazole (as sodium sesquihydrate) as the active ingredient.

It also contains the following inactive ingredients:

  • lactose anhydrous
  • crospovidone
  • cellulose-microcrystalline
  • magnesium stearate
  • hypromellose
  • macrogol 8000
  • anhydrous sodium carbonate
  • methacrylic acid copolymer
  • triethyl citrate
  • talc-purified
  • titanium dioxide
  • iron oxide yellow.

This medicine is gluten-free, sucrose-free, tartrazine-free and free of other azo dyes.

Australian Registration Numbers

APO-Pantoprazole Heartburn Relief 20mg tablets (blisters): AUST R 156332

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:
June 2019.

Published by MIMS October 2019

BRAND INFORMATION

Brand name

APO-Pantoprazole Heartburn Relief

Active ingredient

Pantoprazole

Schedule

S3 | S2

 

1 Name of Medicine

Pantoprazole sodium sesquihydrate.

6.7 Physicochemical Properties

Pantoprazole is a substituted benzimidazole which inhibits basal and stimulated gastric secretion. Pantoprazole sodium sesquihydrate is a white to off white crystalline powder. Solubility is low at neutral pH and increases with increasing pH.
Chemical Name: 1) 1H-benzimidazole, 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridinyl)methyl]-sulfinyl]-, sodium salt, hydrate (2:3).
2) 5-(difluoromethoxy)-2- [[(3,4-dimethoxy-2-pyridinyl)methyl] sulfinyl]benzimidazole, sodium salt, sesquihydrate.
Molecular Formula: C16H14F2N3NaO4S.1.5H2O.
Molecular Weight: 432.4.

Chemical structure.


CAS number.

164579-32-2.

2 Qualitative and Quantitative Composition

Each enteric coated tablet contains 20 mg of the active ingredient pantoprazole (as sodium sesquihydrate).

Excipients with known effect.

Lactose anhydrous.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

APO-Pantoprazole Heartburn Relief tablets 20 mg.

Yellow, oval, biconvex, enteric-coated tablets engraved "APO" on one side, "20" on the other side.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Pantoprazole is a proton pump inhibitor. It inhibits specifically and dose proportionately H+/K+-ATPase, the enzyme which is responsible for gastric acid secretion in the parietal cells of the stomach. The substance is a substituted benzimidazole which accumulates in the acidic environment of the parietal cells after absorption. There, it is converted into the active form, a cyclic sulfenamide which binds to the H+/K+-ATPase, thus inhibiting the proton pump and causing potent and long lasting suppression of basal and stimulated gastric acid secretion. As pantoprazole acts distal to the receptor level it can influence gastric acid secretion irrespective of the nature of the stimulus (acetylcholine, histamine, gastrin). Pantoprazole's selectivity is due to the fact that it only exerts its full effect in a strongly acidic environment (pH < 3), remaining mostly inactive at higher pH values. As a result, its complete pharmacological, and thus therapeutic, effect can only be achieved in the acid secretory parietal cells. By means of a feedback mechanism this effect is diminished at the same rate as acid secretion is inhibited.
As with other proton pump inhibitors and H2-receptor inhibitors, treatment with pantoprazole causes a reduced acidity in the stomach and thereby an increase in gastrin in proportion to the reduction in acidity. The increase in gastrin is reversible.

Clinical trials.

Treatment of symptomatic reflux (GORD).

The relief of symptoms of reflux in patients who showed no oesophageal lesions on endoscopy has been shown in the following double blind, multicentre, placebo controlled study (245/98) using pantoprazole 20 mg once daily. Overall, 219 patients were enrolled into the study. Each patient was to have a normal oesophagus as assessed by endoscopy and to have suffered from at least one episode of heartburn of at least moderate intensity on all three days prior to inclusion into the study. Additionally, patients were to have a history of reflux symptoms (heartburn, acid eructation, pain on swallowing) for at least three months prior to entry into the study. Efficacy of pantoprazole 20 mg is shown in Table 1.

5.2 Pharmacokinetic Properties

Pantoprazole is rapidly absorbed and the maximal plasma concentration appears after one single oral dose. After single and multiple oral doses, the median time to reach maximum serum concentrations was approximately 2.5 hours, with a Cmax of approximately 1.2 microgram/mL. Terminal half-life is approximately one hour. Volume of distribution is approximately 0.15 L/kg and clearance is approximately 0.1 L/hour/kg. Pharmacokinetics do not vary after single or repeated administration. The plasma kinetics of pantoprazole are linear (in the dose range of 10 to 80 mg) after both oral and intravenous (IV) administration. Pantoprazole is completely absorbed after oral administration. The absolute bioavailability of the tablet is approximately 77%. Concomitant intake of food had no influence on area under the curve (AUC), maximum serum concentrations and thus bioavailability.
The serum protein binding of pantoprazole is approximately 98%. Pantoprazole is rapidly eliminated from serum and is almost exclusively metabolised in the liver. Renal elimination represents the most important route of excretion (approximately 80%) for the metabolites of pantoprazole; the rest are excreted with the faeces. The main metabolite in both the serum and urine is desmethyl-pantoprazole which is conjugated with the sulfate. The half-life of the main metabolites (approximately 1.5 hours) is not much longer than that of pantoprazole.
In studies in healthy volunteers, 2% of subjects showed a slower elimination of pantoprazole from serum/ plasma, with an increase in terminal elimination half-life of up to 10 h. Patients with a half-life of greater than 3.5 h and with an apparent clearance of less than 2 L/h/kg are considered to be slow metabolisers of pantoprazole. After a single 20 mg tablet, AUC increased threefold in patients with mild hepatic impairment and fivefold in patients with severe hepatic impairment compared with healthy controls. Mean elimination half-life was 3.3 hours in mild hepatic impairment and six hours in severe hepatic impairment compared with 1.1 hours in controls. The maximum serum concentration only increased slightly by a factor of 1.3 compared with healthy subjects.
In patients with renal impairment (including those undergoing dialysis) no dose reduction is required. Although the main metabolite is moderately increased, there is no accumulation. The half-life of pantoprazole is as short as in healthy subjects. Pantoprazole is poorly dialysable.
The slight increase in AUC and Cmax in elderly volunteers compared with their younger counterparts is also not clinically relevant.

5.3 Preclinical Safety Data

Genotoxicity.

A number of in vitro and in vivo genotoxicity assays covering mutagenicity, clastogenicity and DNA damage endpoints were conducted on pantoprazole and the results were generally negative. Exposures achieved in the in vivo tests in mice and rats were well in excess of exposures expected clinically. However, pantoprazole was clearly positive in carefully conducted cytogenetic assays in human lymphocytes in vitro, both in the presence and absence of metabolic activation. Omeprazole was also positive in a comparable test conducted in the same laboratory, suggesting a possible class effect. A minute amount of radioactivity was bound to rat hepatic DNA after treatment with pantoprazole 200 mg/kg/day for 14 days. However, no distinct DNA adduct has been detected.

Mutagenesis.

Pantoprazole was found to be negative in the following studies: in vivo chromosome aberration assay in rat and bone marrow (126E/95), mouse lymphoma test (222E/95) and a gene mutation test in Chinese hamster ovary cells (in vitro) (188E/95). In addition, toxicokinetic studies were conducted in rats at the doses used in the bone marrow assay (50 to 1,200 mg/kg) (56E/96) and in mice at the high dose from the earlier micronucleus test (710 mg/kg) (89E/96). In both species, pantoprazole exposure was high with the AUCs being 26 to 30 times higher in the rat or mouse, respectively, than in humans using the 20 mg tablet.

Carcinogenicity.

A two year oral carcinogenicity study in Sprague-Dawley rats at doses up to 200 mg/kg/day showed gastric carcinoids after pantoprazole treatment at doses greater than 0.5 mg/kg/day in females and greater than 5 mg/kg/day in males, with none observed in controls. The development of gastric tumours is attributed to chronic elevation of serum gastrin levels with associated histopathological changes in the gastrointestinal system. In both male and female rats the development of hepatocellular adenomas was increased at doses greater than 5 mg/kg/day and development of hepatocellular carcinomas was increased at doses greater than 50 mg/kg/day. Hepatocellular tumours, which were also observed in female mice at oral doses greater than 25 mg/kg/day, may be associated with pantoprazole induced increases in hepatic enzyme activity.
Treatment with pantoprazole at doses greater than 50 mg/kg/day also increased the development of thyroid follicular cell adenomas in male and female rats. Several studies in rats were conducted to investigate the effect of pantoprazole on the thyroid, the results of which suggested that the effect may be secondary to the induction of enzymes in the liver.
In a more recent carcinogenicity study, Fischer rats were studied using lower doses (5, 15 and 50 mg/kg). Gastric carcinoids were detected at all doses in females and at the 15 and 50 mg/kg doses in males, and none were detected in controls. No metastases of these carcinoids were detected. There was no increase in the incidence of liver tumours. The dose of 15 mg/kg is seen to be the no-effect level for liver tumours in rodents. Consideration of the possible mechanisms involved in the development of the above drug related tumour types suggests that it is unlikely that there is any carcinogenic risk in humans at therapeutic dose levels of pantoprazole for short-term treatment.

General toxicity.

Gastrointestinal system.

Treatment with pantoprazole causes dose dependent hypergastrinaemia as a result of inhibition of gastric acid secretion. Gastrin has a trophic effect on the gastric mucosa, and increases in gastric weight have been observed in rats and dogs to be dependent upon both dose and duration of treatment. Accompanying histopathological changes in the gastric mucosa were increased height, dilatation of fundic glands, chief cell hyperplasia and/or atrophy and parietal cell hyperplasia or vacuolation/ degeneration. Increased density of enterochromaffin-like (ECL) cells was observed after 12 months treatment at dose levels from 5 mg/kg/day in rats and 2.5 mg/kg/day in dogs; all changes were reversible after various recovery periods. Since these gastric effects are a consequence of the pharmacological effect of acid secretion inhibition, no-effect doses were not established in all instances.
Although rats might be more susceptible to this effect than other species because of their high ECL cell density and sensitivity to gastrin, ECL cell hyperplasia occurs in other species, including mice and dogs, and has been observed in one of two clinical trials in which ECL cell density was measured (a twofold increase was observed in study RR126/97 after up to five years of treatment with regular and high doses, but no increase was observed in study RR125/97). No dysplastic or neoplastic changes were observed in gastric endocrine cells in either study.

Ocular toxicity and dermal phototoxicity/ sensitivity.

Studies have shown that pantoprazole is retained in low levels in the eyes and skin of pigmented rats. It is likely that the retention reflects a reversible association with melanin. Animal studies investigating the potential for phototoxicity/ photosensitivity have not been conducted.
A two week dog study, conducted specifically to investigate the effects on the eye and ear, did not reveal any changes relating to pantoprazole treatment, but the doses chosen were relatively low (40 and 160 mg (about 4 and 15 mg/kg) orally and 60 mg (about 6 mg/kg) IV). No ophthalmological changes or changes in electroretinographs were observed in cynomolgus monkeys at IV doses of up to 15 mg/kg/day for four weeks.

4 Clinical Particulars

4.1 Therapeutic Indications

The symptomatic relief of heartburn, acid regurgitation and other symptoms associated with gastroesophageal reflux disease (GORD).

4.3 Contraindications

Known hypersensitivity to any components of the formulation; or in cases of cirrhosis or severe liver disease.
Pantoprazole, like other proton pump inhibitors, should not be coadministered with atazanavir (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

4.4 Special Warnings and Precautions for Use

Patients should be referred to their doctor for review if they:
have unintentional weight loss, anaemia, gastrointestinal bleeding, dysphagia, persistent vomiting or vomiting with blood, malaena, gastric ulcer is suspected or present or gastrointestinal surgery, as treatment with pantoprazole may alleviate symptoms and delay diagnosis. In these cases, malignancy should be excluded;
have had to take other medication for indigestion or heartburn continuously for four or more weeks in order to control their symptoms;
are being treated for symptomatic GORD and require pantoprazole for more than 14 days;
have jaundice or other severe hepatic impairment (e.g. cirrhosis); or
have any other significant medical condition.
Patients should consult their doctor before taking this product if they are due to have an endoscopy.
Withdrawal of long-term PPI therapy can lead to aggravation of acid-related symptoms and may result in rebound acid hypersecretion.

Use in the elderly.

No data available.

Paediatric use.

To date there has been limited experience with treatment in children and adolescents under 18 years of age.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Pantoprazole is metabolised in the liver via the cytochrome P450 enzyme system. A study using human liver microsomes suggested that the P450 enzymes CYP2C19 and CYP3A4 are involved in its metabolism. In addition, CYP2D6 and CYP2C9-10 were implicated in another study. An interaction of pantoprazole with other drugs or compounds which are metabolised using the same enzyme system cannot be excluded. However, no clinically significant interactions were observed in specific tests with a number of such drugs or compounds, namely carbamazepine, caffeine, diazepam, diclofenac, digoxin, ethanol, glibenclamide, metoprolol, naproxen, nifedipine, phenytoin, piroxicam, theophylline and the low dose oral contraceptive Triphasil (levonorgestrel and ethinyloestradiol). There was also no interaction with a concomitantly administered antacid (aluminium hydroxide and magnesium hydroxide).
Although no interaction during concomitant administration of phenprocoumon or warfarin has been observed in clinical pharmacokinetic studies, a few isolated cases of changes in international normalised ratio (INR) have been reported during concomitant treatment in the postmarketing period. Therefore, in patients being treated with coumarin anticoagulants, monitoring of prothrombin time/ INR is recommended after initiation, termination or during irregular use of pantoprazole.
Concomitant use of proton pump inhibitors with methotrexate (primarily at high dose), may elevate and prolong serum levels of methotrexate and/or its metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities.
Treatment of dogs with IV famotidine shortened the duration of the pH elevation effect of pantoprazole.
As with all acid suppressant medications, the absorption of drugs whose bioavailability is pH dependent (e.g. ketoconazole, itraconazole, posaconazole, erlotinib) might be altered due to the decrease in gastric acidity.
Four crossover pharmacokinetic studies designed to examine any interactions between pantoprazole and the drugs clarithromycin, amoxycillin and metronidazole, conducted in 66 healthy volunteers, showed no interactions.
It has been shown that coadministration of atazanavir 300 mg/ ritonavir 100 mg with omeprazole (40 mg once daily) or atazanavir 400 mg with lansoprazole (60 mg single dose) to healthy volunteers resulted in a substantial reduction in the bioavailability of atazanavir. The absorption of atazanavir is pH dependent. Therefore, proton pump inhibitors, including pantoprazole, should not be coadministered with atazanavir (see Section 4.3 Contraindications).

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Pantoprazole at oral doses up to 500 mg/kg/day in male rats and 450 mg/kg/day in female rats (estimated exposure at least 60-fold the clinical exposure from the 40 mg tablet) was found to have no effect on fertility and reproductive performance.
(Category B3)
Teratological studies in rats and rabbits gave no evidence of a teratogenic potential for pantoprazole. In oral studies in rats, dose dependent toxic effects were observed on fetuses and pups: increased prenatal and postnatal deaths (450 mg/kg/day), reduced fetal weight (greater than or equal to 150 mg/kg/day) and delayed skeletal ossification and reduced pup growth (greater than or equal to 15 mg/kg/day). For the latter, a no-effect dose was not established. Doses of 450 mg/kg/day were maternotoxic and may have been associated with dystocia and incomplete parturition. Penetration of the placenta was investigated in the rat and was found to increase with advanced gestation. As a result, concentrations of pantoprazole in the foetus are increased shortly before birth regardless of the route of administration. The significance of these findings in humans is unclear. As there is no information on the safety of the drug during pregnancy in women, pantoprazole should not be used during pregnancy unless the benefit clearly outweighs the potential risk to the foetus.
 A perinatal/ postnatal study in rats found that treatment with pantoprazole at doses of 10 mg/kg/day or greater decreased pup growth. A transient effect on one of a series of development tests (startle response) was only evident in the 30 mg/kg/day group at an age when male and female offspring showed lower bodyweights, paralleled with lower brain weight, than the controls. The significance of these findings for humans is unknown, and there is currently no information on the safety of pantoprazole during breastfeeding in humans. Therefore, pantoprazole should only be used during lactation if the benefits clearly outweigh the risks.

4.8 Adverse Effects (Undesirable Effects)

Pantoprazole tablets are well tolerated. Most of the adverse reactions seen with treatment were of mild or moderate intensity in clinical trials and postmarketing surveillance. The following adverse reactions have been reported in patients receiving pantoprazole.
Adverse reactions within each body system are listed in descending order of frequency (very common: ≥ 10%; common: ≥ 1% and < 10%; uncommon: ≥ 0.1% and < 1%; rare: ≥ 0.01% and < 0.1%; very rare: < 0.01%). These include the following.

General disorders and administration site conditions.

Uncommon: fatigue, malaise, asthenia and increased sweating.
Rare: fever and peripheral oedema.
Very rare: reports of substernal chest pain and hot flushes.

Cardiovascular disorders, general.

Rare: hypertension.
Very rare: circulatory collapse.

Nervous system disorders.

Uncommon: headache, dizziness.
Rare: taste disorders.
Very rare: reduced movement and speech disorder, changes the sense of smell and taste.
Not known: metallic taste.

Gastrointestinal system disorders.

Uncommon: diarrhoea, nausea, vomiting, abdominal pain and discomfort, constipation, dry mouth.
Rare: rectal disorder and colonic polyp.
Very rare: faecal discolouration and increased saliva.
Not known: flatulence, severe eructation, withdrawal of long-term PPI therapy can lead to aggravation of acid-related symptoms and may result in rebound acid hypersecretion.

Hearing and vestibular disorders.

Very rare: tinnitus.

Immune system disorders.

Rare: hypersensitivity (including anaphylactic reactions and anaphylactic shock).

Hepatobiliary disorders.

Uncommon: liver enzymes increased (transaminases, gamma-GT).
Rare: bilirubinaemia increased.
Very rare: hepatocellular failure, cholestatic hepatitis, and jaundice.
Not known: hepatocellular injury.
The occurrence of severe hepatocellular damage leading to jaundice or hepatic failure having a temporal relationship to the intake of pantoprazole has been reported with a frequency of approximately one in a million patients.

Metabolism and nutrition disorders.

Rare: hyperlipidaemias and lipid increases (triglycerides, cholesterol), weight changes.
Not known: hyponatraemia, hypomagnesaemia.

Musculoskeletal and connective tissue disorders.

Rare: myalgia and arthralgia.
Very rare: pain including skeletal pain.

Renal and urinary disorders.

Very rare: interstitial nephritis.

Blood and lymphatic system disorders.

Rare: anaemia agranulocytosis.
Very rare: leukopenia, thrombocytopenia, pancytopenia, increased coagulation time.

Psychiatric disorders.

Uncommon: sleep disorders.
Rare: depression, hallucination, disorientation and confusion, especially in predisposed patients, as well as aggravation of these symptoms in the case of pre-existence.
Very rare: anxiety.

Resistance mechanism disorders.

Rare: sepsis.

Respiratory system disorders.

Very rare: dyspnoea.

Skin and subcutaneous tissue disorders.

Uncommon: pruritus, rash, exanthema/ eruption.
Rare: angioedema and urticaria.
Very rare: severe skin reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, Lyell syndrome and photosensitivity.

Reproductive system and breast disorders.

Rare: gynaecomastia.

Eye disorders.

Uncommon: disturbances in vision (blurred vision).
Very rare: conjunctivitis.

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

The enteric coated tablets are intended for oral administration.

Dosage.

APO-Pantoprazole Heartburn Relief is indicated for use in adults 18 years of age and over. Pantoprazole tablets should not be chewed or crushed, but swallowed whole with a little water.

Gastroesophageal reflux disease.

Symptomatic gastroesophageal reflux disease (treatment of symptomatic reflux).

The recommended dosage is one pantoprazole 20 mg tablet per day for at least 7 days, and up to 14 days. If symptom control has not been achieved after two weeks of continuous treatment with pantoprazole 20 mg tablets daily, patients should be referred to their doctor.

Use in children.

There are limited data currently available on the use of pantoprazole in children. Pantoprazole is not recommended for use in children and adolescents under 18 years of age.

Use in the elderly.

No dose adjustment is necessary in elderly patients.

Renal impairment.

No dose adjustment is required when pantoprazole is administered to patients with impaired renal function.

Hepatic impairment.

Pantoprazole is contraindicated in patients with cirrhosis or severe liver disease (see Section 4.3 Contraindications).
No dose adjustment is required when pantoprazole is administered to patients with milder forms of impaired liver function.

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

Symptoms.

There are no known symptoms of overdosage in humans. In individual cases 240 mg has been administered IV or orally and was well tolerated.

Treatment.

Standard detoxification procedures apply.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

7 Medicine Schedule (Poisons Standard)

S2: 7's; S3: 14's.

6 Pharmaceutical Particulars

6.1 List of Excipients

In addition, each enteric coated tablet contains the following inactive ingredients: lactose anhydrous, crospovidone, microcrystalline cellulose, magnesium stearate, hypromellose, macrogol 8000, anhydrous sodium carbonate, methacrylic acid copolymer, triethyl citrate, talc-purified, titanium dioxide and iron oxide yellow.

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. Protect from light and moisture.

6.5 Nature and Contents of Container

APO-Pantoprazole Heartburn Relief tablets 20 mg.

Blisters (Alu/Alu) of 7 or 14 tablets: AUST R 156332.
Not all 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.

Summary Table of Changes