Consumer medicine information

Gastenz

Pantoprazole

BRAND INFORMATION

Brand name

Gastenz Tablets

Active ingredient

Pantoprazole

Schedule

S2: 7's; S3: 14's

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Gastenz.

What is in this leaflet

This leaflet answers some common questions about Gastenz.

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 or pharmacist has weighed the risks of you taking this medicine against the benefits they expect it will have for you.

Take this medicine as directed and follow the advice given in this leaflet.

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 Gastenz is used for

Gastenz contains the active ingredient pantoprazole.

It is used for lasting symptomatic relief of frequent heartburn and stomach acid complaints due to gastro-oesophageal reflux.

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 (GORD).

Gastenz is recommended for adults 18 years of age and over, suffering from heartburn at least 2 times a week.

It is not the right medicine for you if you suffer from heartburn only occasionally (one episode of heartburn a week or less), or if you want immediate relief of heartburn.

How Gastenz works

Pantoprazole 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 the symptoms.

It 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.

This medicine is not addictive.

Before you take Gastenz

When you must not take it

Do not take this medicine if you have an allergy to:

  • the active ingredient pantoprazole or to any of the other ingredients listed at the end of this leaflet under Product Description
  • any other similar medicines.

Some of the symptoms of an allergic reaction may include:

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

Do not take Gastenz in combination with atazanavir (an anti-viral medication).

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

Do not take this medicine if you have recently had trouble swallowing, pain when swallowing, persistent vomiting or experienced unintended weight loss.

Do not take this medicine if you have recently vomited blood, had black stools or notice blood in your stools.

Do not take this medicine if you are pregnant, intend to become pregnant, are breast-feeding or wish to start breast-feeding.

This medicine should not be given to children and adolescents under the age of 18 years.

Safety and effectiveness in children and adolescents has not been established.

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 or pharmacist.

Before you start to take it

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

Tell your doctor or pharmacist if you are pregnant or plan to become pregnant or are breastfeeding.

They can discuss with you the risks and benefits involved.

Tell your doctor or pharmacist if you have or have had any other medical conditions.

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

Talk to your pharmacist or doctor first before taking this medicine if:

  • you have previously taken heartburn / indigestion medications continuously for 4 or more weeks to control your heartburn
  • you have jaundice, liver problems, anaemia, a feeling of weakness or you look pale, previous gastric ulcer or gastrointestinal surgery
  • you have persisting heartburn symptoms despite taking Gastenz (or other similar medicines) continuously for 2 weeks, or your symptoms have recently changed
  • you have heartburn/ indigestion symptoms for the first time and you are over 40 years of age
  • you have new or recently changed symptoms including persistent vomiting or vomiting of blood, blood in the stools or unexplained weight loss
  • you ever had a skin reaction after treatment with a medicine similar to Gastenz that reduces stomach acid.

If you get a rash on your skin, especially in areas exposed to the sun tell your doctor as soon as you can, as you may need to stop your treatment with Gastenz. Remember to also mention any other ill-effects like pain in your joints.

If you have experienced any of the above you should see your doctor immediately.

If you have suffered from frequent heartburn / indigestion symptoms for some time you should see your doctor.

You should also speak to your doctor before taking this medicine if you are due to have an endoscopy (a special test ordered by your doctor).

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 Gastenz may interfere with each other. These include:

  • atazanavir or nelfinavir – medicines used to treat viral infections such as HIV
  • warfarin or phenprocoumon- medicines used to prevent blood clots (anticoagulants)
  • medicines used to treat fungal infection such as ketoconazole, itraconazole, posaconazole
  • tacrolimus, mycophenolate mofetil- medicines used to suppress the immune system
  • methotrexate - a medicine used to treat arthritis and some types of cancer
  • erlotinib or related medicines used to treat cancer
  • fluvoxamine - a medicine used to treat anxiety and depression.

These medicines may be affected by Gastenz or may affect how well it works.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking this medicine. Speak with your doctor or pharmacist if you have any concerns about taking Gastenz with other medications.

How to take Gastenz

Follow the instructions given in this leaflet. If you do not understand the instructions, ask your doctor or pharmacist for help.

How much to take

Take one tablet once a day (every 24 hours).

How to take it

Swallow the tablets whole with a full glass of water with or without food.

Do not crush or chew the tablets.

The tablets have a special coating to protect them from the acidic contents of your stomach. For the tablets to work effectively, this coating must not be broken.

When to take Gastenz

Take your medicine at about the same time each day.

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 Gastenz

Take one tablet daily for at least seven days, and up to 14 days. If the pack has 7 days' supply and if you need to use longer than 7 days, ask your pharmacist for advice. You should not take it for more than 14 days unless directed by a doctor.

If you forget to take it

Take your dose as soon as you remember, and 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 that you missed.

This may increase the chance of you getting an unwanted side effect.

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 Gastenz. Do this even if there are no signs of discomfort or poisoning.

You may need urgent medical attention.

While you are taking Gastenz

Things you must do

Take this medicine exactly as your doctor or pharmacist has advised.

Tell your doctor if you become pregnant while taking Gastenz.

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

Tell your doctor or pharmacist if you do not feel better while taking this medicine.

If symptoms persist or recur within 2 weeks of completing the course, consult a doctor.

Further examination may be recommended.

Things you must not do

Do not take Gastenz 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.

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.

Side effects

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

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 or pharmacist if you notice any of the following and they worry you:

  • headache, dizziness
  • nausea or vomiting
  • diarrhoea, stomach pain, discomfort, excessive gas in the stomach or bowel, constipation, indigestion
  • dry mouth
  • metallic taste
  • mild weakness or tiredness or sleep disturbances
  • increased sweating or body temperature
  • blurred vision
  • skin problems such as itchiness and rash.

The above list includes the more common side effects of your medicine.

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

  • unusual tiredness, weakness, dizziness or fainting
  • chest pain, fast heartbeat, shortness of breath
  • nausea or vomiting in combination with loss of appetite, feeling generally unwell, fever, itching, yellowing of the skin and eyes, and dark coloured urine or bowel movements
  • blood in the urine
  • increased or decreased need to urinate
  • skin problems such as itchiness and rash, or swelling, blistering or peeling of the skin
  • swelling of the face, lips, mouth, tongue or throat which may cause difficulty in swallowing or breathing
  • frequent symptoms of infections such as fever, severe chills, sore throat or mouth ulcers
  • high blood pressure
  • water retention, swelling
  • bleeding or bruising more easily than normal
  • depression, confusion or anxiety
  • bone fracture of the hip, wrist or spine (mainly a risk in people who take high doses of PPIs or use them long term (a year or longer))
  • symptoms such as seizures, abnormal or fast heartbeat or jerking/shaking movements. These can be a sign of low magnesium levels in your blood
  • severe and/or persistent diarrhoea, because this medicine has been associated with a small increase in infectious diarrhoea.

The above list includes serious side effects that may require urgent medical attention. Serious side effects are rare.

Tell your doctor or pharmacist if you notice anything else that is making you feel unwell.

Other side effects not listed above may also occur in some people.

After taking Gastenz

Storage

Keep your medicine in the original container.

If you take it out of its original container it may not keep well.

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

Do not store Gastenz 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 you 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 it looks like

Gastenz 20mg - yellow and oval shaped enteric-coated tablets.

Available in blister packs of 7 and 14 enteric-coated tablets.

Ingredients

Active ingredients:

  • 20mg pantoprazole (as sodium sesquihydrate)

Inactive ingredients:

  • sodium carbonate
  • microcrystalline cellulose
  • crospovidone
  • hyprolose
  • colloidal anhydrous silica
  • calcium stearate
  • Opadry complete film coating system 03B22011 Yellow
  • Eudragit L30D-55
  • triethyl citrate

This medicine does not contain gluten, lactose or sucrose.

Supplier

Gastenz is supplied in Australia by:

Sandoz Pty Ltd
ABN 60 075 449 553
54 Waterloo Road
Macquarie Park, NSW 2113
Australia
Tel: 1800 726 369

This leaflet was prepared in December 2017

Australian Register Number
Gastenz 20mg enteric-coated tablets: AUST R 169322

BRAND INFORMATION

Brand name

Gastenz Tablets

Active ingredient

Pantoprazole

Schedule

S2: 7's; S3: 14's

 

Name of the medicine

Pantoprazole (as sodium sesquihydrate).

Excipients.

Sodium carbonate, microcrystalline cellulose, crospovidone, hyprolose, colloidal anhydrous silica, calcium stearate, Opadry complete film coating system 03B22011 Yellow, Eudragit L30D-55, triethyl citrate.

Description

5-(Difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridinyl)methyl] sulfinyl]-1H-benzimidazole, sodium salt, sesquihydrate. CAS number: 164579-32-2 (pantoprazole sodium sesquihydrate). Empirical formula: C16H14F2N3NaO4S.1.5H2O. MW: 432.
Each Gastenz 20 mg enteric coated tablet contains 22.55 mg pantoprazole sodium sesquihydrate equivalent to 20 mg of pantoprazole.
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.
In addition to pantoprazole sodium sesquihydrate, these tablets also contain sodium carbonate, microcrystalline cellulose, crospovidone, hyprolose, colloidal anhydrous silica, calcium stearate, Opadry complete film coating system 03B22011 Yellow, Eudragit L30D-55 and triethyl citrate.

Pharmacology

Pharmacodynamics.

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 sulphenamide 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.

Pharmacokinetics.

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 h, with a Cmax of approximately 1.2 microgram/mL. Terminal half-life is approximately 1 h. Volume of distribution is approximately 0.15 L/kg and clearance is approximately 0.1 L/h/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 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 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 desmethylpantoprazole which is conjugated with the sulphate. The half-life of the main metabolites (approximately 1.5 h) 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 3-fold in patients with mild hepatic impairment and 5-fold in patients with severe hepatic impairment compared with healthy controls. Mean elimination half-life was 3.3 h in mild hepatic impairment and 6.0 h in severe hepatic impairment compared with 1.1 h 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 dialyzable.
The slight increase in AUC and Cmax in elderly volunteers compared with their younger counterparts is also not clinically relevant.
Following oral administration of pantoprazole 40 mg to healthy subjects under fasting conditions, a mean peak plasma concentration (Cmax) of pantoprazole of approximately 2459.7 nanogram/mL was achieved within approximately 3.07 hours (Tmax).
Following oral administration of pantoprazole 40 mg to healthy subjects under fed conditions, a mean peak plasma concentration (Cmax) of pantoprazole of approximately 2685.9 nanogram/mL was achieved within approximately 6.48 hours (Tmax).

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 3 months prior to entry into the study. Efficacy of pantoprazole 20 mg is shown in Table 1.

Indications

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

Contraindications

Known hypersensitivity to pantoprazole, substituted benzimidazoles or any components of the formulation.
Cases of cirrhosis or severe liver disease.
Pantoprazole, like other proton pump inhibitors, should not be coadministered with atazanavir or nelfinavir (see Interactions with Other Medicines).

Precautions

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, melaena, 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;
they have had to take other medication for indigestion or heartburn continuously for four or more weeks in order to control their symptoms;
they are being treated for symptomatic GORD and require treatment with pantoprazole for more than 14 days;
they have jaundice or severe hepatic impairment (e.g. cirrhosis);
they have any other significant medical condition.

Clostridium difficile.

PPI therapy may be associated with an increased risk of Clostridium difficile infection. Pantoprazole, like all proton pump inhibitors, might be expected to increase the counts of bacteria normally present in the upper gastrointestinal tract. Treatment with pantoprazole may lead to a slightly increased risk of gastrointestinal infections caused by bacteria such as Salmonella, Campylobacter and Clostridium difficile.

Influence on vitamin B12 absorption.

Pantoprazole, as all acid blocking medicines, may reduce the absorption of cyanocobalamin (vitamin B12) due to hypochlorhydria or achlorhydria. This should be considered in patients with reduced body stores or risk factors for reduced vitamin B12 absorption such as the elderly and in patients with Zollinger-Ellison syndrome and other pathological hypersecretory conditions or if respective clinical symptoms are observed. Rare cases of cyanocobalamin deficiency following acid blocking therapy have been reported.

Bone fracture.

PPI therapy may be associated with an increased risk for osteoporosis related fractures of the hip, wrist, or spine. The risk of fracture was increased in patients who received high doses; defined as multiple daily doses, and long-term PPI therapy (a year or longer).

Subacute cutaneous lupus erythematosus (SCLE).

Proton pump inhibitors are associated with very infrequent cases of 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 health care professional should consider stopping pantoprazole. SCLE after previous treatment with a proton pump inhibitor may increase the risk of SCLE with other proton pump inhibitors.

Acute interstitial nephritis.

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

Hypomagnesaemia.

Hypomagnesaemia has been rarely reported in patients treated with PPIs for at least three months (in most cases after a year of therapy). Serious consequences of hypomagnesaemia include tetany, arrhythmia, and seizure.

Use in pregnancy.

(Category B3)
Teratological studies in rats and rabbits gave no evidence of a teratogenic potential for pantoprazole. In oral rat studies, dose dependent toxic effects were observed on foetuses and pups: increased prenatal and postnatal deaths at 450 mg/kg/day, reduced foetal weight at ≥ 150 mg/kg/day and delayed skeletal ossification and reduced pup growth at ≥ 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.
Australian categorisation definition of Category B3: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human foetus having been observed. Studies in animals have shown evidence of an increased occurrence of foetal damage, the significance of which is considered uncertain in humans.

Use in lactation.

A peri/ 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 body weights, 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.

Paediatric use.

To date there is limited experience with treatment in children under 18 years of age.

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 200 mg/kg/day pantoprazole for 14 days. 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 1200 mg/kg) (56E/96) and in mice at the high dose from the earlier micronucleus test (710 mg/kg) (89E/96). Pantoprazole exposure was high with the respective rat and mouse plasma AUCs being 7 to 100 and 9 to 12-fold the clinical exposure from a 40 mg tablet.

Carcinogenicity.

In a two year oral carcinogenicity study in Sprague Dawley rats at doses up to 200 mg/kg/day gastric carcinoids were found 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 the 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 (exposure similar to clinical exposure), 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, while none were detected in controls. No metastases of these carcinoids were detected. There was no increase in 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.

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.

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 2-fold increase was observed in study RR126/97 after up to 5 years of treatment with regular and high doses, but no increase was observed in study RR125/97). No dysplasic 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 2 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 4 weeks.

Interference with laboratory tests.

During treatment with antisecretory medicinal products, serum gastrin increases in response to the decreased acid secretion. Also Chromogranin A (CgA) increases due to decreased gastric acidity. The increased 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. This is to allow CgA levels that might be spuriously elevated following PPI treatment to return to reference range.
Patients should consult their doctor before taking this product if they are due to have an endoscopy.

Effects on ability to drive and use machines.

Pantoprazole does not exert its pharmacological action centrally, therefore it is not expected to adversely affect the ability to drive or use machines, however, adverse drug reactions such as dizziness and visual disturbances may occur (see Adverse Effects). If affected, patients should not drive or operate machines.

Interactions

Pantoprazole is metabolized 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).
Treatment of dogs with IV famotidine shortened the duration of the pH elevation effect of pantoprazole.
Four cross-over pharmacokinetic studies designed to examine any interactions between pantoprazole and the drugs clarithromycin, amoxicillin and metronidazole, conducted in 66 healthy volunteers, showed no interactions.

Drugs with pH dependent absorption pharmacokinetics.

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.

HIV protease inhibitors.

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 Contraindications).

Mycophenolate mofetil.

Coadministration of PPIs in healthy subjects and in transplant patients receiving mycophenolate mofetil has been reported to reduce the 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 pantoprazole with caution in transplant patients receiving mycophenolate mofetil.

Methotrexate.

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.

Drugs that inhibit or induce CYP2C19 (tacrolimus, fluvoxamine).

Concomitant administration of pantoprazole 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 of pantoprazole.

Coumarin anticoagulants (phenprocoumon or warfarin).

Coadministration of pantoprazole with warfarin or phenprocoumon did not affect the pharmacokinetics of warfarin, phenprocoumon or international normalised ratio (INR). However, there have been reports of increased INR and prothrombin time in patients receiving PPIs and warfarin or phenprocoumon concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding, and even death. Therefore, in patients being treated with coumarin anticoagulants (e.g. warfarin or phenprocoumon), monitoring of prothrombin time/ INR is recommended after initiation, termination or during irregular use of pantoprazole.

Adverse 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.
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%; not known: cannot be estimated from the available data). These include the following:

General disorders and administration site conditions.

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

Cardiovascular disorders, general.

Rare: hypertension. Very rare: circulatory collapse.

Nervous system disorders.

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

Gastrointestinal system disorders.

Common: fundic gland polyps (benign). Uncommon: diarrhoea, nausea/ vomiting, abdominal distension and bloating, constipation, dry mouth, abdominal pain and discomfort. Rare: rectal disorder and colonic polyp. Very rare: faecal discolouration and increased saliva. Not known: flatulence, severe eructation.

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, γ-GT). Rare: bilirubin 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.

Metabolic and nutritional disorders.

Rare: hyperlipidaemias and lipid increases (triglycerides, cholesterol), weight changes. Not known: hyponatraemia, hypomagnesaemia, hypocalcaemia in association with hypomagnesaemia, hypokalaemia.

Musculoskeletal and connective tissue disorders.

Uncommon: fracture of the hip, wrist or spine. Rare: arthralgia, myalgia. Very rare: pain including skeletal pain. Not known: muscle spasm as a consequence of electrolyte disturbances.

Renal and urinary disorders.

Very rare: interstitial nephritis (with possible progression to renal failure).

Platelet, bleeding, clotting disorders.

Very rare: increased coagulation time.

Blood and lymphatic system disorders.

Rare: anaemia, agranulocytosis. Very rare: leukopenia, thrombocytopenia, pancytopenia.

Psychiatric disorders.

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

Resistance mechanism disorders.

Rare: sepsis.

Respiratory system disorders.

Very rare: dyspnoea.

Reproductive system and breast disorders.

Rare: gynaecomastia.

Skin and subcutaneous tissue disorders.

Uncommon: pruritus, rash/ exanthema/ eruption. Rare: angioedema, urticaria. Very rare: flushing, severe skin reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, Lyell syndrome and photosensitivity. Not known: subacute cutaneous lupus erythematosus.

Eye disorders.

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

Dosage and Administration

Gastenz is indicated for use in adults 18 years of age and over. The tablets should not be chewed or crushed but swallowed whole with a little water.

Symptomatic GORD.

The recommended dosage is one 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. Gastenz 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.

Impaired renal function.

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

Impaired hepatic function.

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

Overdosage

Contact the Poisons Information Centre on 131 126 for advice on management of overdose.
There are no known symptoms of overdosage in humans. In individual cases, 240 mg was administered i.v. or p.o. and was well tolerated. Standard detoxification procedures apply.
As pantoprazole is extensively protein bound, it is not readily dialyzable. As in any case of overdosage, treatment should be symptomatic and supportive measures should be utilised.

Presentation

Tablets, 20 mg (yellow, oval, enteric coated): 7's, 14's (blister pack).

Storage

Store below 25°C.

Poison Schedule

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