Consumer medicine information

Pantoprazole Sandoz Injection

Pantoprazole

BRAND INFORMATION

Brand name

Pantoprazole Sandoz 40mg Powder for Injection

Active ingredient

Pantoprazole

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Pantoprazole Sandoz Injection.

What is in this leaflet

This leaflet answers some common questions about Pantoprazole Sandoz.

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.

WHAT PANTOPRAZOLE SANDOZ IS USED FOR

This medicine is used to treat

  • Ulcers
    Pantoprazole Sandoz is used to treat and help heal duodenal and gastric ulcers.
    Depending on the position of the ulcer it is called a gastric or duodenal ulcer. A gastric ulcer occurs in the stomach. A duodenal ulcer occurs in the duodenum which is the tube leading out of the stomach.
    These can be caused in part by too much acid being made in the stomach.
  • Reflux disease
    Pantoprazole Sandoz is also used to treat reflux oesophagitis or reflux disease. 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.
    Pantoprazole Sandoz is also used to prevent reflux oesophagitis from coming back.
  • Zollinger-Ellison syndrome
    Pantoprazole Sandoz is used to treat a rare condition called Zollinger- Ellison syndrome, where the stomach produces very large amounts of acid, much more than in ulcers and reflux disease.

This medicine contains the active ingredient pantoprazole sodium. Pantoprazole sodium belongs to a group of medicine called proton pump inhibitors (PPIs). It works by decreasing the amount of acid the stomach makes to give relief from the symptoms 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 it for another reason.

This medicine is not addictive.

There is not enough information to recommend the use of this medicine for children.

This medicine is not expected to affect your ability to drive a car or operate machinery.

However, do not drive a car or operate machines if you experience side effects such as dizziness or blurred vision.

BEFORE YOU ARE GIVEN PANTOPRAZOLE SANDOZ

When you must not be given it

You should not be given this medicine if you have an allergy to:

  • the active ingredient pantoprazole
  • 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.

Pantoprazole Sandoz should not be given in combination with atazanavir or nelfinavir (anti-viral medications).

You should not be given this medicine if you have severe liver disease or cirrhosis.

This medicine should not be given to children. Safety and effectiveness in children has not been established.

This medicine should not be given 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 be given this medicine, talk to your doctor.

Before you given it

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

Tell your doctor if you are pregnant or plan to become pregnant or are breastfeeding. Your doctor can discuss with you the risks and benefits involved.

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

If you have not told your doctor about any of the above, tell him/her before you start receive Pantoprazole Sandoz.

Tell your doctor if you have any of the following symptoms:

  • unintentional weight loss
  • repeated vomiting
  • vomiting blood
  • difficulty or pain when swallowing
  • you look pale and feel weak
  • you notice blood in your stools

Your doctor may need to perform some additional tests before you take Pantoprazole Sandoz

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 Pantoprazole Sandoz may interfere with each other. These include:

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

These medicines may be affected by Pantoprazole Sandoz 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 being given this medicine.

HOW PANTOPRAZOLE SANDOZ IS GIVEN

Pantoprazole Sandoz will be administered by your doctor. Follow all directions given to you by your doctor or pharmacist carefully. They may differ from the information contained in this leaflet.

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

How it is given

The dose and frequency of Pantoprazole Sandoz Injection will be determined by your doctor and will depend on your medical condition. Your doctor may change the dose as your condition changes.

Pantoprazole Sandoz is reconstituted with a sodium chloride solution by your doctor or pharmacist.

Your doctor will ensure that you receive the correct dose of Pantoprazole Sandoz.

Never administer this medicine to yourself.

If you are taking other medicines, like antibiotics, in combination with Pantoprazole Sandoz therapy, follow the instructions for the use of each medicine carefully.

How long it will be given for

Your doctor will determine how long you need to be treated with Pantoprazole Sandoz.

If you miss a dose

Tell your doctor as soon as possible if you realise that you have missed an appointment for receiving your dose of Pantoprazole Sandoz.

If you have problems remembering when your next dose is due, use a diary or calendar, or ask a friend to remind you.

If you are given too much (overdose)

Immediately telephone your doctor or the Poisons Information Centre (telephone Australia 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 been given too much Pantoprazole Sandoz. Do this even if there are no signs of discomfort or poisoning.

As Pantoprazole Sandoz is given to you under the supervision of your doctor, it is very unlikely that you will receive too much. However, if you experience severe side effects (This side effects are listed under the heading, 'Side effects' in this leaflet) after being given this medicine, tell your doctor or nurse immediately.

You may need urgent medical attention.

WHILE YOU ARE BEING GIVEN PANTOPRAZOLE SANDOZ

Things you must do

Always follow your doctor's instructions carefully.

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are being treated with Pantoprazole Sandoz.

Tell any other doctors, dentists and pharmacists who treat you that you are being given Pantoprazole Sandoz.

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

If you become pregnant while you are being given this medicine, tell your doctor immediately. Keep all of your doctor’s appointments so that your progress can be checked.

Your doctor may do some tests from time to time to make sure the medicine is working and to prevent unwanted side effects.

Things you must not do

Do not use Pantoprazole Sandoz 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 using Pantoprazole Sandoz without your doctor's permission. Your doctor may want you to gradually reduce the amount you are taking before stopping completely.

Things to be careful of

Be careful driving or operating machinery until you know how Pantoprazole Sandoz affects you. This medicine may cause dizziness or light-headedness in some people, especially after the first dose. If you have any of these symptoms, do not drive, operate machinery or do anything else that could be dangerous.

If you feel light-headed, dizzy or faint when getting out of bed or standing up, get up slowly. Standing up slowly, especially when you get up from bed or chairs will help your body get used to the change in position and blood pressure. If this problem continues or gets worse, talk to your doctor.

SIDE EFFECTS

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are being given Pantoprazole Sandoz.

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
  • excessive gas in the stomach or bowel
  • constipation
  • indigestion
  • dry mouth
  • metallic taste
  • pain and swelling at the site of injection
  • weakness or tiredness
  • increased sweating or body temperature
  • blurred vision
  • skin problems such as itchiness and rash
  • trouble sleeping.

The above list includes the more common side effects of your medicine. They are usually mild and short-lived.

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

  • unusual tiredness or weakness
  • nausea, vomiting, loss of appetite, feeling generally unwell, fever, itching, yellowing of the skin and eyes, and dark coloured urine
  • blood in the urine
  • increased or decreased need to urinate
  • skin problems such as itchiness and rash with swelling, blistering or peeling of the skin or rash when exposed to the sun, possibly with pain in the joints
  • swelling of the face, lips, mouth, tongue or throat which may cause difficulty in swallowing or breathing
  • frequent infections such as fever, severe chills, sore throat or mouth ulcers
  • chest pain
  • shortness of breath
  • 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 dose 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, calcium or potassium 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 YOU ARE GIVEN PANTOPRAZOLE SANDOZ

Storage

Pantoprazole Sandoz will be stored in the original packaging in the pharmacy or on the ward.

If it is taken out of its original container it may not keep well.

Normally your doctor will provide you Pantoprazole Sandoz injection. If however, you do take your medicine injection (in the form of a dry powder) from the pharmacy to your doctor, it is important to store it in a safe place away from heat (below 25°C).

If for any reason you are given your Pantoprazole Sandoz injection to take home, the liquid product (after reconstitution) should be used as soon as possible after preparation by the pharmacist. If storage is necessary, store at 2-8°C for no longer than 12 hours.

Do not store Pantoprazole Sandoz 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 stops treating you with Pantoprazole Sandoz, your hospital pharmacist will dispose any unused medicine.

PRODUCT DESCRIPTION

What it looks like

Pantoprazole Sandoz is available as a 40mg injection. It is white to off white powder provided in a clear glass vial with a red stopper and aluminium "flip-off" cap.

Ingredients

Active ingredients:

  • Pantoprazole Sandoz 40 mg - 40 mg pantoprazole as pantoprazole sodium

There are no inactive ingredients in Pantoprazole Sandoz

This medicine does not contain gluten, lactose or sucrose.

Supplier

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

This leaflet was revised in August 2020.

Australian Register Number(s)

Pantoprazole Sandoz 40 mg powder for injection: AUST R 147377

Published by MIMS October 2020

BRAND INFORMATION

Brand name

Pantoprazole Sandoz 40mg Powder for Injection

Active ingredient

Pantoprazole

Schedule

S4

 

1 Name of Medicine

Pantoprazole sodium.

2 Qualitative and Quantitative Composition

Pantoprazole Sandoz 40 mg Powder for Injection contains 42.29 mg of pantoprazole sodium equivalent to 40 mg pantoprazole.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Powder for injection.
Pantoprazole sodium is a white to off-white amorphous powder.

4 Clinical Particulars

4.1 Therapeutic Indications

Pantoprazole Sandoz is indicated for short-term use where oral therapy is not appropriate for the following conditions:
1. Symptomatic improvement and healing of gastrointestinal diseases which require a reduction in acid secretion, e.g. duodenal ulcer, gastric ulcer, reflux oesophagitis, gastrointestinal lesions refractory to H2 blockers, Zollinger-Ellison syndrome.
2. Maintenance of healed reflux oesophagitis in patients previously treated for moderate to severe reflux oesophagitis.

Note.

Patients whose gastric or duodenal ulceration is not associated with ingestion of nonsteroidal anti-inflammatory drugs require treatment with antimicrobial agents in addition to antisecretory medicines, whether on first presentation or recurrence.

4.2 Dose and Method of Administration

Dosage.

Adults.

Duodenal ulcer, gastric ulcer, gastrointestinal lesions refractory to H2-blockers, Zollinger-Ellison syndrome.

40 mg per day.

Reflux oesophagitis.

20-40 mg per day.
Intravenous Pantoprazole Sandoz should be replaced with oral therapy as soon as practicable.

Preparation for use.

A ready to use solution is prepared by injecting 10 mL sodium chloride intravenous infusion 0.9% into the vial containing the dry powder. This solution may be administered directly or may be administered after mixing with 100 mL sodium chloride intravenous infusion 0.9%.
After preparation, the solution should be administered over 2 to 15 minutes.

Dosage adjustment.

Renal impairment.

The usual daily dose of 20 mg or 40 mg can be given.

Hepatic impairment.

Pantoprazole is contraindicated in patients with cirrhosis or severe liver disease (see Section 4.3 Contraindications). With milder forms of liver disease, the initial dose should be reduced.

Infants and children.

There are no data currently available on the use of pantoprazole in children.

Elderly.

The usual daily dose of 20 mg or 40 mg can be given.

Instructions for use and handling.

To reduce microbiological hazard, use as soon as practicable after reconstitution/ preparation. If storage is necessary, hold at 2°C-8°C for not more than 12 hours.
This product contains no antimicrobial agent. Pantoprazole Sandoz injection is for single use in one patient only. Any unused product remaining or the visual appearance of which has changed (e.g. if cloudiness or precipitation is observed), should be discarded.

4.3 Contraindications

Pantoprazole should not be used in cases of known hypersensitivity to pantoprazole sodium, substituted benzimidazoles, any of the other excipients, or in cases of cirrhosis or severe liver disease.
Pantoprazole, like other proton pump inhibitors, should not be coadministered with HIV protease inhibitors, such as atazanavir or nelfinavir (see Section 4.4 Special Warnings and Precautions for Use; Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

4.4 Special Warnings and Precautions for Use

Check the following before use.

The intravenous administration of Pantoprazole Sandoz powder for injection is recommended only if oral application is not appropriate.
In the presence of any alarm symptoms (e.g. significant unintentional weight loss, recurrent vomiting, dysphagia, haematemesis, anaemia or melaena) and when gastric ulcer is suspected or present, malignancy should be excluded, as treatment with pantoprazole may alleviate symptoms and delay diagnosis. Further investigation is to be considered if symptoms persist despite adequate treatment.

Clostridium difficile.

PPI therapy may be associated with an increased risk of Clostridium difficile infection.
Pantoprazole, like all proton pump inhibitors (PPIs), 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 C. difficile.

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.

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). Observational studies suggest that proton pump inhibitors 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 care according to current clinical guidelines and they should have an adequate intake of vitamin D and calcium.

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.

Severe hypomagnesaemia has been reported in patients treated with PPIs like pantoprazole for at least three months, and in most cases for a year. Serious manifestations of hypomagnesaemia such as fatigue, tetany, delirium, convulsions, dizziness and ventricular arrhythmia can occur but they may begin insidiously and be overlooked. Hypomagnesaemia may lead to hypocalcaemia and/or hypokalemia (see Section 4.8 Adverse Effects (Undesirable Effects)). In most affected patients, hypomagnesaemia improved after magnesium replacement and discontinuation of the PPI.
For patients expected to be on prolonged treatment or who take PPIs with digoxin or drugs that may cause hypomagnesaemia (e.g. diuretics), healthcare professionals should consider measuring magnesium levels before starting PPI treatment and periodically during treatment.

Influence on vitamin B12 absorption.

In patients with Zollinger-Ellison syndrome and other pathological hypersecretory conditions requiring long-term treatment, pantoprazole, as all acid blocking medicines, may reduce the absorption of vitamin B12 (cyanocobalamin) due to hypo or achlorhydria. This should be considered in patients with reduced body stores or risk factors for reduced vitamin B12 absorption (such as the elderly) on long-term therapy or if respective clinical symptoms are observed.

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 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 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.

Use in hepatic impairment.

In patients with severe liver impairment, the liver enzymes should be monitored regularly during treatment with pantoprazole, particularly on long-term use. In the case of a rise of the liver enzymes, the treatment should be discontinued (see Section 4.2 Dose and Method of Administration).

Use in the elderly.

No dose adjustment is necessary in elderly patients (see Section 4.2 Dose and Method of Administration, Use in the elderly; Section 4.4 Special Warnings and Precautions for Use, Influence on vitamin B12 absorption; Section 5.2 Pharmacokinetic Properties, Excretion).

Paediatric use.

To date there has been no experience with treatment in children.

Effects on 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.

4.5 Interactions with Other Medicines and Other Forms of 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 and CYP2C10 were implicated in another study. An interaction of pantoprazole with other medicines 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 medicines 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.

Drugs with pH-dependent absorption pharmacokinetics.

Because of profound and long lasting inhibition of gastric acid secretion, pantoprazole may reduce the absorption of drugs with a gastric pH dependent bioavailability, e.g. some azole antifungals as ketoconazole, itraconazole, posaconazole and other medicines such as erlotinib.

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 HIV protease inhibitors for which absorption is dependent on acidic intragastric pH, such as atazanavir or nelfinavir (see Section 4.3 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 with methotrexate (primarily at high dose), may elevate and prolong serum levels of methotrexate and/or its metabolite, possibly leading to methotrexate toxicities. Therefore in settings where high dose methotrexate is used, for example cancer and psoriasis, a temporary withdrawal of pantoprazole may need to be considered.

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).

Co-administration 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.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available (see Section 5.3 Preclinical Safety Data).
(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 fetuses and pups: increased pre- 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 fetus are increased shortly before birth regardless of the route of administration.
The significance of these findings in humans is unknown. As there is no information on the safety of the medicine during pregnancy in women, pantoprazole should not be used during pregnancy, unless the benefit clearly outweighs the potential risk to the fetus.
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 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. Excretion into human milk has been reported. Therefore, pantoprazole should only be used during lactation if the benefits clearly outweigh the risks.

4.7 Effects on Ability to Drive and Use Machines

Adverse drug reactions such as dizziness and visual disturbances may occur (see Section 4.8 Adverse Effects (Undesirable Effects)). If affected, patients should not drive or operate machines.

4.8 Adverse Effects (Undesirable Effects)

Pantoprazole injection is well tolerated. Most of the adverse reactions seen with treatment were of mild or moderate intensity. The following adverse reactions have been reported in patients receiving pantoprazole alone or in combination with antibiotics for H. pylori eradication in clinical trials and post-marketing surveillance.
The adverse reactions reported with pantoprazole are ranked under the following frequency classification:
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).

General disorders and administration site conditions.

Common: Injection site thrombophlebitis.
Uncommon: Fatigue and malaise, asthenia and increase sweating.
Rare: Fever, peripheral oedema.
Very rare: Substernal chest pain and hot flushes.

General cardiovascular disorders.

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: Nausea, vomiting, diarrhoea, abdominal distension and bloating, constipation, dry mouth, abdominal pain and discomfort.
Rare: Rectal disorder, colonic polyp.
Very rare: Faecal discolouration, increased saliva.
Not known: 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: Increased liver enzymes (transaminases, gamma-GT).
Rare: Increased bilirubin.
Very rare: Hepatocellular failure, cholestatic hepatitis, bilirubinaemia, jaundice.
Not known: Hepatocellular injury.
The occurrence of severe hepatocellular damage leading to jaundice or hepatic failure having a temporal relationship to the oral administration 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 (see Section 4.4 Special Warnings and Precautions for Use), hypocalcaemia, hypokalemia (hypocalcaemia and/or hypokalemia may be related to the occurence of hypomagnesaemia).

Musculoskeletal and connective tissue disorders.

Uncommon: Fracture of the hip, wrist or spine.
Rare: Myalgia, arthralgia.
Very rare: Pain including skeletal pain.
Not known: Muscle spasm as a consequence of electrolyte disturbances.

Renal and urinary disorders.

Very rare: Interstitial nephritis.

Platelet, bleeding, clotting disorders.

Very rare: Thrombocytopenia, increased coagulation time.

Psychiatric disorders.

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

Blood and lymphatic system disorders.

Rare: Anaemia, agranulocytosis, thrombophlebitis.
Very rare: Thrombocytopenia, leukopenia, pancytopenia.

Resistance mechanism disorders.

Rare: Sepsis.

Respiratory system disorders.

Very rare: Dyspnoea.

Reproductive system and breast disorders.

Rare: Gynaecomastia.

Skin and subcutaneous tissue disorders.

Uncommon: Rash/ exanthema/ eruption, pruritus.
Rare: Angioedema, urticaria.
Very rare: Severe skin reactions such as Stevens Johnson Syndrome, toxic epidermal necrolysis, erythema multiforme, Lyell Syndrome, photosensitivity, flushing.
Not known: subacute cutaneous lupus erythematosus, drug reaction with eosinophilia and systemic symptoms (DRESS).

Special senses, other disorders.

Very rare: Changes to the senses of smell and taste.
Rare: Metallic taste.

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.

4.9 Overdose

As pantoprazole is extensively protein bound, it is not readily dialysable.
In the case of an overdose with clinical signs of intoxication, apart from symptomatic and supportive treatment, no specific therapeutic recommendations can be made.
There are no known symptoms of overdosage in humans. In individual cases, 240 mg was administered intravenously or orally and was well tolerated. Standard detoxification procedures apply.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Pantoprazole is a substituted benzimidazole which inhibits basal and stimulated gastric secretion.

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 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).
Oral and intravenous pantoprazole 40 mg/day for 5 days had equivalent effect on intragastric pH in 20 healthy adult male volunteers in a randomised, open, 2 period crossover trial with 14 day washout. The predefined equivalence range was ± 20% for percentage of time with pH < 3 and 4 and ± 1 pH unit for 24 h median pH. The 24 h median pH on day 5 was 2.7 on oral treatment and 3.2 on intravenous treatment.
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.

Two uncontrolled trials in adults assessed the efficacy of pantoprazole 40 mg/day, administered intravenously for 5-7 days then orally for 3-7 weeks, in the endoscopic healing of Savary-Miller stage 2-3 reflux oesophagitis (Table 1). Using historical data, it was concluded that the intravenous plus oral regimen was at least equivalent to an exclusively oral regimen.
The criterion for at least equivalence was: lower limit of 90% confidence interval of the difference, (IV + oral) - oral, > -15%.

5.2 Pharmacokinetic Properties

Absorption.

A considerably higher Cmax occurs after intravenous administration compared with oral administration. In a study in healthy volunteers given 40 mg/day for 5 days, the steady state Cmax was 5.9 mg/L after intravenous administration and 1.7 mg/L after oral administration. 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.

Distribution.

The serum protein binding of pantoprazole is approximately 98%. Volume of distribution is approximately 0.15 L/kg.

Metabolism.

Pantoprazole is almost exclusively metabolised in the liver.

Excretion.

Terminal half-life is approximately 1 hour and clearance is approximately 0.1 L/h/kg. Pantoprazole is rapidly eliminated from serum. 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 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 hours. Patients with a half-life of greater than 3.5 hours and with an apparent clearance of less than 2 L/h/kg are considered to be slow metabolisers of pantoprazole.
In patients with liver impairment, pantoprazole elimination is significantly delayed. After a 40 mg tablet, AUC increased by a factor of 6-8 and terminal half-life increased from 1 hour to 7-9 hours in patients with liver cirrhosis 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 200 mg/kg/day pantoprazole for 14 days. However, no distinct DNA-adduct has been detected.
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). In both species, pantoprazole exposure was high with the AUCs being 26 to 30 times higher in the rat or mouse respectively, than 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 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, 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 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 medicine 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.

6 Pharmaceutical Particulars

6.1 List of Excipients

Pantoprazole Sandoz powder for injection contains no inactive ingredients.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.
For information on interactions with other medicines and other forms of interactions, see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions.

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.

6.5 Nature and Contents of Container

Pantoprazole Sandoz 40 mg Powder for Injection is in a clear glass vial with a red rubber stopper and aluminium "flip-off" cap.
Available in cartons containing 1 vial or 10 vials.
Not all presentations may be available in Australia.
Vial stopper is not made with natural rubber latex.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Pantoprazole sodium solubility is low at neutral pH and increases with increasing pH.

Chemical structure.


Chemical name: 5-(difluoromethoxy)- 2-[[(3,4-dimethoxy-2-pyridinyl) methyl]-sulfinyl]1H-benzimidazole sodium salt.
Molecular formula: C16H14F2N3NaO4S.
Molecular weight: 405.

CAS number.

138786-67-1 (pantoprazole sodium).

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

Summary Table of Changes