Consumer medicine information

Pantoprazole Sun

Pantoprazole

BRAND INFORMATION

Brand name

Pantoprazole Sun

Active ingredient

Pantoprazole

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Pantoprazole Sun.

What is in this leaflet?

This leaflet answers some common questions about PANTOPRAZOLE SUN. 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 PANTOPRAZOLE SUN against the benefits this medicine is expected to have for you.

Use PANTOPRAZOLE SUN as directed and follow the advice given in the 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 PANTOPRAZOLE SUN is used for

Ulcers
PANTOPRAZOLE SUN 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 SUN 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 SUN is also used to prevent reflux oesophagitis from coming back.

Zollinger-Ellison syndrome
PANTOPRAZOLE SUN 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.

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

PANTOPRAZOLE SUN 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 PANTOPRAZOLE SUN has been prescribed for you Your doctor may have prescribed PANTOPRAZOLE SUN for another reason.

There is no evidence that PANTOPRAZOLE SUN is addictive.

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

Before you use PANTOPRAZOLE SUN

When you must not use it

Do not use PANTOPRAZOLE SUN if you have an allery to:

  • Pantoprazole sodium, the active ingredient of PANTOPRAZOLE SUN
  • Any of the ingredients listed at the end of this leaflet.

Some 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 use PANTOPRAZOLE SUN if you have or have had cirrhosis or moderate to severe liver or kidney disease.

Do not use PANTOPRAZOLE SUN in combination with atazanavir (an anti-viral medication).

Do not use PANTOPRAZOLE SUN if the packaging is torn or shows signs of tampering.

Do not use PANTOPRAZOLE SUN after the expiry date (EXP) printed on the pack has passed. If it has expired or is damaged, return it to your pharmacist for disposal.

PANTOPRAZOLE SUN should not be given to children. Safety and effectiveness of PANTOPRAZOLE SUN in children have not been established.

If you are not sure whether you should start being treated with PANTOPRAZOLE SUN, talk to your doctor.

Before you start to use it

You must tell your doctor if you have any allergies to:

  • PANTOPRAZOLE SUN (pantoprazole sodium)
  • any other medicines, or any other substances, such as foods, preservatives or dyes.

You must tell your doctor if you are pregnant, intend to become pregnant, are breast-feeding or intend to breast-feed. Your doctor will discuss the risks and benefits of being given PANTOPRAZOLE SUN during pregnancy or while breast-feeding.

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

Taking other medicines

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

Some medicines may be affected by PANTOPRAZOLE SUN, or may affect how well it works. These may include atazanavir (an anti-viral medication), medicines used to prevent blood clots (anticoagulants) and medicines whose activity depend on the acidity of the stomach e.g. ketoconazole.

You may need different amounts of your medicine, 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 medicines.

How to use PANTOPRAZOLE SUN

Pantoprazole SUN powder for injection 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 instruction, ask your doctor or pharmacist for help.

How much to use and when to use it

The dose and frequency of your injection PANTOPRAZOLE SUN powder for injection will be determined by your doctor and will depend on your medical condition. Your doctor may change the dose as your condition changes.

How to use it

PANTOPRAZOLE SUN is reconstituted with a sodium chloride solution by your doctor or pharmacist.

Your doctor will ensure that you receive the correct dose of PANTOPRAZOLE SUN.

Never administer this medicine to yourself.

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

How long to use it

Your doctor will determine how long you need to be treated with PANTOPRAZOLE SUN.

If a dose is missed

Tell your doctor as soon as possible if you realize that you missed an appointment for receiving your dose of PANTOPRAZOLE SUN, you doctor will determine when your next dose is due.

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

If too much is given (overdose)

Immediately telephone your doctor or the Poison 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 been given too much PANTOPRAZOLE SUN. Do this even if there are no signs of discomfort or poisoning.

As PANTOPRAZOLE SUN 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 (The side effects are listed under the heading, 'Side effects' in this leaflet.) after being given this medicines, tell your doctor or nurse immediately.

You may need urgent medical attention.

While you are using PANTOPRAZOLE SUN

Things you must do

Always follow your doctor’s instructions carefully.

Tell your doctor immediately if you become pregnant while you are being given PANTOPRAZOLE SUN.

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.

If you are about to start taking a new medicines, tell your doctors, dentists and pharmacists that you are being given PANTOPRAZOLE SUN.

Things you must not do

Do not use PANTOPRAZOLE SUN to treat any other complains unless your doctor tells you to.

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

Do not stop using PANTOPRAZOLE SUN 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 SUN 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 chair, 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 have any problems while being treated with PANTOPRAZOLE SUN, even if you do not think the problems are connected with the medicine or are not listed in this leaflet. Like other medicines, PANTOPRAZOLE SUN can cause some side effects. If they occur, most are likely to be minor and temporary. However, some may be serious and you may need medical attention.

Do not be alarmed by following list of possible side effects. You may not experience any of them.

Ask your doctor or pharmacist any questions you may have.

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

  • headache
  • diarrhoea
  • nausea or vomiting
  • stomach pain
  • excessive gas in the stomach or bowel
  • indigestion
  • constipation
  • increased sweating
  • dry mouth
  • pain and swelling at the site of injection
  • dizziness
  • weakness or tiredness
  • metallic taste
  • blurred vision
  • skin problems such as itchiness and rash

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

Tell your doctor immediately 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.
  • 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 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

These may be serious side effects and you may need urgent medical attention. Serious side effects are rare.

Other side effects not listed above may occur in some people. Tell your doctor if you notice anything that is making you feel unwell when you are being treated with PANTOPRAZOLE SUN.

Ask your doctor or pharmacist if you do not understand some of the information in this list.

After using PANTOPRAZOLE SUN

Storage

Normally your doctor will provide your injection PANTOPRAZOLE SUN powder for injection. If however, you do take your injection PANTOPRAZOLE SUN powder for injection from the pharmacy to your doctor, it is important to store it in a safe place away from heat (below 25°C) and away from light. Do not leave your PANTOPRAZOLE SUN in a car.

If for any reason you take your injection PANTOPRAZOLE SUN powder for injection home, use as soon as possible after preparation. If storage is necessary, store at 2-8°C for no longer than 12 hours.

When taking injection PANTOPRAZOLE SUN powder for injection at home, always ensure that it is stored in a place where children cannot reach it i.e. 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 SUN, your hospital pharmacist will dispose of any unused medicine.

Product Description

What it looks like

PANTOPRAZOLE SUN is available as an injection powder for injection, containing pantoprazole sodium equivalent to 40 mg pantoprazole. PANTOPRAZOLE SUN is a white to off white powder provided in a colourless glass vial sealed with a grey rubber stopper and fitted with red flip off aluminium cap.

PANTOPRAZOLE SUN is available in 1 and 10 vials.

Ingredients

The active ingredient in injection PANTOPRAZOLE SUN powder for injection is pantoprazole (as sodium). There are no inactive ingredients in PANTOPRAZOLE SUN.

Sponsor

Pantoprazole SUN is supplied in Australia by:

Sun Pharma ANZ Pty Ltd
Macquarie Park NSW 2113
Email:
[email protected]
Tel: 1800 726 229

Pantoprazole SUN 40mg powder for injection: AUST R 172172

This leaflet was prepared in July 2020

Published by MIMS September 2020

BRAND INFORMATION

Brand name

Pantoprazole Sun

Active ingredient

Pantoprazole

Schedule

S4

 

1 Name of Medicine

Pantoprazole (present as pantoprazole sodium).

2 Qualitative and Quantitative Composition

Pantoprazole 40 mg powder for injection contains 42.3 mg pantoprazole sodium. Pantoprazole sodium is a white to off white amorphous hygroscopic powder. Solubility is low at neutral pH and increases with increasing pH.

3 Pharmaceutical Form

Pantoprazole Sun 40 mg powder for injection appears as a white to off white coloured lyophilized cake.

4 Clinical Particulars

4.1 Therapeutic Indications

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 anti-secretory drugs, whether on first presentation or recurrence.

4.2 Dose and Method of Administration

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

40 mg/day.

Reflux oesophagitis.

20 to 40 mg/day.
Intravenous Pantoprazole should be replaced with oral therapy as soon as practicable.

Renal impairment.

The usual daily dose of 20 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.

Use in children.

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

Use in the elderly.

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

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% or 100 mL glucose intravenous infusion 5 or 10%. The resulting solution should be used within 12 hours stored at 2°C to 8°C, and is for single use only.
After preparation, the solution should be administered over 2 to 15 minutes.

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 to 8°C for not more than 12 hours.
This product contains no antimicrobial agent and 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 may not be used in cases of 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 co-administered with atazanavir (see 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 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.

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 (orally 40 and 160 mg (about 4 and 15 mg/kg) and intravenously 60 mg (about 6 mg/kg)). No ophthalmological changes or changes in electroretinographs were observed in cynomolgus monkeys at intravenous doses of up to 15 mg/kg/day for four weeks.

Use in hepatic impairment.

Pantoprazole is contraindicated in patients with cirrhosis or severe liver disease. With milder forms of liver disease, the initial dose should be reduced (see Section 4.3 Contraindications; Section 4.2 Dose and Method of Administration).

Use in renal impairment.

The usual daily dose of 20 or 40 mg can be given (see Section 4.2 Dose and Method of Administration).

Use in the elderly.

The usual daily dose of 20 or 40 mg can be given (see Section 4.2 Dose and Method of Administration).

Paediatric use.

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

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, CYP2C9 and CYP2C10 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, nifedipine, phenytoin, theophylline and the low dose oral contraceptive Triphasil (levonorgestrel and ethinyl oestradiol). 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 post marketing 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.
Treatment of dogs with intravenous 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), might be altered due to the decrease in gastric acidity.
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.

No data available.
(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.
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, i.e. increased pre- and postnatal deaths at 450 mg/kg/day, reduced fetal weight at greater than or equal to 150 mg/kg/day and delayed skeletal ossification and reduced pup growth at 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 fetus 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 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. 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

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

4.8 Adverse Effects (Undesirable Effects)

Pantoprazole 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.

Body as a whole.

Fatigue, asthenia and increased sweating.
Rare reports of fever, anaphylactic reactions including anaphylactic shock and peripheral oedema.
Very rare reports of substernal chest pain and hot flushes.

General cardiovascular disorders.

Rare reports of hypertension.
Very rare reports of circulatory collapse.

Central and peripheral nervous system disorders.

Headache.
Uncommon reports of dizziness.
Very rare reports of reduced movement and speech disorder.

Gastrointestinal system disorders.

Diarrhoea, severe eructation, constipation or flatulence, dry mouth and upper abdominal pain.
Uncommon reports of nausea and vomiting.
Rare reports of rectal disorder and colonic polyp.
Very rare reports of faecal discolouration and increased saliva.

Hearing and vestibular disorders.

Very rare reports of tinnitus.

Liver and biliary system disorders.

Rare reports of increased liver enzymes (transaminases, gamma-GT) have occurred in patients receiving long-term maintenance therapy.
Very rare reports of hepatic failure, cholestatic hepatitis, bilirubinaemia and jaundice. 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 reports of hypertriglyceridaemia.

Musculoskeletal.

Rare reports of myalgia and arthralgia.
Very rare reports of pain including skeletal pain.

Renal and urinary disorders.

Very rare reports of interstitial nephritis.

Platelet, bleeding, clotting disorders.

Very rare reports of thrombocytopenia and increased coagulation time.

Psychiatric disorders.

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

Red and white blood cell disorders.

Rare reports of anaemia.
Very rare reports of leucopenia.

Resistance mechanism disorders.

Rare reports of sepsis.

Respiratory system disorders.

Very rare reports of dyspnoea.

Skin and appendages.

Uncommon reports of allergic reactions such as pruritus and skin rash.
Rare reports of angioedema and urticaria.
Very rare reports of severe skin reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, Lyell syndrome and photosensitivity.

Special senses, other disorders.

Metallic taste.
Very rare reports of changes to the senses of smell and taste.

Vascular (extracardiac) disorders.

Rare reports of thrombophlebitis associated with the use of injection only.
Very rare reports of flushing.

Vision disorders.

Uncommon reports of disturbances in vision (blurred vision).
Very rare reports of 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

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

Mechanism of action.

Pantoprazole is a proton pump inhibitor. Pantoprazole 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).
Oral and intravenous pantoprazole 40 mg/day for five days had an equivalent effect on intragastric pH in 20 healthy adult male volunteers in a randomised, open, two 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 hour median pH. The 24 hour median pH on day five 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 2 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 five to seven days then orally for three to seven weeks, in the endoscopic healing of Savary-Miller stage 2 to 3 reflux oesophagitis (see 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 five days, the steady-state Cmax was 5.9 mg/L after intravenous administration and 1.7 mg/L after oral administration.

Distribution.

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 administration.
The serum protein binding of pantoprazole is approximately 98%.

Metabolism.

Pantoprazole is rapidly eliminated from serum and is almost exclusively metabolised in the liver. 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.

Excretion.

Renal elimination represents the most important route of excretion (approximately 80%) for the metabolites of pantoprazole, the rest are excreted with the faeces. 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 ten hours. Patients with a half-life of greater than 3.5 hours and with an apparent clearance of less than 2 L/hour/kg are considered to be slow metabolisers of pantoprazole.
In patients with liver impairment, pantoprazole elimination is significantly delayed. After a 40 mg tablet, area under the curve (AUC) increased by a factor of six to eight and terminal half-life increased from one hour to seven to nine 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 end points 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.

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 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 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.

6 Pharmaceutical Particulars

6.1 List of Excipients

Pantoprazole Sun does not contain any excipients.

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.
The solution should be used as soon as practicable after reconstitution/preparation and for not more than 12 hours stored at 2°C to 8°C ( Section 4.2 Dose and Method of Administration).

6.4 Special Precautions for Storage

Pantoprazole Sun should be stored below 25°C. The reconstituted solution should be stored at 2°C to 8°C for not more than 12 hours.

6.5 Nature and Contents of Container

Pantoprazole Sun is available in a clear type 1 tubular glass vial with grey rubber stopper and sealed with red flip off aluminium seal.
It is available in cartons containing 1 vial and 10 vials.

6.6 Special Precautions for Disposal

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

6.7 Physicochemical Properties

Chemical structure.


CAS number.

102625-70-7 (pantoprazole);
138786-67-1 (pantoprazole sodium).
Chemical Name: ± sodium 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridinyl)-methyl] sulfinyl]-1H-benzimidazolide.
Empirical formula: C16H14F2N3NaO4S.
MW: 405.5.

7 Medicine Schedule (Poisons Standard)

(S4) Prescription Only Medicine.

Summary Table of Changes