Consumer medicine information

Pantoprazole Sun

Pantoprazole

BRAND INFORMATION

Brand name

Pantoprazole Sun

Active ingredient

Pantoprazole

Schedule

SUMMARY CMI

Pantoprazole SUN

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using Pantoprazole SUN?

Pantoprazole SUN contains the active ingredient pantoprazole sodium. Pantoprazole SUN is used to ulcers, reflux disease, Zollinger-Ellison syndrome.

For more information, see Section 1. Why am I using Pantoprazole SUN? in the full CMI.

2. What should I know before I use Pantoprazole SUN?

Do not use if you have ever had an allergic reaction to Pantoprazole SUN or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I use Pantoprazole SUN? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with Pantoprazole SUN and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use Pantoprazole SUN?

Pantoprazole SUN powder for injection will be administered by your doctor. Pantoprazole SUN is reconstituted with a sodium chloride solution by your doctor or pharmacist.

More instructions can be found in Section 4. How do I use Pantoprazole SUN? in the full CMI.

5. What should I know while using Pantoprazole SUN?

Things you should do	Remind any doctor, dentist or pharmacist you visit that you are using Pantoprazole SUN. Call you doctor straight away if you: Become pregnant while you are being given Pantoprazole SUN. Are about to start taking new medicines.
Things you should not do	Do not stop using this medicine suddenly without doctor's permission. 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.
Driving or using machines	Pantoprazole SUN may cause dizziness or light-headedness in some people, especially after the first dose.
Looking after your medicine	Store below 25°C and away from light.

For more information, see Section 5. What should I know while using Pantoprazole SUN? in the full CMI.

6. Are there any side effects?

Common side effects include headache, diarrhea, nausea or vomiting, stomach pain, excessive gas in the stomach or bowel, indigestion, constipation, increased sweating or body temperature, 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, trouble sleeping.

Serious side effects are rare.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

FULL CMI

Pantoprazole SUN

Active ingredient(s): pantoprazole (as sodium)

Consumer Medicine Information (CMI)

This leaflet provides important information about using Pantoprazole SUN. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using Pantoprazole SUN.

Where to find information in this leaflet:

1. Why am I using Pantoprazole SUN?
2. What should I know before I use Pantoprazole SUN?
3. What if I am taking other medicines?
4. How do I use Pantoprazole SUN?
5. What should I know while using Pantoprazole SUN?
6. Are there any side effects?
7. Product details

1. Why am I using Pantoprazole SUN?

Pantoprazole SUN contains the active ingredient pantoprazole (as sodium). 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.

Indications:

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 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 oesophagus.

Reflux can cause burning sensation in the chest rising up 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 amount of acid, much more than in ulcers and reflux disease.

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 purpose.

There is no evidence that Pantoprazole SUN is addictive.

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

2. What should I know before I use Pantoprazole SUN?

Warnings

Do not use Pantoprazole SUN:

you are allergic to pantoprazole (as sodium), or any of the ingredients listed at the end of this leaflet.
always check the ingredients to make sure you can use this medicine.

Symptoms of an allergic reaction may include shortness of breath, wheezing or difficult breathing, swelling of the face, lips, tongue or other parts of the body, rash, itching or hives on the skin.

you have or have had cirrhosis or moderate to severe liver of kidney disease.
in combination with atazanavir or nelfinavir (an anti-viral medications).
if the packaging is torn or shows signs of tampering.
after the expiry date (EXP) printed on the pack has passed.

If it has expired or damaged, return it to your pharmacist for disposal.

in children

Safety and effectiveness of Pantoprazole SUN in children have not been established.

Check with your doctor if you:

are allergies to Pantoprazole SUN (pantoprazole sodium)
any other medicines or substances, such as foods, preservatives or dyes
if you have or had any other medical conditions
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 SUN Injection.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

Your doctor will discuss the risks and benefits of being given Pantoprazole SUN during pregnancy or while breastfeeding.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements 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, 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

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 medicine.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect Pantoprazole SUN.

4. How do I use Pantoprazole SUN?

How much to take / use and when to take / use Pantoprazole SUN

Pantoprazole SUN powder for injection will be administered by your doctor.
Follow the instructions provided to you by your doctor or pharmacist carefully. They may differ from the information contained in this leaflet.
Use Pantoprazole SUN until your doctor tells you to stop.
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 Pantoprazole SUN

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 you forget to use Pantoprazole SUN

Tell your doctor as soon as possible if you realise that you missed an appointment for receiving your dose of Pantoprazole SUN, your 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 Pantoprazole SUN is given

If you think you or anyone else may have been given to much Pantoprazole SUN you may need urgent medical attention.

You should immediately:

phone the Poisons Information Centre
(by calling 13 11 26), or
contact your doctor, or
go to the Emergency Department at your nearest hospital.

You should 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 medicine, tell your doctor or nurse immediately.

5. What should I know while using Pantoprazole SUN?

Things you should do

Always follow your doctor's instructions carefully.

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.

Call your doctor straight away if you:

Become pregnant while you are being given Pantoprazole SUN.

Remind any doctor, dentist or pharmacist you visit that you are using Pantoprazole SUN.

if you are about to start taking new medicines
if you are about to have any blood tests

It may interfere with the results of some tests.

if your reflux symptoms return after you stop taking this medicine

The symptoms of reflux may return after stopping this medicine suddenly, especially if you have taken it for a while.

Things you should not do

Do not stop using this medicine suddenly without your doctor's permission.

Your doctor may want you to gradually reduce the amount you are taking before stopping completely.

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.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how Pantoprazole SUN affects you.

Pantoprazole SUN 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.

Looking after your medicine

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 meter above the ground is a good place to store mediicnes.

Getting rid of any unwanted medicine

If your doctor stops treating you with Pantoprazole SUN, your hospital pharmacist will dispose of any unused medicine.

Do not use this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effects	What to do
headache diarrhoea nausea or vomiting stomach pain excessive gas in the stomach or bowel indigestion constipation increased sweating or body temperature 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 trouble sleeping	Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effects

What to do

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
severe 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 and general fever.
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 or 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, jerking/shaking movements or muscle cramps. 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

Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Serious side effects are rare.

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

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

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

What Pantoprazole SUN contains

Active ingredient (main ingredient)	Pantoprazole (as sodium)
Other ingredients (inactive ingredients)	-
Potential allergens	-

Do not take this medicine if you are allergic to any of these ingredients.

What Pantoprazole SUN looks like

Pantoprazole SUN (Aust R 172172) is a white to off white powder provided in a colourless glass vial sealed with a grey rubber stopper and fitted with green flip off aluminium cap.

Pantoprazole SUN is packed in 1 and 10 vials.

Who distributes Pantoprazole SUN

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

This leaflet was prepared in September 2024.

Published by MIMS November 2024

BRAND INFORMATION

Brand name

Pantoprazole Sun

Active ingredient

Pantoprazole

Schedule

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 HIV protease inhibitors, such as atazanavir or nelfinavir (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.

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.

Severe cutaneous adverse reactions.

Severe cutaneous adverse reactions, including erythema multiforme, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) have been reported in association with the use of PPIs (see Section 4.8 Adverse Effects (Undesirable Effects)). Discontinue pantoprazole at the first signs or symptoms of severe cutaneous adverse reactions or other signs of hypersensitivity and consider further evaluation.

Subacute cutaneous lupus erythematosus (SCLE).

Proton pump inhibitors are associated in rare cases with the occurrence of subacute cutaneous lupus erythematosus (SCLE). If lesions occur, especially in sun exposed areas of the skin, and if accompanied by arthralgia, the patient should seek medical help promptly and the healthcare professional should consider stopping the product.

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).

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. Hypomagnesaemia may lead to hypocalcaemia and/or hypokalaemia (see Section 4.8 Adverse Effects (Undesirable Effects)).

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 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).
Treatment of dogs with intravenous 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.

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, monitoring of prothrombin time/INR is recommended after initiation, termination or during irregular use of pantoprazole.

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 co-administered 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.

Co-administration 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.

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.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(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, 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. 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

Pantoprazole 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 Section 4.8 Adverse Effects (Undesirable Effects)). If affected, patients should not drive or operate machines.

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.
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.

Common reports of injection site thrombophlebitis.
Uncommon reports of fatigue and malaise, asthenia and increased sweating.
Rare reports of fever 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.

Nervous system disorders.

Uncommon reports of headache, dizziness.
Rare reports of taste disorders, metallic taste.
Very rare reports of reduced movement and speech disorder, changes to the senses of smell and taste.

Gastrointestinal system disorders.

Uncommon reports of nausea and vomiting, diarrhoea, abdominal distension and bloating, constipation, dry mouth and abdominal pain and discomfort.
Rare reports of rectal disorder and colonic polyp.
Very rare reports of faecal discolouration and 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 reports of tinnitus.

Immune system disorders.

Rare reports of hypersensitivity (including anaphylactic reactions and anaphylactic shock).

Liver and biliary system disorders.

Uncommon reports of liver enzymes increased.
Rare reports of bilirubin increased.
Very rare reports of 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 oral administration of pantoprazole has been reported with a frequency of approximately one in a million patients.

Metabolic and nutritional disorders.

Rare reports of hyperlipidaemias and lipid increases (triglycerides, cholesterol), weight changes.
Not known: hyponatraemia, hypomagnesaemia, hypocalcaemia, hypokalaemia (hypocalcaemia and/or hypokalaemia may be related to the occurrence of hypomagnesaemia (see Section 4.4 Special Warnings and Precautions for Use).

Musculoskeletal and connective tissue disorders.

Rare reports of myalgia and arthralgia.
Very rare reports of pain including skeletal pain.
Not known: fracture of wrist, hip and spine.

Renal and urinary disorders.

Very rare reports of tubulointerstitial nephritis (TIN) (with possible progression to renal failure).

Platelet, bleeding, clotting disorders.

Very rare reports of increased coagulation time.

Psychiatric disorders.

Uncommon reports of sleep 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, agranulocytosis.
Very rare reports of leukopaenia, thrombocytopaenia, pancytopaenia.

Resistance mechanism disorders.

Rare reports of sepsis.

Respiratory system disorders.

Very rare reports of dyspnoea.

Reproductive system and breast disorders.

Rare reports of gynaecomastia.

Skin and subcutaneous tissue disorders.

Uncommon reports of pruritus, rash/ exanthema/ eruption.
Rare reports of angioedema and urticaria.
Very rare reports of flushing, severe skin reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, Lyell syndrome and photosensitivity.
Not known: subacute cutaneous lupus erythematosus, drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalised exanthematous pustulosis.

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 C_max occurs after intravenous administration compared with oral administration. In a study in healthy volunteers given 40 mg/day for five days, the steady-state C_max 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 C_max 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 (see 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 green 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.

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