Active ingredients: Pantoprazole
Pantorc 20 mg gastro-resistant tablets
Pantorc package inserts are available for pack sizes:- Pantorc 20 mg gastro-resistant tablets
- Pantorc 40 mg gastro-resistant tablets
Indications Why is Pantorc used? What is it for?
Pantorc contains the active substance pantoprazole. Pantorc is a selective 'proton pump inhibitor', a medicine that reduces the amount of acid produced in the stomach. It is used for the treatment of acid-related diseases of the stomach and intestines.
Pantorc is used to treat adults and adolescents aged 12 years and over for
- Symptoms (e.g. heartburn, acid regurgitation, pain when swallowing) associated with gastroesophageal reflux disease caused by acid reflux from the stomach.
- Long-term treatment of reflux esophagitis (inflammation of the esophagus accompanied by regurgitation of stomach acid) and prevention of its recurrence.
Pantorc is used to treat adults for
- Prevention of duodenal and stomach ulcers caused by non-steroidal anti-inflammatory drugs (NSAIDs, for example, ibuprofen) in patients at risk who require continued NSAID treatment.
Contraindications When Pantorc should not be used
Do not take Pantorc
- If you are allergic to pantoprazole or any of the other ingredients of this medicine (listed in section 6).
- If you are allergic to medicines containing other proton pump inhibitors.
Precautions for use What you need to know before taking Pantorc
Talk to your doctor, pharmacist or nurse before taking Pantorc
- If you have severe liver problems. Tell your doctor if you have ever had liver problems. Your doctor will have your liver enzymes checked more frequently, especially if you are taking Pantorc for long-term therapy. In the event of an increase in liver enzymes, the treatment should be discontinued.
- If you need continued treatment with medicines called NSAIDs and take Pantorc as you have an increased risk of developing gastric and intestinal complications. Any increased risk will be assessed based on your personal risk factors such as age (65 years and over), a history of gastric or duodenal ulcers or gastric or intestinal bleeding.
- If you have low body stores or risk factors for reduced vitamin B12 and are on long-term treatment with pantoprazole. As with all acid reducing agents, pantoprazole can lead to reduced absorption of vitamin B12.
- If you are taking HIV protease inhibitors such as atazanavir (for the treatment of HIV infection) at the same time as pantoprazole, ask your doctor for specific advice.
- Taking a proton pump inhibitor such as pantoprazole, especially for longer than a year, may slightly increase the risk of fractures of the hip, wrist or spine. Tell your doctor if you have osteoporosis or are taking corticosteroids ( which may increase the risk of osteoporosis).
- If you have been taking Pantorc for more than three months, it is possible that the magnesium levels in your blood may go down. Low magnesium levels can cause fatigue, involuntary muscle contractions, disorientation, convulsions, dizziness, increased heart rate. Tell your doctor immediately if you get any of these symptoms. Low magnesium levels can also lead to a reduction in potassium or calcium levels in the blood. Your doctor may decide to have regular blood tests to monitor your magnesium levels.
- If you have ever had a skin reaction after treatment with a medicine similar to Pantorc that reduces stomach acid.
- If you notice a skin rash, especially in areas exposed to sunlight, contact your doctor as soon as possible, as it may be necessary to stop taking Pantorc. Remember to also mention any other side effects such as joint pain.
Tell your doctor immediately, before or after taking this medicine, if you notice any of the following symptoms, which may be a sign of "another more serious illness:
- unintentional weight loss
- vomiting, particularly if repeated
- presence of blood in the vomit; this may appear as dark coffee grounds in vomit - blood appearing in stools which may appear dark or tar-colored
- difficulty swallowing or pain when swallowing
- looks pale and feels weak (anemia)
- chest pain
- stomach pain
- severe and / or persistent diarrhea, as this medicinal product has been associated with a modest increase in infectious diarrhea.
Your doctor may decide that you need some tests to rule out a malignant disease as pantoprazole also relieves the symptoms of cancer and may cause a delay in diagnosis. If your symptoms persist despite treatment, further investigation should be considered.
Interactions Which drugs or foods can modify the effect of Pantorc
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including medicines obtained without a prescription.
Pantorc can affect the effectiveness of other medicines, so tell your doctor if you are taking:
- Medicines such as ketoconazole, itraconazole and posaconazole (used to treat fungal infections) or erlotinib (used for some types of cancer) as Pantorc can stop these and other medicines from working properly.
- Warfarin and phenprocoumon, which affect the thickening or thinning of the blood. You may need further checks.
- Medicines used to treat HIV infection, such as atazanavir.
- Methotrexate (used to treat rheumatoid arthritis, psoriasis and cancer) - if you are taking methotrexate, your doctor may temporarily stop your Pantorc treatment because pantoprazole can increase the levels of methotrexate in your blood.
- Fluvoxamine (used to treat depression and other psychiatric diseases) - if you are taking fluvoxamine your doctor may reduce your dose.
- Rifampicin (used to treat infections).
- St. John's wort (Hypericum perforatum) (used to treat mild depression).
Warnings It is important to know that:
If you are taking Pantorc for long-term treatment (longer than 1 year) your doctor will probably monitor you on a regular basis. He should report any new or exceptional symptoms and circumstances whenever he meets the doctor.
Children and adolescents
Pantorc is not recommended for use in children as it has not been shown to be effective in children below 12 years of age.
Pregnancy and breastfeeding
There are no adequate data from the use of pantoprazole in pregnant women. Excretion into human breast milk has been reported.
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.
You should use this medicine only if your doctor considers the benefit to you greater than the potential risk to the fetus or baby.
Driving and using machines
Pantorc has no or negligible influence on the ability to drive and use machines.
If you experience side effects such as dizziness or disturbed vision, you should not drive or operate machinery.
Dose, Method and Time of Administration How to use Pantorc: Posology
Always take this medicine exactly as your doctor or pharmacist has told you. If in doubt, consult your doctor or pharmacist.
Method of administration
Take the tablets 1 hour before meals without chewing or crushing them and swallow them whole with some water.
The recommended dose is:
Adults and adolescents aged 12 and over
- For the treatment of symptoms associated with gastroesophageal reflux disease (e.g. heartburn, acid regurgitation, pain when swallowing)
The usual dose is one tablet a day. This dose usually brings relief within 2 - 4 weeks - at most after another 4 weeks. Your doctor will tell you how long to continue taking the medicine. After this, any recurring symptoms can be controlled by taking one tablet a day, as needed.
- For long-term treatment and to prevent the recurrence of reflux oesophagitis
The usual dose is one tablet a day. If the disease recurs, your doctor may double the dose, in which case you can use Pantorc 40 mg tablets instead, one a day. After healing, the dose can be reduced back to one 20 mg tablet per day.
Adults
- For the prevention of duodenal and gastric ulcers in patients who require continuous treatment with NSAIDs
The usual dose is one tablet a day.
Patients with liver problems
If you have severe liver problems, you should not take more than one 20 mg tablet per day.
Use in children and adolescents
These tablets are not recommended for use in children under 12 years of age.
If you forget to take Pantorc
Do not take a double dose to make up for a forgotten dose. Take your next regular dose at the scheduled time.
If you stop taking Pantorc
Do not stop taking these tablets without first checking with your doctor or pharmacist.
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.
Overdose What to do if you have taken an overdose of Pantorc
If you take more Pantorc than you should
Consult your doctor or pharmacist. There are no known symptoms of overdose.
Side Effects What are the side effects of Pantorc
Like all medicines, this medicine can cause side effects, although not everybody gets them.
If you experience any of the following side effects, stop taking these tablets and consult your doctor immediately, or contact the nearest hospital emergency department:
- Serious allergic reactions (frequency rare: may affect up to 1 in 1000 people): swelling of the tongue and / or throat, difficulty in swallowing, hives, difficulty in breathing, allergic swelling of the face (Quincke's edema / angioedema), severe dizziness with very fast heartbeat and heavy sweating.
- Serious skin disorders (frequency not known: frequency cannot be estimated from the available data): skin blistering and rapid deterioration of your general condition, erosion (including slight bleeding) of eyes, nose, mouth / lips or genitals (Stevens-Johnson syndrome, Lyell syndrome, Erythema multiforme), and sensitivity to light.
- Other serious conditions (frequency not known: frequency cannot be estimated from the available data): yellowing of the skin or whites of the eyes (severe damage to liver cells, jaundice) or fever, rash, and enlarged kidneys sometimes with pain when urinating, and pain in the lower back (severe inflammation of the kidneys), which can lead to possible kidney failure.
Other side effects are:
- Uncommon (may affect up to 1 in 100 people)
Headache; dizziness; diarrhea; feeling of nausea, vomiting; bloating and flatulence (air); constipation; dry mouth; abdominal pain and feeling unwell; rash, rash, rash; itch; feeling weak, tired or generally unwell; sleep disorders; fractures of the hip, wrist or spine.
- Rare (may affect up to 1 in 1,000 people)
Alteration or complete lack of the sense of taste; vision disturbances such as blurred vision; urticaria; joint pain; muscle aches; weight changes; increased body temperature; high fever; swelling of the extremities (peripheral edema); allergic reactions; depression, breast enlargement in men.
- Very Rare (may affect up to 1 in 10,000 people)
Disorientation.
- Not known (frequency cannot be estimated from the available data)
Hallucinations, confusion (especially in patients with a history of these symptoms); decrease in the level of sodium in the blood, decrease in the level of magnesium in the blood (see section 2), tingling sensation, pins and needles, burning sensation or numbness, erythema, possible joint pain.
Side effects identified through blood tests:
- Uncommon (may affect up to 1 in 100 people)
an increase in liver enzymes.
- Rare (may affect up to 1 in 1,000 people)
an increase in bilirubin; increased blood fat levels; drastic decrease in circulating granulocytes, associated with high fever.
- Very Rare (may affect up to 1 in 10,000 people)
a reduction in the number of platelets, which can cause more bleeding or bruising than normal; a reduction in the number of white blood cells, which can lead to more frequent infections; coexisting abnormal reduction in the number of red and white blood cells, as well as platelets.
Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system at www.agenziafarmaco.gov.it. / it / responsible. By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton and container after EXP.
The expiry date refers to the last day of that month.
For the bottles: do not use the tablets 120 days after first opening the bottle.
This medicine does not require any special storage conditions.
Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Other_information "> Other information
What Pantorc contains
- The active ingredient is pantoprazole. Each gastro-resistant tablet contains 20 mg of pantoprazole (as sodium sesquihydrate).
- The other ingredients are:
Core: sodium carbonate (anhydrous), mannitol, crospovidone, povidone K90, calcium stearate.
Coating: hypromellose, povidone K25, titanium dioxide (E171), yellow iron oxide (E172), propylene glycol, methacrylic acid-ethyl acrylate copolymer (1: 1), polysorbate 80, sodium lauryl sulfate, triethyl citrate.
Printing ink: shellac, red, black and yellow iron oxide (E172), concentrated ammonia solution.
What Pantorc looks like and contents of the pack
Yellow, oval, biconvex gastro-resistant tablet (tablet) marked "P20" on one side.
Packaging: bottles (high density polyethylene container with low density polyethylene screw cap) and blister packs (ALU / ALU blister) without cardboard reinforcement or with cardboard reinforcement (wallet blister).
Pantorc is available in the following packs:
Packs of 7, 10, 14, 15, 24, 28, 30, 48, 49, 56, 60, 84, 90, 98, 98 (2x49), 100, 112, 168 gastro-resistant tablets.
Hospital packs of 50, 56, 84, 90, 112, 140, 140 (10x14 or 5x28), 150 (10x15), 280 (20x14 or 10x28), 500, 700 (5x140) gastro-resistant tablets.
Not all pack sizes may be marketed.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT -
PANTORC 20 MG FOOD-RESISTANT TABLETS
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION -
Each gastro-resistant tablet contains 20 mg of pantoprazole (as sodium sesquihydrate).
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM -
Gastro-resistant tablet (tablet).
Yellow, oval biconvex film-coated tablet marked "P20" in brown ink on one side.
04.0 CLINICAL INFORMATION -
04.1 Therapeutic indications -
Pantorc is indicated in adults and adolescents aged 12 years and over for:
• Symptomatic gastroesophageal reflux disease.
• Long-term treatment and prevention of relapse of reflux oesophagitis.
Pantorc is indicated in adults for:
• Prevention of gastroduodenal ulcers induced by non-selective non-steroidal anti-inflammatory drugs (NSAIDs) in patients at risk requiring continued NSAID treatment (see section 4.4).
04.2 Posology and method of administration -
Dosage
Adults and adolescents aged 12 and over
Gastroesophageal reflux symptoms
The recommended dose for oral administration is one Pantorc 20 mg tablet per day. Symptom relief is usually achieved within 2-4 weeks. If this period is not sufficient, relief of symptoms will usually be achieved within a further 4 weeks. Once relief of symptoms is achieved, recurrence of symptoms can be controlled using an on-demand treatment with 20 mg once daily, taking one tablet as needed. In cases where satisfactory symptom control cannot be maintained with on-demand administration, a switch to continued therapy may be considered.
Long-term treatment and prevention of relapse of reflux oesophagitis.
For long-term treatment, a maintenance dose with one Pantorc 20 mg tablet per day is recommended, increasing to 40 mg pantoprazole per day in case of relapse. For these cases, the Pantorc 40 mg tablet is available. After healing of the relapse the dose can be reduced again to one Pantorc 20 mg tablet.
Adults
Prevention of gastroduodenal ulcers induced by non-selective non-steroidal anti-inflammatory drugs (NSAIDs) in patients at risk who require continued treatment with NSAIDs.
The recommended dose for oral administration is one Pantorc 20 mg tablet per day.
Patients with hepatic impairment
In patients with severe hepatic impairment, a daily dose of 20 mg of pantoprazole should not be exceeded (see section 4.4).
Patients with kidney damage
No dose adjustment is necessary in patients with impaired renal function (see section 5.2).
Senior citizens
No dose adjustment is necessary in elderly patients (see section 5.2).
Pediatric population
The use of Pantorc is not recommended in children below 12 years of age due to limited data on safety and efficacy in this age group (see section 5.2).
Method of administration
Oral use
The tablets should not be chewed or crushed and should be swallowed whole with a little water 1 hour before meals.
04.3 Contraindications -
Hypersensitivity to the active substance, to substituted benzimidazoles or to any of the excipients listed in section 6.1.
04.4 Special warnings and appropriate precautions for use -
Hepatic impairment
In patients with severe hepatic impairment, hepatic enzymes should be monitored regularly during therapy with pantoprazole, especially in long-term use. In the event of an increase in liver enzymes, treatment should be discontinued (see section 4.2).
Co-administration with NSAIDs
The use of Pantorc 20 mg in the prevention of gastroduodenal ulcers induced by non-selective non-steroidal anti-inflammatory drugs (NSAIDs) should be limited to patients who require continued treatment with NSAIDs and who have an increased risk of gastrointestinal complications. risk must be carried out based on the presence of individual risk factors, eg. high age (> 65 years), history of gastric or duodenal ulcer or upper gastrointestinal bleeding.
Gastric neoplasm
The symptomatic response of pantoprazole may mask the symptoms of gastric cancer and may delay the diagnosis. In the presence of any alarming symptoms (e.g. significant unintended weight loss, recurrent vomiting, dysphagia, haematemesis, anemia or melaena) and when gastric ulcer is suspected or present, malignancy should be excluded.
If symptoms persist despite adequate treatment, further investigation should be considered.
Co-administration with HIV protease inhibitors
Co-administration of pantoprazole with HIV protease inhibitors whose absorption is dependent on acidic intragastric pH such as atazanavir is not recommended due to the significant reduction in their bioavailability (see section 4.5).
Influence on the absorption of vitamin B12
Pantoprazole, like all medicines that inhibit acid secretion, may reduce the absorption of vitamin B12 (cyanocobalamin) as a consequence of hypo- or achlorhydria. This should be considered in patients with reduced body stores or risk factors for reduced absorption. of vitamin B12 in long-term therapy or when related clinical symptoms are observed.
Long-term treatment
In long-term treatment, especially when a 1 year treatment period is exceeded, patients should be kept under regular surveillance.
Gastrointestinal infections caused by bacteria
Treatment with Pantorc may lead to a slightly increased risk of gastrointestinal infections caused by bacteria such as Salmonella And Campylobacter or C. difficult.
Hypomagnesemia
Proton pump inhibitors (PPIs) such as pantoprazole have been shown to cause severe hypomagnesaemia in patients treated for at least three months and in many cases for one year.
Serious symptoms of hypomagnesaemia include fatigue, tetany, delirium, convulsions, dizziness, and ventricular arrhythmia. They can initially manifest insidiously and be neglected.
Hypomagnesemia improves in most patients after taking magnesium and discontinuing the proton pump inhibitor.
Healthcare professionals should consider measuring magnesium levels before initiating PPI treatment and periodically during treatment in patients on prolonged therapy or on therapy with digoxin or drugs that can cause hypomagnesaemia (eg diuretics).
Bone fractures
Proton pump inhibitors, especially when used in high doses and for prolonged periods (> 1 year), may cause a slightly increased risk of hip, wrist and spine fractures, especially in elderly patients or in the presence of other known risk factors. Observational studies suggest that proton pump inhibitors may increase the overall risk of fracture by 10% to 40%. This increase may be partly due to other risk factors. Patients at risk of osteoporosis should receive treatment according to current clinical practice guidelines and must take an "adequate amount of vitamin D and calcium.
Subacute cutaneous lupus erythematosus (SCLE)
Proton pump inhibitors are associated with extremely infrequent cases of SCLE. In the presence of lesions, especially on the skin parts exposed to sunlight, and if accompanied by arthralgia, the patient should immediately consult a doctor and the healthcare professional should evaluate the opportunity to stop treatment with Pantorc. SCLE following treatment with a proton pump inhibitor may increase the risk of SCLE with other proton pump inhibitors.
Interference with laboratory tests
An increased level of Chromogranin A (CgA) can interfere with diagnostic tests for neuroendocrine tumors. To avoid this interference, Pantorc treatment should be stopped for at least 5 days before CgA measurements (see section 5.1). If the CgA and gastrin levels have not returned to the reference range after the initial measurement, measurements should be repeated 14 days after stopping the proton pump inhibitor treatment.
04.5 Interactions with other medicinal products and other forms of interaction -
Medicinal products whose absorption pharmacokinetics are pH dependent
Due to the marked and long-lasting inhibition of gastric acid secretion, pantoprazole may interfere with the absorption of other drugs where gastric pH is an important determinant of oral availability, eg some azole antifungals such as ketoconazole, itraconazole, posaconazole and other medicinal products such as erlotinib.
HIV protease inhibitors
Co-administration of pantoprazole is not recommended with HIV protease inhibitors whose absorption is dependent on acidic intragastric pH such as atazanavir due to the significant reduction in their bioavailability (see section 4.4).
If the combination of HIV protease inhibitors with a proton pump inhibitor is judged unavoidable, close clinical monitoring (eg viral load) is recommended. A dose of 20 mg of pantoprazole per day should not be exceeded. Adjustment is required. the dosage of HIV protease inhibitors.
Coumarin anticoagulants (phenprocoumon or warfarin)
Co-administration of pantoprazole with warfarin or phenprocoumon did not affect the pharmacokinetics of warfarin, phenprocoumon or the INR. However, there have been reports of increased prothrombin time and INR in patients receiving PPI and warfarin or phenprocoumon concomitantly. Increases in INR and prothrombin time can lead to abnormal bleeding, and even death. Patients treated with pantoprazole and warfarin or phenprocoumon may need to be monitored for increased INR and prothrombin time.
Methotrexate
Concomitant use of high doses of methotrexate (eg 300 mg) and proton pump inhibitors has been reported to increase methotrexate levels in some patients. psoriasis, a temporary withdrawal of pantoprazole should be considered.
Other interaction studies
Pantoprazole is extensively metabolised in the liver by the cytochrome P450 enzyme system. The major route of metabolism is demethylation by CYP2C19 and other metabolic pathways include oxidation by CYP3A4.
Interaction studies with drugs also metabolised through these enzyme systems, such as carbamazepine, diazepam, glibenclamide, nifedipine, and an oral contraceptive containing levonorgestrel and ethinyl estradiol, did not reveal clinically significant interactions.
An "interaction of pantoprazole with other medicinal products or compounds, which are metabolised through the same enzyme system, cannot be excluded.
The results of a series of interaction studies demonstrate that pantoprazole does not affect the metabolism of active substances metabolised by CYP1A2 (such as caffeine, theophylline), CYP2C9 (such as piroxicam, diclofenac, naproxen), CYP2D6 (such as metoprolol), CYP2E1 (such as ethanol) , or does not interfere with p-glycoprotein mediated absorption of digoxin.
There was no evidence of interactions with concomitantly administered antacids.
Interaction studies have also been conducted by concomitantly administering pantoprazole with related antibiotics (clarithromycin, metronidazole, amoxicillin). No clinically relevant interactions were observed.
Medicinal products that inhibit or induce CYP2C19:
CYP2C19 inhibitors such as fluvoxamine may increase the systemic exposure of pantoprazole. A dose reduction may be considered for patients treated long term with high doses of pantoprazole, or those with hepatic insufficiency.
Enzyme inducers affecting CYP2C19 and CYP3A4 such as rifampicin and St. John's wort (Hypericum perforatum) they can reduce plasma concentrations of PPIs which are metabolized through these enzyme systems.
04.6 Pregnancy and breastfeeding -
Pregnancy
A moderate amount of data in pregnant women (between 300 and 1000 exposed pregnancies) indicates that Pantorc does not cause malformations or fetal / neonatal toxicity.
Animal studies have shown reproductive toxicity (see section 5.3).
As a precautionary measure, it is preferable to avoid the use of Pantorc during pregnancy.
Feeding time
Animal studies have shown the excretion of pantoprazole in human milk. There is insufficient information on the excretion of pantoprazole in human milk, but excretion in human breast milk has been reported. A risk to the newborns / infants cannot be excluded. Therefore, a decision must be made whether to discontinue breast-feeding or to discontinue / abstain from Pantorc therapy taking into account the benefit of breast-feeding for the child and the benefit of Pantorc therapy for the woman.
Fertility
There was no evidence of impaired fertility following the administration of pantoprazole in animal studies (see section 5.3).
04.7 Effects on ability to drive and use machines -
Pantoprazole has no or negligible influence on the ability to drive or use machines.
Adverse drug reactions such as dizziness and visual disturbances may occur (see section 4.8). In such cases, patients should not drive or operate machinery.
04.8 Undesirable effects -
Approximately 5% of patients can be expected to experience adverse drug reactions (ADRs). The most commonly reported ADRs are diarrhea and headache, both of which occur in approximately 1% of patients.
The table below lists the adverse reactions reported with pantoprazole, arranged according to the following frequency classification:
Very common (≥1 / 10); common (≥1 / 100,
For all adverse reactions reported from post-marketing experience, it is not possible to establish an Adverse Reaction frequency and therefore they are indicated with a frequency "not known".
Within each frequency class, adverse reactions are reported in order of decreasing severity.
Table 1. Adverse reactions with pantoprazole in clinical studies and post-marketing experience
1. Hypocalcemia in association with hypomagnesaemia
2. Muscle spasm as a result of an electrolyte imbalance
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "address www.agenziafarmaco.gov.it/it/responsabili.
04.9 Overdose -
There are no known symptoms of overdose in humans.
Systemic exposure of up to 240 mg administered intravenously over 2 minutes was well tolerated.
Since pantoprazole is extensively protein bound, it is not readily dialyzable.
In the event of an overdose with clinical signs of intoxication, no specific therapeutic recommendations can be made, with the exception of symptomatic and supportive treatment.
05.0 PHARMACOLOGICAL PROPERTIES -
05.1 "Pharmacodynamic properties -
Pharmacotherapeutic group: proton pump inhibitors.
ATC code: A02BC02.
Mechanism of action
Pantoprazole is a substituted benzimidazole which inhibits the secretion of hydrochloric acid in the stomach via a specific blockade of the proton pumps of the parietal cells.
Pantoprazole is converted to its active form in the acidic environment of the parietal cells where it inhibits the enzyme H +, K + -ATPase, which is the final stage in the production of hydrochloric acid in the stomach. This inhibition is dose-dependent and affects both basal and stimulated acid secretion. In most patients, symptoms resolve within 2 weeks. Like other proton pump inhibitors and H2 receptor inhibitors, treatment with pantoprazole reduces stomach acid and consequently increases gastrin in proportion to the reduction in acidity. The increase in gastrin is reversible. Since pantoprazole binds to the enzyme distal to the cell receptor, it can inhibit the secretion of hydrochloric acid regardless of stimulation by other substances (acetylcholine, histamine, gastrin). The effect is the same after oral or intravenous administration of the product.
Pharmacodynamic effects
Fasting gastrin values increase during treatment with pantoprazole. In short-term use, in most cases they do not exceed the upper limit of normal. During long-term treatment, gastrin levels double in most cases. An excessive increase, however, only occurs in isolated cases. As a result, a mild to moderate increase in the number of specific endocrine cells (ECL) in the stomach (simple to adenomatoid hyperplasia) is observed in a minority of cases during long-term treatment. formation of carcinoid precursors (atypical hyperplasia) or gastric carcinoids as found in animal experiments has not been observed in humans (see section 5.3).
Based on the results of the animal studies, an influence on the endocrine parameters of the thyroid of a long-term treatment with pantoprazole for more than one year cannot be completely excluded.
During treatment with antisecretory medicinal products, serum gastrin increases in response to decreased acid secretion. CgA also increases due to reduced gastric acidity. The increased level of CgA can interfere with diagnostic tests for neuroendocrine tumors.
Available published evidence suggests that proton pump inhibitors should be discontinued between 5 days and 2 weeks prior to CgA measurements. This is to allow CgA levels, which may be falsely elevated following PPI treatment, to return within the reference range.
05.2 "Pharmacokinetic properties -
Absorption
Pantoprazole is rapidly absorbed and maximum plasma concentrations are achieved already after a single oral dose of 20 mg. Maximum serum concentrations around 1-1.5 mcg / ml are reached on average about 2.0 - 2.5 hours after administration, and these values remain constant after repeated administration.
Pharmacokinetic characteristics do not change after single or repeated administration. In the dose range of 10 to 80 mg, the plasma kinetics of pantoprazole are linear after both oral and intravenous administration.
The absolute bioavailability of the tablet is approximately 77%. Concomitant food intake did not affect AUC, maximum serum concentration and hence bioavailability. Only the variability of the lag-time will be increased by the simultaneous intake of food.
Distribution
The binding of pantoprazole to serum proteins is approximately 98%. The volume of distribution is approximately 0.15 l / kg.
Biotransformation
The substance is almost exclusively metabolised in the liver. The major metabolic pathway is demethylation by CYP2C19 with subsequent conjugation with sulfate, the other metabolic pathway includes oxidation by CYP3A4.
Elimination
The terminal phase half-life is approximately 1 hour and clearance is around 0.1 l / h / kg. There have been some cases of patients with slow drug elimination. Due to the specific binding of pantoprazole to the proton pumps of the parietal cells the elimination half-life does not correlate with the longer duration of action (inhibition of acid secretion).
Renal elimination represents the major route of excretion (approximately 80%) for the metabolites of pantoprazole, the remainder is excreted in the faeces. The major metabolite in both serum and urine is desmethylpantoprazole which is conjugated with sulphate. of the main metabolite (approximately 1.5 hours) is not much longer than that of pantoprazole.
Special populations
Slow metabolisers
Approximately 3% of the European population have a lack of CYP2C19 enzyme function and are called poor metabolisers. In these individuals the metabolism of pantoprazole is likely to be catalysed primarily by CYP3A4. After a single administration of pantoprazole 40 mg, the area mean under the plasma concentration-time curve was approximately 6-fold higher in poor metabolisers than in subjects who have a functional CYP2C19 enzyme (extensive metabolisers). The mean peak plasma concentrations had increased by approximately 60%. These findings have no implications for the posology of pantoprazole.
Kidney damage
No dose reduction is recommended when pantoprazole is administered to patients with impaired renal function (including patients on dialysis). The half-life of pantoprazole is short, as observed in healthy subjects. Only very small amounts of pantoprazole are dialyzed.
Although the half-life of the major metabolite is moderately prolonged (2-3 h), excretion is nevertheless rapid and therefore no accumulation occurs.
Hepatic impairment
Although in patients with liver cirrhosis (Child class A and B) the half-life values increase up to 3-6 hours and the AUC values increase by a factor of 3-5, the maximum serum concentration is only modestly increased by a factor of 1.3 compared to that of healthy subjects.
Senior citizens
A slight increase in AUC and Cmax values observed in elderly volunteers compared to the younger group is also not clinically relevant.
Pediatric population
After administration of single oral doses of 20 or 40 mg of pantoprazole to children aged 5 to 16 years, AUC and Cmax were within the range of corresponding values in adults.
After administration of single i.v. doses of 0.8 or 1.6 mg / kg of pantoprazole to children aged 2-16 years there was no significant association between pantoprazole clearance and age or weight. AUC and volume of distribution were in agreement with the data. detected for adults.
05.3 Preclinical safety data -
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity and genotoxicity.
Neuroendocrine tumors were found in two-year carcinogenicity studies in rats. In addition, squamous cell papillomas were found in the anterior part of the stomach of rats. The mechanism by which benzimidazole derivatives induce the formation of gastric carcinoids has been carefully studied and allows us to conclude that this is a secondary reaction to the marked increase in gastrin which occurs in the rat during chronic treatment with high doses.
In the two-year rodent studies, an increased number of liver tumors was observed in rats and female mice and was attributed to the high metabolism of pantoprazole in the liver.
A slight increase in neoplastic changes of the thyroid was observed in the group of rats treated with the highest dose (200 mg / kg). The onset of these neoplasms is associated with pantoprazole-induced changes in the catabolism of thyroxine in the rat liver. Since the therapeutic dose in humans is low, no harmful effects on the thyroid glands are to be expected.
In animal reproduction studies, signs of mild foetotoxicity were observed at doses above 5 mg / kg. Studies have shown no impairment of fertility or teratogenic effects.
Transplacental passage was studied in the rat and it was found to increase as gestation progressed. As a result, the concentration of pantoprazole in the fetus increases just before birth.
06.0 PHARMACEUTICAL INFORMATION -
06.1 Excipients -
Nucleus:
Sodium carbonate, anhydrous
Mannitol (E421)
Crospovidone
Povidone K90
Calcium stearate
Coating:
Hypromellose
Povidone K25
Titanium dioxide (E171)
Yellow iron oxide (E172)
Propylene glycol
Methacrylic acid-ethyl acrylate copolymer (1: 1)
Polysorbate 80
Sodium lauryl sulfate
Triethyl citrate
Printing ink:
Shellac
Red iron oxide (E172)
Black iron oxide (E172)
Yellow iron oxide (E172)
Concentrated ammonia solution
06.2 Incompatibility "-
Not relevant.
06.3 Period of validity "-
Blister packs
3 years.
Bottles
Not open: 3 years
After first opening: 120 days
06.4 Special precautions for storage -
This medicine does not require any special storage conditions.
06.5 Nature of the immediate packaging and contents of the package -
HDPE bottles with LDPE screw cap.
7 gastro-resistant tablets
10 gastro-resistant tablets
14 gastro-resistant tablets
15 gastro-resistant tablets
24 gastro-resistant tablets
28 gastro-resistant tablets
30 gastro-resistant tablets
48 gastro-resistant tablets
49 gastro-resistant tablets
56 gastro-resistant tablets
60 gastro-resistant tablets
84 gastro-resistant tablets
90 gastro-resistant tablets
98 gastro-resistant tablets
98 (2x49) gastro-resistant tablets
100 gastro-resistant tablets
112 gastro-resistant tablets
168 gastro-resistant tablets
Hospital pack of 50 gastro-resistant tablets
56 gastro-resistant tablets
84 gastro-resistant tablets
90 gastro-resistant tablets
112 gastro-resistant tablets
140 gastro-resistant tablets
140 (10x14) (5x28) gastro-resistant tablets
150 (10x15) gastro-resistant tablets
280 (20x14), (10x28) gastro-resistant tablets
500 gastro-resistant tablets
700 (5x140) gastro-resistant tablets
Blister (ALU / ALU blister) without cardboard reinforcement.
Blister (ALU / ALU blister) with cardboard reinforcement (wallet blister).
7 gastro-resistant tablets
10 gastro-resistant tablets
14 gastro-resistant tablets
15 gastro-resistant tablets
28 gastro-resistant tablets
30 gastro-resistant tablets
49 gastro-resistant tablets
56 gastro-resistant tablets
60 gastro-resistant tablets
84 gastro-resistant tablets
90 gastro-resistant tablets
98 gastro-resistant tablets
98 (2x49) gastro-resistant tablets
100 gastro-resistant tablets
112 gastro-resistant tablets
168 gastro-resistant tablets
Hospital pack of 50 gastro-resistant tablets
56 gastro-resistant tablets
84 gastro-resistant tablets
90 gastro-resistant tablets
112 gastro-resistant tablets
140 gastro-resistant tablets
140 (10x14) (5x28) gastro-resistant tablets
150 (10x15) gastro-resistant tablets
280 (20x14), (10x28) gastro-resistant tablets
500 gastro-resistant tablets
700 (5x140) gastro-resistant tablets
Not all pack sizes may be marketed.
06.6 Instructions for use and handling -
No special instructions.
Unused medicine and wastes derived from this medicine must be disposed of in accordance with local regulations.
07.0 HOLDER OF THE "MARKETING AUTHORIZATION" -
Takeda Italia SpA, via Elio Vittorini 129, 00144 Rome
08.0 MARKETING AUTHORIZATION NUMBER -
Pantorc 20 mg gastro-resistant tablets, 14 tablets in bottle AIC n. 031981119 *
Pantorc 20 mg gastro-resistant tablets, 14 tablets in blister AIC n. 031981044
Pantorc 20 mg gastro-resistant tablets, 15 tablets in blister AIC n. 031981057 *
Pantorc 20 mg gastro-resistant tablets, 28 tablets in blister AIC n. 031981069 *
Pantorc 20 mg gastro-resistant tablets, 30 tablets in blister AIC n. 031981071 *
Pantorc 20 mg gastro-resistant tablets, 56 tablets in blister AIC n. 031981083 *
Pantorc 20 mg gastro-resistant tablets, 60 tablets in blister AIC n. 031981095 *
Pantorc 20 mg gastro-resistant tablets, 100 tablets in blister AIC n. 031981107 *
Pantorc 20 mg gastro-resistant tablets, 15 tablets in bottle AIC n. 031981121 *
Pantorc 20 mg gastro-resistant tablets, 28 tablets in bottle AIC n. 031981133 *
Pantorc 20 mg gastro-resistant tablets, 30 tablets in bottle AIC n. 031981145 *
Pantorc 20 mg gastro-resistant tablets, 56 tablets in bottle AIC n. 031981158 *
Pantorc 20 mg gastro-resistant tablets, 60 tablets in bottle AIC n. 031981160 *
Pantorc 20 mg gastro-resistant tablets, 100 tablets in bottle AIC n. 031981172 *
Pantorc 20 mg gastro-resistant tablets, 140 tablets in blister AIC n. 031981184 *
Pantorc 20 mg gastro-resistant tablets, 140 tablets in 10 blisters AIC n. 031981196 *
Pantorc 20 mg gastro-resistant tablets, 140 tablets in 5 blisters AIC n. 031981208 *
Pantorc 20 mg gastro-resistant tablets, 700 tablets in 5 blisters AIC n. 031981210 *
Pantorc 20 mg gastro-resistant tablets, 280 tablets in 20 blisters AIC n. 031981222 *
Pantorc 20 mg gastro-resistant tablets, 280 tablets in 10 blisters AIC n. 031981234 *
Pantorc 20 mg gastro-resistant tablets, 140 tablets in bottle AIC n. 031981246 *
Pantorc 20 mg gastro-resistant tablets, 140 tablets in 10 bottles AIC n. 031981259 *
Pantorc 20 mg gastro-resistant tablets, 140 tablets in 5 bottles AIC n. 031981261 *
Pantorc 20 mg gastro-resistant tablets, 700 tablets in 5 bottles AIC n. 031981273 *
Pantorc 20 mg gastro-resistant tablets, 280 tablets in 20 bottles AIC n. 031981285 *
Pantorc 20 mg gastro-resistant tablets, 280 tablets in 10 bottles AIC n. 031981297 *
(*) packs not marketed
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION -
Date of first authorization: 3 July 2000
Date of most recent renewal: February 22, 2013
10.0 DATE OF REVISION OF THE TEXT -
22 December 2016
