Active ingredients: Pantoprazole
Peptazol 20 mg gastro-resistant tablets
Peptazol package inserts are available for pack sizes:- Peptazol 20 mg gastro-resistant tablets
- Peptazol 40 mg gastro-resistant tablets
Why is Peptazol used? What is it for?
Peptazol contains the active substance pantoprazole (as sodium sesquihydrate). Peptazol 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.
Peptazol 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.
Peptazol is used for the treatment of 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 Peptazol should not be used
Do not take Peptazol
- If you are allergic to pantoprazole or any of the other ingredients of this medicine
- If you are allergic to medicines containing other proton pump inhibitors.
Precautions for use What you need to know before taking Peptazol
Talk to your doctor, pharmacist or nurse before taking Peptazol
- 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 Peptazol 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 Peptazol because 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 a medicine containing atazanavir (for the treatment of HIV infection) at the same time as pantoprazole, ask your doctor for specific advice.
- Patients who take multiple daily doses of proton pump inhibitors over a long period of time (one year or more) may have an increased risk of hip, wrist or spine fractures. Talk to your doctor about the risk of bone fractures if you take Peptazol.
- If you have low levels of magnesium in your blood. This problem can be serious. Low magnesium levels can occur in patients taking a proton pump inhibitor for at least 3 months. If magnesium levels drop, it usually happens after a year of treatment. Symptoms due to decreased magnesium levels may or may not occur.
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 (not due to a diet or increased exercise program)
- vomiting, particularly if repeated
- presence of blood in the vomit; this may appear as dark coffee grounds in vomit
- appearance of blood in the stool which may appear dark or tarry
- difficulty swallowing or pain when swallowing
- looks pale and feels weak (anemia)
- chest pain
- stomach pain
- severe and / or persistent diarrhea, as this medicine 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.
If you are taking Peptazol for long-term treatment (longer than 1 year) your doctor will probably monitor you regularly. He should report any new or exceptional symptoms and circumstances whenever he meets the doctor.
Children and adolescents
Peptazol is not recommended for use in children as it has not been shown to be effective in children under 12 years of age.
Interactions Which drugs or foods can modify the effect of Peptazol
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including medicines obtained without a prescription.
- Medicines such as ketoconazole, itraconazole and posaconazole (used to treat fungal infections) or erlotinib (used for some types of cancer) as Peptazol 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.
- Atazanavir (used to treat HIV infection) and other medicines used to treat HIV.
- Methotrexate (used to treat rheumatoid arthritis, psoriasis and cancer) if you are taking methotrexate, your doctor may temporarily stop your Peptazol treatment because pantoprazole can increase the levels of methotrexate in your blood.
Warnings It is important to know that:
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, think you may be pregnant or are planning to become pregnant, or if you are breast-feeding ask your doctor for advice. doctor or pharmacist 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
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 Peptazol: Posology
Always take this medicine exactly as your doctor or pharmacist has told you. If in doubt, consult your doctor or pharmacist.
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 they can use Peptazol 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.
Method of administration
Take the tablets 1 hour before meals without chewing or crushing them and swallow them whole with a little water
Overdose What to do if you have taken an overdose of Peptazol
If you take more Peptazol than you should
Consult your doctor or pharmacist. There are no known symptoms of overdose.
If you forget to take Peptazol
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 Peptazol
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.
Side Effects What are the side effects of Peptazol
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:
- Severe allergic reactions (frequency rare): 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 heart rate and heavy sweating.
- Serious skin disorders (frequency not known): blistering of the skin and rapid deterioration of your general condition, erosion (including slight bleeding) of the eyes, nose, mouth / lips or genitals (Stevens-Johnson syndrome, Lyell's syndrome, Erythema multiforme), and sensitivity to light.
- Other serious conditions (frequency not known): 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 part of the back (severe inflammation of the kidneys).
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.
If you take a proton pump inhibitor such as Peptazol, especially for longer than one year, you may have a slightly increased risk of fracture of the hip, wrist or spine. If you have osteoporosis or are taking corticosteroids (which may increase the risk of osteoporosis) consult your doctor.
- 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; increase in 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); decreased level of sodium in the blood, tingling, pins and needles sensation, burning sensation or numbness; low potassium levels which can cause muscle weakness, spasms or an abnormal heart rhythm; muscle spasm or cramps; low calcium levels.
If you take Peptazol for more than three months, your blood levels of magnesium may drop. Low levels of magnesium can be manifested by fatigue, involuntary muscle contractions, disorientation, convulsions, dizziness, increased heart rate. If you have any of these symptoms, please consult your doctor immediately. Low levels of magnesium can also lead to a reduction in potassium or calcium levels in the blood. The doctor should decide whether to check the magnesium levels in the blood periodically (see section 2).
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 https: // www. aifa.gov.it/content/segnalazioni-reazioni-avverse. 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.
What Peptazol 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.
Description of what Peptazol 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).
Peptazol is available in the following pack sizes:
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
PEPTAZOL 20 MG FOOD-RESISTANT TABLETS
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each gastro-resistant tablet contains 20 mg of pantoprazole (as sodium sesquihydrate).
Excipients with known effects:
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
Peptazol 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.
Peptazol 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 Peptazol 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 by 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 Peptazol 20 mg tablet per day is recommended, increasing to 40 mg pantoprazole per day in case of relapse. For these cases, the 40 mg Peptazol tablet is available. After healing of the relapse the dose can be reduced again to one 20 mg tablet of Peptazol.
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 Peptazol 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.
Senior citizens
No dose adjustment is necessary in elderly patients.
Pediatric population
The use of Peptazol 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
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 Peptazol 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.
Assessment of increased risk should be made based on the presence of individual risk factors, eg high age (> 65 years), history of gastric or duodenal ulcer or upper gastrointestinal bleeding.
In the presence of alarming symptoms
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 must be excluded, as the treatment with pantoprazole can relieve symptoms and delay diagnosis.
If symptoms persist despite adequate treatment, further investigation should be considered.
Co-administration with atazavanir
Co-administration of atazanavir with proton pump inhibitors is not recommended (see section 4.5). If the combination of atazanavir with a proton pump inhibitor is judged unavoidable, close clinical monitoring (e.g. viral load) is recommended in combination with a dose increase of atazanavir to 400 mg with 100 mg of ritonavir. A pantoprazole dose of 20 mg per day should not be exceeded.
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
Pantoprazole, like all proton pump inhibitors (PPIs), might be expected to increase the counts of bacteria normally present in the upper gastrointestinal tract. Treatment with Peptazol 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. Hypomagnesaemia in most patients improves 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.
04.5 Interactions with other medicinal products and other forms of interaction
Effect of pantoprazole on the absorption of other medicinal products
Due to the marked and long-lasting inhibition of gastric acid secretion, pantoprazole may reduce the absorption of drugs whose bioavailability is dependent on gastric pH, eg some azole antifungals such as ketoconazole, itraconazole, posaconazole and other medicines such as erlotinib.
HIV medicines (atazanavir)
Co-administration of atazanavir and other anti-HIV drugs whose absorption is pH-dependent with proton pump inhibitors may lead to a substantial reduction in the bioavailability of these anti-HIV drugs and may modify the efficacy of these drugs. Therefore, co-administration of proton pump inhibitors with atazanavir is not recommended (see section 4.4).
Coumarin anticoagulants (phenprocoumon or warfarin)
Although no interactions were observed during concomitant treatment with phenprocoumon or warfarin in clinical pharmacokinetic studies, a few isolated cases of International Normalized Ratio (INR) variation during concomitant treatment were observed in the post-marketing period. Thus, in patients treated with coumarin anticoagulants (e.g. phenprocoumon or warfarin), it is recommended to monitor the prothrombin time / INR when starting treatment with pantoprazole, when it is discontinued or when it is administered intermittently.
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. Therefore where high doses of methotrexate are administered, eg for cancer and 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.
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.
04.6 Pregnancy and lactation
Pregnancy
There are no adequate data from the use of pantoprazole in pregnant women.Studies in animals have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Peptazol should not be used during pregnancy unless absolutely necessary.
Feeding time
Animal studies have shown excretion of pantoprazole into breast milk. Excretion into human breast milk has been reported. Therefore, a decision must be made whether to discontinue breast-feeding or to discontinue / abstain from Peptazole therapy taking into account the benefit of the drug. breastfeeding for the baby and the benefit of Peptazol therapy for the woman.
04.7 Effects on ability to drive and 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 from post-marketing experience, it is not possible to establish any frequency of Adverse Reaction and therefore they are indicated with a frequency of "not known".
Within each frequency class, adverse reactions are reported in order of decreasing severity.
Table 1. Adverse reactions with pantoprazole in clinical trials and post marketing experience
1 Hypocalcaemia in association with hypomagnesaemia
2 Muscle spasm as a result of 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 https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
04.9 Overdose
There are no known symptoms of overdose in humans.
Systemic exposure 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. the 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.
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 food intake.
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 subjects 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 dialysis patients). 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 MARKETING AUTHORIZATION HOLDER
RECORDATI Chemical and Pharmaceutical Industries S.p.A. - Via M. Civitali, 1 - 20148 Milan
08.0 MARKETING AUTHORIZATION NUMBER
Peptazol 20 mg gastro-resistant tablets, 14 tablets in bottle AIC n. 031111091 *
Peptazol 20 mg gastro-resistant tablets, 14 tablets in blister AIC n. 031111026
Peptazol 20 mg gastro-resistant tablets, 15 tablets in blister AIC n. 031111038 *
Peptazol 20 mg gastro-resistant tablets, 28 tablets in blister AIC n. 031111040
Peptazol 20 mg gastro-resistant tablets, 30 tablets in blister AIC n. 031111053 *
Peptazol 20 mg gastro-resistant tablets, 56 tablets in blister AIC n. 031111065 *
Peptazol 20 mg gastro-resistant tablets, 60 tablets in blister AIC n. 031111077 *
Peptazol 20 mg gastro-resistant tablets, 100 tablets in blister AIC n. 031111089 *
Peptazol 20 mg gastro-resistant tablets, 15 tablets in bottle AIC n. 031111103 *
Peptazol 20 mg gastro-resistant tablets, 28 tablets in bottle AIC n. 031111115 *
Peptazol 20 mg gastro-resistant tablets, 30 tablets in bottle AIC n. 031111127 *
Peptazol 20 mg gastro-resistant tablets, 56 tablets in bottle AIC n. 031111139 *
Peptazol 20 mg gastro-resistant tablets, 60 tablets in bottle AIC n. 031111141 *
Peptazol 20 mg gastro-resistant tablets, 100 tablets in bottle AIC n. 031111154 *
Peptazol 20 mg gastro-resistant tablets, 140 tablets in blister AIC n. 031111166 *
Peptazol 20 mg gastro-resistant tablets, 140 tablets in 10 blisters AIC n. 031111178 *
Peptazol 20 mg gastro-resistant tablets, 140 tablets in 5 blisters AIC n. 031111180 *
Peptazol 20 mg gastro-resistant tablets, 700 tablets in 5 blisters AIC n. 031111192 *
Peptazol 20 mg gastro-resistant tablets, 280 tablets in 20 blisters AIC n. 031111204 *
Peptazol 20 mg gastro-resistant tablets, 280 tablets in 10 blisters AIC n. 031111216 *
Peptazol 20 mg gastro-resistant tablets, 140 tablets in bottle AIC n. 031111228 *
Peptazol 20 mg gastro-resistant tablets, 140 tablets in 10 bottles AIC n. 031111230 *
Peptazol 20 mg gastro-resistant tablets, 140 tablets in 5 bottles AIC n. 031111242 *
Peptazol 20 mg gastro-resistant tablets, 700 tablets in 5 bottles AIC n. 031111255 *
Peptazol 20 mg gastro-resistant tablets, 280 tablets in 20 bottles AIC n. 031111267 *
Peptazol 20 mg gastro-resistant tablets, 280 tablets in 10 bottles AIC n. 031111279 *
(*) packs not marketed
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Date of first authorization: 03 July 2000
Date of most recent renewal: 27 July 2008
10.0 DATE OF REVISION OF THE TEXT
11/2014
