Active ingredients: Pantoprazole
GASTROLOC 20 mg gastro-resistant tablets
Gastroloc package inserts are available for packs:- GASTROLOC 20 mg gastro-resistant tablets
- GASTROLOC 40 mg gastro-resistant tablets
Why is Gastroloc used? What is it for?
Gastroloc 20 mg 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.
Gastroloc 20 mg is used for:
Adults and adolescents aged 12 years and over:
- Treatment of 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.
Adults:
- 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 Gastroloc should not be used
Do not take Gastroloc 20 mg
- if you are allergic (hypersensitive) to pantoprazole or any of the other ingredients of this medicine (see section 6)
- if you are allergic to medicines containing other proton pump inhibitors.
Precautions for use What you need to know before taking Gastroloc
Talk to your doctor or pharmacist before taking Gastroloc 20 mg:
- 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 Gastroloc 20 mg for long-term therapy. In the event of an increase in liver enzymes, the treatment should be discontinued.
- If you need continued NSAID treatment and take Gastroloc 20 mg because you have an increased risk of developing gastric and intestinal complications. Any increased risk will be assessed based on its personal risk factors such as age (65 years and over), an experience 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.
- If you have ever had a skin reaction after treatment with a medicine similar to Gastroloc 20 mg which reduces stomach acid.
- If you notice skin rash, especially in areas exposed to sunlight, contact your doctor as soon as possible, as it may be necessary to stop taking Gastroloc 20 mg. Remember to also mention any other side effects such as joint pain.
Tell your doctor immediately if you notice any of the following symptoms:
- an involuntary weight reduction
- recurrent vomiting
- difficulty in swallowing
- presence of blood in the vomit
- looks pale and feels weak (anemia)
- presence of blood in the stool
- severe and / or persistent diarrhea, because Gastroloc 20 mg was associated with a modest increase in infectious diarrhea.
Your doctor may decide that you need some tests to rule out malignant disease as pantoprazole also relieves the symptoms of cancer and can cause a delay in diagnosis. If your symptoms persist despite treatment, further investigation should be considered.
If you are taking Gastroloc 20 mg for long-term treatment (more 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.
Interactions Which drugs or foods can change the effect of Gastroloc
Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines, including medicines without a prescription.
Gastroloc 20 mg 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 Gastroloc 20 mg 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).
- Methotrexate (used to treat rheumatoid arthritis, psoriasis and cancer) - if you are taking methotrexate your doctor may temporarily stop your treatment with Gastroloc 20 mg.
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, or are breast-feeding, you should use this medicine only. if your doctor considers the benefit to you greater than the potential risk to the fetus or infant.
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.
Driving and using machines
If you experience side effects such as dizziness or disturbed vision, you should not drive or use machines.
Gastroloc 20 mg contains the coloring agent Ponceau 4R aluminum lake (E124): may cause allergic reactions.
Dose, Method and Time of Administration How to use Gastroloc: Posology
Always take this medicine exactly as your doctor or pharmacist has told you. If in doubt, consult your doctor or pharmacist.
When and how should you take Gastroloc 20 mg?
Take the tablets 1 hour before a meal without chewing or crushing them and swallow them whole with some water.
Unless told otherwise by your doctor, the usual dose is:
- Adults and adolescents aged 12 years and over:
For the treatment of symptoms associated with gastroesophageal reflux disorders (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 that 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 disorder returns, your doctor can double the dose, in which case you can use Gastroloc 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.
Particular groups of patients:
- If you have severe liver problems, you should not take more than one 20 mg tablet per day.
- Children under 12. These tablets are not recommended for use in children under 12 years of age.
If you forget to take Gastroloc 20 mg
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 Gastroloc 20 mg
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 or pharmacist.
Overdose What to do if you have taken an overdose of Gastroloc
If you take more Gastroloc 20 mg than you should
Consult your doctor or pharmacist. There are no known symptoms of overdose.
Side Effects What are the side effects of Gastroloc
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 (may affect up to 1 in 1,000 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 heartbeat very fast and heavy sweating.
- Serious skin disorders (frequency not known): blistering of the skin and rapid worsening 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 painful urination or lower back pain (severe inflammation of the kidneys) .
Other possible side effects are:
Uncommon (may affect up to 1 in 100 patients)
headache; dizziness; diarrhea; feeling sick, vomiting; bloating and flatulence (air); constipation; dry mouth; abdominal pain and feeling unwell; rash, rash, rash; itch; feeling of weakness, fatigue or general malaise; sleep disorders. If you take a proton pump inhibitor such as Gastroloc 20 mg, 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 patients)
Alteration or complete lack of the sense of taste; vision disturbances such as clouding; urticaria; joint pain; muscle aches; weight changes; increased body temperature; swelling of the extremities (peripheral edema); allergic reactions; depression, breast enlargement in men.
Very Rare (may affect up to 1 in 10,000 patients):
disorientation.
Not known (frequency cannot be estimated from the available data):
Hallucinations, confusion (especially in patients who experience these symptoms); tingling sensation (paraesthesia); muscle spasm; decreased blood sodium levels; erythema; possible joint pain.
If you take Gastroloc 20 mg for more than three months your blood levels of magnesium may drop. Low magnesium levels can manifest themselves with fatigue, involuntary muscle contractions, disorientation, convulsions, dizziness, increased heart rate.
If you get any of these symptoms, see your doctor immediately. Low levels of magnesium can also lead to a reduction in potassium or calcium levels in the blood. Your doctor may decide whether to check your blood magnesium levels periodically.
Side effects identified through blood tests:
- Uncommon (may affect up to 1 in 100 patients) an increase in liver enzymes.
- Rare (may affect up to 1 in 1,000 patients) an increase in bilirubin; increased blood fat; sharp 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 may 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 or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system at: http://www.agenziafarmaco.gov.it/it/responsabili. 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 blister or bottle after EXP. The expiry date refers to the last day of the month.
This medicinal product 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.
Deadline "> Other information
What GASTROLOC 20 mg contains
- The active ingredient is pantoprazole. Each gastro-resistant tablet contains 20 mg pantoprazole (as pantoprazole sodium sesquihydrate).
- The other ingredients are:
- Tablet core: calcium stearate, microcrystalline cellulose, crospovidone, hydroxypropyl cellulose (type EXF), anhydrous sodium carbonate, anhydrous colloidal silica.
- Coating: hypromellose, yellow iron oxide (E172), macrogol 400, methacrylic acid-ethyl acrylate copolymer (1: 1), polysorbate 80, Ponceau 4R aluminum lake (E124), quinoline yellow aluminum lake (E104), sodium lauryl sulfate, titanium dioxide (E171), triethyl citrate.
What Gastroloc 20 mg looks like and contents of the pack
Gastroloc 20 mg gastro-resistant tablets are yellow, oval tablets (coated with a special coating layer), available in
- Blister packs of 7, 10, 14, 15, 20, 28, 30, 50, 56, 56x1, 60, 84, 90, 98, 100, 100x1, 140 tablets
- Containers of 14, 28, 98, 100, 250, 500 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 -
GASTROLOC 20 MG GASTRORESISTANT TABLETS
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION -
Each gastro-resistant tablet contains 20 mg pantoprazole (as pantoprazole sodium sesquihydrate).
Excipient with known effect :
Each gastro-resistant tablet contains 1 μg of the coloring agent Ponceau 4R aluminum lake (E124) per gastro-resistant tablet.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM -
Gastro-resistant tablet.
Yellow, oval coated tablet, imprinted with "20" in black.
04.0 CLINICAL INFORMATION -
04.1 Therapeutic indications -
Adults and adolescents aged 12 and over
• Gastroesophageal reflux symptoms
• Long-term treatment and prevention of relapse of reflux oesophagitis
Adults
• 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 -
Recommended dose
Adults and adolescents aged 12 and over
Gastroesophageal reflux symptoms
The recommended dose for oral administration is one Gastroloc 20 mg gastro-resistant tablet per day. Relief of symptoms is usually achieved in 2-4 weeks. If this period is not sufficient, relief of symptoms will normally be obtained by prolonging the therapy for 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 when needed. In cases where satisfactory symptom control cannot be maintained with on-demand administration, a switch to continued therapy should be considered.
Long-term treatment and prevention of relapse of reflux oesophagitis
For long-term treatment, a maintenance dose with one Gastroloc gastro-resistant tablet 20 mg per day is recommended, increasing to 40 mg pantoprazole per day in case of relapse. For these cases Gastroloc 40 mg is available. After healing of the relapse the dosage can be reduced again to 20 mg pantoprazole.
Adults
Prevention of gastric and duodenal ulcers induced by non-selective non-steroidal anti-inflammatory drugs (NSAIDs) in patients at risk who require continued NSAID treatment
The recommended dosage for oral administration is one Gastroloc 20 mg gastro-resistant tablet per day.
Dosage in particular groups of patients
Children under 12 years of age
Gastroloc 20 mg is not recommended for use in children below 12 years of age due to limited data on safety and efficacy in this age group.
Hepatic insufficiency
A daily dose of 20 mg of pantoprazole should not be exceeded in patients with severely impaired hepatic function (see section 4.4).
Kidney failure
No dose adjustment is necessary in people with impaired renal function.
Senior citizens
No dose adjustment is necessary in elderly patients.
Method of administration
The tablets should not be chewed or crushed, and should be swallowed whole with a little water 1 hour before a meal.
04.3 Contraindications -
Hypersensitivity to the active substance, to benzimidazole derivatives or to any of the other excipients listed in section 6.1.
04.4 Special warnings and appropriate precautions for use -
Hepatic insufficiency
In patients with severe hepatic impairment, liver 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 Gastroloc 20 mg in the prevention of drug-induced gastroduodenal ulcers
Non-selective non-steroidal anti-inflammatory drugs (NSAIDs) should be limited to patients who require continued NSAID treatment 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 unintentional 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 atazanavir
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 an increase in the dose of atazanavir to 400 mg using 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 medicinal products that inhibit acid secretion, may reduce the absorption of vitamin B12 (cyanocobalamin) as a consequence of hypo- or achlorhydria. This should be considered in long-term therapy or in the case of observed clinical symptoms. in patients with reduced body stores or risk factors for reduced vitamin B12 absorption.
Long-term treatment
In long-term treatment, especially when a 1 year treatment period is exceeded, patients should be kept under regular surveillance.
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.
Hypomagnesemia
Proton pump inhibitors (PPIs) such as pantoprazole have been observed 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 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).
Gastrointestinal infections caused by bacteria
Pantoprazole, like all proton pump inhibitors (PPIs), can be expected to increase the counts of bacteria normally present in the upper gastrointestinal tract. Treatment with Gastroloc 20 mg may lead to a slightly increased risk of gastrointestinal infections caused by bacteria such as Salmonella And Campylobacter.
This medicine contains the coloring agent Ponceau 4R aluminum lake (E 124) which may cause allergic reactions
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 medicinal products 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 medicinal products whose absorption is pH-dependent with proton pump inhibitors may lead to a substantial reduction in the bioavailability of these anti-HIV medicinal products and may alter the efficacy of these medicinal products. 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.
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 medicinal products also metabolised via 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) and 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 administering pantoprazole concomitantly with the respective antibiotics (clarithromycin, metronidazole, amoxicillin). No clinically significant interactions were noted.
Methotrexate
Concomitant use of high dose methotrexate (eg 300 mg) and proton pump inhibitors has been reported to increase methotrexate levels in some patients. Therefore in situations where methotrexate is used in high doses, such as cancer and psoriasis, a temporary withdrawal of pantoprazole may need to be considered.
04.6 Pregnancy and breastfeeding -
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. Gastroloc 20 mg 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 whether to continue / discontinue breastfeeding or to continue / discontinue therapy with Gastroloc 20 mg should be made taking into account the benefit of breastfeeding for the infant and the benefit of Gastroloc 20 mg therapy for the mother.
Fertility
There was no evidence of impaired fertility following administration of pantoprazole in animal studies (see section 5.3).
04.7 Effects on ability to drive and use machines -
Gastroloc 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
Reporting of suspected adverse reactions
The reporting of suspected adverse reactions occurring after authorization of the medicine is important, as it allows continuous monitoring of the benefit / risk balance of the medicine. Healthcare professionals are asked to report any suspected adverse reactions via the website: www. Agenziafarmaco.gov.it/it/responsabili.
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, except for 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 benzimidazole derivative 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 both oral and intravenous administration of the product.
Fasting gastrin values increase during treatment with pantoprazole. In short-term use, in most cases they do not exceed the normal upper limit. 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, enterochromaffin-like cells) in the stomach is observed in a minority of cases during long-term treatment (simple to adenomatoid hyperplasia). the formation of carcinoid precursors (atypical hyperplasia) or gastric carcinoids as found in animal experiments was not 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 maximal 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 does not affect AUC, maximum serum concentration and therefore 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.
Elimination
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. The terminal phase half-life is about 1 hour and clearance is around 0.1 l / h / kg. Some cases of slow drug elimination have been observed.
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 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. The half-life of the main metabolite (approximately 1.5 hours) is not much longer than that of pantoprazole.
Characteristics in particular patients / groups
About 3% of the European population has 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 40 mg pantoprazole, the mean area 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). Mean peak concentrations. plasma levels was increased by approximately 60% These findings have no implication on the posology of pantoprazole.
Dosage reduction is not 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.
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.
A slight increase in AUC and Cmax values observed in elderly volunteers compared to the younger group is also not clinically relevant.
Children
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. 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 adult data.
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 increase in the 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 has been studied in the rat and increases as gestation progresses. As a result, the concentration of pantoprazole in the fetus increases just before birth.
06.0 PHARMACEUTICAL INFORMATION -
06.1 Excipients -
Core of the tablet
Calcium stearate
Microcrystalline cellulose
Crospovidone
Hydroxypropylcellulose (type EXF)
Sodium carbonate anhydrous
Anhydrous colloidal silica
Coating
Hypromellose
Yellow iron oxide (E172)
Macrogol 400
Methacrylic acid-ethyl acrylate copolymer (1: 1)
Polysorbate 80
Ponceau 4R aluminum lacquer (E124)
Quinoline yellow aluminum lake (E104)
Sodium lauryl sulfate
Titanium dioxide (E171)
Triethyl citrate.
Printing ink:
Macrogol 600
Shellac
Povidone
Black iron oxide (E172)
Red iron oxide (E172)
Yellow iron oxide (E172)
06.2 Incompatibility "-
Not relevant.
06.3 Period of validity "-
3 years.
6 months after first opening the HDPE container.
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 -
Al / OPA / Al / PVC blister packaging: 7, 10, 14, 15, 20, 28, 30, 50, 56, 56x1, 60, 84, 90, 98, 100, 100x1, 140.
HDPE tablet container with polypropylene screw cap equipped with desiccant insert: 14, 28, 98, 100, 250, 500.
Not all pack sizes may be marketed.
06.6 Instructions for use and handling -
No special instructions.
07.0 HOLDER OF THE "MARKETING AUTHORIZATION" -
Novartis Consumer Health S.p.A. - L. Umberto Boccioni, 1 - 21040 Origgio (VA)
08.0 MARKETING AUTHORIZATION NUMBER -
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION -
July 2009
10.0 DATE OF REVISION OF THE TEXT -
12 November 2013
