Instructions for Nolpaza Control gastro-resistant tablets 20 mg No. 14
Composition
active ingredient: pantoprazole;
1 gastro-resistant tablet contains 20 mg of pantoprazole in the form of pantoprazole sodium sesquihydrate;
Excipients: mannitol (E 421), crospovidone, sodium carbonate, sorbitol (E 420), calcium stearate, hypromellose, povidone (K 25), titanium dioxide (E 171), iron oxide yellow (E 172), propylene glycol, methacrylate copolymer dispersion, talc, macrogol 6000.
Dosage form
Gastro-resistant tablets.
Main physicochemical properties: light yellow-brown tablets, oval, slightly biconvex, coated.
Pharmacotherapeutic group
A drug for the treatment of acid-dependent diseases. Proton pump inhibitors. ATC code A02B C02.
Pharmacological properties
Pharmacodynamics
Pantoprazole is a substituted benzimidazole that blocks the secretion of hydrochloric acid in the stomach through a specific effect on the proton pump of parietal cells.
Pantoprazole is transformed into the active form in an acidic environment, namely in the parietal cells, where it inhibits the enzyme H+-K+-ATPase, i.e. blocks the final stage of hydrochloric acid production in the stomach. Inhibition is dose-dependent and suppresses both basal and stimulated acid secretion.
Treatment with pantoprazole, like other proton pump inhibitors and H2-receptor inhibitors, reduces gastric acidity and thus increases gastrin secretion in proportion to the decrease in acidity. The increase in gastrin secretion is reversible. Since pantoprazole binds the enzyme distal to the cell receptor, it can inhibit hydrochloric acid secretion independently of stimulation by other substances (acetylcholine, histamine, gastrin). The efficacy of the drug is the same when administered orally or intravenously.
Pantoprazole increases fasting gastrin levels. In short-term use, they do not exceed the upper limit of normal in most cases. In long-term treatment, gastrin levels in most cases double. However, excessive increases occur only in isolated cases. As a result, in a small number of cases, a slight or moderate increase in the number of enterochromaffin-like cells (ECL cells) of the stomach (adenomatoid hyperplasia) has been observed during long-term treatment. However, according to the studies conducted to date, the formation of precursor cells of neuroendocrine tumors of the stomach, which were detected in animal experiments, has not been observed in humans. However, in long-term (more than 1 year) treatment, the effect of pantoprazole on endocrine parameters of the thyroid gland cannot be excluded.
During treatment with antisecretory drugs, serum gastrin levels increase in response to decreased acid secretion. In addition, chromogranin A (CgA) levels increase due to decreased gastric acidity. Elevated CgA levels may interfere with diagnostic tests for neuroendocrine tumors. Available published data suggest that proton pump inhibitor treatment should be discontinued for 5 days to 2 weeks before CgA measurements. This allows CgA levels, which may be falsely elevated after PPI treatment, to return to the normal range.
Pharmacokinetics
Pantoprazole is rapidly absorbed, with peak plasma concentrations occurring even after a single dose of 40 mg. On average, peak plasma concentrations of 2-3 μg/ml are reached within 2.5 hours after administration and remain constant even after multiple administration. The volume of distribution is approximately 0.15 l/kg and the clearance is approximately 0.1 l/h/kg.
The elimination half-life is approximately 1 hour. In a few cases the elimination time was prolonged. Due to the specific binding of pantoprazole to the proton pump of the parietal cells, the elimination half-life does not correlate with a longer duration of action.
The pharmacokinetics are not affected by single or multiple dosing. At doses from 10 to 80 mg, the kinetics of pantoprazole in plasma are linear after both oral and intravenous administration.
The plasma protein binding of pantoprazole is approximately 98%. The drug is almost completely metabolized in the liver. The main route of excretion is the kidneys - approximately 80% of the metabolites of pantoprazole; the rest is excreted in the feces. The main metabolite in both plasma and urine is desmethylpantoprazole, which is conjugated with sulfate. The half-life of the main metabolite (approximately 1.5 hours) is slightly longer than that of pantoprazole.
Bioavailability. After oral administration, pantoprazole is completely absorbed. The absolute bioavailability of the tablet is approximately 77%. Food intake has no effect on the area under the pharmacokinetic concentration-time curve (AUC), maximum plasma concentration and bioavailability; only the onset of action is altered.
Poor metabolisers. Approximately 3% of Europeans have a low functional activity of the CYP2C19 enzyme; they are called poor metabolisers. In these individuals, the metabolism of pantoprazole is probably mainly catalysed by the CYP3A4 enzyme. After a single dose of 40 mg pantoprazole, the mean area under the plasma concentration-time curve was approximately 6 times larger in poor metabolisers than in subjects with a functional CYP2C19 enzyme (extensive metabolisers). The mean peak plasma concentration was increased by approximately 60%. These findings do not influence the posology of pantoprazole.
For patients with impaired renal function (including patients on hemodialysis), no dose reduction is required. As in healthy subjects, the elimination half-life of pantoprazole is short. Only very small amounts of pantoprazole are dialyzed. Although the elimination half-life of the main metabolite is slightly increased (2-3 hours), it is rapidly excreted and therefore does not accumulate.
In patients with liver cirrhosis (Child-Pugh classes A and B), the half-life increases to 7-9 hours and, accordingly, the AUC value increases 5-7 times and the maximum plasma concentration of pantoprazole increases by 1.5 times compared to healthy subjects.
The slight increase in AUC and maximum plasma concentration of pantoprazole in elderly volunteers compared to young volunteers is also not clinically significant.
Elderly patients: The slight increase in AUC and Cmax in elderly volunteers compared to younger volunteers is also not clinically relevant.
Indication
Treatment of gastroesophageal reflux disease and its symptoms (such as heartburn, acid regurgitation) in adults.
Contraindication
Hypersensitivity to pantoprazole or to any component of the drug.
Pantoprazole is contraindicated for use concomitantly with atazanavir (see section “Interaction with other medicinal products and other types of interactions”).
Interaction with other medicinal products and other types of interactions
Pantoprazole may reduce the absorption of drugs whose bioavailability depends on the pH of the gastric juice (e.g. some antifungal drugs such as ketoconazole, itraconazole, posaconazole, or other drugs such as erlotinib).
Co-administration of atazanavir 300 mg/ritonavir 100 mg with omeprazole (40 mg once daily) or atazanavir 400 mg with lansoprazole (60 mg once daily) in healthy volunteers has been shown to significantly reduce the bioavailability of atazanavir. Absorption of atazanavir is pH dependent. Therefore, co-administration of pantoprazole with atazanavir is contraindicated (see section 4.3).
Despite the absence of interaction with concomitant administration of phenprocoumon and warfarin during clinical trials, isolated cases of changes in INR (International Normalized Ratio) have been reported during post-marketing surveillance. Therefore, in patients taking coumarin anticoagulants (e.g. phenprocoumon and warfarin), it is recommended to monitor prothrombin time/INR at the beginning, end and in case of irregular treatment with pantoprazole.
Concomitant use of high doses of methotrexate (e.g. 300 mg) and proton pump inhibitors has been reported to increase blood levels of methotrexate in some patients. Patients receiving high doses of methotrexate, e.g. patients with cancer or psoriasis, are advised to temporarily discontinue pantoprazole treatment.
Pantoprazole is metabolized in the liver via the cytochrome P450 enzyme system.
Studies with most of these agents have not revealed clinically significant interactions with carbamazepine, caffeine, diazepam, diclofenac, digoxin, ethanol, glibenclamide, metoprolol, naproxen, nifedipine, phenytoin, piroxicam, theophylline and oral contraceptives containing levonorgestrel and ethinyl estradiol. However, interactions of pantoprazole with other drugs metabolized by the same enzyme system cannot be excluded.
No interactions with concomitantly administered antacids were identified.
Studies have been conducted on the interaction of pantoprazole with certain antibiotics (clarithromycin, metronidazole, amoxicillin) administered concomitantly. No clinically significant interactions between these drugs have been identified.
Application features
they have unintentional significant weight loss, anemia, gastrointestinal bleeding, dysphagia, recurrent vomiting or hematemesis, as treatment with pantoprazole may mask symptoms and delay diagnosis of more serious diseases. In these cases, the risk of malignancy should be excluded. If symptoms persist despite continued adequate treatment, further investigation is necessary; they have a history of gastric or duodenal ulcer, or have undergone gastrointestinal surgery; they are on long-term symptomatic treatment for indigestion or heartburn for 4 weeks or more; they have jaundice, liver failure or liver disease; they have other serious diseases that negatively affect their general health; they are over 55 years of age and they have new or recently changed symptoms of indigestion or heartburn.
Patients with long-term recurrent symptoms of indigestion or heartburn should be examined regularly. Patients over the age of 55 who use any over-the-counter indigestion or heartburn medication daily should inform their doctor.
Patients should not take any other proton pump inhibitor or H2-histamine receptor blocker concomitantly.
If an endoscopic examination or urea breath test is required, patients should consult their doctor before taking pantoprazole.
Patients should be aware that pantoprazole tablets are not intended to provide immediate relief of symptoms. Patients may experience relief of symptoms approximately 1 day after starting treatment with pantoprazole, but it may take up to 7 days to achieve complete resolution of heartburn symptoms. Patients should not use pantoprazole as a prophylactic agent.
Liver function disorders: Patients with severe liver function disorders should have their liver enzymes monitored regularly. If liver enzymes increase, treatment with the drug should be discontinued.
HIV protease inhibitors: Concomitant use of pantoprazole with HIV protease inhibitors (such as atazanavir, nelfinavir), whose absorption depends on intragastric pH, is not recommended due to a significant reduction in their bioavailability.
Gastrointestinal infections caused by bacteria. Reducing stomach acid through the use of any medication, including proton pump inhibitors, increases the number of stomach bacteria that are normally present in the gastrointestinal tract. Treatment with acid-reducing drugs slightly increases the risk of developing gastrointestinal infections caused by microorganisms such as Salmonella, Campylobacter, or Clostridium difficile.
Concomitant use with NSAIDs. The use of Nolpaza® Control for the prevention of gastric and duodenal ulcers caused by long-term use of NSAIDs should be limited to patients who are prone to frequent exacerbations of gastric and duodenal ulcers. The risk level is assessed taking into account individual risk factors, including age (> 65 years), history of gastric or duodenal ulcers, and gastrointestinal bleeding.
Vitamin B12 absorption: Pantoprazole, like all drugs that block hydrochloric acid production, may reduce the absorption of vitamin B12 (cyanocobalamin) due to the occurrence of hypo- or achlorhydria. This should be taken into account in patients with reduced body weight or in the presence of risk factors for reduced absorption of vitamin B12 during long-term therapy or if appropriate clinical symptoms are observed.
Long-term treatment. With a long-term treatment period, especially more than 1 year, patients should be under constant medical supervision.
Hypomagnesemia: Severe hypomagnesemia has been reported in patients treated with PPIs such as pantoprazole for at least three months, and in most cases for a year. The following serious clinical manifestations of hypomagnesemia may occur and progress insidiously: fatigue, tetany, delirium, convulsions, dizziness and ventricular arrhythmias. In the case of hypomagnesemia, in most cases the patient's condition improved after magnesium replacement therapy and discontinuation of the PPI.
Patients requiring long-term therapy or patients taking PPIs in combination with digoxin or drugs that can cause hypomagnesemia (e.g. diuretics) should have magnesium levels measured before starting PPI treatment and periodically during treatment.
Subacute cutaneous lupus erythematosus: The use of proton pump inhibitors has been associated with very rare cases of subacute cutaneous lupus erythematosus.
In the event of a lesion, especially in areas exposed to sunlight, and accompanied by arthralgia, the patient should immediately consult a doctor and consider discontinuing Nolpaza® Control. The occurrence of subacute cutaneous lupus erythematosus in patients with previous therapy with proton pump inhibitors may increase the risk of its development when using other proton pump inhibitors.
Impact on laboratory test results.
Elevated levels of chromogranin A (CgA) may interfere with the results of tests for the diagnosis of neuroendocrine tumors. To avoid this interference, treatment with Nolpaza® Control should be temporarily discontinued for at least 5 days before CgA levels are measured (see section 5.2). If CgA and gastrin levels have not returned to the normal range after the initial measurement, repeat measurements should be performed 14 days after discontinuation of proton pump inhibitor treatment.
Ability to influence reaction speed when driving vehicles or other mechanisms
Pantoprazole has no or very minor influence on the ability to drive or use machines. It is necessary to take into account the possible development of side effects such as dizziness and visual disturbances (see section "Adverse reactions"). In such cases, you should not drive or use machines.
Use during pregnancy or breastfeeding
Pregnancy. Available data on the use of Nolpaza® Control in pregnant women indicate no embryonal or foeto/neonatal toxicity of the drug. Reproductive toxicity has been observed in animals. As a precautionary measure, the use of Nolpaza® Control in pregnant women should be avoided.
Breastfeeding. Animal studies have shown excretion of pantoprazole in breast milk. There is insufficient data on the excretion of pantoprazole in human milk, but such excretion has been reported. A risk to newborns/infants cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Nolpaza® Control therapy taking into account the benefit of breast-feeding for the child and the benefit of Nolpaza® Control therapy for the woman.
Fertility: Pantoprazole did not impair fertility in animal studies.
Method of administration and doses
Dosage
The recommended dose is 20 mg pantoprazole (1 tablet) once a day.
To relieve symptoms, it may be necessary to use the tablets for 2-3 days. After the symptoms disappear, treatment with the drug should be discontinued. The duration of treatment should not exceed 4 weeks without additional medical examination (after consultation with a doctor).
If symptoms do not improve after two weeks of continuous treatment, the patient should consult a doctor.
Characteristics of special patient groups
No dose adjustment is required for elderly patients or patients with impaired renal or hepatic function.
Method of administration
Enteric-coated tablets of Nolpaza® Control 20 mg should be swallowed whole, without chewing or breaking, with a small amount of liquid before meals.
Children
Nolpaza® Control is not recommended for use in children due to insufficient data on the safety and efficacy of the drug in this age group.
Overdose
There are no reports of overdose in humans.
Doses up to 240 mg administered intravenously over 2 minutes were well tolerated.
Since pantoprazole is highly bound to plasma proteins, it is not removed by dialysis.
In case of overdose with clinical signs of intoxication, there are no specific therapeutic recommendations other than symptomatic and supportive treatment.
Adverse reactions
Adverse reactions were observed in approximately 5% of patients. The most common adverse reactions were diarrhea and headache (approximately 1%).
Adverse reactions are classified according to the following frequency: very common (≥ 1/10), common (≥ 1/100 and < 1/10), uncommon (≥ 1/1000 and < 1/100), rare (≥ 1/10000 and < 1/1000), very rare
(< 1/10,000), unknown (frequency not determined from available data).
From the blood and lymphatic system.
Rare: agranulocytosis.
Very rare: leukopenia, thrombocytopenia, pancytopenia.
From the immune system.
Rare: hypersensitivity reactions (including anaphylactic reactions, anaphylactic shock).
Metabolism and metabolic disorders.
Rare: hyperlipidemia and increased lipid levels (triglycerides, cholesterol), changes in body weight.
Not known: hyponatremia, hypomagnesemia (see section "Special warnings and precautions for use"), hypocalcemia1, hypokalemia.
Mental disorders.
Uncommon: sleep disorders.
Rare: depression (including exacerbation).
Very rare: disorientation (including exacerbation).
Not known: hallucination, confusion (especially in patients with a predisposition to these disorders, as well as exacerbation of these symptoms in case of pre-existing conditions).
Uncommon: headache, dizziness.
Rare: taste disorders.
Not known: paraesthesia.
From the organs of vision.
Rare: visual disturbances/blurred vision.
From the digestive tract.
Common: fundic gland polyps (benign).
Uncommon: diarrhoea, nausea, vomiting, abdominal bloating, constipation, dry mouth, abdominal pain and discomfort.
On the part of the hepatobiliary system.
Uncommon: increased liver enzymes (transaminases, g-GT).
Rare: increased bilirubin levels.
Not known: hepatocyte damage, jaundice, hepatocellular failure.
On the skin and subcutaneous tissue.
Uncommon: skin rash, exanthema, pruritus.
Rare: urticaria, angioedema.
Not known: Stevens-Johnson syndrome, Lyell's syndrome, erythema multiforme, photosensitivity, subacute cutaneous lupus erythematosus (see section "Special warnings and precautions for use").
On the part of the musculoskeletal system and connective tissue.
Uncommon: fractures of the hip, wrist, spine (see section "Special warnings and precautions for use").
Rare: arthralgia, myalgia.
Not known: muscle spasm2.
On the part of the kidneys and urinary system.
Not known: interstitial nephritis (with possible development of renal failure).
From the reproductive system and mammary glands.
Rare: gynecomastia.
General disorders.
Uncommon: asthenia, fatigue, malaise.
Rare: fever, peripheral edema.
1. Hypocalcemia simultaneously with hypomagnesemia.
2. Muscle spasm as a result of electrolyte imbalance.
Expiration date
5 years.
Storage conditions
Store in the original packaging at a temperature not exceeding 30 °C.
Keep out of reach of children.
Packaging
7 tablets in a blister; 2 blisters in a cardboard box.
Vacation category
Without a prescription.
Producer
KRKA, d.d., Novo mesto, Slovenia.
Location of the manufacturer and its business address
Šmarješka cesta 6, 8501 Novo mesto, Slovenia.
