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Pantoprazole-PHARMEX lyophilisate for solution for injection 40 mg
Instruction
For medical use of the medicinal product
Pantoprazole-Pharmex
(Pantoprazol-pharmex)
Composition:
Active ingredient: pantoprazole;
1 vial contains pantoprazole sodium sesquihydrate equivalent to pantoprazole 40.0 mg; excipients: disodium edetate, sodium hydroxide.
Dosage form.
Lyophilisate for solution for injection.
Main physicochemical properties: lyophilized porous mass or powder from white to almost white.
Pharmacotherapeutic group.
A drug for the treatment of acid-dependent diseases. Proton pump inhibitors.
PBX code A02B C02.
Pharmacological properties.
Pharmacodynamics.
Pantoprazole is a substituted benzimidazole that inhibits gastric acid secretion by specific blockade of the proton pumps of 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, i.e. blocks the final stage of gastric acid production. The inhibition is dose-dependent and inhibits both basal and stimulated acid secretion. These manifestations disappear in most patients within 2 weeks. The use of pantoprazole, like other proton pump inhibitors (PPIs) 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 regardless of stimulation by other substances (acetylcholine, histamine, gastrin). The effect is the same when the drug is administered orally and intravenously.
Pantoprazole increases fasting gastrin levels. In short-term use of pantoprazole, gastrin levels do not exceed the upper limit of normal in most cases. In long-term treatment, gastrin levels double in most cases. Excessive gastrin levels, however, occur only in rare cases. As a result, a slight to moderate increase in the number of enterochromaffin-like cells (ECL cells) in the stomach (similar to adenomatoid hyperplasia) is sometimes observed during long-term treatment. However, according to studies conducted to date, the formation of neuroendocrine tumor precursor cells (atypical hyperplasia) or neuroendocrine tumors of the stomach has not been observed in humans.
Pharmacokinetics.
Absorption.
Pantoprazole is rapidly absorbed and the maximum plasma concentration (Cmax) is reached after a single oral dose of 40 mg. On average, 2.5 hours after administration, the maximum serum concentration is reached at a level of about 2-3 μg/ml; the concentration remains stable after multiple administration. The pharmacokinetic properties do not change after a single or repeated administration. In the dose range from 10 to 80 mg, the pharmacokinetics of pantoprazole in plasma remains linear, both after oral and intravenous administration. It has been established that the absolute bioavailability of the tablets is about 77%. Simultaneous food intake does not affect the area under the concentration-time curve (AUC) or Cmax, and therefore the bioavailability. Only the variability of the latent period increases with simultaneous food intake.
Distribution.
The binding of pantoprazole to serum proteins is approximately 98%. The volume of distribution is approximately 0.15 l/kg.
Breeding.
Pantoprazole is metabolized almost exclusively in the liver. The main metabolic pathway is demethylation by CYP2C19 followed by sulfate conjugation; other metabolic pathways include oxidation by CYP3A4. The terminal half-life is about 1 hour and the clearance is 0.1 l/h/kg. Several cases of delayed elimination have been reported. Due to the specific binding of pantoprazole to the proton pumps of the parietal cells, the half-life does not correlate with the much longer duration of action (inhibition of acid secretion). The main metabolites of pantoprazole are excreted in the urine (about 80%), the remainder is excreted in the feces. The main metabolite in both serum and urine is desmethylpantoprazole conjugated with sulfate. The half-life of the main metabolite (about 1.5 hours) is not much longer than that of pantoprazole.
There are no recommendations for dose reduction when prescribing pantoprazole to patients with impaired renal function (including patients on dialysis). As in healthy volunteers, the elimination half-life of pantoprazole is short. Only a very small amount of pantoprazole is dialyzed. Although the main metabolite has a moderately long half-life (2-3 hours), elimination is still rapid, so accumulation does not occur.
Although in patients with cirrhosis of the liver (Child-Pugh classes A and B) the half-life increases to 7-9 hours and the AUC increases 5-7-fold, the maximum serum concentration increases only slightly - 1.5-fold compared with that in healthy volunteers. The slight increase in AUC and Cmax in elderly volunteers compared with younger volunteers is also not clinically significant.
Children. After a single oral dose of 20 or 40 mg pantoprazole, AUC and Cmax in children aged 5 to 16 years were within the range of the corresponding values in adults. After a single intravenous administration of 0.8 or 1.6 mg/kg pantoprazole to children aged 2 to 16 years, there was no significant relationship between the clearance of pantoprazole and the patient's age or body weight. The AUC and volume of distribution were consistent with those obtained in studies in adults.
Clinical characteristics.
Indication.
Reflux esophagitis. duodenal ulcer. gastric ulcer. Zollinger-Ellison syndrome and other hypersecretory pathological conditions.
Contraindication.
Hypersensitivity to pantoprazole, benzimidazole derivatives or to any other components of the drug.
Interaction with other drugs and other types of interactions.
Effect of pantoprazole on the absorption of other drugs: 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).
Anti-HIV drugs (atazanavir). Co-administration of CCI with atazanavir and other anti-HIV drugs whose adsorption is pH-dependent may result in a significant reduction in the bioavailability of the latter and affect their efficacy. Therefore, co-administration of CCI with atazanavir is not recommended.
Coumarin anticoagulants (phenprocoumon and warfarin). Despite the lack of interaction, isolated cases of changes in the international normalized ratio (INR) have been reported with concomitant administration of phenprocoumon and warfarin. Therefore, in patients taking coumarin anticoagulants (e.g. phenprocoumon and warfarin), it is recommended to monitor prothrombin time/INR after starting and stopping treatment or when taking pantoprazole irregularly.
Other interactions. Pantoprazole is extensively metabolized in the liver via the cytochrome P450 enzyme system. The main metabolic pathway is demethylation by CYP2C19 and other metabolic pathways, including oxidation by CYP3A4. Studies with drugs also metabolized by these pathways, such as carbamazepine, diazepam, glibenclamide, nifedipine, phenprocoumon, and oral contraceptives containing levonorgestrel and ethinylestradiol, have not revealed clinically significant interactions.
It was found that pantoprazole does not affect the metabolism of active substances metabolized by CYP1A2 (such as caffeine, theophylline), CYP2C9 (such as piroxicam, diclofenac, naproxen), CYP2D6 (such as metoprolol), CYP2E1 (such as ethanol), and does not affect p-glycoprotein, which ensures the absorption of digoxin.
No interactions with concomitantly administered antacids were identified.
It has been reported that when pantoprazole was administered concomitantly with certain antibiotics (clarithromycin, metronidazole, amoxicillin), no clinically significant interactions between these drugs were observed.
Methotrexate. Concomitant use of CCI with methotrexate (mainly at high doses) may increase and prolong serum levels of methotrexate and/or its hydromethotrexate metabolite, which may cause toxicity.
Application features.
Alarming symptoms present. In the presence of alarming symptoms (e.g. significant weight loss, recurrent vomiting, dysphagia, haematemesis, anaemia, melena) and in the presence or suspicion of gastric ulcer, malignancy should be excluded, as treatment with pantoprazole may mask the symptoms of malignant ulcer and delay diagnosis. If symptoms persist despite continued adequate treatment, further investigation is necessary.
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.
Gastrointestinal infections caused by bacteria. Pantoprazole, like other proton pump inhibitors, may increase the number of bacteria normally present in the upper digestive tract. Treatment with the drug may slightly increase the risk of gastrointestinal infections caused by bacteria such as Salmonella and Campylobacter.
This medicine contains less than 1 mmol sodium (23 mg) per vial.
Hypomagnesemia. Severe hypomagnesemia has been reported in patients taking CCIs such as pantoprazole for at least 3 months, and in most cases for a year. Serious manifestations of hypomagnesemia, such as fatigue, tetany, delirium, seizures, dizziness, and ventricular arrhythmias, may have an insidious onset and may be missed. In most cases, patients improve after magnesium replacement therapy and discontinuation of CCI treatment.
For patients planning long-term therapy or taking CCIs in combination with digoxin or drugs that can cause hypomagnesemia (e.g., diuretics), it is recommended that magnesium levels be measured before starting CCI treatment and periodically during therapy.
Bone fractures. Proton pump inhibitors, especially when used in high doses and for long periods (more than 1 year), may somewhat increase the risk of hip, wrist, and spine fractures, mainly in elderly patients or in those with other existing risk factors. Studies have shown that PPIs may increase the overall risk of fractures by 10-40%. Some of these may be due to other risk factors. Patients at risk of osteoporosis should receive treatment according to current clinical guidelines and adequate vitamin D and calcium intake.
Use during pregnancy or breastfeeding.
Pregnancy.
Experience with the drug in pregnant women is limited. The potential risk to humans is unknown. The drug should be used during pregnancy only if clearly needed.
Breastfeeding.
There are data on the excretion of pantoprazole in breast milk. The decision to use the drug during breastfeeding should be made after a careful benefit/risk assessment.
The ability to influence the reaction speed when driving vehicles or other mechanisms.
It is necessary to take into account the possible development of adverse reactions, such as dizziness and visual disturbances. In such cases, you should not drive or operate other mechanisms.
Method of administration and doses.
The drug is used by adults as prescribed and under the direct supervision of a physician. Intravenous administration of the drug is recommended only if the oral form of pantoprazole cannot be used. There is data on the duration of intravenous treatment up to 7 days. Therefore, if clinically possible, a transition from intravenous administration of pantoprazole to oral is carried out.
Reflux esophagitis, duodenal ulcer, gastric ulcer.
The recommended dose is 40 mg of pantoprazole (1 vial) per day intravenously.
Treatment of Zollinger-Ellison syndrome and other hypersecretory pathological conditions.
For long-term treatment of Zollinger-Ellison syndrome and other hypersecretory pathological conditions, the recommended starting dose of pantoprazole is 80 mg per day. If necessary, the dose can be titrated up or down, depending on the indicators of acid secretion in the stomach. Doses exceeding 80 mg per day should be divided into two administrations. A temporary increase in the dose of pantoprazole to more than 160 mg is possible, but the duration of use should be limited only to the period necessary for adequate control of acid secretion.
If rapid reduction of acidity is required, an initial dose of 2 * 80 mg is sufficient for most patients to achieve the desired level (
Preparation for use.
The powder is dissolved in 10 ml of 0.9% sodium chloride solution, which is added to the vial. The solution can be administered directly or after mixing with 100 ml of 0.9% sodium chloride solution or 5% glucose solution in plastic or glass vials.
After dilution, chemical and physical stability of the product has been demonstrated for 12 hours at 25 °C. From a microbiological point of view, the diluted product should be used immediately.
Pantoprazole should not be prepared or mixed with solvents other than those specified above. Intravenous administration of the drug should be carried out over 2-15 minutes.
The vial is for single use only. Before use, the vials with the drug should be visually inspected (in particular, for discoloration, the presence of sediment). The diluted solution should be clear and yellowish in color.
Hepatic impairment: Patients with severe hepatic impairment should not exceed a daily dose of 20 mg (A vial of pantoprazole, 40 mg powder).
Renal insufficiency: Patients with impaired renal function do not require dose adjustment.
Elderly patients do not require dose adjustment.
Children.
The safety and effectiveness of pantoprazole in children have not been established, so the drug should not be used in patients under 18 years of age.
Overdose.
Symptoms of overdose are unknown.
In case of overdose with signs of intoxication, general detoxification measures are carried out.
Adverse reactions.
On the part of the blood: agranulocytosis, leukopenia, thrombocytopenia, pancytopenia.
Immune system disorders: hypersensitivity reactions (including anaphylactic reactions, anaphylactic shock).
Metabolic: hyperlipidemia and increased lipid levels (triglycerides, cholesterol), changes in body weight, hyponatremia, hypomagnesemia.
Psychiatric: sleep disorders, depression (with complications), disorientation (with complications), hallucinations, confusion (especially in patients with a predisposition to these disorders, as well as exacerbation of these symptoms if present).
From the nervous system: headache, dizziness, taste disturbance.
On the part of the organs of vision: visual impairment, blurred vision.
Gastrointestinal tract: diarrhea, nausea, vomiting, bloating, constipation, dry mouth, abdominal pain and discomfort.
On the part of the hepatobiliary system: increased levels of liver enzymes (transaminases, γ-GT), increased levels of bilirubin, hepatocyte damage, jaundice, hepatocellular insufficiency.
Skin: skin rashes, exanthema, itching, urticaria, angioedema, Stevens-Johnson syndrome, Lyell's syndrome, erythema multiforme, photosensitivity.
Musculoskeletal system: fractures of the hip, wrist and spine, arthralgia, myalgia.
From the urinary system: interstitial nephritis.
From the reproductive system: gynecomastia.
General disorders and administration site conditions: thrombophlebitis at the injection site, asthenia, fatigue, malaise, fever, peripheral edema.
Expiration date.
2 years.
Storage conditions.
Store in the original packaging at a temperature not exceeding 25 °C.
Keep out of reach of children.
Incompatibility.
Pantoprazole sodium is incompatible with acidic solutions.
Pantoprazole should not be prepared or mixed with other solutions other than those listed in the "Method of administration and dosage" section.
Packaging
40 mg in a vial, 1 vial in a cardboard pack or 5 vials in a blister, 1 contour cell pack in a cardboard pack.
Vacation category.
According to the recipe.
Producer.
"Pharmex Group" LLC.
Location of production and its address of place of business.
Ukraine, 08300, Kyiv region, Boryspil city, Shevchenko st., 100.
Last viewed date.
All cases of adverse reactions must be reported to the manufacturer:
LLC "PHARMEX GROUP", Ukraine, 08300, Kyiv region, Boryspil city, Shevchenko st., 100, tel. +38 (044) 391-19-19, fax: +38 (044) 391-19-18 or via the form on the website:
http: www.pharmex.com.ua/kontakty/farmakonadzor
