Instructions for Pelta powder for solution for injection 40 mg vial No. 1
Composition
active ingredient: pantoprazole;
1 vial contains 45.12 mg of pantoprazole sodium sesquihydrate, equivalent to 40 mg of pantoprazole;
excipients: mannitol (E 421), sodium citrate, sodium hydroxide.
Dosage form
Powder for solution for injection.
Main physicochemical properties: white or almost white lyophilized powder.
The diluted solution is a clear solution from colorless to yellowish.
Pharmacotherapeutic group
Drugs for the treatment of acid-dependent diseases. Proton pump inhibitors. Pantoprazole. ATC code A02B C02.
Pharmacological properties
Pharmacodynamics.
Mechanism of action: Pantoprazole is a substituted benzimidazole that inhibits gastric acid secretion by specific blockade of the proton pumps of parietal cells.
Pantoprazole is transformed into the 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 hydrochloric acid production in the stomach. Inhibition is dose-dependent and affects both basal and stimulated acid secretion. In most patients, symptoms disappear within 2 weeks. The use of pantoprazole, like other proton pump inhibitors (PPIs) and H2-receptor inhibitors, reduces acidity in the stomach and, thus, increases gastrin secretion in proportion to the decrease in acidity. The increase in gastrin secretion is reversible. Since pantoprazole binds the enzyme outside the cellular receptor, it can inhibit hydrochloric acid secretion regardless of stimulation by other substances (acetylcholine, histamine, gastrin). The effect is the same with oral and intravenous administration of the drug.
Pantoprazole increases fasting gastrin levels. In short-term use, it does not exceed the upper limit of normal in most cases. In long-term treatment, gastrin levels are doubled in most cases. Excessive increases occur only in isolated cases. As a result, a slight to moderate increase in specific endocrine (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, which have been identified in animal studies, has not been observed in humans.
Based on the results of animal studies, an effect of long-term (more than one year) treatment with pantoprazole on endocrine parameters of the thyroid gland cannot be completely 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 PPI 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.
The pharmacokinetic properties do not change after single or repeated administration of the drug. In the dose range from 10 to 80 mg, the pharmacokinetics of pantoprazole in blood plasma remain linear both after oral and intravenous administration.
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 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.
Elimination: The terminal half-life is approximately 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 part of the metabolites of pantoprazole is excreted in the urine (approximately 80%), the rest 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 (approximately 1.5 hours) is slightly longer than that of pantoprazole.
Special patient groups
Renal impairment. There are no recommendations for dose reduction when prescribing pantoprazole to patients with reduced 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 dialysable. Although the main metabolite has a moderately long half-life (2-3 hours), elimination is still rapid, so accumulation does not occur.
Hepatic impairment: Although in patients with cirrhosis (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 (Cmax) increases only slightly – 1.5-fold – compared to that in healthy volunteers.
Elderly patients: The slight increase in AUC and Cmax in elderly volunteers compared to younger volunteers is also not clinically relevant.
Children: After single intravenous administration of pantoprazole at doses of 0.8 or 1.6 mg/kg 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.
Indication
- Reflux esophagitis.
- Stomach and duodenal ulcer.
- Zollinger-Ellison syndrome and other hypersecretory pathological conditions.
Contraindication
Hypersensitivity to the active substance, benzimidazole derivatives or to any component of the drug.
Interaction with other medicinal products and other types of interactions
Medicinal products whose absorption is pH-dependent: Due to the complete and long-term inhibition of hydrochloric acid secretion, pantoprazole may affect the absorption of medicinal products for which the pH of the gastric juice is an important factor in their bioavailability (e.g. some antifungals such as ketoconazole, itraconazole, posaconazole, or other medicinal products such as erlotinib).
HIV protease inhibitors: Concomitant use of pantoprazole with HIV protease inhibitors (such as atazanavir) whose absorption is dependent on intragastric pH is not recommended due to a significant reduction in their bioavailability (see section 4.4).
If concomitant use of HIV protease inhibitors with PPIs cannot be avoided, close clinical monitoring (e.g. viral load) is recommended. The daily dose of pantoprazole should not exceed 20 mg. Dose adjustment of HIV protease inhibitors may be necessary.
Coumarin anticoagulants (phenprocoumon and warfarin).
Concomitant use of pantoprazole with warfarin or phenprocoumon did not affect the pharmacokinetics of warfarin, phenprocoumon or the international normalized ratio (INR). However, increases in INR and prolongation of prothrombin time have been reported in patients receiving concomitant PPIs and warfarin or phenprocoumon. Increases in INR and prolongation of prothrombin time may lead to pathological bleeding and even fatal outcome. In such concomitant use, monitoring of INR and prothrombin time is necessary.
Methotrexate: Concomitant use of high doses of methotrexate (e.g. 300 mg) and PPIs has been reported to increase methotrexate blood levels in some patients. Patients receiving high doses of methotrexate, e.g. patients with cancer or psoriasis, are advised to temporarily discontinue pantoprazole treatment.
Other interactions. Pantoprazole is extensively metabolised in the liver via the cytochrome P450 enzyme system. The main metabolic pathway is demethylation by CYP2C19, other metabolic pathways include oxidation by CYP3A4. Studies with medicinal products also metabolised by these pathways, such as carbamazepine, diazepam, glibenclamide, nifedipine and oral contraceptives containing levonorgestrel and ethinylestradiol, have not revealed any clinically significant interactions.
Interactions of pantoprazole with other drugs that are metabolized through the same enzyme system cannot be excluded.
The results of a number of studies on possible interactions indicate that pantoprazole does not affect the metabolism of active substances metabolized by CYP1A2 (e.g. caffeine, theophylline), CYP2C9 (e.g. piroxicam, diclofenac, naproxen), CYP2D6 (e.g. metoprolol), CYP2E1 (e.g. ethanol), and does not affect p-glycoprotein, which is associated with the absorption of digoxin.
No interactions with concomitantly administered antacids were identified.
Studies of the interaction of pantoprazole with certain antibiotics (clarithromycin, metronidazole, amoxicillin) administered concomitantly have also been conducted. No clinically significant interactions between these drugs have been identified.
Medicinal products that inhibit or induce CYP2C19. CYP2C19 inhibitors, such as fluvoxamine, may increase the systemic exposure of pantoprazole. A dose reduction should be considered in patients receiving long-term treatment with high doses of pantoprazole and in patients with impaired liver function. Inducers of enzymes that affect CYP2C19 and CYP3A4, such as rifampicin and St. John's wort (Hypericum perforatum), may reduce plasma concentrations of PPIs that are metabolised by these enzyme systems.
Application features
Gastric malignancies. Symptomatic response to pantoprazole may mask the symptoms of gastric malignancies and delay their diagnosis. In the presence of alarming symptoms (e.g. significant weight loss, recurrent vomiting, dysphagia, haematemesis, anaemia, melena), as well as in the presence or suspicion of gastric ulcer, malignancy should be excluded.
If symptoms persist despite adequate treatment, further examination is necessary.
Hepatic impairment: Patients with severe hepatic impairment should have their liver enzymes monitored regularly. If liver enzymes increase, treatment with the drug should be discontinued (see section 4.2).
HIV protease inhibitors: Concomitant use of pantoprazole with HIV protease inhibitors (such as atazanavir) whose absorption is dependent on intragastric pH is not recommended due to a significant reduction in their bioavailability (see section 4.5).
Gastrointestinal infections caused by bacteria. Treatment with Pelta may slightly increase the risk of developing gastrointestinal infections caused by bacteria such as Salmonella and Campylobacter or C. Difficile.
Sodium: This medicinal product contains less than 1 mmol (23 mg) sodium per vial, i.e. essentially ‘sodium-free’.
Hypomagnesemia: Rare cases of severe hypomagnesemia have been reported in patients taking 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 insidiously and remain undetected: fatigue, tetany, delirium, convulsions, dizziness and ventricular arrhythmias. Hypomagnesemia may lead to hypocalcemia and/or hypokalemia (see section 4.8). In the case of hypomagnesemia (and hypocalcemia associated with 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 concomitantly with digoxin or drugs that may cause hypomagnesemia (e.g., diuretics) should have their magnesium levels measured before starting PPI treatment and periodically during treatment.
Bone fractures: Long-term treatment (more than 1 year) with high doses of PPIs may modestly increase the risk of hip, wrist, and spine fractures, mainly in elderly patients or in those with other risk factors.
Observational studies suggest that PPI use 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 be treated according to current clinical guidelines and consume adequate amounts of vitamin D and calcium.
Subacute cutaneous lupus erythematosus. The use of PPIs has been associated with very rare cases of subacute cutaneous lupus erythematosus. If lesions occur, especially in areas exposed to sunlight, and are accompanied by arthralgia, the patient should immediately consult a doctor who will consider discontinuing Pelta. The occurrence of subacute cutaneous lupus erythematosus in patients on previous PPI therapy may increase the risk of its development with other PPIs.
Impact on laboratory test results
Elevated CgA levels may interfere with the results of diagnostic tests for neuroendocrine tumors. To avoid this interference, treatment with Pelta should be temporarily discontinued for at least 5 days prior to CgA assessment (see section 5.1). If CgA and gastrin levels have not returned to the normal range after initial measurement, repeat measurements should be performed 14 days after discontinuation of PPI treatment.
Use during pregnancy or breastfeeding
Pregnancy: Available data on the use of pantoprazole in pregnant women (approximately 300-1000 pregnancy outcomes) indicate no embryonal or foeto/neonatal toxicity. Reproductive toxicity has been observed in animal studies. As a precautionary measure, the use of Peltava in pregnant women should be avoided.
Breast-feeding. Animal studies have shown excretion of pantoprazole in breast milk. There is insufficient information on the excretion of pantoprazole in human milk, but such excretion has been reported. A risk to the newborn/infants cannot be excluded. A decision on whether to discontinue breast-feeding or to discontinue/abstain from Pelta therapy should be made taking into account the benefit of breast-feeding for the child and the benefit of Pelta therapy for the woman.
Fertility: Pantoprazole did not impair fertility in animal studies.
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.
Method of administration and doses
The drug is used as prescribed by a doctor and under proper medical supervision.
Intravenous administration of the drug is recommended only if oral administration is not possible. There are data on the duration of intravenous treatment up to 7 days. Therefore, as soon as oral administration of pantoprazole becomes possible, a transition from intravenous administration of Pelta to oral administration of pantoprazole at a dose of 40 mg is made.
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 initial dose of Pelta 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 (<10 mEq/h) within 1 hour.
Preparation for use
The powder is dissolved in 10 ml of 0.9% sodium chloride solution, which is added to the vial. The resulting solution can be administered directly or after mixing it with 100 ml of 0.9% sodium chloride solution or 5% glucose solution in plastic or glass vials.
After dilution, chemical and physical in-use stability has been demonstrated for 12 hours at 25°C. From a microbiological safety perspective, the diluted product should be used immediately.
Pelta medicinal product 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. Any unused product or any product that has changed in physical or chemical properties (e.g., color, precipitate) should be disposed of in accordance with local regulations.
The diluted solution should be clear to colorless to yellowish.
Hepatic impairment: Patients with severe hepatic impairment should not exceed a daily dose of 20 mg (½ vial of Pelta, powder for solution for injection 40 mg) (see section 4.4).
Renal impairment: Patients with impaired renal function do not require dose adjustment.
Elderly patients do not require dose adjustment.
Children.
Pelta, powder for solution for injection, is not recommended for use in children (under 18 years of age) as data on safety and efficacy in this age group are limited. Currently available data are described in the Pharmacokinetics section, but no dosage recommendation can be made.
Overdose
Symptoms of overdose are unknown.
Doses up to 240 mg administered intravenously over 2 minutes have been well tolerated. Since pantoprazole is extensively protein bound, it is not readily dialyzable.
In case of overdose with clinical signs of intoxication, symptomatic and supportive therapy is used. There are no specific therapy recommendations.
Side effects
Adverse reactions can be expected to occur in approximately 5% of patients. The most common adverse reaction is thrombophlebitis at the injection site. Diarrhea and headache occurred in approximately 1% of patients.
Adverse reactions are classified according to the frequency of occurrence into the following categories: very common (≥1/10), common (≥1/100 and <1/10), uncommon (≥1/1000 and <1/100), rare (≥1/10000 and <1/1000), very rare (<1/10000), frequency unknown (frequency cannot be estimated from the available data).
For all adverse reactions reported during the post-marketing period, it is not possible to determine the frequency and are therefore listed as “frequency not known”.
Within each frequency category, adverse reactions are presented in order of decreasing seriousness.
Blood and lymphatic system disorders
Rare: agranulocytosis.
Very rare: leukopenia, thrombocytopenia, pancytopenia.
On the part of 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.
Frequency not known: hyponatremia, hypomagnesemia (see section "Special warnings and precautions for use"), hypocalcemia1, hypokalemia1.
Mental disorders
Uncommon: sleep disorders.
Rare: depression (including exacerbation).
Frequency unknown: hallucinations, confusion (especially in patients with a predisposition to such disorders, as well as exacerbation of these symptoms if they pre-exist).
From the nervous system
Uncommon: headache, dizziness.
Rare: taste disorders.
Frequency unknown: paresthesia.
From the organs of vision
Rare: visual disturbances/blurred vision.
From the digestive tract
Common: fundic gland polyps (benign).
Uncommon: diarrhea, nausea, vomiting, flatulence, constipation, dry mouth, abdominal pain and discomfort.
Frequency unknown: microscopic colitis.
Hepatobiliary system
Uncommon: increased liver enzymes (transaminases, g-GT).
Rare: increased bilirubin levels.
Frequency unknown: hepatocyte damage, jaundice, hepatocellular failure.
Skin and subcutaneous tissue disorders
Uncommon: skin rash, exanthema, pruritus.
Rare: urticaria, angioedema.
Frequency unknown: Stevens-Johnson syndrome, Lyell syndrome, erythema multiforme, photosensitivity, drug reaction with eosinophilia and systemic symptoms (DRESS), subacute cutaneous lupus erythematosus (see section "Special warnings and precautions for use").
Musculoskeletal and connective tissue disorders
Uncommon: fractures of the hip, wrist, spine (see section "Special warnings and precautions for use").
Rare: arthralgia, myalgia.
Frequency not known: muscle spasm2.
Renal and urinary disorders
Frequency unknown: interstitial nephritis (with possible development of renal failure).
Reproductive system and breast disorders
Rare: gynecomastia.
General disorders
Common: thrombophlebitis at the injection site.
Uncommon: asthenia, fatigue, malaise.
Rare: fever, peripheral edema.
1 Hypocalcemia and/or hypokalemia may be associated with the occurrence of hypomagnesemia (see section "Special warnings and precautions for use").
2 Muscle spasm as a result of electrolyte imbalance.
Expiration date
2 years from the date of production in bulk.
After reconstitution, the medicinal product is suitable for use for 12 hours when stored at 25 ± 2 °C in an inverted vial.
Do not use the drug after the expiration date indicated on the package.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 ° C. Keep out of the reach of children.
Packaging
1 bottle per pack.
Vacation category
According to the recipe.
Producer
JSC "Farmak", Ukraine
(secondary packaging, production of a series of products in bulk from the manufacturer Demo SA Pharmaceutical Industry, Greece).
Location of the manufacturer and its business address.
Ukraine, 04080, Kyiv, Kyrylivska St., 74.
