Control
Proton pump inhibitor (H+-K+-ATPase). Blocks the final stage of hydrochloric acid secretion, reducing basal and stimulated secretion, regardless of the nature of the stimulus.
Antisecretory activity. After oral administration of the drug Controloc® at a dose of 20 mg, a decrease in gastric juice secretion by 24% occurs after 2.5-3.5 hours and by 26% after 24.5-25.5 hours. After administration once a day for 7 days, antisecretory activity increases to 56% after 2.5-3.5 hours and up to 50% after 24.5-25.5 hours.
In case of duodenal ulcer associated with Helicobacter pylori, a decrease in gastric secretion increases the sensitivity of microorganisms to antibiotics. Does not affect gastrointestinal motility. Secretory activity normalizes 3-4 days after the end of use.
Compared to other proton pump inhibitors, Controloc® has greater chemical stability at neutral pH and a lower potential for interaction with the liver oxidase system, which is dependent on cytochrome P450. Therefore, no clinically significant interactions have been observed between Controloc® and many other drugs.
Pharmacokinetics
Pharmacokinetics are the same after both single and repeated use of the drug.
Suction
Pantoprazole is rapidly absorbed after oral administration. Cmax in blood plasma when administered orally is achieved after the first dose of 20 mg or 40 mg. On average, Cmax is 1.0-1.5 mcg/ml and is achieved after 2-2.5 hours at a dose of 20 mg and 2.0-3.0 mcg/ml after 2.5 hours at a dose of 40 mg. This indicator remains constant after repeated use of this drug. The absolute bioavailability of pantoprazole tablets is 77%. Concomitant use of pantoprazole tablets with food does not affect AUC and Cmax.
Distribution
The binding of pantoprazole to plasma proteins is 98%. Vd is 0.15 l/kg.
Metabolism
Metabolized in the liver. The main metabolite in blood plasma and urine is desmethylpantoprazole, which is conjugated with sulfate.
Removal
T1/2 of the drug - 1 hour. Clearance - 0.1 l/h/kg. The main route of excretion is through the kidneys (about 80%) in the form of pantoprazole metabolites; a small amount is excreted through the intestines.
Pharmacokinetics in special clinical situations
When using pantoprazole in patients with limited renal function (including patients on hemodialysis), no dose reduction is required. As in healthy patients, T1/2 of pantoprazole is short. Only a very small portion of the drug is dialyzed. There is no cumulation.
In patients with liver cirrhosis (classes A, B and C according to the Child-Pugh classification), the T1/2 value increases to 3-6 hours at a dose of 20 mg and to 7-9 hours at a dose of 40 mg. The AUC increases by 3-5 times (for a dose of 20 mg) and 5-7 times (for a dose of 40 mg).
Cmax increases by 1.3 times (for a dose of 20 mg) and 1.5 times (for a dose of 40 mg) compared to healthy patients.
The slight increase in AUC and Cmax in the elderly is not clinically significant.
Controloc®
Before starting treatment with Controloc®, the possibility of malignancy should be excluded, since the drug may mask symptoms and delay the correct diagnosis.
Patients should consult their physician if they are undergoing an endoscopy or urea breath test.
Patients should consult a doctor if the following occur:
- unintentional weight loss, anemia, gastrointestinal bleeding, difficulty swallowing, persistent vomiting or vomiting blood. In these cases, taking the drug may partially relieve symptoms and delay correct diagnosis;
- previous surgery on the gastrointestinal tract or gastric ulcer;
- continuous symptomatic treatment of dyspepsia and heartburn for 4 weeks or more;
- liver diseases, including jaundice and liver failure;
- other serious diseases that worsen general health.
Patients over the age of 55 who have new or recently changed symptoms should consult a doctor.
When taking drugs that reduce the acidity of gastric juice, the risk of gastrointestinal infections caused by bacteria of the genus Salmonella spp., Campylobacter spp. slightly increases. or C. difficile.
In patients with Zollinger-Ellison syndrome and other pathological hypersecretory conditions who require long-term treatment, pantoprazole, like other drugs that block gastric acid secretion, may reduce the absorption of vitamin B12 (cyanocobalamin) due to hypo- and achlorhydria. This should be taken into account when treating patients with reduced reserves of this vitamin in the body, or during long-term treatment of patients with risk factors for developing vitamin B12 deficiency, as well as when observing corresponding clinical symptoms.
Long-term therapy, especially lasting more than 1 year, requires regular monitoring of patients.
Pantoprazole is not recommended for use with HIV protease inhibitors, the absorption of which depends on gastric pH (for example, atazanovir), due to a significant decrease in their bioavailability.
There are reports of the development of severe hypomagnesemia in patients receiving PPIs for at least 3 months, and in most cases for a year. Serious manifestations of hypomagnesemia, such as fatigue, tetany, delirium, convulsions, dizziness and ventricular arrhythmia, may occur, but hypomagnesemia may develop unnoticed and not be recognized in a timely manner. In most patients with hypomagnesemia, it decreases after magnesium replacement therapy and discontinuation of PPIs.
In patients undergoing long-term treatment or in patients receiving PPIs concomitantly with digoxin or other drugs that can cause hypomagnesemia (eg, diuretics), serum magnesium levels should be tested before starting PPI treatment and periodically during treatment.
Proton pump inhibitors, especially when used in high doses and over a long period of time (>1 year), may moderately increase the risk of fractures of the femur, wrist and spine, mainly in older people or in the presence of other well-established risk factors. Observational studies indicate that proton pump inhibitors may increase the overall risk of fracture by 10-40%. Some of these fractures may be due to other risk factors. Patients at risk of osteoporosis should receive treatment in accordance with current clinical guidelines and adequate amounts of vitamin D and calcium.
When treated with proton pump inhibitors, the development of subacute cutaneous lupus erythematosus (SCLE) is very rarely observed. If skin lesions occur, especially in sun-exposed areas, or in the presence of concomitant arthralgia, the patient should seek immediate medical attention and a healthcare provider should evaluate the need to discontinue treatment with Controloc®. The occurrence of PCLE after previous treatment with a proton pump inhibitor may increase the risk of developing PCLE when treated with other proton pump inhibitors.
When conducting laboratory tests, it is necessary to take into account that increased levels of CgA in the blood serum may distort the results of diagnostic studies to identify neuroendocrine tumors. In this regard, the use of the drug Controloc® should be discontinued at least 5 days before testing the CgA content. If CgA and gastrin levels have not returned to normal values after the first determination, the study should be repeated 14 days after stopping the proton pump inhibitor.
When conducting laboratory tests, it is necessary to take into account that increased levels of CgA in the blood serum may distort the results of diagnostic studies to identify neuroendocrine tumors. In this regard, the use of the drug Controloc® should be discontinued at least 5 days before testing the CgA content. If CgA and gastrin levels have not returned to normal values after the first determination, the study should be repeated 14 days after stopping the proton pump inhibitor. The drug is intended for short-term use (up to 4 weeks).
With long-term use of the drug, additional risks may arise, and it is necessary to consult a doctor to prescribe the drug, followed by regular medical supervision.
The following additional risks are considered significant with long-term use of the drug.
Effect on the absorption of Vitamin B12
Pantonrazole, like all proton pump inhibitors, may reduce the absorption of vitamin B12 (cyanocobalamin) as a result of hypo- or achlorhydria. This should be taken into account in patients with reduced body reserves or risk factors for reduced absorption of vitamin B12 during long-term therapy or in the presence of corresponding clinical symptoms.
Effect on bone fractures
Proton pump inhibitors, especially at high doses and during long-term therapy (>1 year), may slightly increase the risk of hip, wrist, and spine fractures, primarily in older adults or those with other known risk factors. Observations have shown that proton pump inhibitors may increase the overall risk of fractures by 10 to 40%. This increase may be due in part to other risk factors.
Patients at risk of developing osteoporosis should be treated in accordance with current clinical guidelines and should have an adequate intake of vitamin D and calcium.
Hypomagnesemia
Patients taking proton pump inhibitors (PPIs), including pantoprazole, for at least three months and, in most cases, for a year, experienced severe hypomagnesemia. In this case, it is possible to develop serious manifestations of hypomagnesemia, such as fatigue, tetany, delirium, convulsions, dizziness and ventricular arrhythmia, they can begin unnoticed and be missed. In most patients with such disorders, hypomagnesemia was corrected after magnesium replacement therapy and discontinuation of PPIs.
In patients undergoing long-term treatment or patients taking PPIs concomitantly with digoxin or other drugs that may cause hypomagnesemia (eg, diuretics), serum magnesium levels should be tested before initiating PPI treatment and monitored periodically during treatment. .
Controloc, 1 piece, 40 mg, lyophilisate for the preparation of solution for intravenous administration
When taking the drug Controloc® in accordance with the indications and in recommended doses, side effects occur extremely rarely. The most common undesirable side reaction is thrombophlebitis at the injection site. Diarrhea and headache occur in approximately 1% of patients.
Below are data on undesirable side reactions depending on the frequency of their occurrence: very often (≥1/10); often (≥1/100 and <1/10); uncommon (≥1/1000 and <1/100); rare (≥1/10000 and <1/1000); very rare (<1/10000, including isolated cases); frequency unknown (cannot be estimated from available data).
From the circulatory and lymphatic system:
rarely - agranulocytosis; very rarely - thrombocytopenia, leukopenia, pancytopenia.
From the nervous system:
infrequently - headache, dizziness; rarely - dysgeusia.
From the side of the organ of vision:
rarely - blurred vision (blurred).
From the gastrointestinal tract:
uncommon - diarrhea, nausea/vomiting, bloating and flatulence, constipation, dry mouth, abdominal pain.
From the kidneys and urinary tract:
frequency unknown - interstitial nephritis.
For the skin and subcutaneous tissues:
uncommon - exanthema/rash, itching; rarely - urticaria, angioedema; frequency unknown - malignant exudative erythema (Stevens-Johnson syndrome), exudative erythema multiforme, toxic epidermal necrolysis, photosensitivity.
From the musculoskeletal system and connective tissue:
rarely - arthralgia, myalgia.
From the side of metabolism:
rarely - hyperlipidemia and increased concentration of lipids (triglycerides, cholesterol), changes in body weight; frequency unknown - hyponatremia, hypomagnesemia.
Common disorders:
often - thrombophlebitis at the injection site; infrequently - weakness, fatigue and malaise; rarely - increased body temperature, peripheral edema.
From the immune system:
rarely - hypersensitivity (including anaphylactic reactions and anaphylactic shock).
From the liver and biliary tract:
infrequently - increased activity of liver enzymes (AST, GGT); rarely - increased bilirubin levels; frequency unknown - hepatocellular damage, jaundice.
From the genital organs and breast:
rarely - gynecomastia.
From the mental side:
infrequently - sleep disturbance; rarely - depression (including exacerbation of existing disorders); very rarely - disorientation (including exacerbation of existing disorders); frequency unknown - hallucinations, confusion (especially in predisposed patients), as well as possible exacerbation of symptoms if they existed before the start of therapy.
