Nolpaza, 20 mg 28 pcs.

Indications

For 20 mg dosage:

Adults and teenagers 12 years and older

– symptomatic gastroesophageal reflux disease

– for long-term treatment and prevention of relapses of reflux esophagitis.

For adults

– prevention of erosive and ulcerative lesions of the stomach and duodenum caused by taking non-selective non-steroidal anti-inflammatory drugs (NSAIDs) in patients at increased risk and requiring constant treatment with NSAIDs (See section “special instructions”)

For a dosage of 40 mg

Adults and teenagers 12 years and older

– reflux esophagitis

For adults

– eradication of Helicobacter pylori (H. pylori) in combination with appropriate antibacterial therapy in patients with peptic ulcer disease associated with H. pylori

-peptic ulcer of the stomach and duodenum

– Zollinger-Ellison syndrome and other pathological hypersecretory conditions

Pharmacological effect

Preparations for the treatment of diseases associated with acidity disorders. Antiulcer drugs and drugs for the treatment of gastroesophageal reflux. Proton pump inhibitors. Pantoprazole

ATX code A02BC02

Pharmacological properties

Pharmacokinetics

Pantoprazole is absorbed quickly, maximum concentrations (for a dosage of 20 mg: 1-1.5 mcg/ml, for a dosage of 40 mg: 2-3 mcg/ml) in the blood plasma are reached approximately 2-2.5 hours after taking the drug orally and remain constant after repeated doses. Absolute bioavailability is 77%, food intake does not affect AUC (area under the concentration-time curve), maximum serum concentrations and bioavailability. In the dose range from 10 mg to 80 mg, the kinetics of pantoprazole in blood plasma is linear.

98% of pantoprazole is bound to plasma proteins. The volume of distribution is approximately 0.15 l/kg.

Pantoprazole is almost completely metabolized in the liver. The terminal half-life is about 1 hour and the clearance is about 0.1 l/h/kg. In some cases, the elimination time may increase. Due to the specific binding of pantoprazole to the proton pump of parietal cells, the half-life does not correlate with the duration of the therapeutic effect (suppression of hydrochloric acid secretion).

The main route of excretion of pantoprazole metabolites (about 80%) is through the kidneys; the remainder is excreted in the feces. The main metabolite detected in plasma and urine, desmethylpantoprazole, is conjugated with sulfate, the half-life of which is only slightly longer (approximately 1.5 hours) than that of pantoprazole.

In patients with impaired renal function (including patients on dialysis), no dose reduction is required when using pantoprazole

In patients with liver cirrhosis (class A and B according to the Child classification), the half-life is longer (from 3 to 6 hours), the AUC is 3-5 times higher, and the maximum plasma concentration is 1.3 times higher, compared with healthy people.

In elderly patients – a slight increase in AUC and Cmax (not clinically significant).

Children

Following administration of a single oral dose of 20 or 40 mg pantoprazole in children aged 5 to 16 years, AUC and Cmax values ​​were within the range of those observed in adults.

Pharmacodynamics

Nolpaza® is a substituted benzimidazole that suppresses the secretion of hydrochloric acid in the stomach by specifically affecting the proton pumps of parietal cells.

Pantoprazole is converted to its active form in the acidic environment of parietal cells, where it inhibits the enzyme H+/K+ATPase and blocks the final stage of hydrochloric acid synthesis in the stomach. Inhibition is dose dependent and affects both basal and stimulated acid secretion. In gastric and duodenal ulcers associated with Helicobacter pylori, such a decrease in gastric secretion increases the sensitivity of the microorganism to antibiotics.

After oral administration of Nolpaza®, the antisecretory effect occurs within 1 hour and reaches a maximum after 2 to 4 hours. Does not affect gastrointestinal motility. Secretory activity returns to the original level 3 to 4 days after the end of administration.

In most patients, resolution of symptoms is achieved within

2 weeks. Like other proton pump inhibitors and H2 receptor inhibitors, pantoprazole therapy reduces gastric acidity and thus a reversible increase in gastrin. Pantoprazole can affect the secretion of hydrochloric acid regardless of stimulation by other substances (acetylcholine, histamine, gastrin).

Special instructions

Liver failure

In patients with severely impaired liver function, liver enzyme levels should be regularly monitored during treatment with pantoprazole, especially with long-term use. If liver enzyme levels increase, treatment should be discontinued.

Concomitant use of NSAIDs

The use of a dosage of 20 mg should be limited for the prevention of gastroduodenal ulcers in patients requiring long-term treatment with non-specific non-steroidal anti-inflammatory drugs (NSAIDs) and who are at increased risk of developing gastrointestinal complications.

The increased risk should be assessed according to individual risk factors, for example: older age (> 65 years), gastric or duodenal ulcer, or history of upper gastrointestinal bleeding.

Combined treatment

When combining therapy for H. pylori eradication, it is necessary to take into account a brief description of the relevant drugs.

If you have warning symptoms

If any alarming symptoms are present (eg, significant unintentional weight loss, repeated bouts of vomiting, dysphagia, haematemesis, anemia or melena), or if a gastric ulcer is present or suspected, malignancy should be excluded as pantoprazole may relieve symptoms and delay diagnosis. Before starting treatment, the possibility of malignancy should be excluded.

Combined treatment with atazanavir

Co-administration of atazanavir with proton pump inhibitors is contraindicated.

Effect on vitamin B12 absorption

Pantoprazole, like all drugs that block the production of hydrochloric acid, can reduce the absorption of vitamin B12 (cyanocobalamin) due to hypo- and achlorhydria. This should be taken into account during long-term therapy in patients with low body weight or with an increased risk of reduced absorption of vitamin B12 or if corresponding clinical symptoms are observed.

Long-term treatment

During long-term treatment, especially when treatment lasts more than 1 year, patients should be monitored regularly.

Gastrointestinal infections caused by bacteria

Pantoprazole, like all proton pump inhibitors, increases the number of bacteria normally present in the upper gastrointestinal tract. Treatment with Nolpaza® may lead to an increased risk of gastrointestinal infections caused by bacteria such as Salmonella and Campilobacter.

Hypomagnesemia

Cases of severe hypomagnesemia have been reported in patients treated with proton pump inhibitors (PPIs) such as pantoprazole for at least three months and, in most cases, for a year. Severe manifestations of hypomagnesemia, such as fatigue, tetany, delirium, seizures, dizziness, and ventricular arrhythmia, may occur, but may be silent and unnoticed. In most patients, hypomagnesemia resolves after replacement of magnesium deficiency and cessation of PPI treatment.

In patients undergoing long-term treatment or in patients taking PPIs concomitantly with digoxin or other drugs that may cause hypomagnesemia (eg, diuretics), magnesium levels should be measured before starting PPI treatment and periodically during treatment.

Fracture of femur, wrist and spine

The use of proton pump inhibitors, especially at high doses and for long periods of time (> 1 year), may slightly increase the risk of hip, wrist and spine fractures, especially in older age or in the presence of other recognized risk factors. Observational studies suggest that proton pump inhibitors may increase the overall risk of fractures by 10% to 40%. Some of this increase may be due to other risk factors. Patients at risk of developing osteoporosis should receive care in accordance with current clinical guidelines and should take adequate vitamin D and calcium.

Excipients

Nolpaza® contains sorbitol. Patients with rare hereditary problems of fructose intolerance should not take this medicine.

Use in pediatrics

Due to insufficient data on safety and effectiveness, the use of pantoprazole in children under 12 years of age for reflux esophagitis, symptomatic gastroesophageal reflux disease, is not recommended.

There are no data on the use of pantoprazole in children and adolescents under 18 years of age for gastric and duodenal ulcers, eradication of Helicobacter pylori, Zollinger-Ellison syndrome, for the prevention of erosive and ulcerative lesions of the stomach and duodenum caused by non-selective NSAIDs.

Pregnancy and lactation

Animal studies indicate reproductive toxicity of pantoprazole.

Nolpaza® should not be used during pregnancy unless necessary.

Pantoprazole is excreted into breast milk. During treatment with the drug, breastfeeding should be stopped.

Features of the effect of the drug on the ability to drive a vehicle or potentially dangerous mechanisms

During treatment, adverse side effects such as dizziness and visual disturbances may occur. In such cases, patients should not drive vehicles or operate machinery.

Active ingredient

Pantoprazole

Composition

One tablet contains

active substance – pantoprazole sodium sesquihydrate 22.55 mg or 45.10 mg

(equivalent to pantoprazole 20 mg or 40 mg, respectively),

excipients: mannitol, crospovidone (type B), anhydrous sodium carbonate, sorbitol (E420), calcium stearate,

enteric coating composition: hypromellose (2.4-3.6 mPas), povidone (K25), titanium dioxide (E171), iron oxide yellow (E172), propylene glycol, *methacrylic acid-ethyl acrylate copolymer (1:1) 30% dispersion, macrogol 6000, talc

* 30% dispersion, in addition to methacrylic acid – ethyl acrylate copolymer and water, contains sodium lauryl sulfate (0.7% in terms of solid matter in the dispersion) and polysorbate 80 (2.3% in terms of solid matter in the dispersion) as emulsifiers

Contraindications

– hypersensitivity to pantoprazole, substituted benzimidazoles

or auxiliary components of the drug

– combined use with atazanavir

Side Effects

Uncommon (≥ 1/1,000 to < 1/100)

sleep disorders

headache, dizziness

diarrhea, nausea, vomiting, bloating and flatulence, constipation, dryness

in the mouth, abdominal pain, discomfort

increased levels of liver enzymes (transaminases, γ-GT)

rash, exanthema, skin rash, itching

fractures of the spine, hip and wrist

asthenia, malaise and fatigue

Rare (≥ 1/10,000 to < 1/1,000)

agranulocytosis

hypersensitivity reactions (including anaphylactic reactions

and anaphylactic shock)

hyperlipidemia, increased levels of triglycerides, cholesterol, changes

body weight, taste disturbance

depression (and all exacerbations)

visual disturbances, blurred vision

increased bilirubin levels

urticaria, Quincke’s edema

arthralgia, myalgia

gynecomastia

increased body temperature, peripheral edema

Very rare (< 1/10,000)

thrombocytopenia, leukopenia

disorientation (and all accompanying exacerbations)

Unknown (cannot be estimated based on available data):

hyponatremia, hypomagnesemia

hallucinations, confusion (especially in genetically

predisposed patients, as well as exacerbation of these symptoms if

they existed before the start of treatment)

hepatocellular damage, jaundice, hepatocellular failure

Stevens-Johnson syndrome, Lyell’s syndrome, erythema multiforme, photosensitivity

interstitial nephritis

Interaction

Due to its profound and long-lasting inhibition of gastric acid secretion, pantoprazole may reduce the absorption of drugs whose bioavailability depends on gastric pH, such as some azole antifungals such as ketoconazole, itraconazole, posaconazole and other drugs such as erlotinib.

Concomitant use of atazanavir and other HIV drugs whose absorption is pH dependent with proton pump inhibitors may result in a significant reduction in the bioavailability of the HIV drugs and may reduce the effectiveness of these drugs. Concomitant therapy of proton pump inhibitors with atazanavir is contraindicated.

In patients taking coumarin anticoagulants (eg, phenprocoumon or warfarin), it is recommended that prothrombin time/INR be monitored at the start of treatment, at the end of treatment, or during intermittent use of pantoprazole.

Carbamazepine, diazepam, glibenclamide, nifedipine and oral contraceptives containing levonorgestrel and ethinyl estradiol, which have the same metabolic pathway as pantoprazole, have not shown clinically significant interactions when used concomitantly.

Pantoprazole does not affect active substances metabolized by CYP1A2 (such as caffeine, theophylline), CYP2C9 (such as piroxicam, diclofenac, naproxen), CYP2D6 (such as metoprolol), CYP2E1 (such as ethanol) or does not participate in p-glycoprotein-bound digoxin absorption.

Pantoprazole does not interact with antacids when used simultaneously.

Co-administration of pantoprazole with antibiotics such as clarithromycin, metronidazole, amoxicillin does not cause clinically significant interactions.

Overdose

Symptoms: increased side effects.
Treatment: symptomatic, it is necessary to carry out regular detoxification measures.

Storage conditions

Store in the original packaging, at a temperature not exceeding 30 ºС, in a place protected from moisture. Store out of the reach of children!

Shelf life

5 years
Do not use after expiration date.

Manufacturer

KRKA dd Novo Mesto, Slovenia