Pemozar

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT PEMOZAR (PEMOZAR)

Composition:

Active substance: esomeprazole;

One tablet contains magnesium esomeprazole (amorphous) equivalent to esomeprazole 20 mg or 40 mg;

Excipients: spherical sugar, hydroxypropylcellulose, crospovidone, povidone, polyethylene glycol 400, talc, hypromellose phthalate, diethyl phthalate, polyethylene glycol 6000, microcrystalline cellulose, sodium stearyl fumarate, polyethylene glycol 4000, Opadry 03B86651 brown (hydroxypropylmethylcellulose, titanium dioxide (E 171), polyethylene glycol 4000, talc, iron oxide red (E 172)).

Pharmaceutical form. Gastro-resistant tablets.

Main physicochemical properties:

20 mg: red-brown, oval, biconvex, film-coated tablets with "E5" embossed on one side and smooth on the other;

40 mg: red-brown, oval, biconvex, film-coated tablets with "E6" embossed on one side and smooth on the other.

Pharmacotherapeutic group. Drugs for treatment of peptic ulcer and gastroesophageal reflux disease. Proton pump inhibitors. ATC code A02BC05.

Pharmacological Properties.

Pharmacodynamics.

Esomeprazole is the S-isomer of omeprazole, which reduces gastric acid secretion through a specific mechanism of action. It is a specific inhibitor of the proton pump in the parietal cell. The R- and S-isomers of omeprazole have equivalent pharmacodynamic activity.

Esomeprazole is a weak base that accumulates and is converted into its active form in the highly acidic environment of the secretory canaliculi of the parietal cell, where it inhibits the H+K+-ATPase enzyme—the proton pump—and thereby suppresses both basal and stimulated acid secretion.

Effect on Gastric Acid Secretion

After oral administration of 20 mg and 40 mg of esomeprazole, the effect begins within one hour. After repeated administration of 20 mg esomeprazole once daily for 5 days, the mean peak acid output following pentagastrin stimulation is reduced by 90% when measured 6–7 hours after dosing on day 5.

After 5 days of treatment with 20 mg and 40 mg esomeprazole orally, gastric pH remained above 4 for an average of 13 and 17 hours, respectively, and for more than 24 hours in patients with symptomatic reflux esophagitis. The proportion of patients with gastric pH above 4 for 8, 12, and 16 hours after administration of 20 mg esomeprazole was 76%, 54%, and 24%, respectively. Corresponding proportions for 40 mg esomeprazole were 97%, 92%, and 56%.

When AUC was used as an indirect measure of plasma concentration, a relationship between acid secretion suppression and drug exposure was demonstrated.

Therapeutic Effects of Acid Secretion Inhibition

Treatment of reflux esophagitis with 40 mg esomeprazole was successful in approximately 70% of patients after 4 weeks of treatment and in 93% after 8 weeks of treatment.

Administration of 20 mg esomeprazole twice daily for 1 week in combination with appropriate antibiotics resulted in successful eradication of Helicobacter pylori in approximately 90% of patients. After this 1-week treatment, no further monotherapy with acid-suppressive agents was required for successful healing of ulcers and resolution of symptoms in uncomplicated duodenal ulcer.

Other Effects Related to Acid Secretion Inhibition

During treatment with acid-suppressive agents, plasma gastrin concentrations increase in response to reduced acid secretion.

An increase in ECL cell numbers may be related to elevated plasma gastrin levels, which has been observed in some patients during long-term treatment with esomeprazole.

There have been reports of several cases of increased occurrence of gastric foveolar hyperplasia with prolonged use of acid-suppressive agents. These findings are considered a physiological consequence of long-term acid suppression and are benign and reversible in nature.

Reduced gastric acid secretion resulting from the use of any proton pump inhibitor increases the number of bacteria normally present in the gastrointestinal tract within the stomach. Treatment with proton pump inhibitors may increase the risk of gastrointestinal infections caused by, for example, Salmonella or Campylobacter.

Pemozar was more effective than ranitidine in treating gastric ulcers in patients receiving NSAIDs (nonsteroidal anti-inflammatory drugs), including selective COX-2 inhibitors.

Pemozar was effective in preventing gastric and duodenal ulcers in patients receiving NSAIDs (in patients aged 60 years and/or with a history of ulcer), including COX-2 selective NSAIDs.

Pharmacokinetics.

Absorption

Esomeprazole is acid-labile and is administered orally in the form of granules with an enteric coating. Conversion to the R-isomer in vivo is negligible. Absorption of esomeprazole is rapid, with peak plasma concentrations reached approximately 1–2 hours after dosing. Absolute bioavailability is 64% after a single 40 mg dose and increases to 89% after repeated once-daily administration. For 20 mg esomeprazole, the corresponding values are 50% and 68%. Food intake slows and reduces esomeprazole absorption, but this does not affect the effect of esomeprazole on gastric acidity.

Distribution

The volume of distribution at steady state in healthy volunteers is 0.22 L/kg body weight. Esomeprazole is 97% bound to plasma proteins.

Metabolism
Esomeprazole is completely metabolized via the cytochrome P450 (CYP) system. The main part of esomeprazole metabolism is mediated by the polymorphic CYP2C19, responsible for formation of hydroxy- and desmethyl metabolites of esomeprazole. Another part is mediated by a second specific isoenzyme, CYP3A4, which is responsible for the formation of esomeprazole sulfone—the main metabolite in plasma.

Elimination

The parameters listed below primarily reflect the pharmacokinetics in individuals with functional CYP2C19 enzyme (extensive metabolizers).

Total plasma clearance is approximately 17 L/h after a single dose and about 9 L/h after repeated administration. The elimination half-life in plasma is approximately 1.3 hours after repeated once-daily dosing. Esomeprazole is completely eliminated from plasma between doses, with no tendency for accumulation when administered once daily.

The main metabolites of esomeprazole do not affect gastric acid secretion. Approximately 80% of an oral dose of esomeprazole is excreted in urine as metabolites, the remainder in feces. Less than 1% of the original drug substance is found in urine.

Linearity/Non-linearity

The pharmacokinetics of esomeprazole have been studied at doses up to 40 mg twice daily. The area under the plasma concentration-time curve increases with repeated dosing. This increase is dose-dependent and results in greater-than-dose-proportional increases in AUC after repeated administration. This time- and dose-dependency is explained by reduced first-pass metabolism and systemic clearance, related to inhibition of the CYP2C19 enzyme by esomeprazole and/or its sulfone metabolite.

Special Patient Populations

Poor Metabolizers

Approximately 2.9±1.5% of the patient population has deficiency of the CYP2C19 enzyme (referred to as poor metabolizers). In these individuals, esomeprazole metabolism is primarily mediated by CYP3A4. After repeated once-daily administration of 40 mg esomeprazole, the mean area under the plasma concentration-time curve in poor metabolizers is approximately 100% higher than in individuals with normal CYP2C19 function (extensive metabolizers). The mean peak plasma concentration is increased by approximately 60%. These findings have no impact on esomeprazole dosing.

Gender

After a single 40 mg dose of esomeprazole, the mean area under the plasma concentration-time curve is 30% higher in women than in men. No gender-related differences were observed after repeated once-daily administration. These findings do not affect esomeprazole dosing.

Patients with Hepatic Impairment

Metabolism of esomeprazole may be impaired in patients with mild to moderate hepatic dysfunction. The rate of metabolism is reduced in patients with severe hepatic impairment, leading to a doubling of the area under the plasma concentration-time curve. Therefore, the maximum recommended dose in patients with severe hepatic impairment is 20 mg. Esomeprazole and its metabolites do not tend to accumulate during once-daily administration.

Patients with Renal Impairment

Studies in patients with impaired renal function have not been conducted. Since the kidneys are responsible for excretion of esomeprazole metabolites, but not the parent compound, changes in metabolism in patients with renal impairment are not expected.

Elderly Patients

Metabolism of esomeprazole does not undergo significant changes in elderly patients (aged 71 to 80 years).

Paediatric Population

Children aged 12–18 years:

After repeated administration of 20 mg and 40 mg esomeprazole, total exposure (AUC) and time to reach maximum plasma concentration (tmax) in children aged 12–18 years were similar to AUC and tmax values in adults when both esomeprazole doses were administered.

Clinical characteristics.

Indications.

Gastroesophageal reflux disease (GERD):

• treatment of erosive reflux esophagitis;
• long-term treatment to prevent relapse;
• symptomatic treatment of gastroesophageal reflux disease.

In combination with antibacterial agents for eradication of Helicobacter pylori:

• treatment of Helicobacter pylori-associated duodenal ulcer;
• prevention of recurrence of peptic ulcers in patients with ulcers caused by Helicobacter pylori.

Treatment and prevention of ulcers associated with long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs):

• treatment of NSAID-induced ulcers;
• prevention of gastric and duodenal ulcers in patients at risk due to NSAID use.

Long-term treatment following intravenous prevention of recurrent bleeding from peptic ulcers.

Treatment of Zollinger-Ellison syndrome.

Children aged 12 years and older

Gastroesophageal reflux disease (GERD):

• treatment of erosive reflux esophagitis;
• long-term treatment of patients with healed esophagitis to prevent relapse;
• symptomatic treatment of gastroesophageal reflux disease (GERD).

In combination with antibiotics for treatment of Helicobacter pylori-induced duodenal ulcer.

Contraindications.

Hypersensitivity to the active substance, substituted benzimidazoles, or to any of the excipients.

Esomeprazole must not be used concomitantly with nelfinavir (see section "Interaction with other medicinal products and other forms of interaction").

Interaction with other medicinal products and other forms of interaction.

Effect of esomeprazole on the pharmacokinetics of other medicinal products.

Protease inhibitors

Interactions between omeprazole and certain protease inhibitors have been reported. The clinical significance and mechanisms of these interactions are not always known. Increased gastric pH during omeprazole therapy may alter the absorption of protease inhibitors. Another possible mechanism of interaction involves inhibition of CYP2C19 activity.

It has been reported that concomitant use of omeprazole reduces serum levels of atazanavir and nelfinavir; therefore, their concomitant use is not recommended. In healthy volunteers, co-administration of omeprazole (40 mg once daily) with atazanavir 300 mg/ritonavir 100 mg significantly reduced atazanavir exposure (AUC, Cmax, and Cmin decreased by approximately 75%). Increasing the atazanavir dose to 400 mg did not compensate for the effect of omeprazole on atazanavir exposure. When omeprazole (20 mg daily) was co-administered with atazanavir 400 mg/ritonavir 100 mg in healthy volunteers, atazanavir exposure decreased by approximately 30% compared to exposure observed with daily administration of 300 mg atazanavir/100 mg ritonavir without omeprazole 20 mg daily. Concomitant use of omeprazole (40 mg daily) reduced mean AUC, Cmax, and Cmin of nelfinavir by 36–39%, and mean AUC, Cmax, and Cmin of its pharmacologically active metabolite M8 decreased by 75–92%. Due to the similarity in pharmacodynamic effects and pharmacokinetic properties between omeprazole and esomeprazole, concomitant use of esomeprazole with atazanavir is not recommended (see section "Special precautions for use"); concomitant use of esomeprazole with nelfinavir is contraindicated (see section "Contraindications").

During concomitant therapy with omeprazole (40 mg daily), increased serum levels of saquinavir (in combination with ritonavir) were reported (80–100% increase). Omeprazole treatment at a dose of 20 mg daily did not affect darunavir (in combination with ritonavir) or amprenavir (in combination with ritonavir) exposure. Esomeprazole treatment at a dose of 20 mg daily did not affect amprenavir exposure (with or without ritonavir). Omeprazole treatment at a dose of 40 mg daily did not affect lopinavir exposure (in combination with ritonavir).

Methotrexate

Elevated blood methotrexate levels have been reported in some patients when administered concomitantly with proton pump inhibitors. In cases where high-dose methotrexate is to be administered, temporary discontinuation of esomeprazole should be considered.

Tacrolimus

Increased serum levels of tacrolimus have been reported with concomitant use of esomeprazole. Close monitoring of tacrolimus blood concentrations and renal function (creatinine clearance) is required, and dose adjustment of tacrolimus may be necessary.

Medicinal products whose absorption is pH-dependent

Suppression of gastric acid secretion during treatment with esomeprazole and other PPIs (proton pump inhibitors) may decrease or increase the absorption of medicinal products whose absorption depends on gastric pH. As with other agents that reduce intragastric acidity, absorption of drugs such as ketoconazole, itraconazole, and erlotinib may be reduced, whereas absorption of drugs such as digoxin may be increased during esomeprazole treatment. Concomitant administration of omeprazole (20 mg daily) and digoxin in healthy volunteers increased digoxin bioavailability by 10% (up to 30% in two out of ten subjects). Rare cases of digoxin toxicity have been reported. However, caution should be exercised when prescribing high doses of esomeprazole to elderly patients. Therapeutic drug monitoring of digoxin should be intensified.

Medicinal products metabolized by CYP2C9

Esomeprazole inhibits CYP2C19, the main enzyme responsible for esomeprazole metabolism. Therefore, when esomeprazole is used in combination with drugs metabolized by CYP2C19 (such as diazepam, citalopram, imipramine, clomipramine, phenytoin), plasma concentrations of these drugs may increase, and dose reduction may be necessary. This should be taken into account, especially when esomeprazole is prescribed "as needed."

Diazepam

Concomitant administration of 30 mg esomeprazole reduces CYP2C19-mediated clearance of diazepam by 45%.

Phenytoin

Concomitant administration of 40 mg esomeprazole increases plasma phenytoin levels by 13% in patients with epilepsy. Monitoring of plasma phenytoin concentrations is recommended when initiating or discontinuing esomeprazole therapy.

Voriconazole

Administration of omeprazole (40 mg once daily) increased Cmax and AUCτ of voriconazole (a CYP2C19 substrate) by 15% and 41%, respectively.

Cilostazol

Omeprazole and esomeprazole act as inhibitors of CYP2C19. Administration of omeprazole 40 mg to healthy volunteers in a study resulted in an increase in Cmax and area under the concentration-time curve (AUC) for cilostazol by 18% and 26%, respectively, and for one of its active metabolites by 29% and 69%, respectively.

• Cisapride*

In healthy volunteers, concomitant administration of 40 mg esomeprazole with cisapride increased the area under the concentration-time curve (AUC) by 32% and prolonged elimination half-life (t1/2) by 31%, but there was no significant increase in peak plasma concentration of cisapride. A moderately prolonged QT interval was observed after cisapride alone, which did not further increase when cisapride was administered with esomeprazole.

Warfarin

Clinical studies using 40 mg esomeprazole in patients taking warfarin showed that coagulation time remained within normal limits. Post-marketing experience with oral esomeprazole indicates several isolated cases of clinically significant increases in international normalized ratio (INR) during concomitant use of esomeprazole and warfarin. Monitoring of INR is recommended at the beginning and end of concomitant treatment with esomeprazole and warfarin or other coumarin derivatives.

Clopidogrel

Results from pharmacokinetic (PK)/pharmacodynamic (PD) interaction studies between clopidogrel (loading dose 300 mg/maintenance dose 75 mg daily) and esomeprazole (oral 40 mg daily) in healthy volunteers showed a 40% reduction in exposure to the active metabolite of clopidogrel and a 14% reduction in maximum inhibition of ADP-induced platelet aggregation.

In a study involving healthy volunteers, when clopidogrel was administered together with esomeprazole and acetylsalicylic acid (ASA) in fixed combination doses (20 mg + 81 mg, respectively), exposure to the active metabolite of clopidogrel decreased by nearly 40% compared to clopidogrel monotherapy.

However, maximum levels of inhibition of ADP-induced platelet aggregation were similar in the clopidogrel monotherapy group and the group receiving clopidogrel with esomeprazole and ASA.

Observational and clinical studies have yielded conflicting data regarding the clinical implications of PK/PD interactions between esomeprazole and major cardiovascular events. As a precautionary measure, concomitant use of esomeprazole and clopidogrel should be avoided.

Investigated medicinal products without clinically significant interaction

Amoxicillin and quinidine

Esomeprazole showed no clinically significant effect on the pharmacokinetics of amoxicillin or quinidine.

Naproxen or rofecoxib

No clinically significant pharmacokinetic interactions were observed during short-term concomitant use of esomeprazole with naproxen or rofecoxib.

Effect of other medicinal products on the pharmacokinetics of esomeprazole.

Medicinal products that inhibit CYP2C19 and/or CYP3A4 activity

Esomeprazole is metabolized by CYP2C19 and CYP3A4. Concomitant administration of esomeprazole and clarithromycin (an inhibitor of CYP3A4, 500 mg twice daily) resulted in a doubling of esomeprazole exposure. Concomitant use of esomeprazole with combined inhibitors of CYP2C19 and CYP3A4, such as voriconazole, may increase esomeprazole exposure by more than two-fold.

The CYP2C19 and CYP3A4 inhibitor voriconazole increased AUCτ of omeprazole by 280%. Dose adjustment of esomeprazole is generally not required in either of these situations. However, dose adjustment of esomeprazole should be considered in patients with severe hepatic impairment and in cases of long-term treatment.

Medicinal products that induce CYP2C19 and/or CYP3A4 activity

Agents that induce CYP2C19, CYP3A4, or both enzymes (such as rifampicin or St. John's wort) may reduce esomeprazole serum levels by accelerating its metabolism.

Paediatric population

Drug interaction studies have been conducted only in adults.

Special precautions for use.

In the presence of alarm symptoms (e.g., marked weight loss, nausea, dysphagia, hematemesis, or melena) or when gastric ulcer is suspected or present, malignancy must be excluded, since treatment with Pemozar may mask symptoms and delay diagnosis.

Long-term use

Patients receiving long-term treatment (especially those treated for more than 1 year) should be under regular medical supervision.

On-demand treatment

Patients using the drug on an "as-needed" basis should inform their physician if there is a change in the pattern of symptoms.

Eradication of Helicobacter pylori

When prescribing esomeprazole, interactions with other medicinal products affecting esomeprazole plasma concentrations should be considered.

When esomeprazole is prescribed for Helicobacter pylori eradication, potential drug interactions of all components of triple therapy must be taken into account. Clarithromycin is a potent inhibitor of CYP3A4, and its contraindications and interactions must be considered (e.g., if triple therapy is prescribed to patients concurrently receiving other CYP3A4-metabolized drugs such as cisapride together with esomeprazole).

Gastrointestinal infections

Use of proton pump inhibitors (PPIs) may slightly increase the risk of gastrointestinal infections such as Salmonella and Campylobacter.

Absorption of vitamin B12

Esomeprazole, like all medicinal products that inhibit gastric acid secretion, may reduce absorption of vitamin B12 (cyanocobalamin) due to the development of hypo- or achlorhydria. This should be considered when treating patients long-term, especially those with low body stores of vitamin B12 or those with risk factors for reduced vitamin B12 absorption.

Hypomagnesemia

Severe hypomagnesemia has been reported in patients treated with proton pump inhibitors (PPIs), such as esomeprazole, for at least 3 months, and in most cases, for over 1 year. Serious manifestations of hypomagnesemia such as fatigue, tetany, delirium, seizures, dizziness, and ventricular arrhythmias may occur; however, symptoms may present insidiously and may be overlooked. In most cases, the condition improved after magnesium replacement therapy and discontinuation of PPI treatment.

For patients expected to be on long-term therapy, or for patients receiving PPIs concomitantly with digoxin or other drugs that may cause hypomagnesemia (e.g., diuretics), healthcare professionals should consider measuring magnesium levels prior to initiating PPI therapy and periodically during treatment.

Risk of fractures

Proton pump inhibitors, particularly when used at high doses and over long durations (>1 year), may modestly increase the risk of fractures of the hip, wrist, and spine, primarily in elderly patients or those with other risk factors. Observational study data suggest that PPIs may increase the overall fracture risk by 10–40%. Some of these increased fracture cases may be related to other risk factors. Patients at risk of osteoporosis should receive treatment according to current clinical guidelines and adequate supplementation with vitamin D and calcium.

Subacute cutaneous lupus erythematosus

The use of proton pump inhibitors has been associated with very rare cases of subacute cutaneous lupus erythematosus. If skin lesions develop, particularly in sun-exposed areas, and are accompanied by arthralgia, the patient should seek immediate medical advice, and discontinuation of esomeprazole should be considered. Previous exposure to PPIs associated with the development of subacute cutaneous lupus erythematosus may increase the risk of recurrence when other PPIs are used.

Combination with other medicinal products

Concomitant use of esomeprazole with atazanavir is not recommended (see section "Interaction with other medicinal products and other forms of interaction"). If combining atazanavir with a proton pump inhibitor cannot be avoided, close monitoring in an inpatient setting is recommended, along with increasing the atazanavir dose to 400 mg with 100 mg ritonavir; the esomeprazole dose should not exceed 20 mg.

Esomeprazole is an inhibitor of CYP2C19. Therefore, potential interactions between esomeprazole and other drugs metabolized by CYP2C19 should be considered at the initiation or discontinuation of therapy. An interaction has been observed between clopidogrel and esomeprazole (see section "Interaction with other medicinal products and other forms of interaction"). The clinical significance of this interaction remains uncertain. As a precautionary measure, concomitant use of esomeprazole and clopidogrel should be avoided.

When prescribing esomeprazole for on-demand use, potential interactions with other medicinal products due to fluctuations in esomeprazole plasma concentrations should be considered (see section "Interaction with other medicinal products and other forms of interaction").

Sucrose

This medicinal product contains sucrose. Patients with rare hereditary fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase deficiency should not take this medicine.

Effect on laboratory test results

Increased chromogranin A (CgA) levels may interfere with laboratory tests for neuroendocrine tumors. To avoid this interference, esomeprazole treatment should be discontinued at least 5 days before measuring CgA levels (see section "Pharmacodynamics"). If CgA and gastrin levels have not returned to reference ranges after initial testing, the test should be repeated 14 days after stopping PPI therapy.

Use during pregnancy or breastfeeding.

Pregnancy

Currently, there is insufficient data on the use of Pemozar during pregnancy. Epidemiological studies on the use of the racemic mixture of omeprazole during pregnancy show no increased risk of congenital malformations or fetal toxicity. Animal studies with esomeprazole have not revealed any direct or indirect harmful effects on embryonal/fetal development. Animal studies with the racemic mixture have not shown any direct or indirect adverse effects on pregnancy, delivery, or postnatal development. The drug should be used with caution in pregnant women. A moderate amount of data in pregnant women (from 300 to 1000 pregnancy cases) indicates no teratogenic effects or toxic effects of esomeprazole on the fetus or newborn. Animal studies indicate no direct or indirect harmful effects of the drug on reproductive function due to its toxicological impact.

Breastfeeding

It is unknown whether esomeprazole passes into human breast milk. There is insufficient information on the effects of esomeprazole on newborns/infants. Esomeprazole should not be used during breastfeeding.

Fertility

Animal studies with the racemic mixture of omeprazole indicate no effect of omeprazole on fertility following oral administration.

Ability to influence the ability to drive and use machines.

Esomeprazole has minimal influence on the ability to drive vehicles or operate machinery. However, if dizziness or blurred vision occurs during treatment, patients should refrain from driving or operating machinery.

Method of Administration and Dosage

Adults

Gastroesophageal reflux disease (GERD)

Treatment of erosive reflux esophagitis: 40 mg once daily for 4 weeks. An additional 4 weeks of treatment is recommended for patients in whom esophagitis has not healed or symptoms persist.

Maintenance treatment of relapse in patients with healed esophagitis: 20 mg once daily.

Symptomatic treatment of gastroesophageal reflux disease: 20 mg once daily for patients without esophagitis. If symptom control is not achieved within 4 weeks of treatment, the patient should be evaluated. After symptom relief, ongoing control may be maintained with 20 mg once daily. For adults, an "on-demand" regimen may be used, taking 20 mg once daily as needed. However, in patients receiving NSAIDs who are at risk of developing gastric or duodenal ulcers, continued symptom control using an "on-demand" regimen is not recommended.

In combination with antibacterial agents for eradication of Helicobacter pylori

Treatment of duodenal ulcer associated with Helicobacter pylori and
Prevention of recurrence of peptic ulcers in patients with ulcers caused by Helicobacter pylori: 20 mg of Pemozar with 1 g of amoxicillin and 500 mg of clarithromycin twice daily for 7 days.

Treatment and prevention of ulcers caused by long-term NSAID therapy

Treatment of gastric ulcers caused by NSAID therapy: The recommended dose is 20 mg once daily. The duration of treatment is 4–8 weeks.

Prevention of gastric and duodenal ulcers associated with NSAID therapy in high-risk patients: The recommended dose is 20 mg once daily.

Long-term treatment following intravenous administration of the drug for prevention of recurrent bleeding from peptic ulcers

40 mg once daily for 4 weeks following intravenous administration of the drug for prevention of recurrent bleeding from peptic ulcers.

Treatment of Zollinger-Ellison syndrome: 40 mg twice daily. Dosage should be individually adjusted; the duration of treatment is determined by clinical indications. According to available clinical data, most patients can be controlled with daily doses of esomeprazole ranging from 80 to 160 mg. If the daily dose exceeds 80 mg, it should be divided into two doses.

Special patient populations

Patients with renal impairment

Dose adjustment is not required in patients with impaired renal function. Due to the lack of experience with Pemozar in patients with severe renal impairment, the drug should be used with caution in these patients (see section "Pharmacological properties").

Patients with hepatic impairment

Dose adjustment is not required in patients with mild to moderate hepatic impairment. In patients with severe hepatic impairment, the maximum dose of Pemozar should not exceed 20 mg (see section "Pharmacological properties").

Elderly patients

Dose adjustment is not required in elderly patients.

Pediatric population

Children aged 12 years and older

Gastroesophageal reflux disease (GERD)

• Treatment of erosive reflux esophagitis:
  40 mg once daily for 4 weeks.
  An additional 4 weeks of treatment is recommended for patients with persistent esophagitis or ongoing symptoms.

• Long-term treatment of patients with healed esophagitis to prevent relapse:
  20 mg once daily.

• Symptomatic treatment of gastroesophageal reflux disease (GERD):
  The dose for patients without esophagitis is 20 mg once daily. If symptom control is not achieved after 4 weeks of treatment, the patient should undergo further evaluation. After symptom resolution, ongoing symptom control may be maintained with 20 mg once daily.

Treatment of duodenal ulcer caused by Helicobacter pylori

When selecting appropriate combination therapy, official national, regional, and local guidelines regarding bacterial resistance, duration of treatment (usually 7 days, but sometimes up to 14 days), and proper use of antibacterial agents should be considered. Treatment should be conducted under the supervision of a specialist.

Table 1

Dosage recommendations

Children under 12 years of age

Pemozar should not be used in children under 12 years of age, as data on such use are lacking.

Method of administration

Pemozar tablets should be swallowed whole with an adequate amount of liquid. The tablets must not be chewed or crushed.

For patients who have difficulty swallowing, it is recommended to dissolve the tablet in 100 ml of non-carbonated water. No other liquids should be used, as they may damage the enteric coating. The water in the glass should be shaken to dissolve the tablet. The liquid containing the microgranules should be consumed immediately or within 30 minutes. Half a glass of water should then be added, the glass swirled to rinse its walls, and the water consumed. The microgranules must not be chewed or crushed.

For patients who have difficulty swallowing, the tablet may be administered through a nasogastric tube after dissolving it in half a glass of non-carbonated water. It is very important that the syringe and tube used for this procedure are appropriate.

Administration via nasogastric tube

1. Place the tablet into an appropriate syringe and fill it with approximately 25 ml of water and 5 ml of air. For some tubes, 50 ml of water may be required to prevent obstruction of the tube.
2. Shake the syringe for 2 minutes to disintegrate the tablet.
3. Hold the syringe vertically with the tip facing upward and check the patency of the tip.
4. Attach the syringe to the tube while holding it vertically.
5. Shake the syringe and turn it with the tip facing downward. Rapidly administer 5–10 ml of the liquid. After administration, turn the syringe again and shake it (the syringe should be held vertically to prevent clogging the tip).
6. Turn the syringe again and administer another 5–10 ml of liquid into the tube. Repeat the procedure until the syringe is empty.
7. To flush any remaining residue, fill the syringe with 25 ml of water and 5 ml of air, shake the syringe, turn it, and rapidly administer the liquid. For some tubes, 50 ml of water may be required.

Children

Pemozar should not be used in children under 12 years of age, as data on such use are lacking.

Use in children aged 12 years and older for the following indications:

Gastroesophageal reflux disease (GERD)

• Treatment of erosive reflux esophagitis;
• Long-term treatment of patients with healed esophagitis to prevent relapse;
• Symptomatic treatment of gastroesophageal reflux disease (GERD).

In combination with antibiotics for the treatment of duodenal ulcer caused by Helicobacter pylori.

Overdose

Data on intentional overdose are very limited. Symptoms reported after ingestion of 280 mg of the drug included gastrointestinal symptoms and weakness. A single dose of esomeprazole up to 80 mg did not result in any adverse effects. There is no specific antidote. Esomeprazole is highly protein-bound in plasma, so elimination by dialysis is not significant. As with any overdose, symptomatic and supportive treatment should be provided.

Adverse Reactions.

Summary of safety profile

The most commonly reported adverse reactions during clinical trials (as well as in the post-marketing period of esomeprazole use) include headache, abdominal pain, diarrhea, and nausea. Furthermore, the safety profile of esomeprazole is consistent across different dosage forms, indications, age groups, and patient populations. No dose-dependent adverse reactions have been identified.

Adverse events were classified according to their frequency of occurrence: common (>1/100, <1/10); uncommon (>1/1000, <1/100); rare (>1/10000, <1/1000); very rare (<1/10000), and frequency not known (cannot be estimated based on available data).

Blood and lymphatic system disorders

Rare: leukopenia, thrombocytopenia.

Very rare: agranulocytosis, pancytopenia.

Immune system disorders

Rare: hypersensitivity reactions such as fever, angioedema, and anaphylactic reaction/shock.

Metabolism and nutrition disorders

Uncommon: peripheral edema.

Rare: hyponatremia.

Frequency not known: hypomagnesemia; severe hypomagnesemia may lead to hypocalcemia. Hypomagnesemia may also be associated with hypokalemia.

Psychiatric disorders

Uncommon: insomnia.

Rare: agitation, depression, confusion.

Very rare: aggression, hallucinations.

Nervous system disorders

Common: headache.

Uncommon: asthenia, paresthesia, somnolence.

Rare: taste disturbance.

Eye disorders

Rare: blurred vision.

Ear and labyrinth disorders

Uncommon: dizziness.

Respiratory system disorders

Rare: bronchospasm.

Gastrointestinal disorders

Common: abdominal pain, constipation, diarrhea, bloating, nausea, vomiting, fundic gland polyps (benign).

Uncommon: dry mouth.

Rare: stomatitis, gastrointestinal candidiasis.

Frequency not known: microscopic colitis.

Hepatobiliary disorders

Uncommon: increased liver enzymes.

Rare: hepatitis with or without jaundice.

Very rare: hepatic failure, encephalopathy in patients with liver disease.

Skin and subcutaneous tissue disorders

Uncommon: dermatitis, pruritus, urticaria, rash.

Rare: alopecia, photosensitivity.

Very rare: erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis.

Frequency not known: lupus erythematosus.

Musculoskeletal and connective tissue disorders

Uncommon: fracture of the hip, wrist, or spine (see section "Special warnings and precautions for use").

Rare: arthralgia, myalgia.

Very rare: muscle weakness.

Renal and urinary disorders

Very rare: interstitial nephritis; in some patients, renal failure has also been reported concurrently.

Reproductive system disorders

Very rare: gynecomastia.

General disorders

Rare: asthenia, increased sweating.

Shelf life. 2 years.

Storage conditions.

Store at temperatures not exceeding 30 °C in the original packaging.

Keep out of reach of children.

Packaging.

7 tablets per blister pack, 2 blister packs per cardboard box.

30 tablets per bottle, 1 bottle per cardboard box.

Prescription category. Prescription only.

Manufacturer.

San Pharmaceutical Industries Limited /
Sun Pharmaceutical Industries Limited.

Manufacturer's address and location of operations.

V. Ganguwala, Paonta Sahib, District Sirmour, Himachal Pradesh 173025, India /
V. Ganguwala, Paonta Sahib, District Sirmour, Himachal Pradesh 173025, India.