Indications of Nexum 40

Esomeprazole is indicated:

• To relieve from chronic heartburn symptoms and other symptoms associated with GERD
• For the healing of erosive esophagitis
• For maintenance of healing of erosive esophagitis
• In combination with amoxicillin and clarithromycin for eradication of Helicobacter pylori infection in patients with duodenal ulcer disease.
• Zollinger-Ellison Syndrome
• Acid related Dyspepsia
• Duodenal & Gastric ulcer

Pharmaceutical Name of Nexum 40

Square Pharmaceuticals Ltd.

Pharmacology

Esomeprazole is a proton pump inhibitor that inhibits gastric acid secretion by specifically inhibiting ATPase H + / K + in parietal cells. Esomeprazole (omeprazole sisomer) is the first unique optical isomer of a proton pump inhibitor and provides better acid control than a racemic proton pump inhibitor.

Absorption: Esomeprazole capsules contain enteric coated granules of esomeprazole magnesium. The maximum plasma level (Cmax) after oral administration occurs at approximately 1.5 hours (Tmax). When the dose was increased, Cmax increased proportionally and the area under the plasma concentration-time curve (AUC) increased three-fold from 20 to 40 mg. With repeated administration once a day, the systemic bioavailability is approximately 90%, compared to 64% for a single administration. Compared with fasting conditions, AUC after a single dose of esomeprazole reduced food intake by 3353b. Esomeprazole should be taken at least one hour before meals.

Distribution: The binding rate of esomeprazole to plasma protein is 97%. The binding to plasma proteins remains constant within the concentration range of 20 mmol/L. The apparent volume of distribution of healthy volunteers at steady state is about 16 L.

Metabolism: The cytochrome P450 (CYP) enzyme system extensively metabolizes esomeprazole in the liver. Esomeprazole metabolites lack antisecretory activity. The major part of esomeprazole metabolism is dependent on the CYP2C19 isoenzyme which forms hydroxyl and demethylated metabolites. The amount remaining depends on CYP3A4, which forms the sulfone metabolite.

Excretion: The plasma elimination half-life of esomeprazole is approximately 1-1.5 hours. Less than 1% of the parent drug is excreted in the urine. Approximately 80% of the oral dose of esomeprazole is excreted in the urine as inactive metabolites and the remainder in the faeces as inactive metabolites.

Combined antibacterial therapy: esomeprazole magnesium 40 mg once a day, combined with clarithromycin 500 mg twice a day and amoxicillin 1000 mg twice a day for 7 days. Compared with esomeprazole treatment alone, the average steady-state AUC and Cmax of esomeprazole during triple therapy increased by 70% and 18%, respectively. The pharmacokinetic parameters of clarithromycin and amoxicillin are similar during triple therapy and during the administration of each drug alone. However, compared with treatment with clarithromycin alone, the average AUC and Cmax of 14-hydroxylamithromycin increased by 19% and 22%, respectively, during the triple treatment period. This increase in exposure to 14-hydroxylaxithromycin is not considered clinically significant.

Dosage & Administration

Healing of Erosive Esophagitis: 20 mg or 40 mg Once Daily for 4-8 Weeks. The majority of patients are healed within 4 to 8 weeks. For patients who don’t heal after 4-8 weeks, an additional 4-8 weeks of treatment may be considered. Maintenance of Healing of Erosive

Esophagitis: 20 mg Once Daily (Clinical studies did not extend 6 months).

Symptomatic GERD: 20 mg Once Daily for 4 Weeks. If symptoms do not resolve completely after 4 weeks, an additional 4 weeks of treatment may be considered.

Helicobacter Pylori eradication: Triple Therapy to reduce the risk of Duodenal Ulcer recurrence-Esomeprazole 40 mg Once Daily for 10 days, Amoxicillin 1000 mg Twice Daily for 10 days, Clarithromycin 500 mg Twice Daily for 10 days.

Zollinger-Ellison Syndrome: The dose is 20-80 mg once daily. The dosage should be adjusted individually and treatment continued as long as clinically indicated.

Acid-related Dyspepsia: 20-40 mg once daily for 2-4 weeks according to the response.

Duodenal ulcer: 20 mg once daily for 2-4 weeks. Gastric ulcer: 20-40 mg once daily for 4-8 weeks.

Injection: The recommended adult dose is 40 mg Esomeprazole given once daily by intravenous injection (not less than 3 minutes) or intravenous infusion (10 to 30 minutes). Esomeprazole IV injection should not be administered concomitantly with any other medications through the same intravenous site. Treatment with Esomeprazole IV injection should be discontinued as soon as the patient is able to resume treatment with Esomeprazole delayed-release capsules. Safety and effectiveness in paediatric patients have not been established.

Esomeprazole tablet or capsule: should be swallowed whole and taken one hour before a meal.

Direction for use of Delayed-Release Oral Suspension: Whole contents of the packet should be taken into a small glass containing 15 ml. of water. The mixer should be stirred well and leave 2 to 3 minutes to thicken. Stir again and drink within 30 minutes. If any medicine remains after drinking, add more water, stir, and drink immediately. If the suspension is to be administered through a nasogastric or gastric tube, the volume of water in the syringe should be 15 ml. & immediately shake the syringe and leave 2 to 3 minutes to thicken. Shake the syringe and inject it through the nasogastric or gastric tube into the stomach within 30 minutes. An appropriately sized syringe should be used. Shake and flush any remaining contents from the nasogastric or gastric tube into the stomach.

Esomeprazole IV Injection: Esomeprazole IV should be given as a slow intravenous injection. The solution for IV injection is obtained by adding to the vial 5 ml of the solvent (WFI) provided. After reconstitution, the injection should be given slowly over a period of at least 3 minutes. The solution should be used within 12 hours of reconstitution when stored at room temperature up to 30°C. No refrigeration is required. The reconstituted solution should not be used if it contains visible particulate.

Interactions of Nexum 40

Esomeprazole is extensively metabolized in the liver by CYP2C19 and CYP3A4. In vitro and in vivo studies have shown that esomeprazole is unlikely to inhibit CYP 1A2, 2A6, 2C9, 2D6, 2E1 and 3A4. No clinically relevant interactions with drugs metabolized by these CYP enzymes are expected. Drug interaction studies have shown that esomeprazole has no clinically significant interaction with phenytoin, warfarin, quinidine, clarithromycin or amoxicillin.

Esomeprazole may interfere with CYP2C19, the main metabolic enzyme of esomeprazole. The co-administration of 30 mg of esomeprazole and diazepam (a CYP2C19 substrate) resulted in a 45% increase in diazepam clearance. An increase in the plasma concentration of diazepam was observed at 12 hours and after the administration. Esomeprazole inhibits gastric acid secretion. Therefore, esomeprazole may interfere with drug absorption, where gastric pH is an important determinant of bioavailability (for example, ketoconazole, iron salts, and digoxin).

Co-administration of oral contraceptives, diazepam, phenytoin, or quinidine does not seem to change the pharmacokinetic characteristics of esomeprazole.

Clarithromycin combination therapy: The combined administration of esomeprazole, clarithromycin, and amoxicillin resulted in increased plasma levels of esomeprazole and 14-hydroxylamithromycin.

Contraindications

Esomeprazole is contraindicated in hospitalized patients who are known to be allergic to any preparation.

Side Effects of Nexum 40

The most common adverse reactions of esomeprazole include headache, diarrhea, nausea, flatulence, abdominal pain, constipation and dry mouth. Compared with short-term treatment, there was no difference in the types of related adverse events observed during maintenance treatment up to 12 months.

Pregnancy & Lactation

There are no adequate and well-controlled studies of pregnant women. Animal studies have not found teratogenic effects. The excretion of esomeprazole in milk has not been studied. Therefore, if it is deemed necessary to use esomeprazole, breastfeeding should be stopped.

Precautions & Warnings

• General: Symptomatic response to esomeprazole treatment does not exclude the presence of gastric malignancies.
• Note to patients: Esomeprazole capsules should be taken at least one hour before meals. For patients who have difficulty swallowing capsules, add a tablespoon of applesauce to the empty container, open the esomeprazole capsule, and carefully pour the particles in the capsule onto the applesauce. The pellets should be mixed with applesauce and swallowed immediately. The applesauce used should not be hot and should be soft enough to be swallowed without chewing. The granules should not be chewed or crushed. The granules / applesauce mixture should not be stored for future use. Antacids can be used when taking esomeprazole.

Therapeutic Class

Proton Pump Inhibitor

Storage Conditions

Store at a temperature not exceeding 30°C in a dry place. Protect from light and moisture. Keep out of reach of children.

Generic of Nexum 40

Esomeprazole Magnesium Trihydrate