NEXPRO-40 Esomeprazole Magnesium 40mg Enteric-Coated Tablet 1's
RXDRUG-DR-XY41252-1pc
Discreet Packaging
We recognize that purchasing medications can be a deeply personal matter. To respect your privacy, we ensure that all orders are packaged discreetly, with no indication of the contents on the packaging. This means that even our couriers remain unaware of the package contents.
Furthermore, we uphold strict confidentiality standards. We guarantee that your order information will never be disclosed to any third party. Your trust is paramount to us, and we are committed to safeguarding your privacy at every step of the process. Our dedication to discretion and confidentiality is part of our unwavering commitment to you, our valued customer.
FDA-registered Products
FDA-licensed Pharmacies
Features
Brand
Nexpro-40
Full Details
Dosage Strength
40 mg
Drug Ingredients
- Esomeprazole
Drug Packaging
Enteric-Coated Tablet 1's
Generic Name
Esomeprazole Magnesium
Dosage Form
Enteric-Coated Tablet
Registration Number
DR-XY41252
Drug Classification
Prescription Drug (RX)
Description
Indications/Uses
Nexpro-20/Nexpro-40: Esomeprazole is indicated in the following conditions: Gastro-esophageal Reflux Disease (GERD): treatment of erosive reflux esophagitis; long-term management of patients with healed esophagitis to prevent relapse; symptomatic treatment of gastro-esophageal reflux disease (GERD).
Patients requiring continued NSAID therapy: prevention of gastric and duodenal ulcers associated with non-steroidal anti-inflammatory drug (NSAID) therapy in patients at risk.
In combination with appropriate antibacterial therapeutic regimens for the eradication of Helicobacter pylori: healing of Helicobacter pylori associated duodenal ulcer; prevention of relapse of peptic ulcers in patients with Helicobacter pylori associated ulcer disease.
Nexpro IV: Treatment of peptic ulcer disease, NSAID associated ulceration, gastroesophageal reflux disease and Zollinger-Ellison syndrome.
Patients requiring continued NSAID therapy: prevention of gastric and duodenal ulcers associated with non-steroidal anti-inflammatory drug (NSAID) therapy in patients at risk.
In combination with appropriate antibacterial therapeutic regimens for the eradication of Helicobacter pylori: healing of Helicobacter pylori associated duodenal ulcer; prevention of relapse of peptic ulcers in patients with Helicobacter pylori associated ulcer disease.
Nexpro IV: Treatment of peptic ulcer disease, NSAID associated ulceration, gastroesophageal reflux disease and Zollinger-Ellison syndrome.
Dosage/Direction for Use
Nexpro-20/Nexpro-40: Gastro-esophageal Reflux Disease (GERD): treatment of erosive reflux oesophagitis 40mg once daily for 4 weeks. An additional 4 weeks treatment is recommended for patients in whom esophagitis has not healed or who have persistent symptoms.
Long-term management of patients with healed esophagitis to prevent relapse 20mg once daily.
Symptomatic treatment of gastro-esophageal reflux disease (GERD) 20mg once daily in patients without esophagitis. If symptom control has not been achieved after 4 weeks, the patient should be further investigated. Once symptoms have resolved, subsequent symptom control can be achieved using an on demand regimen, taking 20mg once daily, when needed.
Patients requiring continued NSAID therapy: prevention of gastric and duodenal ulcers associated with NSAID therapy in patients at risk: 20 mg or 40mg once daily.
In combination with appropriate antibacterial therapeutic regimens for the eradication of Helicobacter pylori: healing of Helicobacter pylori associated duodenal ulcer.
Prevention of relapse of peptic ulcers in patients with Helicobacter pylori associated ulcer disease. 20mg Esomeprazole with 1 g amoxicillin and 500mg clarithromycin, all twice daily for 7 days.
Children: There is no experience with Esomeprazole in children.
Impaired renal function: Dose adjustment is not required in patients with impaired renal function. Due to limited experience in patients with severe renal insufficiency, such patients should be treated with caution.
Impaired hepatic function: Dose adjustment is not required in patients with mild to moderate liver impairment. For patients with severe liver impairment, a maximum daily dose of 20 mg Esomeprazole should be used.
Elderly: Dose adjustment is not required in the elderly.
Directions for Use: The tablets should be swallowed whole with liquid. The tablets should not be chewed or crushed.
The tablets can also be dispersed in half a glass of non-carbonated water. No other liquids should be used. Stir until the tablets disintegrate and drink the liquid with the pellets immediately or within 30 minutes. Rinse the glass with half a glass of water and drink. For patients who cannot swallow, the tablets can be dispersed in non-carbonated water and administered through a gastric tube.
Nexpro IV: The recommended adult dose of Esomeprazole I.V is either 20 or 40 mg given once daily by intravenous injection (no less than 3 minutes) or intravenous infusion (10 to 30 minutes). Esomeprazole I.V. should not be administered concomitantly with any other medications through the same intravenous site and/or tubing. The intravenous line should always be flushed with either 0.9% Sodium Chloride Injection USP, Lactated Ringer Injection USP, or 5% Dextrose Injection USP, both prior to and after administration of Esomeprazole I.V. for Injection. Or as Prescribed by the physician.
DIRECTION FOR RECONSTITUTION: Reconstitute with 10 mL of 0.9% Sodium Chloride Injection.
Long-term management of patients with healed esophagitis to prevent relapse 20mg once daily.
Symptomatic treatment of gastro-esophageal reflux disease (GERD) 20mg once daily in patients without esophagitis. If symptom control has not been achieved after 4 weeks, the patient should be further investigated. Once symptoms have resolved, subsequent symptom control can be achieved using an on demand regimen, taking 20mg once daily, when needed.
Patients requiring continued NSAID therapy: prevention of gastric and duodenal ulcers associated with NSAID therapy in patients at risk: 20 mg or 40mg once daily.
In combination with appropriate antibacterial therapeutic regimens for the eradication of Helicobacter pylori: healing of Helicobacter pylori associated duodenal ulcer.
Prevention of relapse of peptic ulcers in patients with Helicobacter pylori associated ulcer disease. 20mg Esomeprazole with 1 g amoxicillin and 500mg clarithromycin, all twice daily for 7 days.
Children: There is no experience with Esomeprazole in children.
Impaired renal function: Dose adjustment is not required in patients with impaired renal function. Due to limited experience in patients with severe renal insufficiency, such patients should be treated with caution.
Impaired hepatic function: Dose adjustment is not required in patients with mild to moderate liver impairment. For patients with severe liver impairment, a maximum daily dose of 20 mg Esomeprazole should be used.
Elderly: Dose adjustment is not required in the elderly.
Directions for Use: The tablets should be swallowed whole with liquid. The tablets should not be chewed or crushed.
The tablets can also be dispersed in half a glass of non-carbonated water. No other liquids should be used. Stir until the tablets disintegrate and drink the liquid with the pellets immediately or within 30 minutes. Rinse the glass with half a glass of water and drink. For patients who cannot swallow, the tablets can be dispersed in non-carbonated water and administered through a gastric tube.
Nexpro IV: The recommended adult dose of Esomeprazole I.V is either 20 or 40 mg given once daily by intravenous injection (no less than 3 minutes) or intravenous infusion (10 to 30 minutes). Esomeprazole I.V. should not be administered concomitantly with any other medications through the same intravenous site and/or tubing. The intravenous line should always be flushed with either 0.9% Sodium Chloride Injection USP, Lactated Ringer Injection USP, or 5% Dextrose Injection USP, both prior to and after administration of Esomeprazole I.V. for Injection. Or as Prescribed by the physician.
DIRECTION FOR RECONSTITUTION: Reconstitute with 10 mL of 0.9% Sodium Chloride Injection.
Administration
May be taken with or without food: Best taken before meals/breakfast. Swallow whole, do not chew/crush. For patients w/ swallowing difficulties, disperse tab in ½ glass of non-carbonated water. No other liqd should be used. Stir until tab dissolves into little pellets & drink immediately or w/in 30 min. Rinse the glass w/ ½ glass of water & drink. The dispersion may also be administered via gastric tube.
Contraindications
Nexpro-20/Nexpro-40: Hypersensitivity to Esomeprazole, substituted Benzimidazoles or any of the excipients of the product.
Nexpro IV: Esomeprazole for Injection is contraindicated in patients with known hypersensitivity to the formulation.
Nexpro IV: Esomeprazole for Injection is contraindicated in patients with known hypersensitivity to the formulation.
Special Precautions
Nexpro-20/Nexpro-40: In the presence of any alarm symptom (e.g. significant unintentional weight loss, recurrent vomiting, dysphagia, haematemesis or melaena) and when gastric ulcer is suspected or present, malignancy should be excluded, as treatment with Esomeprazole may alleviate symptoms and delay diagnosis.
Patients on long-term treatment (particularly those treated for more than a year) should be kept under regular surveillance.
Patients on on-demand treatment should be instructed to contact their physician if their symptoms change in character. When prescribing esomeprazole for on-demand therapy, the implications for interactions with other pharmaceuticals, due to fluctuating plasma concentrations of esomeprazole should be considered.
When prescribing esomeprazole for eradication of Helicobacter pylori possible drug interactions for all components in the triple therapy should be considered. Clarithromycin is a potent inhibitor of CYP3A4 and hence contraindications and interactions for clarithromycin should be considered when the triple therapy is used in patients concurrently taking other drugs metabolized via CYP3A4 such as cisapride.
Treatment with proton pump inhibitors may lead to slightly increased risk of gastrointestinal infections such as Salmonella and Campylobacter.
Co-administration of esomeprazole with atazanavir is not recommended. If the combination of atazanavir with a proton pump inhibitor is judged unavoidable, close clinical monitoring is recommended. Esomeprazole dose should not exceed 20 mg and must be taken approximately 12 hours prior to atazanavir 300 mg with ritonavir 100 mg dose.
Effects on the Ability to Drive and Use Machines: Esomeprazole is not likely to affect the ability to drive or use machines.
Nexpro IV: Do not use Esomeprazole if it contains particles, is cloudy or discolored, or if the vial is cracked or damaged. If you also take an imidazole antifungal (eg, ketoconazole), take it at least 2 hours before using Esomeprazole.
Patients on long-term treatment (particularly those treated for more than a year) should be kept under regular surveillance.
Patients on on-demand treatment should be instructed to contact their physician if their symptoms change in character. When prescribing esomeprazole for on-demand therapy, the implications for interactions with other pharmaceuticals, due to fluctuating plasma concentrations of esomeprazole should be considered.
When prescribing esomeprazole for eradication of Helicobacter pylori possible drug interactions for all components in the triple therapy should be considered. Clarithromycin is a potent inhibitor of CYP3A4 and hence contraindications and interactions for clarithromycin should be considered when the triple therapy is used in patients concurrently taking other drugs metabolized via CYP3A4 such as cisapride.
Treatment with proton pump inhibitors may lead to slightly increased risk of gastrointestinal infections such as Salmonella and Campylobacter.
Co-administration of esomeprazole with atazanavir is not recommended. If the combination of atazanavir with a proton pump inhibitor is judged unavoidable, close clinical monitoring is recommended. Esomeprazole dose should not exceed 20 mg and must be taken approximately 12 hours prior to atazanavir 300 mg with ritonavir 100 mg dose.
Effects on the Ability to Drive and Use Machines: Esomeprazole is not likely to affect the ability to drive or use machines.
Nexpro IV: Do not use Esomeprazole if it contains particles, is cloudy or discolored, or if the vial is cracked or damaged. If you also take an imidazole antifungal (eg, ketoconazole), take it at least 2 hours before using Esomeprazole.
Use In Pregnancy & Lactation
Nexpro-20/Nexpro-40: Safety during pregnancy and lactation has not been established.
Adverse Reactions
Nexpro-20/Nexpro-40: The following adverse drug reactions have been identified or suspected in the clinical trials program for esomeprazole and post-marketing. None was found to be dose-related. The reactions are classified according to frequency (common>1/100, <1/10; uncommon>1/1000, <1/100; rare>1/10000, <1/1000; very rare <1/10000).
Blood and Lymphatic System Disorders: Rare: Leukopenia, thrombocytopenia; Very rare: Agranulocytosis, pancytopenia.
Immune System Disorders: Rare: Hypersensitivity reactions e.g. fever, angioedema and anaphylactic reaction/shock.
Metabolism and Nutrition Disorders: Uncommon: Peripheral oedema; Rare: Hyponatraemia.
Psychiatric Disorders: Uncommon: Insomnia; Rare: Agitation, confusion, depression; Very rare: Aggression, hallucinations.
Nervous System Disorders: Common: Headache; Uncommon: Dizziness, paraesthesia, somnolence; Rare: Taste disturbance.
Eye Disorders: Rare: Blurred vision.
Ear and Labyrinth Disorders: Uncommon: Vertigo.
Respiratory, Thoracic and Mediastinal Disorders: Rare: Bronchospasm.
Gastrointestinal Disorders: Common: Abdominal pain, constipation, diarrhoea, flatulence, nausea/vomiting; Uncommon: Dry mouth; Rare: Stomatitis, gastrointestinal candidiasis.
Hepatobiliary Disorders: Uncommon: Increased liver enzymes; Rare: Hepatitis with or without jaundice; Very rare: Hepatic failure, encephalopathy in patients with pre-existing liver disease.
Skin and Subcutaneous Tissue Disorders: Uncommon: Dermatitis, pruritus, rash, urticaria; Rare: Alopecia, photosensitivity; Very rare: Erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN).
Musculoskeletal, Connective Tissue and Bone Disorders: Rare: Arthralgia, myalgia; Very rare: Muscular weakness.
Renal and Urinary Disorders: Very rare: Interstitial nephritis.
Reproductive System and Breast Disorders: Very rare: Gynaecomastia.
General Disorders and Administration Site Conditions: Rare: Malaise, increased sweating.
Nexpro IV: Common Side effects: Constipation; diarrhea; dry mouth; gas; headache; nausea; pain, swelling, or redness at the injection site; stomach pain.
Severe Side effects: Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue; unusual hoarseness); chest pain; fast heartbeat; fever, chills, or sore throat; red, swollen, blistered, or peeling skin; unusual bruising or bleeding; unusual tiredness. Seek medical attention right away if any of these severe side effects occur.
Blood and Lymphatic System Disorders: Rare: Leukopenia, thrombocytopenia; Very rare: Agranulocytosis, pancytopenia.
Immune System Disorders: Rare: Hypersensitivity reactions e.g. fever, angioedema and anaphylactic reaction/shock.
Metabolism and Nutrition Disorders: Uncommon: Peripheral oedema; Rare: Hyponatraemia.
Psychiatric Disorders: Uncommon: Insomnia; Rare: Agitation, confusion, depression; Very rare: Aggression, hallucinations.
Nervous System Disorders: Common: Headache; Uncommon: Dizziness, paraesthesia, somnolence; Rare: Taste disturbance.
Eye Disorders: Rare: Blurred vision.
Ear and Labyrinth Disorders: Uncommon: Vertigo.
Respiratory, Thoracic and Mediastinal Disorders: Rare: Bronchospasm.
Gastrointestinal Disorders: Common: Abdominal pain, constipation, diarrhoea, flatulence, nausea/vomiting; Uncommon: Dry mouth; Rare: Stomatitis, gastrointestinal candidiasis.
Hepatobiliary Disorders: Uncommon: Increased liver enzymes; Rare: Hepatitis with or without jaundice; Very rare: Hepatic failure, encephalopathy in patients with pre-existing liver disease.
Skin and Subcutaneous Tissue Disorders: Uncommon: Dermatitis, pruritus, rash, urticaria; Rare: Alopecia, photosensitivity; Very rare: Erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN).
Musculoskeletal, Connective Tissue and Bone Disorders: Rare: Arthralgia, myalgia; Very rare: Muscular weakness.
Renal and Urinary Disorders: Very rare: Interstitial nephritis.
Reproductive System and Breast Disorders: Very rare: Gynaecomastia.
General Disorders and Administration Site Conditions: Rare: Malaise, increased sweating.
Nexpro IV: Common Side effects: Constipation; diarrhea; dry mouth; gas; headache; nausea; pain, swelling, or redness at the injection site; stomach pain.
Severe Side effects: Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue; unusual hoarseness); chest pain; fast heartbeat; fever, chills, or sore throat; red, swollen, blistered, or peeling skin; unusual bruising or bleeding; unusual tiredness. Seek medical attention right away if any of these severe side effects occur.
Drug Interactions
Nexpro-20/Nexpro-40: Interaction with other medicinal products and other forms of interaction: Effects of Esomeprazole on the Pharmacokinetics of Other Drugs: The decreased intragastric acidity during treatment with esomeprazole might increase or decrease the absorption of drugs if the mechanism of absorption is influenced by gastric acidity. In common with the use of other inhibitors of acid secretion or antacids, the absorption of ketoconazole and itraconazole can decrease during treatment with esomeprazole.
Esomeprazole inhibits CYP2C19, the major Esomeprazole metabolizing enzyme. Concomitant administration of 30mg Esomeprazole resulted in a 45% decrease in clearance of the CYP2C19 substrate diazepam. This interaction is unlikely to be of clinical relevance. Concomitant administration of 40mg Esomeprazole resulted in a 13% increase in trough plasma levels of phenytoin in epileptic patients.
Concomitant administration of 40 mg esomeprazole to warfarin treated patients showed that, despite a slight elevation in the trough plasma concentration of the less potent R-isomer of warfarin, the coagulation times were within the accepted range. However, as with all patients receiving warfarin, monitoring is recommended during concomitant treatment with esomeprazole.
In healthy volunteers it was reported that, concomitant administration of 40mg esomeprazole resulted in a 32% increase in area under the plasma concentration-time curve (AUC) and a 31% prolongation of elimination half-life (t½) but no significant increase in peak plasma levels of cisapride. This interaction did not alter the influence of cisapride on cardiac electrophysiology.
Esomeprazole has no pharmacokinetic interaction with amoxicillin or quinidine.
Studies evaluating concomitant administration of esomeprazole and either naproxen (non-selective NSAID) or rofecoxib (COX-2-selective NSAID) did not identify any clinically relevant interaction.
Effects of Other Drugs on the Pharmacokinetics of Esomeprazole: Esomeprazole is metabolized by CYP2C19 and CYP3A4. Concomitant administration of esomeprazole and a CYP3A4 inhibitor, clarithromycin (500mg twice a day), resulted in a doubling of the exposure (AUC) to esomeprazole. Dose adjustment of esomeprazole is not required.
Esomeprazole inhibits CYP2C19, the major Esomeprazole metabolizing enzyme. Concomitant administration of 30mg Esomeprazole resulted in a 45% decrease in clearance of the CYP2C19 substrate diazepam. This interaction is unlikely to be of clinical relevance. Concomitant administration of 40mg Esomeprazole resulted in a 13% increase in trough plasma levels of phenytoin in epileptic patients.
Concomitant administration of 40 mg esomeprazole to warfarin treated patients showed that, despite a slight elevation in the trough plasma concentration of the less potent R-isomer of warfarin, the coagulation times were within the accepted range. However, as with all patients receiving warfarin, monitoring is recommended during concomitant treatment with esomeprazole.
In healthy volunteers it was reported that, concomitant administration of 40mg esomeprazole resulted in a 32% increase in area under the plasma concentration-time curve (AUC) and a 31% prolongation of elimination half-life (t½) but no significant increase in peak plasma levels of cisapride. This interaction did not alter the influence of cisapride on cardiac electrophysiology.
Esomeprazole has no pharmacokinetic interaction with amoxicillin or quinidine.
Studies evaluating concomitant administration of esomeprazole and either naproxen (non-selective NSAID) or rofecoxib (COX-2-selective NSAID) did not identify any clinically relevant interaction.
Effects of Other Drugs on the Pharmacokinetics of Esomeprazole: Esomeprazole is metabolized by CYP2C19 and CYP3A4. Concomitant administration of esomeprazole and a CYP3A4 inhibitor, clarithromycin (500mg twice a day), resulted in a doubling of the exposure (AUC) to esomeprazole. Dose adjustment of esomeprazole is not required.
Storage
Store at temperatures not exceeding 30°C.
Nexpro-20/Nexpro-40: Protect from light and moisture.
Nexpro IV: Reconstituted solution may be stored at room temperature and must be used within 24 hours from the time of initial reconstitution.
Nexpro-20/Nexpro-40: Protect from light and moisture.
Nexpro IV: Reconstituted solution may be stored at room temperature and must be used within 24 hours from the time of initial reconstitution.
Action
Pharmacology: Pharmacodynamics: Nexpro-20/Nexpro-40: Esomeprazole, the S-isomer of omeprazole, reduces gastric acid secretion through specific inhibition of the acid pump in the parietal cell, where it is concentrated and converted to the active form in the acidic environment of the secretory canaliculi and inhibits the enzyme H+K+ ATPase the proton pump. This effect on the final step of the gastric secretion is dose-dependent and provides for effective inhibition of both basal and stimulated acid secretion.
Effects on Gastric acid secretion: After oral dosing with esomeprazole 20mg and 40mg the onset of effects occurs within 1 hour. After repeated administration with 20mg esomeprazole once daily for 5 days, mean acid output after pentagastrin stimulation is decreased by 90% when measured 6-7 hours after dosing on day 5. After 5 days of oral dosing with 20mg and 40mg of esomeprazole, intragastric pH above 4 was maintained for a mean time of 13 hours and 17 hours, respectively over 24 hours in symptomatic gastro-esophageal reflux disease (GERD) patients. The proportion of patients maintaining an intragastric pH above 4 for at least 8, 12 and 16 hours were 76%, 54% and 24% respectively for esomeprazole 20mg. Corresponding proportions for esomeprazole 40mg were 97%, 92% and 56% respectively.
Using AUC as a surrogate parameter for plasma concentration, a relationship between inhibition of acid secretion and exposure has been shown.
Food intake had no significant influence on the effect of esomeprazole on intragastric acidity.
Other effects related to acid inhibition: During treatment with antisecretory drugs serum gastrin increases in response to the decreased acid secretion. During long-term treatment with antisecretory drugs gastric glandular cysts occur. These changes are a physiological consequence of pronounced inhibition of acid secretion, are benign and appear to be reversible.
Nexpro IV: Mechanism of Action: Esomeprazole is a weak base and is concentrated and converted to the active form in the highly acidic environment of the secretory canaliculi of the parietal cell, where it inhibits the enzyme H+K+-ATPase C the acid pump and inhibits both basal and stimulated acid secretion.
Pharmacokinetics: Nexpro-20/Nexpro-40: Esomeprazole is rapidly absorbed after oral doses, with peak plasma levels occurring after about 1 to 2 hours. Bioavailability of esomeprazole increases with both dose and repeated administration to about 68 and 89% for doses of 20 and 40 mg respectively. Food delays and decreases the absorption of esomeprazole, but this does not significantly change its effect on intragastric acidity. Esomeprazole is about 97% bound to plasma proteins. It is extensively metabolized in the liver by the cytochrome P450 isoenzyme CYP2C19 to hydroxy and desmethyl metabolites, which have no effect on gastric acid secretion. The remainder is metabolized by the cytochrome P450 isoenzyme CYP3A4 to esomeprazole sulfone. With repeated dosage, there is a decrease in first-pass metabolism and systemic clearance, probably caused by an inhibition of the CYP2C19 isoenzyme.
However, there is no accumulation during once daily use. The plasma elimination half-life is about 1.3 hours. Almost 80% of an oral dose is eliminated as metabolites in the urine, the remainder in the feces.
Geriatric Patients: The metabolism of esomeprazole is not significantly changed in elderly subjects (71-80 years of age).
Patients with renal impairment: No studies have been reported in patients with decreased renal function. Since the kidney is responsible for the excretion of the metabolites of esomeprazole, but not for the elimination of the parent compound, the metabolism of esomeprazole is not expected to be changed in patients with impaired renal function.
Patients with hepatic impairment: The metabolism of esomeprazole in patients with mild to moderate liver dysfunction may be impaired. The metabolic rate is decreased in patients with severe liver dysfunction resulting in a doubling of the area under the plasma concentration-time curve of esomeprazole. Therefore, a maximum of 20 mg should not be exceeded in patients with severe dysfunction.
Pharmacogenetics: Approximately 1-2% of the population lack a functional CYP2C19 enzyme and are called poor metabolizers. In these individuals, the metabolism of esomeprazole is probably mainly catalyzed by CYP3A4. It is reported that after repeated once-daily administration of 40mg esomeprazole, the mean area under the plasma concentration-time curve was approximately 100% higher in poor metabolizers than in subjects having a functional CYP2C19 enzyme (extensive metabolizers). Mean peak plasma concentrations were increased by about 60%.
Effects on Gastric acid secretion: After oral dosing with esomeprazole 20mg and 40mg the onset of effects occurs within 1 hour. After repeated administration with 20mg esomeprazole once daily for 5 days, mean acid output after pentagastrin stimulation is decreased by 90% when measured 6-7 hours after dosing on day 5. After 5 days of oral dosing with 20mg and 40mg of esomeprazole, intragastric pH above 4 was maintained for a mean time of 13 hours and 17 hours, respectively over 24 hours in symptomatic gastro-esophageal reflux disease (GERD) patients. The proportion of patients maintaining an intragastric pH above 4 for at least 8, 12 and 16 hours were 76%, 54% and 24% respectively for esomeprazole 20mg. Corresponding proportions for esomeprazole 40mg were 97%, 92% and 56% respectively.
Using AUC as a surrogate parameter for plasma concentration, a relationship between inhibition of acid secretion and exposure has been shown.
Food intake had no significant influence on the effect of esomeprazole on intragastric acidity.
Other effects related to acid inhibition: During treatment with antisecretory drugs serum gastrin increases in response to the decreased acid secretion. During long-term treatment with antisecretory drugs gastric glandular cysts occur. These changes are a physiological consequence of pronounced inhibition of acid secretion, are benign and appear to be reversible.
Nexpro IV: Mechanism of Action: Esomeprazole is a weak base and is concentrated and converted to the active form in the highly acidic environment of the secretory canaliculi of the parietal cell, where it inhibits the enzyme H+K+-ATPase C the acid pump and inhibits both basal and stimulated acid secretion.
Pharmacokinetics: Nexpro-20/Nexpro-40: Esomeprazole is rapidly absorbed after oral doses, with peak plasma levels occurring after about 1 to 2 hours. Bioavailability of esomeprazole increases with both dose and repeated administration to about 68 and 89% for doses of 20 and 40 mg respectively. Food delays and decreases the absorption of esomeprazole, but this does not significantly change its effect on intragastric acidity. Esomeprazole is about 97% bound to plasma proteins. It is extensively metabolized in the liver by the cytochrome P450 isoenzyme CYP2C19 to hydroxy and desmethyl metabolites, which have no effect on gastric acid secretion. The remainder is metabolized by the cytochrome P450 isoenzyme CYP3A4 to esomeprazole sulfone. With repeated dosage, there is a decrease in first-pass metabolism and systemic clearance, probably caused by an inhibition of the CYP2C19 isoenzyme.
However, there is no accumulation during once daily use. The plasma elimination half-life is about 1.3 hours. Almost 80% of an oral dose is eliminated as metabolites in the urine, the remainder in the feces.
Geriatric Patients: The metabolism of esomeprazole is not significantly changed in elderly subjects (71-80 years of age).
Patients with renal impairment: No studies have been reported in patients with decreased renal function. Since the kidney is responsible for the excretion of the metabolites of esomeprazole, but not for the elimination of the parent compound, the metabolism of esomeprazole is not expected to be changed in patients with impaired renal function.
Patients with hepatic impairment: The metabolism of esomeprazole in patients with mild to moderate liver dysfunction may be impaired. The metabolic rate is decreased in patients with severe liver dysfunction resulting in a doubling of the area under the plasma concentration-time curve of esomeprazole. Therefore, a maximum of 20 mg should not be exceeded in patients with severe dysfunction.
Pharmacogenetics: Approximately 1-2% of the population lack a functional CYP2C19 enzyme and are called poor metabolizers. In these individuals, the metabolism of esomeprazole is probably mainly catalyzed by CYP3A4. It is reported that after repeated once-daily administration of 40mg esomeprazole, the mean area under the plasma concentration-time curve was approximately 100% higher in poor metabolizers than in subjects having a functional CYP2C19 enzyme (extensive metabolizers). Mean peak plasma concentrations were increased by about 60%.
MedsGo Class
Antacids, Antireflux Agents & Antiulcerants
Please sign in so that we can notify you about a reply