Esomeprazole

Mechanism Of Action:

Esomeprazole is a proton pump inhibitor that suppresses gastric acid secretion by specific inhibition of the H+/K+-ATPase in the gastric parietal cell. The S- and R-isomers of omeprazole are protonated and converted in the acidic compartment of the parietal cell forming the active inhibitor, the achiral sulphenamide. By acting specifically on the proton pump, esomeprazole blocks the final step in acid production, thus reducing gastric acidity. This effect is dose-related up to a daily dose of 20 to 40 mg and leads to inhibition of gastric acid secretion.

Drug Label Information | Brands:

BRANDS OF ESOMEPRAZOLE IN KENYA

Cidopraz® , Opera Pharma (K) Ltd
Esocip®, Lords Healthcare Ltd
Esofag® ,Micro Labs Limited
Esofast®, Innocia Lifesciences Pvt. Ltd.
Esoflux®, The ACME Laboratories Ltd
Esofred®, Fredun Pharmaceuticals Ltd.
Esomac® , Cipla Ltd
Esome®, Getz Pharma (Pvt) Limited
Esomep®, Advanced Chemical Industries Limited
Esomezol® , Inventia Healthcare Pvt. Ltd.
Esonium®,Galaxy Pharmaceutical Limited
Esonix® , Incepta Pharmaceuticals Ltd
Esop® ,Swiss Parenterals (Pvt.) Ltd
Esopra® , PSA International (Export Division Of PSA Chemicals And Pharmaceuticals Pvt Ltd)
Esomepram® , MOL Chem Limited
Esopraz® , Highchem Marketing Ltd
Esopride®, Stallion Laboratories Pvt. Ltd
Esoral® , Eskayef Bangladesh Ltd.
Esose®, Glenmark Pharmaceuticals Limited
Esoxium®, Signature Healthcare Ltd
Espra® , CCL Pharmaceuticals (Pvt.) Ltd.
Esta® , Mac Heal Laboratories Ltd.
Esostar® , Medistar Pharmaceuticals Ltd
Esotid® , Radiance Pharmaceuticals Ltd
Eszed® , Zawadi Healthcare Ltd
Exium®, Radiant Pharmaceuticals Limited
Ezo®, Ind-Swift Limited
Grasozole®, Gracure pharmaceuticals Ltd
Gastrotab®, Krishna Chemist Ltd
Izra®, Unichem Laboratories Ltd.
Nexium®,AstraZeneca
Nexpro®, Torrent Pharmaceuticals Ltd
Prezola® , Medisel Kenya Ltd
Protas®, Square Pharmaceuticals Ltd.
Rayzium®, Biodeal Laboratories Ltd
Sergel® , Healthcare Pharmaceuticals Ltd
Sompraz® , Sun Pharmaceutical Industries Limited
Stulcer®, Gufic Stridden Biopharma Private Ltd.
Yesom®, Hetero Labs Limited
Zomep®, Zawadi Healthcare Ltd

INDICATIONS / DOSAGE & ADMINISTRATION

1.Treatment of Gastroesophageal Reflux Disease (GERD)
a) Healing of Erosive Esophagitis
20 mg or 40 mg Once Daily for 4 to 8 Weeks

b)Maintenance of Healing of Erosive Esophagitis
20 mg Once Daily

c) Symptomatic Gastroesophageal Reflux Disease
20 mg Once Daily for 4 Week

2. Pediatric GERD
12 to 17 Year Olds

a)Healing of Erosive Esophagitis
20 mg or 40 mg Once Daily for 4 to 8 Weeks

b) Symptomatic GERD
20 mg Once Daily for 4 Weeks

1 to 11 Year Olds
a) Short-term Treatment of Symptomatic GERD
10 mg Once Daily for up to 8 Weeks

b) Healing of Erosive Esophagitis weight < 20 kg 10 mg Once Daily for 8 Weeks weight > 20 kg
10 mg or 20 mg Once Daily for 8 Weeks

c) Risk Reduction of NSAID-Associated Gastric Ulcer
20 mg or 40 mg Once Daily for up to 6 months

d) Pathological Hypersecretory ConditionsIncluding Zollinger­- Ellison Syndrome
40 mg Twice Daily

ADVERSE DRUG REACTIONS:

Body as a Whole: abdomen enlarged, allergic reaction, asthenia, back pain, chest pain, substernal chest pain, facial edema, peripheral edema, hot flushes, fatigue, fever, flu-like disorder, generalized edema, leg edema, malaise, pain, rigors;

Cardiovascular: flushing, hypertension, tachycardia;

Endocrine: goiter;

Gastrointestinal: bowel irregularity, constipation aggravated, dyspepsia, dysphagia, dysplasia GI, epigastric pain, eructation, esophageal disorder, frequent stools, gastroenteritis, GI hemorrhage, GI symptoms not otherwise specified, hiccup, melena, mouth disorder, pharynx disorder, rectal disorder, serum gastrin increased, tongue disorder, tongue edema, ulcerative stomatitis, vomiting;

Hearing: earache, tinnitus;

Hematologic: anemia, anemia hypochromic, cervical lymphadenopathy, epistaxis, leukocytosis, leukopenia, thrombocytopenia;

Hepatic: bilirubinemia, hepatic function abnormal, SGOT increased, SGPT increased;

Metabolic/Nutritional: glycosuria, hyperuricemia, hyponatremia, increased alkaline phosphatase, thirst, vitamin B12 deficiency, weight increase, weight decrease;

Musculoskeletal: arthralgia, arthritis aggravated, arthropathy, cramps, fibromyalgia syndrome, hernia, polymyalgia rheumatica;

Nervous System/Psychiatric: anorexia, apathy, appetite increased, confusion, depression aggravated, dizziness, hypertonia, nervousness, hypoesthesia, impotence, insomnia, migraine, migraine aggravated, paresthesia, sleep disorder, somnolence, tremor, vertigo, visual field defect;

Reproductive: dysmenorrhea, menstrual disorder, vaginitis;

Respiratory: asthma aggravated, coughing, dyspnea, larynx edema, pharyngitis, rhinitis, sinusitis;

Skin and Appendages: acne, angioedema, dermatitis, pruritus, pruritus ani, rash, rash erythematous, rash maculo-papular, skin inflammation, sweating increased, urticaria;

Special Senses: otitis media, parosmia, taste loss, taste perversion;

Urogenital: abnormal urine, albuminuria, cystitis, dysuria, fungal infection, hematuria, micturition frequency, moniliasis, genital moniliasis, polyuria;

Visual: conjunctivitis, vision abnormal.

ESOMEPRAZOLE DRUG REACTIONS:

Co-administration of atazanavir with proton pump inhibitors is expected to substantially decrease atazanavir plasma concentrations and may result in a loss of therapeutic effect and the development of drug resistance. Co-administration of saquinavir with proton pump inhibitors is expected to increase saquinavir concentrations, which may increase toxicity and require dose reduction.

Like with other drugs that decrease the intragastric acidity, the absorption of drugs such as ketoconazole, atazanavir, iron salts, erlotinib and mycophenolate mofetil (MMF) can decrease, while the absorption of drugs such as digoxin can increase during treatment with esomeprazole.

Esomeprazole may potentially interfere with CYP2C19, the major esomeprazole metabolizing enzyme. Concomitant use of esomeprazole 40 mg results in reduced plasma concentrations of the active metabolite of clopidogrel and a reduction in platelet inhibition

Concomitant use of esomeprazole 40 mg results in reduced plasma concentrations of the active metabolite of clopidogrel and a reduction in platelet inhibition

Drugs known to induce CYP2C19 or CYP3A4 or both (such as rifampin) may lead to decreased esomeprazole serum levels.

Concomitant administration of esomeprazole and tacrolimus may increase the serum levels of tacrolimus.

Case reports, published population pharmacokinetic studies, and retrospective analyses suggest that concomitant administration of PPIs and methotrexate (primarily at high dose; see methotrexate prescribing information) may elevate and prolong serum levels of methotrexate and/or its metabolite hydroxymethotrexate

Pharmacokinetics

Absorption
Esomeprazole magnesium delayed-release capsules contain a bioequivalent enteric-coated granule formulation of esomeprazole magnesium. Bioequivalency is based on a single dose (40 mg) study in 94 healthy male and female volunteers under fasting condition. After oral administration peak plasma levels (Cmax) occur at approximately 1.5 hours (Tmax). The Cmax increases proportionally when the dose is increased, and there is a three-fold increase in the area under the plasma concentration-time curve (AUC) from 20 to 40 mg. At repeated once-daily dosing with 40 mg, the systemic bioavailability is approximately 90% compared to 64% after a single dose of 40 mg. The mean exposure (AUC) to esomeprazole increases from 4.32 μmol*hr/L on Day 1 to 11.2 μmol*hr/L on Day 5 after 40 mg once daily dosing.

Distribution
Esomeprazole is 97% bound to plasma proteins. Plasma protein binding is constant over the concentration range of 2 to 20 μmol/L. The apparent volume of distribution at steady state in healthy volunteers is approximately 16 L.

Metabolism
Esomeprazole is extensively metabolized in the liver by the cytochrome P450 (CYP) enzyme system. The metabolites of esomeprazole lack antisecretory activity. The major part of esomeprazole’s metabolism is dependent upon the CYP 2C19 isoenzyme, which forms the hydroxy and desmethyl metabolites. The remaining amount is dependent on CYP 3A4 which forms the sulphone metabolite.

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