Esomeprazole Sodium

Name: Esomeprazole Sodium

Description

The active ingredient in NEXIUM® I.V. (esomeprazole sodium) for Injection is (S)-5-methoxy-2[[(4-methoxy-3,5dimethyl-2-pyridinyl)-methyl]sulfinyl]-1 H-benzimidazole sodium, a proton pump inhibitor that inhibits gastric acid secretion. Esomeprazole is the S-isomer of omeprazole, which is a mixture of the S- and R- isomers. Its empirical formula is C17H18N3O3SNa with molecular weight of 367.4 g/mol (sodium salt) and 345.4 g/mol (parent compound). Esomeprazole sodium is very soluble in water and freely soluble in ethanol (95%). The structural formula is:

NEXIUM I.V. for Injection is supplied as a sterile, freeze-dried, white to off-white, porous cake or powder in a 5 mL vial, intended for intravenous administration after reconstitution with 0.9% Sodium Chloride Injection, USP; Lactated Ringer's Injection, USP or 5% Dextrose Injection, USP. NEXIUM I.V. for Injection contains esomeprazole sodium 21.3 mg or 42.5 mg equivalent to esomeprazole 20 mg or 40 mg, edetate disodium 1.5 mg and sodium hydroxide q.s. for pH adjustment. The pH of reconstituted solution of NEXIUM I.V. for Injection depends on the reconstitution volume and is in the pH range of 9 to 11. The stability of esomeprazole sodium in aqueous solution is strongly pH dependent. The rate of degradation increases with decreasing pH.

Where can i get more information?

Your pharmacist can provide more information about esomeprazole.

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Interactions for Esomeprazole Sodium

Extensively metabolized by CYP isoenzymes, principally CYP2C19; also to lesser extent by CYP3A4.1 19 34 May inhibit CYP2C19; unlikely to inhibit CYP3A4, 1A2, 2A6, 2C9, 2D6, or 2E1.1 34

Drugs Metabolized by Hepatic Microsomal Enzymes

Potential to inhibit metabolism of drugs metabolized by CYP2C19.1 34 Interaction unlikely with drugs metabolized by other CYP isoenzymes.1 34

Drugs Affecting Hepatic Microsomal Enzymes

Combined inhibitors of CYP2C19 and CYP3A4: Potential pharmacokinetic interaction (increased esomeprazole exposure); esomeprazole dosage adjustment usually not required but may be considered in patients receiving high dosages (up to 240 mg daily), such as those with Zollinger-Ellison syndrome.1 34

Inducers of CYP2C19 and/or CYP3A4: Potential pharmacokinetic interaction (decreased esomeprazole concentrations).1 34

Drugs that Cause Hypomagnesemia

Potential pharmacologic interaction (possible increased risk of hypomagnesemia).327 Consider monitoring magnesium concentrations prior to initiation of prescription proton-pump inhibitor therapy and periodically thereafter.1 34 327 (See Hypomagnesemia under Cautions.)

Specific Drugs and Laboratory Tests

Drug or Test

Interaction

Comments

Amoxicillin

Pharmacokinetic interaction unlikely1 34

Atazanavir

Possible altered oral absorption of atazanavir, resulting in decreased plasma atazanavir concentrations; possible loss of virologic response and development of drug resistance1 31 34

Manufacturer of esomeprazole states that concomitant administration with atazanavir is not recommended1 34

Antiretroviral treatment-naive patients: If a proton-pump inhibitor is used concomitantly with atazanavir, administer ritonavir-boosted atazanavir (atazanavir 300 mg and ritonavir 100 mg once daily with food); administer the proton-pump inhibitor approximately 12 hours before ritonavir-boosted atazanavir31 32

For treatment-naive patients, dosage of proton-pump inhibitor should not exceed omeprazole 20 mg daily (or equivalent)31 32

Antiretroviral treatment-experienced patients: Concomitant use of proton-pump inhibitors with atazanavir not recommended31 32

Cilostazol

Possible increased concentrations of cilostazol and its active metabolite1 34

Consider reducing cilostazol dosage (from 100 mg twice daily to 50 mg twice daily)1 34

Clarithromycin

Increased plasma concentrations of esomeprazole and 14-hydroxyclarithromycin 1

Not considered clinically important1 34 316

Clopidogrel

Esomeprazole (or omeprazole) reduces exposure to clopidogrel's active metabolite and decreases platelet inhibitory effects;44 224 225 228 232 233 236 350 additional data needed to fully elucidate potential clinical consequences (e.g., increased cardiovascular events)40 41 42 44 45 224 225 228 229 230 235 236 237 238 240 311

Dexlansoprazole, lansoprazole, or pantoprazole had less effect on clopidogrel's antiplatelet activity than did omeprazole or esomeprazole224 350 351

Avoid concomitant use of esomeprazole (or omeprazole) and clopidogrel224

Assess risks and benefits of concomitant proton-pump inhibitor and clopidogrel use in individual patients312 313 314 315 316

American College of Cardiology Foundation/American College of Gastroenterology/American Heart Association (ACCF/ACG/AHA) states that GI bleeding risk reduction with concomitant proton-pump inhibitor in patients with risk factors for GI bleeding (e.g., advanced age; concomitant use of warfarin, corticosteroids, or NSAIAs; H. pylori infection) may outweigh potential reduction in cardiovascular efficacy of antiplatelet treatment associated with a drug-drug interaction.311 In patients without such risk factors, ACCF/ACG/AHA states that risk/benefit balance may favor use of antiplatelet therapy without a proton-pump inhibitor.311

If concomitant therapy with a proton-pump inhibitor and clopidogrel is deemed necessary, consider using an agent with little or no CYP2C19-inhibitory activity;44 45 46 224 230 350 alternatively, consider using a histamine H2-receptor antagonist (ranitidine, famotidine, nizatidine)44 45 230 but not cimetidine (also a potent CYP2C19 inhibitor)232 233

Diazepam

Decreased diazepam metabolism and increased plasma concentrations1 34

Not considered clinically important1 34

Digoxin

Hypomagnesemia (e.g., resulting from long-term use of proton-pump inhibitors) sensitizes the myocardium to digoxin and, thus, may increase risk of digoxin-induced cardiotoxic effects327 331

See table entry for gastric pH-dependent drugs

Consider monitoring magnesium concentrations prior to initiation of prescription proton-pump inhibitor therapy and periodically thereafter1 327

Diuretics (i.e., loop or thiazide diuretics)

Possible increased risk of hypomagnesemia327

Consider monitoring magnesium concentrations prior to initiation of prescription proton-pump inhibitor therapy and periodically thereafter1 327

Fosamprenavir

Fosamprenavir: Increased esomeprazole AUC; no substantial effect on concentrations of amprenavir (active metabolite of fosamprenavir)345

Ritonavir-boosted fosamprenavir: No substantial effect on amprenavir or esomeprazole concentrations345

Fosamprenavir (with or without ritonavir): No dosage adjustment required32 345

Gastric pH-dependent drugs (e.g., atazanavir, digoxin, erlotinib, iron salts, ketoconazole)

Atazanavir, erlotinib, iron salts, ketoconazole: Possible decreased absorption1 34

Digoxin: Possible increased exposure1 34

Digoxin: May need to monitor for manifestations of digoxin toxicity1 34

Lopinavir

Lopinavir/ritonavir: Omeprazole had no clinically important effect on lopinavir plasma concentrations or AUC32 344

No dosage adjustment required when proton-pump inhibitors used with lopinavir/ritonavir32

Methotrexate

Possible delayed clearance and increased serum concentrations of methotrexate and/or its metabolite hydroxymethotrexate; possible methotrexate toxicity1 34 333 334

Reported mainly with high-dose methotrexate (300 mg/m2 to 12 g/m2),1 34 333 but also reported with low dosages (e.g., 15 mg per week)333

Manufacturer of esomeprazole recommends considering temporary discontinuance of proton-pump inhibitor therapy in some patients receiving high-dose methotrexate1 34

Some clinicians recommend withholding the proton-pump inhibitor for several days before and after administration of either high-dose or low-dose methotrexate or, alternatively, substituting a histamine H2-receptor antagonist for the proton-pump inhibitor333 334

Nelfinavir

Omeprazole decreased peak plasma concentrations and AUCs of nelfinavir and its major active metabolite1 34 347

Concomitant use of nelfinavir with proton-pump inhibitors not recommended1 34

NSAIAs (naproxen, rofecoxib)

Pharmacokinetic interaction unlikely1 34

Oral contraceptives

No change in esomeprazole pharmacokinetics1 34

Phenytoin

Pharmacokinetic interaction unlikely1 34

Quinidine

Pharmacokinetic interaction unlikely1 34

Raltegravir

Omeprazole increased peak plasma concentration and AUC of raltegravir32 348

No dosage adjustment recommended when proton-pump inhibitors used with raltegravir32 348

Rifampin

Possible decreased esomeprazole concentrations1 34

Avoid concomitant use1 34

Rilpivirine

Omeprazole decreased plasma concentrations and AUC of rilpivirine32 343

Concomitant use of rilpivirine and proton-pump inhibitors contraindicated32 343

Saquinavir

Ritonavir-boosted saquinavir: Omeprazole increased peak plasma concentration and AUC of saquinavir1 32 34 346

Caution advised if proton-pump inhibitor used with ritonavir-boosted saquinavir; monitor for saquinavir toxicity1 32 34 346

Manufacturer of esomeprazole recommends considering saquinavir dosage reduction on an individual basis1 34

St. John’s wort (Hypericum perforatum)

Possible decreased esomeprazole concentrations1 34

Avoid concomitant use1 34

Sucralfate

Possible delayed proton-pump inhibitor absorption and decreased bioavailability 47

Administer proton-pump inhibitor at least 30 minutes before sucralfate47

Tacrolimus

Possible increased tacrolimus concentrations1 34

Tests for neuroendocrine tumors

Increased serum chromogranin A (CgA) concentrations (secondary to esomeprazole-induced increase in intragastric pH) may produce false-positive results1 34

Temporarily discontinue esomeprazole before assessing CgA concentrations and consider repeating test if initial CgA concentrations are high1 34

Voriconazole

Possible increase in esomeprazole exposure1 34

Esomeprazole dosage adjustment usually not required but may be considered in patients receiving high dosages (up to 240 mg daily), such as those with Zollinger-Ellison syndrome1 34

Warfarin

Potential for decreased warfarin metabolism and changes in prothrombin measures1 34

Monitor PT and INR1 34

Esomeprazole Sodium Pharmacokinetics

Absorption

Bioavailability

Delayed-release esomeprazole: Bioavailability is 64% after a single 40-mg oral dose.1 Bioavailability is 90% after repeated oral doses of 40 mg once daily.1

Food

Delayed-release esomeprazole: AUC decreased by 43–53% when a 40-mg oral dose was administered with food.1

Immediate-release esomeprazole/delayed-release naproxen tablets: Administration with high-fat food decreases rate and extent of esomeprazole absorption (peak plasma concentration delayed by 1 hour, AUC decreased 52%, peak concentration decreased 74%).342 Administration 30 minutes before high-fat food does not substantially alter rate or extent of esomeprazole absorption relative to fasted state.342 Administration 1 hour before high-fat food increases esomeprazole AUC and peak concentration by 25 and 50%, respectively, but peak concentration is lower than that observed with labeled dosage of esomeprazole 40 mg daily.342

Special Populations

Following oral dosage of 40 mg once daily in patients with severe (Child-Pugh class C) hepatic impairment, steady-state AUCs were 2–3 times greater than those in patients with normal hepatic function.1 34

Distribution

Extent

Not known whether esomeprazole is distributed into milk, but omeprazole is distributed into milk.1 34 Not known whether esomeprazole crosses the placenta.1 34

Prolonged binding to gastric parietal proton pump enzyme.1 6

Plasma Protein Binding

97%.1 34

Elimination

Metabolism

Metabolized to inactive metabolites in the liver by CYP isoenzymes, principally by CYP2C19, and to lesser extent by CYP3A4.1 34

Elimination Route

Excreted principally in urine (80% as inactive metabolites, <1% as active drug); remainder in feces as inactive metabolites.1 34

Half-life

Adults, oral administration: 1–1.5 hours.1 Slower elimination than R-omeprazole or racemic omeprazole (0.5–1 hour).1 5 6

Adults, IV administration: 1.1–1.4 hours; prolonged with increasing dose.34

Adolescents 12–17 years of age, oral administration: 0.8–1.2 hours.1

Children 1–11 years of age, oral administration: 0.7–0.9 hours.1

Infants 1–11 months of age, oral administration: 0.9 hours.1

Special Populations

In patients with poor CYP2C19 metabolizer phenotype, steady-state AUCs were 2 times greater than those in patients with extensive (or rapid) metabolizer phenotype.1 34

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Esomeprazole Magnesium

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules, delayed-release (containing enteric-coated pellets)

20 mg (of esomeprazole)

NexIUM

AstraZeneca

40 mg (of esomeprazole)

NexIUM

AstraZeneca

For suspension, delayed-release (containing enteric-coated granules)

2.5 mg (of esomeprazole) per packet

NexIUM

AstraZeneca

5 mg (of esomeprazole) per packet

NexIUM

AstraZeneca

10 mg (of esomeprazole) per packet

NexIUM

AstraZeneca

20 mg (of esomeprazole) per packet

NexIUM

AstraZeneca

40 mg (of esomeprazole) per packet

NexIUM

AstraZeneca

Esomeprazole Magnesium Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, delayed-release core (naproxen only)

20 mg (of esomeprazole) with Naproxen 375 mg

Vimovo

AstraZeneca

20 mg (of esomeprazole) with Naproxen 500 mg

Vimovo

AstraZeneca

Esomeprazole Sodium

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for IV use

20 mg (of esomeprazole)

NexIUM I.V.

AstraZeneca

40 mg (of esomeprazole)

NexIUM I.V.

AstraZeneca

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