Esomeprazole Sodium

Pronunciation

Class: Proton-pump Inhibitors
Note: This monograph also contains information on Esomeprazole Magnesium
VA Class: GA900
Chemical Name: 5-Methoxy-2-[(S)[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazole magnesium salt trihydrate
Molecular Formula: C34H36MgN6O6S2•3H2OC17H18N3O3S•Na
CAS Number: 217087-09-7
Brands: Nexium, Vimovo (combination)

Introduction

Acid- or proton-pump inhibitor; gastric antisecretory agent.1 3 5 19 34 S-isomer of omeprazole.1 5 9 34

Uses for Esomeprazole Sodium

Gastroesophageal Reflux (GERD)

Short-term treatment of symptomatic GERD (e.g., heartburn) in patients without erosive esophagitis.1

Short-term treatment of erosive esophagitis (diagnostically confirmed) in patients with GERD.1 Short-term treatment of erosive esophagitis due to acid-mediated GERD in infants.1

Maintain healing, symptom resolution, and decrease recurrence of erosive esophagitis.1

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IV as short-term alternative to oral therapy in patients with erosive esophagitis who are unable to take the drug orally; safety and efficacy not established beyond 10 days.34

Duodenal Ulcer

Treatment of Helicobacter pylori infection and duodenal ulcer disease (active duodenal ulcer or history of duodenal ulcer in the past 5 years).1 Used in conjunction with amoxicillin and clarithromycin (triple therapy).1

NSAIA-associated Ulcers

Reduction in the occurrence of gastric ulcers associated with chronic NSAIA therapy in patients at risk (i.e., ≥60 years of age and/or history of gastric ulcer).1 33 342 Effect on occurrence of duodenal ulcers not established.1 33

Crohn’s Disease-associated Ulcers

Some evidence for use of proton-pump inhibitors (e.g., omeprazole) for gastric acid suppressive therapy as an adjunct in the management of upper GI Crohn’s disease, including esophageal, gastroduodenal, and jejunoileal disease.22 23 24 25 26 27 28

Esomeprazole Sodium Dosage and Administration

Administration

Administer orally or IV.1 34

Oral Administration

Administer esomeprazole capsules and oral suspension orally at least 1 hour before a meal.1 Administer esomeprazole/naproxen fixed-combination tablets at least 30 minutes before a meal.342 (See Food under Pharmacokinetics.)

Antacids may be used concomitantly as needed for pain relief.1

Capsules

Swallow capsules intact; do not chew or crush.1

Alternatively, open capsule and mix contents with 1 tablespoon applesauce; swallow immediately without chewing.1 Applesauce should not be hot and should be soft enough to swallow without chewing.1

Powder for Oral Suspension

Mix contents of 2.5- or 5-mg packet with 5 mL of water.1

Mix contents of 10-, 20-, or 40-mg packet with 15 mL of water.1

If a single dose requires 2 packets, reconstitute oral suspension with twice the water needed for 1 packet.1

After mixing suspension with appropriate amount of water, allow mixture to thicken for 2–3 minutes.1 Stir mixture and consume within 30 minutes of preparation.1 If any drug mixture remains in container after ingestion, mix with additional water and ingest immediately.1

NG Tube

May administer suspension prepared from opened capsules through NG tube; may administer suspension prepared from powder for oral suspension through NG tube or gastric tube (6 French or larger).1

Capsules: Open capsule, empty intact granules into 60-mL catheter-tipped syringe, and mix with 50 mL of water.1 Replace plunger and shake well for 15 seconds.1 Hold syringe with tip upright and check tip for remaining granules.1 Administer immediately through NG tube; flush with additional water.1 Do not administer if pellets have dissolved or disintegrated.1

Powder for oral suspension: Mix contents of 2.5- or 5-mg packet with 5 mL of water and contents of 10-, 20-, or 40-mg packet with 15 mL of water in a catheter-tipped syringe; shake immediately, then allow mixture to thicken for 2–3 minutes.1 Shake syringe and administer through NG or gastric tube (6 French or larger) within 30 minutes of preparation.1 Refill syringe with additional water (5 or 15 mL, respectively) and flush NG or gastric tube.1

Esomeprazole/Naproxen Fixed-combination Tablets

Swallow tablets whole with liquid; do not split, chew, crush, or dissolve tablets.342

IV Administration

For solution compatibility information, see Compatibility under Stability.

Administer by slow direct IV injection or by IV infusion.34

Flush the IV line with 0.9% sodium chloride, lactated Ringer’s, or 5% dextrose injection before and after administration.34

Do not administer with any other drugs or diluents because of potential incompatibilities.34

Reconstitution

For direct IV injection in adults, reconstitute vial containing 20 or 40 mg of esomeprazole with 5 mL of 0.9% sodium chloride injection.34

For IV infusion in adults, reconstitute vial containing 20 or 40 mg of esomeprazole with 5 mL of 5% dextrose, 0.9% sodium chloride, or lactated Ringer’s injection.34 Dilute reconstituted solution prior to infusion.34

For IV infusion in pediatric patients 1 month to 17 years of age, reconstitute vial containing 20 or 40 mg of esomeprazole with 5 mL of 0.9% sodium chloride injection to provide a solution containing 4 or 8 mg/mL, respectively.34 Dilute reconstituted solution prior to infusion.34

Dilution

For IV infusion in adults, dilute the reconstituted solution to a final volume of 50 mL with a compatible IV solution (see Compatibility under Stability).34

For IV infusion in pediatric patients 1 month to 17 years of age, dilute the reconstituted 4- or 8-mg/mL solution to a final volume of 50 mL with 0.9% sodium chloride injection to yield a final concentration of 0.4 or 0.8 mg/mL, respectively.34 Withdraw the appropriate dose from the diluted solution.34

Rate of Administration

IV injection in adults: Administer reconstituted solution by slow (over ≥3 minutes) direct IV injection.34

IV infusion in adults and pediatric patients: Administer diluted solution by IV infusion over 10–30 minutes.34

Dosage

Available as esomeprazole magnesium and esomeprazole sodium; dosage expressed in terms of esomeprazole.1 34

Pediatric Patients

GERD
GERD Without Erosive Esophagitis
Oral

Children 1–11 years of age: 10 mg once daily for up to 8 weeks.1

Adolescents 12–17 years of age: 20 or 40 mg once daily for up to 8 weeks.1

Treatment of Erosive Esophagitis
Oral
Oral Esomeprazole Dosage for Treatment of Erosive Esophagitis in Pediatric Patients1

Age

Body Weight

Esomeprazole Dosage

1 month to <1 year of age

3–5 kg

2.5 mg once daily for up to 6 weeks

>5 to 7.5 kg

5 mg once daily for up to 6 weeks

>7.5 to 12 kg

10 mg once daily for up to 6 weeks

1–11 years of age

<20 kg

10 mg once daily for up to 8 weeks

≥20 kg

10 or 20 mg once daily for up to 8 weeks

IV

Infants 1 month to <1 year of age: 0.5 mg/kg once daily.34 48

Children and adolescents 1–17 years of age: 10 mg once daily in those weighing <55 kg; 20 mg once daily in those weighing ≥55 kg.34 48

Discontinue IV administration as soon as patient can take the drug orally.34

Adults

GERD
GERD Without Erosive Esophagitis
Oral

20 mg once daily for 4 weeks; may give an additional 4 weeks of therapy.1 Chronic proton-pump inhibitor therapy may be appropriate.21

Treatment of Erosive Esophagitis
Oral

20 or 40 mg once daily for 4–8 weeks;1 may give an additional 4–8 weeks of therapy.1

IV

20 or 40 mg once daily.34 Safety and efficacy not established beyond 10 days; discontinue IV administration as soon as patient can take the drug orally.34

Maintenance of Healing of Erosive Esophagitis
Oral

20 mg once daily; not studied >6 months.1

Duodenal Ulcer
Helicobacter pylori Infection and Duodenal Ulcer
Oral

Triple therapy: 40 mg once daily for 10 days in conjunction with amoxicillin and clarithromycin.1

NSAIA-associated Ulcers
Prevention of Gastric Ulcers
Oral

20 or 40 mg once daily; not studied >6 months.1

Esomeprazole/naproxen fixed combination: Esomeprazole 20 mg (with naproxen 375 or 500 mg) twice daily.342 Do not use fixed combination if esomeprazole dosage requirement is <40 mg daily.342

Prescribing Limits

Pediatric Patients

GERD
GERD Without Erosive Esophagitis
Oral

Children 1–11 years of age: Dosages >1 mg/kg daily not studied.1

Treatment of Erosive Esophagitis
Oral

Infants 1 month to <1 year of age: Dosages >1.33 mg/kg daily not studied.1

Children 1–11 years of age: Dosages >1 mg/kg daily not studied.1

Special Populations

Hepatic Impairment

Oral or IV dosage should not exceed 20 mg once daily in patients with severe (Child-Pugh class C) hepatic impairment.1 34 342 No dosage adjustment required for mild or moderate (Child-Pugh class A or B, respectively) hepatic impairment.1 34

Esomeprazole/naproxen fixed combination not recommended in patients with severe hepatic impairment.342

Renal Impairment

Esomeprazole/naproxen fixed combination not recommended in patients with Clcr <30 mL/minute.342

Cautions for Esomeprazole Sodium

Contraindications

  • Known hypersensitivity to esomeprazole, any ingredient in the formulation, or other substituted benzimidazoles (e.g., lansoprazole, omeprazole, pantoprazole, rabeprazole).1 34

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity Reactions

Hypersensitivity reactions (e.g., angioedema, anaphylactic shock) reported.1 34

Gastric Malignancy

Response to esomeprazole does not preclude presence of occult gastric neoplasm.1 34

Atrophic Gastritis

Atrophic gastritis reported occasionally with long-term omeprazole use.1 34

Clostridium difficile Infection

Proton-pump inhibitors associated with possible increased (1.4–2.75 times) risk of Clostridium difficile infection, including C. difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis).335 336 339 340 Many patients also had other risk factors for CDAD.335 May be severe; colectomy and, rarely, death reported.335

Use the lowest effective dosage and shortest duration of therapy appropriate for the patient's clinical condition.335

Consider CDAD if persistent diarrhea develops and manage accordingly; initiate supportive therapy (e.g., fluid and electrolyte management), anti-infective therapy directed against C. difficile (e.g., metronidazole, vancomycin), and surgical evaluation as clinically indicated.335 336

Bone Fracture

Several observational studies suggest that use of proton-pump inhibitors, particularly in high dosages (i.e., multiple daily doses) and/or for prolonged periods of time (i.e., ≥1 year), may be associated with increased risk of osteoporosis-related fractures of the hip, wrist, or spine.1 34 35 300 301 302 303 304 305 Magnitude of risk is unclear;35 300 301 302 303 304 305 310 causality not established.305 FDA is continuing to evaluate this safety concern.305

Use the lowest effective dosage and shortest duration of therapy appropriate for the patient’s clinical condition.1 34 35 301 303 305 307

Individuals at risk for osteoporosis-related fractures should receive an adequate intake of calcium and vitamin D; assess and manage these patients’ bone health according to current standards of care.1 34 35 303 305 307

Hypomagnesemia

Hypomagnesemia, symptomatic and asymptomatic, reported rarely in patients receiving long-term therapy (≥3 months or, in most cases, >1 year) with proton-pump inhibitors, including esomeprazole.1 34 317 318 319 320 321 322 323 324 325 326 327 328 329 330 Serious adverse effects include tetany, seizures, tremors, carpopedal spasm, arrhythmias (e.g., atrial fibrillation, supraventricular tachycardia), and abnormal QT interval.1 34 318 319 321 322 323 325 327 328 329 Paresthesia, muscle weakness, muscle cramps, lethargy, fatigue, and unsteadiness may occur.319 320 321 325 330 Most patients required magnesium replacement and discontinuance of the proton-pump inhibitor.1 34 317 319 321 322 323 324 325 326 327 330 Hypomagnesemia resolved within 1 week (median) following discontinuance and recurred within 2 weeks (median) of rechallenge.327

In patients expected to receive long-term proton-pump inhibitor therapy or in patients currently receiving digoxin or drugs that may cause hypomagnesemia (e.g., diuretics), consider measuring serum magnesium concentrations prior to initiation of prescription proton-pump inhibitor therapy and periodically thereafter.1 34 319 326 327 328 330

Cardiovascular Effects

Preliminary safety data from 2 long-term clinical trials comparing esomeprazole or omeprazole with antireflux surgery in patients with severe GERD raised concerns about a potential increased risk of cardiac events (e.g., MI, heart failure, sudden death) in patients receiving these drugs.36 37 38 After reviewing data from these and other studies, FDA has concluded that long-term use of these drugs is not likely to be associated with an increased risk of such cardiac events.36 37 38 FDA recommends that clinicians continue to prescribe and patients continue to use these drugs in the manner described in the manufacturers’ labelings.36 37 38

Respiratory Effects

Administration of proton-pump inhibitors has been associated with an increased risk for developing certain infections (e.g., community-acquired pneumonia).29 30

Use of Fixed Combinations

When used in fixed combination with naproxen, consider the cautions, precautions, and contraindications associated with naproxen.342

Specific Populations

Pregnancy

Category B.1 34

Lactation

Not known whether esomeprazole is distributed into milk, but omeprazole is distributed into milk.1 34 Discontinue nursing or the drug.1 34

Pediatric Use

Safety and efficacy of oral esomeprazole for short-term (4–8 weeks) treatment of GERD established in pediatric patients 1–17 years of age.1 Adverse effects and pharmacokinetics in children and adolescents similar to those reported in adults.1

Safety and efficacy of oral esomeprazole for short-term (up to 6 weeks) treatment of erosive esophagitis due to acid-mediated GERD established in infants 1 month to <1 year of age.1 Oral esomeprazole was not more effective than placebo in a randomized, controlled, treatment-withdrawal study in infants 1–11 months of age with symptomatic GERD.1 Common adverse effects include irritability and vomiting.1

Efficacy of oral esomeprazole not established in infants <1 month of age.1

Safety and efficacy of IV esomeprazole for short-term treatment of GERD with erosive esophagitis established in pediatric patients 1 month to 17 years of age.34 Adverse effects consistent with the drug's known safety profile.34

Safety and efficacy of IV esomeprazole in neonates <1 month of age not established.34

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults, but increased sensitivity cannot be ruled out.1 34

Hepatic Impairment

Use with caution in patients with severe hepatic impairment.1 20 (See Hepatic Impairment under Dosage and Administration.)

Common Adverse Effects

Oral: Headache, diarrhea, nausea, flatulence, abdominal pain, constipation, dry mouth.1 19

IV: Similar adverse effects as oral esomeprazole; also injection site reaction, dizziness/vertigo, pruritus.34

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

Stability

Storage

Oral

Capsules

25°C (may be exposed to 15–30°C) in tightly-closed containers.1

Fixed-combination Tablet (Vimovo)

25°C (may be exposed to 15–30°C) in tightly-closed containers.342

Powder for Oral Suspension

25°C (may be exposed to 15–30°C).1

Parenteral

Powder for IV Injection or Infusion

Powder: 25°C (may be exposed to 15–30°C).34 Protect from light.34

Reconstituted solution: Room temperature (up to 30°C) for up to 12 hours.34

Admixture: Room temperature (up to 30°C) for up to 6 hours (in 50 mL of 5% dextrose injection) or 12 hours (in 50 mL of lactated Ringer’s or 0.9% sodium chloride injection).34

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Oral

Capsules

Use extemporaneous mixture of capsule contents (enteric-coated pellets) and applesauce immediately; do not store for future use.1 Applesauce should not be hot.1

Parenteral

Solution Compatibility34 HID

Compatible

Dextrose 5% in water

Ringer’s injection, lactated

Sodium chloride 0.9%

Drug Compatibility
Y-Site CompatibilityHID

Compatible

Doripenem

Actions

  • Inhibits basal and stimulated gastric acid secretion.1 2 7 8 9

  • Concentrates in acid conditions of parietal cell secretory canaliculi; forms active sulfonamide metabolite that irreversibly binds to and inactivates hydrogen-potassium ATPase (proton- or acid pump), blocking final step in secretion of hydrochloric acid.1 2 4 7 8 9 10 34 Acid secretion is inhibited until additional hydrogen-potassium ATPase is synthesized, resulting in prolonged duration of action.2 4 7 8 9 10

  • More esomeprazole reaches and blocks proton pump than does R-omeprazole; therefore, provides greater intragastric pH control than racemic omeprazole.1 5

  • Suppresses H. pylori in patients with duodenal ulcer and/or reflux esophagitis who are infected with the organism.2 Combined therapy with esomeprazole and appropriate anti-infectives (i.e., amoxicillin, clarithromycin) can effectively eradicate H. pylori gastric infection.1 2

Advice to Patients

  • Importance of swallowing capsule intact, without crushing or chewing.1

  • Importance of taking 1 hour before a meal.1

  • If capsule contents are mixed with applesauce for administration, importance of applesauce being soft enough to swallow without chewing.1 Importance of not using hot applesauce.1 Importance of immediately swallowing mixture without crushing or chewing;1 do not store for later use.1

  • If oral suspension is used, importance of mixing packet contents with an appropriate amount of water, allowing mixture to thicken for 2–3 minutes, and then drinking mixture (without crushing or chewing the granules) within 30 minutes of preparation.1

  • Importance of advising patients that use of multiple daily doses of the drug for an extended period of time may increase the risk of fractures of the hip, wrist, or spine.1 305

  • Risk of hypomagnesemia; importance of immediately reporting and seeking care for any cardiovascular or neurologic manifestations (e.g., palpitations, dizziness, seizures, tetany).1

  • Possible increased risk of Clostridium difficile infection; importance of contacting a clinician if persistent watery stools, abdominal pain, and fever occur.335

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1 Antacids may be used concomitantly as needed for pain relief.1

  • Importance of women informing their clinicians if they are or plan to become pregnant or plan to breast-feed.1 34

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

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

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

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

NexIUM 10MG Packet (ASTRAZENECA LP): 30/$195.99 or 90/$559.00

NexIUM 20MG Delayed-release Capsules (ASTRAZENECA LP): 30/$200.99 or 90/$559.99

NexIUM 20MG Packet (ASTRAZENECA LP): 30/$205.99 or 90/$595.97

NexIUM 40MG Delayed-release Capsules (ASTRAZENECA LP): 30/$189.99 or 90/$549.97

NexIUM 40MG Packet (ASTRAZENECA LP): 30/$195.99 or 90/$559.99

Vimovo 375-20MG Enteric-coated Tablets (ASTRAZENECA LP): 60/$109.99 or 180/$305.97

Vimovo 500-20MG Enteric-coated Tablets (ASTRAZENECA LP): 60/$109.99 or 180/$309.96

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions January 31, 2013. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

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229. Aubert RE, Epstein RS, Teagarden JR et al. Proton pump inhibitors effect on clopidogrel effectiveness: The clopidogrel Medco outcomes study. Circulation. 2008; 118:S_815, Abstract 3998.

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312. Last EJ, Sheehan AH. Review of recent evidence: potential interaction between clopidogrel and proton pump inhibitors. Am J Health Syst Pharm. 2009; 66:2117-22. [PubMed 19923312]

313. Stockl KM, Le L, Zakharyan A et al. Risk of rehospitalization for patients using clopidogrel with a proton pump inhibitor. Arch Intern Med. 2010; 170:704-10. [PubMed 20421557]

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335. Food and Drug Administration. Drug safety communication: Clostridium difficile-associated diarrhea can be associated with stomach acid drugs known as proton pump inhibitors (PPIs). Rockville, MD; 2012 Feb 8. From FDA website. Accessed 2012 May 3l.

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338. Leonard AD, Ho KM, Flexman J. Proton pump inhibitors and diarrhoea related to Clostridium difficile infection in hospitalised patients: a case-control study. Intern Med J. 2012; 42:591-4. [PubMed 22616966]

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341. Nerandzic MM, Pultz MJ, Donskey CJ. Examination of potential mechanisms to explain the association between proton pump inhibitors and Clostridium difficile infection. Antimicrob Agents Chemother. 2009; 53:4133-7. [PubMed 19667292]

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350. Frelinger AL, Lee RD, Mulford DJ et al. A randomized, 2-period, crossover design study to assess the effects of dexlansoprazole, lansoprazole, esomeprazole, and omeprazole on the steady-state pharmacokinetics and pharmacodynamics of clopidogrel in healthy volunteers. J Am Coll Cardiol. 2012; 59:1304-11. [PubMed 22464259]

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