Esomeprazole

Pronunciation

Pronunciation: ES-oh-MEP-ra-zole
Class: Proton pump inhibitor Esomeprazole Magnesium

Trade Names

Nexium
- Capsules, delayed release, oral 20 mg
- Capsules, delayed release, oral 40 mg

Nexium
- Powder for suspension, delayed release, oral 2.5 mg
- Powder for suspension, delayed release, oral 5 mg
- Powder for suspension, delayed release, oral 10 mg
- Powder for suspension, delayed release, oral 20 mg
- Powder for suspension, delayed release, oral 40 mg

Esomeprazole Sodium

Nexium I.V.
- Injection, lyophilized powder for solution 20 mg
- Injection, lyophilized powder for solution 40 mg

Pharmacology

Suppresses gastric acid secretion by blocking proton pump within gastric parietal cells.

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Pharmacokinetics

Absorption

T max is 1.5 h. Bioavailability is approximately 90% (repeated once-daily dosing) and 64% (single dose). Food decreases AUC by 43% to 53%. C max following IV administration of 20 and 40 mg for 5 days is 3.86 and 7.51 mcmol/L, respectively.

Distribution

Esomeprazole is 97% protein bound. Vd is approximately 16 L (at steady state).

Metabolism

Metabolized in the liver by CYP2C19 and CYP3A4 to inactive metabolites.

Elimination

The plasma elimination half-life is approximately 1 to 1.5 h. Less than 1% of parent drug is excreted in the urine; approximately 80% is excreted as inactive metabolites in the urine, and the remainder is found in feces.

Special Populations

Renal Function Impairment

Pharmacokinetics in patients with renal impairment are not expected to be altered because less than 1% of the dose is excreted unchanged in the urine.

Hepatic Function Impairment

AUC was 2 to 3 times higher in patients with severe hepatic impairment. AUC is unchanged in patients with mild and moderate hepatic impairment.

Elderly

AUC and C max were increased by 25% and 18%, respectively. Dosage adjustment is not necessary.

Children

Pharmacokinetics of oral esomeprazole in pediatric patients 12 to 17 y of age were similar to those observed in adults. Total exposure of esomeprazole 20 mg was higher in pediatric patients 6 to 11 y of age compared with pediatric patients 12 to 17 y of age and adults who received a 20 mg dose but lower than that observed with a 40 mg dose in pediatric patients 12 to 17 y of age and adults. AUC values after a 20 mg IV dose were 183% and 60% higher in pediatric patients 6 to 11 y of age and 12 to 17 y of age, respectively, compared with adults who received the same dose.

Gender

AUC and C max were 13% higher in women than men. Dosage adjustment is not necessary.

Indications and Usage

Oral

Short-term treatment of heartburn and other symptoms of gastroesophageal reflux disease (GERD); short-term treatment in healing and symptomatic resolution of erosive esophagitis; maintenance of symptom resolution and healing of erosive esophagitis; in combination with amoxicillin and clarithromycin for treatment of Helicobacter pylori infection and duodenal ulcer disease to eradicate H. pylori ; reduction in occurrence of gastric ulcers associated with continuous NSAID therapy in patients at risk of developing gastric ulcers; long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison syndrome.

IV

As an alternative to oral therapy when oral therapy with esomeprazole delayed-release capsules or suspension is not possible or appropriate for the short-term treatment of GERD with erosive esophagitis.

Unlabeled Uses

Non-GERD dyspepsia; Barrett esophagus; stress ulcer prophylaxis; prevention of GI bleeding in patients receiving antiplatelets.

Contraindications

Hypersensitivity to any component of the formulation, substituted benzimidazoles, or other proton pump inhibitors.

Dosage and Administration

Gastroesophageal Reflux Disease With Erosive Esophagitis
Adults

IV 20 or 40 mg once daily.

Pediatric patients 1 to 17 y of age

IV 10 mg (weight less than 55 kg) or 20 mg (weight 55 kg or more) once daily.

Pediatric patients 1 mo to younger than 1 y

IV 0.5 mg/kg once daily.

Healing of Erosive Esophagitis
Adults

PO 20 or 40 mg once daily for 4 to 8 wk. For patients who do not heal after 4 to 8 wk, consider an additional 4 to 8 wk of treatment. Maintenance treatment is 20 mg once daily.

Pediatric patients 1 to 11 y of age Weight less than 20 kg

PO Administer 10 mg once daily for 8 wk.

Weight at least 20 kg

PO Administer 10 or 20 mg once daily for 8 wk.

H. Pylori Eradication to Reduce Risk of Duodenal Ulcer Recurrence
Adults

PO 40 mg once daily in combination with amoxicillin 1,000 mg twice daily and clarithromycin 500 mg twice daily for 10 days.

Pathological Hypersecretory Conditions, Including Zollinger-Ellison Syndrome
Adults

PO 40 mg twice daily. Adjust the dose to individual patient needs. Dosages of up to 240 mg daily have been administered.

Risk Reduction of NSAID-Associated Gastric Ulcer
Adults

PO 20 or 40 mg once daily for up to 6 mo.

Short-Term Treatment of Gastroesophageal Reflux Disease
Pediatric patients 12 to 17 y of age

PO 20 or 40 mg once daily for up to 8 wk.

Pediatric patients 1 to 11 y of age

PO 10 mg once daily for up to 8 wk.

Erosive esophagitis due to acid-mediated Gastroesophageal Reflux Disease
Pediatric patients 1 mo to younger than 1 y

PO 2.5 mg (weight, 3 to 5 kg), 5 mg (weight, more than 5 kg to 7.5 kg), or 10 mg (weight, more than 7.5 kg to 12 kg) once daily for up to 6 wk. Dosages more than 1.33 mg/kg/day have not been studied.

Symptomatic Gastroesophageal Reflux Disease
Adults

PO 20 mg once daily for 4 wk. If symptoms do not resolve after 4 wk, an additional 4 wk of treatment may be considered.

Hepatic Function Impairment

For patients with severe impairment (Child-Pugh class C), do not exceed a dosage of 20 mg/day.

General Advice

  • Administer esomeprazole oral at least 1 h before meals.
  • Delayed-Release Capsules
  • Instruct patients to swallow the capsule whole and not to chew or crush it.
  • For patients who have difficulty swallowing the capsule, the contents of the capsule (pellets) may be emptied onto 1 Tbsp of applesauce in a bowl, gently mixed, and then swallowed immediately without chewing. Do not prepare the mixture ahead of time and store it for future use.
  • For administration via nasogastric (NG) tube, remove the plunger from a 60 mL catheter-tipped syringe and empty the contents of capsule into the syringe. Add 50 mL of water, replace the plunger, and shake vigorously for 15 sec to produce a suspension. Hold the syringe with the tip up and check for pellets remaining in the tip. Immediately attach the syringe to the NG tube and deliver the contents through the NG tube into the stomach. Flush the NG tube with additional water. Do not administer if pellets have dissolved or disintegrated. Do not prepare the suspension ahead of time and store it for future use.
  • Delayed-Release Oral Suspension
  • To administer the delayed-release oral suspension, empty the contents of a 2.5 or 5 mg packet into a container containing 5 mL of water or a 10, 20, or 40 mg packet into a container containing 15 mL of water and stir. Leave 2 to 3 min to thicken, then stir and drink within 30 min. If material remains after drinking, add more water, stir, and drink immediately.
  • For patients who have an NG or gastric tube, add 5 mL of water to the catheter-tipped syringe and add the contents of a 2.5 or 5 mg packet or 15 mL of water to a catheter-tipped syringe and add the contents of a 10, 20, or 40 mg packet. Immediately shake the syringe and leave 2 to 3 min to thicken. Shake the syringe and inject through the NG or gastric tube, French size 6 or larger, into the stomach within 30 min. Refill the syringe with 5 or 15 mL of water. Shake and flush any remaining contents from the NG or gastric tube into the stomach.
  • IV
  • For use when oral therapy is not possible or appropriate. Replace IV therapy with oral therapy as soon as possible.
  • For IV injection or infusion only. Administer only by IV infusion in children.
  • For IV injection in adults, reconstitute the lyophilized powder with 5 mL of sodium chloride 0.9% injection. Withdraw 5 mL of reconstituted solution and administer as an IV injection over no less than 3 min.
  • For IV infusion in adults, reconstitute 1 vial with 5 mL of sodium chloride 0.9%, Ringer's lactate, or dextrose 5% injection, and further dilute the resulting solution to 50 mL. For IV infusion in children, reconstitute 1 vial with 5 mL of sodium chloride 0.9% injection, and further dilute the resulting solution to 50 mL. The resulting concentration is 0.4 mg/mL (20 mg vial) or 0.8 mg/mL (40 mg vial). Administer over 10 to 30 min.
  • Do not add other medications or additives to the IV container or infuse simultaneously through the same IV line.
  • Flush the IV line with compatible IV fluid (sodium chloride 0.9%, Ringer's lactate, or dextrose 5% injection) before and after esomeprazole administration.

Storage/Stability

Oral

Store capsules and suspension between 59° and 86°F.

IV

Store vials for injection between 59° and 86°F. Store reconstituted IV injection solution at room temperature up to 86°F and administer within 12 h after reconstitution. Store IV infusion admixture at room temperature up to 86°F and administer within 12 h after mixing with sodium chloride 0.9% injection or Ringer's lactate injection or 6 h after mixing with dextrose 5% injection. Protect from light. Store in carton until time of use.

Drug Interactions

Azole antifungals (eg, itraconazole, ketoconazole, voriconazole)

Coadministration of voriconazole may result in more than doubling of esomeprazole exposure. Consider dose adjustment in patients who require high doses (eg, Zollinger-Ellison syndrome). Bioavailability of itraconazole and ketoconazole may be reduced. Avoid coadministration if possible. If concurrent use cannot be avoided, consider instructing the patient to take with an acidic beverage (eg, Coca-Cola ) to help increase itraconazole or ketoconazole absorption.

Benzodiazepines (eg, diazepam)

Coadministration of esomeprazole and diazepam may decrease diazepam Cl. The CNS effects of diazepam may be increased (eg, ataxia, sedation). Monitor for increased CNS impairment and adjust the benzodiazepine dose as needed.

Calcium salts (eg, calcium carbonate)

The inhibition of gastric acid secretion may interfere with the GI absorption of calcium salts. Closely monitor the clinical response to calcium. Larger dosages of calcium may be needed.

Cilostazol

Coadministration is expected to increase concentrations of cilostazol and its active metabolite, 3,4-dihydrocilostazol. Consider a cilostazol dose reduction when esomeprazole is given concurrently.

Clarithromycin

Esomeprazole plasma concentrations may be elevated, increasing the pharmacologic effects and adverse reactions.

Clopidogrel

The antiplatelet activity of clopidogrel may be decreased. Avoid coadministration unless there is a specific indication for a proton pump inhibitor. H 2 -receptor antagonists (eg, ranitidine) may be a safer alternative.

Clozapine

Clozapine plasma concentrations may be elevated, increasing the pharmacologic effects and risk of toxicity. Close clinical and laboratory monitoring is warranted.

Dasatinib, erlotinib, nilotinib

Esomeprazole may interfere with the absorption of these agents. Plasma concentration and pharmacologic effects of these agents may be decreased. Avoid coadministration.

Digoxin

Increased serum digoxin levels may occur. The magnitude of change is not expected to be clinically important in most patients. Because digoxin has a narrow therapeutic index, monitor digoxin concentrations and the clinical response. If an interaction is suspected, adjust the digoxin dose as needed.

Fluvoxamine

Esomeprazole plasma concentrations may be elevated, increasing the risk of adverse reactions.

Food

The esomeprazole AUC may be decreased when esomeprazole is taken after food compared with fasting conditions. Esomeprazole should be taken at least 1 h before eating.

Iron salts (eg, ferrous sulfate)

The inhibition of gastric acid secretion may interfere with the absorption of iron salts. Temporary cessation of esomeprazole may be required in order to achieve the appropriate clinical response to oral iron. If stopping esomeprazole is not an option, parenteral iron may be a suitable alternative.

Methotrexate

Renal elimination of methotrexate may be decreased, increasing methotrexate concentrations and the risk of toxicity. Close monitoring of methotrexate plasma concentrations is warranted. Coadminister high-dose methotrexate with caution.

Mycophenolate

Mycophenolate plasma concentrations and pharmacologic effects may be decreased. Monitor the clinical response and adjust the mycophenolate dose as needed.

Protease inhibitors (eg, atazanavir, indinavir, nelfinavir, saquinavir)

Dissolution, GI absorption, and plasma levels of certain protease inhibitors may be reduced. Saquinavir plasma levels may be increased. Saquinavir dose reduction may be needed. Appropriate clinical monitoring is recommended. Coadministration of atazanavir or nelfinavir and proton pump inhibitors is not recommended.

Rifampin, St. John's wort

Plasma concentrations of esomeprazole may be reduced, decreasing the pharmacologic effects. Avoid coadministration.

Rilpivirine

Plasma concentrations and pharmacologic effects of rilpivirine may be reduced, possibly resulting in loss of virologic response or resistance. Coadministration is contraindicated.

Tacrolimus

Tacrolimus plasma concentrations may be elevated, increasing the pharmacologic effects and risk of adverse reactions. Closely monitor tacrolimus trough concentrations when starting or stopping esomeprazole. Adjust the tacrolimus dose as needed.

Tolterodine ER

An increase in the release of tolterodine from the ER doseform may occur as a result of the increase in gastric pH associated with proton pump inhibitor administration. Plasma concentrations of tolterodine and its active metabolite may be elevated, increasing the pharmacologic effects and risk of adverse reactions. Closely monitor the patient and adjust the tolterodine dose as needed.

Warfarin

Risk of bleeding may be increased. Monitor for increases in INR and PT. Adjust the warfarin dose as needed.

Laboratory Test Interactions

Serum chromogranin A (CgA) concentrations increase secondary to drug-induced decreases in gastric acidity. The increased CgA concentration may result in false-positive results in diagnostic investigations for neuroendocrine tumors. Temporarily suspend esomeprazole treatment before assessing CgA concentrations and consider repeating the test if initial CgA concentrations are high.

Adverse Reactions

CNS

Headache (11%); dizziness/vertigo (3%); somnolence (2%); aggression, agitation, depression, hallucination (postmarketing).

Dermatologic

Pruritus (1%); alopecia, erythema multiforme, hyperhidrosis, photosensitivity, Stevens-Johnson syndrome, TEN (some fatal) (postmarketing).

EENT

Blurred vision (postmarketing).

GI

Flatulence (10%); abdominal pain, nausea (6%); diarrhea, dry mouth (4%); constipation (3%); regurgitation (1%); GI candidiasis, pancreatitis, stomatitis, taste disturbance (postmarketing).

Genitourinary

Gynecomastia, interstitial nephritis (postmarketing).

Hepatic

Increased ALT (1%); hepatic encephalopathy, hepatic failure, hepatitis with or without jaundice (postmarketing).

Hematologic-Lymphatic

Agranulocytosis, pancytopenia (postmarketing).

Lab Tests

Increased alkaline phosphate, ALT, AST, creatinine, Hgb, platelets, potassium, serum gastrin, sodium, thyroxine, total bilirubin, TSH, uric acid, and WBC; decreased Hgb, platelets, potassium, sodium, thyroxine, and WBC.

Local

Injection-site reaction (2%).

Musculoskeletal

Bone fracture, muscular weakness, myalgia (postmarketing).

Respiratory

Tachypnea (1%); bronchospasm (postmarketing).

Miscellaneous

Anaphylactic reaction/shock, hypomagnesemia (postmarketing).

Precautions

Monitor

For patients expected to be on prolonged therapy or who take proton pump inhibitors with digoxin or drugs that may cause hypomagnesemia (eg, diuretics), consider monitoring magnesium levels prior to initiation of treatment and periodically thereafter.


Pregnancy

Category B .

Lactation

Undetermined.

Children

Oral

Safety and efficacy have been established in neonates. Safety and efficacy have been established for the short-term treatment of GERD in patients 1 to 17 y of age and for the short-term treatment of erosive esophagitis due to acid-mediated GERD in patients 1 mo to younger than 1 y.

IV

Safety and efficacy have not been established in patients younger than 1 mo.

Elderly

Greater sensitivity of some older individuals cannot be ruled out.

Hypersensitivity

May occur; angioedema and anaphylactic reaction/shock have been reported.

Atrophic gastritis

Has been reported in patients receiving long-term treatment with omeprazole, of which esomeprazole is an enantiomer.

Bone fracture

Proton pump inhibitor therapy may be associated with an increased risk of osteoporosis-related fracture of the hip, wrist, or spine, especially in patients receiving high-dose and long-term (1 y or longer) therapy. Use the lowest dose and shortest duration of proton pump inhibitor therapy appropriate to the condition being treated.

Gastric malignancy

Symptomatic response to therapy with esomeprazole does not preclude the presence of gastric malignancy.

Hypomagnesemia

Has been reported rarely in patients treated with proton pump inhibitors for at least 3 mo; most cases were reported after a year of therapy.

Overdosage

Symptoms

Blurred vision, confusion, diaphoresis, drowsiness, dry mouth, flushing, headache, nausea, tachycardia.

Patient Information

  • IV
  • Advise patients or caregivers that injection is used when oral therapy is not feasible or appropriate.
  • Advise patients or caregivers that the injection will be prepared and administered by a health care provider in a health care setting and that oral therapy will be started as soon as possible.
  • Oral
  • Instruct patients to take each dose on an empty stomach at least 1 h before eating.
  • Inform patients that antacids may be used while taking esomeprazole.
  • Instruct patients to swallow the capsule whole and not to crush or chew it.
  • Advise patients that if they experience difficulty swallowing the capsule, they may open the capsule and gently mix the pellets with 1 Tbsp of cool or cold applesauce and then immediately swallow the mixture without chewing. Remind patients not to crush or chew the pellets and not to prepare the pellet/applesauce mixture ahead of time or store it for future use.
  • Instruct patients to administer esomeprazole oral suspension by emptying the contents of a 2.5 or 5 mg packet into a container with 5 mL of water or the 10, 20, or 40 mg packet into a container with 15 mL of water. Stir, leave for 2 to 3 min to thicken, and then stir and drink within 30 min. If material remains in the container, instruct the patient to add more water, stir, and drink immediately.
  • Remind patients that esomeprazole is to be taken every day and not as needed or only when symptoms are present.
  • Instruct patients to report any of the following to health care provider: black, tarry stools; bloody or coffee ground–like vomit; bothersome adverse reactions (eg, constipation, gas, headache); increased need for antacid use; recurrent heartburn; recurrent indigestion or abdominal pain.
  • Advise patients to immediately contact their health care provider if any CV or neurological symptoms, such as palpitations, dizziness, seizures, and tetany, occur because these may be signs of hypomagnesemia.

Copyright © 2009 Wolters Kluwer Health.

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