Esomeprazole

Pharmacologic Category

Proton Pump Inhibitor; Substituted Benzimidazole

Dosing: Adult

Note: All dosing is expressed in terms of esomeprazole base, regardless of the salt associated with the dosing information. Esomeprazole strontium 24.65 mg is equivalent to 20 mg of esomeprazole base; esomeprazole strontium 49.3 mg is equivalent to 40 mg of esomeprazole base.

Barrett esophagus (off-label use): Oral: Utilize standard doses (20 or 40 mg) once daily (Shaheen 2016; Singh 2014; Spechler 2011); poorly controlled reflux symptoms or esophagitis may require twice-daily dosing (Shaheen 2016). The use of 40 mg twice daily (in combination with aspirin) also has been reported (Jankowski 2018).

Dyspepsia (off-label use): Oral: 40 mg once daily for up to 8 weeks (Talley 2007; Pinto-Sanchez 2017; van Zanten 2006).

Erosive esophagitis (healing): Oral: Esomeprazole magnesium, esomeprazole strontium: Initial: 20 to 40 mg once daily for 4 to 8 weeks; if incomplete healing, may continue for an additional 4 to 8 weeks; maintenance: 20 mg once daily (controlled studies did not extend beyond 6 months).

Heartburn (OTC labeling): Oral: 20 mg once daily for 14 days (maximum: 20 mg/day); treatment may be repeated after 4 months if needed.

Helicobacter pylori eradication: Oral:

American College of Gastroenterology guidelines (Chey 2007; Chey 2017):

Clarithromycin triple regimen: 20 to 40 mg twice daily in combination with clarithromycin 500 mg twice daily and either amoxicillin 1 g twice daily or metronidazole 500 mg 3 times daily; continue regimen for 14 days. Note: Avoid use of clarithromycin triple therapy in patients with risk factors for macrolide resistance (eg, prior macrolide exposure, local clarithromycin resistance rates ≥15%, eradication rates with clarithromycin-based regimens ≤85%) (ACG [Chey 2017]; Fallone 2016).

Bismuth quadruple regimen: 20 mg twice daily in combination with tetracycline 500 mg 4 times daily, metronidazole 250 mg 4 times daily or 500 mg 3 or 4 times daily, and either bismuth subcitrate 120 to 300 mg 4 times daily or bismuth subsalicylate 300 mg 4 times daily; continue regimen for 10 to 14 days.

Concomitant regimen: 20 mg twice daily in combination with amoxicillin 1 g twice daily, clarithromycin 500 mg twice daily, and either metronidazole or tinidazole 500 mg twice daily; continue regimen for 10 to 14 days.

Sequential regimen: 20 mg twice daily plus amoxicillin 1 g twice daily for 5 to 7 days; then continue esomeprazole along with clarithromycin 500 mg twice daily, and either metronidazole or tinidazole 500 mg twice daily for 5 to 7 days.

Hybrid regimen: 20 mg twice daily plus amoxicillin 1 g twice daily for 7 days; then continue esomeprazole and amoxicillin along with clarithromycin 500 mg twice daily, and either metronidazole or tinidazole 500 mg twice daily for 7 days.

Levofloxacin triple regimen: 20 mg twice daily in combination with amoxicillin 1 g twice daily and levofloxacin 500 mg once daily; continue regimen for 10 to 14 days.

Manufacturer's labeling: Dosing in the prescribing information may not reflect current clinical practice. Esomeprazole magnesium, esomeprazole strontium: 40 mg once daily

Pathological hypersecretory conditions (Zollinger-Ellison syndrome): Oral: Esomeprazole magnesium, esomeprazole strontium: 40 mg twice daily; adjust regimen to individual patient needs; doses up to 240 mg daily have been administered

Peptic ulcer disease, treatment of bleeding ulcers:

Note: Optimal pre-endoscopic proton pump inhibitor (PPI) therapy is uncertain. Some experts suggest initiating high-dose IV PPI with continuous or intermittent dosing in patients with suspected active upper GI bleed prior to endoscopy (Saltzman 2020). Following endoscopy, for patients with high-risk stigmata of recent bleeding (eg, active bleed, visible vessel, adherent clot), a continuous infusion of an IV PPI for at least 72 hours before transitioning to an oral PPI is recommended (Barkun 2019). Patients without high-risk stigmata of recent bleeding can be switched to an oral PPI immediately after endoscopy (Saltzman 2020).

IV: Continuous infusion: Loading dose of 80 mg, followed by 8 mg/hour continuous infusion for a total of 72 hours (Barkun 2019).

IV: Intermittent dosing (off-label dose): Loading dose of 80 mg, followed by 40 mg every 12 hours (Saltzman 2020).

Oral:

Patients with high-risk stigmata of recent bleeding on endoscopy (following IV PPI therapy): 40 mg twice daily for 14 days, followed by 40 mg once daily (Barkun 2019; Saltzman 2020).

Patients with no high-risk stigmata of recent bleeding on endoscopy: 20 mg once daily (Saltzman 2020).

Duration: The total duration of treatment depends on size, location, and cause of the ulcer and ranges from 4 to 12 weeks (Barkun 2019; Saltzman 2020; Vakil 2020a; Vakil 2020b).

Prevention of NSAID-induced gastric ulcers: Oral: Esomeprazole magnesium, esomeprazole strontium: 20 to 40 mg once daily for up to 6 months; Note: 40 mg daily did not show additional benefit over 20 mg daily in clinical trials.

Symptomatic gastroesophageal reflux: Oral: Esomeprazole magnesium, esomeprazole strontium: 20 mg once daily for 4 weeks; may consider an additional 4 weeks of treatment if symptoms do not resolve.

Treatment of GERD (short-term): IV: 20 mg or 40 mg once daily. Note: Indicated only in cases where oral therapy is inappropriate or not possible; safety/efficacy ≥10 days has not been established.

Treatment of NSAID-induced gastric ulcers (off-label use): Oral: Esomeprazole magnesium: 20 mg once daily for 8 weeks (Goldstein 2007).

Discontinuation of therapy: Oral: Some experts recommend a step-down approach in order to avoid worsening or rebound symptoms. One recommendation is to decrease the dose by 50% over 2 weeks to 4 weeks. If the patient is already on the lowest possible dose, alternate day therapy may be considered. If symptoms worsen during treatment or after discontinuation, patient should be re-evaluated (Kim 2018).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

* See Dosage and Administration in AHFS Essentials for additional information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment: Adult

Oral:

Esomeprazole magnesium: Mild-to-severe impairment: No dosage adjustment necessary.

Esomeprazole strontium:

Mild-to-moderate impairment: No dosage adjustment necessary.

Severe impairment: Use is not recommended (has not been studied).

IV: Mild-to-severe impairment: No dosage adjustment necessary.

Dosing: Hepatic Impairment: Adult

Oral:

Mild to moderate impairment (Child-Pugh class A or B): No dosage adjustment necessary.

Severe impairment (Child-Pugh class C): Maximum: 20 mg daily.

IV:

Treatment of GERD (short-term):

Mild to moderate impairment (Child-Pugh class A or B): No dosage adjustment necessary.

Severe impairment (Child-Pugh class C): Dose should not exceed 20 mg daily

Peptic ulcer disease, treatment of bleeding ulcers:

Continuous infusion:

Mild to moderate impairment (Child-Pugh class A or B): 80 mg over 30 minutes, followed by a maximum continuous infusion of 6 mg/hour for a total of 72 hours.

Severe impairment (Child-Pugh class C): 80 mg over 30 minutes, followed by a maximum continuous infusion of 4 mg/hour for a total of 72 hours.

Dosing: Pediatric

Erosive esophagitis associated with GERD:

Oral:

Infants:

3 to 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 kg: 10 mg once daily for up to 6 weeks.

Children 1 to 11 years:

<20 kg: 10 mg once daily for 8 weeks.

≥20 kg: 10 or 20 mg once daily for 8 weeks.

Children ≥12 years and Adolescents: 20 to 40 mg once daily for 4 to 8 weeks.

IV: Note: Indicated only in cases where oral therapy is inappropriate or not possible; safety and efficacy >10 days has not been established.

Infants: 0.5 mg/kg/dose once daily.

Children and Adolescents ≤17 years:

<55 kg: 10 mg once daily.

≥55 kg: 20 mg once daily.

GERD, symptomatic: Note: Guidelines recommend a 4- to 8-week treatment course; if improvement seen after 4 to 8 weeks, consider possible wean; if no response after 4 to 8 weeks, reevaluate diagnosis and consider referral to pediatric GI specialist (NASPGHAN/ESPGHAN [Rosen 2018]).

Weight-based dosing: Infants, Children, and Adolescents: Oral: 0.7 to 3.3 mg/kg/day (AAP [Lightdale 2013]); maximum dose: 40 mg/dose (NASPGHAN/ESPGHAN [Rosen 2018]).

Fixed dosing (NASPGHAN/ESPGHAN [Rosen 2018]): Children and Adolescents: Oral:

<20 kg: 10 mg once daily.

≥20 kg: 20 mg once daily.

Helicobacter pylori eradication (NASPGHAN/ESPGHAN [Jones 2017]): Children and Adolescents: Oral: Note: Usual duration of therapy is 14 days as part of triple therapy; use in combination with 2 antimicrobials (eg, clarithromycin, metronidazole, amoxicillin); preferred agents determined by susceptibility. Bismuth may be added to regimens as an alternative if resistance is present or susceptibility is unknown.

15 to <25 kg: 20 mg twice daily.

25 to 34 kg: 30 mg twice daily.

>34 kg: 40 mg twice daily.

Discontinuation of therapy: Oral: Based on experience in adults, some experts recommend a step-down approach in order to avoid worsening or rebound symptoms. One recommendation is to decrease the dose by 50% over 2 to 4 weeks. If the patient is already on the lowest possible dose, alternate day therapy may be considered. If symptoms worsen during treatment or after discontinuation, patient should be reevaluated (Kim 2018).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Renal Impairment: Pediatric

Infants, Children, and Adolescents: Oral, IV: No dosage adjustments necessary.

Dosing: Hepatic Impairment: Pediatric

There are no specific pediatric recommendations; based on experience in adult patients, adjustment suggested in severe impairment.

Use: Labeled Indications

Oral, IV:

Peptic ulcer disease, treatment of bleeding ulcers: Decrease the risk of rebleeding after successful endoscopy for acute bleeding gastric or duodenal ulcers in adults.

Oral:

Esomeprazole magnesium and esomeprazole strontium:

Gastroesophageal reflux disease (Rx only):

Healing of erosive esophagitis: Short-term (4 to 8 weeks) treatment of erosive esophagitis

Maintenance of healing of erosive esophagitis: Maintaining symptom resolution and healing of erosive esophagitis

Symptomatic gastroesophageal reflux disease: Short-term (4 to 8 weeks) treatment of symptomatic gastroesophageal reflux disease (GERD)

Helicobacter pylori eradication (Rx only): As part of a multidrug regimen for Helicobacter pylori eradication in patients with duodenal ulcer disease (active or history of within the past 5 years)

Risk reduction of nonsteroidal anti-inflammatory drug-associated gastric ulcer (Rx only): Prevention of gastric ulcers associated with continuous NSAID therapy in patients at risk (age ≥60 years and/or history of gastric ulcer)

Pathological hypersecretory conditions, including Zollinger-Ellison syndrome (Rx only): Treatment (long-term) of pathological hypersecretory conditions including Zollinger-Ellison syndrome

Esomeprazole magnesium:

Heartburn (OTC labeling): Treatment of frequent heartburn (≥2 days per week).

IV: Esomeprazole sodium:

Gastroesophageal reflux disease (Rx only): Short-term (≤10 days) treatment of gastroesophageal reflux disease (GERD) with erosive esophagitis in pediatric patients 1 month to 17 years of age and adults when oral therapy is not possible or appropriate.

* See Uses in AHFS Essentials for additional information.

Use: Off-Label: Adult

​Barrett esophagusLevel of Evidence [B, G]

Data from a meta-analysis of observational studies evaluating acid suppressive therapy and the risk of esophageal adenocarcinoma or high-grade dysplasia in patients with Barrett esophagus showed that proton pump inhibitors were associated with a reduction in the risk of esophageal adenocarcinoma and high-grade dysplasia associated with Barrett esophagus; a longer duration of PPI use was associated with a greater protective effect Ref. The use of esomeprazole in combination with aspirin for the treatment of Barrett esophagus, including preventing neoplastic progression, has also been reported Ref.

Guidelines from the American College of Gastroenterology for the diagnosis and management of Barrett esophagus and a position statement from the American Gastroenterological Association on the management of Barrett esophagus recommend the use of proton pump inhibitors in the management of Barrett esophagus.

​DyspepsiaLevel of Evidence [A, G]

Data from two randomized, double-blinded, placebo-controlled trials supports the use of esomeprazole for the treatment of dyspepsia Ref. In addition, data from a systematic review support the use of esomeprazole for the treatment of patients with ulcer and reflux-like functional dyspepsia Ref.

Based on the American College of Gastroenterology (ACG) and Canadian Association of Gastroenterology (CAG) guidelines for the management of dyspepsia, the use of esomeprazole is effective and recommended treatment for dyspepsia and functional dyspepsia in patients <60 years of age who are H. pylori negative or who remain symptomatic after H. pylori eradication therapy Ref.

​Stress ulcer prophylaxis in critically ill patientsLevel of Evidence [G]

Based on the Surviving Sepsis Campaign International Guidelines for the Management of Severe Sepsis and Septic Shock, stress ulcer prophylaxis using a proton pump inhibitor or a histamine H2-receptor antagonist is recommended in sepsis or septic shock patients who have GI bleeding risk factors.

​Treatment of NSAID-induced gastric ulcersLevel of Evidence [A]

Data from a multicenter, randomized, double-blind, parallel-group clinical trial supports the use of esomeprazole in the treatment of NSAID-induced gastric ulcers Ref.

Level of Evidence Definitions

​Level of Evidence Scale

Class and Related Monographs

Proton Pump Inhibitors

Comparative Efficacy

• ESOMEPRAZOLE

Clinical Practice Guidelines

Barrett Esophagus:

ACG, “Diagnosis and Management of Barrett’s Esophagus,” January 2016

AGA, “Management of Barrett’s Esophagus,” 2011

Critical Care:

“Surviving Sepsis Campaign: International Guidelines for the Management of Severe Sepsis and Septic Shock: 2016,” March 2017

Dyspepsia:

ACG/CAG “Guidelines for the Management of Dyspepsia,” June 2017

Gastroesophageal Reflux Disease:

ACG, "Guidelines for the Diagnosis and Management of Gastroesophageal Reflux Disease,” March 2013

AGA, "Medical Position Statement on the Management of Gastroesophageal Reflux Disease,” October 2008

Helicobacter pylori Infection:

“ACG Guideline on the Management of Helicobacter pylori Infection,” August 2007

“ACG Guideline on the Treatment of Helicobacter pylori Infection,” February 2017

NSAID-Related Ulcers:

“ACG Guidelines for Prevention of NSAID-Related Ulcer Complications,” February 2009

Proton Pump Inhibitors & Thienopyridines:

ACCF/AHA/SCAI "2011 Guideline for Percutaneous Coronary Intervention,” November 2011

“ACCF/ACG/AHA 2010 Expert Consensus Document on the Concomitant Use of Proton Pump Inhibitors and Thienopyridines,” December 2010

Canadian Cardiovascular Society, “The Use of Antiplatelet Therapy in the Outpatient Setting: Canadian Cardiovascular Society Guidelines,” 2011

Upper Gastrointestinal Bleeding:

International Consensus Group, "Management of Nonvariceal Upper Gastrointestinal Bleeding," October 2019

Usual Infusion Concentrations: Adult

IV infusion: 20 mg in 50 mL (concentration: 0.4 mg/mL) or 40 mg in 50 mL (concentration: 0.8 mg/mL) of D5W, LR, or NS

Administration: IV

Flush line prior to and after administration with NS, LR, or D5W.

Treatment of GERD: May be administered by injection (≥3 minutes), intermittent infusion (10 to 30 minutes)

Peptic ulcer disease, treatment of bleeding ulcers: May be administered as continuous infusion or intermittent infusion (infuse over 30 minutes), depending on risk of rebleeding.

Administration: Injectable Detail

pH: 9 to 11

Administration: Oral

Capsule: Swallow whole and take at least 1 hour before eating (best if taken before breakfast). Capsule can be opened and contents mixed with 1 tablespoon of applesauce. Swallow immediately; mixture should not be chewed or warmed. For patients with difficulty swallowing, use of granules may be more appropriate.

Granules: Empty the 2.5 mg or 5 mg packet into a container with 5 mL of water or the 10 mg, 20 mg, or 40 mg packet into a container with 15 mL of water and stir; leave 2 to 3 minutes to thicken. Stir and drink within 30 minutes. If any medicine remains after drinking, add more water, stir and drink immediately.

Tablet: Swallow whole; do not crush or chew; administer with a full glass of water before breakfast in the morning.

Tablet [Canadian product]: Swallow whole with water or may be dispersed in a half a glass of noncarbonated water. Stir until tablets disintegrate, and drink the liquid with pellets immediately or within 30 minutes. Do not chew or crush pellets. After drinking, rinse glass with water and drink.

Bariatric surgery: Tablet, delayed release: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. Delayed-release tablet cannot be cut or crushed. Switch to delayed-release capsule since capsule can be opened and contents sprinkled onto soft food of choice as long as patient does not chew the mixture.

Administration: Other

Nasogastric tube:

Capsule: Open capsule and place intact granules into a 60 mL catheter-tip syringe; mix with 50 mL of water. Replace plunger and shake vigorously for 15 seconds. Ensure that no granules remain in syringe tip. Do not administer if pellets dissolve or disintegrate. Use immediately after preparation. After administration, flush nasogastric tube with additional water.

Granules: Delayed release oral suspension granules can also be given by nasogastric or gastric tube. If using a 2.5 mg or 5 mg packet, first add 5 mL of water to a catheter-tipped syringe, then add granules from packet. If using a 10 mg, 20 mg, or 40 mg packet, first add 15 mL of water to a catheter-tipped syringe, then add granules from packet. Shake the syringe, leave 2 to 3 minutes to thicken. Shake the syringe and administer through nasogastric or gastric tube (size 6 French or greater) within 30 minutes. Refill the syringe with equal amount (5 mL or 15 mL) of water, shake and flush nasogastric/gastric tube.

Tablet [Canadian product]: Dispersed tablets can also be given by nasogastric tube (size 8 to 20 French) using a 25 to 60 mL disposable syringe. Disperse tablet in 50 mL of water. After administration, flush with additional 25 to 50 mL of water to clear the syringe and tube. In larger nasogastric feeding tubes (ie, size 14 French or greater), the dispersion volume may be reduced to 25 mL.

Administration: Pediatric

Oral: Administer at least 1 hour before food or meals

Capsule: Swallow whole, do not chew or crush. For patients with difficulty swallowing the capsule, capsule may be opened and the enteric coated pellets may be mixed with 1 tablespoon of applesauce (applesauce should not be hot) and swallowed immediately; do not chew or crush granules; do not store mixture for future use.

Nasogastric tube administration: Open capsule and place intact granules into a 60 mL catheter-tipped syringe; mix with 50 mL of water. Replace plunger and shake vigorously for 15 seconds. Ensure that no granules remain in syringe tip. Do not administer if pellets dissolve or disintegrate. Use immediately after preparation. After administration, flush nasogastric tube with additional water.

Granules: Mix contents of the 2.5 mg or 5 mg packet with 5 mL of water or the 10 mg, 20 mg, or 40 mg packet with 15 mL water and stir; leave for 2 to 3 minutes to thicken; stir and drink within 30 minutes. If any medicine remains after drinking, add more water, stir and drink immediately.

Nasogastric or gastric tube administration: If using a 2.5 mg or 5 mg packet, first add 5 mL of water to a catheter-tipped syringe, then add granules from packet. If using a 10 mg, 20 mg, or 40 mg packet, first add 15 mL of water to a catheter-tipped syringe, then add granules from packet. Shake the syringe, leave 2 to 3 minutes to thicken. Shake the syringe and administer through nasogastric or gastric tube (French size 6 or greater) within 30 minutes. Refill the syringe with an equal amount (5 mL or 15 mL) of water, shake and flush tube.

IV: Flush line prior to and after administration with NS, LR, or D5W. Administer desired dose by intermittent infusion over 10 to 30 minutes. The manufacturer recommends that pediatric patients receive intravenous esomeprazole by intermittent infusion only.

Dietary Considerations

Take at least 1 hour before meals; best if taken before breakfast.

Storage/Stability

Capsules:

Esomeprazole magnesium: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).

Esomeprazole strontium: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).

Granules: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).

Powder for injection: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from light. Per the manufacturer, following reconstitution, solution for injection prepared in NS, and solution for infusion prepared in NS or LR should be used within 12 hours; solution for infusion prepared in D5W should be used within 6 hours. Refrigeration is not required following reconstitution.

Additional stability data: Following reconstitution, solutions for infusion prepared in D5W, NS, or LR in PVC bags are chemically and physically stable for 48 hours at room temperature (25°C) and for at least 120 hours under refrigeration (4°C) (Kupiec 2008).

Tablets: Store at 20°C to 25°C (68°F to 77°F).

Preparation for Administration: Adult

Granules for oral administration: Empty the 2.5 mg or 5 mg packet into a container with 5 mL of water or empty the 10 mg, 20 mg, or 40 mg packet into a container with 15 mL of water and stir; leave 2-3 minutes to thicken.

Powder for injection:

For IV injection (≥3 minutes): Adults: Reconstitute powder with 5 mL NS.

For IV infusion (10 to 30 minutes): Initially reconstitute powder with 5 mL of NS, LR, or D5W, then further dilute to a final volume of 50 mL.

For IV infusion (loading dose and continuous infusion): Prepare the 80 mg loading dose by reconstituting two 40 mg vials with NS (5 mL each); the contents of the two vials should then be further diluted in NS 100 mL. To prepare the continuous infusion, also reconstitute two 40 mg vials with NS (5 mL each); the contents of the two vials should then be further diluted in NS 100 mL.

Preparation for Administration: Pediatric

Oral: Granules: Mix contents of the 2.5 mg or 5 mg packet with 5 mL of water or the 10 mg, 20 mg, or 40 mg packet with 15 mL of water and stir; leave 2 to 3 minutes to thicken.

IV: For IV infusion (10 to 30 minutes): Reconstitute powder (20 mg or 40 mg) with 5 mL of NS, LR, or D5W; further dilute to a final volume of 50 mL to achieve a final concentration of 0.4 mg/mL or 0.8 mg/mL, respectively

Medication Patient Education with HCAHPS Considerations

What is this drug used for?

• It is used to treat gastroesophageal reflux disease (GERD; acid reflux).

• It is used to treat or prevent GI (gastrointestinal) ulcers caused by infection.

• It is used to treat or prevent ulcers of the swallowing tube (esophagus).

• It is used to treat syndromes caused by lots of stomach acid.

• It is used to treat or prevent NSAID-associated gastric ulcers in patients with a history of ulcers.

• It is used to treat heartburn.

• It is used to lower the chance of bleeding ulcers after a certain procedure (endoscopy).

• It may be given for other reasons.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Headache

• Fatigue

• Diarrhea

• Constipation

• Passing gas

• Abdominal pain

• Nausea

• Dry mouth

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Low magnesium like mood changes; muscle pain or weakness; muscle cramps or spasms; seizures; tremors; lack of appetite; severe nausea or vomiting; or an abnormal heartbeat

• Kidney problems like unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain

• Lupus like rash on the cheeks or other body parts, sunburn easy, muscle or joint pain, chest pain or shortness of breath, or swelling in the arms or legs

• Severe dizziness

• Passing out

• Bone pain

• Chills

• Sore throat

• Shortness of breath

• Excessive weight loss

• Clostridioides (formerly Clostridium) difficile colitis (C. diff)-associated diarrhea like abdominal pain or cramps, severe diarrhea or watery stools, or bloody stools

• Stevens-Johnson syndrome/toxic epidermal necrolysis like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in mouth, throat, nose, or eyes

• Injection site irritation

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Medication Safety Issues

​Sound-alike/look-alike issues:

​Geriatric Patients: High-Risk Medication:

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:

Esomeprazole strontium delayed release capsuleshttps://www.accessdata.fda.gov/drugsatfda_docs/label/2018/202342s005lbl.pdf#page=29

NexIUM capsules, granules for oral suspension: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/021153s053,022101s017,021957s020lbl.pdf#page=33

Contraindications

Hypersensitivity (eg, anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute interstitial nephritis, urticaria) to esomeprazole, other substituted benzimidazole proton pump inhibitors, or any component of the formulation; concomitant use with products that contain rilpivirine.

OTC labeling: When used for self-medication (OTC), do not use if you have trouble or pain when swallowing food; vomiting with blood, or bloody or black stools; heartburn with light-headedness, dizziness, or sweating; chest pain or shoulder pain with shortness of breath, sweating, pain spreading to arms, neck or shoulders, or light-headedness; frequent chest pain.

Warnings/Precautions

Concerns related to adverse effects:

• Carcinoma: No reports of enterochromaffin-like (ECL) cell carcinoids, dysplasia, or neoplasia have occurred.

• Clostridioides (formerly Clostridium) difficile-associated diarrhea (CDAD): Use of proton pump inhibitors (PPIs) may increase risk of CDAD, especially in hospitalized patients; consider CDAD diagnosis in patients with persistent diarrhea that does not improve. Use the lowest dose and shortest duration of PPI therapy appropriate for the condition being treated.

• Cutaneous and systemic lupus erythematosus: Has been reported as new onset or exacerbation of existing autoimmune disease; most cases were cutaneous lupus erythematosus (CLE), most commonly, subacute CLE (occurring within weeks to years after continuous therapy). Systemic lupus erythematosus (SLE) is less common (typically occurs within days to years after initiating treatment) and occurred primarily in young adults up to the elderly. Discontinue therapy if signs or symptoms of CLE or SLE occur and refer to specialist for evaluation; most patients improve 4 to 12 weeks after discontinuation of esomeprazole.

• Fractures: Increased incidence of osteoporosis-related bone fractures of the hip, spine, or wrist may occur with proton pump inhibitor (PPI) therapy. Patients on high-dose or long-term therapy (≥1 year) should be monitored. Use the lowest effective dose for the shortest duration of time, use vitamin D and calcium supplementation, and follow appropriate guidelines to reduce risk of fractures in patients at risk.

• Fundic gland polyps: Use of proton pump inhibitors (PPIs) increases risk of fundic gland polyps, especially with long-term use >1 year. May occur without symptoms but nausea, vomiting, or abdominal pain may occur; GI bleeding and/or anemia may occur with ulcerated polyps. Diagnosis of polyps may also increase risk for small intestinal blockage. Use the lowest dose and shortest duration of PPI therapy appropriate for the condition being treated.

• Gastrointestinal infection (eg, Salmonella, Campylobacter): Use of proton pump inhibitors may increase risk of these infections.

• Hypomagnesemia: Reported rarely, usually with prolonged PPI use of ≥3 months (most cases >1 year of therapy). May be symptomatic or asymptomatic; severe cases may cause tetany, seizures, and cardiac arrhythmias. Consider obtaining serum magnesium concentrations prior to beginning long-term therapy, especially if taking concomitant digoxin, diuretics, or other drugs known to cause hypomagnesemia; and periodically thereafter. Hypomagnesemia may be corrected by magnesium supplementation, although discontinuation of esomeprazole may be necessary; magnesium levels typically return to normal within 1 week of stopping.

• Interstitial nephritis: Acute interstitial nephritis has been observed in patients taking PPIs; may occur at any time during therapy and is generally due to an idiopathic hypersensitivity reaction. Discontinue if acute interstitial nephritis develops.

• Vitamin B12 deficiency: Prolonged treatment (≥2 years) may lead to vitamin B12 malabsorption and subsequent vitamin B12 deficiency. The magnitude of the deficiency is dose-related and the association is stronger in females and those younger in age (<30 years); prevalence is decreased after discontinuation of therapy (Lam 2013).

Disease-related concerns:

• Gastric malignancy: Relief of symptoms does not preclude the presence of a gastric malignancy.

• Hepatic impairment: Patients with severe hepatic impairment may require dosage reductions.

• Renal impairment: Pharmacokinetics of esomeprazole are not expected to be altered in renal impairment; dosage adjustments are not necessary for any degree of renal impairment when using esomeprazole magnesium or esomeprazole sodium. However, since pharmacokinetics of the strontium may be reduced in mild to moderate renal impairment, esomeprazole strontium is not recommended for use in severe impairment (has not been studied).

Concurrent drug therapy issues:

• Clopidogrel: Proton pump inhibitors (PPIs) may diminish the therapeutic effect of clopidogrel, thought to be due to reduced formation of the active metabolite of clopidogrel. The manufacturer of clopidogrel recommends either avoidance of both omeprazole (even when scheduled 12 hours apart) and esomeprazole or use of a PPI with comparatively less effect on the active metabolite of clopidogrel (eg, pantoprazole). In contrast to these warnings, others have recommended the continued use of PPIs, regardless of the degree of inhibition, in patients with a history of GI bleeding or multiple risk factors for GI bleeding who are also receiving clopidogrel since no evidence has established clinically meaningful differences in outcome; however, a clinically significant interaction cannot be excluded in those who are poor metabolizers of clopidogrel (Abraham 2010; Levine 2011).

Special populations:

• Elderly: Bioavailability may be increased in elderly patients.

• Pediatric: Esomeprazole strontium: Strontium competes with calcium for intestinal absorption and is incorporated into bone; use of esomeprazole strontium in pediatric patients is not recommended.

Dosage form specific issues:

• Intravenous: Safety and efficacy of IV treatment for GERD beyond 10 days have not been established; transition from IV to oral therapy as soon possible.

Other warnings/precautions:

• Appropriate use: Helicobacter pylori eradication: Short-term combination therapy (≤7 days) has been associated with a higher incidence of treatment failure. The American College of Gastroenterology recommends 10 to 14 days of therapy (triple or quadruple) for eradication of H. pylori (Chey 2017).

• Laboratory test interference: Serum chromogranin A (CgA) levels increase secondary to drug-induced decreases in gastric acid; may cause false-positive results in diagnostic investigations for neuroendocrine tumors. Temporarily stop esomeprazole treatment ≥14 days before CgA test; if CgA level high, repeat test to confirm. Use same commercial laboratory for testing to prevent variable results.

• Self-medication (OTC use): When used for self-medication (OTC), notify health care provider before use if any of the following are present: heartburn for >3 months; frequent wheezing, particularly with heartburn; unexplained weight loss; nausea or vomiting; or stomach pain. Discontinue use and notify health care provider if heartburn continues or worsens; diarrhea occurs; if >14 days of therapy is needed; or if >1 course of therapy is needed every 4 months.

* See Cautions in AHFS Essentials for additional information.

Geriatric Considerations

Dose adjustment is not necessary.

Use has been associated with C. difficile infection, bone loss and fractures, and hypomagnesemia.

Warnings: Additional Pediatric Considerations

Use of gastric acid inhibitors, including proton pump inhibitors (PPIs) and H2 blockers, has been associated with an increased risk for development of acute gastroenteritis and community-acquired pneumonia in pediatric patients 4 to 36 months of age (Canani 2006). Routine use in preterm infants is not recommended (AAP [Eichenwald 2018]).

Gastric acid suppression medications have been associated with an increase in Clostridioides (formerly Clostridium) difficile infection (CDI) and recurrent CDI in pediatric patients (Nylund 2014). In a retrospective, observational, case control study of pediatric patients 1 to 18 years old who were hospitalized for diarrhea and abdominal pain, the use of PPIs was significantly higher in patients who tested positive for C. difficile compared to patients who tested negative for C. difficile (22.1% vs 5.9%) (Turco 2010). Consider CDI diagnosis in patients with persistent diarrhea that does not improve. Use the lowest dose and shortest duration of PPI therapy appropriate for the condition being treated.

A large retrospective cohort study reviewed records for patients with a low baseline risk for fractures who were initiated on acid suppression therapy in the first year of life and evaluated the fracture risk in the first 5 years of life; a total of 97,286 patients were prescribed acid suppression therapy; 73% were prescribed H2 blockers, 9% were prescribed PPIs, and 18% were prescribed both. H2 blocker use alone was not associated with an increased fracture hazard; however, PPI use was associated with a 21% increase and use of PPI plus H2 blocker was associated with a 30% increase. Longer duration of therapy and earlier age at initiation seemed to also increase the fracture hazard. Study findings do not establish a causal relationship between PPI use and fractures. If acid suppression therapy is necessary in the first year of life, limiting therapy to a single drug and limiting the duration should be considered (Malchodi 2019). A second large cohort study reviewed records for 115,933 children <18 years initiated on a PPI. PPI initiation was associated with a statistically significant 11% relative increase in risk of any fracture in patients ≥6 years. The increased risk also seemed to be more pronounced with a longer cumulative duration of PPI use (Wang 2020).

Pregnancy Considerations

Esomeprazole crosses the placenta (Saito 2020).

Following a maternal dose of esomeprazole 10 mg/day throughout pregnancy, cord blood concentrations at delivery were ~40% of those in the maternal serum (~12 hours after the last maternal dose). Twelve hours after delivery (~23 hours after the last maternal dose), esomeprazole was no longer detected in the infant serum (Saito 2020).

Recommendations for the treatment of GERD in pregnancy are available. As in nonpregnant patients, lifestyle modifications followed by other medications are the initial recommended treatments (Body 2016; Huerta-Iga 2016; Katz 2013; van der Woude 2014). Based on available data, PPIs may be used when clinically indicated (use of an agent with more data in pregnancy may be preferred) (Body 2016; Matok 2012; Pasternak 2010; van der Woude 2014).

Breast-Feeding Considerations

Esomeprazole is present in breast milk (Saito 2020).

A case report describes maternal use of esomeprazole 10 mg/day throughout pregnancy and postpartum. Breast milk was sampled multiple times between 2 and 4 days after delivery at term. The highest breast milk concentration was 4 hours after the maternal dose (19.6 ng/mL) and esomeprazole was no longer detected in breast milk 10 hours after the maternal dose. Using the highest breast milk concentration, authors of the study determined the estimated daily infant dose via breast milk to be 0.003 mg/kg/day. This infant received >50% of nutrition via breast milk and was developing normally as of 6 months of age (Saito 2020).

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.

Briggs' Drugs in Pregnancy & Lactation

• Esomeprazole

Adverse Reactions

Unless otherwise specified, percentages represent adverse reactions identified in clinical trials evaluating the oral formulation.

>10%: Central nervous system: Headache (2% to 11%)

1% to 10%:

Central nervous system: Irritability (infants: ≥5%), dizziness (intravenous: ≤3%; oral: <1%), vertigo (intravenous: ≤3%), drowsiness (children: 2%; adults: <1%)

Dermatologic: Pruritus (intravenous: 1%; oral: <1%)

Endocrine & metabolic: Altered thyroid hormone levels (increased thyroxine: ≤1%), decreased serum potassium (≤1%), decreased serum sodium (≤1%), decreased thyroid hormones (thyroxine: ≤1%), increased gastrin (≤1%), increased serum potassium (≤1%), increased serum sodium (≤1%), increased thyroid stimulating hormone level (≤1%), increased uric acid (≤1%)

Gastrointestinal: Flatulence (intravenous: 10%; oral: ≥1%), diarrhea (2% to 4%), abdominal pain (1% to 6%), nausea (intravenous: 6%; oral: ≥1% to 2%), vomiting (infants: 1% to ≥5%; adults: <1%), xerostomia (intravenous: 4%; oral: ≥1%), constipation (intravenous: 3%; oral: ≥1%)

Hematologic & oncologic: Quantitative disorders of platelets (≤1%)

Hepatic: Increased serum alkaline phosphatase (≤1%), increased serum alanine aminotransferase (≤1%), increased serum aspartate aminotransferase (≤1%)

Local: Injection site reaction (intravenous: 2% to 4%)

Renal: Increased serum creatinine (≤1%)

Respiratory: Cough (intravenous: 1%; oral: <1%), tachypnea (infants, oral: 1%)

Miscellaneous: Fever (intravenous: 4%; oral: <1%)

Frequency not defined:

Cardiovascular: Esophageal varices

Gastrointestinal: Barrett esophagus, duodenitis, esophageal stenosis, esophageal ulcer, esophagitis, gastritis, mucosal discoloration

Hematologic & oncologic: Benign polyp

Miscellaneous: Benign nodule

<1%, postmarketing, and/or case reports: Acne vulgaris, acute interstitial nephritis, aggressive behavior, ageusia, agitation, agranulocytosis, albuminuria, alopecia, altered sense of smell, anaphylactic shock, anaphylaxis, anemia, angioedema, anorexia, apathy, aphthous stomatitis, arthralgia, arthropathy, asthenia, back pain, blurred vision, bone fracture, bronchospasm, candidiasis (urogenital), cervical lymphadenopathy, change in bowel habits, chest pain, Clostridioides (formerly Clostridium) difficile-associated diarrhea, colitis (microscopic), confusion, conjunctivitis, cutaneous lupus erythematosus (including exacerbations), cyanocobalamin deficiency, cystitis, depression, dermatitis, diaphoresis, dysgeusia, dysmenorrhea, dyspepsia, dysphagia, dyspnea, dysuria, edema, enlargement of abdomen, epigastric pain, epistaxis, eructation, erythema multiforme, erythematous rash, exacerbation of arthritis, exacerbation of asthma, facial edema, fatigue, fibromyalgia syndrome, flu-like symptoms, flushing, frequent bowel movements, fungal infection, gastroenteritis, gastrointestinal candidiasis, gastrointestinal dysplasia, gastrointestinal hemorrhage, genital candidiasis, glycosuria, goiter, gynecomastia, hallucination, hematuria, hepatic encephalopathy, hepatic failure, hepatitis, hepatotoxicity (idiosyncratic) (Chalasani 2014), hernia of abdominal cavity, hiccups, hot flash, hyperbilirubinemia, hyperhidrosis, hypersensitivity reaction, hypertension, hypertonia, hyperuricemia, hypochromic anemia, hypoesthesia, hypomagnesemia (with or without hypocalcemia and/or hypokalemia), hyponatremia, impotence, increased appetite, increased thirst, insomnia, interstitial nephritis, jaundice, laryngeal edema, leukocytosis, leukopenia, maculopapular rash, malaise, melena, menstrual disease, migraine, mouth disease, muscle cramps, myalgia, myasthenia, nervousness, otalgia, otitis media, pain, pancreatitis, pancytopenia, paresthesia, pathological fracture due to osteoporosis, peripheral edema, pharyngeal disease, pharyngitis, polymyalgia rheumatica, polyp (fundic gland), polyuria, pruritus ani, rectal disease, renal disease (chronic; [Lazarus 2016]), rhinitis, rigors, sinusitis, skin photosensitivity, skin rash, sleep disorder, Stevens-Johnson syndrome, stomatitis, systemic lupus erythematosus (including exacerbations), tachycardia, thrombocytopenia, tinnitus, tongue disease, tongue edema, toxic epidermal necrolysis, tremor, urinary frequency, urine abnormality, urticaria, vaginitis, vertigo, visual disturbance, visual field defect, weight gain, weight loss

* See Cautions in AHFS Essentials for additional information.

Allergy and Idiosyncratic Reactions

• Proton Pump Inhibitor, Benzimidazole Allergy

Metabolism/Transport Effects

Substrate of CYP2C19 (minor), CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2C19 (weak), OAT1/3

Drug Interactions Open Interactions

Acalabrutinib: Proton Pump Inhibitors may decrease the serum concentration of Acalabrutinib. Risk X: Avoid combination

Amphetamine: Proton Pump Inhibitors may increase the absorption of Amphetamine. Risk C: Monitor therapy

Atazanavir: Proton Pump Inhibitors may decrease the serum concentration of Atazanavir. Management: Avoid use in treatment-experienced patients. In treatment-naive patients, administer boosted atazanavir 12 hours after the PPI and the PPI dose should not exceed the equivalent of 20 mg omeprazole. Monitor for reduced atazanavir efficacy. Risk D: Consider therapy modification

Bisphosphonate Derivatives: Proton Pump Inhibitors may diminish the therapeutic effect of Bisphosphonate Derivatives. Risk C: Monitor therapy

Bosutinib: Proton Pump Inhibitors may decrease the serum concentration of Bosutinib. Management: Consider alternatives to proton pump inhibitors, such as short-acting antacids or histamine-2 receptor antagonists. Administer alternative agents more than 2 hours before or after bosutinib. Risk D: Consider therapy modification

Capecitabine: Proton Pump Inhibitors may diminish the therapeutic effect of Capecitabine. Risk C: Monitor therapy

Cefditoren: Proton Pump Inhibitors may decrease the serum concentration of Cefditoren. Management: If possible, avoid use of cefditoren with proton pump inhibitors (PPIs). Consider alternative methods to minimize/control acid reflux (eg, diet modification) or alternative antimicrobial therapy if use of PPIs can not be avoided. Risk D: Consider therapy modification

Cefpodoxime: Proton Pump Inhibitors may decrease the serum concentration of Cefpodoxime. Risk C: Monitor therapy

Cefuroxime: Proton Pump Inhibitors may decrease the absorption of Cefuroxime. Risk X: Avoid combination

Cilostazol: Esomeprazole may increase serum concentrations of the active metabolite(s) of Cilostazol. Esomeprazole may increase the serum concentration of Cilostazol. Risk C: Monitor therapy

Citalopram: Esomeprazole may increase the serum concentration of Citalopram. Management: Limit citalopram dose to a maximum of 20 mg/day if used with esomeprazole. Patients using this combination should be monitored closely for evidence of citalopram toxicity (eg, serotonin syndrome, QT prolongation, etc.). Risk D: Consider therapy modification

CloBAZam: CYP2C19 Inhibitors (Weak) may increase serum concentrations of the active metabolite(s) of CloBAZam. CYP2C19 Inhibitors (Weak) may increase the serum concentration of CloBAZam. Risk C: Monitor therapy

Clopidogrel: Esomeprazole may diminish the antiplatelet effect of Clopidogrel. Esomeprazole may decrease serum concentrations of the active metabolite(s) of Clopidogrel. Management: Clopidogrel prescribing information recommends avoiding concurrent use with esomeprazole. Rabeprazole or pantoprazole may be lower-risk alternatives to esomeprazole. Risk D: Consider therapy modification

CYP2C19 Inducers (Strong): May decrease the serum concentration of Esomeprazole. Risk X: Avoid combination

Cysteamine (Systemic): Proton Pump Inhibitors may diminish the therapeutic effect of Cysteamine (Systemic). Risk C: Monitor therapy

Dacomitinib: Proton Pump Inhibitors may decrease the serum concentration of Dacomitinib. Management: Avoid concurrent use of dacomitinib with proton pump inhibitors. Antacids may be used. Histamine H2-receptor antagonists (HR2A) may be used if dacomitinib is given at least 6 hours before or 10 hours after the H2RA. Risk X: Avoid combination

Dasatinib: Proton Pump Inhibitors may decrease the serum concentration of Dasatinib. Management: Antacids (taken 2 hours before or after dasatinib administration) can be used in place of the proton pump inhibitor if some acid-reducing therapy is needed. Risk X: Avoid combination

Delavirdine: Proton Pump Inhibitors may decrease the serum concentration of Delavirdine. Management: Chronic therapy with proton pump inhibitors (PPIs) should be avoided in patients treated with delavirdine. The clinical significance of short-term PPI therapy with delavirdine is uncertain, but such therapy should be undertaken with caution. Risk X: Avoid combination

Dexmethylphenidate: Proton Pump Inhibitors may increase the absorption of Dexmethylphenidate. Specifically, proton pump inhibitors may interfere with the normal release of drug from the extended-release capsules (Focalin XR brand), which could result in both increased absorption (early) and decreased delayed absorption. Risk C: Monitor therapy

Dextroamphetamine: Proton Pump Inhibitors may increase the absorption of Dextroamphetamine. Specifically, the dextroamphetamine absorption rate from mixed amphetamine salt extended release (XR) capsules may be increased in the first hours after dosing. Risk C: Monitor therapy

Dichlorphenamide: OAT1/3 Inhibitors may increase the serum concentration of Dichlorphenamide. Risk C: Monitor therapy

Doxycycline: Proton Pump Inhibitors may decrease the bioavailability of Doxycycline. Risk C: Monitor therapy

Enoxacin: Proton Pump Inhibitors may decrease the absorption of Enoxacin. Risk C: Monitor therapy

Erlotinib: Proton Pump Inhibitors may decrease the serum concentration of Erlotinib. Risk X: Avoid combination

Escitalopram: Esomeprazole may increase the serum concentration of Escitalopram. Risk C: Monitor therapy

Fosphenytoin-Phenytoin: CYP2C19 Inhibitors (Weak) may increase the serum concentration of Fosphenytoin-Phenytoin. Risk C: Monitor therapy

Gefitinib: Proton Pump Inhibitors may decrease the serum concentration of Gefitinib. Management: Avoid use of proton pump inhibitors (PPIs) with gefitinib when possible. If required, administer gefitinib 12 hours after administration of the PPI or 12 hours before the next dose of the PPI. Closely monitor clinical response to gefitinib. Risk D: Consider therapy modification

Indinavir: Proton Pump Inhibitors may decrease the serum concentration of Indinavir. Risk C: Monitor therapy

Iron Preparations: Proton Pump Inhibitors may decrease the absorption of Iron Preparations. Exceptions: Ferric Carboxymaltose; Ferric Citrate; Ferric Derisomaltose; Ferric Gluconate; Ferric Hydroxide Polymaltose Complex; Ferric Pyrophosphate Citrate; Ferumoxytol; Iron Dextran Complex; Iron Sucrose. Risk C: Monitor therapy

Itraconazole: Proton Pump Inhibitors may decrease the serum concentration of Itraconazole. Proton Pump Inhibitors may increase the serum concentration of Itraconazole. Management: Exposure to Tolsura brand itraconazole may be increased by PPIs; consider itraconazole dose reduction. Exposure to Sporanox brand itraconazole capsules may be decreased by PPIs. Give Sporanox brand itraconazole at least 2 hrs before or 2 hrs after PPIs Risk D: Consider therapy modification

Ketoconazole (Systemic): Proton Pump Inhibitors may decrease the absorption of Ketoconazole (Systemic). Ketoconazole (Systemic) may increase the serum concentration of Proton Pump Inhibitors. Management: Administer ketoconazole with an acidic beverage, such as non-diet cola, to increase gastric acidity and improve absorption if concomitant use with proton pump inhibitors is necessary. Risk D: Consider therapy modification

Ledipasvir: Proton Pump Inhibitors may decrease the serum concentration of Ledipasvir. Management: PPI doses equivalent to omeprazole 20 mg or lower may be given with ledipasvir under fasted conditions. Administration with higher doses of PPIs, 2 hours after a PPI, or in combination with food and PPIs may reduce ledipasvir bioavailability. Risk D: Consider therapy modification

Lumacaftor and Ivacaftor: May decrease the serum concentration of Proton Pump Inhibitors. Risk C: Monitor therapy

Mesalamine: Proton Pump Inhibitors may diminish the therapeutic effect of Mesalamine. Proton pump inhibitor-mediated increases in gastrointestinal pH may cause the premature release of mesalamine from specific sustained-release mesalamine products. Management: Consider avoiding concurrent administration of high-dose proton pump inhibitors (PPIs) with sustained-release mesalamine products. Risk D: Consider therapy modification

Methotrexate: Proton Pump Inhibitors may increase the serum concentration of Methotrexate. Risk C: Monitor therapy

Methylphenidate: Proton Pump Inhibitors may increase the absorption of Methylphenidate. Specifically, proton pump inhibitors may interfere with the normal release of drug from the extended-release capsules (Ritalin LA brand), which could result in both increased absorption (early) and decreased delayed absorption. Risk C: Monitor therapy

Multivitamins/Minerals (with ADEK, Folate, Iron): Proton Pump Inhibitors may decrease the serum concentration of Multivitamins/Minerals (with ADEK, Folate, Iron). Specifically, the absorption of iron may be decreased. Risk C: Monitor therapy

Mycophenolate: Proton Pump Inhibitors may decrease the serum concentration of Mycophenolate. Specifically, concentrations of the active mycophenolic acid may be reduced. Risk C: Monitor therapy

Nelfinavir: Proton Pump Inhibitors may decrease serum concentrations of the active metabolite(s) of Nelfinavir. Proton Pump Inhibitors may decrease the serum concentration of Nelfinavir. Management: Due to potentially significant reductions in nelfinavir exposure, avoid concurrent use of nelfinavir with a PPI when possible. If unavoidable, consider PPI use for a short duration (less than 30 days) and closely monitor viral load during coadministration Risk D: Consider therapy modification

Neratinib: Proton Pump Inhibitors may decrease the serum concentration of Neratinib. Specifically, proton pump inhibitors may reduce neratinib absorption. Risk X: Avoid combination

Nilotinib: Proton Pump Inhibitors may decrease the serum concentration of Nilotinib. Management: Avoid this combination when possible since separation of doses is not likely to be an adequate method of minimizing the interaction. Risk D: Consider therapy modification

Octreotide: Proton Pump Inhibitors may decrease the serum concentration of Octreotide. Risk C: Monitor therapy

PAZOPanib: Proton Pump Inhibitors may decrease the serum concentration of PAZOPanib. Risk X: Avoid combination

Pexidartinib: Proton Pump Inhibitors may decrease the serum concentration of Pexidartinib. Management: If acid-reduction is needed, consider administering an antacid 2 hours before or after pexidartinib, or administer pexidartinib 2 hours before or 10 hours after an H2 receptor antagonist. Risk X: Avoid combination

Posaconazole: Proton Pump Inhibitors may decrease the serum concentration of Posaconazole. Management: Avoid coadministration of proton pump inhibitors (PPIs) and posaconazole oral suspension. Posaconazole delayed-release tablets do not appear to be sensitive to this interaction and do not required dose adjustment if coadministered with PPIs. Risk D: Consider therapy modification

Rilpivirine: Proton Pump Inhibitors may decrease the serum concentration of Rilpivirine. Risk X: Avoid combination

Riociguat: Proton Pump Inhibitors may decrease the serum concentration of Riociguat. Risk C: Monitor therapy

Risedronate: Proton Pump Inhibitors may diminish the therapeutic effect of Risedronate. Proton Pump Inhibitors may increase the serum concentration of Risedronate. This applies specifically to use of delayed-release risedronate. Management: Coadministration of PPIs with delayed-release risedronate formulations is not recommended. Limit PPI dose and duration during coadministration with risedronate as possible. Patients over age 70 years are at higher risk of adverse effects. Risk D: Consider therapy modification

Saquinavir: Proton Pump Inhibitors may increase the serum concentration of Saquinavir. Risk C: Monitor therapy

Secretin: Proton Pump Inhibitors may diminish the diagnostic effect of Secretin. Specifically, use of PPIs may cause a hyperresponse in gastrin secretion in response to secretin stimulation testing, falsely suggesting gastrinoma. Management: Avoid concomitant use of proton pump inhibitors (PPIs) and secretin, and discontinue PPIs several weeks prior to secretin administration, with the duration of separation determined by the specific PPI. See full monograph for details. Risk D: Consider therapy modification

Selpercatinib: Proton Pump Inhibitors may decrease the serum concentration of Selpercatinib. Management: Coadministration of selpercatinib and proton pump inhibitors should be avoided. If coadministration cannot be avoided, selpercatinib and proton pump inhibitors should be administered simultaneously with food. Risk D: Consider therapy modification

SORAfenib: Proton Pump Inhibitors may decrease the absorption of SORAfenib. Risk C: Monitor therapy

St John's Wort: May decrease the serum concentration of Esomeprazole. Risk X: Avoid combination

Tacrolimus (Systemic): Proton Pump Inhibitors may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy

Tipranavir: May decrease the serum concentration of Proton Pump Inhibitors. These data are derived from studies with Ritonavir-boosted Tipranavir. Risk C: Monitor therapy

Velpatasvir: Proton Pump Inhibitors may decrease the serum concentration of Velpatasvir. Risk X: Avoid combination

Vitamin K Antagonists (eg, warfarin): Esomeprazole may increase the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy

Voriconazole: May increase the serum concentration of Proton Pump Inhibitors. Proton Pump Inhibitors may increase the serum concentration of Voriconazole. Risk C: Monitor therapy

Food Interactions

Prolonged treatment (≥2 years) may lead to malabsorption of dietary vitamin B12 and subsequent vitamin B12 deficiency (Lam, 2013).

Test Interactions

Esomeprazole may falsely elevate serum chromogranin A (CgA) levels. The increased CgA level may cause false-positive results in the diagnosis of a neuroendocrine tumor. Temporarily stop esomeprazole ≥14 days prior to assessing CgA level; repeat level if initially elevated; use the same laboratory for all testing of CgA levels.

Genes of Interest

• CYP2C19 - Esomeprazole

Monitoring Parameters

Susceptibility testing recommended in patients who fail H. pylori eradication regimen. Monitor for rebleeding in patients with peptic ulcer bleed. For patients expected to be on prolonged therapy or who take PPIs with medications such as digoxin or drugs that may cause hypomagnesemia (eg, diuretics), consider monitoring magnesium levels prior to initiation of treatment and periodically thereafter.

Advanced Practitioners Physical Assessment/Monitoring

Assess effectiveness and interactions of other medications patient may be taking that are dependent on cytochrome P450 metabolism or on an acid environment for absorption.

Nursing Physical Assessment/Monitoring

Monitor for rebleeding; ongoing diarrhea related to C. difficile; fractures in patients with a history of osteoporosis, tetany, arrhythmias; and seizures related to hypomagnesemia. Monitor for common side effects including headache, nausea, abdominal discomfort, dry mouth, diarrhea, gas, constipation, and drowsiness.

Dosage Forms Considerations

Esomeprazole strontium 49.3 mg is equivalent to 40 mg of esomeprazole base.

Esomep-EZS Kit contains delayed release capsules, packaged with Pill Swallowing Spray

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Capsule Delayed Release, Oral, as magnesium [strength expressed as base]:

GoodSense Esomeprazole: 20 mg [gluten free; contains brilliant blue fcf (fd&c blue #1)]

NexIUM: 20 mg, 40 mg [contains brilliant blue fcf (fd&c blue #1), fd&c red #40, fd&c yellow #10 (quinoline yellow)]

NexIUM 24HR: 20 mg [contains brilliant blue fcf (fd&c blue #1), fd&c red #40]

NexIUM 24HR Clear Minis: 20 mg [contains corn starch, fd&c blue #2 (indigotine), fd&c blue #2 aluminum lake, fd&c red #40]

Generic: 20 mg, 40 mg

Capsule Delayed Release, Oral, as strontium:

Generic: 24.65 mg [DSC], 49.3 mg

Kit, Oral, as magnesium [strength expressed as base]:

Esomep-EZS: 20 mg [contains brilliant blue fcf (fd&c blue #1), sodium benzoate]

Packet, Oral, as magnesium [strength expressed as base]:

NexIUM: 2.5 mg (30 ea); 5 mg (30 ea); 10 mg (30 ea); 20 mg (30 ea); 40 mg (30 ea)

Generic: 10 mg (30 ea); 20 mg (30 ea); 40 mg (30 ea)

Solution Reconstituted, Intravenous, as sodium [strength expressed as base]:

NexIUM I.V.: 40 mg (1 ea) [contains edetate disodium]

Generic: 20 mg (1 ea [DSC]); 40 mg (1 ea)

Solution Reconstituted, Intravenous, as sodium [strength expressed as base, preservative free]:

Generic: 40 mg (1 ea)

Tablet Delayed Release, Oral, as magnesium [strength expressed as base]:

NexIUM 24HR: 20 mg [contains fd&c blue #2 aluminum lake, fd&c red #40 aluminum lake]

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule Delayed Release, Oral, as magnesium [strength expressed as base]:

Generic: 40 mg

Packet, Oral, as magnesium [strength expressed as base]:

NexIUM: 10 mg (30 ea)

Tablet Delayed Release, Oral, as magnesium:

NexIUM: 40 mg

Generic: 40 mg

Tablet Delayed Release, Oral, as magnesium [strength expressed as base]:

NexIUM: 20 mg

Generic: 20 mg

Anatomic Therapeutic Chemical (ATC) Classification

• A02BC05

Generic Available (US)

May be product dependent

Pricing: US

Capsule, delayed release (Esomeprazole Magnesium Oral)

20 mg (per each): $1.02 - $9.02

40 mg (per each): $1.02 - $9.02

Capsule, delayed release (Esomeprazole Strontium Oral)

49.3 mg (per each): $49.30

Capsule, delayed release (GoodSense Esomeprazole Oral)

20 mg (per each): $0.66

Capsule, delayed release (NexIUM 24HR Clear Minis Oral)

20 mg (per each): $0.65

Capsule, delayed release (NexIUM 24HR Oral)

20 mg (per each): $0.70

Capsule, delayed release (NexIUM Oral)

20 mg (per each): $10.64

40 mg (per each): $10.64

Kit (Esomep-EZS Oral)

20 mg (per each): $3,610.00

Pack (Esomeprazole Magnesium Oral)

10 mg (per each): $9.76

20 mg (per each): $9.76

40 mg (per each): $9.76

Pack (NexIUM Oral)

2.5 mg (per each): $11.49

5 mg (per each): $11.49

10 mg (per each): $11.49

20 mg (per each): $11.49

40 mg (per each): $11.49

Solution (reconstituted) (Esomeprazole Sodium Intravenous)

40 mg (per each): $41.88 - $60.00

Solution (reconstituted) (NexIUM I.V. Intravenous)

40 mg (per each): $53.58

Tablet, EC (NexIUM 24HR Oral)

20 mg (per each): $0.65

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Mechanism of Action

Proton pump inhibitor suppresses gastric acid secretion by inhibition of the H+/K+-ATPase in the gastric parietal cell. Esomeprazole is the S-isomer of omeprazole.

Pharmacodynamics/Kinetics

Distribution: Vdss: 16 L

Protein binding: 97%

Metabolism: Hepatic via CYP2C19 primarily and (to a lesser extent) via 3A4 to hydroxy, desmethyl, and sulfone metabolites (all inactive)

Bioavailability: Oral: 64 after a single dose; 90% with repeat dosing

Half-life elimination:

Infants: 0.93 hours

Children 1 to 5 years: 0.42 to 0.74 hours (Zhao 2006)

Children 6 to 11 years: 0.73 to 0.88 hours (Zhao 2006)

Children ≥12 years and Adolescents ≤17 years: 0.82 to 1.22 hours (Li 2006)

Adults: ~1 to 1.5 hours

Time to peak: Oral:

Infants: Median: 3 hours

Children 1 to 5 years: 1.33 to 1.44 hours (Zhao 2006)

Children 6 to 11 years: 1.75 to 1.79 hours (Zhao 2006)

Children ≥12 years and Adolescents ≤17 years: 1.96 to 2.04 hours (Li 2006)

Adults: 1.5 to 2 hours

Excretion: Urine (80%, primarily as inactive metabolites; <1% as active drug); feces (20%)

Clearance (with repeated dosing):

Children 1 to 5 years: 6 to 19.44 L/hour (Zhao 2006)

Children 6 to 11 years: 7.84 to 9.22 L/hour (Zhao 2006)

Children ≥12 years and Adolescents ≤17 years: 8.36 to 15.88 L/hour (Li 2006)

Pharmacodynamics/Kinetics: Additional Considerations

Hepatic function impairment: AUC was 2 to 3 times higher in patients with severe hepatic impairment.

Geriatric: AUC and Cmax were increased by 25% and 18%, respectively, following administration of esomeprazole magnesium.

Gender: AUC and Cmax were 13% higher in women than men following administration of esomeprazole magnesium.

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Xerostomia (normal salivary flow resumes upon discontinuation)

Effects on Bleeding

No information available to require special precautions

Related Information

• Beers Criteria 2019: Potentially Inappropriate Medication Use in Older Adults ≥65 Years of Age
• Drugs With Actionable Pharmacogenomic Recommendations
• Oral Medications That Should Not Be Crushed or Altered

Index Terms

Esomeprazole Magnesium; Esomeprazole Sodium; Esomeprazole Strontium; Nexium 24HR

FDA Approval Date

February 20, 2001

References

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Brand Names: International

Acidal (FI); Adikan (AR); Aesopra (PH); Almiprazole (EG); Alton (LK); Aspepraz (ZA); Axagon (IT); Axiago (ES); Ceso (IN); Demoel (PT); Durotiv (AT); Emanera (RU, SG, UA); Emazole (IE, PH); Emep (PH); Emess (LK); Emozul (GB, HU); Empel (LK); Epral (CL); Escadra (LV); Esio (BR); Esmopump (EG); Esobax (NL); Esodec (DK); Esofag (IN, PH); Esofax (CR, DO, GT, HN, NI, PA, SV); Esoflux (PH); Esoget DRT (PH); Esola (ID); Esom (TR); Esomax (ID); Esomep (BD, CH, LB, PH); Esonexa (UA); Esopra (BD); Esorest (IN); Esoroxen (KR); Esotec (PH); Esoxium (UA, VN); Esoz (VE); Esoz-20 (ET, ZW); Esoz-40 (ZW); Esozid (ID); Esural (BH); Exmezol (KR); Exocid (ID); Exozole (KR); Exzium (LK); Ezobloc (BR); Haxium (VN); Helides (CZ, PL); Ignis (IN); Inexium (FR); Jubium-20 (SG); Jubium-40 (SG); Lanxium (ID); Maxima (BD); Nedox (CO, PE); Neksium (IN); Nemeol (KR); Neopral (PE); Neoren (CL); Nepramel (IE); Nesopram (ZA); Nexazol (KR); Nexazole (IE); Nexiam (LU, ZA); Nexigas (ID); Neximash (EG); Nexipra (KR); Nexird (KR); Nexium (AE, AR, AT, AU, BB, BE, BF, BG, BH, BJ, BM, BO, BR, BS, BZ, CH, CI, CL, CO, CR, CU, CY, CZ, DE, DK, DO, EE, EG, ES, ET, FI, FR, GB, GH, GM, GN, GR, GT, GY, HK, HN, HR, HU, ID, IE, IL, IS, IT, JM, JO, JP, KE, KR, KW, LB, LK, LR, LT, LV, MA, ML, MR, MT, MU, MW, MY, NE, NG, NI, NL, NO, PA, PE, PH, PL, PR, PT, PY, QA, RO, RU, SA, SC, SD, SE, SG, SI, SK, SL, SN, SR, SV, TH, TN, TR, TT, TW, TZ, UA, UG, UY, VE, VN, ZM, ZW); Nexium IV (MX); Nexium-MUPS (MX); Nexmezol (LV, ZW); Nexole (AU); Nexpa (KR); Nexpro (IN, PH, ZW); Nexpro-20 (ET, TZ); Nexpro-40 (TZ); Nexum (PK); Noxicid (AU); Peprazom (PH); Prazia (BD); Proxium (ID); Raciper (IN); Reflux (AR); S-Omipin (PH); Solezol (IL); Sompraz (IN); Sompraz IV (TZ); Stadnex (VN); Ulcium (EC); Xsom (PH); Zemep (PH); Zoleric (LK); Zutura (EC)

Last Updated 10/16/20