Version May 2024
Gastroesophageal reflux disease: Note: Routine use is not recommended in preterm neonates (AAP [Eichenwald 2018]). Limited data available: Term and preterm neonates: Oral: 0.5 mg/kg/dose once daily. Dosing based on an open label study and a randomized, double-blind, placebo-controlled phase 3 study. Both studies included preterm and term neonates (Total esomeprazole patients n=52; GA: 23 to 41 weeks) with clinical symptoms of GERD; patients were treated for 7 to 14 days. While both studies showed a reduction in esophageal acid exposure and improved gastric acidity, the total number of GERD-related gastrointestinal or cardiorespiratory symptoms did not decrease or differ from placebo group; however, both studies showed an improvement in neurobehavioral symptoms such as back arching, irritability, and fussiness (Davidson 2013; Omari 2009).
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.
Gastroesophageal reflux disease, 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.
Infants, Children, and Adolescents: Oral, IV: No dosage adjustments necessary.
There are no specific pediatric recommendations; based on experience in adult patients, adjustment suggested in severe impairment.
(For additional information see "Esomeprazole: Drug information")
Dosage guidance:
Dosing: 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.
Eosinophilic esophagitis (off-label use): Oral: 20 to 40 mg twice daily for an 8-week trial (Laserna-Mendieta 2020; Lucendo 2016; Philpott 2016). Once 8-week trial is complete and remission is achieved, the dose may be gradually lowered to an individualized maintenance level (Laserna-Mendieta 2020). Some experts initiate with once-daily dosing and increase to twice-daily dosing after 4 weeks if symptoms fail to improve (Bonis 2021).
Gastroesophageal reflux disease, erosive or nonerosive:
Note: For patients with alarm symptoms (eg, dysphagia), referral to a specialist is recommended (ACG [Katz 2022]). For maximal efficacy, administer 30 to 60 minutes prior to a meal (Shin 2013). Maximal acid suppression is generally observed after ~3 days of continuous therapy (Shin 2013; Weisner 2021).
Initial therapy:
Mild/intermittent disease (<2 episodes/week) without erosive esophagitis or Barrett esophagus:
Note: Some experts reserve proton pump inhibitors (PPIs) as alternatives to H2-receptor antagonists (H2RAs) for patients who have residual acid reflux symptoms despite twice-daily H2RA (Kahrilas 2022).
Oral: 20 mg once daily for 4 to 8 weeks (ACG [Katz 2022]; Bayerdörffer 2016). Note: Some experts continue therapy until patient has been asymptomatic for 8 weeks (Kahrilas 2022).
Severe and/or frequent symptoms (≥2 episodes/week) without erosive esophagitis or Barrett esophagus:
Oral: 20 to 40 mg once daily for 4 to 8 weeks (Hsu 2015; Kahrilas 2000). Note: Some experts use 20 mg once daily and continue therapy until patient has been asymptomatic for 8 weeks (Kahrilas 2022).
Erosive esophagitis or Barrett esophagus:
Oral: 40 mg once daily for 4 to 8 weeks then 20 mg once daily indefinitely, (ACG [Shaheen 2022]; AGA [Targownik 2022]; Labenz 2005; manufacturer's labeling) or 20 mg once daily indefinitely (preferred by some experts) (Kahrilas 2022).
IV (alternative route): 20 or 40 mg once daily for ≤10 days. Note: For use in patients with erosive esophagitis when oral therapy is not appropriate. Safety and efficacy have not been established for use >10 days (manufacturer’s labeling).
Residual symptoms despite 20 mg once daily:
Note: Referral to a specialist is recommended. Options include doubling the PPI dose, switching to a different PPI, or adding an H2RA (Talley 2021). For patients requiring concomitant H2RA therapy, some experts administer the H2RA at bedtime (Fass 2022; Wang 2009); however, others advocate concurrent administration to ensure adherence (Abdul-Hussein 2015; Fandriks 2007; Sugimoto 2006).
Recurrent symptoms after discontinuing acid suppression:
Intermittent symptoms: Oral: 20 mg once daily as needed (ACG [Katz 2022]; Bayerdörffer 2016; Zacny 2005). Note: Some experts do not recommend intermittent use due to reduced efficacy (Kahrilas 2022; Wolfe 2022).
Persistent symptoms (eg consistent with symptoms at diagnosis):
Recurrent symptoms after ≥3 months: Repeat an 8-week course at the previously effective dose (Kahrilas 2022).
Recurrent symptoms after <3 months: Long-term maintenance at the lowest effective dose necessary; referral to a specialist is recommended (ACG [Katz 2022]; Kahrilas 2022).
OTC labeling (patient-guided therapy): Heartburn, frequent symptoms (≥2 episodes/week): Oral: 20 mg once daily for 14 days (maximum: 20 mg/day); may repeat 14-day course every 4 months if needed. Seek medical referral if symptoms do not resolve within 14 days of treatment; do not take for >14 days or more often than every 4 months unless directed by a physician (manufacturer's labeling).
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. Note: Esomeprazole strontium capsules have been discontinued in the United States for >1 year.
Nonsteroidal anti-inflammatory drug–induced gastric ulcers, prevention: 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. Esomeprazole strontium capsules have been discontinued in the United States for >1 year.
Nonsteroidal anti-inflammatory drug–induced gastric ulcers, treatment (off-label use): Oral: Esomeprazole magnesium: 20 mg once daily for 8 weeks (Goldstein 2007).
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. Note: Esomeprazole strontium capsules have been discontinued in the United States for >1 year.
Peptic ulcer disease, treatment of complicated ulcers (perforation, penetration, or gastric outlet obstruction) (off-label use):
Oral, IV: 40 mg twice daily for 4 weeks, followed by 40 mg once daily. Duration depends on the location and etiology of ulcer (Vakil 2020c).
Upper GI bleed, acute:
Pre-endoscopy (unknown etiology) (off label): Note: Optimal proton pump inhibitor (PPI) therapy is uncertain. For patients with suspected active upper GI bleed, some experts suggest initiating high-dose IV PPI with continuous or intermittent dosing prior to endoscopy (ACG [Laine 2021]). Where IV PPIs are unavailable, high-dose oral PPI therapy is a reasonable alternative (ESGE [Gralnek 2021]).
Continuous infusion: IV: 80 mg bolus, followed by 8 mg/hour until endoscopy with subsequent dosing based on endoscopic findings (ACG [Laine 2021]; Barkun 2019; ESGE [Gralnek 2021]; Lau 2007; Liu 2012).
Intermittent dosing: IV: 80 mg once (active bleeding) or 40 mg once (no evidence of active bleeding); if endoscopy is not performed within 12 hours, begin 40 mg every 12 hours until endoscopy. Subsequent dosing is based on endoscopic findings (ACG [Laine 2021]; ESGE [Gralnek 2021]; Leung 2022; Sachar 2014).
Oral (alternative route): 40 mg twice daily (ESGE [Gralnek 2021]; Keyvani 2006). Note: For select patients at low risk for rebleeding (ie, GBS of 0 to 1, clinically stable, timely access to medical care) who are to receive outpatient endoscopy, some experts use 20 mg once daily (Saltzman 2022).
Postendoscopy (peptic ulcer hemorrhage): Note: Treatment should address the underlying cause of the bleed. In patients with bleeding peptic ulcers, continue PPI therapy and direct further treatment at healing the ulcers and eliminating precipitating factors (eg, H. pylori, nonsteroidal anti-inflammatory drugs) (ACG [Laine 2021]; ESGE [Gralnek 2021]).
Peptic ulcer with high-risk stigmata of recent hemorrhage (eg, active bleed, visible vessel, adherent clot):
Continuous infusion: IV: 80 mg bolus, followed by 8 mg/hour; if patient received 80 mg bolus prior to endoscopy, may omit bolus dose. Continue for ≥72 hours, then transition to high-dose oral maintenance therapy when able to tolerate (ACG [Laine 2021]; Barkun 2019; ESGE [Gralnek 2021]; Lau 2007; Liu 2012).
Intermittent dosing (alternative administration): IV: 80 mg bolus once, then 40 mg every 12 hours; if 80 mg bolus was received prior to endoscopy, may omit bolus dose. Continue for ≥72 hours, then transition to high-dose oral maintenance therapy when able to tolerate (ACG [Laine 2021]; Barkun 2019; ESGE [Gralnek 2021]; Hsieh 2021; Leung 2022).
Maintenance therapy: Oral: 40 mg twice daily for 14 days, followed by 40 mg once daily (ACG [Laine 2021]; Barkun 2019; ESGE [Gralnek 2021]; Sung 2014).
Duration: The total duration of treatment depends on size, location, and cause of the ulcer and ranges from 4 to 12 weeks (ACG [Laine 2012]; Barkun 2010; Barkun 2019; Vakil 2022).
Peptic ulcer with clean base or flat pigmented spot: Note: May transition to an oral PPI immediately after endoscopy (ACG [Laine 2021).
Maintenance therapy: Oral: 20 mg once daily (ACG [Laine 2012]; ACG [Laine 2021]; Saltzman 2022; Stanley 2019).
Duration: The total duration of treatment depends on size, location, and cause of the ulcer and ranges from 4 to 12 weeks (ACG [Laine 2012]; Barkun 2010; Barkun 2019; Vakil 2022).
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.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Kidney impairment prior to treatment initiation:
Altered kidney function:
Oral:
Esomeprazole magnesium: No dosage adjustment necessary for any degree of kidney dysfunction (<1% excreted in the urine) (manufacturer's labeling).
Esomeprazole strontium:
eGFR ≥30 mL/minute/1.73 m2: No dosage adjustment necessary.
eGFR <30 mL/minute/1.73 m2: Use is not recommended (has not been studied); strontium is eliminated by the kidney (manufacturer's labeling; expert opinion) and other esomeprazole formulations are available.
IV: No dosage adjustment necessary for any degree of kidney impairment (<1% excreted in the urine) (manufacturer's labeling).
Hemodialysis, intermittent (thrice weekly): Unlikely to be significantly dialyzable (highly protein bound) (manufacturer's labeling):
Oral:
Esomeprazole magnesium: No dosage adjustment necessary (<1% excreted in the urine) (manufacturer's labeling; expert opinion).
Esomeprazole strontium: Use is not recommended (has not been studied); strontium is eliminated by the kidney (manufacturer's labeling) and other esomeprazole formulations are available.
IV: No dosage adjustment necessary (<1% excreted in the urine) (manufacturer's labeling; expert opinion).
Peritoneal dialysis: Unlikely to be significantly dialyzable (highly protein bound) (manufacturer's labeling):
Oral:
Esomeprazole magnesium: No dosage adjustment necessary (<1% excreted in the urine) (manufacturer's labeling; expert opinion).
Esomeprazole strontium: Use is not recommended (has not been studied); strontium is eliminated by the kidney and other esomeprazole formulations are available.
IV: No dosage adjustment necessary (<1% excreted in the urine) (manufacturer's labeling; expert opinion).
CRRT:
Oral:
Esomeprazole magnesium: No dosage adjustment necessary (<1% excreted in the urine) (manufacturer's labeling; expert opinion).
Esomeprazole strontium: Use is not recommended (has not been studied); strontium is eliminated by the kidney (manufacturer's labeling; expert opinion) and other esomeprazole formulations are available.
IV: No dosage adjustment necessary (<1% excreted in the urine) (manufacturer's labeling; expert opinion).
PIRRT (eg, sustained, low-efficiency diafiltration):
Oral:
Esomeprazole magnesium: No dosage adjustment necessary (<1% excreted in the urine) (manufacturer's labeling; expert opinion).
Esomeprazole strontium: Use is not recommended (has not been studied); strontium is eliminated by the kidney (manufacturer's labeling; expert opinion) and other esomeprazole formulations are available.
IV: No dosage adjustment necessary (<1% excreted in the urine) (manufacturer's labeling; expert opinion).
Acute kidney injury during therapy:
Tubulointerstitial nephritis: Discontinue and evaluate patients if acute tubulointerstitial nephritis is suspected.
Oral:
Mild to moderate impairment (Child-Pugh class A or B): No dosage adjustment necessary.
Severe impairment (Child-Pugh class C):
Erosive esophagitis, H. pylori eradication or prevention of nonsteroidal anti-inflammatory drug–induced gastric ulcers: The manufacturer's labeling recommends a maximum dose of 20 mg once daily.
Pathological hypersecretory conditions (Zollinger-Ellison syndrome): Initial: 20 mg twice 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.
Upper GI bleed, acute (unknown etiology or peptic ulcer hemorrhage):
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.
Cutaneous lupus erythematosus, most often subacute cutaneous lupus erythematosus (SCLE), has been reported with use of proton pump inhibitors (PPIs), including esomeprazole (Ref). SCLE is reversible (resolution ~3 months following discontinuation [range: 4 weeks to 8 months]), and cross-reactivity between PPIs has been reported (Ref). SCLE may present as a widespread skin rash which may include bullous lesions and focal skin necrosis (Ref). In addition, systemic lupus erythematosus secondary to PPIs may occur, although less often as compared to SCLE. Presentation often includes rash; however, arthralgia or cytopenia may also occur.
Mechanism: Non–dose-related; immunologic. SCLE is typically associated with positive antinuclear antibodies, anti-Ro/SSA, and anti-La/SSB antibodies (Ref).
Onset: Varied.
Cutaneous lupus erythematosus: Approximately 8 months following treatment initiation (range: 3 days to 3.5 years) (Ref).
Systemic lupus erythematosus: According to the manufacturer, may occur within days to years after initiating treatment.
Risk factors:
• Prior history or family history of SCLE, especially secondary to PPIs (Ref)
• Presence of risk factors for SCLE (eg, female of childbearing age, periods of female hormone changes, prior history of drug allergies, sun-reactive skin, exposure to UV radiation) (Ref)
Use of proton pump inhibitors (PPIs), including esomeprazole, may increase risk of enteric infections in adult and pediatric patients, including gastroenteritis and Clostridioides difficile-associated diarrhea (CDAD); however, data are conflicting, especially with regard to CDAD (Ref). Diarrhea, which may be a result of enteric infection, is the most common adverse effect secondary to long-term PPI use and often results in treatment discontinuation (Ref). Consider CDAD diagnosis in patients with persistent diarrhea that does not improve, especially in hospitalized patients.
Mechanism: Dose-related (Ref); related to the pharmacologic action. The increase in gastric pH secondary to PPI administration leads to changes in intestinal microbial environment which may allow for intestinal germination and growth of C. difficile spores, as well as colonization by other bacteria responsible for enteric infections (eg, Salmonella, Campylobacter, Shigella, norovirus) and multidrug-resistant microorganisms (Ref).
Onset: Varied; hospitalized patients receiving high doses may experience CDAD within days of treatment initiation (Ref), whereas others develop gastroenteritis with long-term therapy in the community setting (Ref).
Risk factors:
• High doses of PPIs (eg, daily or more frequently than daily use) (Ref)
• Hospitalized patients (Ref)
• Infants and children with defective immune systems or indwelling catheters (Ref)
Use of proton pump inhibitors (PPIs), including esomeprazole, may increase the risk of bone fracture in children, young adults, and older adults, including osteoporosis-related fractures (Ref). However, data regarding the impact of PPIs on fractures, as well as bone mineral density (BMD), are inconclusive and some have concluded that any association with fracture may be related to other independent risk factors (Ref).
Mechanism: Dose-related; related to the pharmacologic action (hypergastrinemia and hypochlorhydria). Hypergastrinemia causes secondary hyperparathyroidism which can increase bone resorption and subsequent decreased BMD. Hypochlorhydria results in decreased absorption of calcium, magnesium, and vitamin B12. Impaired calcium absorption may cause secondary hyperparathyroidism and decreased BMD. Decreased vitamin B12 absorption may decrease osteoblastic activity leading to decreased BMD, as well as decreased collagen cross-linking leading to weakened bone structure (Ref).
Onset: Delayed (≥1 year) (Ref).
Risk factors:
• Presence of risk factors for fractures and/or osteoporosis (Ref)
• Duration of therapy (eg, ≥1 year) (Ref)
• High doses of PPIs (≥1.5 doses per day) (Ref)
• Pediatric: Initiation of therapy at age <1 year or ≥6 years (Ref)
• Pediatric: Concurrent use of PPI plus H2 blocker (Ref)
Long-term use of proton pump inhibitors (PPIs), including esomeprazole, has been associated with the development of reversible gastric polyp (fundic gland) (Ref). Most PPI users who developed fundic gland polyps were asymptomatic. Symptomatic patients may report nausea, vomiting, or abdominal pain. GI bleeding and/or anemia may occur with ulcerated polyp. Clinicians should note that Helicobacter pylori infection may be protective against fundic gland polyps as bacterial proteases help glandular outflow by breaking down blockages (Ref).
Mechanism: Time-related; long-term use of PPIs is associated with an increase in the prevalence of parietal cell protrusions which cause outflow blockage of the isthmus and subsequent formation of fundic gland cysts. As therapy continues, fundic gland cysts may enlarge and develop into fundic gland polyps (Ref).
Onset: Delayed (>1 year) (Ref).
Risk factors:
• Patients with familial adenomatous polyposis (Ref)
• Duration of treatment (>1 year and especially ≥5 years) (Ref)
Immediate hypersensitivity reactions secondary to proton pump inhibitors (PPIs) are rare and range from urticaria and angioedema to anaphylaxis (Ref). Delayed hypersensitivity reactions include maculopapular rash (Ref), as well as rare severe cutaneous adverse reactions (SCARs), such as acute generalized exanthematous pustulosis (Ref), drug reaction with eosinophilia and systemic symptoms, fixed drug eruption, Stevens-Johnson syndrome, and toxic epidermal necrolysis (Ref).
Mechanism: Non–dose-related; immunologic.
Immediate hypersensitivity reactions (eg, anaphylaxis, urticaria): IgE-mediated (Ref)
Delayed hypersensitivity reactions (including maculopapular rash and SCARs): T-cell-mediated (Ref).
Onset:
Immediate hypersensitivity reactions: Rapid; occurs within 1 hour of administration but may occur up to 6 hours after exposure (Ref).
Delayed hypersensitivity reactions:
Maculopapular reactions: Intermediate; generally occurs 7 to 10 days after initiation, but may occur up to 1 month following initiation of therapy (Ref).
Other reactions (including SCARs): Varied; occurs after 7 to 14 days up to 3 months following initiation of therapy (Ref).
Risk factors:
• Prior history of hypersensitivity reaction to PPIs (Ref)
• Cross-reactivity has been noted with PPIs, although cross-reactivity patterns have been variable (Ref)
Long-term use of proton pump inhibitors (PPIs), including esomeprazole, has resulted in reversible hypomagnesemia (Ref); rate of occurrence may be highest with omeprazole as compared to other PPIs (Ref). Symptoms may be severe (eg, tetany, cardiac arrhythmias, cerebellar syndrome, seizures) and resistant to treatment with supplementation (Ref). May require discontinuation of PPI in addition to magnesium supplementation in ~25% of patients. Following discontinuation, magnesium normalizes after ~1 week (Ref). Hypomagnesemia may recur if PPI therapy is restarted (Ref).
Mechanism: Time-related; the specific mechanism is unknown; however, long-term use of PPIs may be associated with changes in intestinal absorption of magnesium (Ref).
Onset: Delayed; hypomagnesemia occurs most often after 1 year of therapy but may occur as early as 3 months (Ref). In patients with prior PPI-induced hypomagnesemia, re-initiation may result in recurrence within 2 weeks (Ref).
Risk factors:
• Duration of therapy (≥3 months and especially >1 year) (Ref)
• Concurrent use of other drugs that cause hypomagnesemia (eg, loop diuretics, thiazide diuretics) (Ref)
• Patients who have undergone kidney transplantation (Ref)
Acute interstitial nephritis (AIN) may occur rarely with use of proton pump inhibitors (PPIs), including esomeprazole (Ref), with renal biopsy showing diffuse interstitial infiltrate and tubulitis (Ref). Patients generally achieve complete or partial recovery by 6 months following treatment of AIN (Ref). Signs of systemic hypersensitivity (fever, rash, eosinophilia) often seen in other cases of drug-induced AIN are not typically observed in proton pump inhibitor (PPI)-induced AIN (Ref). Clinicians should note that there appears to be no correlation between duration of exposure to PPI and duration or severity of acute kidney failure after resolution of AIN (Ref).
Mechanism: Non–dose-related; unknown although may be immunologic (Ref) or idiosyncratic, with direct toxic effect on tubular cells demonstrated with omeprazole (Ref).
Onset: Varied; usually occurs within 3 months (Ref) although has been reported to occur up to 10 months with other PPIs (Ref). Upon reexposure symptoms often present more rapidly, often within 12 hours (Ref).
Risk factors:
• Older adults; although this may be due to increased use of PPIs (Ref)
• Cross-reactions among PPIs in patients who developed AIN is not known
• Concomitant use of a PPI may increase the risk of immune checkpoint inhibitor-induced nephritis (Ref)
Long-term use of acid suppressive therapies, including esomeprazole, may result in reversible vitamin B12 deficiency; however, data regarding the clinical significance of these changes and causality are conflicted (Ref).
Mechanism: Dose- and time-related; acid suppressive therapies interfere with acid-activated proteolytic digestion of dietary protein-bound vitamin B12 in the stomach, thereby resulting in malabsorption of vitamin B12 (Ref).
Onset: Delayed (Ref).
Risk factors:
• Duration of therapy (≥2 to 3 years); the association between ≥2 years of proton pump inhibitor (PPI) use and vitamin B12 deficiency was stronger among people <30 years of age and in females (Ref)
• High doses of PPIs (≥1.5 pills per day) (Ref)
• Presence of risk factors for vitamin B12 deficiency (eg, malnourished patients, vegan diet) (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Incidences are for the oral formulation in adults unless otherwise indicated; IV formulation reported in adults.
>10%: Nervous system: Headache (IV: 11%; oral: children, adolescents, adults: 2% to 8%)
1% to 10%:
Dermatologic: Pruritus (IV: 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 serum potassium (≤1%), increased serum sodium (≤1%), increased thyroid stimulating hormone level (≤1%), increased uric acid (≤1%)
Gastrointestinal: Abdominal pain (IV: 6%; oral: infants, children, adolescents, adults: 1% to 4%), acid regurgitation (infants: 1%), constipation (IV: 3%; oral: ≥1%), diarrhea (IV: 4%; oral: children, adolescents, adults: 2% to 4%), flatulence (IV: 10%; oral: ≥1%), increased gastrin (≤1%), nausea (IV: 6%; oral: adolescents, adults: 2%), vomiting (infants: ≥5%; adults: <1%), xerostomia (IV: 4%; oral: ≥1%)
Hematologic & oncologic: Increased hemoglobin (≤1%), quantitative disorders of platelets (≤1%)
Hepatic: Increased serum alanine aminotransferase (infants, adults: ≤1%), increased serum alkaline phosphatase (≤1%), increased serum aspartate aminotransferase (≤1%)
Local: Injection-site reaction (IV: 2% to 4%)
Nervous system: Dizziness (IV: ≤3%; oral: <1%), drowsiness (children: 2%; adults: <1%), irritability (infants: ≥5%), vertigo (IV: ≤3%; oral: <1%)
Renal: Increased serum creatinine (≤1%)
Respiratory: Cough (IV: 1%; oral: <1%), tachypnea (infants: 1%)
Miscellaneous: Fever (IV: 4%; oral: <1%)
<1%:
Cardiovascular: Chest pain, edema, flushing, hypertension, lower extremity edema, peripheral edema, substernal pain, tachycardia
Dermatologic: Acne vulgaris, dermatitis, diaphoresis, erythematous rash, maculopapular rash, skin rash, urticaria
Endocrine & metabolic: Albuminuria, goiter, hot flash, hyperuricemia, hyponatremia, increased thirst, menstrual disease, vitamin B12 deficiency, weight gain, weight loss
Gastrointestinal: Ageusia, anorexia, aphthous stomatitis, change in bowel habits, dysgeusia, dysphagia, enlargement of abdomen, eructation, exacerbation of constipation, gastroenteritis, gastrointestinal hemorrhage, hernia of abdominal cavity, hiccups, increased appetite, melena, mouth disease, pruritus ani, rectal disease, tongue disease
Genitourinary: Cystitis, dysmenorrhea, dysuria, erectile dysfunction, genitourinary fungal infection, glycosuria, hematuria, polyuria, urinary frequency, urine abnormality, vaginitis
Hematologic & oncologic: Anemia, cervical lymphadenopathy, gastrointestinal dysplasia, hypochromic anemia, leukocytosis, leukopenia, thrombocytopenia
Hepatic: Hyperbilirubinemia
Hypersensitivity: Angioedema, facial edema, hypersensitivity reaction, tongue edema
Infection: Candidiasis (including esophageal candidiasis [Ma 2020], gastrointestinal candidiasis, genital candidiasis, and urogenital candidiasis)
Nervous system: Altered sense of smell, apathy, asthenia, confusion, exacerbation of depression, fatigue, fibromyalgia syndrome, hypertonia, hypoesthesia, insomnia, malaise, migraine (including exacerbation of migraine headache), nervousness, pain, paresthesia, rigors, sleep disorder, tremor
Neuromuscular & skeletal: Arthralgia, arthropathy, back pain, exacerbation of arthritis, muscle cramps, polymyalgia rheumatica
Ophthalmic: Conjunctivitis, visual disturbance, visual field defect
Otic: Otalgia, otitis media, tinnitus
Respiratory: Dyspnea, epistaxis, exacerbation of asthma, flu-like symptoms, laryngeal edema, pharyngeal disease, pharyngitis, rhinitis, sinusitis
Frequency not defined: Gastrointestinal: Barrett esophagus, benign gastric nodule, benign polyp of stomach, duodenitis, esophageal stenosis, esophageal ulcer, esophageal varices, mucosal discoloration
Postmarketing:
Dermatologic: Acute generalized exanthematous pustulosis, alopecia, cutaneous lupus erythematosus (including exacerbations) (Kaur 2022), erythema multiforme, fixed drug eruption (Salloum 2020), hyperhidrosis, skin photosensitivity (Shukla 2010), Stevens-Johnson syndrome (Lin 2020), toxic epidermal necrolysis
Endocrine & metabolic: Gynecomastia, hypomagnesemia (Negri 2011)
Gastrointestinal: Clostridioides difficile-associated diarrhea (Wade 2014), colitis (microscopic) (Wilcox 2009), gastric polyp (fundic gland) (Flick 2005), pancreatitis, stomatitis
Hematologic & oncologic: Agranulocytosis (Dury 2012), pancytopenia
Hepatic: Hepatic encephalopathy, hepatic failure, hepatitis (Zaccardi 2014), hepatotoxicity (idiosyncratic) (Chalasani 2014; Thomas 2016), jaundice
Hypersensitivity: Anaphylactic shock, anaphylaxis (Li 2020), drug reaction with eosinophilic and systemic symptoms (Caboni 2007)
Nervous system: Aggressive behavior, agitation, depression, hallucination, myasthenia
Neuromuscular & skeletal: Bone fracture (Lespessailles 2022), myalgia (Grattaliano 2005), osteonecrosis of the jaw (Marconcini 2019); rhabdomyolysis (Jeon 2016), systemic lupus erythematosus (including exacerbation of systemic lupus erythematous; Rowell syndrome [Almansouri 2020])
Ophthalmic: Blurred vision
Renal: Interstitial nephritis (including acute interstitial nephritis [Geevasinga 2005]), kidney disease (chronic) (Lazarus 2016)
Respiratory: Bronchospasm
Hypersensitivity (eg, anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute tubulointerstitial nephritis, urticaria) to esomeprazole, other substituted benzimidazole proton pump inhibitors, or any component of the formulation; concomitant use with products that contain rilpivirine.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
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.
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 clearance of strontium is 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:
• Older adult: Bioavailability may be increased in older adult 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.
Use of gastric acid inhibitors, including proton pump inhibitors, has been associated with 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]).
Esomeprazole strontium capsules have been discontinued in the United States for >1 year.
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
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]:
NexIUM: 20 mg, 40 mg [contains fd&c blue #1 (brilliant blue), fd&c red #40 (allura red ac dye), quinoline yellow (d&c yellow #10)]
NexIUM 24HR: 20 mg [contains fd&c blue #1 (brilliant blue), fd&c red #40 (allura red ac dye)]
NexIUM 24HR Clear Minis: 20 mg [contains corn starch, fd&c blue #2 (indigo carm) aluminum lake, fd&c blue #2 (indigotine,indigo carmine), fd&c red #40 (allura red ac dye)]
Generic: 20 mg, 40 mg
Capsule Delayed Release, Oral, as strontium:
Generic: 49.3 mg [DSC]
Kit, Oral, as magnesium [strength expressed as base]:
Esomep-EZS: 20 mg [DSC] [contains fd&c blue #1 (brilliant blue), 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 (1 ea, 30 ea); 40 mg (1 ea, 30 ea)
Solution Reconstituted, Intravenous, as sodium [strength expressed as base]:
NexIUM I.V.: 40 mg (1 ea) [contains edetate (edta) disodium]
Generic: 40 mg (1 ea)
Solution Reconstituted, Intravenous, as sodium [strength expressed as base, preservative free]:
Generic: 40 mg (1 ea [DSC])
Tablet Delayed Release, Oral, as magnesium [strength expressed as base]:
NexIUM 24HR: 20 mg [contains fd&c blue #2 (indigo carm) aluminum lake, fd&c red #40(allura red ac)aluminum lake]
May be product dependent
Capsule, delayed release (Esomeprazole Magnesium Oral)
20 mg (per each): $0.42 - $9.02
40 mg (per each): $0.28 - $9.02
Capsule, delayed release (NexIUM 24HR Clear Minis Oral)
20 mg (per each): $0.65
Capsule, delayed release (NexIUM 24HR Oral)
20 mg (per each): $0.72
Capsule, delayed release (NexIUM Oral)
20 mg (per each): $11.01
40 mg (per each): $11.01
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.
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]:
Generic: 40 mg [DSC]
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
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.
Oral:
Capsule: Swallow whole; do not chew or crush; 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. Do not store mixture for future use. For patients with difficulty swallowing, use of granules may be more appropriate.
Granules: Take at least 1 hour before eating. 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 (use double the amount of water if 2 packets are needed) 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.
IV: Flush line prior to and after administration with NS, LR, or D5W.
Treatment of GERD: May be administered by injection (≥3 minutes), or intermittent infusion (10 to 30 minutes)
Upper GI bleed, acute (unknown etiology or peptic ulcer hemorrhage): May be administered as continuous infusion or intermittent infusion (infuse over 30 minutes), depending on risk of rebleeding.
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 at least 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.
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).
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 capsules: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/202342s006lbl.pdf#page=29
NexIUM capsules, granules for oral suspension: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/021153s060,021957s027,022101s024lbl.pdf#page=40
Oral: Short-term treatment (4 to 8 weeks) of symptomatic gastroesophageal reflux disease (GERD) (Esomeprazole magnesium: FDA approved in ages ≥1 year and adults; esomeprazole strontium: FDA approved in adults); short-term treatment (up to 6 weeks) of erosive esophagitis due to acid mediated GERD (Esomeprazole magnesium: FDA approved in ages 1 month to <1 year); short-term treatment (4 to 8 weeks) of erosive esophagitis (Esomeprazole magnesium: FDA approved in ages ≥1 year and adults; esomeprazole strontium: FDA approved in adults); maintenance of healing of erosive esophagitis (Esomeprazole magnesium, esomeprazole strontium: FDA approved in adults); treatment (in combination with amoxicillin and clarithromycin) for Helicobacter pylori eradication in patients with duodenal ulcer disease (active or history of within the past 5 years) to reduce recurrence of duodenal ulcer (Esomeprazole magnesium, esomeprazole strontium: FDA approved in adults); prevention of gastric ulcers associated with continuous NSAID therapy in patients at high risk (Esomeprazole magnesium, esomeprazole strontium: FDA approved in adults); long-term treatment of pathological hypersecretory conditions including Zollinger-Ellison syndrome (Esomeprazole magnesium, esomeprazole strontium: FDA approved in adults); relief of frequent (≥2 days per week) heartburn (OTC product: Esomeprazole magnesium: FDA approved in adults)
IV: Short-term alternative treatment (≤10 days) of GERD with erosive esophagitis when oral therapy is not possible or appropriate (FDA approved in ages ≥1 month and adults); decrease the risk of rebleeding postendoscopy for acute bleeding gastric or duodenal ulcers (FDA approved in adults)
Esomeprazole may be confused with ARIPiprazole, omeprazole
NexIUM may be confused with NexAVAR
Beers Criteria: Esomeprazole is identified in the Beers Criteria as a potentially inappropriate medication to be avoided (as scheduled use for >8 weeks) in patients 65 years and older due to its risk of C. difficile infection, pneumonia, GI malignancies, and bone loss/fractures unless given for high-risk patients (eg, oral corticosteroid or chronic NSAID use), patients with erosive esophagitis, Barrett esophagitis, a pathological hypersecretory condition, or if the patient has demonstrated a need for maintenance therapy (eg, failure of drug discontinuation trial or failure of H2 blockers) (Beers Criteria [AGS 2023]).
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
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Acalabrutinib: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Acalabrutinib. This interaction is only applicable to acalabrutinib capsules. Risk X: Avoid combination
Amphetamine: Inhibitors of the Proton Pump (PPIs and PCABs) may increase the absorption of Amphetamine. Risk C: Monitor therapy
Atazanavir: Inhibitors of the Proton Pump (PPIs and PCABs) 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
Belumosudil: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Belumosudil. Management: Increase the dose of belumosudil to 200 mg twice daily when coadministered with inhibitors of the proton pump (PPIs and PCABs). Risk D: Consider therapy modification
Bisphosphonate Derivatives: Inhibitors of the Proton Pump (PPIs and PCABs) may diminish the therapeutic effect of Bisphosphonate Derivatives. Risk C: Monitor therapy
Bosutinib: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Bosutinib. Management: Consider alternatives to proton pump inhibitors and potassium-competitive acid blockers, 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: Inhibitors of the Proton Pump (PPIs and PCABs) may diminish the therapeutic effect of Capecitabine. Risk C: Monitor therapy
Cefditoren: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Cefditoren. Risk X: Avoid combination
Cefpodoxime: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Cefpodoxime. Risk C: Monitor therapy
Cefuroxime: Inhibitors of the Proton Pump (PPIs and PCABs) 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
Clofarabine: OAT1/3 Inhibitors may increase the serum concentration of Clofarabine. 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. Risk X: Avoid combination
CYP2C19 Inducers (Strong): May decrease the serum concentration of Esomeprazole. Risk X: Avoid combination
Cysteamine (Systemic): Inhibitors of the Proton Pump (PPIs and PCABs) may diminish the therapeutic effect of Cysteamine (Systemic). Risk C: Monitor therapy
Dacomitinib: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Dacomitinib. Management: Avoid concurrent use of dacomitinib with PPIs and PCABs. 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: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Dasatinib. Management: Antacids (taken 2 hours before or after dasatinib administration) can be used in place of PPIs or PCABs if some acid-reducing therapy is needed. Risk X: Avoid combination
Delavirdine: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Delavirdine. Management: Chronic therapy with PPIs or PCABs should be avoided in patients treated with delavirdine. The clinical significance of short-term PPI or PCAB therapy with delavirdine is uncertain, but such therapy should be undertaken with caution. Risk X: Avoid combination
Dextroamphetamine: Inhibitors of the Proton Pump (PPIs and PCABs) 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: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the bioavailability of Doxycycline. Risk C: Monitor therapy
Enoxacin: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the absorption of Enoxacin. Risk C: Monitor therapy
Erlotinib: Inhibitors of the Proton Pump (PPIs and PCABs) 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: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Gefitinib. Management: Avoid use of inhibitors of the proton pump (PPIs or PCABs) with gefitinib when possible. If required, administer gefitinib 12 hours after the PPI/PCAB or 12 hours before the next dose of the PPI/PCAB. Closely monitor clinical response to gefitinib. Risk D: Consider therapy modification
Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies): Inhibitors of the Proton Pump (PPIs and PCABs) may diminish the therapeutic effect of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor therapy
Indinavir: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Indinavir. Risk C: Monitor therapy
Infigratinib: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease serum concentrations of the active metabolite(s) of Infigratinib. Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Infigratinib. Risk X: Avoid combination
Itraconazole: Inhibitors of the Proton Pump (PPIs and PCABs) may increase the serum concentration of Itraconazole. This specifically applies to the super bioavailable itraconazole products (eg, Tolsura brand). Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Itraconazole. This specifically applies to the non-super bioavailable itraconazole products (eg, Sporanox brand and its generics). Management: Exposure to Tolsura brand itraconazole may be increased by PPIs or PCABs ; consider itraconazole dose reduction. Exposure to Sporanox brand itraconazole may be decreased. Give Sporanox brand itraconazole at least 2 hrs before or 2 hrs after PPIs or PCABs. Risk D: Consider therapy modification
Ketoconazole (Systemic): Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the absorption of Ketoconazole (Systemic). Ketoconazole (Systemic) may increase the serum concentration of Inhibitors of the Proton Pump (PPIs and PCABs). 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 or potassium-competitive acid blockers is necessary. Risk D: Consider therapy modification
Ledipasvir: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Ledipasvir. Management: PPI or PCAB doses equivalent to omeprazole 20 mg or lower may be given with ledipasvir under fasted conditions. Use of ledipasvir with higher doses or with food, or 2 hours after a these agents, may reduce ledipasvir bioavailability. Risk D: Consider therapy modification
Levoketoconazole: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the absorption of Levoketoconazole. Levoketoconazole may increase the serum concentration of Inhibitors of the Proton Pump (PPIs and PCABs). Risk X: Avoid combination
Lumacaftor and Ivacaftor: May decrease the serum concentration of Inhibitors of the Proton Pump (PPIs and PCABs). Risk C: Monitor therapy
Mavacamten: CYP2C19 Inhibitors (Weak) may increase the serum concentration of Mavacamten. Management: Start mavacamten at 5 mg/day if stable on a weak CYP2C19 inhibitor. For those stable on mavacamten who are initiating a weak CYP2C19 inhibitor, reduce mavacamten dose by one dose level. Risk D: Consider therapy modification
Methotrexate: Inhibitors of the Proton Pump (PPIs and PCABs) may increase the serum concentration of Methotrexate. Management: Consider temporarily interrupting PPI or PCAB therapy in patients receiving high-dose methotrexate. If coadministered, monitor for increased methotrexate toxicity (eg, mucositis, myalgias) and/or delayed methotrexate elimination. Risk D: Consider therapy modification
Multivitamins/Minerals (with ADEK, Folate, Iron): Inhibitors of the Proton Pump (PPIs and PCABs) 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: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Mycophenolate. Specifically, concentrations of the active mycophenolic acid may be reduced. Risk C: Monitor therapy
Nelfinavir: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease serum concentrations of the active metabolite(s) of Nelfinavir. Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Nelfinavir. Management: Due to potentially significant reductions in nelfinavir exposure, avoid concurrent use of nelfinavir with a PPI or PCAB when possible. If unavoidable, consider PPI or PCAB use for a short duration (less than 30 days) and closely monitor viral load. Risk D: Consider therapy modification
Neratinib: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Neratinib. Specifically, proton pump inhibitors may reduce neratinib absorption. Risk X: Avoid combination
Nilotinib: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Nilotinib. Management: Avoid this combination. Histamine H2 receptor antagonists (H2RAs) given 10 hours before or 2 hours after nilotinib, or antacids given 2 hours before or 2 hours after nilotinib are acceptable alternatives. Risk D: Consider therapy modification
Nirogacestat: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Nirogacestat. Risk X: Avoid combination
Octreotide: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Octreotide. Risk C: Monitor therapy
Palbociclib: Inhibitors of the Proton Pump (PPIs and PCABs) may diminish the therapeutic effect of Palbociclib. Specifically, this has been reported with the use of palbociclib capsules. Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Palbociclib. Specifically, this may occur with the use of palbociclib capsules, and to the greatest extent when taken without food. Management: Carefully evaluate potential risks and benefits of coadministration of palbociclib capsules and proton pump inhibitors or potassium-competitive acid blockers due to the risk of reduced palbociclib efficacy. Palbociclib capsules should be taken with food. Risk D: Consider therapy modification
PAZOPanib: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of PAZOPanib. Risk X: Avoid combination
Pexidartinib: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Pexidartinib. Management: Avoid this combination. 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: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Posaconazole. Management: Avoid coadministration of PPIs or PCABs 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 or PCABs. Risk D: Consider therapy modification
Rilpivirine: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Rilpivirine. Risk X: Avoid combination
Riociguat: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Riociguat. Risk C: Monitor therapy
Risedronate: Inhibitors of the Proton Pump (PPIs and PCABs) may diminish the therapeutic effect of Risedronate. Inhibitors of the Proton Pump (PPIs and PCABs) may increase the serum concentration of Risedronate. This applies specifically to use of delayed-release risedronate. Management: Coadministration of PPIs or PCABs with delayed-release risedronate formulations is not recommended. Limit PPI/PCAB dose and duration during coadministration with risedronate as possible. Patients over age 70 are at higher risk of adverse effects. Risk D: Consider therapy modification
Saquinavir: Inhibitors of the Proton Pump (PPIs and PCABs) may increase the serum concentration of Saquinavir. Risk C: Monitor therapy
Secretin: Inhibitors of the Proton Pump (PPIs and PCABs) 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 PPIs or PCABs and secretin, and discontinue PPI or PCAB several weeks prior to secretin administration, with the duration of separation determined by the specific acid suppressant. See full monograph for details. Risk D: Consider therapy modification
Selpercatinib: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Selpercatinib. Management: Coadministration of selpercatinib and PPIs or PCABs should be avoided. If coadministration cannot be avoided, selpercatinib and PPIs or PCABs should be administered simultaneously with food. Risk D: Consider therapy modification
SORAfenib: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the absorption of SORAfenib. Risk C: Monitor therapy
Sotorasib: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Sotorasib. Risk X: Avoid combination
Sparsentan: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Sparsentan. Risk X: Avoid combination
St John's Wort: May decrease the serum concentration of Esomeprazole. Risk X: Avoid combination
Tacrolimus (Systemic): Inhibitors of the Proton Pump (PPIs and PCABs) may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy
Technetium Tc 99m Sestamibi: Inhibitors of the Proton Pump (PPIs and PCABs) may diminish the diagnostic effect of Technetium Tc 99m Sestamibi. Management: Consider holding/stopping proton pump inhibitor therapy for at least 3 days prior to the use technetium Tc 99m sestamibi in cardiac imaging procedures. Risk D: Consider therapy modification
Technetium Tc 99m Tetrofosmin: Inhibitors of the Proton Pump (PPIs and PCABs) may diminish the diagnostic effect of Technetium Tc 99m Tetrofosmin. Risk C: Monitor therapy
Thiazolidinediones: Inhibitors of the Proton Pump (PPIs and PCABs) may enhance the adverse/toxic effect of Thiazolidinediones. Specifically, the risk of osteoporosis or fracture may be increased. Risk C: Monitor therapy
Tipranavir: May decrease the serum concentration of Inhibitors of the Proton Pump (PPIs and PCABs). These data are derived from studies with Ritonavir-boosted Tipranavir. Risk C: Monitor therapy
Velpatasvir: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Velpatasvir. Management: Sofosbuvir/velpatasvir should be administered with food and taken 4 hours before omeprazole 20 mg. Sofosbuvir/velpatasvir/voxilaprevir can be administered with omeprazole 20 mg. Use with other PPIs or PCABs has not been studied. Risk D: Consider therapy modification
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 Inhibitors of the Proton Pump (PPIs and PCABs). Inhibitors of the Proton Pump (PPIs and PCABs) may increase the serum concentration of Voriconazole. Risk C: Monitor therapy
Prolonged treatment (≥2 years) may lead to malabsorption of dietary vitamin B12 and subsequent vitamin B12 deficiency (Lam, 2013).
Take at least 1 hour before meals; best if taken before breakfast.
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).
Outcome data following use of proton pump inhibitors (PPIs) during pregnancy are available (Choi 2023; Hussain 2022; Peron 2023).
Due to pregnancy-induced physiologic changes, some pharmacokinetic properties of esomeprazole may be altered. Data from a single dose study of esomeprazole in patients with preterm preeclampsia suggest clearance may be decreased, possibly due to inhibition of CYP2C19 (Gebreyesus 2022).
Recommendations for the treatment of gastroesophageal reflux disease in pregnant patients are available. When initiating treatment during pregnancy, a step-up approach, starting with diet and lifestyle modifications, is recommended. PPIs are considered acceptable for use during pregnancy when other medications are not effective (Ali 2022; Dunbar 2022; Thélin 2020).
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.
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 40 mg dose; 90% with repeat 40 mg once-daily 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).
Hepatic function impairment: AUC was 2 to 3 times higher in patients with severe hepatic impairment.
Older adult: AUC and Cmax were increased by 25% and 18%, respectively, following administration of esomeprazole magnesium.
Sex: AUC and Cmax were 13% higher in women than men following administration of esomeprazole magnesium.
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