esomeprazole (Rx, OTC)

>10%

Headache (2-11%)

1-10%

Flatulence (10%)

Indigestion (6%)

Nausea (6%)

Abdominal pain (1-6%)

Diarrhea (2-4%)

Xerostomia (3-4%)

Dizziness (2-3%)

Constipation (2-3%)

Somnolence (1-2%)

Pruritus (1%)

<1%

Blood and lymphatic system disorders: Agranulocytosis, pancytopenia

Blurred vision

GI disorders: Pancreatitis, stomatitis, microscopic colitis

Hepatobiliary disorders: Hepatic failure, hepatitis with or without jaundice

Anaphylactic reaction/shock

GI candidiasis

Hypomagnesemia

Musculoskeletal disorders: Muscular weakness, myalgia, bone fracture

Nervous system disorders: Hepatic encephalopathy, taste disturbance

Psychiatric disorders: Aggression, agitation, depression, hallucination

Interstitial nephritis

Gynecomastia

Bronchospasm

Skin and subcutaneous tissue disorders: Alopecia, erythema multiforme, hyperhidrosis, photosensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis (sometimes fatal fatal)

Postmarketing Reports

Cutaneous and systemic lupus erythematosus

Cyanocobalamin (vitamin B-12) deficiency

Clostridium difficile-associated diarrhea

Fundic gland polyps

Contraindications

Hypersensitivity to esomeprazole or other proton pump inhibitors (PPIs)

Cautions

PPIs are possibly associated with increased incidence of Clostridium difficile-associated diarrhea (CDAD); consider diagnosis of CDAD for patients taking PPIs who have diarrhea that does not improve

PPIs may decrease the efficacy of clopidogrel by reducing the formation of the active metabolite

Severe hepatic impairment

Cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE) reported with PPIs; avoid using for longer than medically indicated; discontinue if signs or symptoms consistent with CLE or SLE are observed and refer patient to specialist; most patients improve with discontinuation of PPI alone in 4-12 weeks; serological testing (e.g. ANA) may be positive and elevated serological test results may take longer to resolve than clinical manifestations

Relief of symptoms does not eliminate the possibility of a gastric malignancy; consider additional follow-up and diagnostic testing in adult patients who have suboptimal response or early symptomatic relapse after completing treatment with a PPI

Breastfeeding

Therapy increases risk of Salmonella, Campylobacter, and other infections

Contains enteric coated granules (acid labile); do not chew or crush; take 1 hr before meals

Published observational studies suggest that PPI therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist, or spine; particularly with prolonged (>1 yr), high-dose therapy

Decreased gastric acidity increases serum chromogranin A (CgA) levels and may cause false-positive diagnostic results for neuroendocrine tumors; temporarily discontinue PPIs before assessing CgA levels

Hypomagnesemia may occur with prolonged use (ie, >1 yr; adverse effects may result and include tetany, arrhythmias, and seizures; in 25% of cases reviewed, magnesium supplementation alone did not improve low serum magnesium levels, and the PPI had to be discontinued; consider monitoring magnesium levels prior to initiation of PPI treatment and periodically

Daily long-term use (e.g., longer than 3 years) may lead to malabsorption or a deficiency of cyanocobalamin

If patient taking a prescription drug, the patient should ask a doctor or a pharmacist whether acid reducers can be taken concomitantly with it

Acute interstitial nephritis reported in patients taking proton pump inhibitors

May elevate and/or prolong serum concentrations of methotrexate and/or its metabolite when administered oncomitantly with PPIs, possibly leading to toxicity; consider a temporary withdrawal of PPI therapy with high dose methotrexate administration

Stop use and inform a healthcare professional if rash or joint pain develops

PPI therapy is associated with increased risk of fundic gland polyp; risk increases with long-term use >1 year; patient may be asymptomatic; problem usually identified incidentally on endoscopy; use shortest duration of therapy appropriate to condition being treated

Pregnancy

There are no adequate and well-controlled studies in pregnant women; esomeprazole is the S-isomer of omeprazole; available epidemiologic data fail to demonstrate an increased risk of major congenital malformations or other adverse pregnancy outcomes with first trimester omeprazole use; reproduction studies in rats and rabbits resulted in dose-dependent embryo-lethality at omeprazole doses that were approximately 3.4 to 34 times an oral human dose of 40 mg (based on a body surface area for a 60 kg person)

Lactation

Esomeprazole is the S-isomer of omeprazole and limited data suggest that omeprazole may be present in human milk; there are no clinical data on effects of esomeprazole on breastfed infant or on milk production; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed infant from treatment or from underlying maternal condition

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

S-isomer of omeprazole; PPI; binds to H+/K+-exchanging ATPase (proton pump) in gastric parietal cells, resulting in blockage of acid secretion

Absorption

Bioavailability: PO: 89-90%; food decreases AUC by 33-53%; take 1 hr before meal

Onset: 1-2 hr (gastric acid inhibition); within 4 wk (GERD)

Duration (multiple dose): Gastric acid inhibition; PO: 17 hr

Peak plasma time: PO: 1-1.6 hr

Distribution

Protein bound: 97%

Vd: 16 L

Metabolism

Liver; extensively metabolized by hepatic P450 enzyme; major metabolic pathway is via CYP2C19; the rest is via CYP3A4

Metabolites: 5-hydroxyesomeprazole (inactive), esomeprazole sulfone (inactive), desmethyl-esomeprazole (activity unknown)

Enzymes inhibited: CYP2C19

Slow metabolizers (3% of Caucasians and African-Americans) are deficient in CPY2C19 enzyme system; plasma concentration can be higher than in persons who have the enzyme

Elimination

Half-life: 1.2-1.5 hr

Total body clearance: 9-16 L/hr

Excretion: Urine (80%); feces (20%)

Pharmacogenomics

Metabolites of esomeprazole lack antisecretory activity

The major part of esomeprazole’s metabolism is dependent on the CYP2C19 isoenzyme, which forms the hydroxy and desmethyl metabolites

CYP2C19 isoenzyme exhibits polymorphism in the metabolism of esomeprazole, since some 3% of Caucasians and 15-20% of Asians lack CYP2C19 and are termed poor metabolizers

At steady state, the ratio of AUC in poor metabolizers to AUC in the rest of the population (extensive metabolizers) is approximately 2

Oral Administration

If unable to swallow capsule whole, capsule can be opened, emptied on applesauce, mixed, and swallowed immediately

IV Compatibilities

Solution: NS, LR, D5W

IV Preparation

IV injection

• Reconstitute contents of 1 vial with 5 mL NS
• Store at room temp (no refrigeration required) and administer within 12 hr

Intermittent IV infusion

• Reconstitute 1 vial with 5 mL NS, LR, or D5W
• Further dilute to 50 mL
• Store at room temp (no refrigeration required) and administer within 12 hr if diluted in NS or LR, and within 6 hr if diluted in D5W

Continuous IV infusion

• Reconstitute two 40 mg vials with 5 mL each of 0.9% NaCl
• Further dilute the 2 reconstituted vials in 100 mL 0.9% NaCl

IV Administration

IV injection

• Injection: Over no less than 3 min

Intermittent IV infusion

• Infuse over 10-30 min regardless of amount
• Flush IV line with NS, LR, or D5W prior to and after administration
• Do not administer with any other drugs

Continuous IV infusion

• Administer initial 80 mg IV dose over 30 min, THEN follow with
• Continuous IV infusion of 8 mg/hr for total treatment duration of 72 hr