General

**BEERS Drug**

Genetic Implications:

Pronunciation:
es-oh-mep-ra-zole

Trade Name(s)

• NexIUM
• NexIUM 24hr

Ther. Class.

antiulcer agents

Pharm. Class.

proton pump inhibitors

Indications

• PO IV GERD/erosive esophagitis (IV therapy should only be used if PO therapy is not possible/appropriate).
• IV Reduction in risk of rebleeding following therapeutic endoscopy for acute bleeding gastric or duodenal ulcers.
• PO Hypersecretory conditions, including Zollinger-Ellison syndrome.
• PO Eradication of Helicobacter pylori in duodenal ulcer disease or history of duodenal ulcer disease (in combination with amoxicillin and clarithromycin).
• PO Reduction in risk of gastric ulcer during continuous NSAID therapy.
• OTC: Heartburn occurring at least twice/wk.

Action

Binds to an enzyme on gastric parietal cells in the presence of acidic gastric pH, preventing the final transport of hydrogen ions into the gastric lumen.

Therapeutic Effect(s):

• Diminished accumulation of acid in the gastric lumen with lessened gastroesophageal reflux.
• Healing of duodenal ulcers.
• Decreased incidence of gastric ulcer during continuous NSAID therapy.

Pharmacokinetics

Absorption: 90% absorbed following oral administration; food ↓ absorption.

Distribution: Unknown.

Protein Binding: 97%.

Metabolism and Excretion: Primarily metabolized by the liver via the CYP2C19 isoenzyme, with some metabolism by the CYP3A4 isoenzyme;  (the CYP2C19 enzyme system exhibits genetic polymorphism; 15–20% of Asian patients and 3–5% of White and Black patients may be poor metabolizers and may have significantly ↑ esomeprazole concentrations and an ↑ risk of adverse effects); <1% excreted unchanged in urine.

Half-life: Children 1–11 yr:  0.42–0.88 hr;  Adults:  1.0–1.5 hr.

TIME/ACTION PROFILE ( plasma concentrations*)

Contraindication/Precautions

Contraindicated in:

• Hypersensitivity to esomeprazole or related drugs (benzimidazoles);
• Hypersensitivity;
• Concurrent use of rilpivirine.

Use Cautiously in:

• Severe hepatic impairment;
• Patients using high doses for >1 yr (↑ risk of hip, wrist, or spine fractures and fundic gland polyps);
• Patients using therapy for >3 yr (↑ risk of vitamin B₁₂  deficiency);
• Pre-existing risk of hypocalcemia;
• OB:  Safety not established in pregnancy;
• Lactation: Safety not established in breastfeeding;
• Geri:   Appears on Beers list. ↑ risk of Clostridioides difficile infection, pneumonia, GI malignancies, bone loss, and fractures in older adults. Avoid scheduled use for >8 wk in older adults unless for high-risk patients (e.g., oral corticosteroid or chronic NSAID use) or patients with erosive esophagitis, Barrett esophagitis, pathological hypersecretory condition, or demonstrated need for maintenance therapy (e.g., failure of H₂  antagonist).

Adverse Reactions/Side Effects

Derm: ACUTE GENERALIZED EXANTHEMATOUS PUSTULOSIS, cutaneous lupus erythematosus, DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS

F and E: hypocalcemia (especially if treatment duration ≥3 mo), hypokalemia (especially if treatment duration ≥3 mo), hypomagnesemia (especially if treatment duration ≥3 mo)

GI: abdominal pain, CLOSTRIDIOIDES DIFFICILE-ASSOCIATED DIARRHEA (CDAD), constipation, diarrhea, dry mouth, flatulence, fundic gland polyps, nausea

GU: acute tubulointerstitial nephritis

Hemat: vitamin B₁₂  deficiency

MS: bone fracture

Neuro: headache

Misc: HYPERSENSITIVITY REACTIONS (including anaphylaxis, angioedema, or tubulointerstitial nephritis), systemic lupus erythematosus

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

• May significantly ↓ levels and effectiveness of  rilpivirine ; concurrent use contraindicated.
• May ↓ levels and effectiveness of  atazanavir  and  nelfinavir ; avoid concurrent use.
• May ↓ absorption and effectiveness of drugs requiring acidic pH, including  ketoconazole,  itraconazole,  ampicillin esters,  iron salts,  erlotinib, and  mycophenolate mofetil.
• May ↑ levels and risk of toxicity of  digoxin  and  methotrexate.
• May ↑ risk of bleeding with  warfarin ; monitor INR and PT.
•  Voriconazole  may ↑ levels and risk of toxicity.
• May ↓ the antiplatelet effects of  clopidogrel ; avoid concurrent use.
• May ↑ levels and risk of toxicity of  cilostazol ; consider ↓ dose of cilostazol from 100 mg twice daily to 50 mg twice daily.
•  Rifampin  may ↓ levels and effectiveness; avoid concurrent use.
• Hypomagnesemia and hypokalemia ↑ risk of  digoxin  toxicity.
• May ↑ levels and risk of toxicity of  tacrolimus  and  methotrexate.

Drug-Natural Products:

 St. John's wort  may ↓ levels and effectiveness; avoid concurrent use.

Route/Dosage

Gastroesophageal Reflux Disease

PO (Adults): Healing of erosive esophagitis:  20 mg or 40 mg once daily for 4–8 wk;  Maintenance of healing of erosive esophagitis:  20 mg once daily;  Symptomatic GERD:  20 mg once daily for 4 wk (additional 4 wk may be considered for nonresponders);  Heartburn:  20 mg once daily for 2 wk.

PO (Children 12–17 yr): Short-term treatment of GERD:  20–40 mg once daily for up to 8 wk.

PO (Children 1–11 yr): Short-term treatment of GERD:  10 mg once daily for up to 8 wk;  Healing of erosive esophagitis:  <20 kg: 10 mg once daily for 8 wk; ≥20 kg: 10–20 mg once daily for 8 wk.

PO (Infants and Children 1 mo–<1 yr): >7.5–12 kg:  10 mg once daily for up to 6 wk;  >5–7.5 kg:  5 mg once daily for up to 6 wk;  3–5 kg:  2.5 mg once daily for up to 6 wk.

IV (Adults): 20 or 40 mg once daily.

IV (Children 1–17 yr): <55 kg:  10 mg once daily;  ≥55 kg:  20 mg once daily.

IV (Children 1 mo–<1 yr): 0.5 mg/kg once daily.

Hepatic Impairment 
PO IV (Adults): Severe hepatic impairment:  Dose should not exceed 20 mg/day.

Reduction of Risk of Rebleeding of Gastric or Duodenal Ulcers After Therapeutic Endoscopy

IV (Adults): 80 mg over 30 min; then 8 mg/hr continuous infusion for 71.5 hr.

Hepatic Impairment 
IV (Adults): Mild to moderate hepatic impairment:  Do not exceed continuous infusion rate of 6 mg/hr;  Severe hepatic impairment:  Do not exceed continuous infusion rate of 4 mg/hr.

H. pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence (Triple Therapy)

PO (Adults): 40 mg once daily for 10 days with amoxicillin 1000 mg twice daily for 10 days and clarithromycin 500 mg twice daily for 10 days.

Hepatic Impairment 
PO (Adults): Severe hepatic impairment:  Dose should not exceed 20 mg/day.

Reduction in Risk of Gastric Ulcer During Continuous NSAID Therapy

PO (Adults): 20 or 40 mg once daily for up to 6 mo.

Hepatic Impairment 
PO (Adults): Severe hepatic impairment:  Dose should not exceed 20 mg/day.

Pathological Hypersecretory Conditions, Including Zollinger-Ellison Syndrome

PO (Adults): 40 mg twice daily.

Hepatic Impairment 
PO (Adults): Severe hepatic impairment:  Dose should not exceed 20 mg/day.

Availability (generic available)

Delayed-release tablets: 20 mg^OTC

Delayed-release capsules: 20 mg^{Rx, OTC}, 40 mg

Delayed-release oral suspension packets: 2.5 mg/pkt, 5 mg/pkt, 10 mg/pkt, 20 mg/pkt, 40 mg/pkt

Powder for injection: 40 mg/vial

In Combination with: naproxen (generic only).

Assessment

• Assess routinely for epigastric or abdominal pain and frank or occult blood in the stool, emesis, or gastric aspirate.
• Monitor bowel function. Diarrhea, abdominal cramping, fever, and bloody stools should be reported to health care professional promptly as a sign of CDAD.

Lab Test Considerations:

May ↑ serum creatinine, uric acid, total bilirubin, alkaline phosphatase, AST, and ALT.

• May alter hemoglobin, WBC, platelets, serum sodium, potassium, and thyroxine levels.
• Monitor serum magnesium and calcium before and periodically during therapy. May ↓ magnesium and calcium.
• May cause false positive results in diagnostic investigations for neuroendocrine tumors due to ↑ serum chromogranin A (CgA) levels secondary to drug-induced ↓ gastric acidity. Temporarily stop esomeprazole >14 days before assessing CgA levels and consider repeating test if initial CgA levels are high.

Implementation

• High Alert: Do not confuse Nexium with Nexavar.
• Antacids may be used while taking esomeprazole.
• PO Administer >1 hr before meals.  DNC:  Swallow tablets and capsules whole. Do not chew or crush. 
  • Delayed-release capsules:  For patients with difficulty swallowing, place 15 mL of applesauce in an empty bowl. Open capsule and empty the pellets inside onto applesauce. Mix pellets with applesauce and swallow immediately. Applesauce should not be hot and should be soft enough to swallow without chewing. Do not store applesauce mixture for future use. Tap water, orange juice, apple juice, and yogurt have also been used. Do not crush or chew pellets.
  • For delayed-release capsules for NG tube,  hold enteral nutrition 30–60 min before administering, if applicable. Delayed-release capsules can be opened and intact granules emptied into a 60-mL syringe and mixed with 50 mL of water. Replace plunger and shake syringe vigorously for 15 sec. Hold syringe with tip up and check for granules in tip. Attach syringe to NG tube and administer solution. After administering, flush syringe with additional water. Do not administer if granules have dissolved or disintegrated. Administer immediately after mixing.
  • For delayed-release oral suspension , mix contents of packet with 15 mL of water; leave 2–3 min to thicken, and then stir and drink within 30 min.
  • For delayed-release oral suspension for NG or gastric tube,  add 15 mL of water to a syringe and then add contents of packet. Shake syringe; leave 2–3 min to thicken. Shake syringe and inject through NG or gastric tube within 30 min.

Patient/Family Teaching

• Explain purpose and side effects of medication. Advise patient to read  Patient Information  before starting therapy. Instruct to take medication as directed. Take missed doses as soon as remembered but not if almost time for next dose. Do not double doses.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications, especially St. John's wort.
• Advise patient to avoid alcohol, products containing aspirin or NSAIDs, and foods that may cause an ↑ in GI irritation.
• Advise patient to report onset of black, tarry stools; diarrhea; abdominal pain; or persistent headache to health care professional promptly.
• Advise patient to notify health care professional if signs of hypomagnesemia (seizures, dizziness, abnormal or fast heartbeat, jitteriness, jerking movements or shaking, muscle weakness, spasms of the hands and feet, cramps or muscle aches, spasm of the voice box) occur.
• Caution patient to notify health care professional if fever and diarrhea occur, especially if stool contains blood, pus, or mucus. Advise patient not to treat diarrhea without consulting health care professional.
• Rep:   Advise women of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

Evaluation/Desired Outcomes

• Diminished accumulation of acid in the gastric lumen with lessened gastroesophageal reflux.
• Healing of duodenal ulcers.
• Decreased incidence of gastric ulcer during continuous NSAID therapy.