Asozit

Approved Indications:

• Gastroesophageal Reflux Disease (GERD):
• Short-term treatment of erosive esophagitis confirmed by endoscopy
• Maintenance of healing of erosive esophagitis
• Treatment of symptomatic GERD without erosions
• Helicobacter pylori Eradication (Triple Therapy):
• Used in combination with amoxicillin and clarithromycin for the eradication of H. pylori and reduction in the risk of duodenal ulcer recurrence
• Risk Reduction of NSAID-Associated Gastric Ulcers:
• In patients requiring continued NSAID therapy and at risk of developing gastric ulcers
• Zollinger-Ellison Syndrome and Other Pathological Hypersecretory Conditions
• Prevention of Rebleeding Post-Endoscopic Hemostasis (IV Form)
• Pediatric GERD (1–17 years):
• Treatment of erosive esophagitis
• Symptomatic GERD (without esophagitis)

Clinically Accepted Off-Label Indications:

• Barrett’s Esophagus: For symptom control and acid suppression
• Peptic Ulcer Disease: Not associated with NSAIDs or H. pylori
• Functional Dyspepsia: Symptom management
• Stress Ulcer Prophylaxis: In critically ill hospitalized patients
• Aspiration Pneumonitis Prevention: Before surgery (IV use)

Adults:

• GERD (Erosive Esophagitis): 20–40 mg once daily for 4–8 weeks
  Maintenance: 20 mg once daily
• Symptomatic GERD: 20 mg once daily for up to 4 weeks
• H. pylori Eradication:
  Esomeprazole 40 mg once daily with amoxicillin 1000 mg and clarithromycin 500 mg twice daily for 10 days
• Zollinger-Ellison Syndrome:
  Initial: 40 mg twice daily; dose may be increased up to 240 mg/day in divided doses
• NSAID-Induced Ulcer Prevention: 20–40 mg once daily
• IV Use (when oral therapy not feasible):
  20 or 40 mg once daily, administered via IV injection over at least 3 minutes or infusion over 10–30 minutes

Pediatric:

• 1–11 years: 10 mg once daily (oral)
• 12–17 years: 20–40 mg once daily (oral)

Elderly:

• No dosage adjustment necessary

Renal Impairment:

• No adjustment required

Hepatic Impairment:

• Mild to moderate: No adjustment
• Severe (Child-Pugh Class C): Max dose 20 mg/day

Esomeprazole is the S-isomer of omeprazole and functions as a proton pump inhibitor. It selectively and irreversibly inhibits the H⁺/K⁺-ATPase enzyme system located on the luminal surface of gastric parietal cells, which constitutes the final step in acid production. By blocking this enzyme, esomeprazole reduces both basal and stimulated gastric acid secretion, promoting healing in acid-related disorders such as erosive esophagitis and peptic ulcer disease.

• Absorption: Rapidly absorbed after oral administration, with peak plasma levels reached in 1.5 hours. Bioavailability increases from 50% after a single dose to 68% after repeated dosing.
• Distribution: Highly protein bound (~97%). Volume of distribution: ~16 L.
• Metabolism: Extensively metabolized in the liver via cytochrome P450 enzymes, primarily CYP2C19 and to a lesser extent CYP3A4. Converted into inactive metabolites.
• Excretion: Eliminated primarily in the urine (~80%) and feces (~20%) as metabolites. Terminal half-life is approximately 1.3 hours, prolonged in poor CYP2C19 metabolizers.
• Food Effect: Food delays absorption but does not affect overall exposure (AUC).

• Pregnancy:
  Esomeprazole is not assigned a formal FDA pregnancy category under the updated labeling system. Animal studies show no fetal harm at standard doses, but high doses may affect bone development. Human data (mainly from omeprazole) do not suggest an increased risk of birth defects. Use only if clearly needed, especially during the first trimester.
• Lactation:
  Esomeprazole is excreted in breast milk in small amounts. Due to its low oral bioavailability, adverse effects in infants are unlikely. Generally considered compatible with breastfeeding, but caution and monitoring are advised.

• Primary Class: Proton Pump Inhibitor (PPI)
• Subclass: Second-generation PPI (S-isomer of omeprazole)

• Known hypersensitivity to esomeprazole, substituted benzimidazoles, or any component of the formulation
• Concomitant use with rilpivirine (due to significant reduction in rilpivirine plasma concentration)
• History of serious hypersensitivity reactions to other PPIs (e.g., anaphylaxis, angioedema)

• Clostridioides difficile-associated diarrhea: Particularly with prolonged use
• Bone fractures: Risk of hip, wrist, or spine fractures, especially with high-dose or long-term therapy
• Hypomagnesemia: May occur with long-term use; monitor magnesium levels periodically
• Vitamin B12 deficiency: May result from prolonged use due to impaired absorption
• Cutaneous/Systemic Lupus Erythematosus: Rare cases reported; discontinue if symptoms arise
• Acute interstitial nephritis: Discontinue immediately if suspected
• Masking of gastric malignancy: Symptomatic response does not preclude gastric cancer; investigate appropriately
• Hepatic impairment: Dose reduction required in severe cases
• Monitoring recommended: Serum magnesium, renal function, and signs of infection in long-term users

Common (≥1%):

• Gastrointestinal: Nausea, diarrhea, constipation, abdominal pain, flatulence
• Central Nervous System: Headache, dizziness
• Others: Dry mouth

Serious or Rare:

• Renal: Acute interstitial nephritis
• Electrolyte: Hypomagnesemia, hyponatremia
• Hematologic: Thrombocytopenia, neutropenia
• Dermatologic: Stevens-Johnson syndrome, toxic epidermal necrolysis
• Musculoskeletal: Bone fractures with long-term use

• CYP2C19 Substrates: May increase plasma levels of drugs like diazepam
• Clopidogrel: May reduce antiplatelet effect due to CYP2C19 inhibition
• Drugs with pH-dependent absorption: May reduce absorption of ketoconazole, atazanavir, iron salts
• Methotrexate: Increased serum levels when co-administered
• Digoxin: Increased absorption; monitor levels if used with high-dose PPI
• Warfarin: May enhance anticoagulant effects; monitor INR
• Alcohol: No significant interactions
• Food: Slows absorption rate but does not affect the extent

• FDA Alerts: Emphasized risks of bone fractures and hypomagnesemia with prolonged use
• ACG Guidelines: Recommend periodic reassessment for patients on long-term PPIs and encourage deprescribing when appropriate
• NICE Recommendations: Advise short-term use for GERD and ulcer protection, with dose review
• EMA Warnings: Reinforce magnesium monitoring and assessment of nutritional deficiencies in chronic users

• Oral Formulations:
• Store at temperatures below 25°C
• Protect from moisture and light
• Do not refrigerate
• IV Powder for Injection:
• Store dry powder at room temperature
• After reconstitution, use within 12 hours at room temperature or within 24 hours if refrigerated (2–8°C)
• Handling Instructions:
• Protect from light
• Do not freeze
• Shake oral suspension well before administration