Dosing and uses of Nexium, Nexium 24HR (esomeprazole)
Adult dosage forms and strengths
capsule, delayed-release
- 20mg (Rx/OTC)
- 40mg
injection, powder for reconstitution
- 20mg/vial
- 40mg/vial
packets for oral suspension
- 10mg
- 20mg
- 40mg
GERD Without Erosive Esophagitis
20 mg PO qDay for 4 weeks; consider an additional 4 weeks of treatment if symptoms do not resolve completely in the first 4 weeks
GERD With Erosive Esophagitis
20-40 mg PO qDay for 4-8 weeks
If oral therapy inappropriate or not possible: 20-40 mg qDay IV up to 10 days; switch to PO once patient able to swallow
Maintenance: 20 mg PO qDay for up to 6 months
Helicobacter Pylori Eradication
Combination therapy (with amoxicillin and clarithromycin) for eradication of H pylori in patients with duodenal ulcer
40 mg PO qDay for 10 days, PLUs
Amoxicillin 1000 mg PO q12hr for 10 days, PLUs
Clarithromycin 500 mg PO q12hr for 10 days
Risk Reduction of NSAID-Associated Gastric Ulcer
20-40 mg PO qDay for up to 6 months
NSAID-Induced Gastric Ulcer
20 mg PO qDay for 4-8 weeks
Zollinger-Ellison Syndrome
80 mg PO divided q12hr (initial); adjust regimen to efficacy; up to 240 mg PO qDay, Or
120 mg PO q12hr administered to patients
Gastric or Duodenal Ulcers Following Therapeutic Endoscopy
IV indicated for risk reduction of rebleeding of gastric or duodenal ulcers following therapeutic endoscopy in adults
80 mg IV infused over 30 min, THEN continuous IV infusion of 8 mg/hr for total treatment duration of 72 hr
Follow IV therapy with oral acid suppressive therapy
Frequent Heartburn
OTC: 20 mg PO qDay x14 days
Hepatic Impairment
Oral administration
- Mild to moderate (Child-Pugh A/B): No dosage adjustment required
- Severe (Child-Pugh C): Not to exceed 20 mg/day
GERD (IV)
- Mild to moderate (Child-Pugh A/B): No dosage adjustment required
- Severe (Child-Pugh C): Not to exceed 20 mg/day IV
Bleeding gastric or duodenal ulcers (IV)
- No dosage adjustment required with initial 80 mg/30 min IV dose
- Adjust dose for continuous IV infusion
- Mild-to-moderate (Child Pugh A/B): Not to exceed 6 mg/hr
- Severe (Child Pugh C): Not to exceed 4 mg/hr
Administration
If patient unable to swallow capsule whole, capsule can be opened, emptied on applesauce, mixed, and swallowed immediately
Infuse intermittent IV over 10-30 minutes, OR not less than 3 minutes for IV injection
Pediatric dosage forms and strengths
capsule, delayed-release
- 20mg
- 40mg
- 24.65 mg (strontium salt)
- 49.3 mg (strontium salt)
injection, powder for reconstitution
- 20mg/vial
- 40mg/vial
packets for oral suspension
- 10mg
- 20mg
- 40mg
GERD Without Erosive Esophagitis
OraL
- <1 year: Safety and efficacy not established
- 1-12 years: 10-20 mg PO qDay for up to 8 weeks
- >12 years: 20-40 mg PO qDay for up to 8 weeks
Short-term Treatment of GERD
IV
- Short-term treatment of GERD with erosive esophagitis when oral therapy is not possible or appropriate
- <1 month: Safety and efficacy not established
- 1 month to 1 year: 0.5 mg/kg IV qDay
- >1 year (<55 kg): 10 mg IV qDay
- >1 year (≥55 kg): 20 mg IV qDay
GERD With Erosive Esophagitis (Healing)
<1 month: Safety and efficacy not established
1 month to 1 year
- 3.5 kg: 2.5 mg PO qDay for up to 6 weeks
- >3.5-7.5 kg: 5 mg PO qDay for up to 6 weeks
- >7.5 kg: 10 mg PO qDay for up to 6 weeks
1-12 years
- <20 kg: 10 mg PO qDay for 8 weeks
- ≥20 kg: 10-20 mg qDay for 8 weeks
>12 years
- 20-40 mg PO qDay for 4-8 weeks
- Maintenance: 20 mg PO qDay up to 6 months
Administration
If patient unable to swallow capsule whole, capsule can be opened, emptied on applesauce, mixed, and swallowed immediately
Infuse intermittent IV over 10-30 minutes, OR not less than 3 minutes for IV injection
Nexium, Nexium 24HR (esomeprazole) adverse (side) effects
>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)
Warnings
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
Gastric atrophy reported with long-term use of another PPI
Severe hepatic impairment
Relief of symptoms does not eliminate the possibility of a gastric malignancy
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
Daily long-term use (e.g., longer than 3 years) may lead to malabsorption or a deficiency of cyanocobalamin
Acute interstitial nephritis reported in patients taking proton pump inhibitors
Pregnancy and lactation
Pregnancy category: C (oral); B (IV)
Lactation: Unknown whether esomeprazole is distributed into breast milk; discontinue drug or do not nurse
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.
Pharmacology of Nexium, Nexium 24HR (esomeprazole)
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
Administration
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
