esomeprazole (es-oh-mep-ra-zole) NexIUM, NexIUM 24hr

 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: With amoxicillin and clarithromycin

to eradicate Helicobacter pylori in duodenal

ulcer disease or history of duodenal ulcer disease.

PO: Decrease risk of gastric ulcer during continuous

NSAID therapy. OTC: Heartburn occurring 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

Effects: 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;

foodpabsorption.

Distribution: Unknown.

Protein Binding: 97%.

Metabolism and Excretion: Extensively metabolized

by the liver (cytochrome P450 [CYP450] system,

primarily CYP2C19 isoenzyme, but also the CYP3A4 isoenzyme)

(the CYP2C19 enzyme system exhibits genetic

polymorphism; 15–20% of Asian patients and 3–

5% of Caucasian and Black patients may be poor metabolizers

and may have significantlyqesomeprazole

concentrations and anqrisk of adverse effects); 1%

excreted unchanged in urine.

Half-life: Children 1–11 yrs: 0.42–0.88 hr; Adults:

1.0–1.5 hr.

TIME/ACTION PROFILE (blood levels*)

ROUTE ONSET PEAK DURATION

PO rapid 1.6 hr 24 hr

IV rapid end of infusion

24 hr

*Resolution of symptoms takes 5–8 days.

Contraindications/Precautions

Contraindicated in: Hypersensitivity to esomeprazole

or related drugs (benzimidazoles); Hypersensitivity.

Use Cautiously in: Severe hepatic impairment; Patients

using high-doses for 1 year (qrisk of hip, wrist,

or spine fractures); Patients using therapy for 3 yr (q

risk of vitamin B12 deficiency; OB, Lactation: Use only if

potential benefit outweighs potential risk.

Adverse Reactions/Side Effects

CNS: headache. Derm: cutaneous lupus erythematosus.

GI: CLOSTRIDIUM DIFFICILE-ASSOCIATED DIARRHEA

(CDAD), abdominal pain, constipation, diarrhea, dry

mouth, flatulence, nausea. F and E: hypomagnesemia

(especially if treatment duration 3 mo). GU: acute

interstitial nephritis. Hemat: vitamin B12 deficiency.

MS: bone fracture. Misc: systemic lupus erythematosus.

Interactions

Drug-Drug: Mayplevels of atazanavir and nelfinavir;

avoid concurrent use with either of these antiretrovirals.

Mayqlevels and risk of toxicity of saquinavir

(may need topdose of saquinavir). Mayp

absorption of drugs requiring acid pH, including ketoconazole,

itraconazole, ampicillin esters, iron

salts, erlotinib, and mycophenolate mofetil. May

qlevels of digoxin and methotrexate. Mayqrisk of

bleeding with warfarin (monitor INR and PT). Voriconazole

mayqlevels. Maypthe antiplatelet effects of

clopidogrel; avoid concurrent use. Mayqlevels of cilostazol;

considerpdose of cilostazol from 100 mg

twice daily to 50 mg twice daily. Rifampin mayplevels

and maypresponse (avoid concurrent use). Hypomagnesemiaqrisk

of digoxin toxicity. Mayqlevels of tacrolimus

and methotrexate.

Drug-Natural Products: St. John’s wort mayp

levels and maypresponse (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.

Decrease 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 capsules: 20 mgRx, OTC, 40mg.

Cost: 20 mg $713.55/90, 40 mg $731.22/90. Delayed-

release tablets: 20 mgOTC. Delayed-release

oral suspension packets: 2.5 mg/pkt, 5 mg/pkt, 10

mg/pkt, 20 mg/pkt, 40 mg/pkt. Cost: All strengths

$268.01/30 pkts. Powder for injection (requires

reconstitution and further dilution): 20 mg/vial,

40 mg/vial. In combination with: naproxen (Vimovo).