Omeprazole

Omeprazole  [om-eh-pray′zole]

CATEGORY AND SCHEDULE

Pregnancy Risk Category: C

Classification: Gastrointestinal agents, antiulcer agents, proton pump-inhibitors (PPI)

MECHANISM OF ACTION

A benzimidazole that is converted to active metabolites that irreversibly bind to and inhibit
hydrogen-potassium adenosine triphosphatase, an enzyme on the surface of gastric parietal cells. Inhibits hydrogen ion transport into gastric lumen.

Therapeutic Effect: Increases gastric pH, reduces gastric acid production.

PHARMACOKINETICS

Route: PO

Onset: 1 h

Peak: 2 h

Duration: 72 h

Rapidly absorbed from the GI tract.

Protein binding: 95%. Primarily distributed into gastric parietal cells.

Metabolized extensively in the liver.

Primarily excreted in urine. Unknown whether removed by hemodialysis.

Half-life: 0.5-1 h (increased in patients with hepatic impairment).

AVAILABILITY

Capsules (Delayed Release [Prilosec]): 10 mg, 20 mg, 40 mg.

Delayed-Release Tablets (Prilosec OTC): 20 mg.

Delayed-Release Granules for Oral Suspension: 2.5-mg, 10-mg packets.

INDICATIONS AND DOSAGES

‣Erosive esophagitis, poorly responsive gastroesophageal reflux disease (GERD), active duodenal ulcer, prevention and treatment of NSAID-induced ulcers

PO

Adults, Elderly. 20 mg/day.

‣To maintain healing of erosive esophagitis

PO: Adults, Elderly. 20 mg/day.

‣Pathologic hypersecretory conditions

PO: Adults, Elderly. Initially, 60 mg/day up to 120 mg 3 times a day.

‣Duodenal ulcer caused by Helicobacter pylori

PO: Adults, Elderly. 20 mg twice a day for 10 days, with antibiotics.

‣Active benign gastric ulcer

PO: Adults, Elderly. 40 mg/day for 4-8€wks.

‣Dyspepsia (OTC use)

Adults. 20 mg once daily for no more than 14 days. Contact physician regarding long-term treatment if heartburn continues.

‣Usual pediatric dosage

Children 1-16 yr and ≥ 20 kg. 20 mg once daily. See adult dosage if > 16 yr.

Children 1-16 yr and 10 to < 20 kg. 10 mg once daily.

Children 1-16 yr and 5 to < 10 kg. 5 mg/day.

OFF-LABEL USES

Prevention of NSAID-induced ulcers, stress-ulcer prophylaxis.

CONTRAINDICATIONS

Hypersensitivity to omeprazole or related drugs, including interstitial nephritis.

INTERACTIONS

Drug

Clopidogrel: Do not use omeprazole with clopidogrel. PPI may decrease the conversion of clopidogrel to its active metabolite, thereby reducing its effectiveness.

Diazepam, oral anticoagulants

(warfarin), phenytoin: May increase the blood concentration of diazepam, oral anticoagulants, and phenytoin.

Ketoconazole: Decreases ketoconazole absorption.

Methotrexate: May increase risk of methotrexate toxicity.

Protease inhibitors: Reduces absorption of many. Some contraindicate use of omeprazole concurrently.

Rifampin: May decrease levels and efficacy of omeprazole.

Tacrolimus: May increase serum levels.

Herbal

St. John’s wort: May decrease the levels of omeprazole.

Food

None known.

DIAGNOSTIC TEST EFFECTS

May increase serum alkaline phosphatase, AST (SGOT), and ALT (SGPT) levels. Rare decreases in platelet counts. May decrease serum magnesium in chronic use.

SIDE EFFECTS

Frequent (7%): Headache.

Occasional (2%-3%): Diarrhea, abdominal pain, nausea.

Rare (2%): Dizziness, asthenia or loss of strength, vomiting, constipation, upper respiratory tract infection, back pain, rash, cough.

SERIOUS REACTIONS

• Anaphylaxis/angioedema.

• Interstitial nephritis.

• In chronic use, may cause hypomagnesemia.

• In chronic use, may increase risk of bone fracture.

• Possible alteration of GI microflora which increases risk of C. dificile–assosiated diarrhea (CDAD).

PRECAUTIONS AND CONSIDERATION

PRECAUTIONS & CONSIDERATIONS

It is unknown whether omeprazole crosses the placenta; caution warranted in pregnancy. Omeprazole is excreted in human milk; a decision should be made whether to discontinue breastfeeding. Safety and efficacy have not been established in children under 1 yr. No age-related precautions have been noted in elderly patients. Consider dose reduction in chronic hepatic disease or Asian patients. Notify the physician if headache, diarrhea, discomfort, or nausea occurs during omeprazole therapy. Serum chemistry laboratory values, particularly serum alkaline phosphatase, AST, and ALT levels should be obtained to assess liver function. Loose or soft stool may be noted early in the therapy protocol. Do

not use Prilosec OTC for more than 2 wks without medical consultation.

Storage

Store at room temperature. Do not prepare granules ahead of time of administration.

MOSBY’S DRUG REFERENCE for HEALTH PROFESSIONS, 4th EDITION

PUBLISHER: ELSEVIER