omeprazole (Rx, OTC)

1-10%

Headache (7%)

Abdominal pain (5%)

Diarrhea (4%)

Nausea (4%)

Vomiting (3%)

Flatulence (3%)

Dizziness (2%)

Upper respiratory infection (2%)

Acid regurgitation (2%)

Constipation (2%)

Rash (2%)

Cough (1%)

Frequency Not Defined

Fracture of bone, osteoporosis-related

Hepatotoxicity (rare)

Agranulocytosis

Anorexia

Gastric polyps

Hip fracture

Alopecia

Atrophic gastritis

Interstitial nephritis (rare)

Pancreatitis (rare)

Rhabdomyolysis

Taste perversion

Abnormal dreams

Toxic epidermal necrolysis (rare)

Postmarketing Reports

Bone fracture

Fundic gland polyps

Acute tubulointerstitial nephritis

Contraindications

Hypersensitivity to omeprazole 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

May require dosage reduction with liver disease

Cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE) reported with PPIs; avoid using for longer than medically indicated; discontinue if signs or symptoms consistent with CLE or SLE are observed and refer patient to specialist

Shown to cause gastric carcinoid tumors in rats with increased doses, but risk in humans unconfirmed

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

Hypomagnesemia may occur with prolonged use (>1 year); 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

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

Inhibits hepatic isoenzyme CYP2C19 and may alter metabolism of drugs that are CYP2C19 substrates

PPIs may decrease the efficacy of clopidogrel by reducing the formation of the active metabolite

Stop use and inform a healthcare professional if rash or joint pain develops

Daily long-term use (e.g., longer than 3 years) may lead to malabsorption or a deficiency of cyanocobalamin

Acute interstitial nephritis has been observed in patients taking PPIs

Relief of symptoms does not eliminate the possibility of a gastric malignancy

Therapy increases risk of Salmonella, Campylobacter, and other infections

May elevate and/or prolong serum concentrations of methotrexate and/or its metabolite when administered concomitantly with PPIs, possibly leading to toxicity; consider a temporary withdrawal of PPI therapy therapy with high dose methotrexate administration

PPI therapy is associated with increased risk of fundic gland polyp; risk increases with long-term use >1 year; patient may be asymptomatic; problem usually identified incidentally on endoscopy; use shortest duration of therapy appropriate to condition being treated

If patient taking a prescription drug, the patient should ask a doctor or a pharmacist whether acid reducers can be taken concomitantly with it

Acute tubulointerstitial nephritis (TIN) reported in patients taking PPIs; may occur at any point during PPI therapy; patients may present with varying signs and symptoms from symptomatic hypersensitivity reactions to non-specific symptoms of decreased renal function (eg, malaise, nausea, anorexia); in reported case series, some patients were diagnosed on biopsy and in absence of extra-renal manifestations (eg, fever, rash or arthralgia); discontinue therapy and evaluate patients with suspected acute TIN

Pregnancy

There are no adequate and well-controlled studies in pregnant women; available epidemiologic data fail to demonstrate an increased risk of major congenital malformations or other adverse pregnancy outcomes with first trimester omeprazole use; reproduction studies in rats and rabbits resulted in dose-dependent embryo-lethality at omeprazole doses that were approximately 3.4 to 34 times an oral human dose of 40 mg (based on a body surface area for a 60 kg person)

Teratogenicity was not observed in animal reproduction studies with administration of oral esomeprazole (an enantiomer of omeprazole) magnesium in rats and rabbits during organogenesis with doses about 68 times and 42 times, respectively, an oral human dose of 40 mg esomeprazole or 40 mg omeprazole (based on body surface area for a 60 kg person); changes in bone morphology were observed in offspring of rats dosed through most of pregnancy and lactation at doses equal to or greater than approximately 34 times an oral human dose of 40 mg esomeprazole or 40 mg omeprazole; when maternal administration was confined to gestation only, there were no effects on bone physeal morphology in offspring at any age

Lactation

Limited data suggest omeprazole may be present in human milk; there are no clinical data on effects of omeprazole on breastfed infant or on milk production; developmental and health benefits of breastfeeding should be considered along with mother's clinical need for therapy and any potential adverse effects on breastfed infant from treatment or from underlying maternal condition

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.

Mechanism of Action

PPI; binds to H+/K+-exchanging ATPase (proton pump) in gastric parietal cells, resulting in suppression of basal and stimulated acid secretion

Absorption

Bioavailability: 30-40%

Onset of action: 1 hr (antisecretory effect)

Duration: 73 hr

Peak plasma time: 0.5-3.5 hr

Peak response (PUD): 2 hr (initial); 5 days (peak)

Distribution

Protein bound: 95-96%

Vd: 0.39 L/kg

Metabolism

Metabolized extensively by hepatic CYP2C19; slow metabolizers are deficient in CYP2C19 enzyme system; plasma concentration can increase by 5-fold or higher in comparison with that found in persons with the enzyme

Metabolites: Hydroxyomeprazole, omeprazole sulfone, omeprazole sulfide (inactive)

Enzymes inhibited: CYP2C19

Elimination

Half-life: 0.5-1 hr; increases to 3 hr with hepatic impairment

Dialyzable: No

Total body clearance: 500-600 mL/min

Excretion: Urine (77%); feces (16-19%; mainly in bile)

Pharmacogenomics

CYP2C19 poor metabolizers

• Asians have ~4-fold higher exposure to omeprazole than whites
• CYP2C19, a polymorphic enzyme, is involved in the metabolism of omeprazole
• ~15-20% of Asians are CYP2C19 poor metabolizers
• Tests are available to identify a patient’s CYP2C19 genotype
• Avoid use in Asian patients with unknown CYP2C19 genotype or those who are known to be poor metabolizers