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Omeprazole

Pronunciation

Class: Proton-pump Inhibitors
VA Class: GA900
Chemical Name: 5-Methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazole
Molecular Formula: C17H19N3O317H19N3O3S)2 Mg
CAS Number: 73590-58-6
Brands: Prilosec, Zegerid

Introduction

Acid- or proton-pump inhibitor; gastric antisecretory agent.1 2 3 4 5 8 132 207 208

Uses for Omeprazole

Gastroesophageal Reflux (GERD)

Short-term treatment of symptomatic GERD (e.g., heartburn).1 5 97 207 208

Short-term treatment of erosive esophagitis (endoscopically diagnosed) in patients with GERD.1 2 3 4 5 8 92 93 94 95 96 97 98 207

Maintain healing and decrease recurrence of erosive esophagitis.1 92 93 94 95 96 207 208

Slideshow: OTC Medication Use In Pregnancy: Wise or Worrisome?

Short-term self-medication for symptomatic relief of frequent (e.g., 2 or more days a week) heartburn in adults ≥18 years of age.187

Duodenal Ulcer

Short-term treatment of active duodenal ulcer (endoscopically or radiographically confirmed).1 2 3 4 8 207 208

Treatment of Helicobacter pylori infection and duodenal ulcer disease.1 138 Used in conjunction with amoxicillin and clarithromycin (triple therapy) or clarithromycin (dual therapy);1 138 has been used in other multidrug regimens.27 28 29 37 38 39 61 62 66 67 75 76 77 78 79 81 82 106 108 110 111 112 113 115 138

Gastric Ulcer

Short-term treatment and symptomatic relief of active benign gastric ulcer.1 207 208

Crohn’s Disease-associated Ulcers

Some evidence for use of proton-pump inhibitors (e.g., omeprazole) for gastric acid suppressive therapy as an adjunct in the management of upper GI Crohn’s disease, including esophageal, gastroduodenal, and jejunoileal disease.190 191 192 194 195 196

Pathologic GI Hypersecretory Conditions

Long-term treatment of Zollinger-Ellison syndrome, multiple endocrine adenomas, or systemic mastocytosis in adults.1 2 3 4 5 8 13

Upper GI Bleeding

Used to decrease risk of upper GI bleeding in critically ill patients.207 208 211

Omeprazole Dosage and Administration

Administration

Omeprazole is acid-labile.1 207 208 To avoid decomposition in acidic pH of the stomach, delayed-release capsules and delayed-release oral suspension (Prilosec) contain enteric-coated granules of the drug;1 2 4 immediate-release capsules and immediate-release oral suspension (Zegerid) contain sodium bicarbonate to protect the drug.207 208

Oral Administration

Immediate-release Capsules

Swallow intact with a glass of water at least 1 hour prior to a meal.207 Do not use with any other liquid.207 Do not open capsules or mix the contents with food.207

Do not substitute two 20-mg capsules for one 40-mg capsule because the 20-mg and 40-mg capsules contain the same amount of sodium bicarbonate.207

Delayed-release Capsules

Administer orally at least 1 hour before a meal.1

Swallow capsules intact; do not chew or crush.1

Antacids may be used concomitantly as needed for pain relief.1 3

Alternatively, open capsule and mix contents with 1 tablespoon applesauce; swallow immediately without chewing and with glass of cool water to ensure complete swallowing.1 Applesauce should not be hot and should be soft enough to swallow without chewing.1

Delayed-release Tablets

Tablets for self-medication: swallow intact with a glass of water before breakfast; do not chew, crush, or crush in food.187 189

Powder for Immediate-release Oral Suspension

Administer at least 1 hour prior to a meal.207 208

May use antacids, antacid/alginic acid combinations, histamine H2-receptor antagonists, or histamine H2-receptor antagonist and antacid combinations for “breakthrough” symptoms, but efficacy of these preparations has not been established.208

Empty 20- or 40-mg single-dose packet for oral suspension into small cup containing 15–30 mL of water, stir well, and swallow immediately.207 208 Rinse container with more water and swallow to ensure complete consumption of the dose.207 208 Do not mix with any other liquid or food.207 208

Do not substitute two 20-mg packets for one 40-mg packet because the 20- and 40-mg powder for oral suspension packets contain the same amount of sodium bicarbonate.207

Powder for Delayed-release Oral Suspension

Administer at least 1 hour before a meal.1

Antacids may be used concomitantly.1

Empty contents of 2.5- or 10-mg single-dose packet into small cup containing 5 or 15 mL, respectively, of water.1 Stir well, then allow to thicken for 2–3 minutes.1 Stir again and administer within 30 minutes of preparation.1 If any material remains in the cup, add additional water, mix, and ingest immediately to ensure complete consumption of the dose.1

NG Tube

Powder for delayed-release oral suspension: Reconstitute 2.5- or 10-mg single-dose packet with 5 or 15 mL of water, respectively, in a catheter-tipped syringe and shake immediately.1 Allow mixture to thicken for 2–3 minutes.1 Shake syringe and administer within 30 minutes through NG or gastric tube (6 French or larger).1 Refill syringe with additional water (5 or 15 mL, respectively), shake, and flush any remaining drug mixture from the tube.1

Powder for immediate-release oral suspension: Reconstitute 20- or 40-mg single-dose packet with 20 mL of water, stir well, administer immediately through NG or orogastric tube using appropriately sized syringe.207 208 Flush the tube with 20 mL of water after administration.207 208 Temporarily stop continuous enteral feeding via NG or orogastric tube for 3 hours before and 1 hour after administration.207 208

Dosage

Available as omeprazole and omeprazole magnesium; dosage expressed in terms of omeprazole.1 187

Pediatric Patients

Gastroesophageal Reflux
GERD.
Oral (Delayed-release Capsules or Delayed-release Oral Suspension)
Oral Omeprazole Dosage for Treatment of GERD in Pediatric Patients 1–16 Years of Age1

Body Weight

Omeprazole Dosage

5 to <10 kg

5 mg once daily

10 to <20 kg

10 mg once daily

≥20 kg

20 mg once daily

Administered for 4 weeks in one study.1 198

Treatment of Erosive Esophagitis.
Oral (Delayed-release Capsules or Delayed-release Oral Suspension)
Oral Omeprazole Dosage for Treatment of Erosive Esophagitis in Pediatric Patients 1–16 Years of Age1

Body Weight

Omeprazole Dosage

5 to <10 kg

5 mg once daily

10 to <20 kg

10 mg once daily

≥20 kg

20 mg once daily

On a mg/kg basis, dosage of omeprazole required to heal erosive esophagitis is greater in children than that required in adults.1 197 198 In an uncontrolled open-label study, dosages required for healing were 0.7–3.5 mg/kg daily (maximum 80 mg daily) for 3–6 months; about 90% of children healed in the first 3 months, and about 5% required a second course of treatment.1 197 198 Dosage of 0.7 mg/kg daily resulted in healing in 44% of children; an additional 28% of the children studied required a dosage of 1.4 mg/kg daily for healing to occur.1 197 198

Maintenance of Healing of Erosive Esophagitis.
Oral (Delayed-release Capsules or Delayed-release Oral Suspension)
Oral Omeprazole Dosage for Maintenance Therapy in Pediatric Patients 1–16 Years of Age1

Body Weight

Omeprazole Dosage

5 to <10 kg

5 mg once daily

10 to <20 kg

10 mg once daily

≥20 kg

20 mg once daily

Maintenance therapy continued 2 years in one study.1 198 In an uncontrolled open-label study, maintenance dosages were half the dosages required for initial healing in 54% of children, while 46% required dosage increase (0.7–2.8 mg/kg daily) for all or part of the study.1 198

Adults

GERD
GERD without Erosive Esophagitis
Oral (Immediate-release Capsules or Oral Suspension, Delayed-release Capsules or Oral Suspension)

20 mg once daily for up to 4 weeks.1 2 207 208

Treatment of Erosive Esophagitis
Oral (Immediate-release Capsules or Oral Suspension, Delayed-release Capsules or Oral Suspension)

20 mg once daily until healing occurs (usually within 4–8 weeks);1 2 207 208 40 mg once daily may be required.2 98 May give an additional 4 weeks of therapy (up to 12 weeks for a single course).1 2 98 207 If recurs, consider additional 4–8 weeks of therapy.1 207

Maintenance of Healing of Erosive Esophagitis
Oral (Immediate-release Capsules or Oral Suspension, Delayed-release Capsules or Oral Suspension)

20 mg once daily.1 207 208 Chronic, lifelong therapy may be appropriate.143

Self-medication for Frequent Heartburn
Oral (Delayed-release Tablets)

20 mg daily in the morning for 14 days.187 188 Do not exceed recommended dosage or duration; do not administer more than one course every 4 months.187 188 May relieve symptoms within 24 hours, but 1–4 days may be required for complete relief.187 188 189

Duodenal Ulcer
Treatment of Active Duodenal Ulcer
Oral (Immediate-release Capsules or Oral Suspension, Delayed-release Capsules or Oral Suspension)

20 mg once daily until healing occurs (usually within 2–4 weeks); an additional 4 weeks with therapy may be beneficial.1 2 207 208 Patients who responded poorly to histamine H2-receptor antagonists may require up to 40 mg daily.2

Treatment of Helicobacter pylori Infection and Duodenal Ulcer
Oral (Delayed-release Capsules or Oral Suspension)

Triple therapy: 20 mg twice daily (morning and evening) for 10 days in conjunction with amoxicillin and clarithromycin; additional omeprazole therapy with 20 mg once daily for 18 days recommended if active ulcer present initially.1

Dual therapy: 40 mg once daily (in the morning) for 14 days in conjunction with clarithromycin; omeprazole 20 mg once daily for additional 14 days recommended if active ulcer present initially.1

Gastric Ulcer
Treatment
Oral (Immediate-release Capsules or Oral Suspension, Delayed-release Capsules or Oral Suspension)

40 mg once daily for 4–8 weeks.1 207 208

Pathologic GI Hypersecretory Conditions
Zollinger-Ellison Syndrome
Oral (Delayed-release Capsules or Delayed-release Oral Suspension)

60 mg once daily initially.1 2 Adjust dosage according to patient response and tolerance; continue therapy as long as necessary.1 2 13 Administer daily dosages >80 mg in divided doses.1 13 May require dosages of up to 360 mg daily (given in 3 divided doses).1 2

Multiple Endocrine Adenomas
Oral (Delayed-release Capsules or Delayed-release Oral Suspension)

60 mg once daily initially.1 2 Adjust dosage according to patient response and tolerance; continue therapy as long as necessary.1 2 13 Administer daily dosages >80 mg in divided doses.1 13 May require dosages of up to 360 mg daily (given in 3 divided doses).1 2

Systemic Mastocytosis
Oral (Delayed-release Capsules or Delayed-release Oral Suspension)

60 mg once daily initially.1 2 Adjust dosage according to patient response and tolerance; continue therapy as long as necessary.1 2 13 Administer daily dosages >80 mg in divided doses.1 13 May require dosages of up to 360 mg daily (given in 3 divided doses).1 2

Upper GI Bleeding
Reduction of Risk of Upper GI Bleeding in Critically Ill Adults
Oral (Immediate-release Oral Suspension)

Initially, 40 mg followed by 40 mg after 6–8 hours on the first day, then 40 mg once daily for up to 14 days.207 Safety and efficacy for >14 days not established.207

Special Populations

Hepatic Impairment

Consider dosage reduction, particularly in patients receiving long-term therapy for maintenance of healing of erosive esophagitis.1 207

Renal Impairment

No dosage adjustment necessary.1 207

Asians

Consider dosage reduction, especially in patients receiving long-term therapy for maintenance of healing of erosive esophagitis.1 207

Cautions for Omeprazole

Contraindications

  • Known hypersensitivity to omeprazole, any ingredient in the formulation, or esomeprazole or other substituted benzimidazoles (e.g., lansoprazole, pantoprazole, rabeprazole).1 25 139 207

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity Reactions

Hypersensitivity reactions (e.g., anaphylaxis, angioedema, bronchospasm, interstitial nephritis, urticaria) reported.1

Warnings/Precautions

Gastric Malignancy

Response to omeprazole does not preclude presence of occult gastric neoplasm.1 207 208

Atrophic Gastritis

Atrophic gastritis reported occasionally with long-term use.1 207 208

Clostridium difficile Infection

Proton-pump inhibitors associated with possible increased (1.4–2.75 times) risk of Clostridium difficile infection, including C. difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis).335 336 339 340 Many patients also had other risk factors for CDAD.335 May be severe; colectomy and, rarely, death reported.335

Use the lowest effective dosage and shortest duration of therapy appropriate for the patient's clinical condition.335

Consider CDAD if persistent diarrhea develops and manage accordingly; initiate supportive therapy (e.g., fluid and electrolyte management), anti-infective therapy directed against C. difficile (e.g., metronidazole, vancomycin), and surgical evaluation as clinically indicated.335 336

Sodium Bicarbonate

Each 20- and 40- mg conventional immediate-release capsule contains 1100 mg of sodium bicarbonate (304 mg [13 mEq] of sodium), and each 20- and 40-mg single-dose packet of powder for immediate-release oral suspension contains 1680 mg of sodium bicarbonate (460 mg [20 mEq] of sodium).207 Consider sodium content when used in patients requiring restricted salt intake.207

Caution in patients with Bartter’s syndrome, hypokalemia, respiratory alkalosis, and acid-base abnormalities.207 208 Long-term administration of sodium bicarbonate with calcium or milk may cause milk-alkali syndrome.207 Long-term use of sodium bicarbonate may lead to systemic alkalosis, and increased sodium intake can produce edema and weight increase.207 Sodium bicarbonate is contraindicated in patients with metabolic alkalosis or hypocalcemia.208

Respiratory Effects

Administration of proton-pump inhibitors has been associated with an increased risk for developing certain infections (e.g., community-acquired pneumonia).199 200

Bone Fracture

Several observational studies suggest that use of proton-pump inhibitors, particularly in high dosages (i.e., multiple daily doses) and/or for prolonged periods of time (i.e., ≥1 year), may be associated with increased risk of osteoporosis-related fractures of the hip, wrist, or spine.1 212 300 301 302 303 304 305 Magnitude of risk is unclear;212 300 301 302 303 304 305 310 causality not established.305 FDA is continuing to evaluate this safety concern.305

Use the lowest effective dosage and shortest duration of therapy appropriate for the patient’s clinical condition.1 212 301 303 305 307

Individuals at risk for osteoporosis-related fractures should receive an adequate intake of calcium and vitamin D; assess and manage these patients’ bone health according to current standards of care.1 212 303 305 307

Hypomagnesemia

In patients expected to receive long-term proton-pump inhibitor therapy or in patients currently receiving digoxin or drugs that may cause hypomagnesemia (e.g., diuretics), consider measuring serum magnesium concentrations prior to initiation of prescription proton-pump inhibitor therapy and periodically thereafter.1 207 313 314 316 319 326

Hypomagnesemia, symptomatic and asymptomatic, reported rarely in patients receiving long-term therapy (≥3 months or, in most cases, >1 year) with proton-pump inhibitors, including omeprazole.1 207 313 314 315 316 317 318 319 320 321 322 323 324 325 326 Serious adverse effects include tetany, seizures, tremors, carpopedal spasm, arrhythmias (e.g., atrial fibrillation, supraventricular tachycardia), and abnormal QT interval.1 207 313 314 315 318 319 321 322 323 325 Paresthesia, muscle weakness, muscle cramps, lethargy, fatigue, and unsteadiness may occur.316 319 320 321 325 Most patients required magnesium replacement and discontinuance of the proton-pump inhibitor.1 207 313 316 317 319 321 322 323 324 325 326 Hypomagnesemia resolved within 1 week (median) following discontinuance and recurred within 2 weeks (median) of rechallenge.313

Cardiovascular Effects

Preliminary safety data from 2 long-term clinical trials comparing esomeprazole or omeprazole with antireflux surgery in patients with severe GERD raised concerns about a potential increased risk of cardiac events (e.g., MI, heart failure, sudden death) in patients receiving these drugs.213 214 215 After reviewing data from these and other studies, FDA has concluded that long-term use of these drugs is not likely to be associated with an increased risk of such cardiac events.213 214 215 FDA recommends that clinicians continue to prescribe and patients continue to use these drugs in the manner described in the manufacturers’ labelings.213 214 215

Specific Populations

Pregnancy

Category C.1 207 208

Lactation

Distributed into milk.1 139 202 207 Discontinue nursing or the drug.1 139 207

Pediatric Use

Safety and efficacy of delayed-release capsules or delayed-release oral suspension established for treatment of symptomatic GERD, treatment of erosive esophagitis, and maintenance of healing of erosive esophagitis in pediatric patients 1–16 years of age.1 198 Safety and efficacy not established in infants <1 year of age or for other uses in pediatric patients.1

Safety and efficacy for self-medication of frequent heartburn not established in children <18 years of age.187

Safety and efficacy of immediate-release capsules or immediate-release oral suspension not established in pediatric patients <18 years of age.207

Geriatric Use

No substantial differences in efficacy and safety relative to younger adults, but increased sensitivity cannot be ruled out.1 207

Hepatic Impairment

Increased bioavailability and decreased clearance.1 207 Monitor patients receiving >20 mg daily for possible adverse effects.3 (See Hepatic Impairment under Dosage and Administration.)

Common Adverse Effects

In adults, diarrhea, nausea, constipation, abdominal pain, vomiting, headache, flatulence.1 2 3 207 208

In pediatric patients, respiratory effects, fever (in children 1–2 years of age), accidental injuries (in children 2–16 years of age); otherwise, adverse effects generally similar to those in adults.1

Interactions for Omeprazole

Metabolized in the liver by CYP isoenzymes, principally CYP2C19, and to lesser extent by CYP3A4.1 139 Inhibits CYP2C19.1

Drugs Metabolized by Hepatic Microsomal Enzymes

Potential to prolong elimination of drugs metabolized by oxidation in the liver.1 2 207 Interaction reported with drugs metabolized by CYP isoenzymes; monitor and adjust dosage of these drugs if necessary.1 207

Drugs that Cause Hypomagnesemia

Potential pharmacologic interaction (possible increased risk of hypomagnesemia).313 Consider monitoring magnesium concentrations prior to initiation of prescription proton-pump inhibitor therapy and periodically thereafter.1 313 (See Hypomagnesemia under Cautions.)

Specific Drugs

Drug

Interaction

Comments

Atazanavir

Possible altered oral absorption of atazanavir, resulting in decreased plasma atazanavir concentrations; possible loss of virologic response1 207 218

Manufacturers of omeprazole state that concomitant use with atazanavir is not recommended1 207

Antiretroviral treatment-naive patients: If a proton-pump inhibitor is used concomitantly with atazanavir, administer ritonavir-boosted atazanavir (atazanavir 300 mg and ritonavir 100 mg once daily with food); administer the proton-pump inhibitor approximately 12 hours before ritonavir-boosted atazanavir217 218

For treatment-naive patients, dosage of proton-pump inhibitor should not exceed omeprazole 20 mg daily (or equivalent)217 218

Antiretroviral treatment-experienced patients: Concomitant use of proton-pump inhibitors with atazanavir not recommended217 218

Benzodiazepines

Potential for altered benzodiazepine metabolism1 207

Monitor and adjust benzodiazepine dosage if needed1 207

Cilostazol

Increased peak plasma concentrations and AUC of cilostazol and its active metabolite1

Consider reducing cilostazol dosage (from 100 mg twice daily to 50 mg twice daily)1

Clarithromycin

Increased plasma concentrations and AUC of omeprazole, clarithromycin, and 14-hydroxyclarithromycin 1 207

Clopidogrel

Omeprazole (or esomeprazole) reduces exposure to clopidogrel's active metabolite and decreases platelet inhibitory effects;1 223 224 225 228 350 additional data needed to fully elucidate potential clinical consequences (e.g., increased cardiovascular events)230 236 237 240 243 244 245 246 247 248 249 250 251 252

Dexlansoprazole, lansoprazole, or pantoprazole had less effect on clopidogrel's antiplatelet activity than did omeprazole or esomeprazole224 350 351

Avoid concomitant use of omeprazole (or esomeprazole) and clopidogrel1 224 232 233 312

Assess risks and benefits of concomitant proton-pump inhibitor use in individual patients237 240 243 248 250 311

American College of Cardiology Foundation/American College of Gastroenterology/American Heart Association (ACCF/ACG/AHA) states that GI bleeding risk reduction with concomitant proton-pump inhibitor in patients with risk factors for GI bleeding (e.g., advanced age; concomitant use of warfarin, corticosteroids, or NSAIAs; H. pylori infection) may outweigh potential reduction in cardiovascular efficacy of antiplatelet treatment associated with a drug-drug interaction.311 In patients without such risk factors, ACCF/ACG/AHA states that risk/benefit balance may favor use of antiplatelet therapy without a proton-pump inhibitor.311

If concomitant therapy with a proton-pump inhibitor and clopidogrel is deemed necessary, consider using an agent with little or no CYP2C19-inhibitory activity;223 230 234 312 350 alternatively, consider using a histamine H2-receptor antagonist (ranitidine, famotidine, nizatidine)223 224 230 234 251 but not cimetidine (also a potent CYP2C19 inhibitor)232 233

Cyanocobalamin

Potential for decreased cyanocobalamin absorption86 98 99 100 101

Monitor serum cyanocobalamin concentrations during long-term omeprazole therapy99

Cyclosporine

Potential for altered cyclosporine metabolism1 207

Monitor and adjust cyclosporine dosage if needed1 207

Darunavir

Ritonavir-boosted darunavir: Decreased plasma concentrations of omeprazole; no effect on darunavir concentrations217

Ritonavir-boosted darunavir: No dosage adjustments required349

Diazepam

Potential for prolonged diazepam elimination1 207

Digoxin

Increased digoxin bioavailability1

Hypomagnesemia (e.g., resulting from long-term use of proton-pump inhibitors) sensitizes the myocardium to digoxin and, thus, may increase risk of digoxin-induced cardiotoxic effects313 331

Monitor for manifestations of digoxin toxicity1

Consider monitoring magnesium concentrations prior to initiation of prescription proton-pump inhibitor therapy and periodically thereafter1 313

Disulfiram

Potential for altered disulfiram metabolism1 207

Monitor and adjust disulfiram dosage if needed1 207

Diuretics (i.e., loop or thiazide diuretics)

Possible increased risk of hypomagnesemia313

Consider monitoring magnesium concentrations prior to initiation of prescription proton-pump inhibitor therapy and periodically thereafter1 313

Fosamprenavir

Fosamprenavir with esomeprazole: Increased esomeprazole AUC; did not substantially alter concentrations of amprenavir (active metabolite of fosamprenavir)345

Ritonavir-boosted fosamprenavir with esomeprazole: Did not substantially affect amprenavir or esomeprazole concentrations345

No dosage adjustment required when proton-pump inhibitors used with fosamprenavir (with or without ritonavir)217 345

Gastric pH-dependent drugs (e.g., ampicillin esters, erlotinib, iron salts, ketoconazole)

Omeprazole may alter drug absorption1 207

Lopinavir

Lopinavir/ritonavir: No clinically important effect on lopinavir plasma concentrations or AUC217 344

Lopinavir/ritonavir: No dosage adjustment required when proton-pump inhibitors used concomitantly217

Methotrexate

Possible delayed clearance and increased serum concentrations of methotrexate and/or its metabolite hydroxymethotrexate; possible methotrexate toxicity1 333 334

Reported mainly with high-dose methotrexate (300 mg/m2 to 12 g/m2),1 333 but also reported with low dosages (e.g., 15 mg per week)333

Manufacturer of omeprazole recommends considering temporary discontinuance of proton-pump inhibitor therapy in some patients receiving high-dose methotrexate1

Some clinicians recommend withholding the proton-pump inhibitor for several days before and after administration of either high-dose or low-dose methotrexate or, alternatively, substituting a histamine H2-receptor antagonist for the proton-pump inhibitor333 334

Nelfinavir

Decreased peak serum concentrations and AUC of nelfinavir and its active metabolite1 207 347

Concomitant use not recommended1 207

Phenytoin

Potential for prolonged phenytoin elimination1 207

Raltegravir

Increased peak plasma concentration and AUC of raltegravir217 348

No dosage adjustment recommended217 348

Rifampin

Potential for decreased omeprazole concentrations1

Avoid concomitant use1

Rilpivirine

Decreased plasma concentrations and AUC of rilpivirine217 343

Concomitant use contraindicated217 343

Saquinavir

Ritonavir-boosted saquinavir: Increased peak serum concentrations and AUC of saquinavir1 207 217

Ritonavir-boosted saquinavir: Monitor for manifestations of saquinavir toxicity; consider reducing saquinavir dosage 1 207 217

St. John’s wort (Hypericum perforatum)

Decreased peak serum concentrations and AUC of omeprazole1

Avoid concomitant use1

Sucralfate

Possible delayed proton-pump inhibitor absorption and decreased bioavailability134

Administer proton-pump inhibitor at least 30 minutes before sucralfate134

Tacrolimus

Potential for increased tacrolimus concentrations1 207

Tests for neuroendocrine tumors

Increased serum chromogranin A (CgA) concentrations (secondary to omeprazole-induced increase in intragastric pH) may produce false-positive results1

Temporarily discontinue omeprazole before assessing CgA concentrations and consider repeating test if initial CgA concentrations are high1

Tipranavir

Ritonavir-boosted tipranavir: Decreased omeprazole plasma concentrations; no effect on tipranavir concentrations217

Ritonavir-boosted tipranavir: Increased omeprazole dosage may be required217

Voriconazole

Increased peak plasma concentrations and AUC of omeprazole1 207

Omeprazole dosage adjustment usually not required but may be considered in patients receiving high dosages (up to 240 mg daily), such as those with Zollinger-Ellison syndrome1 207

Warfarin

Potential for decreased warfarin metabolism and changes in prothrombin measures1 134 139 207

Monitor prothrombin time and INR1 134 139 207

Omeprazole Pharmacokinetics

Absorption

Bioavailability

Absolute bioavailability with 20–40 mg dose is about 30–40%.1 207 Bioavailability increases slightly with repeated dosing.1 207

Following administration of delayed-release oral suspension, peak concentration and AUC are 88 and 87%, respectively, of values achieved after oral administration of delayed-release capsules.1

In children 2–5 years of age, AUCs were lower than in children 6–16 years of age or in adults.1

Onset

Within 1 hour; maximum effect within 2 hours.1

Duration

Duration of secretion inhibition is up to 72 hours; inhibition is 50% of maximum at 24 hours.1 Inhibition increases with repeated daily dosing, reaching steady-state plateau at 4 days.1 After discontinuance, gastric secretion gradually increases over 3–5 days.1

Food

Rate of absorption is decreased with meals.3 5 Most effective given about 30 minutes before a meal;5 108 132 bioavailability may be unaffected if given up to 2 minutes before a meal.3

Administration of immediate-release oral suspension 1 hour after a meal decreases peak plasma concentrations (by 62%) and AUCs (by 26%).207 208

Special Populations

In patients with chronic hepatic disease, bioavailability is increased to 100% due to decreased first-pass effect.1 207

In Asians, AUCs increased 4-fold after a 20-mg dose.1 207

Distribution

Extent

Omeprazole crosses the placenta and is distributed into milk.1 139 202 207 209 210

Prolonged binding to gastric parietal proton pump enzyme.1 207

Plasma Protein Binding

95%.1 207

Elimination

Metabolism

Undergoes first-pass metabolism.1 207 Metabolized to inactive metabolites in the liver by CYP isoenzymes, principally CYP2C19, and to lesser extent by CYP3A4.1 139

Elimination Route

Excreted principally in urine (77%) as metabolites and to a lesser extent in feces.1 207

Half-life

0.5–1 hour.1 207

Special Populations

In patients with chronic hepatic disease, clearance is decreased, and plasma half-life is increased to almost 3 hours.1 207

Stability

Storage

Oral

Delayed-release Capsules

Tight, light-resistant containers at 15–30°C.1

Immediate-release Capsules

25°C (may be exposed to 15–30°C).207

Powder for Delayed-release or Immediate-release Suspension

Single-dose packets: 25°C (may be exposed to 15–30°C).1 207

Tablets for Self-medication

Tight containers at 20–25°C; protect from high heat, humidity, and moisture.187

Actions

  • Inhibits basal and stimulated gastric acid secretion.1 2 3 4 5 207

  • Concentrates in acid conditions of parietal cell secretory canaliculi; forms active sulfenamide metabolite that irreversibly binds to and inactivates hydrogen-potassium ATPase (proton- or acid pump),2 3 5 132 blocking final step in secretion of hydrochloric acid.1 2 3 4 5 8 132 207 Acid secretion inhibited until additional hydrogen-potassium ATPase is synthesized, resulting in prolonged duration of action.2 3 4 5 8 132

  • Suppresses H. pylori in patients with duodenal ulcer and/or reflux esophagitis infected with the organism.2 Combined therapy with omeprazole and 1 or more appropriate anti-infectives (e.g., amoxicillin, clarithromycin) can effectively eradicate H. pylori gastric infection.1 2 67 98 138

Advice to Patients

  • Importance of swallowing delayed-release capsule intact, without crushing or chewing.1 Importance of taking delayed-release capsule at least 1 hour before a meal.1

  • If mixed with applesauce, importance of mixing delayed-release capsule contents with applesauce soft enough to swallow without chewing.1 Importance of not using hot applesauce.1 Importance of immediately swallowing mixture with a glass of cool water, without crushing or chewing; importance of not storing for later use.1

  • Importance of swallowing immediate-release capsule intact with water and not with other fluid.207 Importance of not opening capsule or mixing the contents with food.207

  • Importance of taking immediate-release capsule and oral suspension at least 1 hour before a meal.207 208

  • Importance of not substituting two 20-mg immediate-release capsules for one 40-mg capsule or two 20-mg powder for immediate-release oral suspension packets for one 40-mg packet.207

  • Importance of mixing powder for oral suspension in small cup with water, not with other fluids or food.1 207 208 Importance of swallowing suspension immediately, then refilling cup with water and swallowing to ensure complete ingestion of dose.1 207 208

  • Possible increased risk of Clostridium difficile infection; importance of contacting a clinician if persistent watery stools, abdominal pain, and fever occur.335

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1 Antacids may be used concomitantly with delayed-release capsules or oral suspension as needed for pain relief.1 Antacids, antacids/alginic acid combinations, histamine H2-receptor antagonists, or histamine H2-receptor antagonist and antacid combinations may be used in conjunction with immediate-release oral suspension for “breakthrough” symptoms.208

  • Importance of advising patients that use of multiple daily doses of the drug for an extended period of time may increase the risk of fractures of the hip, wrist, or spine.1 305

  • Risk of hypomagnesemia; importance of immediately reporting and seeking care for any cardiovascular or neurologic manifestations (e.g., palpitations, dizziness, seizures, tetany).1 207

  • Importance of women informing their clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of following dosage instructions when omeprazole magnesium is administered for self-medication.187 188 Advise patients that they should use the drug for self-medication only as directed for no longer than 14 days of continuous use and that they should not exceed one course of therapy every 4 months.305

  • Importance of discontinuing use as self-medication and consulting a clinician if heartburn persists or worsens, use of the drug for >14 days is needed, or >1 course of therapy is required every 4 months.187

  • Self-medication with omeprazole magnesium is not intended for immediate relief of heartburn; may relieve symptoms within 24 hours, but 1–4 days may be required for complete relief.187 188 189 Not intended to treat occasional (e.g., occurring once weekly or less) symptoms or to prevent occasional meal- or beverage-induced heartburn.187 189

  • Advise patients to consult their clinician before using omeprazole magnesium for self-medication if they have had heartburn for >3 months or are experiencing heartburn with lightheadedness, dizziness, or sweating; chest or shoulder pain with shortness of breath, sweating, lightheadedness, or pain spreading to the arms, neck, or shoulders; frequent chest pain; frequent wheezing (especially with heartburn); unexplained weight loss; nausea or vomiting; or stomach pain.187

  • Advise patients not to use omeprazole magnesium for self-medication and to consult a clinician if they have difficulty or pain with swallowing, are vomiting blood, or have bloody or blackened stools.187

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Omeprazole

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

20 mg

Zegerid

Santarus

40 mg

Zegerid

Santarus

Capsules, delayed-release (containing enteric-coated granules)

10 mg*

Omeprazole Delayed-release Capsules

Prilosec

AstraZeneca

20 mg*

Omeprazole Delayed-release Capsules

Prilosec

AstraZeneca

40 mg*

Omeprazole Delayed-release Capsules

Prilosec

AstraZeneca

For suspension, powder

20 mg/packet

Zegerid

Santarus

40 mg/packet

Zegerid

Santarus

Omeprazole Magnesium

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

For suspension, delayed-release (containing enteric-coated granules)

2.5 mg (of omeprazole) per packet

Prilosec

AstraZeneca

10 mg (of omeprazole) per packet

Prilosec

AstraZeneca

Tablets, delayed-release

20 mg (of omeprazole)

Prilosec OTC

Procter & Gamble

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2013. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Omeprazole 10MG Delayed-release Capsules (KREMERS URBAN): 30/$34.99 or 90/$88.96

Omeprazole 20MG Delayed-release Capsules (SANDOZ): 90/$99.97 or 180/$186.01

Omeprazole 20MG Enteric-coated Tablets (MAJOR PHARMACEUTICALS): 14/$19.99 or 28/$29.99

Omeprazole 40MG Delayed-release Capsules (WATSON LABS): 30/$195.00 or 90/$524.95

PriLOSEC 10MG Delayed-release Capsules (ASTRAZENECA LP): 30/$170.99 or 90/$490.95

PriLOSEC 20MG Delayed-release Capsules (ASTRAZENECA LP): 30/$195.99 or 90/$555.96

PriLOSEC 40MG Delayed-release Capsules (ASTRAZENECA LP): 30/$291.00 or 90/$813.94

PriLOSEC OTC 20MG Enteric-coated Tablets (P &amp; G HEALTH): 14/$21.99 or 42/$45.97

Zegerid 20-1680MG Packet (SANTARUS): 30/$282.14 or 90/$815.06

Zegerid 40-1100MG Capsules (SANTARUS): 30/$298.94 or 90/$850.89

Zegerid 40-1680MG Packet (SANTARUS): 30/$296.69 or 90/$844.25

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2013, Selected Revisions February 15, 2013. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

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107. Sung JJY, Chung SCS, Ling TKW et al. Dual therapy versus triple therapy for Helicobacter pylori-associated duodenal ulcers. Dig Dis Sci. 1996; 41:453-7. [IDIS 365161] [PubMed 8617114]

108. Soll AH. Medical treatment of peptic ulcer disease. JAMA. 1996; 275:622-9. [IDIS 361115] [PubMed 8594244]

109. Soll AH. Practice guidelines for treatment of peptic ulcer disease. JAMA. 1996; 276:1136-7.

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115. Lind T, Veldhuyzen van Zanten S, Unge P et al. Eradication of Helicobacter pylori using one-week triple therapies combining omeprazole with two antimicrobials: the MACH I study. Helicobacter. 1996; 1:138-44. [PubMed 9398894]

116. Anon. The choice of antibacterial drugs. Med Lett Drugs Ther. 1996; 38:25-34. [PubMed 8598824]

117. Graham DY, Go MF. Evaluation of new antiinfective drugs for Helicobacter pylori infection: revisited and updated. Clin Infect Dis. 1993; 17:293-4. [PubMed 8399892]

118. Murray DM, DuPont HL. Reply. (Evaluation of new antiinfective drugs for Helicobacter pylori infection: revisited and updated.) Clin Infect Dis. 1993; 17:294-5.

119. George LL, Borody TJ, Andrews P et al. Cure of duodenal ulcer after eradication of H. pylori. Med J Aust. 1990; 153:145-9. [IDIS 273364] [PubMed 1974027]

120. Farrell MK. Dr. Apley meets Helicobacter pylori. J Pediatr Gastroenterol Nutr. 1993; 16:118-9. [PubMed 8450375]

121. Fiocca R, Solcia E, Santoro B. Duodenal ulcer relapse after eradication of Helicobacter pylori. Lancet. 1991; 337:1614. [PubMed 1675746]

122. Marshall BJ. Campylobacter pylori: its link to gastritis and peptic ulcer disease. Clin Infect Dis. 1990; 12(Suppl 1):S87-93.

123. Graham DY, Lew GM, Klein PD et al. Effect of treatment of Helicobacter pylori infection on the long-term recurrence of gastric or duodenal ulcer. A randomized, controlled study. Ann Intern Med. 1992; 116:705-8. [IDIS 295138] [PubMed 1558340]

124. Cutler AF, Schubert TT. Patient factors affecting Helicobacter pylori eradication with triple therapy. Am J Gastroenterol. 1993; 88:505-9. [IDIS 313343] [PubMed 8470629]

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343. Tibotec Therapeutics. Edurant (rilpivirine) tablets prescribing information. Raritan, NJ; 2011 May.

344. Abbott Laboratories. Kaletra (lopinavir/ritonavir) oral tablets and solution prescribing information. North Chicago, IL; 2012 May.

345. ViiV Healthcare. Lexiva (fosamprenavir calcium) tablets and oral suspension prescribing information. Research Triangle Park, NC; 2012 Apr.

347. ViiV Healthcare. Viracept (nelfinavir mesylate) tablets and oral powder prescribing information. Research Triangle Park, NC; 2012 Apr.

348. Merck Sharp & Dohme. Isentress (raltegravir) film-coated tablets and chewable tablets prescribing information. Whitehouse Station, NJ; 2012 Apr.

349. Janssen. Prezista (darunavir) prescribing information. Titusville, NJ; 2012 Jun.

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