Omeprazole

Prilosec, Zegerid, Prilosec OTC, Zegerid OTC

The active ingredient in PRILOSEC (omeprazole) Delayed-Release Capsules is a substituted benzimidazole, 5-methoxy-2-[[(4-methoxy-3, 5-dimethyl-2-pyridinyl) methyl] sulfinyl]-1H-benzimidazole, a compound that inhibits gastric acid secretion. Its empirical formula is C17H19N3O3S, with a molecular weight of 345.42. The structural formula is:

Omeprazole is a white to off-white crystalline powder that melts with decomposition at about 155°C. It is a weak base, freely soluble in ethanol and methanol, and slightly soluble in acetone and isopropanol and very slightly soluble in water. The stability of omeprazole is a function of pH; it is rapidly degraded in acid media, but has acceptable stability under alkaline conditions.

The active ingredient in PRILOSEC (omeprazole magnesium) for Delayed-Release Oral Suspension, is 5-Methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazole, magnesium salt (2:1)

Omeprazole magnesium is a white to off white powder with a melting point with degradation at 200°C. The salt is slightly soluble (0.25 mg/mL) in water at 25°C, and it is soluble in methanol. The half-life is highly pH dependent.

The empirical formula for omeprazole magnesium is (C17H18N3O3S)2 Mg, the molecular weight is 713.12 and the structural formula is:

PRILOSEC is supplied as delayed-release capsules for oral administration. Each delayed-release capsule contains either 10 mg, 20 mg or 40 mg of omeprazole in the form of enteric-coated granules with the following inactive ingredients: cellulose, disodium hydrogen phosphate, hydroxypropyl cellulose, hypromellose, lactose, mannitol, sodium lauryl sulfate and other ingredients. The capsule shells have the following inactive ingredients: gelatin-NF, FD&C Blue #1, FD&C Red #40, D&C Red #28, titanium dioxide, synthetic black iron oxide, isopropanol, butyl alcohol, FD&C Blue #2, D&C Red #7 Calcium Lake, and, in addition, the 10 mg and 40 mg capsule shells also contain D&C Yellow #10.

Each packet of PRILOSEC For Delayed-Release Oral Suspension contains either 2.8 mg or 11.2 mg of omeprazole magnesium (equivalent to 2.5 mg or 10 mg of omeprazole), in the form of enteric-coated granules with the following inactive ingredients: glyceryl monostearate, hydroxypropyl cellulose, hypromellose, magnesium stearate, methacrylic acid copolymer C, polysorbate, sugar spheres, talc, and triethyl citrate, and also inactive granules. The inactive granules are composed of the following ingredients: citric acid, crospovidone, dextrose, hydroxypropyl cellulose, iron oxide and xantham gum. The omeprazole granules and inactive granules are constituted with water to form a suspension and are given by oral, nasogastric or direct gastric administration.

Dosage Forms And Strengths

PRILOSEC Delayed-Release Capsules, 10 mg, are opaque, hard gelatin, apricot and amethyst colored capsules, coded 606 on cap and PRILOSEC 10 on the body.

PRILOSEC Delayed-Release Capsules, 20 mg, are opaque, hard gelatin, amethyst colored capsules, coded 742 on cap and PRILOSEC 20 on the body.

PRILOSEC Delayed-Release Capsules, 40 mg, are opaque, hard gelatin, apricot and amethyst colored capsules, coded 743 on cap and PRILOSEC 40 on the body.

PRILOSEC For Delayed-Release Oral Suspension, 2.5 mg or 10 mg, is supplied as a unit dose packet containing a fine yellow powder, consisting of white to brownish omeprazole granules and pale yellow inactive granules.

Storage And Handling

PRILOSEC Delayed-Release Capsules, 10 mg, are opaque, hard gelatin, apricot and amethyst colored capsules, coded 606 on cap and PRILOSEC 10 on the body. They are supplied as follows:

NDC 0186-0606-31 unit of use bottles of 30

PRILOSEC Delayed-Release Capsules, 20 mg, are opaque, hard gelatin, amethyst colored capsules, coded 742 on cap and PRILOSEC 20 on body. They are supplied as follows:

NDC 0186-0742-31 unit of use bottles of 30
NDC 0186-0742-82 bottles of 1000

PRILOSEC Delayed-Release Capsules, 40 mg, are opaque, hard gelatin, apricot and amethyst colored capsules, coded 743 on cap and PRILOSEC 40 on the body. They are supplied as follows:

NDC 0186-0743-31 unit of use bottles of 30
NDC 0186-0743-68 bottles of 100

PRILOSEC For Delayed-Release Oral Suspension, 2.5 mg or 10 mg, is supplied as a unit dose packet containing a fine yellow powder, consisting of white to brownish omeprazole granules and pale yellow inactive granules. PRILOSEC unit dose packets are supplied as follows:

NDC 0186-0625-01 unit dose packages of 30: 2.5 mg packets
NDC 0186-0610-01 unit dose packages of 30: 10 mg packets

Storage

Store PRILOSEC Delayed-Release Capsules in a tight container protected from light and moisture. Store between 15°C and 30°C (59°F and 86°F).

Store PRILOSEC For Delayed-Release Oral Suspension at 25°C (77°F); excursions permitted to 15 – 30°C (59 – 86°F). [See USP Controlled Room Temperature]

AstraZeneca Pharmaceuticals LP Wilmington, DE 19850. Revised December 2014

Heartburn is often confused with the first symptoms of a heart attack. Seek emergency medical attention if you have chest pain or heavy feeling, pain spreading to the arm or shoulder, nausea, sweating, and a general ill feeling.

You should not take this medication if you are allergic to omeprazole or to any other benzimidazole medication such as albendazole or mebendazole.

Ask a doctor or pharmacist if it is safe for you to take omeprazole if you have liver disease or heart disease, or if you have low levels of magnesium in your blood.

Do not use over-the-counter omeprazole (Prilosec OTC) without the advice of a doctor if you have:

• trouble or pain with swallowing;
• bloody or black stools;
• vomit that looks like blood or coffee grounds;
• heartburn that has lasted for over 3 months;
• frequent chest pain;
• heartburn with wheezing;
• unexplained weight loss;
• osteoporosis, low bone mineral density;
• nausea or vomiting; or
• stomach pain.

Some people taking omeprazole may have an increased risk of bone fracture in the hip, wrist, or spine. This effect has occurred mostly in people taking omeprazole long term or at high doses, and in people who are age 50 and older. Omeprazole may not be the actual cause of increased fracture risk. Before you take this medication, tell your doctor if you have a bone disorder.

Some conditions are treated with a combination of omeprazole and antibiotics. Use all medications as directed by your doctor. Read the medication guide or patient instructions provided with each medication. Do not change your doses or medication schedule without your doctor's advice.

FDA pregnancy category C. It is not known whether omeprazole will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication.

Omeprazole can pass into breast milk and may harm a nursing baby. You should not breast-feed while you are taking omeprazole.

Do not give this medication to a child younger than 1 year old without the advice of a doctor.

Omeprazole is both an over-the-counter and a prescription medication. The over-the-counter form is used to treat heartburn. The prescription form is used to treat gastroesophageal reflux disease (GERD), certain ulcers, Zollinger-Ellison Syndrome, erosive esophagitis (EE), and infections cause by the bacteria H. pylori. This medication page refers to the prescription form of omeprazole.

Omeprazole belongs to a group of drugs called proton-pump inhibitors, which work by reducing the amount of acid made in the stomach.

This medication comes in delayed capsule form and in packets to be mixed with water to form a liquid (suspension). It is taken once or twice daily, one hour before a meal.

Common side effects of omeprazole include constipation, gas, nausea, vomiting, and headache.

Omeprazole can cause dizziness, drowsiness, and blurred vision. Do not drive or operate heavy machinery until you know how omeprazole affects you.

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X - are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Omeprazole falls into category C. There are no good studies that have been done in humans with omeprazole. In animals, pregnant animals were given this medication and had some babies born with problems. However, this medication may sometimes still help human mothers and their babies more than it might cause harm.

Take omeprazole exactly as prescribed.

This medication comes in delayed capsule form and in packets to be mixed with water to form a liquid (suspension). It is taken once or twice daily, one hour before a meal.

Swallow omeprazole capsules whole. Never chew or crush omeprazole capsules.

If you have difficulty swallowing omeprazole capsules, you may open the capsule and empty the contents into a tablespoon of applesauce. Be sure to swallow the applesauce right away. Do not store it for later use.

If you miss a dose, take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and take your next dose at the regular time. Do not take 2 doses of omeprazole at the same time.

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

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

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

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

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For omeprazole, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to omeprazole or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of omeprazole in children 1 to 16 years of age. Safety and efficacy have not been established in children younger than 1 month of age. .

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of omeprazole in the elderly.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking omeprazole, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using omeprazole with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Rilpivirine

Using omeprazole with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Atazanavir
• Bendamustine
• Bosutinib
• Cilostazol
• Citalopram
• Clopidogrel
• Clorazepate
• Conivaptan
• Dasabuvir
• Dasatinib
• Delavirdine
• Erlotinib
• Escitalopram
• Eslicarbazepine Acetate
• Gefitinib
• Indinavir
• Ketoconazole
• Ledipasvir
• Methotrexate
• Mycophenolate Mofetil
• Mycophenolic Acid
• Nelfinavir
• Netupitant
• Nilotinib
• Ombitasvir
• Paritaprevir
• Pazopanib
• Ritonavir
• Saquinavir
• Tacrolimus
• Velpatasvir
• Vismodegib
• Voriconazole

Using omeprazole with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Armodafinil
• Carbamazepine
• Digoxin
• Disulfiram
• Fluconazole
• Ginkgo Biloba
• Iron
• Levothyroxine
• Raltegravir
• St John's Wort
• Tipranavir
• Triazolam
• Warfarin

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using omeprazole with any of the following may cause an increased risk of certain side effects but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use omeprazole, or give you special instructions about the use of food, alcohol, or tobacco.

• Cranberry

Other Medical Problems

The presence of other medical problems may affect the use of omeprazole. Make sure you tell your doctor if you have any other medical problems, especially:

• Diarrhea or
• Hypomagnesemia (low magnesium in the blood), history of or
• Osteoporosis (bone problem) or
• Seizures, history of or
• Systemic lupus erythematosus (SLE)—Use with caution. May make these conditions worse.

• Liver disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

• Omeprazole Magnesium

Stress ulcer prophylaxis in the critically-ill patient

Data from a prospective randomized clinical trial in patients at high risk for stress ulcer prophylaxis administered either omeprazole or IV ranitidine, supports the use of omeprazole for the prevention of stress ulcers [Levy 1997]. Additional trials may be necessary to further define the role of omeprazole in this setting.

Based on the 2012 Surviving Sepsis Campaign Guidelines, the use of proton pump inhibitors (PPIs) is effective and recommended in the prevention of stress ulcer in the critically-ill patient with severe sepsis/septic shock when bleeding risk factors exist. The 1999 ASHP Stress Ulcer Prophylaxis guidelines recommends 40 mg loading dose followed by 20 to 40 mg once daily administered orally or via NG tube [ASHP 1999]. However, data from an open-label intragastric pH study demonstrated that 20 mg once daily via NG tube may be less effective than the 40 mg dose in some critically ill populations [Balaban 1997].

Additional Off-Label Uses

Healing NSAID-induced ulcers; Prevention of NSAID-induced ulcer

Granules for oral suspension: For oral administration, empty the contents of the 2.5 mg packet into 5 mL of water (10 mg packet into 15 mL of water); stir. For NG administration, add 5 mL of water into a catheter-tipped syringe, and then add the contents of a 2.5 mg packet (15 mL water for the 10 mg packet); immediately shake syringe. Note: Regardless of the route of administration, the suspension should be left to thicken for 2 to 3 minutes prior to administration.

Concerns related to adverse effects:

• Carcinoma: In long-term (2-year) studies in rats, omeprazole produced a dose-related increase in gastric carcinoid tumors. While available endoscopic evaluations and histologic examinations of biopsy specimens from human stomachs have not detected a risk from short-term exposure to omeprazole, further human data on the effect of sustained hypochlorhydria and hypergastrinemia are needed to rule out the possibility of an increased risk for the development of tumors in humans receiving long-term therapy.

• Clostridium difficile-associated diarrhea (CDAD): Use of proton pump inhibitors (PPIs) may increase risk of CDAD, especially in hospitalized patients; consider CDAD diagnosis in patients with persistent diarrhea that does not improve. Use the lowest dose and shortest duration of PPI therapy appropriate for the condition being treated.

• Cutaneous and systemic lupus erythematosus: Has been reported as new onset or exacerbation of existing autoimmune disease; most cases were cutaneous lupus erythematosus (CLE), most commonly, subacute CLE (occurring within weeks to years after continuous therapy). Systemic lupus erythematosus (SLE) is less common (typically occurs within days to years after initiating treatment) and occurred primarily in young adults up to the elderly. Discontinue therapy if signs or symptoms of CLE or SLE occur and refer to specialist for evaluation; most patients improve 4 to 12 weeks after discontinuation of omeprazole.

• Fractures: Increased incidence of osteoporosis-related bone fractures of the hip, spine, or wrist may occur with proton pump inhibitor (PPI) therapy. Patients on high-dose (multiple daily doses) or long-term (≥1 year) therapy should be monitored. Use the lowest effective dose for the shortest duration of time, use vitamin D and calcium supplementation, and follow appropriate guidelines to reduce risk of fractures in patients at risk.

• Hypomagnesemia: Reported rarely, usually with prolonged PPI use of ≥3 months (most cases >1 year of therapy). May be symptomatic or asymptomatic; severe cases may cause tetany, seizures, and cardiac arrhythmias. Consider obtaining serum magnesium concentrations prior to beginning long-term therapy, especially if taking concomitant digoxin, diuretics, or other drugs known to cause hypomagnesemia; and periodically thereafter. Hypomagnesemia may be corrected by magnesium supplementation, although discontinuation of omeprazole may be necessary; magnesium levels typically return to normal within 1 week of stopping.

• Interstitial nephritis: Acute interstitial nephritis has been observed in patients taking PPIs; may occur at any time during therapy and is generally due to an idiopathic hypersensitivity reaction. Discontinue if acute interstitial nephritis develops.

• Vitamin B12 deficiency: Prolonged treatment (>3 years) may lead to vitamin B12 malabsorption and subsequent vitamin B12 deficiency. The magnitude of the deficiency is dose-related and the association is stronger in females and those younger in age (<30 years); prevalence is decreased after discontinuation of therapy (Lam, 2013).

Disease-related concerns:

• Gastric malignancy: Relief of symptoms does not preclude the presence of a gastric malignancy.

• Gastrointestinal infection (eg, Salmonella, Campylobacter): Use of PPIs may increase risk of these infections.

• Hepatic impairment: In patients with hepatic impairment (Child-Pugh class A, B, or C) exposure to omeprazole is increased; dosage reduction is recommended.

Concurrent drug therapy issues:

• Clopidogrel: Proton pump inhibitors (PPIs) may diminish the therapeutic effect of clopidogrel, thought to be due to reduced formation of the active metabolite of clopidogrel. The manufacturer of clopidogrel recommends either avoidance of both omeprazole (even when scheduled 12 hours apart) and esomeprazole or use of a PPI with comparatively less effect on the active metabolite of clopidogrel (eg, pantoprazole). In contrast to these warnings, others have recommended the continued use of PPIs, regardless of the degree of inhibition, in patients with a history of GI bleeding or multiple risk factors for GI bleeding who are also receiving clopidogrel since no evidence has established clinically meaningful differences in outcome; however, a clinically significant interaction cannot be excluded in those who are poor metabolizers of clopidogrel (Abraham, 2010; Levine, 2011).

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Asian ethnicity: Bioavailability is increased in patients of Asian descent; dosage reduction is recommended for maintenance healing of erosive esophagitis.

• Elderly: Bioavailability may be increased in the elderly.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC, 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors, 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer’s labeling.

Other warnings/precautions:

• Appropriate use: Helicobacter pylori eradication: Short-term combination therapy (≤7 days) has been associated with a higher incidence of treatment failure. The American College of Gastroenterology recommends 10 to 14 days of therapy (triple or quadruple) for eradication of H. pylori (Chey, 2007).

• Laboratory test interference: Serum chromogranin A (CgA) levels increase secondary to drug-induced decreases in gastric acid; may cause false-positive results in diagnostic investigations for neuroendocrine tumors. Temporarily stop omeprazole treatment at least 14 days before CgA test; if initial CgA levels are high, repeat test to confirm. Use same commercial laboratory for testing to prevent variable results.

• Self-medication (OTC use): When used for self-medication (OTC), notify health care provider before use if any of the following are present: heartburn for >3 months; frequent wheezing, particularly with heartburn; unexplained weight loss; nausea or vomiting; or stomach pain. Discontinue use and notify health care provider if heartburn continues or worsens; diarrhea occurs; if >14 days of therapy is needed; or if >1 course of therapy is needed every 4 months.

An increased risk of hypospadias was reported following maternal use of proton pump inhibitors (PPIs) during pregnancy (Anderka 2012), but this was based on a small number of exposures and the same association was not found in another study (Erichsen 2012). Most available studies have not shown an increased risk of major birth defects following maternal use of omeprazole during pregnancy (Diav-Citrin 2005; Källén 2001; Lalkin 1998; Matok 2012; Pasternak 2010). When treating GERD in pregnancy, PPIs may be used when clinically indicated (ACT [Katz 2013]).

Keep these considerations in mind if your doctor prescribes omeprazole oral capsule sprinkles for you.

General

• Take this drug at the time(s) recommended by your doctor, at least 1 hour before a meal.
• Don’t chew or crush the capsules. You should swallow capsules whole. If you have trouble swallowing it, you can open the capsule and empty its contents (pellets) onto 1 tablespoon of applesauce. Mix the pellets with the applesauce. Swallow the mixture right away with a glass of cool water. Don’t chew or crush the pellets. Don’t store the mixture for later use.
• Not every pharmacy stocks this drug. When filling your prescription, be sure to call ahead.

Storage

• Delayed-release oral capsule:
  • Store the delayed-release oral capsules at room temperature. Keep them between 59°F and 86°F (15°C and 30°C).
  • Keep this medication away from light.
  • Don’t store this medication in moist or damp areas, such as bathrooms.
• Delayed-release oral suspension:
  • Store the oral suspension at room temperature at 77°F (25°C). You can store it briefly between 59°F and 86°F (15°C and 30°C).

Refills

A prescription for this medication is refillable. You should not need a new prescription for this medication to be refilled. Your doctor will write the number of refills authorized on your prescription.

Travel

When traveling with your medication:

• Always carry your medication with you. When flying, never put it into a checked bag. Keep it in your carry-on bag.
• Don’t worry about airport x-ray machines. They can’t hurt your medication.
• You may need to show airport staff the pharmacy label for your medication. Always carry the original prescription-labeled box with you.
• Don’t put this medication in your car’s glove compartment or leave it in the car. Be sure to avoid doing this when the weather is very hot or very cold.

Self-management

Your doctor or pharmacist will show you how to take the oral suspension. The oral suspension may also be given through a nasogastric tube or gastric tube as prescribed by your doctor. Talk to your doctor or pharmacist about how to give the oral suspension through a tube.

Clinical monitoring

Your doctor should monitor certain health issues. This can help make sure you stay safe while you take this drug. These issues include:

• Liver function. Your doctor may do blood tests to check how well your liver is working. If your liver isn’t working well, your doctor may lower your dose of this drug.
• Magnesium levels. Your doctor may do blood tests to check how high your magnesium levels are. If your magnesium levels are too high, your doctor may lower your dose or have you stop taking this drug.

Insurance

Many insurance companies require a prior authorization for this drug. This means your doctor will need to get approval from your insurance company before your insurance company will pay for the prescription.