HIGHLIGHTS OF PRESCRIBING INFORMATION

United States - English - NLM (National Library of Medicine)

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Active ingredient:
OMEPRAZOLE (UNII: KG60484QX9) (OMEPRAZOLE - UNII:KG60484QX9)
Available from:
Golden State Medical Supply, Inc.
INN (International Name):
OMEPRAZOLE
Composition:
OMEPRAZOLE 20 mg
Administration route:
ORAL
Prescription type:
PRESCRIPTION DRUG
Therapeutic indications:
Omeprazole delayed-release capsules are indicated for short-term treatment of active duodenal ulcer in adults. Most patients heal within four weeks. Some patients may require an additional four weeks of therapy. Eradication of H. pylori has been shown to reduce the risk of duodenal ulcer recurrence. Omeprazole delayed-release capsules in combination with clarithromycin and amoxicillin, is indicated for treatment of patients with H. pylori infection and duodenal ulcer disease (active or up to 1-year history) to eradicate H. pylori in adults. Omeprazole delayed-release capsules in combination with clarithromycin is indicated for treatment of patients with H. pylori infection and duodenal ulcer disease to eradicate H. pylori in adults. Among patients who fail therapy, omeprazole delayed-release capsules with clarithromycin are more likely to be associated with the development of clarithromycin resistance as compared with trip
Product summary:
Omeprazole Delayed-Release Capsules, USP are available containing 20 mg or 40 mg of omeprazole, USP. The 20 mg capsules are hard-shell gelatin capsules with a dark green opaque cap and a blue-green opaque body filled with white to off-white beads. The capsule is axially printed with MYLAN over 6150 in white ink both on the cap and the body. They are available as follows: NDC 60429-270-90 bottles of 90 capsules NDC 60429-270-10 bottles of 1000 capsules The 40 mg capsules are hard-shell gelatin capsules with a dark green opaque cap and a light-blue opaque body filled with white to off-white beads. The capsule is axially printed with MYLAN over 5222 in white ink both on the cap and the body. They are available as follows: NDC 60429-271-90 bottles of 90 capsules NDC 60429-271-05 bottles of 500 capsules Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Protect from light and moisture. Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure. PHARMACIST: Dispense a Medication Guide with each prescription.
Authorization status:
Abbreviated New Drug Application
Authorization number:
60429-270-10, 60429-270-90, 60429-271-05, 60429-271-90

Golden State Medical Supply, Inc.

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Medication Guide

Omeprazole Delayed-Release Capsules, USP

(oh mep' ra zole)

Read this Medication Guide before you start taking omeprazole delayed-release capsules and each time you

get a refill. There may be new information. This information does not take the place of talking with your

doctor about your medical condition or your treatment.

What is the most important information I should know about omeprazole delayed-release capsules?

Omeprazole delayed-release capsules may help your acid-related symptoms, but you could still have serious

stomach problems. Talk with your doctor.

Omeprazole delayed-release capsules can cause serious side effects, including:

A type of kidney problem (acute interstitial nephritis). Some people who take proton pump inhibitor

(PPI) medicines, including omeprazole delayed-release capsules, may develop a kidney problem

called acute interstitial nephritis that can happen at any time during treatment with omeprazole

delayed-release capsules. Call your doctor if you have a decrease in the amount that you urinate or if

you have blood in your urine.

Diarrhea. Omeprazole delayed-release capsules may increase your risk of getting severe diarrhea.

This diarrhea may be caused by an infection ( Clostridium difficile) in your intestines. Call your

doctor right away if you have watery stool, stomach pain, and fever that does not go away.

Bone fractures. People who take multiple daily doses of PPI medicines for a long period of time (a

year or longer) may have an increased risk of fractures of the hip, wrist, or spine. You should take

omeprazole delayed-release capsules exactly as prescribed, at the lowest dose possible for your

treatment and for the shortest time needed. Talk to your doctor about your risk of bone fracture if you

take omeprazole delayed-release capsules.

Certain types of lupus erythematosus. Lupus erythematosus is an autoimmune disorder (the body’s

immune cells attack other cells or organs in the body). Some people who take PPI medicines,

including omeprazole delayed-release capsules, may develop certain types of lupus erythematosus or

have worsening of the lupus they already have. Call your doctor right away if you have new or

worsening joint pain or a rash on your cheeks or arms that gets worse in the sun.

Omeprazole delayed-release capsules can have other serious side effects. See “What are the possible side

effects of omeprazole delayed-release capsules?”

What are omeprazole delayed-release capsules?

Omeprazole delayed-release capsules are a prescription medicine called a proton pump inhibitor (PPI).

Omeprazole delayed-release capsules reduce the amount of acid in your stomach.

Omeprazole delayed-release capsules are used in adults:

for up to 8 weeks for the healing of duodenal ulcers. The duodenal area is the area where food passes

when it leaves the stomach.

with certain antibiotics for 10 to 14 days to treat an infection caused by bacteria called H. pylori. If

needed, your doctor may decide to prescribe another 14 to 18 days of omeprazole delayed-release

capsules by itself after the antibiotics. Sometimes H. pylori bacteria can cause duodenal ulcers. The

infection needs to be treated to prevent the ulcers from coming back.

for up to 8 weeks for healing stomach ulcers.

for up to 4 weeks to treat heartburn and other symptoms that happen with gastroesophageal reflux

disease (GERD). GERD happens when acid in your stomach backs up into the tube (esophagus) that

connects your mouth to your stomach. This may cause a burning feeling in your chest or throat, sour

taste, or burping.

for up to 8 weeks to heal acid-related damage to the lining of the esophagus (called erosive

esophagitis or EE). If needed, your doctor may decide to prescribe another 4 weeks of omeprazole

delayed-release capsules.

to maintain healing of the esophagus. It is not known if omeprazole delayed-release capsules are safe

and effective when used for longer than 12 months (1 year) for this purpose.

for the long-term treatment of conditions where your stomach makes too much acid. This includes a

rare condition called Zollinger-Ellison syndrome.

For children 1 to 16 years of age, omeprazole delayed-release capsules are used:

for up to 4 weeks to treat heartburn and other symptoms that happen with gastroesophageal reflux

disease (GERD).

for up to 8 weeks to treat gastroesophageal reflux disease (GERD) with acid-related damage to the

lining of the esophagus [called erosive esophagitis (or EE) due to acid-mediated GERD].

to maintain healing of the esophagus. It is not known if omeprazole delayed-release capsules are safe

and effective when used longer than 12 months (1 year) for this purpose.

For children 1 month to less than 12 months (1 year) of age, omeprazole is used:

for up to 6 weeks to treat gastroesophageal reflux disease (GERD) with acid-related damage to the

lining of the esophagus [called erosive esophagitis (or EE) due to acid-mediated GERD]. It is not

known if omeprazole is safe and effective for other uses in children 1 month to less than 12 months

(1 year) of age, or in children less than 1 month of age.

Who should not take omeprazole delayed-release capsules?

Do not take omeprazole delayed-release capsules if you:

are allergic to omeprazole or any of the ingredients in omeprazole delayed-release capsules. See the

end of this Medication Guide for a complete list of ingredients in omeprazole delayed-release

capsules.

are allergic to any other proton pump inhibitor (PPI) medicine.

are taking a medicine that contains rilpivirine (EDURANT, COMPLERA) used to treat HIV-1

(Human Immunodeficiency Virus).

What should I tell my doctor before taking omeprazole delayed-release capsules?

Before taking omeprazole delayed-release capsules, tell your doctor about all of your medical conditions,

including if you:

have been told that you have low magnesium levels in your blood.

have liver problems.

have any other medical conditions.

are pregnant or plan to become pregnant. It is not known if omeprazole delayed-release capsules will

harm your unborn baby.

are breastfeeding or plan to breastfeed. Omeprazole passes into your breast milk. Talk to your doctor

about the best way to feed your baby if you take omeprazole delayed-release capsules.

Tell your doctor about all of the medicines you take including prescription and over-the-counter

medicines, vitamins and herbal supplements. Omeprazole delayed-release capsules may affect how

other medicines work, and other medicines may affect how omeprazole delayed-release capsules

work. Especially tell your doctor if you take an antibiotic that contains clarithromycin or amoxicillin,

or if you take clopidogrel (Plavix), methotrexate (Otrxup, Rasuvo, Trexall), St. John’s Wort

( Hypericum perforatum), or rifampin (Rimactane, Rifater, Rifamate).

Know the medicines that you take. Keep a list of them to show your doctor and pharmacist when you

get a new medicine.

How should I take omeprazole delayed-release capsules?

Take omeprazole delayed-release capsules exactly as prescribed by your doctor.

Do not change your dose or stop omeprazole delayed-release capsules without talking to your doctor.

Omeprazole delayed-release capsules are usually taken 1 time each day. Your doctor will tell you the

time of day to take omeprazole delayed-release capsules, based on your medical condition.

Take omeprazole delayed-release capsules before a meal.

Antacids may be taken with omeprazole delayed-release capsules.

OmeprazoleDelayed-Release Capsules

Swallow omeprazole delayed-release capsules whole. Do not chew or crush omeprazole delayed-

release capsules.

If you have trouble swallowing a whole capsule, you can open the capsule and take the contents in

applesauce. See the “Instructions for Use” at the end of this Medication Guide for instructions on

how to take omeprazole delayed-release capsules with applesauce.

If you miss a dose of omeprazole delayed-release capsules, take it as soon as you remember. If it is almost

time for your next dose, do not take the missed dose. Take the next dose at your regular time. Do not take 2

doses at the same time to make up for the missed dose.

If you take too many omeprazole delayed-release capsules, call your doctor or your poison control center at

1-800-222-1222 right away or go to the nearest emergency room.

What are the possible side effects of omeprazole delayed-release capsules?

Omeprazole delayed-release capsules can cause serious side effects, including:

See “What is the most important information I should know about omeprazole delayed-release

capsules?”

Vitamin B-12 deficiency. Omeprazole delayed-release capsules reduce the amount of acid in your

stomach. Stomach acid is needed to absorb vitamin B-12 properly. Talk with your doctor about the

possibility of vitamin B-12 deficiency if you have been on omeprazole delayed-release capsules for a

long time (more than 3 years).

Low magnesium levels in your body. This problem can be serious. Low magnesium can happen in

some people who take a PPI medicine for at least 3 months. If low magnesium levels happen, it is

usually after a year of treatment.

You may or may not have symptoms of low magnesium. Tell your doctor right away if you develop any of

these symptoms:

seizures

dizziness

abnormal or fast heart beat

jitteriness

jerking movements or shaking (tremors)

muscle weakness

spasms of the hands and feet

cramps or muscle aches

spasm of the voice box

Your doctor may check the level of magnesium in your body before you start taking omeprazole delayed-

release capsules or during treatment if you will be taking omeprazole delayed-release capsules for a long

period of time.

Low Stomach growths (fundic gland polyps). People who take PPI medicines for a long time have an

increased risk of developing a certain type of stomach growths called fundic gland polyps, especially

after taking PPI medicines for more than 1 year.

The most common side effects with omeprazole delayed-release capsules in adults and children include:

headache

stomach pain

nausea

diarrhea

vomiting

In addition to the side effects listed above, the most common side effects in children 1 to 16 years of age

include:

respiratory system events

fever

Other side effects:

Serious allergic reactions. Tell your doctor if you get any of the following symptoms with omeprazole

delayed-release capsules:

rash

throat tightness

face swelling

difficulty breathing

Your doctor may stop omeprazole delayed-release capsules if these symptoms happen. Tell your doctor if

you have any side effect that bothers you or that do not go away. These are not all the possible side effects

with omeprazole delayed-release capsules. For more information, ask your doctor or pharmacist. Call your

doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store omeprazole delayed-release capsules?

Store omeprazole delayed-release capsules at room temperature between 20° to 25°C (68° to 77°F).

Keep the container of omeprazole delayed-release capsules closed tightly.

Keep the container of omeprazole delayed-release capsules dry and away from light.

Keep omeprazole delayed-release capsules and all medicines out of the reach of children.

General information about the safe and effective use of omeprazole delayed-release capsules.

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use

omeprazole delayed-release capsules for a condition for which they were not prescribed. Do not give

omeprazole delayed-release capsules to other people, even if they have the same symptoms you have. They

may harm them.

This Medication Guide summarizes the most important information about omeprazole delayed-release

capsules. For more information, ask your doctor. You can ask your doctor or pharmacist for information that

is written for healthcare professionals.

What are the ingredients in omeprazole delayed-release capsules?

Active ingredient in omeprazole delayed-release capsules: omeprazole

Inactive ingredients in omeprazole delayed-release capsules: ammonium hydroxide, dibutyl sebacate, D&C

Yellow No. 10, FD&C Green No. 3, gelatin, ethylcellulose, fumed silica, hypromellose, methacrylic acid,

oleic acid, silicon dioxide, sodium lauryl sulfate, sugar spheres, talc, titanium dioxide and triethyl citrate.

The 40 mg empty gelatin capsule shell also contains FD&C Blue No. 1. In addition, the white imprinting ink

contains ammonium hydroxide, propylene glycol, shellac glaze, simethicone and titanium dioxide.

Manufactured for: Mylan Pharmaceuticals Inc., Morgantown, WV 26505 U.S.A.

Jointly Manufactured by: Mylan Pharmaceuticals Inc., Morgantown, WV 26505 U.S.A. and Laboratorios

Dr. Esteve, S.A.,08107 Martorelles (Barcelona), Spain

For more information, call Mylan at 1-877-446-3679 (1-877-4-INFO-RX).

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Instructions for Use

Omeprazole Delayed-Release Capsules, USP

(oh mep′ ra zole)

Omeprazole Delayed-Release Capsules: Taking omeprazole delayed-release capsules with applesauce:

Place 1 tablespoon of applesauce into a clean container.

Carefully open the capsule and sprinkle the pellets onto the applesauce. Mix the pellets with the

applesauce.

Swallow the applesauce and pellet mixture right away. Do not chew or crush the pellets. Do not store

the applesauce and pellet mixture for later use.

The brands listed are trademarks of their respective owners.

Jointly manufactured by:

Mylan Pharmaceuticals Inc.

Morgantown, WV 26505 U.S.A.

Laboratorios Dr. Esteve, S.A.

08107 Martorelles (Barcelona), Spain

Marketed/Packaged by:

GSMS, Inc.

Camarillo, CA USA 93012

Revised: 5/2018

OMEP:R32mpbmh

Revised: 12/2019

Document Id: 92c8082e-131d-4593-e053-2a95a90a91c1

34391-3

Set id: f26025f6-d093-4aad-8c3b-be0bde1d8032

Version: 6

Effective Time: 20191217

Golden State Medical Supply, Inc.

OMEPRAZOLE- omeprazole capsule, delayed release

Golden State Medical Supply, Inc.

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HIGHLIGHTS OF PRESCRIBING INFORMATION

OMEPRAZOLE DELAYED-RELEASE CAPSULES

These highlights do not include all the information needed to use OMEPRAZOLE DELAYED-RELEASE

CAPSULES safely and effectively. See full prescribing information for OMEPRAZOLE DELAYED-RELEASE

CAPSULES.

OMEPRAZOLE delayed-release capsules, for oral use

Initial U.S. Approval: 1989

RECENT MAJOR CHANGES

Warnings and Precautions, Fundic Gland Polyps ( 5.12) 5/2018

INDICATIONS AND USAGE

Omeprazole is a proton pump inhibitor (PPI) indicated for the:

Treatment of active duodenal ulcer in adults ( 1.1)

Eradication of Helicobacter pylori to reduce the risk of duodenal ulcer recurrence in adults ( 1.2)

Treatment of active benign gastric ulcer in adults ( 1.3)

Treatment of symptomatic gastroesophageal reflux disease (GERD) in patients 1 year of age and older ( 1.4)

Treatment of erosive esophagitis (EE) due to acid-mediated GERD in patients 1 month of age and older ( 1.5)

Maintenance of healing of EE due to acid-mediated GERD in patients 1 year of age and older ( 1.6)

Pathologic hypersecretory conditions in adults ( 1.7)

DOSAGE AND ADMINISTRATION

Indic atio n

Recommended Adult ( 2.1) and Pediatric Dosage ( 2.2)

Treatment of Active Duodenal Ulcer

20 mg once daily for 4 weeks; some patients may require an

additional 4 weeks ( 2.1)

H. pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence

Triple Therapy:

Omeprazole Delayed-Release Capsules

Amoxicillin

Clarithromycin

20 mg

1000 mg

500 mg

Each drug twice daily for 10 days ( 2.1)*

Dual Therapy:

Omeprazole Delayed-Release Capsules

Clarithromycin

40 mg once daily for 14 days**

500 mg three times daily for 14 days ( 2.1)

Active Benign Gastric Ulcer

40 mg once daily for 4 to 8 weeks ( 2.1)

Symptomatic GERD

20 mg once daily for up to 4 weeks ( 2.1)

See full prescribing information for weight based dosing in

pediatric patients 1 year of age and older ( 2.2)

EE due to Acid-Mediated GERD

20 mg once daily for 4 to 8 weeks ( 2.1)***

See full prescribing information for weight based dosing in

pediatric patients 1 month of age and older ( 2.2)

Maintenance of Healing of EE due to Acid-Mediated GERD 20 mg once daily ( 2.1)****

See full prescribing information for weight based dosing in

pediatric patients 1 year of age and older ( 2.2)

Pathological Hypersecretory Conditions

Starting dose is 60 mg once daily (varies with individual

patient, see full prescribing information) as long as clinically

indicated ( 2.1)

* if ulcer present, continue omeprazole delayed-release capsules 20 mg once daily for an additional 18 days.

** if ulcer present, continue omeprazole delayed-release capsules 20 mg once daily for an additional 14 days.

*** an additional 4 weeks of treatment may be given if no response; if recurrence additional 4 to 8 week courses may be

conside re d.

**** studied for 12 months. Reduce the dosage to 10 mg once daily for patients with hepatic impairment (Child-Pugh Class

A, B, or C) and Asian patients. ( 8.6, 8.7)

DOSAGE FORMS AND STRENGTHS

Omeprazole delayed-release capsules: 10 mg, 20 mg and 40 mg ( 3)

CONTRAINDICATIONS

Patients with known hypersensitivity to substituted benzimidazoles or any component of the formulation. ( 4)

Patients receiving rilpivirine-containing products. ( 4, 7)

Refer to the Contraindications section of the prescribing information for clarithromycin and amoxicillin, when

administered in combination with omeprazole delayed-release capsules. ( 4)

WARNINGS AND PRECAUTIONS

Gastric Malignancy: In adults, symptomatic response does not preclude the presence of gastric malignancy. Consider

additional follow-up and diagnostic testing. ( 5.1)

Acute Interstitial Nephritis: Observed in patients taking PPIs. ( 5.2)

Clostridium difficile-Associated Diarrhea: PPI therapy may be associated with increased risk. ( 5.3)

Bone Fracture: Long-term and multiple daily dose PPI therapy may be associated with an increased risk for

osteoporosis-related fractures of the hip, wrist or spine. ( 5.4)

Cutaneous and Systemic Lupus Erythematosus: Mostly cutaneous; new onset or exacerbation of existing disease;

discontinue omeprazole delayed-release capsules and refer to specialist for evaluation. ( 5.5)

Interaction with Clopidogrel: Avoid concomitant use of omeprazole delayed-release capsules. ( 5.6, 7)

Cyanocobalamin (Vitamin B-12) Deficiency: Daily long-term use (e.g., longer than 3 years) may lead to malabsorption

or a deficiency of cyanocobalamin. ( 5.7)

Hypomagnesemia: Reported rarely with prolonged treatment with PPIs. ( 5.8)

Interaction with St. John’s Wort or Rifampin: Avoid concomitant use of omeprazole delayed-release capsules. ( 5.9, 7)

Interactions with Diagnostic Investigations for Neuroendocrine Tumors: Increased Chromogranin A (CgA) levels may

interfere with diagnostic investigations for neuroendocrine tumors; temporarily stop omeprazole delayed-release

capsules at least 14 days before assessing CgA levels. ( 5.10, 7)

Interaction with Methotrexate: Concomitant use with PPIs may elevate and/or prolong serum concentrations of

methotrexate and/or its metabolite, possibly leading to toxicity. With high dose methotrexate administration, consider a

temporary withdrawal of omeprazole delayed-release capsules. ( 5.11, 7)

Fundic Gland Polyps: Risk increases with long-term use, especially beyond one year. Use the shortest duration of

therapy. ( 5.12)

ADVERSE REACTIONS

Adults: Most common adverse reactions in adults (incidence ≥ 2%) are:

Headache, abdominal pain, nausea, diarrhea, vomiting, and flatulence. (6)

Pediatric patients (1 to 16 years of age):

Safety profile similar to that in adults, except that respiratory system events and fever were the most frequently

reported reactions in pediatric studies. ( 8.4)

To report SUSPECTED ADVERSE REACTIONS, contact Mylan at 1-877-446-3679 (1-877-4-INFO-RX) or FDA at

1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS

See full prescribing information for a list of clinically important drug interactions. ( 7)

See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.

Revised: 5/2018

FULL PRESCRIBING INFORMATION: CONTENTS*

1 INDICATIONS AND USAGE

1.1 Treatment of Active Duodenal Ulcer

1.2 Helicobacter pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence

1.3 Treatment of Active Benign Gastric Ulcer

1.4 Treatment of Symptomatic Gastroesophageal Reflux Disease (GERD)

1.5 Treatment of Erosive Esophagitis (EE) Due to Acid-Mediated GERD

1.6 Maintenance of Healing of EE Due to Acid-Mediated GERD

1.7 Pathological Hypersecretory Conditions

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Adult Dosage Regimen by Indication

2.2 Recommended Pediatric Dosage Regimen by Indication

2.3 Administration Instructions

3 DOSAGE FORMS AND STRENGTHS

4 CONTRAINDICATIONS

5 WARNINGS AND PRECAUTIONS

5.1 Presence of Gastric Malignancy

5.2 Acute Interstitial Nephritis

5.3 Clostridium difficile-Associated Diarrhea

5.4 Bone Fracture

5.5 Cutaneous and Systemic Lupus Erythematosus

5.6 Interaction with Clopidogrel

5.7 Cyanocobalamin (Vitamin B-12) Deficiency

5.8 Hypomagnesemia

5.9 Interaction with St. John’s Wort or Rifampin

5.10 Interactions with Diagnostic Investigations for Neuroendocrine Tumors

5.11 Interaction with Methotrexate

5.12 Fundic Gland Polyps

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience with Omeprazole Delayed-Release Capsules

6.2 Clinical Trials Experience with Omeprazole Delayed-Release Capsules in Combination

Therapy for H. pylori Eradication

6.3 Postmarketing Experience

7 DRUG INTERACTIONS

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

8.2 Lactation

8.4 Pediatric Use

8.5 Geriatric Use

8.6 Hepatic Impairment

8.7 Asian Population

10 OVERDOSAGE

11 DESCRIPTION

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

12.2 Pharmacodynamics

12.3 Pharmacokinetics

12.4 Microbiology

12.5 Pharmacogenomics

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

14 CLINICAL STUDIES

14.1 Active Duodenal Ulcer

14.2 H. pylori Eradication in Patients with Duodenal Ulcer Disease

14.3 Active Benign Gastric Ulcer

14.4 Symptomatic GERD

14.5 EE due to Acid-Mediated GERD

14.6 Maintenance of Healing of EE due to Acid-Mediated GERD

14.7 Pathological Hypersecretory Conditions

14.8 Pediatric Studies for the Treatment of Symptomatic GERD, Treatment of EE due to Acid-

Mediated GERD, and Maintenance of Healing of EE due to Acid-Mediated GERD

15 REFERENCES

16 HOW SUPPLIED/STORAGE AND HANDLING

17 PATIENT COUNSELING INFORMATION

FULL PRESCRIBING INFORMATION

1 INDICATIONS AND USAGE

1.1 Treatment of Active Duodenal Ulcer

Omeprazole delayed-release capsules are indicated for short-term treatment of active duodenal ulcer in

adults. Most patients heal within four weeks. Some patients may require an additional four weeks of

therapy.

1.2 Helicobacter pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence

Eradication of H. pylori has been shown to reduce the risk of duodenal ulcer recurrence.

Triple Therapy

Omeprazole delayed-release capsules in combination with clarithromycin and amoxicillin, is indicated

for treatment of patients with H. pylori infection and duodenal ulcer disease (active or up to 1-year

history) to eradicate H. pylori in adults.

Dual Therapy

Omeprazole delayed-release capsules in combination with clarithromycin is indicated for treatment of

patients with H. pylori infection and duodenal ulcer disease to eradicate H. pylori in adults.

Among patients who fail therapy, omeprazole delayed-release capsules with clarithromycin are more

likely to be associated with the development of clarithromycin resistance as compared with triple

therapy. In patients who fail therapy, susceptibility testing should be done. If resistance to

clarithromycin is demonstrated or susceptibility testing is not possible, alternative antimicrobial therapy

should be instituted [see Clinical Pharmacology (12.4) and the clarithromycin prescribing information,

Microbiology section ].

1.3 Treatment of Active Benign Gastric Ulcer

Omeprazole delayed-release capsules are indicated for short-term treatment (4 to 8 weeks) of active

benign gastric ulcer in adults.

1.4 Treatment of Symptomatic Gastroesophageal Reflux Disease (GERD)

Omeprazole delayed-release capsules are indicated for the treatment of heartburn and other symptoms

associated with GERD for up to 4 weeks in patients 1 year of age and older.

1.5 Treatment of Erosive Esophagitis (EE) Due to Acid-Mediated GERD

Pediatric Patients 1 Year of Age to Adults

Omeprazole delayed-release capsules are indicated for the short-term treatment (4 to 8 weeks) of EE

due to acid-mediated GERD that has been diagnosed by endoscopy in patients 1 year of age and older.

The efficacy of omeprazole delayed-release capsules used for longer than 8 weeks in patients with EE

Sections or subsections omitted from the full prescribing information are not listed.

has not been established. If a patient does not respond to 8 weeks of treatment, an additional 4 weeks of

treatment may be given. If there is recurrence of EE or GERD symptoms (e.g., heartburn), additional 4

to 8 week courses of omeprazole delayed-release capsules may be considered.

Pediatric Patients 1 Month to Less than 1 Year of Age

Omeprazole is indicated for the short-term treatment (up to 6 weeks) of EE due to acid-mediated GERD

in pediatric patients 1 month to less than 1 year of age.

1.6 Maintenance of Healing of EE Due to Acid-Mediated GERD

Omeprazole delayed-release capsules are indicated for the maintenance healing of EE due to acid-

mediated GERD in patients 1 year of age and older.

Controlled studies do not extend beyond 12 months.

1.7 Pathological Hypersecretory Conditions

Omeprazole delayed-release capsules are indicated for the long-term treatment of pathological

hypersecretory conditions (e.g., Zollinger-Ellison syndrome, multiple endocrine adenomas and systemic

mastocytosis) in adults.

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Adult Dosage Regimen by Indication

Table 1 shows the recommended dosage of omeprazole delayed-release capsules in adult patients by

indication.

Table 1: Recommended Dosage Regimen of Omeprazole Delayed-Release Capsules in Adults by

Indication

Indication

Dosage of Omeprazole Delayed-

Release Capsules

Treatment Duration

Treatment of Active Duodenal

Ulcer

20 mg once daily

4 weeks

Helicobacter pylori Eradication to

Reduce the Risk of Duodenal

Ulcer Recurrence

Triple Therapy

Omeprazole delayed-release

capsules 20 mg

Amoxicillin 1000 mg

Clarithromycin 500 mg

Take all three drugs twice daily.

10 days

In patients with an ulcer present

at the time of initiation of

therapy, continue omeprazole

delayed-release capsules 20 mg

once daily for an additional 18

days for ulcer healing and

symptom relief.

Dual Therapy

Omeprazole delayed-release

capsules 40 mg once daily.

Clarithromycin 500 mg three times

daily.

14 days

In patients with an ulcer present

at the time of initiation of

therapy, an additional 14 days of

omeprazole delayed-release

capsules 20 mg once daily is

recommended for ulcer healing

and symptom relief.

Active Benign Gastric Ulcer

40 mg once daily

4 to 8 weeks

Treatment of Symptomatic GERD 20 mg once daily

Up to 4 weeks

Treatment of EE due to Acid-

20 mg once daily

4 to 8 weeks

Mediated GERD

Maintenance of Healing of EE

due to Acid-Mediated GERD

20 mg once daily

Controlled studies do not extend

beyond 12 months.

Pathological Hypersecretory

Conditions

Starting dose is 60 mg once daily;

adjust to patient needs.

Daily dosages of greater than 80

mg should be administered in

divided doses.

Dosages up to 120 mg three times

daily have been administered.

As long as clinically indicated.

Some patients with Zollinger-

Ellison syndrome have been

treated continuously for more

than 5 years.

2.2 Recommended Pediatric Dosage Regimen by Indication

Table 2 shows the recommended dosage of omeprazole in pediatric patients by indication.

Table 2: Recommended Dosage Regimen of Omeprazole in Pediatric Patients by Indication

Indication

Omeprazole Dosage Regimen and Duration

Patient Age

Weight-Based Dose

(mg)

Regimen and Duration

Treatment of Symptomatic

GERD

1 to 16 years

5 kg to less than 10 kg: 5

Once daily for up to 4

weeks

10 kg to less than 20 kg:

10 mg

20 kg and greater: 20 mg

Treatment of EE due to

Acid-Mediated GERD

1 to 16 years

5 kg to less than 10 kg: 5

Once daily for 4 to 8

weeks

10 kg to less than 20 kg:

10 mg

20 kg and greater: 20 mg

1 month to less than 1

year

3 kg to less than 5 kg: 2.5

Once daily up to 6

weeks

5 kg to less than 10 kg: 5

10 kg and greater: 10 mg

Maintenance of Healing of

EE due to Acid-Mediated

GERD

1 to 16 years

5 kg to less than 10 kg: 5

Once daily. Controlled

studies do not extend

beyond 12 months

10 kg to less than 20 kg:

10 mg

20 kg and greater: 20 mg

Most patients heal within 4 weeks; some patients may require an additional 4 weeks of therapy to achieve healing.

The efficacy of omeprazole delayed-release capsules used for longer than 8 weeks in patients with EE has not

been established. If a patient does not respond to 8 weeks of treatment, an additional 4 weeks of treatment may

be given. If there is recurrence of EE or GERD symptoms (e.g., heartburn), additional 4 to 8 week courses of

omeprazole delayed-release capsules may be considered.

Dosage reduction to 10 mg once daily is recommended for patients with hepatic impairment (Child-Pugh Class A,

B or C) and Asian patients when used for the maintenance of healing of EE [see Use in Specific Populations (

8.6, 8.7) and Clinical Pharmacology ( 12.3, 12.5)] .

The efficacy of omeprazole used for longer than 8 weeks in patients with EE has not been established. If a patient

does not respond to 8 weeks of treatment, an additional 4 weeks of treatment may be given. If there is

recurrence of EE or GERD symptoms (e.g., heartburn), additional 4 to 8 week courses of omeprazole may be

considered.

2.3 Administration Instructions

Take omeprazole delayed-release capsules before meals.

Antacids may be used concomitantly with omeprazole delayed-release capsules.

Missed doses: If a dose is missed, administer as soon as possible. However, if the next scheduled

dose is due, do not take the missed dose, and take the next dose on time. Do not take two doses at one

time to make up for a missed dose.

Omeprazole Delayed-Release Capsules:

Swallow omeprazole delayed-release capsules whole; do not chew.

For patients unable to swallow an intact capsule, omeprazole delayed-release capsules can be

opened and administered as follows:

Place one tablespoon of applesauce into a clean container (e.g., empty bowl). The applesauce used

should not be hot and should be soft enough to be swallowed without chewing.

Open the capsule.

Carefully empty all of the pellets inside the capsule on the applesauce.

Mix the pellets with the applesauce.

Swallow applesauce and pellets immediately with a glass of cool water to ensure complete

swallowing of the pellets. Do not chew or crush the pellets. Do not save the applesauce and pellets

for future use.

3 DOSAGE FORMS AND STRENGTHS

Omeprazole Delayed-Release Capsules

Omeprazole Delayed-Release Capsules, USP are available containing 10 mg, 20 mg or 40 mg of

omeprazole, USP.

The 10 mg capsules are hard-shell gelatin capsules with a dark green opaque cap and a dark green

opaque body filled with white to off-white beads. The capsule is axially printed with MYLAN over

5211 in white ink both on the cap and the body.

The 20 mg capsules are hard-shell gelatin capsules with a dark green opaque cap and a blue-green

opaque body filled with white to off-white beads. The capsule is axially printed with MYLAN over

6150 in white ink both on the cap and the body.

The 40 mg capsules are hard-shell gelatin capsules with a dark green opaque cap and a light-blue

opaque body filled with white to off-white beads. The capsule is axially printed with MYLAN over

5222 in white ink both on the cap and the body.

4 CONTRAINDICATIONS

Omeprazole delayed-release capsules are contraindicated in patients with known hypersensitivity to

substituted benzimidazoles or to any component of the formulation. Hypersensitivity reactions may

include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, interstitial nephritis, and

urticaria [see Warnings and Precautions (5.2), Adverse Reactions (6)] .

Proton pump inhibitors (PPIs), including omeprazole delayed-release capsules, are contraindicated

in patients receiving rilpivirine-containing products [see Drug Interactions (7)] .

For information about contraindications of antibacterial agents (clarithromycin and amoxicillin)

indicated in combination with omeprazole delayed-release capsules, refer to the

CONTRAINDICATIONS section of their package inserts.

5 WARNINGS AND PRECAUTIONS

5.1 Presence of Gastric Malignancy

In adults, symptomatic response to therapy with omeprazole delayed-release capsules does not preclude

In adults, symptomatic response to therapy with omeprazole delayed-release capsules does not preclude

the presence of gastric malignancy. Consider additional follow-up and diagnostic testing in adult

patients who have a suboptimal response or an early symptomatic relapse after completing treatment

with a PPI. In older patients, also consider an endoscopy.

5.2 Acute Interstitial Nephritis

Acute interstitial nephritis has been observed in patients taking PPIs including omeprazole delayed-

release capsules. Acute interstitial nephritis may occur at any point during PPI therapy and is generally

attributed to an idiopathic hypersensitivity reaction. Discontinue omeprazole delayed-release capsules

if acute interstitial nephritis develops [see Contraindications (4)].

5.3 Clostridium difficile-Associated Diarrhea

Published observational studies suggest that PPI therapy like omeprazole delayed-release capsules may

be associated with an increased risk of Clostridium difficile-associated diarrhea, especially in

hospitalized patients. This diagnosis should be considered for diarrhea that does not improve [see

Adverse Reactions (6.2)].

Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition

being treated.

Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial

agents. For more information specific to antibacterial agents (clarithromycin and amoxicillin) indicated

for use in combination with omeprazole delayed-release capsules, refer to Warnings and Precautions

sections of the corresponding prescribing information.

5.4 Bone Fracture

Several published observational studies suggest that proton pump inhibitor (PPI) therapy may be

associated with an increased risk for osteoporosis-related fractures of the hip, wrist, or spine. The risk

of fracture was increased in patients who received high-dose, defined as multiple daily doses, and

long-term PPI therapy (a year or longer). Patients should use the lowest dose and shortest duration of

PPI therapy appropriate to the condition being treated. Patients at risk for osteoporosis-related fractures

should be managed according to established treatment guidelines [see Dosage and Administration (2.1),

Adverse Reactions (6.3)].

5.5 Cutaneous and Systemic Lupus Erythematosus

Cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE) have been reported in

patients taking PPIs, including omeprazole. These events have occurred as both new onset and an

exacerbation of existing autoimmune disease. The majority of PPI-induced lupus erythematosus cases

were CLE.

The most common form of CLE reported in patients treated with PPIs was subacute CLE (SCLE) and

occurred within weeks to years after continuous drug therapy in patients ranging from infants to the

elderly. Generally, histological findings were observed without organ involvement.

Systemic lupus erythematosus (SLE) is less commonly reported than CLE in patients receiving PPIs. PPI

associated SLE is usually milder than non-drug induced SLE. Onset of SLE typically occurred within

days to years after initiating treatment primarily in patients ranging from young adults to the elderly. The

majority of patients presented with rash; however, arthralgia and cytopenia were also reported.

Avoid administration of PPIs for longer than medically indicated. If signs or symptoms consistent with

CLE or SLE are noted in patients receiving omeprazole delayed-release capsules, discontinue the drug

and refer the patient to the appropriate specialist for evaluation. Most patients improve with

discontinuation of the PPI alone in 4 to 12 weeks. Serological testing (e.g., ANA) may be positive and

elevated serological test results may take longer to resolve than clinical manifestations.

5.6 Interaction with Clopidogrel

Avoid concomitant use of omeprazole delayed-release capsules with clopidogrel. Clopidogrel is a

prodrug. Inhibition of platelet aggregation by clopidogrel is entirely due to an active metabolite. The

metabolism of clopidogrel to its active metabolite can be impaired by use with concomitant medications,

such as omeprazole, that inhibit CYP2C19 activity. Concomitant use of clopidogrel with 80 mg

omeprazole reduces the pharmacological activity of clopidogrel, even when administered 12 hours

apart. When using omeprazole delayed-release capsules, consider alternative anti-platelet therapy [see

Drug Interactions (7) and Clinical Pharmacology (12.3)] .

5.7 Cyanocobalamin (Vitamin B-12) Deficiency

Daily treatment with any acid-suppressing medications over a long period of time (e.g., longer than 3

years) may lead to malabsorption of cyanocobalamin (vitamin B-12) caused by hypo- or achlorhydria.

Rare reports of cyanocobalamin deficiency occurring with acid-suppressing therapy have been

reported in the literature. This diagnosis should be considered if clinical symptoms consistent with

cyanocobalamin deficiency are observed in patients treated with omeprazole delayed-release capsules.

5.8 Hypomagnesemia

Hypomagnesemia, symptomatic and asymptomatic, has been reported rarely in patients treated with PPIs

for at least three months, in most cases after a year of therapy. Serious adverse events include tetany,

arrhythmias, and seizures. In most patients, treatment of hypomagnesemia required magnesium

replacement and discontinuation of the PPI.

For patients expected to be on prolonged treatment or who take PPIs with medications such as digoxin

or drugs that may cause hypomagnesemia (e.g., diuretics), health care professionals may consider

monitoring magnesium levels prior to initiation of PPI treatment and periodically [see Adverse Reactions

(6.3)].

5.9 Interaction with St. John’s Wort or Rifampin

Drugs which induce CYP2C19 or CYP3A4 (such as St. John’s Wort or rifampin) can substantially

decrease omeprazole concentrations [see Drug Interactions (7)]. Avoid concomitant use of omeprazole

delayed-release capsules with St. John’s Wort or rifampin.

5.10 Interactions with Diagnostic Investigations for Neuroendocrine Tumors

Serum chromogranin A (CgA) levels increase secondary to drug-induced decreases in gastric acidity.

The increased CgA level may cause false positive results in diagnostic investigations for

neuroendocrine tumors. Healthcare providers should temporarily stop omeprazole delayed-release

capsules treatment at least 14 days before assessing CgA levels and consider repeating the test if initial

CgA levels are high. If serial tests are performed (e.g., for monitoring), the same commercial

laboratory should be used for testing, as reference ranges between tests may vary [see Drug Interactions

(7)].

5.11 Interaction with Methotrexate

Literature suggests that concomitant use of PPIs with methotrexate (primarily at high dose) may elevate

and prolong serum levels of methotrexate and/or its metabolite, possibly leading to methotrexate

toxicities. In high-dose methotrexate administration a temporary withdrawal of the PPI may be

considered in some patients [see Drug Interactions (7)] .

5.12 Fundic Gland Polyps

use is associated with an increased risk of fundic gland polyps that increases with long-term use,

especially beyond one year. Most PPI users who developed fundic gland polyps were asymptomatic and

fundic gland polyps were identified incidentally on endoscopy. Use the shortest duration of PPI

therapy appropriate to the condition being treated. PPI use is associated with an increased risk of fundic

gland polyps that increases with long-term use, especially beyond one year. Most PPI users who

developed fundic gland polyps were asymptomatic and fundic gland polyps were identified incidentally

on endoscopy. Use the shortest duration of PPI therapy appropriate to the condition being treated.

6 ADVERSE REACTIONS

The following serious adverse reactions are described below and elsewhere in labeling:

Acute Interstitial Nephritis [see Warnings and Precautions (5.2)]

Clostridium difficile-Associated Diarrhea [see Warnings and Precautions (5.3)]

Bone Fracture [see Warnings and Precautions (5.4)]

Cutaneous and Systemic Lupus Erythematosus [see Warnings and Precautions (5.5)]

Cyanocobalamin (Vitamin B-12) Deficiency [see Warnings and Precautions (5.7)]

Hypomagnesemia [see Warnings and Precautions (5.8)]

Fundic Gland Polyps [see Warnings and Precautions (5.12)]

6.1 Clinical Trials Experience with Omeprazole Delayed-Release Capsules

Monotherapy

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed

in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug

and may not reflect the rates observed in practice.

The safety data described below reflects exposure to omeprazole delayed-release capsules in 3,096

patients from worldwide clinical trials (465 patients from U.S. studies and 2,631 patients from

international studies). Indications clinically studied in U.S. trials included duodenal ulcer, resistant

ulcer, and Zollinger-Ellison syndrome. The international clinical trials were double blind and open-

label in design. The most common adverse reactions reported (i.e., with an incidence rate ≥ 2%) from

omeprazole delayed-release capsules-treated patients enrolled in these studies included headache (7%),

abdominal pain (5%), nausea (4%), diarrhea (4%), vomiting (3%), and flatulence (3%).

Additional adverse reactions that were reported with an incidence ≥ 1% included acid regurgitation

(2%), upper respiratory infection (2%), constipation (2%), dizziness (2%), rash (2%), asthenia (1%), back

pain (1%), and cough (1%).

The clinical trial safety profile in patients greater than 65 years of age was similar to that in patients 65

years of age or less.

The clinical trial safety profile in pediatric patients who received omeprazole delayed-release capsules

was similar to that in adult patients. Unique to the pediatric population, however, adverse reactions of

the respiratory system were frequently reported in the 1 month to < 1 year age group, the 1 to < 2 year

age group, and the 2 to 16 year age group (42%, 75%, and 19%, respectively). In addition, otitis media

was frequently reported in the 1 month to < 1 year age group (22%), fever was frequently reported in

the 1 to < 2 year age group (33%), and accidental injuries were frequently reported in the 2 to 16 year

age group (4%) [see Use in Specific Populations (8.4)].

6.2 Clinical Trials Experience with Omeprazole Delayed-Release Capsules in Combination

Therapy for H. pylori Eradication

In clinical trials using either dual therapy with omeprazole delayed-release capsules and clarithromycin,

or triple therapy with omeprazole delayed-release capsules, clarithromycin, and amoxicillin, no adverse

reactions unique to these drug combinations were observed. Adverse reactions observed were limited

to those previously reported with omeprazole, clarithromycin, or amoxicillin alone.

Dual Therapy (Omeprazole Delayed-Release Capsules/Clarithromycin)

Adverse reactions observed in controlled clinical trials using combination therapy with omeprazole

delayed-release capsules and clarithromycin (n = 346) that differed from those previously described

for omeprazole delayed-release capsules alone were taste perversion (15%), tongue discoloration

(2%), rhinitis (2%), pharyngitis (1%) and flu-syndrome (1%). (For more information on clarithromycin,

refer to the clarithromycin prescribing information, Adverse Reactions section.)

Triple Therapy (Omeprazole Delayed-Release Capsules/Clarithromycin/Amoxicillin)

The most frequent adverse reactions observed in clinical trials using combination therapy with

omeprazole delayed-release capsules, clarithromycin, and amoxicillin (n = 274) were diarrhea (14%),

taste perversion (10%), and headache (7%). None of these occurred at a higher frequency than that

reported by patients taking antimicrobial agents alone. (For more information on clarithromycin or

amoxicillin, refer to the respective prescribing information, Adverse Reactions sections.)

6.3 Postmarketing Experience

The following adverse reactions have been identified during post-approval use of omeprazole delayed-

release capsules. Because these reactions are voluntarily reported from a population of uncertain size,

it is not always possible to reliably estimate their actual frequency or establish a causal relationship to

drug exposure.

Body As a Whole: Hypersensitivity reactions including anaphylaxis, anaphylactic shock, angioedema,

bronchospasm, interstitial nephritis, urticaria, (see also Skin below); fever; pain; fatigue; malaise;

systemic lupus erythematosus

Cardiovascular: Chest pain or angina, tachycardia, bradycardia, palpitations, elevated blood pressure,

peripheral edema

Endocrine: Gynecomastia

Gastrointestinal: Pancreatitis (some fatal), anorexia, irritable colon, fecal discoloration, esophageal

candidiasis, mucosal atrophy of the tongue, stomatitis, abdominal swelling, dry mouth, microscopic

colitis, fundic gland polyps.

Gastroduodenal carcinoids have been reported in patients with ZE syndrome on long-term treatment with

omeprazole delayed-release capsules. This finding is believed to be a manifestation of the underlying

condition, which is known to be associated with such tumors.

Hepatic: Liver disease including hepatic failure (some fatal), liver necrosis (some fatal), hepatic

encephalopathy hepatocellular disease, cholestatic disease, mixed hepatitis, jaundice, and elevations of

liver function tests [ALT, AST, GGT, alkaline phosphatase, and bilirubin]

Infections and Infestations: Clostridium difficile-associated diarrhea

Metabolism and Nutritional Disorders: Hypoglycemia, hypomagnesemia, with or without hypocalcemia

and/or hypokalemia, hyponatremia, weight gain

Musculoskeletal: Muscle weakness, myalgia, muscle cramps, joint pain, leg pain, bone fracture

Nervous System/Psychiatric: Psychiatric and sleep disturbances including depression, agitation,

aggression, hallucinations, confusion, insomnia, nervousness, apathy, somnolence, anxiety, and dream

abnormalities; tremors, paresthesia; vertigo

Respiratory: Epistaxis, pharyngeal pain

Skin: Severe generalized skin reactions including toxic epidermal necrolysis (some fatal), Stevens-

Johnson syndrome, cutaneous lupus erythematosus and erythema multiforme; photosensitivity; urticaria;

rash; skin inflammation; pruritus; petechiae; purpura; alopecia; dry skin; hyperhidrosis

Special Senses: Tinnitus, taste perversion

Ocular: Optic atrophy, anterior ischemic optic neuropathy, optic neuritis, dry eye syndrome, ocular

irritation, blurred vision, double vision

Urogenital: Interstitial nephritis, hematuria, proteinuria, elevated serum creatinine, microscopic pyuria,

urinary tract infection, glycosuria, urinary frequency, testicular pain

Hematologic: Agranulocytosis (some fatal), hemolytic anemia, pancytopenia, neutropenia, anemia,

thrombocytopenia, leukopenia, leukocytosis

7 DRUG INTERACTIONS

Tables 3 and 4 include drugs with clinically important drug interactions and interaction with diagnostics

when administered concomitantly with omeprazole delayed-release capsules and instructions for

preventing or managing them.

Consult the labeling of concomitantly used drugs to obtain further information about interactions with

PPIs.

Table 3: Clinically Relevant Interactions Affecting Drugs Co-Administered with Omeprazole

Delayed-Release Capsules and Interaction with Diagnostics

Antiretrovirals

Clinical Impact:

The effect of PPIs on antiretroviral drugs is variable. The clinical importance and

the mechanisms behind these interactions are not always known.

Decreased exposure of some antiretroviral drugs (e.g., rilpivirine, atazanavir

and nelfinavir) when used concomitantly with omeprazole may reduce antiviral

effect and promote the development of drug resistance [see Clinical

Pharmacology (12.3)].

Increased exposure of other antiretroviral drugs (e.g., saquinavir) when used

concomitantly with omeprazole may increase toxicity [see Clinical

Pharmacology (12.3)] .

There are other antiretroviral drugs which do not result in clinically relevant

interactions with omeprazole.

Intervention:

Rilpivirine-containing products: Concomitant use with omeprazole delayed-release

capsules is contraindicated [see Contraindications (4)] .

Atazanavir: Avoid concomitant use with omeprazole delayed-release capsules. See

prescribing information for atazanavir for dosing information.

Nelfinavir: Avoid concomitant use with omeprazole delayed-release capsules. See

prescribing information for nelfinavir.

Saquinavir: See the prescribing information for saquinavir for monitoring of

potential saquinavir-related toxicities.

Other antiretrovirals: See prescribing information for specific antiretroviral drugs.

Warfarin

Clinical Impact:

Increased INR and prothrombin time in patients receiving PPIs, including

omeprazole, and warfarin concomitantly. Increases in INR and prothrombin time may

lead to abnormal bleeding and even death.

Intervention:

Monitor INR and prothrombin time and adjust the dose of warfarin, if needed, to

maintain target INR range.

Methotrexate

Clinical Impact:

Concomitant use of omeprazole with methotrexate (primarily at high dose) may

elevate and prolong serum concentrations of methotrexate and/or its metabolite

hydroxymethotrexate, possibly leading to methotrexate toxicities. No formal drug

interaction studies of high-dose methotrexate with PPIs have been conducted [see

Warnings and Precautions (5.11)].

Intervention:

A temporary withdrawal of omeprazole delayed-release capsules may be

Intervention:

considered in some patients receiving high-dose methotrexate.

CYP2C19 Substrates (e.g., clopidogrel, citalopram, cilostazol, phenytoin, diazepam)

Clopidogrel

Clinical Impact:

Concomitant use of omeprazole 80 mg results in reduced plasma concentrations of

the active metabolite of clopidogrel and a reduction in platelet inhibition [see

Clinical Pharmacology (12.3)].

There are no adequate combination studies of a lower dose of omeprazole or a

higher dose of clopidogrel in comparison with the approved dose of clopidogrel.

Intervention:

Avoid concomitant use with omeprazole delayed-release capsules. Consider use of

alternative anti-platelet therapy [see Warnings and Precautions (5.6)] .

Citalopram

Clinical Impact:

Increased exposure of citalopram leading to an increased risk of QT prolongation

[see Clinical Pharmacology (12.3)] .

Intervention:

Limit the dose of citalopram to a maximum of 20 mg per day. See prescribing

information for citalopram.

Cilos tazol

Clinical Impact:

Increased exposure of one of the active metabolites of cilostazol (3,4-dihydro-

cilostazol) [see Clinical Pharmacology (12.3)].

Intervention:

Reduce the dose of cilostazol to 50 mg twice daily. See prescribing information

for cilostazol.

Phenytoin

Clinical Impact:

Potential for increased exposure of phenytoin.

Intervention:

Monitor phenytoin serum concentrations. Dose adjustment may be needed to maintain

therapeutic drug concentrations. See prescribing information for phenytoin.

Diazepam

Clinical Impact:

Increased exposure of diazepam [see Clinical Pharmacology (12.3)].

Intervention:

Monitor patients for increased sedation and reduce the dose of diazepam as needed.

Digoxin

Clinical Impact:

Potential for increased exposure of digoxin [see Clinical Pharmacology (12.3)].

Intervention:

Monitor digoxin concentrations. Dose adjustment may be needed to maintain

therapeutic drug concentrations. See digoxin prescribing information.

Drugs Dependent on Gastric pH for Absorption (e.g., iron salts, erlotinib, dasatinib, nilotinib,

mycophenolate mofetil, ketoconazole/itraconazole)

Clinical Impact:

Omeprazole can reduce the absorption of other drugs due to its effect on reducing

intragastric acidity.

Intervention:

Mycophenolate mofetil (MMF): Co-administration of omeprazole in healthy

subjects and in transplant patients receiving MMF has been reported to reduce the

exposure to the active metabolite, mycophenolic acid (MPA), possibly due to a

decrease in MMF solubility at an increased gastric pH. The clinical relevance of

reduced MPA exposure on organ rejection has not been established in transplant

patients receiving omeprazole delayed-release capsules and MMF. Use omeprazole

delayed-release capsules with caution in transplant patients receiving MMF [see

Clinical Pharmacology (12.3)].

See the prescribing information for other drugs dependent on gastric pH for

absorption.

Combination Therapy with Clarithromycin and Amoxicillin

Clinical Impact:

Concomitant administration of clarithromycin with other drugs can lead to serious

adverse reactions, including potentially fatal arrhythmias, and are contraindicated.

Amoxicillin also has drug interactions.

Intervention:

See Contraindications, Warnings and Precautions in prescribing information for

Intervention:

clarithromycin. See Drug Interactions in prescribing information for amoxicillin.

Tacrolimus

Clinical Impact:

Potential for increased exposure of tacrolimus, especially in transplant patients who

are intermediate or poor metabolizers of CYP2C19.

Intervention:

Monitor tacrolimus whole blood concentrations. Dose adjustment may be needed to

maintain therapeutic drug concentrations. See prescribing information for

tacrolimus.

Interactions with Investigations of Neuroendocrine Tumors

Clinical Impact:

Serum chromogranin A (CgA) levels increase secondary to PPI-induced decreases

in gastric acidity. The increased CgA level may cause false positive results in

diagnostic investigations for neuroendocrine tumors [see Warnings and Precautions

(5.10), Clinical Pharmacology (12.2)].

Intervention:

Temporarily stop omeprazole delayed-release capsules treatment at least 14 days

before assessing CgA levels and consider repeating the test if initial CgA levels

are high. If serial tests are performed (e.g., for monitoring), the same commercial

laboratory should be used for testing, as reference ranges between tests may vary.

Interaction with Secretin Stimulation Test

Clinical Impact:

Hyper-response in gastrin secretion in response to secretin stimulation test, falsely

suggesting gastrinoma.

Intervention:

Temporarily stop omeprazole delayed-release capsules treatment at least 14 days

before assessing to allow gastrin levels to return to baseline [see Clinical

Pharmacology (12.2)].

False Positive Urine Tests for THC

Clinical Impact:

There have been reports of false positive urine screening tests for

tetrahydrocannabinol (THC) in patients receiving PPIs.

Intervention:

An alternative confirmatory method should be considered to verify positive results.

Other

Clinical Impact:

There have been clinical reports of interactions with other drugs metabolized via

the cytochrome P450 system (e.g., cyclosporine, disulfiram).

Intervention:

Monitor patients to determine if it is necessary to adjust the dosage of these other

drugs when taken concomitantly with omeprazole delayed-release capsules.

Table 4: Clinically Relevant Interactions Affecting Omeprazole Delayed-Release Capsules When

Co-Administered with Other Drugs

CYP2C19 or CYP3A4 Inducers

Clinical Impact:

Decreased exposure of omeprazole when used concomitantly with strong

inducers [see Clinical Pharmacology (12.3)].

Intervention:

St. John’s Wort, rifampin: Avoid concomitant use with omeprazole delayed-

release capsules [see Warnings and Precautions (5.9)] .

Ritonavir-containing products: see prescribing information for specific drugs.

CYP2C19 or CYP3A4 Inhibitors

Clinical Impact:

Increased exposure of omeprazole [see Clinical Pharmacology (12.3)].

Intervention:

Voriconazole: Dose adjustment of omeprazole delayed-release capsules is not

normally required. However, in patients with Zollinger-Ellison syndrome, who

may require higher doses, dose adjustment may be considered.

See prescribing information for voriconazole.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

There are no adequate and well-controlled studies with omeprazole delayed-release capsules 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 the offspring at any age [see Data].

The estimated background risks of major birth defects and miscarriage for the indicated population are

unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the

U.S. general population, the estimated background risk of major birth defects and miscarriage in

clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Data

Human Data

Four published epidemiological studies compared the frequency of congenital abnormalities among

infants born to women who used omeprazole during pregnancy with the frequency of abnormalities

among infants of women exposed to H

-receptor antagonists or other controls.

A population-based retrospective cohort epidemiological study from the Swedish Medical Birth

Registry, covering approximately 99% of pregnancies, from 1995 to 1999, reported on 955 infants

(824 exposed during the first trimester with 39 of these exposed beyond first trimester, and 131

exposed after the first trimester) whose mothers used omeprazole during pregnancy. The number of

infants exposed in utero to omeprazole that had any malformation, low birth weight, low Apgar score, or

hospitalization was similar to the number observed in this population. The number of infants born with

ventricular septal defects and the number of stillborn infants was slightly higher in the omeprazole-

exposed infants than the expected number in this population.

A population-based retrospective cohort study covering all live births in Denmark from 1996 to 2009,

reported on 1,800 live births whose mothers used omeprazole during the first trimester of pregnancy

and 837,317 live births whose mothers did not use any proton pump inhibitor. The overall rate of birth

defects in infants born to mothers with first trimester exposure to omeprazole was 2.9% and 2.6% in

infants born to mothers not exposed to any proton pump inhibitor during the first trimester.

A retrospective cohort study reported on 689 pregnant women exposed to either H

-blockers or

omeprazole in the first trimester (134 exposed to omeprazole) and 1,572 pregnant women unexposed to

either during the first trimester. The overall malformation rate in offspring born to mothers with first

trimester exposure to omeprazole, an H

-blocker, or were unexposed was 3.6%, 5.5%, and 4.1%,

respectively.

A small prospective observational cohort study followed 113 women exposed to omeprazole during

pregnancy (89% with first trimester exposures). The reported rate of major congenital malformations

was 4% in the omeprazole group, 2% in controls exposed to non-teratogens, and 2.8% in disease-paired

controls. Rates of spontaneous and elective abortions, preterm deliveries, gestational age at delivery,

and mean birth weight were similar among the groups.

Several studies have reported no apparent adverse short-term effects on the infant when single dose

oral or intravenous omeprazole was administered to over 200 pregnant women as premedication for

cesarean section under general anesthesia.

Animal Data

Omeprazole

Reproductive studies conducted with omeprazole in rats at oral doses up to 138 mg/kg/day (about 34

times an oral human dose of 40 mg on a body surface area basis) and in rabbits at doses up to 69.1

mg/kg/day (about 34 times an oral human dose of 40 mg on a body surface area basis) during

organogenesis did not disclose any evidence for a teratogenic potential of omeprazole. In rabbits,

omeprazole in a dose range of 6.9 mg/kg/day to 69.1 mg/kg/day (about 3.4 to 34 times an oral human

dose of 40 mg on a body surface area basis) administered during organogenesis produced dose-related

increases in embryo-lethality, fetal resorptions, and pregnancy disruptions. In rats, dose-related

embryo/fetal toxicity and postnatal developmental toxicity were observed in offspring resulting from

parents treated with omeprazole at 13.8 mg/kg/day to 138.0 mg/kg/day (about 3.4 to 34 times an oral

human doses of 40 mg on a body surface area basis), administered prior to mating through the lactation

period.

Esomeprazole

The data described below was generated from studies using esomeprazole, an enantiomer of

omeprazole. The animal to human dose multiples are based on the assumption of equal systemic

exposure to esomeprazole in humans following oral administration of either 40 mg esomeprazole or 40

mg omeprazole.

No effects on embryo-fetal development were observed in reproduction studies with esomeprazole

magnesium in rats at oral doses up to 280 mg/kg/day (about 68 times an oral human dose of 40 mg on a

body surface area basis) or in rabbits at oral doses up to 86 mg/kg/day (about 42 times an oral human

dose of 40 mg esomeprazole or 40 mg omeprazole on a body surface area basis) administered during

organogenesis.

A pre- and postnatal developmental toxicity study in rats with additional endpoints to evaluate bone

development was performed with esomeprazole magnesium at oral doses of 14 mg/kg/day to 280

mg/kg/day (about 3.4 to 68 times an oral human dose of 40 mg esomeprazole or 40 mg omeprazole on a

body surface area basis). Neonatal/early postnatal (birth to weaning) survival was decreased at doses

equal to or greater than 138 mg/kg/day (about 34 times an oral human dose of 40 mg esomeprazole or

40 mg omeprazole on a body surface area basis). Body weight and body weight gain were reduced and

neurobehavioral or general developmental delays in the immediate post-weaning timeframe were

evident at doses equal to or greater than 69 mg/kg/day (about 17 times an oral human dose of 40 mg

esomeprazole or 40 mg omeprazole on a body surface area basis). In addition, decreased femur length,

width and thickness of cortical bone, decreased thickness of the tibial growth plate and minimal to mild

bone marrow hypocellularity were noted at doses equal to or greater than 14 mg/kg/day (about 3.4 times

an oral human dose of 40 mg esomeprazole or 40 mg omeprazole on a body surface area basis).

Physeal dysplasia in the femur was observed in offspring of rats treated with oral doses of

esomeprazole magnesium at doses equal to or greater than 138 mg/kg/day (about 34 times an oral human

dose of 40 mg esomeprazole or 40 mg omeprazole on a body surface area basis).

Effects on maternal bone were observed in pregnant and lactating rats in the pre- and postnatal toxicity

study when esomeprazole magnesium was administered at oral doses of 14 mg/kg/day to 280 mg/kg/day

(about 3.4 to 68 times an oral human dose of 40 mg esomeprazole or 40 mg omeprazole on a body

surface area basis). When rats were dosed from gestational day 7 through weaning on postnatal day 21, a

statistically significant decrease in maternal femur weight of up to 14% (as compared to placebo

treatment) was observed at doses equal to or greater than 138 mg/kg/day (about 34 times an oral human

dose of 40 mg esomeprazole or 40 mg omeprazole on a body surface area basis).

A pre- and postnatal development study in rats with esomeprazole strontium (using equimolar doses

compared to esomeprazole magnesium study) produced similar results in dams and pups as described

above.

A follow up developmental toxicity study in rats with further time points to evaluate pup bone

development from postnatal day 2 to adulthood was performed with esomeprazole magnesium at oral

doses of 280 mg/kg/day (about 68 times an oral human dose of 40 mg on a body surface area basis)

where esomeprazole administration was from either gestational day 7 or gestational day 16 until

parturition. When maternal administration was confined to gestation only, there were no effects on bone

physeal morphology in the offspring at any age.

8.2 Lactation

Risk Summary

Limited data suggest omeprazole may be present in human milk. There are no data on the effects of

omeprazole on the breastfed infant or on milk production. The developmental and health benefits of

breastfeeding should be considered along with the mother's clinical need for omeprazole delayed-

release capsules and any potential adverse effects on the breastfed infant from omeprazole delayed-

release capsules or from the underlying maternal condition.

8.4 Pediatric Use

The safety and effectiveness of omeprazole delayed-release capsules have been established in

pediatric patients 1 to 16 years for the treatment of symptomatic GERD, treatment of EE due to acid-

mediated GERD, and maintenance of healing of EE due to acid-mediated GERD. Use of omeprazole

delayed-release capsules in this age group is supported by adequate and well-controlled studies in

adults and uncontrolled safety, efficacy and pharmacokinetic studies performed in pediatric and

adolescent patients [see Clinical Pharmacology (12.3), Clinical Studies (14.8)].

The safety and effectiveness of omeprazole have been established in pediatric patients 1 month to less

than 1 year of age for the treatment of EE due to acid-mediated GERD and is supported by adequate and

well-controlled studies in adults and safety, pharmacokinetic, and pharmacodynamic studies performed

in pediatric patients [see Clinical Pharmacology (12.3)].

In the pediatric population, adverse reactions of the respiratory system were frequently reported in the

entire (1 month to 16 year) age group. Otitis media was frequently reported in the 1 month to < 1 year

age group, fever was frequently reported in the 1 to < 2 year age group, and accidental injuries were

frequently reported in the 2 to 16 year age group [see Adverse Reactions (6.1)] .

The safety and effectiveness of omeprazole have not been established in:

patients less than 1 year of age for:

Treatment of symptomatic GERD

Maintenance of healing of EE due to acid-mediated GERD

pediatric patients for:

Treatment of active duodenal ulcer

H. pylori eradication to reduce the risk of duodenal ulcer recurrence

Treatment of active benign gastric ulcer

Pathological hypersecretory conditions

patients less than 1 month of age for any indication.

Juvenile Animal Data

Esomeprazole, an enantiomer of omeprazole, was shown to decrease body weight, body weight gain,

femur weight, femur length, and overall growth at oral doses about 34 to 68 times a daily human dose of

40 mg esomeprazole or 40 mg omeprazole based on body surface area in a juvenile rat toxicity study.

The animal to human dose multiples are based on the assumption of equal systemic exposure to

esomeprazole in humans following oral administration of either 40 mg esomeprazole or 40 mg

omeprazole.

A 28-day toxicity study with a 14-day recovery phase was conducted in juvenile rats with esomeprazole

magnesium at doses of 70 mg/kg/day to 280 mg/kg/day (about 17 to 68 times a daily oral human dose of

40 mg esomeprazole or 40 mg omeprazole on a body surface area basis). An increase in the number of

deaths at the high dose of 280 mg/kg/day was observed when juvenile rats were administered

esomeprazole magnesium from postnatal day 7 through postnatal day 35. In addition, doses equal to or

greater than 140 mg/kg/day (about 34 times a daily oral human dose of 40 mg esomeprazole or 40 mg

omeprazole on a body surface area basis), produced treatment-related decreases in body weight

(approximately 14%) and body weight gain, decreases in femur weight and femur length, and affected

overall growth. Comparable findings described above have also been observed in this study with

another esomeprazole salt, esomeprazole strontium, at equimolar doses of esomeprazole.

8.5 Geriatric Use

Omeprazole was administered to over 2,000 elderly individuals (≥ 65 years of age) in clinical trials in

the U.S. and Europe. There were no differences in safety and effectiveness between the elderly and

younger subjects. Other reported clinical experience has not identified differences in response between

the elderly and younger subjects, but greater sensitivity of some older individuals cannot be ruled out.

Pharmacokinetic studies have shown the elimination rate was somewhat decreased in the elderly and

bioavailability was increased. The plasma clearance of omeprazole was 250 mL/min (about half that of

young volunteers) and its plasma half-life averaged one hour, about twice that of young healthy

volunteers. However, no dosage adjustment is necessary in the elderly [see Clinical Pharmacology

(12.3)].

8.6 Hepatic Impairment

In patients with hepatic impairment (Child-Pugh Class A, B, or C) exposure to omeprazole substantially

increased compared to healthy subjects. Dosage reduction of omeprazole delayed-release capsules to

10 mg once daily is recommended for patients with hepatic impairment for maintenance of healing of EE

[see Dosage and Administration (2.1), Clinical Pharmacology (12.3)].

8.7 Asian Population

In studies of healthy subjects, Asians had approximately a four-fold higher exposure than Caucasians.

Dosage reduction of omeprazole delayed-release capsules to 10 mg once daily is recommended for

Asian patients for maintenance of healing of EE [see Dosage and Administration (2.1), Clinical

Pharmacology (12.5)].

10 OVERDOSAGE

Reports have been received of overdosage with omeprazole in humans. Doses ranged up to 2400 mg

(120 times the usual recommended clinical dose). Manifestations were variable, but included confusion,

drowsiness, blurred vision, tachycardia, nausea, vomiting, diaphoresis, flushing, headache, dry mouth,

and other adverse reactions similar to those seen in normal clinical experience [see Adverse Reactions

(6)]. Symptoms were transient, and no serious clinical outcome has been reported when omeprazole

delayed-release capsules were taken alone. No specific antidote for omeprazole overdosage is known.

Omeprazole is extensively protein bound and is, therefore, not readily dialyzable. In the event of

overdosage, treatment should be symptomatic and supportive.

If over-exposure occurs, call your Poison Control Center at 1-800-222-1222 for current information on

the management of poisoning or overdosage.

11 DESCRIPTION

The active ingredient in omeprazole delayed-release capsules, USP is a substituted benzimidazole, 5-

methoxy-2-[[(4-methoxy-3, 5-dimethyl-2-pyridinyl) methyl] sulfinyl]-1 H-benzimidazole, a compound

that inhibits gastric acid secretion. Its molecular formula is C

S, with a molecular weight

of 345.42. The structural formula is:

Omeprazole, USP 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.

Omeprazole 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 beads with

the following inactive ingredients: ammonium hydroxide, dibutyl sebacate, D&C Yellow No. 10, FD&C

Green No. 3, gelatin, ethylcellulose, fumed silica, hypromellose, methacrylic acid, oleic acid, silicon

dioxide, sodium lauryl sulfate, sugar spheres, talc, titanium dioxide and triethyl citrate. The 40 mg

empty gelatin capsule shell also contains FD&C Blue No. 1. In addition, the white imprinting ink

contains ammonium hydroxide, propylene glycol, shellac glaze, simethicone and titanium dioxide.

Meets USP Dissolution Test 2.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Omeprazole belongs to a class of antisecretory compounds, the substituted benzimidazoles, that

suppress gastric acid secretion by specific inhibition of the H

ATPase enzyme system at the

secretory surface of the gastric parietal cell. Because this enzyme system is regarded as the acid

(proton) pump within the gastric mucosa, omeprazole has been characterized as a gastric acid-pump

inhibitor, in that it blocks the final step of acid production. This effect is dose-related and leads to

inhibition of both basal and stimulated acid secretion irrespective of the stimulus.

12.2 Pharmacodynamics

Antisecretory Activity

After oral administration, the onset of the antisecretory effect of omeprazole occurs within one hour,

with the maximum effect occurring within two hours. Inhibition of secretion is about 50% of maximum

at 24 hours and the duration of inhibition lasts up to 72 hours. The antisecretory effect thus lasts far

longer than would be expected from the very short (less than one hour) plasma half-life, apparently due

to prolonged binding to the parietal H

ATPase enzyme. When the drug is discontinued, secretory

activity returns gradually, over 3 to 5 days. The inhibitory effect of omeprazole on acid secretion

increases with repeated once-daily dosing, reaching a plateau after four days.

Results from numerous studies of the antisecretory effect of multiple doses of 20 mg and 40 mg of

omeprazole in healthy subjects and patients are shown below. The “max” value represents

determinations at a time of maximum effect (2 to 6 hours after dosing), while “min” values are those 24

hours after the last dose of omeprazole.

Table 5: Range of Mean Values from Multiple Studies of the Mean Antisecretory Effects of

Omeprazole After Multiple Daily Dosing

Omeprazole 20 mg

Omeprazole 40 mg

Parameter

Max

Min

Max

Min

% Decrease in Basal Acid Output

58 to 80

80 to 93

% Decrease in Peak Acid Output

50 to 59

62 to 68

% Decrease in 24-hr. Intragastric Acidity

80 to 97

92 to 94

Single daily oral doses of omeprazole ranging from a dose of 10 mg to 40 mg have produced 100%

inhibition of 24-hour intragastric acidity in some patients.

Serum Gastrin Effects

In studies involving more than 200 patients, serum gastrin levels increased during the first 1 to 2 weeks

of once-daily administration of therapeutic doses of omeprazole in parallel with inhibition of acid

secretion. No further increase in serum gastrin occurred with continued treatment. In comparison with

histamine H

-receptor antagonists, the median increases produced by 20 mg doses of omeprazole were

higher (1.3 to 3.6 fold versus 1.1 to 1.8 fold increase). Gastrin values returned to pretreatment levels,

usually within 1 to 2 weeks after discontinuation of therapy.

Increased gastrin causes enterochromaffin-like cell hyperplasia and increased serum Chromogranin A

(CgA) levels. The increased CgA levels may cause false positive results in diagnostic investigations

for neuroendocrine tumors [see Warnings and Precautions (5.10)].

Enterochromaffin-like (ECL) Cell Effects

Human gastric biopsy specimens have been obtained from more than 3,000 patients (both children and

adults) treated with omeprazole in long-term clinical trials. The incidence of ECL cell hyperplasia in

these studies increased with time; however, no case of ECL cell carcinoids, dysplasia, or neoplasia has

been found in these patients. However, these studies are of insufficient duration and size to rule out the

possible influence of long-term administration of omeprazole on the development of any premalignant

or malignant conditions.

Other Effects

Systemic effects of omeprazole in the CNS, cardiovascular and respiratory systems have not been found

to date. Omeprazole, given in oral doses of 30 mg or 40 mg for 2 to 4 weeks, had no effect on thyroid

function, carbohydrate metabolism, or circulating levels of parathyroid hormone, cortisol, estradiol,

testosterone, prolactin, cholecystokinin or secretin.

No effect on gastric emptying of the solid and liquid components of a test meal was demonstrated after a

single dose of omeprazole 90 mg. In healthy subjects, a single intravenous dose of omeprazole (0.35

mg/kg) had no effect on intrinsic factor secretion. No systematic dose-dependent effect has been

observed on basal or stimulated pepsin output in humans.

However, when intragastric pH is maintained at 4.0 or above, basal pepsin output is low, and pepsin

activity is decreased.

As do other agents that elevate intragastric pH, omeprazole administered for 14 days in healthy subjects

produced a significant increase in the intragastric concentrations of viable bacteria. The pattern of the

bacterial species was unchanged from that commonly found in saliva. All changes resolved within three

Single Studies

days of stopping treatment.

The course of Barrett’s esophagus in 106 patients was evaluated in a U.S. double-blind controlled

study of omeprazole delayed-release capsules 40 mg twice daily for 12 months followed by 20 mg

twice daily for 12 months or ranitidine 300 mg twice daily for 24 months. No clinically significant

impact on Barrett’s mucosa by antisecretory therapy was observed. Although neosquamous epithelium

developed during antisecretory therapy, complete elimination of Barrett’s mucosa was not achieved. No

significant difference was observed between treatment groups in development of dysplasia in Barrett’s

mucosa and no patient developed esophageal carcinoma during treatment. No significant differences

between treatment groups were observed in development of ECL cell hyperplasia, corpus atrophic

gastritis, corpus intestinal metaplasia, or colon polyps exceeding 3 mm in diameter.

12.3 Pharmacokinetics

Omeprazole is a time-dependent inhibitor of CYP2C19, resulting in autoinhibition and nonlinear

pharmacokinetics. The systemic exposure increases in a more than dose proportional manner after

multiple oral doses of omeprazole. Compared to the first dose, the systemic exposure (C

and AUC

) at steady state following once a day dosing increased by 61% and 62%, respectively, compared to

after the first dose for the 20 mg dose of omeprazole delayed-release capsules and increased by 118%

and 175%, respectively, for the 40 mg dose of omeprazole delayed-release capsules.

Absorption

Omeprazole delayed-release capsules contain an enteric-coated bead formulation of omeprazole

(because omeprazole is acid-labile), so that absorption of omeprazole begins only after the beads leave

the stomach. Absorption is rapid, with peak plasma concentrations of omeprazole occurring within 0.5

to 3.5 hours. Peak plasma concentrations of omeprazole and AUC are approximately proportional to

doses up to 40 mg, but because of a saturable first-pass effect, a greater than linear response in peak

plasma concentration and AUC occurs with doses greater than 40 mg. Absolute bioavailability

(compared with intravenous administration) is about 30% to 40% at doses of 20 mg to 40 mg, due in

large part to presystemic metabolism. In healthy subjects the plasma half-life is 0.5 to 1 hour, and the

total body clearance is 500 mL/min to 600 mL/min.

The bioavailability of omeprazole increases slightly upon repeated administration of omeprazole

delayed-release capsules.

The systemic exposure (C

and AUC) are similar when a 40 mg omeprazole delayed-release

capsule is administered with and without applesauce. However, administration of a 20 mg omeprazole

delayed-release capsule with applesauce, results in a mean 25% reduction in C

without a significant

change in AUC compared to administration without applesauce. The clinical relevance of this finding is

unknown.

Distribution

Protein binding is approximately 95%.

Elimination

Metabolism

Omeprazole is extensively metabolized by the cytochrome P450 (CYP) enzyme system. The major part

of its metabolism is dependent on the polymorphically expressed CYP2C19, responsible for the

formation of hydroxyomeprazole, the major metabolite in plasma. The remaining part is dependent on

another specific isoform, CYP3A4, responsible for the formation of omeprazole sulphone.

Excretion

Following single dose oral administration of a buffered solution of omeprazole, little if any unchanged

0-24h

drug was excreted in urine. The majority of the dose (about 77%) was eliminated in urine as at least six

metabolites. Two were identified as hydroxyomeprazole and the corresponding carboxylic acid. The

remainder of the dose was recoverable in feces. This implies a significant biliary excretion of the

metabolites of omeprazole. Three metabolites have been identified in plasma the sulfide and sulfone

derivatives of omeprazole, and hydroxyomeprazole. These metabolites have very little or no

antisecretory activity.

Combination Therapy with Antimicrobials

Omeprazole 40 mg daily was given in combination with clarithromycin 500 mg every 8 hours to healthy

adult male subjects. The steady state plasma concentrations of omeprazole were increased (C

, AUC

, and T

increases of 30%, 89% and 34%, respectively) by the concomitant administration of

clarithromycin. The observed increases in omeprazole plasma concentration were associated with the

following pharmacological effects. The mean 24-hour gastric pH value was 5.2 when omeprazole was

administered alone and 5.7 when co-administered with clarithromycin.

The plasma concentrations of clarithromycin and 14-hydroxy-clarithromycin were increased by the

concomitant administration of omeprazole. For clarithromycin, the mean C

was 10% greater, the

mean C

was 27% greater, and the mean AUC

was 15% greater when clarithromycin was

administered with omeprazole than when clarithromycin was administered alone. Similar results were

seen for 14-hydroxy-clarithromycin, the mean C

was 45% greater, the mean C

was 57% greater,

and the mean AUC

was 45% greater. Clarithromycin concentrations in the gastric tissue and mucus

were also increased by concomitant administration of omeprazole.

Table 6: Clarithromycin Tissue Concentrations 2 hours after Dose

Tis s ue

Clarithromycin

Clarithromycin + Omeprazole

Antrum

10.48 ± 2.01 (n = 5)

19.96 ± 4.71 (n = 5)

Fundus

20.81 ± 7.64 (n = 5)

24.25 ± 6.37 (n = 5)

Mucus

4.15 ± 7.74 (n = 4)

39.29 ± 32.79 (n = 4)

Specific Populations

Age

Geriatric Population

The elimination rate of omeprazole was somewhat decreased in the elderly, and bioavailability was

increased. Omeprazole was 76% bioavailable when a single 40 mg oral dose of omeprazole (buffered

solution) was administered to healthy elderly volunteers, versus 58% in young volunteers given the

same dose. Nearly 70% of the dose was recovered in urine as metabolites of omeprazole and no

unchanged drug was detected. The plasma clearance of omeprazole was 250 mL/min (about half that of

young volunteers) and its plasma half-life averaged one hour, about twice that of young healthy

volunteers.

Pediatric Population

2 to 16 Yea rs o f Ag e

The pharmacokinetics of omeprazole have been investigated in pediatric patients 2 to 16 years of age:

Table 7: Pharmacokinetic Parameters of Omeprazole Following Single and Repeated Oral

0-24

*

Mean ± SD (μg/g)

Administration in Pediatric Populations Compared with Adults

Single or Repeated Oral

Dos ing/Parameter

Children ≤ 20 kg

2 to 5 years

10 mg

Children > 20 kg

6 to 16 years

20 mg

Adults

(mean 76 kg)

23 to 29 years

(n = 12)

Single Dosing

(ng/mL)

288 (n = 10)

495 (n = 49)

(ng h/mL)

511 (n = 7)

1140 (n = 32)

1220

Repeated Dosing

(ng/mL)

539 (n = 4)

851 (n = 32)

1458

(ng h/mL)

1179 (n = 2)

2276 (n = 23)

3352

Following comparable mg/kg doses of omeprazole, younger children (2 to 5 years of age) have lower

AUCs than children 6 to 16 years of age or adults; AUCs of the latter two groups did not differ [see

Dosage and Administration (2)].

1 to 11 Mo nths o f Ag e

A population pharmacokinetics model was used to determine appropriate doses of omeprazole in

pediatric patients 1 month to less than 1 year of age for treatment (up to 6 weeks) of erosive esophagitis

due to acid-mediated GERD. The model was based on data from 64 children 0.5 month to 16 years of

age. Only limited data were available in children below the age of 1 year. Pediatric doses were

simulated in the age group of 1 to 11 months, to achieve comparable omeprazole exposures with adults

following treatment with 20 mg once daily [see Dosage and Administration (2.2)].

Race/Ethnicity

[See Clinical Pharmacology (12.5).]

Renal Impairment

In patients with chronic renal impairment (creatinine clearance between 10 mL/min/1.73 m

and 62

mL/min/1.73 m

), the disposition of omeprazole was very similar to that in healthy subjects, although

there was a slight increase in bioavailability. Because urinary excretion is a primary route of excretion

of omeprazole metabolites, their elimination slowed in proportion to the decreased creatinine clearance.

This increase in bioavailability is not considered to be clinically meaningful.

Hepatic Impairment

In patients with chronic hepatic disease classified as Child-Pugh Class A (n = 3), B (n = 4) and C (n = 1),

the bioavailability increased to approximately 100% compared to healthy subjects, reflecting decreased

first-pass effect, and the plasma half-life of the drug increased to nearly 3 hours compared with the

half-life in healthy subjects of 0.5 to 1 hour. Plasma clearance averaged 70 mL/min, compared with a

value of 500 mL/min to 600 mL/min in healthy subjects [see Dosage and Administration (2.1), Use in

Specific Populations (8.6)].

Drug Interaction Studies

Effect of Omeprazole on Other Drugs

Data from single and repeated dose studies. Doses of 10 mg, 20 mg and 4 0 mg omeprazole as enteric-coated

granules.

Data from a single and repeated dose study. Doses of 10 mg, 20 mg and 4 0 mg omeprazole as enteric-coated

granules.

Plasma concentration adjusted to an oral dose of 1 mg/kg.

Omeprazole is a time-dependent inhibitor of CYP2C19 and can increase the systemic exposure of co-

administered drugs that are CYP2C19 substrates. In addition, administration of omeprazole increases

intragastric pH and can alter the systemic exposure of certain drugs that exhibit pH-dependent

solubility.

Antiretrovirals

For some antiretroviral drugs, such as rilpivirine, atazanavir and nelfinavir, decreased serum

concentrations have been reported when given together with omeprazole [see Drug Interactions (7)].

Rilpivirine: Following multiple doses of rilpivirine (150 mg, daily) and omeprazole (20 mg, daily),

AUC was decreased by 40%, C

by 40%, and C

by 33% for rilpivirine.

Nelfinavir: Following multiple doses of nelfinavir (1250 mg, twice daily) and omeprazole (40 mg

daily), AUC was decreased by 36% and 92%, C

by 37% and 89% and C

by 39% and 75%,

respectively for nelfinavir and M8.

Atazanavir: Following multiple doses of atazanavir (400 mg, daily) and omeprazole (40 mg, daily, 2

hours before atazanavir), AUC was decreased by 94%, C

by 96%, and C

by 95%.

Saquinavir: Following multiple dosing of saquinavir/ritonavir (1000 mg/100 mg) twice daily for 15 days

with omeprazole 40 mg daily co-administered days 11 to 15.

AUC was increased by 82%, C

by 75%, and C

by 106%. The mechanism behind this interaction

is not fully elucidated. Therefore, clinical and laboratory monitoring for saquinavir toxicity is

recommended during concurrent use with omeprazole delayed-release capsules.

Clopidogrel

In a crossover clinical study, 72 healthy subjects were administered clopidogrel (300 mg loading dose

followed by 75 mg per day) alone and with omeprazole (80 mg at the same time as clopidogrel) for 5

days. The exposure to the active metabolite of clopidogrel was decreased by 46% (Day 1) and 42%

(Day 5) when clopidogrel and omeprazole were administered together.

Results from another crossover study in healthy subjects showed a similar pharmacokinetic interaction

between clopidogrel (300 mg loading dose/75 mg daily maintenance dose) and omeprazole 80 mg daily

when co-administered for 30 days. Exposure to the active metabolite of clopidogrel was reduced by

41% to 46% over this time period.

In another study, 72 healthy subjects were given the same doses of clopidogrel and 80 mg omeprazole

but the drugs were administered 12 hours apart; the results were similar, indicating that administering

clopidogrel and omeprazole at different times does not prevent their interaction [see Warnings and

Precautions (5.6), Drug Interactions (7)].

Mycophenolate Mofetil

Administration of omeprazole 20 mg twice daily for 4 days and a single 1000 mg dose of MMF

approximately one hour after the last dose of omeprazole to 12 healthy subjects in a cross-over study

resulted in a 52% reduction in the C

and 23% reduction in the AUC of MPA [see Drug Interactions

(7)].

Cilostazol

Omeprazole acts as an inhibitor of CYP2C19. Omeprazole, given in doses of 40 mg daily for one week

to 20 healthy subjects in cross-over study, increased C

and AUC of cilostazol by 18% and 26%,

respectively. The C

and AUC of one of the active metabolites, 3,4- dihydro-cilostazol, which has 4

to 7 times the activity of cilostazol, were increased by 29% and 69%, respectively. Co-administration

of cilostazol with omeprazole is expected to increase concentrations of cilostazol and the above

mentioned active metabolite [see Drug Interactions (7)].

Diazepam

Concomitant administration of omeprazole 20 mg once daily and diazepam 0.1 mg/kg given intravenously

resulted in 27% decrease in clearance and 36% increase in diazepam half-life [see Drug Interactions

(7)].

Digoxin

Concomitant administration of omeprazole 20 mg once daily and digoxin in healthy subjects increased

the bioavailability of digoxin by 10% (30% in two subjects) [see Drug Interactions (7)].

Effect of Other Drugs on Omeprazole

Voriconazole

Concomitant administration of omeprazole and voriconazole (a combined inhibitor of CYP2C19 and

CYP3A4) resulted in more than doubling of the omeprazole exposure. When voriconazole (400 mg

every 12 hours for one day, followed by 200 mg once daily for 6 days) was given with omeprazole (40

mg once daily for 7 days) to healthy subjects, the steady state C

and AUC

of omeprazole

significantly increased: an average of 2 times (90% CI: 1.8, 2.6) and 4 times (90% CI: 3.3, 4.4),

respectively, as compared to when omeprazole was given without voriconazole [see Drug Interactions

(7)].

12.4 Microbiology

Omeprazole and clarithromycin dual therapy and omeprazole, clarithromycin and amoxicillin triple

therapy have been shown to be active against most strains of Helicobacter pylori in vitro and in clinical

infections [see Indications and Usage (1.2), Clinical Studies (14.2)].

Helicobacter pylori

Susceptibility testing of H. pylori isolates was performed for amoxicillin and clarithromycin using agar

dilution methodology

, and minimum inhibitory concentrations (MICs) were determined.

Standardized susceptibility test procedures require the use of laboratory control microorganisms to

control the technical aspects of the laboratory procedures.

Pretreatment Resistance

Clarithromycin pretreatment resistance rates were 3.5% (4/113) in the omeprazole/clarithromycin dual

therapy studies (4 and 5) and 9.3% (41/439) in omeprazole/clarithromycin/amoxicillin triple therapy

studies (1, 2 and 3).

Amoxicillin pretreatment susceptible isolates (≤ 0.25 μg/mL) were found in 99.3% (436/439) of the

patients in the omeprazole/clarithromycin/amoxicillin triple therapy studies (1, 2, and 3). Amoxicillin

pretreatment minimum inhibitory concentrations (MICs) > 0.25 μg/mL occurred in 0.7% (3/439) of the

patients, all of whom were in the clarithromycin and amoxicillin study arm. One patient had an

unconfirmed pretreatment amoxicillin minimum inhibitory concentration (MIC) of > 256 μg/mL by Etest

Table 8: Clarithromycin Susceptibility Test Results and Clinical/Bacteriological Outcomes

Clarithromycin Susceptibility Test Results and Clinical/Bacteriological Outcomes

Clarithromycin

Pretreatment Results

Clarithromycin Post-treatment Results

H. pylori negative –

eradicated

H. pylori positive – not eradicated Post-treatment

susceptibility results

0-24

Dual Therapy – (omeprazole 40 mg once daily/clarithromycin 500 mg three times daily for 14 days

followed by omeprazole 20 mg once daily for another 14 days) (Studies 4, 5)

Susceptible

Intermediate

Resistant

Triple Therapy – (omeprazole 20 mg twice daily/clarithromycin 500 mg twice daily/amoxicillin 1 g

twice daily for 10 days – Studies 1, 2, 3; followed by omeprazole 20 mg once daily for another 18 days

– Studies 1, 2)

Susceptible

Intermediate

Resistant

Patients not eradicated of H. pylori following omeprazole/clarithromycin/amoxicillin triple therapy or

omeprazole/clarithromycin dual therapy will likely have clarithromycin resistant H. pylori isolates.

Therefore, clarithromycin susceptibility testing should be done, if possible. Patients with

clarithromycin resistant H. pylori should not be treated with any of the following:

omeprazole/clarithromycin dual therapy, omeprazole/clarithromycin/amoxicillin triple therapy, or other

regimens which include clarithromycin as the sole antimicrobial agent.

Amoxicillin Susceptibility Test Results and Clinical/Bacteriological Outcomes

In the triple therapy clinical trials, 84.9% (157/185) of the patients in the

omeprazole/clarithromycin/amoxicillin treatment group who had pretreatment amoxicillin susceptible

MICs (≤ 0.25 μg/mL) were eradicated of H. pylori and 15.1% (28/185) failed therapy. Of the 28 patients

who failed triple therapy, 11 had no post-treatment susceptibility test results and 17 had post-treatment

H. pylori isolates with amoxicillin susceptible MICs. Eleven of the patients who failed triple therapy

also had post-treatment H. pylori isolates with clarithromycin resistant MICs.

Susceptibility Test for Helicobacter pylori

For susceptibility testing information about Helicobacter pylori, see Microbiology section in

prescribing information for clarithromycin and amoxicillin.

Effects on Gastrointestinal Microbial Ecology

Decreased gastric acidity due to any means including proton pump inhibitors, increases gastric counts

of bacteria normally present in the gastrointestinal tract. Treatment with proton pump inhibitors may lead

to slightly increased risk of gastrointestinal infections such as Salmonella and Campylobacter and, in

hospitalized patients, possibly also Clostridium difficile.

12.5 Pharmacogenomics

CYP2C19, a polymorphic enzyme, is involved in the metabolism of omeprazole. The CYP2C19*1 allele

is fully functional while the CYP2C19*2 and *3 alleles are nonfunctional. There are other alleles

associated with no or reduced enzymatic function. Patients carrying two fully functional alleles are

extensive metabolizers and those carrying two loss-of-function alleles are poor metabolizers. In

extensive metabolizers, omeprazole is primarily metabolized by CYP2C19. The systemic exposure to

omeprazole varies with a patient’s metabolism status: poor metabolizers > intermediate metabolizers >

extensive metabolizers. Approximately 3% of Caucasians and 15% to 20% of Asians are CYP2C19

poor metabolizers.

In a pharmacokinetic study of single 20 mg omeprazole dose, the AUC of omeprazole in Asian subjects

Includes only patients with pretreatment clarithromycin susceptibility test results.

Susceptible (S) MIC ≤ 0.25 μg/mL, Intermediate (I) MIC 0.5 μg/mL to 1.0 μg/mL, Resistant (R) MIC ≥ 2 μg/mL.

was approximately four-fold of that in Caucasians [see Dosage and Administration (2.1), Use in Specific

Populations (8.7)].

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

In two 24-month carcinogenicity studies in rats, omeprazole at daily doses of 1.7 mg/kg/day, 3.4

mg/kg/day, 13.8 mg/kg/day, 44.0 mg/kg/day and 140.8 mg/kg/day (about 0.4 to 34 times a human dose of

40 mg/day, as expressed on a body surface area basis) produced gastric ECL cell carcinoids in a dose-

related manner in both male and female rats; the incidence of this effect was markedly higher in female

rats, which had higher blood levels of omeprazole. Gastric carcinoids seldom occur in the untreated

rat. In addition, ECL cell hyperplasia was present in all treated groups of both sexes. In one of these

studies, female rats were treated with 13.8 mg omeprazole/kg/day (about 3.4 times a human dose of 40

mg/day, based on body surface area) for one year, and then followed for an additional year without the

drug. No carcinoids were seen in these rats. An increased incidence of treatment-related ECL cell

hyperplasia was observed at the end of one year (94% treated versus 10% controls). By the second year

the difference between treated and control rats was much smaller (46% versus 26%) but still showed

more hyperplasia in the treated group. Gastric adenocarcinoma was seen in one rat (2%). No similar

tumor was seen in male or female rats treated for two years. For this strain of rat no similar tumor has

been noted historically, but a finding involving only one tumor is difficult to interpret. In a 52-week

toxicity study in Sprague-Dawley rats, brain astrocytomas were found in a small number of males that

received omeprazole at dose levels of 0.4 mg/kg/day, 2 mg/kg/day, and 16 mg/kg/day (about 0.1 to 3.9

times the human dose of 40 mg/day, based on a body surface area basis). No astrocytomas were

observed in female rats in this study. In a 2-year carcinogenicity study in Sprague-Dawley rats, no

astrocytomas were found in males or females at the high dose of 140.8 mg/kg/day (about 34 times the

human dose of 40 mg/day on a body surface area basis). A 78-week mouse carcinogenicity study of

omeprazole did not show increased tumor occurrence, but the study was not conclusive. A 26-week p53

(+/-) transgenic mouse carcinogenicity study was not positive.

Omeprazole was positive for clastogenic effects in an in vitro human lymphocyte chromosomal

aberration assay, in one of two in vivo mouse micronucleus tests, and in an in vivo bone marrow cell

chromosomal aberration assay. Omeprazole was negative in the in vitro Ames test, an in vitro mouse

lymphoma cell forward mutation assay, and an in vivo rat liver DNA damage assay.

Omeprazole at oral doses up to 138 mg/kg/day in rats (about 34 times an oral human dose of 40 mg on a

body surface area basis) was found to have no effect on fertility and reproductive performance.

In 24-month carcinogenicity studies in rats, a dose-related significant increase in gastric carcinoid

tumors and ECL cell hyperplasia was observed in both male and female animals [see Warnings and

Precautions (5)]. Carcinoid tumors have also been observed in rats subjected to fundectomy or long-

term treatment with other proton pump inhibitors or high doses of H

-receptor antagonists.

14 CLINICAL STUDIES

14.1 Active Duodenal Ulcer

In a multicenter, double-blind, placebo-controlled study of 147 patients with endoscopically

documented duodenal ulcer, the percentage of patients healed (per protocol) at 2 and 4 weeks was

significantly higher with omeprazole delayed-release capsules 20 mg once daily than with placebo (p ≤

0.01).

Treatment of Active Duodenal Ulcer % of Patients Healed

Omeprazole Delayed-Release Capsules

Placebo

20 mg a.m.

(n = 99)

a.m.

(n = 48)

Week 2

Week 4

Complete daytime and nighttime pain relief occurred significantly faster (p ≤ 0.01) in patients treated

with omeprazole delayed-release capsules 20 mg than in patients treated with placebo. At the end of the

study, significantly more patients who had received omeprazole delayed-release capsules had complete

relief of daytime pain (p ≤ 0.05) and nighttime pain (p ≤ 0.01).

In a multicenter, double-blind study of 293 patients with endoscopically documented duodenal ulcer, the

percentage of patients healed (per protocol) at 4 weeks was significantly higher with omeprazole

delayed-release capsules 20 mg once daily than with ranitidine 150 mg b.i.d. (p < 0.01).

Treatment of Active Duodenal Ulcer % of Patients Healed

Omeprazole Delayed-Release Capsules

20 mg a.m.

(n = 145)

Ranitidine

150 mg twice daily

(n = 148)

Week 2

Week 4

Healing occurred significantly faster in patients treated with omeprazole delayed-release capsules than

in those treated with ranitidine 150 mg b.i.d. (p < 0.01).

In a foreign multinational randomized, double-blind study of 105 patients with endoscopically

documented duodenal ulcer, 20 mg and 40 mg of omeprazole delayed-release capsules were compared

with 150 mg b.i.d. of ranitidine at 2, 4 and 8 weeks. At 2 and 4 weeks both doses of omeprazole

delayed-release capsules were statistically superior (per protocol) to ranitidine, but 40 mg was not

superior to 20 mg of omeprazole delayed-release capsules, and at 8 weeks there was no significant

difference between any of the active drugs.

Treatment of Active Duodenal Ulcer % of Patients Healed

Omeprazole Delayed-Release Capsules

Ranitidine

20 mg

(n = 34)

40 mg

(n = 36)

150 mg twice daily

(n = 35)

Week 2

Week 4

Week 8

14.2 H. pylori Eradication in Patients with Duodenal Ulcer Disease

Triple Therapy (Omeprazole Delayed-Release Capsules/Clarithromycin/Amoxicillin)

Three U.S., randomized, double-blind clinical studies in patients with H. pylori infection and duodenal

ulcer disease (n = 558) compared omeprazole delayed-release capsules plus clarithromycin plus

amoxicillin with clarithromycin plus amoxicillin. Two studies (1 and 2) were conducted in patients with

an active duodenal ulcer, and the other study (3) was conducted in patients with a history of a duodenal

ulcer in the past 5 years but without an ulcer present at the time of enrollment. The dose regimen in the

(p ≤ 0.01)

(p < 0.01)

(p ≤ 0.01)

studies was omeprazole delayed-release capsules 20 mg twice daily plus clarithromycin 500 mg twice

daily plus amoxicillin 1 g twice daily for 10 days; or clarithromycin 500 mg twice daily plus

amoxicillin 1 g twice daily for 10 days. In studies 1 and 2, patients who took the omeprazole regimen

also received an additional 18 days of omeprazole delayed-release capsules 20 mg once daily.

Endpoints studied were eradication of H. pylori and duodenal ulcer healing (studies 1 and 2 only). H.

pylori status was determined by CLOtest

, histology and culture in all three studies. For a given patient

, H. pylori was considered eradicated if at least two of these tests were negative, and none was positive.

The combination of omeprazole plus clarithromycin plus amoxicillin was effective in eradicating H.

pylori.

Table 9: Per Protocol and Intent-to-Treat H. pylori Eradication Rates % of Patients Cured [95%

Confidence Interval]

Omeprazole Delayed-Release Capsules +

Clarithromycin + Amoxicillin

Clarithromycin + Amoxicillin

Per Protocol

Intent-to-T reat

Per Protocol

Intent-to-T reat

Study 1

[64, 86]

(n = 64)

[57, 79]

(n = 80)

43 [31, 56]

(n = 67)

37 [27, 48]

(n = 84)

Study 2

[67, 88]

(n = 65)

[61, 82]

(n = 77)

41 [29, 54]

(n = 68)

36 [26, 47]

(n = 83)

Study 3

[80, 96]

(n = 69)

[74, 91]

(n = 84)

33 [24, 44]

(n = 93)

32 [23, 42]

(n = 99)

Dual Therapy (Omeprazole Delayed-Release Capsules/Clarithromycin)

Four randomized, double-blind, multi-center studies (4, 5, 6, and 7) evaluated omeprazole delayed-

release capsules 40 mg once daily plus clarithromycin 500 mg three times daily for 14 days, followed

by omeprazole delayed-release capsules 20 mg once daily, (Studies 4, 5, and 7) or by omeprazole

delayed-release capsules 40 mg once daily (Study 6) for an additional 14 days in patients with active

duodenal ulcer associated with H. pylori. Studies 4 and 5 were conducted in the U.S. and Canada and

enrolled 242 and 256 patients, respectively. H. pylori infection and duodenal ulcer were confirmed in

219 patients in Study 4 and 228 patients in Study 5. These studies compared the combination regimen to

omeprazole delayed-release capsules and clarithromycin monotherapies. Studies 6 and 7 were

conducted in Europe and enrolled 154 and 215 patients, respectively. H. pylori infection and duodenal

ulcer were confirmed in 148 patients in Study 6 and 208 patients in Study 7. These studies compared the

combination regimen with omeprazole monotherapy. The results for the efficacy analyses for these

studies are described below. H. pylori eradication was defined as no positive test (culture or histology)

at 4 weeks following the end of treatment, and two negative tests were required to be considered

eradicated of H. pylori. In the per protocol analysis, the following patients were excluded: dropouts,

patients with missing H. pylori tests post-treatment, and patients that were not assessed for H. pylori

eradication because they were found to have an ulcer at the end of treatment.

The combination of omeprazole and clarithromycin was effective in eradicating H. pylori.

Patients were included in the analysis if they had confirmed duodenal ulcer disease (active ulcer, studies 1 and 2;

history of ulcer within 5 years, study 3) and H. pylori infection at baseline defined as at least two of three positive

endoscopic tests from CLOtest®, histology, and/or culture. Patients were included in the analysis if they

completed the study. Additionally, if patients dropped out of the study due to an adverse event related to the study

drug, they were included in the analysis as failures of therapy. The impact of eradication on ulcer recurrence has

not been assessed in patients with a past history of ulcer.

Patients were included in the analysis if they had documented H. pylori infection at baseline and had confirmed

duodenal ulcer disease. All dropouts were included as failures of therapy.

(p < 0.05) versus clarithromycin plus amoxicillin.

Table 10: H. pylori Eradication Rates (Per Protocol Analysis at 4 to 6 Weeks) % of Patients

Cured [95% Confidence Interval]

Omeprazole Delayed-Release

Capsules + Clarithromycin

Omeprazole Delayed-

Release Capsules

Clarithromycin

U.S. Studies

Study 4

74 [60, 85]

(n = 53)

0 [0, 7]

(n = 54)

31 [18, 47]

(n = 42)

Study 5

64 [51, 76]

(n = 61)

0 [0, 6]

(n = 59)

39 [24, 55]

(n = 44)

Non U.S. Studies

Study 6

83 [71, 92]

(n = 60)

1 [0, 7]

(n = 74)

Study 7

74 [64, 83]

(n = 86)

1 [0, 6]

(n = 90)

Ulcer healing was not significantly different when clarithromycin was added to omeprazole therapy

compared with omeprazole therapy alone.

The combination of omeprazole and clarithromycin was effective in eradicating H. pylori and reduced

duodenal ulcer recurrence.

Table 11: Duodenal Ulcer Recurrence Rates by H. pylori Eradication Status % of Patients with

Ulcer Recurrence

H. pylori eradicated

H. pylori not eradicated

U.S. Studies

6 months post-treatment

Study 4

(n = 49)

(n = 88)

Study 5

(n = 53)

(n = 106)

Non U.S. Studies

6 months post-treatment

Study 6

(n = 43)

(n = 78)

Study 7

(n = 53)

(n = 107)

12 months post-treatment

Study 6

(n = 39)

(n = 71)

14.3 Active Benign Gastric Ulcer

Statistically significantly higher than clarithromycin monotherapy (p < 0.05).

Statistically significantly higher than omeprazole monotherapy (p < 0.05).

H. pylori eradication status assessed at same time point as ulcer recurrence.

Combined results for omeprazole delayed-release capsules + clarithromycin, omeprazole delayed-release

capsules, and clarithromycin treatment arms.

(p ≤ 0.01) versus proportion with duodenal ulcer recurrence who were not H. pylori eradicated.

Combined results for omeprazole delayed-release capsules + clarithromycin and omeprazole delayed-release

capsules treatment arms.

In a U.S. multicenter, double-blind, study of omeprazole 40 mg once daily, 20 mg once daily, and

placebo in 520 patients with endoscopically diagnosed gastric ulcer, the following results were

obtained.

Treatment of Gastric Ulcer % of Patients Healed (All Patients Treated)

Omeprazole Delayed-

Release Capsules

20 mg once daily

(n = 202)

Omeprazole Delayed-

Release Capsules

40 mg once daily

(n = 214)

Placebo

(n = 104)

Week 4

47.5

55.6

30.8

Week 8

74.8

82.7

48.1

For the stratified groups of patients with ulcer size less than or equal to 1 cm, no difference in healing

rates between 40 mg and 20 mg was detected at either 4 or 8 weeks. For patients with ulcer size greater

than 1 cm, 40 mg was significantly more effective than 20 mg at 8 weeks.

In a foreign, multinational, double-blind study of 602 patients with endoscopically diagnosed gastric

ulcer, omeprazole 40 mg once daily, 20 mg once daily, and ranitidine 150 mg twice a day were

evaluated.

Treatment of Gastric Ulcer % of Patients Healed (All Patients Treated)

Omeprazole Delayed-

Release Capsules

20 mg once daily

(n = 200)

Omeprazole Delayed-

Release Capsules

40 mg once daily

(n = 187)

Ranitidine

150 mg twice daily

(n = 199)

Week 4

63.5

78.1

56.3

Week 8

81.5

91.4

78.4

14.4 Symptomatic GERD

A placebo-controlled study was conducted in Scandinavia to compare the efficacy of omeprazole 20 mg

or 10 mg once daily for up to 4 weeks in the treatment of heartburn and other symptoms in GERD

patients without EE. Results are shown below.

% Successful Symptomatic Outcome

Omeprazole

Delayed-Releas e

Caps ules

20 mg a.m.

Omeprazole Delayed-

Release Capsules

10 mg a.m.

Placebo

a.m.

All patients

(n = 205)

(n = 199)

(n = 105)

Patients with confirmed GERD

(n = 115)

(n = 109)

(n = 59)

(p < 0.01) omeprazole delayed-release capsules 4 0 mg or 20 mg versus placebo.

(p < 0.05) omeprazole delayed-release capsules 4 0 mg versus 20 mg.

*,†

(p < 0.01) omeprazole delayed-release capsules 4 0 mg versus ranitidine.

(p < 0.01) omeprazole delayed-release capsules 4 0 mg versus 20 mg.

*†

*†

*

Defined as complete resolution of heartburn.

(p < 0.005) versus 10 mg.

(p < 0.005) versus placebo.

†,‡

†,‡

14.5 EE due to Acid-Mediated GERD

In a U.S. multicenter double-blind placebo controlled study of 20 mg or 40 mg of omeprazole delayed-

release capsules in patients with symptoms of GERD and endoscopically diagnosed EE of grade 2 or

above, the percentage healing rates (per protocol) were as follows:

20 mg

Omeprazole Delayed-

Release Capsules

(n = 83)

40 mg

Omeprazole Delayed-

Release Capsules

(n = 87)

Placebo

(n = 43)

Week 4

Week 8

In this study, the 40 mg dose was not superior to the 20 mg dose of omeprazole delayed-release

capsules in the percentage healing rate. Other controlled clinical trials have also shown that omeprazole

delayed-release capsules is effective in severe GERD. In comparisons with histamine H

-receptor

antagonists in patients with EE, grade 2 or above, omeprazole delayed-release capsules in a dose of 20

mg was significantly more effective than the active controls. Complete daytime and nighttime heartburn

relief occurred significantly faster (p < 0.01) in patients treated with omeprazole delayed-release

capsules than in those taking placebo or histamine H

-receptor antagonists.

In this and five other controlled GERD studies, significantly more patients taking 20 mg omeprazole

(84%) reported complete relief of GERD symptoms than patients receiving placebo (12%).

14.6 Maintenance of Healing of EE due to Acid-Mediated GERD

In a U.S. double-blind, randomized, multicenter, placebo controlled study, two dose regimens of

omeprazole delayed-release capsules were studied in patients with endoscopically confirmed healed

esophagitis. Results to determine maintenance of healing of EE are shown below.

Life Table Analysis

Omeprazole Delayed-

Release Capsules

20 mg once daily

(n = 138)

Omeprazole Delayed-Release

Caps ules

20 mg 3 days per week

(n = 137)

Placebo

(n = 131)

Percent in endoscopic

remission at 6 months

In an international multicenter double-blind study, omeprazole delayed-release capsules 20 mg daily and

10 mg daily were compared with ranitidine 150 mg twice daily in patients with endoscopically

confirmed healed esophagitis. The table below provides the results of this study for maintenance of

healing of EE.

Life Table Analysis

Omeprazole Delayed-

Release Capsules

20 mg once daily

(n = 131)

Omeprazole Delayed-

Release Capsules

10 mg once daily

(n = 133)

Ranitidine

150 mg twice daily

(n = 128)

(p < 0.01) omeprazole delayed-release capsules versus placebo.

(p < 0.01) omeprazole delayed-release capsules 20 mg once daily versus omeprazole delayed-release capsules

20 mg 3 consecutive days per week or placebo.

Percent in endoscopic

remission at 12 months

In patients who initially had grades 3 or 4 erosive esophagitis, for maintenance after healing 20 mg

daily of omeprazole delayed-release capsules were effective, while 10 mg did not demonstrate

effectiveness.

14.7 Pathological Hypersecretory Conditions

In open studies of 136 patients with pathological hypersecretory conditions, such as Zollinger-Ellison

(ZE) syndrome with or without multiple endocrine adenomas, omeprazole delayed-release capsules

significantly inhibited gastric acid secretion and controlled associated symptoms of diarrhea, anorexia,

and pain. Doses ranging from 20 mg every other day to 360 mg per day maintained basal acid secretion

below 10 mEq/hr in patients without prior gastric surgery, and below 5 mEq/hr in patients with prior

gastric surgery.

Initial doses were titrated to the individual patient need, and adjustments were necessary with time in

some patients [see Dosage and Administration (2)] . Omeprazole delayed-release capsules were well

tolerated at these high dose levels for prolonged periods (> 5 years in some patients). In most ZE

patients, serum gastrin levels were not modified by omeprazole delayed-release capsules. However, in

some patients serum gastrin increased to levels greater than those present prior to initiation of

omeprazole therapy. At least 11 patients with ZE syndrome on long-term treatment with omeprazole

delayed-release capsules developed gastric carcinoids. These findings are believed to be a

manifestation of the underlying condition, which is known to be associated with such tumors, rather than

the result of the administration of omeprazole delayed-release capsules [see Adverse Reactions (6)].

14.8 Pediatric Studies for the Treatment of Symptomatic GERD, Treatment of EE due to Acid-

Mediated GERD, and Maintenance of Healing of EE due to Acid-Mediated GERD

Treatment of Symptomatic GERD

The effectiveness of omeprazole delayed-release capsules for the treatment of symptomatic GERD in

pediatric patients 1 to 16 years of age is based in part on data obtained from 125 pediatric patients in two

uncontrolled clinical studies.

The first study enrolled 12 pediatric patients 1 to 2 years of age with a history of clinically diagnosed

GERD. Patients were administered a single dose of omeprazole (0.5 mg/kg, 1 mg/kg, or 1.5 mg/kg) for 8

weeks as an open capsule in 8.4% sodium bicarbonate solution. Seventy-five percent (9/12) of the

patients had vomiting/regurgitation episodes decreased from baseline by at least 50%.

The second study enrolled 113 pediatric patients 2 to 16 years of age with a history of symptoms

suggestive of symptomatic GERD. Patients were administered a single dose of omeprazole (10 mg or

20 mg, based on body weight) for 4 weeks either as an intact capsule or as an open capsule in

applesauce. Successful response was defined as no moderate or severe episodes of either pain-related

symptoms or vomiting/regurgitation during the last 4 days of treatment. Results showed success rates of

60% (9/15; 10 mg omeprazole) and 59% (58/98; 20 mg omeprazole), respectively.

Treatment of EE due to Acid-Mediated GERD

In an uncontrolled, open-label dose-titration study, for the treatment of EE in pediatric patients 1 to 16

years of age required doses that ranged from 0.7 mg/kg/day to 3.5 mg/kg/day (80 mg/day). Doses were

initiated at 0.7 mg/kg/day. Doses were increased in increments of 0.7 mg/kg/day (if intraesophageal pH

showed a pH of < 4 for less than 6% of a 24-hour study). After titration, patients remained on treatment

(p = 0.01) omeprazole delayed-release capsules 20 mg once daily versus omeprazole delayed-release capsules

10 mg once daily or ranitidine.

(p = 0.03) omeprazole delayed-release capsules 10 mg once daily versus ranitidine.

for 3 months. Forty-four percent of the patients were healed on a dose of 0.7 mg/kg body weight; most

of the remaining patients were healed with 1.4 mg/kg after an additional 3 months’ treatment. EE was

healed in 51 of 57 (90%) children who completed the first course of treatment in the healing phase of

the study. In addition, after 3 months of treatment, 33% of the children had no overall symptoms, 57%

had mild reflux symptoms, and 40% had less frequent regurgitation/vomiting.

Maintenance of Healing of EE due to Acid-Mediated GERD

In an uncontrolled, open-label study of maintenance of healing of EE in 46 pediatric patients 1 to 16

years of age, 54% of patients required half the healing dose. The remaining patients increased the

healing dose (0.7 to a maximum of 2.8 mg/kg/day) either for the entire maintenance period, or returned

to half the dose before completion. Of the 46 patients who entered the maintenance phase, 19 (41%) had

no relapse during follow-up (range 4 to 25 months). In addition, maintenance therapy in EE patients

resulted in 63% of patients having no overall symptoms.

15 REFERENCES

1. Clinical and Laboratory Standards Institute (CLSI). Methods for Dilution Antimicrobial Susceptibility

Tests for Bacteria That Grow Aerobically; Approved Standard-Tenth Edition. CLSI Document M07-A10,

Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania,

19087, USA 2015.

16 HOW SUPPLIED/STORAGE AND HANDLING

Omeprazole Delayed-Release Capsules, USP are available containing 20 mg or 40 mg of omeprazole,

USP.

The 20 mg capsules are hard-shell gelatin capsules with a dark green opaque cap and a blue-green

opaque body filled with white to off-white beads. The capsule is axially printed with MYLAN over

6150 in white ink both on the cap and the body. They are available as follows:

NDC 60429-270-90

bottles of 90 capsules

NDC 60429-270-10

bottles of 1000 capsules

The 40 mg capsules are hard-shell gelatin capsules with a dark green opaque cap and a light-blue

opaque body filled with white to off-white beads. The capsule is axially printed with MYLAN over

5222 in white ink both on the cap and the body. They are available as follows:

NDC 60429-271-90

bottles of 90 capsules

NDC 60429-271-05

bottles of 500 capsules

Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.]

Protect from light and moisture.

Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.

PHARMACIST: Dispense a Medication Guide with each prescription.

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for

Use).

Adverse Reactions:Advise patients to report to their healthcare provider if they experience any signs

or symptoms consistent with:

Hypersensitivity reactions [see Contraindications (4)] .

Acute Interstitial Nephritis [see Warnings and Precautions (5.2)] .

Clostridium difficile-Associated Diarrhea [see Warnings and Precautions (5.3)] .

Bone Fracture [see Warnings and Precautions (5.4)] .

Cutaneous and Systemic Lupus Erythematosus [see Warnings and Precautions (5.5)] .

Cyanocobalamin (Vitamin B-12) Deficiency [see Warnings and Precautions (5.7)] .

Hypomagnesemia [see Warnings and Precautions (5.8)] .

Drug Interactions:Advise patients to report to their healthcare provider if they start treatment with

clopidogrel, St. John’s Wort or rifampin; or, if they take high-dose methotrexate [see Warnings and

Precautions ( 5.6, 5.9, 5.11)].

Adminis tration:

Take omeprazole delayed-release capsules before meals.

Antacids may be used concomitantly with omeprazole delayed-release capsules.

Missed doses: If a dose is missed, administer as soon as possible. However, if the next scheduled

dose is due, do not take the missed dose, and take the next dose on time. Do not take two doses at one

time to make up for a missed dose.

OmeprazoleDelayed-Release Capsules:

Swallow omeprazole delayed-release capsules whole; do not chew.

For patients unable to swallow an intact capsule, omeprazole delayed-release capsules can be

opened and administered in applesauce, as described in the Medication Guide.

Medication Guide

Omeprazole Delayed-Release Capsules, USP

(oh mep' ra zole)

Read this Medication Guide before you start taking omeprazole delayed-release capsules and each time

you get a refill. There may be new information. This information does not take the place of talking with

your doctor about your medical condition or your treatment.

What is the most important information I should know about omeprazole delayed-release

caps ules ?

Omeprazole delayed-release capsules may help your acid-related symptoms, but you could still

have serious stomach problems. Talk with your doctor.

Omeprazole delayed-release capsules can cause serious side effects, including:

A type of kidney problem (acute interstitial nephritis). Some people who take proton pump

inhibitor (PPI) medicines, including omeprazole delayed-release capsules, may develop a kidney

problem called acute interstitial nephritis that can happen at any time during treatment with

omeprazole delayed-release capsules. Call your doctor if you have a decrease in the amount that

you urinate or if you have blood in your urine.

Diarrhea. Omeprazole delayed-release capsules may increase your risk of getting severe diarrhea.

This diarrhea may be caused by an infection ( Clostridium difficile) in your intestines. Call your

doctor right away if you have watery stool, stomach pain, and fever that does not go away.

Bone fractures. People who take multiple daily doses of PPI medicines for a long period of time (a

year or longer) may have an increased risk of fractures of the hip, wrist, or spine. You should take

omeprazole delayed-release capsules exactly as prescribed, at the lowest dose possible for your

treatment and for the shortest time needed. Talk to your doctor about your risk of bone fracture if

you take omeprazole delayed-release capsules.

Certain types of lupus erythematosus. Lupus erythematosus is an autoimmune disorder (the

body’s immune cells attack other cells or organs in the body). Some people who take PPI medicines,

including omeprazole delayed-release capsules, may develop certain types of lupus erythematosus

or have worsening of the lupus they already have. Call your doctor right away if you have new or

worsening joint pain or a rash on your cheeks or arms that gets worse in the sun.

Omeprazole delayed-release capsules can have other serious side effects. See “What are the

possible side effects of omeprazole delayed-release capsules?”

What are omeprazole delayed-release capsules?

Omeprazole delayed-release capsules are a prescription medicine called a proton pump inhibitor (PPI).

Omeprazole delayed-release capsules reduce the amount of acid in your stomach.

Omeprazole delayed-release capsules are used in adults:

for up to 8 weeks for the healing of duodenal ulcers. The duodenal area is the area where food

passes when it leaves the stomach.

with certain antibiotics for 10 to 14 days to treat an infection caused by bacteria called H. pylori. If

needed, your doctor may decide to prescribe another 14 to 18 days of omeprazole delayed-release

capsules by itself after the antibiotics. Sometimes H. pylori bacteria can cause duodenal ulcers. The

infection needs to be treated to prevent the ulcers from coming back.

for up to 8 weeks for healing stomach ulcers.

for up to 4 weeks to treat heartburn and other symptoms that happen with gastroesophageal reflux

disease (GERD). GERD happens when acid in your stomach backs up into the tube (esophagus) that

connects your mouth to your stomach. This may cause a burning feeling in your chest or throat, sour

taste, or burping.

for up to 8 weeks to heal acid-related damage to the lining of the esophagus (called erosive

esophagitis or EE). If needed, your doctor may decide to prescribe another 4 weeks of omeprazole

delayed-release capsules.

to maintain healing of the esophagus. It is not known if omeprazole delayed-release capsules are

safe and effective when used for longer than 12 months (1 year) for this purpose.

for the long-term treatment of conditions where your stomach makes too much acid. This includes a

rare condition called Zollinger-Ellison syndrome.

For children 1 to 16 years of age, omeprazole delayed-release capsules are used:

for up to 4 weeks to treat heartburn and other symptoms that happen with gastroesophageal reflux

disease (GERD).

for up to 8 weeks to treat gastroesophageal reflux disease (GERD) with acid-related damage to the

lining of the esophagus [called erosive esophagitis (or EE) due to acid-mediated GERD].

to maintain healing of the esophagus. It is not known if omeprazole delayed-release capsules are

safe and effective when used longer than 12 months (1 year) for this purpose.

For children 1 month to less than 12 months (1 year) of age, omeprazole is used:

for up to 6 weeks to treat gastroesophageal reflux disease (GERD) with acid-related damage to the

lining of the esophagus [called erosive esophagitis (or EE) due to acid-mediated GERD]. It is not

known if omeprazole is safe and effective for other uses in children 1 month to less than 12 months

(1 year) of age, or in children less than 1 month of age.

Who should not take omeprazole delayed-release capsules?

Do not take omeprazole delayed-release capsules if you:

are allergic to omeprazole or any of the ingredients in omeprazole delayed-release capsules. See

the end of this Medication Guide for a complete list of ingredients in omeprazole delayed-release

capsules.

are allergic to any other proton pump inhibitor (PPI) medicine.

are taking a medicine that contains rilpivirine (EDURANT, COMPLERA) used to treat HIV-1

(Human Immunodeficiency Virus).

What should I tell my doctor before taking omeprazole delayed-release capsules?

Before taking omeprazole delayed-release capsules, tell your doctor about all of your medical

conditions, including if you:

have been told that you have low magnesium levels in your blood.

have liver problems.

have any other medical conditions.

are pregnant or plan to become pregnant. It is not known if omeprazole delayed-release capsules

will harm your unborn baby.

are breastfeeding or plan to breastfeed. Omeprazole passes into your breast milk. Talk to your

doctor about the best way to feed your baby if you take omeprazole delayed-release capsules.

Tell your doctor about all of the medicines you take including prescription and over-the-counter

medicines, vitamins and herbal supplements. Omeprazole delayed-release capsules may affect how

other medicines work, and other medicines may affect how omeprazole delayed-release capsules

work. Especially tell your doctor if you take an antibiotic that contains clarithromycin or

amoxicillin, or if you take clopidogrel (Plavix), methotrexate (Otrxup, Rasuvo, Trexall), St. John’s

Wort ( Hypericum perforatum), or rifampin (Rimactane, Rifater, Rifamate).

Know the medicines that you take. Keep a list of them to show your doctor and pharmacist when you

get a new medicine.

How should I take omeprazole delayed-release capsules?

Take omeprazole delayed-release capsules exactly as prescribed by your doctor.

Do not change your dose or stop omeprazole delayed-release capsules without talking to your

doctor.

Omeprazole delayed-release capsules are usually taken 1 time each day. Your doctor will tell you

the time of day to take omeprazole delayed-release capsules, based on your medical condition.

Take omeprazole delayed-release capsules before a meal.

Antacids may be taken with omeprazole delayed-release capsules.

OmeprazoleDelayed-Release Capsules

Swallow omeprazole delayed-release capsules whole. Do not chew or crush omeprazole

delayed-release capsules.

If you have trouble swallowing a whole capsule, you can open the capsule and take the contents in

applesauce. See the “Instructions for Use” at the end of this Medication Guide for instructions on

how to take omeprazole delayed-release capsules with applesauce.

If you miss a dose of omeprazole delayed-release capsules, take it as soon as you remember. If it is

almost time for your next dose, do not take the missed dose. Take the next dose at your regular time. Do

not take 2 doses at the same time to make up for the missed dose.

If you take too many omeprazole delayed-release capsules, call your doctor or your poison control

center at 1-800-222-1222 right away or go to the nearest emergency room.

What are the possible side effects of omeprazole delayed-release capsules?

Omeprazole delayed-release capsules can cause serious side effects, including:

See “What is the most important information I should know about omeprazole delayed-

release capsules?”

Vitamin B-12 deficiency. Omeprazole delayed-release capsules reduce the amount of acid in your

stomach. Stomach acid is needed to absorb vitamin B-12 properly. Talk with your doctor about the

possibility of vitamin B-12 deficiency if you have been on omeprazole delayed-release capsules

for a long time (more than 3 years).

Low magnesium levels in your body. This problem can be serious. Low magnesium can happen in

some people who take a PPI medicine for at least 3 months. If low magnesium levels happen, it is

usually after a year of treatment.

You may or may not have symptoms of low magnesium. Tell your doctor right away if you develop

any of these symptoms:

seizures

dizziness

abnormal or fast heart beat

jitteriness

jerking movements or shaking (tremors)

muscle weakness

spasms of the hands and feet

cramps or muscle aches

spasm of the voice box

Your doctor may check the level of magnesium in your body before you start taking omeprazole

delayed-release capsules or during treatment if you will be taking omeprazole delayed-release

capsules for a long period of time.

Low Stomach growths (fundic gland polyps). People who take PPI medicines for a long time

have an increased risk of developing a certain type of stomach growths called fundic gland polyps,

especially after taking PPI medicines for more than 1 year.

The most common side effects with omeprazole delayed-release capsules in adults and children

include:

headache

stomach pain

nausea

diarrhea

vomiting

In addition to the side effects listed above, the most common side effects in children 1 to 16 years of

age include:

respiratory system events

fever

Other side effects:

Serious allergic reactions. Tell your doctor if you get any of the following symptoms with

omeprazole delayed-release capsules:

rash

throat tightness

face swelling

difficulty breathing

Your doctor may stop omeprazole delayed-release capsules if these symptoms happen. Tell your

doctor if you have any side effect that bothers you or that do not go away. These are not all the

possible side effects with omeprazole delayed-release capsules. For more information, ask your

doctor or pharmacist. Call your doctor for medical advice about side effects. You may report side

effects to FDA at 1-800-FDA-1088.

How should I store omeprazole delayed-release capsules?

Store omeprazole delayed-release capsules at room temperature between 20° to 25°C (68° to 77°F).

Keep the container of omeprazole delayed-release capsules closed tightly.

Keep the container of omeprazole delayed-release capsules dry and away from light.

Keep omeprazole delayed-release capsules and all medicines out of the reach of children.

General information about the safe and effective use of omeprazole delayed-release capsules.

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not

use omeprazole delayed-release capsules for a condition for which they were not prescribed. Do not

give omeprazole delayed-release capsules to other people, even if they have the same symptoms you

have. They may harm them.

This Medication Guide summarizes the most important information about omeprazole delayed-release

capsules. For more information, ask your doctor. You can ask your doctor or pharmacist for information

that is written for healthcare professionals.

What are the ingredients in omeprazole delayed-release capsules?

Active ingredient in omeprazole delayed-release capsules: omeprazole

Inactive ingredients in omeprazole delayed-release capsules: ammonium hydroxide, dibutyl

sebacate, D&C Yellow No. 10, FD&C Green No. 3, gelatin, ethylcellulose, fumed silica,

hypromellose, methacrylic acid, oleic acid, silicon dioxide, sodium lauryl sulfate, sugar spheres, talc,

titanium dioxide and triethyl citrate. The 40 mg empty gelatin capsule shell also contains FD&C Blue

No. 1. In addition, the white imprinting ink contains ammonium hydroxide, propylene glycol, shellac

glaze, simethicone and titanium dioxide.

Manufactured for: Mylan Pharmaceuticals Inc., Morgantown, WV 26505 U.S.A.

Jointly Manufactured by: Mylan Pharmaceuticals Inc., Morgantown, WV 26505 U.S.A. and

Laboratorios Dr. Esteve, S.A.,08107 Martorelles (Barcelona), Spain

For more information, call Mylan at 1-877-446-3679 (1-877-4-INFO-RX).

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Instructions for Use

Omeprazole Delayed-Release Capsules, USP

(oh mep′ ra zole)

Omeprazole Delayed-Release Capsules: Taking omeprazole delayed-release capsules with

apples auce:

1. Place 1 tablespoon of applesauce into a clean container.

2. Carefully open the capsule and sprinkle the pellets onto the applesauce. Mix the pellets with the

applesauce.

3. Swallow the applesauce and pellet mixture right away. Do not chew or crush the pellets. Do not

store the applesauce and pellet mixture for later use.

The brands listed are trademarks of their respective owners.

Jointly manufactured by:

Mylan Pharmaceuticals Inc.

Morgantown, WV 26505 U.S.A.

Laboratorios Dr. Esteve, S.A.

08107 Martorelles (Barcelona), Spain

Marketed/Packaged by:

GSMS, Inc.

Camarillo, CA USA 93012

Revised: 5/2018

OMEP:R32mpbmh

PRINCIPAL DISPLAY PANEL - 20 mg

NDC 60429-270-90

Omeprazole

Delayed-Release

Capsules, USP

20 mg

PHARMACIST: Dispense the accompanying

Medication Guide to each patient.

Rx only 90 capsules

Each capsule contains:

Omeprazole, USP 20 mg

Dispense in a tight, light-resistant

container as defined in the USP

using a child-resistant closure.

Keep container tightly closed.

Keep this and all medication

out of the reach of children.

Store at 20° to 25°C (68° to 77°F).

[See USP Controlled Room

Temperature.]

Protect from light and moisture.

Usual Dosage: See accompanying

prescribing information.

The omeprazole delayed-release capsule

should be swallowed whole and not

opened, chewed, or crushed.

PRINCIPAL DISPLAY PANEL - 40 mg

NDC 60429-271-90

Omeprazole

Delayed-Release

Capsules, USP

40 mg

PHARMACIST: Dispense the accompanying

Medication Guide to each patient.

Rx only 90 Capsules

Each capsule contains:

Omeprazole, USP 40 mg

Dispense in a tight, light-resistant

container as defined in the USP

using a child-resistant closure.

Keep container tightly closed.

Keep this and all medication

out of the reach of children.

Store at 20° to 25°C (68° to 77°F).

[See USP Controlled Room

Temperature.]

Protect from light and moisture.

Usual Dosage: See accompanying

prescribing information.

The omeprazole delayed-release capsule

should be swallowed whole and not

opened, chewed, or crushed.

OMEPRAZOLE

omeprazole capsule, delayed release

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:6 0 429 -270 (NDC:0 378 -6 150 )

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

O MEPRAZO LE (UNII: KG6 0 48 4QX9 ) (OMEPRAZOLE - UNII:KG6 0 48 4QX9 )

OMEPRAZOLE

20 mg

Inactive Ingredients

Ingredient Name

Stre ng th

AMMO NIA (UNII: 5138 Q19 F1X)

DIBUTYL SEBACATE (UNII: 4W5IH7FLNY)

ETHYLCELLULO SE, UNSPECIFIED (UNII: 7Z8 S9 VYZ4B)

SILICO N DIO XIDE (UNII: ETJ7Z6 XBU4)

HYPRO MELLO SE, UNSPECIFIED (UNII: 3NXW29 V3WO)

METHACRYLIC ACID (UNII: 1CS0 2G8 6 56 )

O LEIC ACID (UNII: 2UMI9 U37CP)

SUCRO SE (UNII: C151H8 M554)

STARCH, CO RN (UNII: O8 232NY3SJ)

TALC (UNII: 7SEV7J4R1U)

TITANIUM DIO XIDE (UNII: 15FIX9 V2JP)

TRIETHYL CITRATE (UNII: 8 Z9 6 QXD6 UM)

D&C YELLO W NO . 10 (UNII: 35SW5USQ3G)

FD&C GREEN NO . 3 (UNII: 3P3ONR6 O1S)

GELATIN, UNSPECIFIED (UNII: 2G8 6 QN327L)

SO DIUM LAURYL SULFATE (UNII: 36 8 GB5141J)

PRO PYLENE GLYCO L (UNII: 6 DC9 Q16 7V3)

SHELLAC (UNII: 46 N10 7B71O)

Product Characteristics

Color

green (dark green o paque) , blue (blue-green o paque)

S core

no sco re

S hap e

CAPSULE

S iz e

18 mm

Flavor

Imprint Code

MYLAN;6 150

Contains

Packag ing

#

Item Code

Package Description

Marketing Start

Date

Marketing End

Date

1

NDC:6 0 429 -270 -

9 0 in 1 BOTTLE, PLASTIC; Type 0 : No t a Co mbinatio n

Pro duc t

0 6 /21/20 13

2

NDC:6 0 429 -270 -

10 0 0 in 1 BOTTLE, PLASTIC; Type 0 : No t a Co mbinatio n

Pro duc t

0 6 /21/20 13

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA0 758 76

0 5/29 /20 0 3

OMEPRAZOLE

omeprazole capsule, delayed release

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:6 0 429 -271(NDC:0 378 -5222)

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

O MEPRAZO LE (UNII: KG6 0 48 4QX9 ) (OMEPRAZOLE - UNII:KG6 0 48 4QX9 )

OMEPRAZOLE

40 mg

Inactive Ingredients

Ingredient Name

Stre ng th

AMMO NIA (UNII: 5138 Q19 F1X)

DIBUTYL SEBACATE (UNII: 4W5IH7FLNY)

ETHYLCELLULO SE, UNSPECIFIED (UNII: 7Z8 S9 VYZ4B)

SILICO N DIO XIDE (UNII: ETJ7Z6 XBU4)

HYPRO MELLO SE, UNSPECIFIED (UNII: 3NXW29 V3WO)

METHACRYLIC ACID (UNII: 1CS0 2G8 6 56 )

O LEIC ACID (UNII: 2UMI9 U37CP)

SUCRO SE (UNII: C151H8 M554)

STARCH, CO RN (UNII: O8 232NY3SJ)

TALC (UNII: 7SEV7J4R1U)

TITANIUM DIO XIDE (UNII: 15FIX9 V2JP)

TRIETHYL CITRATE (UNII: 8 Z9 6 QXD6 UM)

D&C YELLO W NO . 10 (UNII: 35SW5USQ3G)

FD&C GREEN NO . 3 (UNII: 3P3ONR6 O1S)

GELATIN, UNSPECIFIED (UNII: 2G8 6 QN327L)

SO DIUM LAURYL SULFATE (UNII: 36 8 GB5141J)

FD&C BLUE NO . 1 (UNII: H3R47K3TBD)

PRO PYLENE GLYCO L (UNII: 6 DC9 Q16 7V3)

SHELLAC (UNII: 46 N10 7B71O)

Product Characteristics

Color

green (dark green o paque) , blue (light-blue o paque)

S core

no sco re

S hap e

CAPSULE

S iz e

21mm

Flavor

Imprint Code

MYLAN;5222

Contains

Packag ing

#

Item Code

Package Description

Marketing Start

Date

Marketing End

Date

1

NDC:6 0 429 -271-

9 0 in 1 BOTTLE, PLASTIC; Type 0 : No t a Co mbinatio n

Pro duc t

0 6 /21/20 13

2

NDC:6 0 429 -271-

50 0 in 1 BOTTLE, PLASTIC; Type 0 : No t a Co mbinatio n

Pro duc t

0 6 /21/20 13

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA0 758 76

0 1/21/20 0 9

Labeler -

Golden State Medical Supply, Inc. (603184490)

Golden State Medical Supply, Inc.

Establishment

Name

Ad d re s s

ID/FEI

Busine ss Ope rations

Go lden State Medical Supply, Inc.

6 0 318 449 0

repack(6 0 429 -270 , 6 0 429 -271) , relabel(6 0 429 -270 , 6 0 429 -271)

Revised: 12/2019

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