Omeprazole: Package Insert and Label Information

OMEPRAZOLE — omeprazole capsule, delayed release
Rising Health, LLC

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, are 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 are 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 2 years of age and older.

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

Pediatric Patients 2 Years 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 2 years of age and older.

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.

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 2 years 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

1. Most patients heal within 4 weeks; some patients may require an additional 4 weeks of therapy to achieve healing2. 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.3. 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)].
Indication	Dosage of Omeprazole Delayed-Release Capsules	Treatment Duration
Treatment of Active DuodenalUlcer	20 mg once daily	4 weeks1
Helicobacter pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence	Triple Therapy Omeprazole delayed-release capsules 20 mgAmoxicillin 1000 mgClarithromycin 500 mgTake all three drugs twice daily	10 daysIn 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 daysIn 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-Mediated GERD	20 mg once daily	4 to 8 weeks2
Maintenance of Healing of EE due to Acid-Mediated GERD	20 mg once daily3	Controlled studies do not extend beyond 12 months.
Pathological Hypersecretory Conditions	Starting dose is 60 mg once daily;adjust to patient needsDaily dosages of greater than 80 mg should be administered in divided doses.Dosages up to 120 mg three timesdaily 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 delayed-release capsules in pediatric patients by indication.

Table 2: Recommended Dosage Regimen of Omeprazole Delayed-Release Capsules in Pediatric Patients by Indication

1. 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.
Indication	Omeprazole Delayed-Release Capsules Dosage Regimen and Duration
	Patient Age	Weight-Based Dose (mg)	Regimen and Duration
Treatment of Symptomatic GERD	2 to 16 years	10 to less than 20 kg: 10 mg	Once daily for up to 4 weeks
		20 kg and greater: 20 mg
Treatment of EE due to Acid- Mediated GERD	2 to 16 years	10 to less than 20 kg: 10 mg	Once daily for 4 to 8 weeks1
		20 kg and greater: 20 mg
Maintenance of Healing of EE due to Acid-Mediated GERD	2 to 16 years	10 to less than 20 kg: 10 mg	Once daily. Controlled studies do not extend beyond 12 months
		20 kg and greater: 20 mg

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:

1. 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.
2. Open the capsule.
3. Carefully empty all of the pellets inside the capsule on the applesauce.
4. Mix the pellets with the applesauce.
5. 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 USP, 10 mg are pink/pink size ‘3’ hard gelatin capsule filled with white to off-white enteric-coated granules and imprinted with ‘E’ on pink cap and ‘65’ on pink body with black ink.

Omeprazole Delayed-Release Capsules USP, 20 mg are reddish brown/pink size ‘1’ hard gelatin capsule filled with white to off-white enteric-coated granules and imprinted with ‘E’ on reddish brown cap and ‘67’ on pink body with black ink.

Omeprazole Delayed-Release Capsules USP, 40 mg are reddish brown/reddish brown size ‘0’ hard gelatin capsule filled with white to off-white enteric-coated granules and imprinted with ‘E’ on reddish brown cap and ‘69’ on reddish brown body with black ink.

4 CONTRAINDICATIONS

• Omeprazole delayed-release capsules are contraindicated in patients with known hypersensitivity reactions including anaphylaxis to the formulation or any substituted benzimidazole. Hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute tubulointerstitial 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 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 Tubulointerstitial Nephritis

Acute tubulointerstitial nephritis (TIN) has been observed in patients taking PPIs and may occur at any point during PPI therapy. Patients may present with varying signs and symptoms from symptomatic hypersensitivity reactions, to non-specific symptoms of decreased renal function (e.g., malaise, nausea, anorexia). In reported case series, some patients were diagnosed on biopsy and in the absence of extra-renal manifestations (e.g., fever, rash or arthralgia). Discontinue omeprazole delayed-release capsules and evaluate patients with suspected acute TIN [see Contraindications (4)].

5.3 Clostridium difficile -Associated Diarrhea

Published observational studies suggest that PPI therapy like omeprazole 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, 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 Severe Cutaneous Adverse Reactions

Severe cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) have been reported in association with the use of PPIs [see Adverse Reactions (6.3)]. Discontinue omeprazole delayed-release capsules at the first signs or symptoms of severe cutaneous adverse reactions or other signs of hypersensitivity and consider further evaluation.

5.6 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, 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.