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NEXIUM(esomeprazole magnesium)capsule, delayed release

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HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use NEXIUM safely and effectively. See full prescribing information for NEXIUM.
NEXIUM (esomeprazole magnesium) DELAYED-RELEASE CAPSULES
NEXIUM (esomeprazole magnesium) FOR DELAYED-RELEASE ORAL SUSPENSION
Initial U.S. Approval: 1989 (omeprazole)

INDICATIONS AND USAGE

NEXIUM is a proton pump inhibitor indicated for the following:

: Treatment of gastroesophageal reflux disease (GERD) (1.1)
: Risk reduction of NSAID-associated gastric ulcer (1.2)
: H. pylori eradication to reduce the risk of duodenal ulcer recurrence (1.3)
: Pathological hypersecretory conditions including Zollinger-Ellison syndrome (1.4)

DOSAGE AND ADMINISTRATION

Indication	Dose	Frequency
Gastroesophageal Reflux Disease (GERD)
Adults	20 mg or 40 mg	Once daily for 4 to 8 weeks
12 to17 years	20 mg or 40 mg	Once daily for up to 8 weeks
1 to 11 years	10 mg or 20 mg	Once daily for up to 8 weeks
Risk Reduction of NSAID-Associated Gastric Ulcer
	20 mg or 40 mg	Once daily for up to 6 months
H. pylori Eradication (Triple Therapy):
NEXIUM	40 mg	Once daily for 10 days
Amoxicillin	1000 mg	Twice daily for 10 days
Clarithromycin	500 mg	Twice daily for 10 days
Pathological Hypersecretory Conditions	40 mg	Twice daily

See full prescribing information for administration options (2)

DOSAGE FORMS AND STRENGTHS

: NEXIUM Delayed-Release Capsules, 20 mg and 40 mg (3)
: NEXIUM For Delayed-Release Oral Suspension, 10 mg, 20 mg, and 40 mg (3)

CONTRAINDICATIONS

Patients with known hypersensitivity to any component of the formulation or to substituted benzimidazoles (angioedema and anaphylaxis have occurred) (4)

WARNINGS AND PRECAUTIONS

: Symptomatic response does not preclude the presence of gastric malignancy (5.1)
: Atrophic gastritis has been noted with long-term omeprazole therapy (5.2)
: Triple therapy for H. pylori – there are risks due to the antibiotics; see separate prescribing information for individual antibiotics (5.3, 5.4)

ADVERSE REACTIONS

Most common adverse reactions:

Adult (> 18 years) use (incidence > 1%):

: Headache, diarrhea, nausea, flatulence, abdominal pain, constipation, and dry mouth (6.1)

Pediatric (1 - 17 years) use (incidence > 1–2%):

: Headache, diarrhea, abdominal pain, nausea, and somnolence (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact AstraZeneca at 1-800-236-9933 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

DRUG INTERACTIONS

: May affect plasma levels of antiretroviral drugs – use with atazanavir and nelfinavir is not recommended; if saquinavir is used with NEXIUM, monitor for toxicity and consider saquinavir dose reduction (7.1)
: May interfere with drugs for which gastric pH affects bioavailability (e.g., ketoconazole, iron salts, and digoxin) (7.2)
: Combined inhibitor of CYP 2C19 and 3A4 may raise esomeprazole levels (7.3)
: May increase systemic exposure of cilostazol and an active metabolite. Consider dose reduction (7.3)

USE IN SPECIFIC POPULATIONS

: Severe liver impairment – do not exceed dose of 20 mg (2)

See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling

Revised: 05/2011

Back to Highlights and Tabs

FULL PRESCRIBING INFORMATION: CONTENTS*

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

1 INDICATIONS AND USAGE

1.1 Treatment of Gastroesophageal Reflux Disease (GERD)

1.2 Risk Reduction of NSAID-Associated Gastric Ulcer

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

1.4 Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome

2 DOSAGE AND ADMINISTRATION

3 DOSAGE FORMS AND STRENGTHS

4 CONTRAINDICATIONS

5 WARNINGS AND PRECAUTIONS

5.1 Concurrent Gastric Malignancy

5.2 Atrophic Gastritis

5.3 Risks of Amoxicillin (as Part of H. pylori Triple Therapy)

5.4 Risks of Clarithromycin (as Part of H. pylori Triple Therapy)

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

6.2 Combination Treatment with Amoxicillin and Clarithromycin

6.3 Postmarketing Experience

7 DRUG INTERACTIONS

7.1 Interference with Antiretroviral Therapy

7.2 Drugs for Which Gastric pH Can Affect Bioavailability

7.3 Effects on Hepatic Metabolism/Cytochrome P-450 Pathways

7.4 Combination Therapy with Clarithromycin

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

8.3 Nursing Mothers

8.4 Pediatric Use

8.5 Geriatric Use

10 OVERDOSAGE

11 DESCRIPTION

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

12.2 Pharmacodynamics

12.3 Pharmacokinetics

12.4 Microbiology

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

13.2 Animal Toxicology and/or Pharmacology

14 CLINICAL STUDIES

14.1 Healing of Erosive Esophagitis

14.2 Symptomatic Gastroesophageal Reflux Disease (GERD)

14.3 Pediatric Gastroesophageal Reflux Disease (GERD)

14.4 Risk Reduction of NSAID-Associated Gastric Ulcer

14.5 Helicobacter pylori (H.pylori) Eradication in Patients with Duodenal Ulcer Disease

14.6 Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome

15 REFERENCES

16 HOW SUPPLIED/STORAGE AND HANDLING

17 PATIENT COUNSELING INFORMATION

FDA-APPROVED PATIENT LABELING

PRINCIPAL DISPLAY PANEL

Principal Display Panel

FULL PRESCRIBING INFORMATION

1 INDICATIONS AND USAGE

1.1 Treatment of Gastroesophageal Reflux Disease (GERD)

Healing of Erosive Esophagitis

NEXIUM is indicated for the short-term treatment (4 to 8 weeks) in the healing and symptomatic resolution of diagnostically confirmed erosive esophagitis. For those patients who have not healed after 4 to 8 weeks of treatment, an additional 4 to 8 week course of NEXIUM may be considered.

Maintenance of Healing of Erosive Esophagitis

NEXIUM is indicated to maintain symptom resolution and healing of erosive esophagitis. Controlled studies do not extend beyond 6 months.

Symptomatic Gastroesophageal Reflux Disease

NEXIUM is indicated for short-term treatment (4 to 8 weeks) of heartburn and other symptoms associated with GERD in adults and children 1 year or older.

1.2 Risk Reduction of NSAID-Associated Gastric Ulcer

NEXIUM is indicated for the reduction in the occurrence of gastric ulcers associated with continuous NSAID therapy in patients at risk for developing gastric ulcers. Patients are considered to be at risk due to their age (≥ 60) and/or documented history of gastric ulcers. Controlled studies do not extend beyond 6 months.

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

Triple Therapy (NEXIUM plus amoxicillin and clarithromycin): NEXIUM, in combination with amoxicillin and clarithromycin, is indicated for the treatment of patients with H. pylori infection and duodenal ulcer disease (active or history of within the past 5 years) to eradicate H. pylori. Eradication of H. pylori has been shown to reduce the risk of duodenal ulcer recurrence [see Clinical Studies (14) and Dosage and Administration. (2)].

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 package insert, Clinical Pharmacology, Microbiology].

1.4 Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome

NEXIUM is indicated for the long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison Syndrome.

2 DOSAGE AND ADMINISTRATION

NEXIUM is supplied as delayed-release capsules for oral administration or in packets for preparation of delayed-release oral suspensions. The recommended dosages are outlined in the table below. NEXIUM should be taken at least one hour before meals.

The duration of proton pump inhibitor administration should be based on available safety and efficacy data specific to the defined indication and dosing frequency, as described in the Prescribing Information, and individual patient medical needs. Proton pump inhibitor treatment should only be initiated and continued if the benefits outweigh the risks of treatment.

Table 1

Recommended Dosage Schedule of NEXIUM
* [See Clinical Studies (14.1) ]The majority of patients are healed within 4 to 8 weeks. For patients who do not heal after 4 to 8 weeks, an additional 4 to 8 weeks of treatment may be considered. † Controlled studies did not extend beyond six months. ‡ If symptoms do not resolve completely after 4 weeks, an additional 4 weeks of treatment may be considered. § Doses over 1 mg/kg/day have not been studied. ¶ The dosage of NEXIUM in patients with pathological hypersecretory conditions varies with the individual patient. Dosage regimens should be adjusted to individual patient needs. # Doses up to 240 mg daily have been administered [see Drug Interactions (7)].
Indication	Dose	Frequency
Gastroesophageal Reflux Disease (GERD)
Healing of Erosive Esophagitis	20 mg or 40 mg	Once Daily for 4 to 8 Weeks*
Maintenance of Healing of Erosive Esophagitis	20 mg	Once Daily†
Symptomatic Gastroesophageal Reflux Disease	20 mg	Once Daily for 4 Weeks‡
Pediatric GERD
12 to 17 Year Olds Short-term Treatment of GERD	20 mg or 40 mg	Once Daily for up to 8 Weeks
1 to 11 Year Olds§ Short-term Treatment of Symptomatic GERD	10 mg	Once Daily for up to 8 Weeks
Healing of Erosive Esophagitis
weight < 20 kg	10 mg	Once Daily for 8 Weeks
weight ≥ 20 kg	10 mg or 20 mg	Once Daily for 8 Weeks
Risk Reduction of NSAID-Associated Gastric Ulcer	20 mg or 40 mg	Once Daily for up to 6 months†
H. pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence
Triple Therapy:
NEXIUM	40 mg	Once Daily for 10 Days
Amoxicillin	1000 mg	Twice Daily for 10 Days
Clarithromycin	500 mg	Twice Daily for 10 Days
Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome	40 mg¶	# Twice Daily

Please refer to amoxicillin and clarithromycin full prescribing information for Contraindications, Warnings and dosing in elderly and renally-impaired patients.

Special Populations

Geriatric

No dosage adjustment is necessary [see Clinical Pharmacology (12.3)].

Renal Insufficiency

No dosage adjustment is necessary [see Clinical Pharmacology (12.3)].

Hepatic Insufficiency

In patients with mild to moderate liver impairment (Child Pugh Classes A and B), no dosage adjustment is necessary. For patients with severe liver impairment (Child Pugh Class C), a dose of 20 mg of NEXIUM should not be exceeded [see Clinical Pharmacology (12.3)].

Gender

No dosage adjustment is necessary [see Clinical Pharmacology (12.3)].

Administration Options

Directions for use specific to the route and available methods of administration for each of these dosage forms are presented below.

Table 2

Administration Options (See text following table for additional instructions.)

Type	Route	Options

Delayed-Release Capsule	Oral	Capsule can be swallowed whole. -or- Capsule can be opened and mixed with applesauce.

Delayed-Release Capsule	Nasogastric Tube	Capsule can be opened and the intact granules emptied into a syringe and delivered through the nasogastric tube.

For Delayed-Release Oral Suspension	Oral	Mix contents of packet with 1 tablespoon (15 mL) of water, leave 2 to 3 minutes to thicken, stir and drink within 30 minutes.

For Delayed-Release Oral Suspension	Nasogastric or Gastric Tube	Add 15 mL of water to a syringe and then add contents of packet. Shake the syringe; leave 2 to 3 minutes to thicken. Shake the syringe and inject through the nasogastric or gastric tube within 30 minutes.

NEXIUM Delayed-Release Capsules

NEXIUM Delayed-Release Capsules should be swallowed whole.

Alternatively, for patients who have difficulty swallowing capsules, one tablespoon of applesauce can be added to an empty bowl and the NEXIUM Delayed-Release Capsule can be opened, and the granules inside the capsule carefully emptied onto the applesauce. The granules should be mixed with the applesauce and then swallowed immediately. The applesauce used should not be hot and should be soft enough to be swallowed without chewing. The granules should not be chewed or crushed. The granules/applesauce mixture should not be stored for future use.

For patients who have a nasogastric tube in place, NEXIUM Delayed-Release Capsules can be opened and the intact granules emptied into a 60 mL catheter tipped syringe and mixed with 50 mL of water. It is important to only use a catheter tipped syringe when administering NEXIUM through a nasogastric tube. Replace the plunger and shake the syringe vigorously for 15 seconds. Hold the syringe with the tip up and check for granules remaining in the tip. Attach the syringe to a nasogastric tube and deliver the contents of the syringe through the nasogastric tube into the stomach. After administering the granules, the nasogastric tube should be flushed with additional water. Do not administer the granules if they have dissolved or disintegrated.

The suspension must be used immediately after preparation.

NEXIUM For Delayed-Release Oral Suspension

NEXIUM For Delayed-Release Oral Suspension should be administered as follows:

: Empty the contents of a 10 mg, 20 mg, or 40 mg packet into a container containing 1 tablespoon (15 mL) of water.
: Stir.
: Leave 2 to 3 minutes to thicken.
: Stir and drink within 30 minutes.
: If any material remains after drinking, add more water, stir, and drink immediately.

For patients who have a nasogastric or gastric tube in place, NEXIUM For Delayed-Release Oral Suspension can be administered as follows:

: Add 15 mL of water to a catheter tipped syringe and then add the contents of a 10 mg, 20 mg, or 40 mg NEXIUM packet. It is important to only use a catheter tipped syringe when administering NEXIUM through a nasogastric tube or gastric tube.
: Immediately shake the syringe and leave 2 to 3 minutes to thicken.
: Shake the syringe and inject through the nasogastric or gastric tube, French size 6 or larger, into the stomach within 30 minutes.
: Refill the syringe with 15 mL of water.
: Shake and flush any remaining contents from the nasogastric or gastric tube into the stomach.

3 DOSAGE FORMS AND STRENGTHS

NEXIUM Delayed-Release Capsules, 20 mg - opaque, hard gelatin, amethyst colored capsules with two radial bars in yellow on the cap and NEXIUM 20 mg in yellow on the body.

NEXIUM Delayed-Release Capsules, 40 mg - opaque, hard gelatin, amethyst colored capsules with three radial bars in yellow on the cap and NEXIUM 40 mg in yellow on the body.

NEXIUM For Delayed-Release Oral Suspension, 10 mg, 20 mg or 40 mg - unit dose packet containing a fine yellow powder, consisting of white to pale brownish esomeprazole granules and pale yellow inactive granules.

4 CONTRAINDICATIONS

NEXIUM is contraindicated in patients with known hypersensitivity to any component of the formulation [see Description (11)] or to substituted benzimidazoles. Hypersensitivity reactions, e.g., angioedema and anaphylactic shock, have been reported with NEXIUM use.

5 WARNINGS AND PRECAUTIONS

5.1 Concurrent Gastric Malignancy

Symptomatic response to therapy with NEXIUM does not preclude the presence of gastric malignancy.

5.2 Atrophic Gastritis

Atrophic gastritis has been noted occasionally in gastric corpus biopsies from patients treated long-term with omeprazole, of which esomeprazole is an enantiomer.

5.3 Risks of Amoxicillin (as Part of H. pylori Triple Therapy)

[See Warnings and Precautions in the prescribing information for amoxicillin for complete information.]

Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients on penicillin therapy. These reactions are more apt to occur in individuals with a history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens.

There have been well documented reports of individuals with a history of penicillin hypersensitivity reactions that have experienced severe hypersensitivity reactions when treated with a cephalosporin. Before initiating therapy with any penicillin, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, and other allergens. If an allergic reaction occurs, amoxicillin should be discontinued and the appropriate therapy instituted.

Serious anaphylactic reactions require immediate emergency treatment with epinephrine. Oxygen, intravenous steroids, and airway management, including intubation, should also be administered as indicated.

Pseudomembranous colitis has been reported with nearly all antibacterial agents, including clarithromycin and amoxicillin, and may range in severity from mild to life threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents.

Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridia. Studies indicate that a toxin produced by Clostridium difficile is a primary cause of “antibiotic-associated colitis”.

After the diagnosis of pseudomembranous colitis has been established, therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to discontinuation of the drug alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation, and treatment with an antibacterial drug clinically effective against Clostridium difficile colitis.

5.4 Risks of Clarithromycin (as Part of H. pylori Triple Therapy)

[See Warnings and Precautions in the prescribing information for clarithromycin for complete information.]

Clarithromycin should not be used in pregnant women except in clinical circumstances where no alternative therapy is appropriate. If pregnancy occurs while taking clarithromycin, the patient should be apprised of the potential hazard to the fetus.

Concomitant administration of clarithromycin with cisapride, pimozide, astemizole, terfenadine, ergotamine, or dihydroergotamine is contraindicated.

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

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 of NEXIUM was eva luated in over 15,000 patients (aged 18 to 84 years) in clinical trials worldwide including over 8,500 patients in the United States and over 6,500 patients in Europe and Canada. Over 2,900 patients were treated in long-term studies for up to 6-12 months. In general, NEXIUM was well tolerated in both short and long-term clinical trials.

The safety of NEXIUM was eva luated in 316 pediatric and adolescent patients aged 1 to 17 years in four clinical trials for the treatment of symptomatic GERD [see Clinical Studies (14.2)]. In 109 pediatric patients aged 1 to 11 years, the most frequently reported (at least 1%) treatment-related adverse reactions in these patients were diarrhea (2.8%), headache (1.9%) and somnolence (1.9%). In 149 pediatric patients aged 12 to 17 years the m