TOP

NEXIUM(esomeprazole magnesium) for delayed-release oral suspension

2016-06-28 02:16:24 来源: 作者: 【大中小】浏览:336次评论:0条

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, for oral use
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 to 17 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
1 month to less than 1 year: 2.5 mg, 5 mg or 10 mg (based on weight). Once daily, up to 6 weeks for erosive esophagitis (EE) due to acid-mediated GERD only.
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)

Patients with severe liver impairment-do not exceed dose of 20 mg. (2)
DOSAGE FORMS AND STRENGTHS

•: NEXIUM Delayed-Release Capsules: 20 mg and 40 mg. ( 3)
•: NEXIUM For Delayed-Release Oral Suspension: 2.5 mg, 5 mg, 10 mg, 20 mg, and 40 mg. ( 3)

CONTRAINDICATIONS

Patients with known hypersensitivity to proton pump inhibitors (PPIs) (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)
•: Acute interstitial nephritis has been observed in patients taking PPIs. (5.3)
•: Cyanocobalamin (vitamin B-12) Deficiency: Daily long-term use (e.g., longer than 3 years) may lead to malabsorption or a deficiency of cyanocobalamin. (5.4)
•: PPI therapy may be associated with increased risk of Clostridium difficile associated diarrhea. (5.5)
•: Avoid concomitant use of NEXIUM with clopidogrel. (5.6)
•: 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. (5.7)
•: Hypomagnesemia has been reported rarely with prolonged treatment with PPIs. (5.8)
•: Avoid concomitant use of NEXIUM with St. John’s Wort or rifampin due to the potential reduction in esomeprazole levels. ( 5.9, 7.3)
•: Interactions with diagnostic investigations for Neuroendocrine Tumors: Increases in intragastric pH may result in hypergastrinemia and enterochromaffin-like cell hyperplasia and increased chromogranin A levels which may interfere with diagnostic investigations for neuroendocrine tumors. ( 5.10, 12.2)

ADVERSE REACTIONS

Most common adverse reactions (6.1):

•: Adults (≥ 18 years) (incidence >1%) are headache, diarrhea, nausea, flatulence, abdominal pain, constipation, and dry mouth.
•: Pediatric (1 to 17 years) (incidence >2%) are headache, diarrhea, abdominal pain, nausea, and somnolence.
•: Pediatric (1 month to less than 1 year) (incidence 1%) are abdominal pain, regurgitation, tachypnea, and increased ALT.

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, erlotinib, digoxin and mycophenolate mofetil). Patients treated with NEXIUM and digoxin may need to be monitored for digoxin toxicity. ( 7.2)
•: Combined inhibitor of CYP2C19 and 3A4 may raise esomeprazole levels. ( 7.3)
•: Clopidogrel: NEXIUM decreases exposure to the active metabolite of clopidogrel. ( 7.3)
•: May increase systemic exposure of cilostazol and an active metabolite. Consider dose reduction. ( 7.3)
•: Tacrolimus: NEXIUM may increase serum levels of tacrolimus. ( 7.5)
•: Methotrexate: NEXIUM may increase serum levels of methotrexate. ( 7.7)

USE IN SPECIFIC POPULATIONS

•: Pregnancy: Based on animal data, may cause fetal harm. (8.1)

See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.

Revised: 1/2016

FULL PRESCRIBING INFORMATION: CONTENTS*

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 Acute Interstitial Nephritis

5.4 Cyanocobalamin (vitamin B-12) Deficiency

5.5 Clostridium difficile associated diarrhea

5.6 Interaction with Clopidogrel

5.7 Bone Fracture

5.8 Hypomagnesemia

5.9 Concomitant use of NEXIUM with St. John’s Wort or Rifampin

5.10 Interactions with Diagnostic Investigations for Neuroendocrine Tumors

5.11 Concomitant use of NEXIUM with Methotrexate

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

6.2 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 Interactions With Investigations of Neuroendocrine Tumors

7.5 Tacrolimus

7.6 Combination Therapy with Clarithromycin

7.7 Methotrexate

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

16 HOW SUPPLIED/STORAGE AND HANDLING

17 PATIENT COUNSELING INFORMATION

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

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.

In infants 1 month to less than 1 year, NEXIUM is indicated for short-term treatment (up to 6 weeks) of erosive esophagitis due to acid-mediated GERD.

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 Dosage and Administration (2)and Clinical Studies (14)].

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 prescribing information for clarithromycin].

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 Table 1. 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 for 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. ¶ Doses over 1.33 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. Þ 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
Healing of Erosive Esophagitis Symptomatic GERD	20 mg or 40 mg 20 mg	Once Daily for 4 to 8 Weeks Once Daily for 4 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
1 month to < 1 year old¶
Erosive esophagitis due to acid-mediated GERD
weight 3 kg to 5 kg	2.5 mg	Once Daily for up to 6 Weeks
weight > 5 kg to 7.5 kg	5 mg	Once Daily for up to 6 Weeks
weight > 7.5 kg to 12 kg	10 mg	Once Daily for up to 6 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 DailyÞ

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

Special Populations

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)].

Directions for use specific to the route and available methods of administration for each of these dosage forms are presented in Table 2.

Table 2: Administration Options
Administration Options (See text following table for additional instructions.)
Dosage Form	Route	Options
Delayed-Release Capsules	Oral	Capsule can be swallowed whole. -or- Capsule can be opened and mixed with applesauce.
Delayed-Release Capsules	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	For the 2.5 mg and 5 mg strengths, mix the contents of packet with 5 mL of water, leave 2 to 3 minutes to thicken, stir and drink within 30 minutes. For the 10 mg, 20 mg and 40 mg strengths, mix contents of packet with 15 mL of water, and follow the instructions above.
For Delayed-Release Oral Suspension	Nasogastric or Gastric Tube	For the 2.5 mg and 5 mg strengths, add 5 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. For the 10 mg, 20 mg and 40 mg strengths, add 15 mL of water, and follow the instructions above.

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: do not store for future use. 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. If the granules/applesauce mixture is not used in its entirety, the remaining mixture should be discarded immediately.

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 mixture 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 2.5 mg or 5 mg packet into a container containing 5 mL of water. For the 10 mg, 20 mg, and 40 mg strengths, the contents of a packet should be emptied into a container containing 15 mL of water.