WILMINGTON, Del., May 30 DE-AstraZeneca-sNDA
WILMINGTON, Del., May 30 /PRNewswire-FirstCall/ -- AstraZeneca (NYSE: AZN)
today announced the submission of a supplemental New Drug Application (sNDA)
to the U.S. Food and Drug Administration (FDA) for NEXIUM(R) I.V.
(esomeprazole sodium) for Injection to seek approval for use in patients with
peptic ulcer bleeding (PUB) following therapeutic endoscopy. The regulatory
submission incorporates data from the NEXIUM I.V. Peptic Ulcer Bleed study, a
multinational, randomized trial of 767 patients with peptic ulcer bleeding
(PUB).(1) To date, there is no proton pump inhibitor (PPI) therapy globally
approved for this indication.(2) Presently, NEXIUM I.V. for Injection is
indicated for the short-term treatment (up to 10 days) of GERD adult patients
with a history of erosive esophagitis, as an alternative to oral therapy in
patients when therapy with NEXIUM(R) (esomeprazole magnesium) Delayed-Release
Capsules is not possible or appropriate.(3)
Peptic ulcer bleeding can be a life-threatening complication of peptic
ulcer disease that affects approximately 50 people per 100,000 each year.(4 5
6 7) Patients experiencing re-bleeding after initial treatment of peptic ulcer
bleeding have a greater than 3-fold risk of death,(8) and up to 14 percent of
patients suffering an acute bleed die.(4 6 7 8 9)
The NEXIUM(R) I.V. (esomeprazole sodium) Peptic Ulcer Bleed study was a
prospective multinational, randomized, placebo-controlled, double-blind trial
of 767 men and women, ages 18 years or older, who had undergone successful
endoscopic treatment of a bleeding gastric or duodenal ulcer.(1) The primary
objective was to compare the rate of clinically significant re-bleeding of
patients within 72 hours of starting NEXIUM I.V. treatment, compared with
placebo. Secondary objectives included endoscopic re-treatment due to
re-bleeding, surgery, hospitalization, blood transfusions, mortality, and
safety outcomes.(2) Secondary end points measured the rate of re-bleeding
within seven and 30 days.(2) Patients received an I.V. infusion of NEXIUM 80
mg over 30 minutes plus an I.V. infusion of NEXIUM 8 mg/hour for 72 hours,
followed by oral NEXIUM 40 mg once daily for 27 days. A control group
received an I.V. infusion of placebo for 72 hours followed by the same 27-day
period of oral NEXIUM.(2) The study was performed at 91 centers in 16
countries across Europe, Africa and Asia.
About Peptic Ulcer Bleed (PUB)
PUB is a potentially life-threatening event that occurs as a result of
peptic ulcer disease. PUB occurs when the ulcer erodes into an underlying
blood vessel. The resulting blood loss can be significant as clotting can be
impaired in the acidic environment. If after treatment, a peptic ulcer
re-bleeds, there is an increased risk of morbidity and mortality(8) and
associated healthcare costs.(10 11)
About NEXIUM(R) I.V. (esomeprazole sodium) for Injection
NEXIUM I.V. for Injection is indicated for the short-term treatment (up to
10 days) of GERD adult patients with a history of erosive esophagitis as an
alternative to oral therapy in patients when therapy with NEXIUM
Delayed-Release Capsules is not possible or appropriate.
When oral therapy is possible or appropriate, intravenous therapy with
NEXIUM I.V. for Injection should be discontinued and the therapy should be
continued orally.
The recommended adult dose is either 20 or 40 mg esomeprazole given once
daily by intravenous injection (no less than 3 minutes) or intravenous
infusion (10 to 30 minutes).
NEXIUM I.V. for Injection should not be administered concomitantly with
any other medications through the same intravenous site and or tubing. The
intravenous line should always be flushed with either 0.9% Sodium Chloride
Injection, USP, Lactated Ringer's Injection, USP or 5% Dextrose Injection, USP
both prior to and after administration of NEXIUM I.V. for Injection.
Treatment with NEXIUM I.V. for Injection should be discontinued as soon as
the patient is able to resume treatment with NEXIUM Delayed-Release Capsules.
Safety and efficacy of NEXIUM I.V. for Injection as a treatment of GERD
patients with a history of erosive esophagitis for more than 10 days have not
been demonstrated.
For more information visit www.NEXIUM-US.com.
About NEXIUM(R) (esomeprazole magnesium) Delayed-Release Capsules
In adults, NEXIUM is approved for treating frequent, persistent heartburn
and other symptoms associated with acid reflux disease as well as healing
erosive esophagitis. Most erosions heal in four to eight weeks. Individual
results may vary, and only a doctor can determine if erosions to the esophagus
have occurred. Symptom relief does not rule out the existence of other
serious stomach conditions.
NEXIUM received approval in April 2006 for the short-term treatment (up to
8 weeks) of GERD in adolescent patients ages 12 to 17 years old. NEXIUM is
now approved for the short-term treatment (up to 8 weeks) of GERD in children
ages 1 to 11 years old. The approvals are supported by extrapolation of
results from adequate and well-controlled studies that supported the approval
of NEXIUM for adults, and safety and pharmacokinetic studies. The safety and
effectiveness of NEXIUM for the treatment of GERD in patients less than 1 year
of age have not been established. The safety and effectiveness of NEXIUM for
other pediatric uses have not been established.
In adults, the most frequently reported adverse reactions with NEXIUM
include headache, diarrhea, and abdominal pain. In patients 1 to 17 years of
age, the most frequently reported adverse reactions with NEXIUM include
headache, diarrhea, abdominal pain, nausea, and somnolence. Symptomatic
response to therapy does not preclude the presence of gastric malignancy.
NEXIUM should be used only for the conditions, dosages, and durations
specified in the Prescribing Information.
For more information visit www.NEXIUM-US.com.
For additional information, questions, or to request a copy of the NEXIUM
prescribing information, please contact the Information Center at AstraZeneca
at 1-800-236-9933, Monday through Friday, from 8 a.m. to 7 p.m. ET, excluding
holidays.
IMPORTANT SAFETY INFORMATION
NEXIUM and NEXIUM I.V. are contraindicated in patients with known
hypersensitivity to any component of the formulation or to substituted
benzimidazoles.
The most frequently reported adverse events with NEXIUM include headache,
diarrhea, and abdominal pain. Injection site reactions have also been reported
with NEXIUM I.V.
Symptomatic response to therapy does not preclude the presence of gastric
malignancy.
Atrophic gastritis has been noted occasionally in gastric corpus biopsies
from patients treated long-term with omeprazole, of which NEXIUM is an
enantiomer.
As with all PPIs, patients treated concomitantly with warfarin may need to
be monitored for increases in INR and prothrombin time. Like other proton pump
inhibitors, esomeprazole may interfere with the absorption of drugs where
gastric pH is an important determinant of bioavailability (e.g., ketoconazole,
iron salts, and digoxin). Concomitant administration of esomeprazole may
reduce the plasma levels of atazanavir.
NEXIUM should be used only for the conditions, dosages, and durations
specified in the Prescribing Information. Please see full Prescribing
Information for NEXIUM.
About AstraZeneca
AstraZeneca is a major international healthcare business engaged in the
research, development, manufacturing and marketing of meaningful prescription
medicines and supplier for healthcare services. AstraZeneca is one of the
world's leading pharmaceutical companies with healthcare sales of $29.55
billion and is a leader in gastrointestinal, cardiovascular, neuroscience,
respiratory, oncology and infectious disease medicines. In the United States,
AstraZeneca is a $13.35 billion healthcare business with 12,200 employees
committed to improving people's lives. AstraZeneca is listed in the Dow Jones
Sustainability Index (Global) as well as the FTSE4Good Index.
For more information visit www.astrazeneca-us.com.
References
(1) Data on File. AstraZeneca Pharmaceuticals LP. 263698.
(2) J. J.Y. Sung et al. Intravenous esomeprazole for prevention of peptic
ulcer re-bleeding: rationale/design of the Peptic Ulcer Bleed study.
Aliment Pharmacol Ther 2008; 27:666-677.
(3) NEXIUM I.V. Prescribing Information. Indications and usage section.
(4) Lassen et al. Complicated and uncomplicated peptic ulcers in a Danish
county 1993-2002: a population-based cohort study. Am J Gastroenterol
2006;101(5):945-53.
(5) Kang JY et al. Recent trends in hospital admissions and mortality
rates for peptic ulcer in Scotland 1982-2002. Aliment Pharmacol Ther
2006;24(1):65-79.
(6) Soplepmann et al. Peptic ulcer haemorrhage in Tartu County, Estonia:
epidemiology and mortality risk factors. Scand J Gastroenterol
1997;32(12):1195-200.
(7) Thomsen et al. Diabetes and 30-day mortality from peptic ulcer
bleeding and perforation: a Danish population-based cohort study.
Diabetes Care 2006;29(4):805-10.
(8) van Leerdam ME et al Acute upper GI bleeding: Did anything change?
Time trend analysis of incidence and outcome of acute upper GI
bleeding between 1993/1994 and 2000. American Journal of
Gastroenterology 2003;98(7):1494-1499. Table 5.
(9) Mose et al. Thirty-day mortality after peptic ulcer bleeding in
hospitalized patients receiving low-dose aspirin at time of
admission. Am J Geriatr Pharmacother 2006;4(3):244-50.
(10) Barkun et al. The cost-effectiveness of high-dose oral proton pump
inhibition after endoscopy in the acute treatment of peptic ulcer
bleeding. Aliment Pharmacol Ther 2004; 20: 195-202.
(11) Barkun et al. High-dose intravenous proton pump inhibition following
endoscopic therapy in the acute management of patients with bleeding
peptic ulcers in the USA and Canada: a cost-effectiveness analysis
Aliment Pharmacol Ther 2004; 19: 591-600.
SOURCE AstraZeneca
