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All about: Nexium capsules

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Generic Name: esomeprazole
Dosage Form: Capsules

Nexium Description

The active ingredient in NEXIUM® (esomeprazole magnesium) Delayed-Release Capsules is bis(5-methoxy-2-[(S)-[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazole-1-yl) magnesium trihydrate, a compound that inhibits gastric acid secretion. Esomeprazole is the S-isomer of omeprazole, which is a mixture of the S- and R- isomers. Its empirical formula is (C17H18N3O3S)2Mg x 3 H2O with molecular weight of 767.2 as a trihydrate and 713.1 on an anhydrous basis. The structural formula is:

The magnesium salt is a white to slightly colored crystalline powder. It contains 3 moles of water of solvation and is slightly soluble in water.

The stability of esomeprazole magnesium is a function of pH; it rapidly degrades in acidic media, but it has acceptable stability under alkaline conditions. At pH 6.8 (buffer), the half-life of the magnesium salt is about 19 hours at 25°C and about 8 hours at 37°C.

Nexium is supplied as Delayed-Release Capsules for oral administration. Each delayed-release capsule contains 20 mg or 40 mg of esomeprazole (present as 22.3 mg or 44.5 mg esomeprazole magnesium trihydrate) in the form of enteric-coated pellets with the following inactive ingredients: glyceryl monostearate 40-50, hydroxypropyl cellulose, hypromellose, magnesium stearate, methacrylic acid copolymer type C, polysorbate 80, sugar spheres, talc, and triethyl citrate. The capsule shells have the following inactive ingredients: gelatin, FD&C Blue #1, FD&C Red #40, D&C Red #28, titanium dioxide, shellac, ethyl alcohol, isopropyl alcohol, n-butyl alcohol, propylene glycol, sodium hydroxide, polyvinyl pyrrolidone, and D&C Yellow #10.

Nexium - Clinical Pharmacology

Pharmacokinetics

Absorption:

Nexium Delayed-Release Capsules contain an enteric-coated pellet formulation of esomeprazole magnesium. After oral administration peak plasma levels (Cmax) occur at approximately 1.5 hours (Tmax). The Cmax increases proportionally when the dose is increased, and there is a three-fold increase in the area under the plasma concentration-time curve (AUC) from 20 to 40 mg. At repeated once-daily dosing with 40 mg, the systemic bioavailability is approximately 90% compared to 64% after a single dose of 40 mg. The mean exposure (AUC) to esomeprazole increases from 4.32 µmol*hr/L on day 1 to 11.2 µmol*hr/L on day 5 after 40 mg once daily dosing.

The AUC after administration of a single 40 mg dose of esomeprazole is decreased by 43-53% after food intake compared to fasting conditions. Esomeprazole should be taken at least one hour before meals.

The pharmacokinetic profile of esomeprazole was determined in 36 patients with symptomatic gastroesophageal reflux disease following repeated once daily administration of 20 mg and 40 mg capsules of Nexium over a period of five days. The results are shown in the following table:

Pharmacokinetic Parameters of Nexium Following Oral Dosing for 5 days
*
Values represent the geometric mean, except the Tmax, which is the arithmetic mean.

Parameter

Nexium

40 mg

Nexium

20 mg

AUC (μmol*h/L)

12.6

4.2

Coefficient of variation

42%

59%

Cmax (μmol/L)

4.7

2.1

Tmax (h)

1.6

1.6

T1/2 (h)

1.5

1.2

Distribution:

Esomeprazole is 97% bound to plasma proteins. Plasma protein binding is constant over the concentration range of 2-20 μmol/L. The apparent volume of distribution at steady state in healthy volunteers is approximately 16 L.

Metabolism:

Esomeprazole is extensively metabolized in the liver by the cytochrome P450 (CYP) enzyme system. The metabolites of esomeprazole lack antisecretory activity. The major part of esomeprazole’s metabolism is dependent upon the CYP2C19 isoenzyme, which forms the hydroxy and desmethyl metabolites. The remaining amount is dependent on CYP3A4 which forms the sulphone metabolite. CYP2C19 isoenzyme exhibits polymorphism in the metabolism of esomeprazole, since some 3% of Caucasians and 15-20% of Asians lack CYP2C19 and are termed Poor metabolizers. At steady state, the ratio of AUC in Poor metabolizers to AUC in the rest of the population (Extensive metabolizers) is approximately 2.

Following administration of equimolar doses, the S- and R-isomers are metabolized differently by the liver, resulting in higher plasma levels of the S- than of the R-isomer.

Excretion:

The plasma elimination half-life of esomeprazole is approximately 1-1.5 hours. Less than 1% of parent drug is excreted in the urine. Approximately 80% of an oral dose of esomeprazole is excreted as inactive metabolites in the urine, and the remainder is found as inactive metabolites in the feces.

Special Populations

Geriatric:

The AUC and Cmax values were slightly higher (25% and 18%, respectively) in the elderly as compared to younger subjects at steady state. Dosage adjustment based on age is not necessary.

Pediatric:

The pharmacokinetics of esomeprazole have not been studied in patients < 18 years of age.

Gender:

The AUC and Cmax values were slightly higher (13%) in females than in males at steady state. Dosage adjustment based on gender is not necessary.

Hepatic Insufficiency:

The steady state pharmacokinetics of esomeprazole obtained after administration of 40 mg once daily to 4 patients each with mild (Child Pugh A), moderate (Child Pugh Class B), and severe (Child Pugh Class C) liver insufficiency were compared to those obtained in 36 male and female GERD patients with normal liver function. In patients with mild and moderate hepatic insufficiency, the AUCs were within the range that could be expected in patients with normal liver function. In patients with severe hepatic insufficiency the AUCs were 2 to 3 times higher than in the patients with normal liver function. No dosage adjustment is recommended for patients with mild to moderate hepatic insufficiency (Child Pugh Classes A and B). However, in patients with severe hepatic insufficiency (Child Pugh Class C) a dose of 20 mg once daily should not be exceeded (See DOSAGE AND ADMINISTRATION)

Renal Insufficiency:

The pharmacokinetics of esomeprazole in patients with renal impairment are not expected to be altered relative to healthy volunteers as less than 1% of esomeprazole is excreted unchanged in urine.

Pharmacokinetics: Combination Therapy with Antimicrobials

Esomeprazole magnesium 40 mg once daily was given in combination with clarithromycin 500 mg twice daily and amoxicillin 1000 mg twice daily for 7 days to 17 healthy male and female subjects. The mean steady state AUC and Cmax of esomeprazole increased by 70% and 18%, respectively during triple combination therapy compared to treatment with esomeprazole alone. The observed increase in esomeprazole exposure during co-administration with clarithromycin and amoxicillin is not expected to produce significant safety concerns.

The pharmacokinetic parameters for clarithromycin and amoxicillin were similar during triple combination therapy and administration of each drug alone. However, the mean AUC and Cmax for 14-hydroxyclarithromycin increased by 19% and 22%, respectively, during triple combination therapy compared to treatment with clarithromycin alone. This increase in exposure to 14-hydroxyclarithromycin is not considered to be clinically significant.

Pharmacodynamics

Mechanism of Action:

Esomeprazole is a proton pump inhibitor that suppresses gastric acid secretion by specific inhibition of the H+/K+-ATPase in the gastric parietal cell. The S- and R-isomers of omeprazole are protonated and converted in the acidic compartment of the parietal cell forming the active inhibitor, the achiral sulphenamide. By acting specifically on the proton pump, esomeprazole blocks the final step in acid production, thus reducing gastric acidity. This effect is dose-related up to a daily dose of 20 to 40 mg and leads to inhibition of gastric acid secretion.

Antisecretory Activity:

The effect of esomeprazole on intragastric pH was determined in patients with symptomatic gastroesophageal reflux disease in two separate studies. In the first study of 36 patients, Nexium 40 mg and 20 mg capsules were administered over 5 days. The results are shown in the following table:

Effect on Intragastric pH on Day 5 (N=36)
*
Gastric pH was measured over a 24-hour period
p< 0.01 Nexium 40 mg vs Nexium 20 mg

Parameter

NEXIUM

40 mg

NEXIUM

20 mg

% Time Gastric pH >4* (Hours)

70%

(16.8 h)

53%

(12.7 h)

Coefficient of variation

26%

37%

Median 24 Hour pH

4.9*

4.1

Coefficient of variation

16%

27%

In a second study, the effect on intragastric pH of Nexium 40 mg administered once daily over a five day period was similar to the first study, (% time with pH>4 was 68% or 16.3 hours).

Serum Gastrin Effects:

The effect of Nexium on serum gastrin concentrations was evaluated in approximately 2,700 patients in clinical trials up to 8 weeks and in over 1,300 patients for up to 6-12 months. The mean fasting gastrin level increased in a dose-related manner. This increase reached a plateau within two to three months of therapy and returned to baseline levels within four weeks after discontinuation of therapy.

Enterochromaffin-like (ECL) Cell Effects:

In 24-month carcinogenicity studies of omeprazole in rats, a dose-related significant occurrence of gastric ECL cell carcinoid tumors and ECL cell hyperplasia was observed in both male and female animals (see PRECAUTIONS, Carcinogenesis, Mutagenesis, Impairment of Fertility). Carcinoid tumors have also been observed in rats subjected to fundectomy or long-term treatment with other proton pump inhibitors or high doses of H2-receptor antagonists.

Human gastric biopsy specimens have been obtained from more than 3,000 patients 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.

In over 1,000 patients treated with Nexium (10, 20 or 40 mg/day) up to 6-12 months, the prevalence of ECL cell hyperplasia increased with time and dose. No patient developed ECL cell carcinoids, dysplasia, or neoplasia in the gastric mucosa.

Endocrine Effects:

Nexium had no effect on thyroid function when given in oral doses of 20 or 40 mg for 4 weeks. Other effects of Nexium on the endocrine system were assessed using omeprazole studies. Omeprazole given in oral doses of 30 or 40 mg for 2 to 4 weeks had no effect on carbohydrate metabolism, circulating levels of parathyroid hormone, cortisol, estradiol, testosterone, prolactin, cholecystokinin or secretin.

Microbiology

Esomeprazole magnesium, amoxicillin and clarithromycin triple therapy has been shown to be active against most strains of Helicobacter pylori (H. pylori)in vitro and in clinical infections as described in the Clinical Studies and INDICATIONS AND USAGE sections.

Helicobacter

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.

Pretreatment Resistance:

Clarithromycin pretreatment resistance rate (MIC ≥ 1 μg/mL) to H. pylori was 15% (66/445) at baseline in all treatment groups combined. A total of > 99% (394/395) of patients had H. pylori isolates which were considered to be susceptible (MIC ≤ 0.25 μg/mL) to amoxicillin at baseline. One patient had a baseline H. pylori isolate with an amoxicillin MIC = 0.5 μg/mL.

Clarithromycin Susceptibility Test Results and Clinical/Bacteriologic Outcomes:

The baseline H. pylori clarithromycin susceptibility results and the H. pylori eradication results at the Day 38 visit are shown in the table below:

Clarithromycin Susceptibility Test Results and Clinical/Bacteriologtical Outcomes* for a Triple Therapy (Esomeprazole magnesium 40 mg once daily/amoxicillin 1000 mg twice daily/clarithromycin 500 mg twice daily for 10 days)

Clarithromycin Pretreatment Results

H. pylori negative (Eradicated)

H. pylori positive

(Not Eradicated)

Post-treatment susceptibility results

*
Includes only patients with pretreatment and post-treatment clarithromycin susceptibility test results
Susceptible (S) MIC ≤ 0.25 μg/mL, Intermediate (I) MIC = 0.5 μg/mL, Resistant (R) MIC ≥ 1.0 μg/mL

S

I

R

No MIC

Susceptible

182

162

4

0

2

14

Intermediate

1

1

0

0

0

0

Resistant

29

13

1

0

13

2

Patients not eradicated of H. pylori following esomeprazole magnesium/amoxicillin/clarithromycin triple therapy will likely have clarithromycin resistant H. pylori isolates. Therefore, clarithromycin susceptibility testing should be done, when possible. Patients with clarithromycin resistant H. pylori should not be re-treated with a clarithromycin-containing regimen.

Amoxicillin Susceptibility Test Results and Clinical/Bacteriological Outcomes:

In the esomeprazole magnesium/amoxicillin/clarithromycin clinical trials, 83% (176/212) of the patients in the esomeprazole magnesium/amoxicillin/clarithromycin treatment group who had pretreatment amoxicillin susceptible MICs (≤ 0.25 μg/mL) were eradicated of H. pylori, and 17% (36/212) were not eradicated of H. pylori. Of the 36 patients who were not eradicated of H. pylori on triple therapy, 16 had no post-treatment susceptibility test results and 20 had post-treatment H. pylori isolates with amoxicillin susceptible MICs. Fifteen of the patients who were not eradicated of H. pylori on triple therapy also had post-treatment H. pylori isolates with clarithromycin resistant MICs. There were no patients with H. pylori isolates who developed treatment emergent resistance to amoxicillin.

Susceptibility Test for Helicobacter pylori:

The reference methodology for susceptibility testing of H. pylori is agar dilution MICs. One to three microliters of an inoculum equivalent to a No.2 McFarland standard (1 x 107 - 1 x 108 CFU/mL for H. pylori) are inoculated directly onto freshly prepared antimicrobial containing Mueller-Hinton agar plates with 5% aged defibrinated sheep blood (> 2 weeks old). The agar dilution plates are incubated at 35°C in a microaerobic environment produced by a gas generating system suitable for Campylobacter. After 3 days of incubation, the MICs are recorded as the lowest concentration of antimicrobial agent required to inhibit growth of the organism. The clarithromycin and amoxicillin MIC values should be interpreted according to the following criteria:

*
These are breakpoints for the agar dilution methodology and they should not be used to interpret results obtained using alternative methods.
There were not enough organisms with MICs > 0.25 μg/mL to determine a resistance breakpoint.

Clarithromycin MIC(μg/mL)*

Interpretation

≤ 0.25

Susceptible (S)

0.5

Intermediate (I)

≥1.0

Resistant (R)

Amoxicillin MIC (μg/mL)*

Interpretation

≤ 0.25

Susceptible (S)

Standardized susceptibility test procedures require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures. Standard clarithromycin and amoxicillin powders should provide the following MIC values:

*
These are quality control ranges for the agar dilution methodology and they should not be used to control test results obtained using alternative methods

Microorganism

Antimicrobial Agent

MIC (μg/mL)*

H. pylori ATCC 43504

Clarithromycin

0.016 − 0.12 (μg/mL)

H. pylori ATCC 43504

Amoxicillin

0.016 − 0.12 (μg/mL)

Clinical Studies

Healing of Erosive Esophagitis:

The healing rates of Nexium 40 mg, Nexium 20 mg, and omeprazole 20 mg (the approved dose for this indication) were evaluated in patients with endoscopically diagnosed erosive esophagitis in four multicenter, double-blind, randomized studies. The healing rates at weeks 4 and 8 were evaluated and are shown in the table below:

Erosive Esophagitis Healing Rate (Life-Table Analysis)

Study

No. of Patients

Treatment Groups

Week 4

Week 8

Significance Level*

*
log-rank test vs omeprazole 20 mg
N.S. = not significant (p > 0.05).

1

588

Nexium 20 mg

68.7%

90.6%

N.S.

588

Omeprazole 20 mg

69.5%

88.3%

2

654

Nexium 40 mg

75.9%

94.1%

p < 0.001

656

Nexium 20 mg

70.5%

89.9%

p < 0.05

650

Omeprazole 20 mg

64.7%

86.9%

3

576

Nexium 40 mg

71.5%

92.2%

N.S.

572

Omeprazole 20 mg

68.6%

89.8%

4

1216

Nexium 40 mg

81.7%

93.7%

p < 0.001

1209

Omeprazole 20 mg

68.7%

84.2%

In these same studies of patients with erosive esophagitis, sustained heartburn resolution and time to sustained heartburn resolution were evaluated and are shown in the table below:

Sustained Resolution* of Heartburn (Erosive Esophagitis Patients)

Cumulative Percent with Sustained Resolution

Study

No. of Patients

Treatment Groups

Day 14

Day 28

Significance Level

*
Defined as 7 consecutive days with no heartburn reported in daily patient diary.
Defined as the cumulative proportion of patients who have reached the start of sustained resolution
log-rank test vs omeprazole 20 mg

1

573

Nexium 20 mg

64.3%

72.7%

N.S.

555

Omeprazole 20 mg

64.1%

70.9%

2

621

Nexium 40 mg

64.8%

74.2%

p <0.001

620

Nexium 20 mg

62.9%

70.1%

N.S.

626

Omeprazole 20 mg

56.5%

66.6%

3

568

Nexium 40 mg

65.4%

73.9%

N.S.

551

Omeprazole 20 mg

65.5%

73.1%

4

1187

Nexium 40 mg

67.6%

75.1%

P <0.001

1188

Omeprazole 20 mg

62.5%

70.8%

In these four studies, the range of median days to the start of sustained resolution (defined as 7 consecutive days with no heartburn) was 5 days for Nexium 40 mg, 7-8 days for Nexium 20 mg and 7-9 days for omeprazole 20 mg.

There are no comparisons of 40 mg of Nexium with 40 mg of omeprazole in clinical trials assessing either healing or symptomatic relief of erosive esophagitis.

Long-Term Maintenance of Healing of Erosive Esophagitis:

Two multicenter, randomized, double-blind placebo-controlled 4-arm trials were conducted in patients with endoscopically confirmed, healed erosive esophagitis to evaluate Nexium 40 mg (n=174), 20 mg (n=180), 10 mg (n= 168) or placebo (n=171) once daily over six months of treatment.

No additional clinical benefit was seen with Nexium 40 mg over Nexium 20 mg.

The percentage of patients that maintained healing of erosive esophagitis at the various time points are shown in the figures below:

Maintenance of Healing Rates by Month (Study 177)s= scheduled visit

Maintenance of Healing Rates by Month (Study 178)s=scheduled visit

Patients remained in remission significantly longer and the number of recurrences of erosive esophagitis was significantly less in patients treated with Nexium compared to placebo.

In both studies, the proportion of patients on Nexium who remained in remission and were free of heartburn and other GERD symptoms was well differentiated from placebo.

In a third multicenter open label study of 808 patients treated for 12 months with Nexium 40 mg, the percentage of patients that maintained healing of erosive esophagitis was 93.7% for six months and 89.4% for one year.

Symptomatic Gastroesophageal Reflux Disease (GERD):

Two multicenter, randomized, double-blind, placebo-controlled studies were conducted in a total of 717 patients comparing four weeks of treatment with Nexium 20 mg or 40 mg once daily versus placebo for resolution of GERD symptoms. Patients had ≥ 6-month history of heartburn episodes, no erosive esophagitis by endoscopy, and heartburn on at least four of the seven days immediately preceding randomization.

The percentage of patients that were symptom-free of heartburn was significantly higher in the Nexium groups compared to placebo at all follow-up visits (Weeks 1, 2, and 4).

No additional clinical benefit was seen with Nexium 40 mg over Nexium 20 mg.

The percent of patients symptom-free of heartburn by day are shown in the figures below:

Percent of Patients Symptom-Free of Heartburn by Day (Study 225)

Percent of Patients Symptom-Free of Heartburn by Day (Study 226)

In three European symptomatic GERD trials, Nexium 20 mg and 40 mg and omeprazole 20 mg were evaluated. No significant treatment related differences were seen.

Risk Reduction of NSAID-Associated Gastric Ulcer:

Two multicenter, double-blind, placebo-controlled studies were conducted in patients at risk of developing gastric and/or duodenal ulcers associated with continuous use of non-selective and COX-2 selective NSAIDs. A total of 1429 patients were randomized across the 2 studies. Patients ranged in age from 19 to 89 (median age 66.0 years) with 70.7% female, 29.3% male, 82.9% Caucasian, 5.5% Black, 3.7% Asian, and 8.0% Others. At baseline, the patients in these studies were endoscopically confirmed not to have ulcers but were determined to be at risk for ulcer occurrence due to their age (≥60 years) and/or history of a documented gastric or duodenal ulcer within the past 5 years. Patients receiving NSAIDs and treated with Nexium 20 mg or 40 mg once-a-day experienced significant reduction in gastric ulcer occurrences relative to placebo treatment at 26 weeks. No additional benefit was seen with Nexium 40 mg over Nexium 20 mg. These studies did not demonstrate significant reduction in the development of NSAID-associated duodenal ulcer due to the low incidence.

Cumulative percentage of patients without gastric ulcers at 26 weeks:

Study

No. of Patients

Treatment Group

% of Patients Remaining Gastric Ulcer Free*

*
%= Life Table Estimate. Significant difference from placebo (p<0.01).

1

191

Nexium 20 mg

95.4

194

Nexium 40 mg

96.7

184

Placebo

88.2

2

267

Nexium 20 mg

94.7

271

Nexium 40 mg

95.3

257

Placebo

83.3

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

Triple Therapy (NEXIUM/amoxicillin/clarithromycin): Two multicenter, randomized, double-blind studies were conducted using a 10 day treatment regimen. The first study (191) compared Nexium 40 mg once daily in combination with amoxicillin 1000 mg twice daily and clarithromycin 500 mg twice daily to Nexium 40 mg once daily plus clarithromycin 500 mg twice daily. The second study (193) compared Nexium 40 mg once daily in combination with amoxicillin 1000 mg twice daily and clarithromycin 500 mg twice daily to Nexium 40 mg once daily. H. pylori eradication rates, defined as at least two negative tests and no positive tests from CLOtest®, histology and/or culture, at 4 weeks post-therapy were significantly higher in the Nexium plus amoxicillin and clarithromycin group than in the Nexium plus clarithromycin or Nexium alone group. The results are shown in the following table:

H. pylori Eradication Rates at 4 Weeks after 10 Day Treatment Regimen
*
Patients were included in the analysis if they had H. pylori infection documented at baseline, had at least one endoscopically verified duodenal ulcer ≥ 0.5 cm in diameter at baseline or had a documented history of duodenal ulcer disease within the past 5 years, and were not protocol violators. Patients who dropped out of the study due to an adverse event related to the study drug were included in the analysis as not H. pylori eradicated.
Patients were included in the analysis if they had documented H. pylori infection at baseline, had at least one documented duodenal ulcer at baseline, or had a documented history of duodenal ulcer disease, and took at least one dose of study medication. All dropouts were included as not H. pylori eradicated.
p < 0.05 compared to Nexium plus clarithromycin
§
p < 0.05 compared to Nexium alone

% of Patients Cured [95% Confidence Interval] (Number of patients)

Study

Treatment Group

Pre-Protocol*

Intent-to-Treat

191

Nexium plus amoxicillin and clarithromycin

84%

[78, 89]

(n=196)

77%

[71, 82]

(n=233)

Nexium plus clarithromycin

55%

[48, 62]

(n=187

52%

[45, 59]

(n=215)

193

Nexium plus amoxicillin and clarithromycin

85%§

[74, 93]

(n=67)

78%§

[67, 87]

(n=74)

NEXIUM

5%

[0, 23]

(n=22)

4%

[0, 21]

(n=24)

The percentage of patients with a healed baseline duodenal ulcer by 4 weeks after the 10 day treatment regimen in the Nexium plus amoxicillin and clarithromycin group was 75% (n=156) and 57% (n=60) respectively, in the 191 and 193 studies (per-protocol analysis).

Indications and Usage for Nexium

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 4-8 weeks of treatment, an additional 4-8-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 treatment of heartburn and other symptoms associated with GERD.

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.

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

Triple Therapy (NEXIUMplus 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 and DOSAGE AND ADMINISTRATION)

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, Microbiology and the clarithromycin package insert, CLINICAL PHARMACOLOGY,Microbiology.)

Contraindications

Nexium is contraindicated in patients with known hypersensitivity to any component of the formulation or to substituted benzimidazoles.

Clarithromycin is contraindicated in patients with a known hypersensitivity to any macrolide antibiotic.

Concomitant administration of clarithromycin with pimozide is contraindicated. There have been post-marketing reports of drug interactions when clarithromycin and/or erythromycin are co-administered with pimozide resulting in cardiac arrhythmias (QT prolongation, ventricular tachycardia, ventricular fibrillation, and torsade de pointes) most likely due to inhibition of hepatic metabolism of pimozide by erythromycin and clarithromycin. Fatalities have been reported. (Please refer to full prescribing information for clarithromycin.)

Amoxicillin is contraindicated in patients with a known hypersensitivity to any penicillin. (Please refer to full prescribing information for amoxicillin.)

Warnings

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. (See WARNINGSin prescribing information for clarithromycin.)

Amoxicillin: 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 who 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.

Precautions

General

Symptomatic response to therapy with Nexium 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.

Information for Patients

Patients should be informed of the following:

Nexium Delayed-Release Capsules should be taken at least on

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Some commonly used brand names are: In the U.S.— Aclovate 1 Acticort 100 7 Aeroseb-Dex 4 Aeroseb-HC 7 Ala-Cort 7 Ala-Scalp HP 7 Allercort 7 Alphaderm 7 Bactine 7 Beta-HC 7 CaldeCORT Anti-Itch 8 CaldeCORT Light 9 Carmol-HC 9 Cetacort 7 Cloderm 2 Cortaid 8 Cort-Dome 7 Cortef Feminine Itch 9 more...

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Generic Name: Chlorpheniramine/Phenylephrine/Methscopolamine Sustained-Release Tablets (klor-fen-EER-a-meen/fen-ill-EF-rin/meth-skoe-POL-a-meen) Brand Name: Examples include Aerohist Plus and DallergyDallergy Sustained-Release Tablets is used for:Relieving congestion, sneezing, runny nose, and more...

Dramamine Dramamine
Generic Name: dimenhydrinate (dye men HYE dri nate) Brand Names: Dramamine, Driminate What is Dramamine (dimenhydrinate)? Dimenhydrinate is used to prevent and treat nausea, vomiting, dizziness, and vertigo associated with motion sickness. Dimenhydrinate may also be used for purposes ot more...

Ioversol Diagnostic Ioversol Diagnostic
This information applies to the following medicines: 1. Diatrizoates (dye-a-tri-ZOE-ates) 2. Iodipamide (eye-oh-DI-pa-mide) 3. Iohexol (eye-oh-HEX-ole) 4. Iopamidol (eye-oh-PA-mi-dole) 5. Iothalamate (eye-oh-thal-A-mate) 6. Ioversol (eye-oh-VER-sole) 7. Ioxaglate (eye-OX-a-glate) more...

M-M-R II M-M-R II
Generic Name: Measles, Mumps, and Rubella Vaccine (MEE-zills, mumps, and rue-BELL-a) Brand Name: M-M-R IIM-M-R II is used for:Preventing measles, mumps, and rubella. M-M-R II is a vaccine. It stimulates the body to produce antibodies against infection of measles, mumps, or rubella. Do NOT use more...

Propulsid Propulsid
Some commonly used brand names are: In the U.S.— Propulsid In Canada— Prepulsid *† Not commercially available in the U.S. and Canada. Category Cholinergic enhancer Gastrointestinal emptying (delayed) adjunct Description Cisapride (SIS-a-pride) is a medicine that in more...

Prostin VR Pediatric Local Prostin VR Pediatric Local
Some commonly used brand names are: In the U.S.— Caverject Edex Muse Prostin VR Pediatric In Canada— Caverject Prostin VR Other commonly used names are PGE 1 and prostaglandin E 1 . Category Impotence therapy agent Diagnostic aid, erectile dysfunction Diagnostic aid, penile v more...