1 INDICATIONS AND USAGE Rabeprazole sodium delayed-release tablets is a proton pump inhibitor (PPI) indicated in adults for: · Healing of Erosive or Ulcerative Gastroesophageal Reflux Disease (GERD) ( 1.1 ).

· Maintenance of Healing of Erosive or Ulcerative GERD ( 1.2 ).

· Treatment of Symptomatic GERD ( 1.3 ).

· Healing of Duodenal Ulcers ( 1.4 ).

· Helicobacter pylori Eradication to Reduce Risk of Duodenal Ulcer Recurrence ( 1.5 ).

· Treatment of Pathological Hypersecretory Conditions, Including Zollinger-Ellison Syndrome ( 1.6 ).

In adolescent patients 12 years of age and older for: · Short-term Treatment of Symptomatic GERD ( 1.7 ) 1.1 Healing of Erosive or Ulcerative GERD in Adults Rabeprazole sodium delayed-release tablets are indicated for short-term (4 to 8 weeks) treatment in the healing and symptomatic relief of erosive or ulcerative gastroesophageal reflux disease (GERD).

For those patients who have not healed after 8 weeks of treatment, an additional 8-week course of rabeprazole sodium delayed-release tablets may be considered.

1.2 Maintenance of Healing of Erosive or Ulcerative GERD in Adults Rabeprazole sodium delayed-release tablets are indicated for maintaining healing and reduction in relapse rates of heartburn symptoms in patients with erosive or ulcerative gastroesophageal reflux disease (GERD Maintenance).

Controlled studies do not extend beyond 12 months.

1.3 Treatment of Symptomatic GERD in Adults Rabeprazole sodium delayed-release tablets are indicated for the treatment of daytime and nighttime heartburn and other symptoms associated with GERD in adults for up to 4 weeks.

1.4 Healing of Duodenal Ulcers in Adults Rabeprazole sodium delayed-release tablets are indicated for short-term (up to four weeks) treatment in the healing and symptomatic relief of duodenal ulcers.

Most patients heal within four weeks.

1.5 Helicobacter pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence in Adults Rabeprazole sodium delayed-release tablets, in combination with amoxicillin and clarithromycin as a three drug regimen, are indicated for the treatment of patients with H.

pylori infection and duodenal ulcer disease (active or history within the past 5 years) to eradicate H.

pylori .

Eradication of H.

pylori has been shown to reduce the risk of duodenal ulcer recurrence.

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 (12.2) and the full prescribing information for clarithromycin].

1.6 Treatment of Pathological Hypersecretory Conditions, Including Zollinger-Ellison Syndrome in Adults Rabeprazole sodium delayed-release tablets are indicated for the long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison syndrome.

1.7 Treatment of Symptomatic GERD in Adolescent Patients 12 Years of Age and Older Rabeprazole sodium delayed-release tablets are indicated for the treatment of symptomatic GERD in adolescents 12 years of age and above for up to 8 weeks.

6 ADVERSE REACTIONS The following serious adverse reactions are described below and elsewhere in labeling: Acute Tubulointerstitial Nephritis [see Warnings and Precautions (5.3)] Clostridium difficile-Associated Diarrhea [see Warnings and Precautions (5.4)] Bone Fracture [see Warnings and Precautions (5.5)] Cutaneous and Systemic Lupus Erythematosus [see Warnings and Precautions (5.6)] Cyanocobalamin (Vitamin B-12) Deficiency [see Warnings and Precautions (5.7)] Hypomagnesemia [see Warnings and Precautions (5.8)] Fundic Gland Polyps [see Warnings and Precautions (5.10 )] Most common adverse reactions in adults (>2%) are pain, pharyngitis, flatulence, infection, and constipation ( 6.1 ).

Most common adverse reactions in adolescents (≥2%) are headache, diarrhea, nausea, vomiting, and abdominal pain ( 6.1 ).

To report SUSPECTED ADVERSE REACTIONS, contact Ascend Laboratories, LLC at 1-877-ASC-RX01 (877-272-7901) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Studies Experience Because clinical trials are conducted under 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.

Adults The data described below reflect exposure to rabeprazole sodium delayed-release tablets in 1,064 adult patients exposed for up to 8 weeks.

The studies were primarily placebo-and active-controlled trials in adult patients with Erosive or Ulcerative Gastroesophageal Reflux Disease (GERD), Duodenal Ulcers and Gastric Ulcers.

The population had a mean age of 53 years (range 18 to 89 years) and had a ratio of approximately 60% male: 40% female.

The racial distribution was 86% Caucasian, 8% African American, 2% Asian, and 5% other.

Most patients received either 10 mg, 20 mg or 40 mg per day of rabeprazole sodium delayed-release tablets.

An analysis of adverse reactions appearing in ≥2% of patients treated with rabeprazole sodium delayed-release tablets (n=1,064) and with a greater frequency than placebo (n=89) in controlled North American and European acute treatment trials, revealed the following adverse reactions: pain (3% vs.

1%), pharyngitis (3% vs.

2%), flatulence (3% vs.

1%), infection (2% vs.

1%), and constipation (2% vs.

1%).

Three long-term maintenance studies consisted of a total of 740 adult patients; at least 54% of adult patients were exposed to rabeprazole sodium delayed-release tablets for 6 months and at least 33% were exposed for 12 months.

Of the 740 adult patients, 247 (33%) and 241 (33%) patients received 10 mg and 20 mg of rabeprazole sodium delayed-release tablets, respectively, while 169 (23%) patients received placebo and 83 (11%) received omeprazole.

The safety profile of rabeprazole in the maintenance studies in adults was consistent with what was observed in the acute studies.

Less common adverse reactions seen in controlled clinical trials (<2% of patients treated with rabeprazole sodium delayed-release tablets and greater than placebo) and for which there is a possibility of a causal relationship to rabeprazole, include the following: headache, abdominal pain, diarrhea, dry mouth, dizziness, peripheral edema, hepatic enzyme increase, hepatitis, hepatic encephalopathy, myalgia, and arthralgia.

Combination Treatment with Amoxicillin and Clarithromycin: In clinical trials using combination therapy with rabeprazole plus amoxicillin and clarithromycin (RAC), no adverse reactions unique to this drug combination were observed.

In the U.S.

multicenter study, the most frequently reported drug related adverse reactions for patients who received RAC therapy for 7 or 10 days were diarrhea (8% and 7%) and taste perversion (6% and 10%), respectively.

No clinically significant laboratory abnormalities particular to the drug combinations were observed.

For more information on adverse reactions or laboratory changes with amoxicillin or clarithromycin, refer to their respective prescribing information, Adverse Reactions section.

Pediatrics In a multicenter, open-label study of adolescent patients 12 to 16 years of age with a clinical diagnosis of symptomatic GERD or endoscopically proven GERD, the adverse event profile was similar to that of adults.

The adverse reactions reported without regard to relationship to rabeprazole sodium delayed-release tablets that occurred in ≥2% of 111 patients were headache (9.9%), diarrhea (4.5%), nausea (4.5%), vomiting (3.6%), and abdominal pain (3.6%).

The related reported adverse reactions that occurred in ≥2% of patients were headache (5.4%) and nausea (1.8%).

There were no adverse reactions reported in this study that were not previously observed in adults.

6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of rabeprazole.

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: Blood and Lymphatic System Disorders: agranulocytosis, hemolytic anemia, leukopenia, pancytopenia, thrombocytopenia Ear and Labyrinth Disorders: vertigo Eye Disorders: blurred vision Gastrointestinal Disorders: fundic gland polyps General Disorders and Administration Site Conditions: sudden death Hepatobiliary Disorders: jaundice Immune System Disorders: anaphylaxis, angioedema, systemic lupus erythematosus, Stevens-Johnson syndrome, toxic epidermal necrolysis (some fatal) Infections and Infestations: Clostridium difficile -associated diarrhea Investigations: Increases in prothrombin time/INR (in patients treated with concomitant warfarin), TSH elevations Metabolism and Nutrition Disorders: hyperammonemia, hypomagnesemia Musculoskeletal System Disorders: bone fracture, rhabdomyolysis Nervous System Disorders: coma Psychiatric Disorders: delirium, disorientation Renal and Urinary Disorders: interstitial nephritis Respiratory, Thoracic and Mediastinal Disorders: interstitial pneumonia Skin and Subcutaneous Tissue Disorders: severe dermatologic reactions including bullous and other drug eruptions of the skin, cutaneous lupus erythematosus, erythema multiforme