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 the 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 is 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 is 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 is indicated for the treatment of daytime and nighttime heartburn and other symptoms associated with GERD in adults.

1.4 Healing of Duodenal Ulcers in Adults Rabeprazole Sodium Delayed-Release Tablets is 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, is 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 [ see Clinical Studies (14.5) and Dosage and Administration (2.5) ].

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 clarithromycin package insert, Clinical Pharmacology (12.2) ].

1.6 Treatment of Pathological Hypersecretory Conditions, Including Zollinger-Ellison Syndrome in Adults Rabeprazole Sodium Delayed-Release Tablets is indicated for the long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison Syndrome.

1.7 Short-term Treatment of Symptomatic GERD in Adolescent Patients 12 Years of Age and Older Rabeprazole Sodium Delayed-Release Tablets is indicated for the treatment of symptomatic GERD in adolescents 12 years of age and above for up to 8 weeks.

6 ADVERSE REACTIONS Worldwide, over 2900 patients have been treated with rabeprazole in Phase II-III clinical trials involving various dosages and durations of treatment.

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.

• In the adult studies (4 to 8 weeks), adverse reactions that occurred at a rate greater than 2% and greater than placebo included pain, pharyngitis, flatulence, infection and constipation ( 6.1 ).

• In studies of adolescent patients (ages 12 to 16 years, and up to 36 weeks exposure) adverse reactions that occurred at a rate of ≥5% of patients included abdominal pain, diarrhea and headache ( 6.1 ).

To report SUSPECTED ADVERSE REACTIONS, contact UCB, Inc.

at 1-866-822-0068 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Studies Experience Adults The data described below reflect exposure to Rabeprazole Sodium Delayed-Release Tablets in 1064 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 18-89 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/day of Rabeprazole Sodium Delayed-Release Tablets.

An analysis of adverse reactions appearing in ³ 2% of Rabeprazole Sodium Delayed-Release Tablet patients (n=1064) 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 for 6 months while 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.

Other adverse reactions that were seen in controlled clinical trials, which do not meet the above criteria (≥ 2% of Rabeprazole Sodium Delayed-Release Tablets treated patients 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 package prescribing information, Adverse Reactions section.

Pediatric In a multicenter, open-label study of adolescent patients aged 12 to 16 years 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 these studies that were not previously observed in adults.

6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of Rabeprazole Sodium Delayed-Release Tablets.

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: sudden death; coma, hyperammonemia; jaundice; rhabdomyolysis; disorientation and delirium; anaphylaxis; angioedema; bullous and other drug eruptions of the skin; severe dermatologic reactions, including toxic epidermal necrolysis (some fatal), Stevens-Johnson syndrome, and erythema multiforme; interstitial pneumonia; interstitial nephritis; TSH elevations, bone fractures, hypomagnesemia and Clostridium difficile associated diarrhea.

In addition, agranulocytosis, hemolytic anemia, leukopenia, pancytopenia, and thrombocytopenia have been reported.

Increases in prothrombin time/INR in patients treated with concomitant warfarin have been reported.