Rabeprazole

FDA Drug Information • Also known as: Rabeprazole Sodium

Brand Names: Rabeprazole Sodium
Route: ORAL
Dosage Form: TABLET, DELAYED RELEASE
Product Type: HUMAN PRESCRIPTION DRUG

Description

11 DESCRIPTION The active ingredient in rabeprazole sodium delayed-release tablets is rabeprazole sodium, USP which is a proton pump inhibitor. It is a substituted benzimidazole known chemically as 2-[[[4-(3-methoxypropoxy)-3-methyl-2-pyridinyl]-methyl]sulfinyl]-1 H –benzimidazole sodium salt. It has an empirical formula of C 18 H 20 N 3 NaO 3 S and a molecular weight of 381.42. Rabeprazole sodium, USP is a white to slightly yellowish-white solid. It is very soluble in water and methanol, freely soluble in ethanol, chloroform, and ethyl acetate and insoluble in ether and n- hexane. The stability of rabeprazole sodium is a function of pH; it is rapidly degraded in acid media, and is more stable under alkaline conditions. The structural figure is: Figure 1 Rabeprazole sodium, USP is available for oral administration as delayed-release, enteric-coated tablets containing 20 mg of rabeprazole sodium, USP. Inactive ingredients of the 20 mg tablet are ammonium hydroxide, crospovidone, diethyl phthalate, ethyl cellulose, hydroxypropyl cellulose, hypromellose phthalate, iron oxide black, iron oxide yellow, light magnesium oxide, magnesium stearate, mannitol, propylene glycol, shellac, sodium stearyl fumarate, talc, and titanium dioxide. 1

What Is Rabeprazole Used For?

1 INDICATIONS AND USAGE Rabeprazole sodium delayed-release tablets are 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 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...

Dosage and Administration

2 DOSAGE AND ADMINISTRATION Table 1 shows the recommended dosage of rabeprazole sodium delayed-release tablets in adults and adolescent patients 12 years of age and older. The use of rabeprazole sodium delayed-release tablets is not recommended for use in pediatric patients 1 year to less than 12 years of age because the lowest available tablet strength (20 mg) exceeds the recommended dose for these patients. Use another rabeprazole formulation for pediatric patients 1 year to less than 12 years of age. Table 1: Recommended Dosage and Duration of Rabeprazole Sodium Delayed-Release Tablets in Adults and Adolescents 12 Years of Age and Older Indication Dosage of rabeprazole sodiumdelayed-release tablets Treatment Duration Adults Healing of Erosive or Ulcerative Gastroesophageal Reflux Disease (GERD) 20 mg once daily 4 to 8 weeks * Maintenance of Healing of Erosive or Ulcerative GERD 20 mg once daily Controlled studies do not extend beyond 12 months Symptomatic GERD in Adults 20 mg once daily Up to 4 weeks ** Healing of Duodenal Ulcers 20 mg once daily after the morning meal Up to 4 weeks *** Helicobacter pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence Rabeprazole sodium delayed-release tablets 20 mg Amoxicillin 1,000 mg Clarithromycin 500 mg Take all three medications twice daily with morning and evening meals; it is important that patients comply with the full 7-day regimen [see Clinical Studies (14.5) ] 7 days Pathological Hypersecretory Conditions, Including Zollinger-Ellison Syndrome Starting dose 60 mg once daily then adjust to patient needs; some patients require divided doses Dosages of 100 mg once daily and 60 mg twice daily have been administered As long as clinically indicated Some patients with Zollinger-Ellison syndrome have been treated continuously for up to one year Adolescents 12 Years of Age and Older Symptomatic GERD 20 mg once daily Up to 8 weeks * 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. ** If symptoms do not resolve completely after 4 weeks, an additional course of treatment may be considered. *** Most patients heal within 4 weeks; some patients may require additional therapy to achieve healing. Administration Instructions Swallow rabeprazole sodium delayed-release tablets whole. Do not chew, crush, or split tablets. For the treatment of duodenal ulcers take rabeprazole sodium delayed-release tablets after a meal. For Helicobacter pylori eradication take rabeprazole sodium delayed-release tablets with food. For all other indications rabeprazole sodium delayed-release tablets can be taken with or without food. Take a missed dose as soon as possible. If it is almost time for the next dose, skip the missed dose and go back to the normal schedule. Do not take two doses at the same time. Indication Recommended Dosage ( 2 ) Healing of Erosive or Ulcerative Gastroesophageal Reflux Disease (GERD) 20...

Side Effects (Adverse Reactions)

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 (5.7) ]. Cyanocobalamin (Vitamin B-12) Deficiency [see Warnings and Precautions (5.8) ]. Hypomagnesemia and Mineral Metabolism [see Warnings and Precautions (5.9) ]. Fundic Gland Polyps [see Warnings and Precautions (5.11) ]. 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 Amneal Pharmaceuticals at 1-877-835-5472 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,...

Drug Interactions

7 DRUG INTERACTIONS Table 2 includes drugs with clinically important drug interactions and interaction with diagnostics when administered concomitantly with rabeprazole sodium delayed-release tablets and instructions for preventing or managing them. Consult the labeling of concomitantly used drugs to obtain further information about interactions with PPIs. Table 2: Clinically Relevant Interactions Affecting Drugs Co-Administered with Rabeprazole Sodium Delayed-Release Tablets and Interactions with Diagnostics Antiretrovirals Clinical Impact: The effect of PPI on antiretroviral drugs is variable. The clinical importance and the mechanisms behind these interactions are not always known. Decreased exposure of some antiretroviral drugs (e.g., rilpivirine, atazanavir, and nelfinavir) when used concomitantly with rabeprazole may reduce antiviral effect and promote the development of drug resistance. Increased exposure of other antiretroviral drugs (e.g., saquinavir) when used concomitantly with rabeprazole may increase toxicity. There are other antiretroviral drugs which do not result in clinically relevant interactions with rabeprazole. Intervention: Rilpivirine-containing products: Concomitant use with rabeprazole sodium delayed-release tablets is contraindicated [see Contraindications (4) ] . See prescribing information. Atazanavir: See prescribing information for atazanavir for dosing information. Nelfinavir: Avoid concomitant use with rabeprazole sodium delayed-release tablets. See prescribing information for nelfinavir. Saquinavir: See the prescribing information for saquinavir and monitor for potential saquinavir toxicities. Other antiretrovirals: See prescribing information. Warfarin Clinical Impact: Increased INR and prothrombin time in patients receiving PPIs, including rabeprazole, and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death [see Warnings and Precautions (5.2) ]. Intervention: Monitor INR and prothrombin time. Dose adjustment of warfarin may be needed to maintain target INR range. See prescribing information for warfarin. Methotrexate Clinical Impact: Concomitant use of rabeprazole with methotrexate (primarily at high dose) may elevate and prolong serum levels of methotrexate and/or its metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities. No formal drug interaction studies of methotrexate with PPIs have been conducted [see Warnings and Precautions (5.9) ]. Intervention: A temporary withdrawal of rabeprazole sodium delayed-release tablets may be considered in some patients receiving high dose methotrexate administration. Digoxin Clinical Impact: Potential for increased exposure of digoxin [see Clinical Pharmacology (12.3) ]. Intervention: Monitor digoxin concentrations. Dose adjustment of digoxin may be needed to maintain therapeutic drug concentrations. See prescribing information for digoxin. Drugs Dependent on Gastric pH for Absorption (e.g., iron...

Contraindications

4 CONTRAINDICATIONS Rabeprazole delayed-release sodium tablets are contraindicated in patients with known hypersensitivity to rabeprazole, substituted benzimidazoles, or to any component of the formulation. Hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute tubulointerstitial nephritis, and urticaria [see Warnings and Precautions (5.3) , Adverse Reactions (6) ]. PPIs, including rabeprazole sodium, are contraindicated with rilpivirine-containing products [see Drug Interactions (7) ]. For information about contraindications of antibacterial agents (clarithromycin and amoxicillin) indicated in combination with rabeprazole sodium delayed-release tablets, refer to the Contraindications section of their package inserts. Patients with a history of hypersensitivity to rabeprazole. ( 4 ) PPIs, including rabeprazole sodium delayed-release tablets, are contraindicated in patients receiving rilpivirine-containing products. ( 4 , 7 ) Refer to the Contraindications section of the prescribing information for clarithromycin and amoxicillin, when administered in combination with rabeprazole sodium. ( 4 )

Overdosage

10 OVERDOSAGE Seven reports of accidental overdosage with rabeprazole have been received. The maximum reported overdose was 80 mg. There were no clinical signs or symptoms associated with any reported overdose. Patients with Zollinger-Ellison syndrome have been treated with up to 120 mg rabeprazole once daily. No specific antidote for rabeprazole is known. Rabeprazole is extensively protein bound and is not readily dialyzable. In the event of overdosage, treatment should be symptomatic and supportive. If over-exposure occurs, call your Poison Control Center at 1-800-222-1222 for current information on the management of poisoning or overdosage.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING Rabeprazole sodium delayed-release tablets, 20 mg are supplied as light yellow to yellow color, round shaped, biconvex enteric-coated tablets imprinted “AR” with black ink on one side and plain on the other side. They are available as follows: Bottles of 30: NDC 65162-724-03 Bottles of 90: NDC 65162-724-09 Bottles of 500: NDC 65162-724-50 Bottles of 1000: NDC 65162-724-11 Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Protect from moisture.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.