Rabeprazole sodium tablet, delayed release

Recent major changes

Warnings and Precautions, Fundic Gland Polyps ( 5.10) 06/2018

1 indications and usage

Rabeprazole sodium delayed-release tablet 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 pyloriEradication 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).

2 dosage and administration

Indication
Recommended Dosage ( 2 )
HealingofErosiveorUlcerativeGastroesophageal
RefluxDisease(GERD)
20mgoncedailyfor4to8weeks
MaintenanceofHealingofErosiveorUlcerative
GERD*studiedfor12months
20mgoncedaily*
SymptomaticGERDinAdults
20mgoncedailyfor4weeks
HealingofDuodenalUlcers
20mgoncedailyaftermorningmeal
forupto4weeks
Helicobacter pyloriEradicationtoReducetheRiskofDuodenalUlcerRecurrence
ThreeDrugRegimen:

Rabeprazolesodiumdelayed-release
tablets20mg
Amoxicillin1000mg
Clarithromycin500mg
All three medications should be taken
twice daily with morning and evening
meals for 7 days .
PathologicalHypersecretoryConditions,Including
Zollinger-EllisonSyndrome
Startingdose60mgoncedailythen
adjusttopatientneeds
SymptomaticGERDinAdolescents12YearsofAge
andOlder
20mgoncedailyforupto8weeks

Administration Instructions ( 2):

  • Swallow rabeprazole sodium delayed-release tablets whole. Do not chew, crush or split the tablets.
  • For the treatment of duodenal ulcers take rabeprazole sodium delayed-release tablets after a meal.
  • For Helicobacter pylorieradication take rabeprazole sodium delayed-release tablets with food.
  • For all other indications rabeprazole sodium delayed-release tablets can be taken with or without food.

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Table 1 shows the recommended dosage of rabeprazole delayed-release tablets in adults and adolescent patients 12 years of age and older. The use of rabeprazole 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 Delayed-Release Tablets in Adults and Adolescents 12 Years of Age and Older

* For those patients who have not healed after 8 weeks of treatment, an additional 8-week course of rabeprazole 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.

Indication
Dosage of Rabeprazole delayed - release tablets
Treatment Duration
Adults


HealingofErosiveorUlcerativeGastroesophageal
RefluxDisease(GERD)
20mgoncedaily

4to8weeks*

MaintenanceofHealingofErosiveorUlcerativeGERD
20mgoncedaily

Controlledstudiesdonotextend
beyond12months
SymptomaticGERDinAdults
20mgoncedaily
Upto4weeks**
HealingofDuodenalUlcers

20mgoncedailyafterthemorningmeal
Upto4weeks***

Helicobacter pyloriEradicationtoReducetheRiskof
DuodenalUlcerRecurrence
Rabeprazole20mg Amoxicillin1000mg Clarithromycin500mg Takeallthreemedicationstwicedailywithmorningandevening meals;itisimportantthatpatientscomplywiththefull 7-dayregimen[seeCLINICALSTUDIES( 14.5)] 7days

PathologicalHypersecretoryConditions,Including
Zollinger-EllisonSyndrome

Startingdose60mgoncedailythenadjusttopatientneeds;
somepatientsrequiredivideddoses
Dosagesof100mgoncedailyand60mg
twicedailyhavebeenadministered
Aslongasclinicallyindicated

SomepatientswithZollinger-Ellisonsyndromehavebeentreated
continuouslyforuptooneyear

Adolescents 12 Years of Age and Older
SymptomaticGERD
20mgoncedaily
Upto8weeks

Administration Instructions

  • Swallow rabeprazole sodium delayed-release tablets whole. Do not chew, crush, or split tablets.
  • For the treatment of duodenal ulcers take rabeprazole delayed-release tablets after a meal.
  • For Helicobacter pylorieradication take rabeprazole 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.

3 dosage forms and strengths

Delayed-Release Tablets: 20 mg ( 3).

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Rabeprazole sodium delayed-release tablets are provided in one strength, 20 mg. The tablets are yellow, round, biconvex, coated tablets, imprinted with "L020" (black ink) on one side.

4 contraindications

  • 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 ( 4).

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  • Rabeprazole sodium delayed-release 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 interstitial nephritis, and urticaria [see ADVERSE REACTIONS ( 6)].
  • PPIs, including rabeprazole sodium delayed-release tablets, 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.

5 warnings and precautions

Gastric Malignancy: In adults, symptomatic response to therapy with rabeprazole does not preclude the presence of gastric malignancy. Consider additional follow-up and diagnostic testing ( 5.1).

Use with Warfarin: Monitor for increases in INR and prothombin time ( 5.2, 7).

Acute Interstitial Nephritis:Observed in patients taking PPIs ( 5.3).

Clostridium difficile- Associated Diarrhea: PPI therapy may be associated with increased risk of ( 5.4).

Bone Fracture:Long-term and multiple daily dose PPI therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist, or spine ( 5.5).

Cutaneous and Systemic Lupus Erythematosus:Mostly cutaneous, new onset or exacerbation of existing disease; discontinue rabeprazole sodium delayed-release tablets and refer to specialist for evaluation ( 5.6).

Cyanocobalamin (Vitamin B-12) Deficiency: Daily long-term use (e.g., longer than 3 years) may lead to malabsorption or a deficiency of cyanocobalamin ( 5.7).

Hypomagnesemia: Reported rarely with prolonged treatment with PPIs ( 5.8).

  • Interaction with Methotrexate: Concomitant use with PPIs may elevate and/or prolong serum concentrations of methotrexate and/or its metabolite, possibly leading to toxicity. With high dose methotrexate administration, consider a temporary withdrawal of rabeprazole delayed-release tablets ( 5.9, 7).
  • Fundic Gland Polyps:Risk increases with long-term use, especially beyond one year. Use the shortest duration of therapy ( 5.10).

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6 adverse reactions

  • 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 Lupin Pharmaceuticals, Inc. at 1-800-399-2561 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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The following serious adverse reactions are described below and elsewhere in labeling:

  • Acute Interstitial 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)]

7 drug interactions

See full prescribing information for a list of clinically important drug interactions ( 7).

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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 salts, erlotinib, dasatinib, nilotinib, mycophenolate mofetil, ketoconazole, itraconazole)
Clinical Impact:
Rabeprazole can reduce the absorption of other drugs due to its effect on reducing intragastric acidity.
Intervention:
Mycophenolate mofetil (MMF): Co-administration of PPIs in healthy subjects and in transplant patients receiving MMF has been reported to reduce the exposure to the active metabolite, mycophenolic acid (MPA), possibly due to a decrease in MMF solubility at an increased gastric pH. The clinical relevance of reduced MPA exposure on organ rejection has not been established in transplant patients receiving rabeprazole sodium delayed-release tablets and MMF. Use rabeprazole sodium delayed-release tablets with caution in transplant patients receiving MMF.
See the prescribing information for other drugs dependent on gastric pH for absorption.
Combination Therapy with Clarithromycin and Amoxicillin
Clinical Impact:
Concomitant administration of clarithromycin with other drugs can lead to serious adverse reactions, including potentially fatal arrhythmias, and are contraindicated.
Amoxicillin also has drug interactions.
Intervention:
See CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS in prescribing information for clarithromycin.
See DRUG INTERACTIONS in prescribing information for amoxicillin.
Tacrolimus
Clinical Impact:
Potentially increased exposure of tacrolimus, especially in transplant patients who are intermediate or poor metabolizers of CYP2C19 .
Intervention:
Monitor tacrolimus whole blood trough concentrations. Dose adjustment of tacrolimus may be needed to maintain therapeutic drug concentrations. See prescribing information for tacrolimus.
Interactions with Investigations of Neuroendocrine Tumors
Clinical Impact:
Serum chromogranin A (CgA) levels increase secondary to PPI-induced decreases in gastric acidity. The increased CgA level may cause false positive results in diagnostic investigations for neuroendocrine tumors .
Intervention:
Temporarily stop rabeprazole sodium delayed-release tablets treatment at least 14 days before assessing CgA levels and consider repeating the test if initial CgA levels are high. If serial tests are performed (e.g. for monitoring), the same commercial laboratory should be used for testing, as reference ranges between tests may vary.
Interaction with Secretin Stimulation Test
Clinical Impact:
Hyper-response in gastrin secretion in response to secretin stimulation test, falsely suggesting gastrinoma.
Intervention:
Temporarily stop treatment with rabeprazole sodium delayed-release tablets at least 14 days before assessing to allow gastrin levels to return to baseline.
False Positive Urine Tests for THC
Clinical Impact:
There have been reports of false positive urine screening tests for tetrahydrocannabinol (THC) in patients receiving PPIs.
Intervention:
An alternative confirmatory method should be considered to verify positive results.

8 use in specific populations

Pediatric Use: Dosage strength not appropriate for patients less than 12 years ( 2, 8.4).

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8.1 pregnancy

Risk Summary

There are no available human data on rabeprazole sodium delayed-release tablets use in pregnant women to inform the drug associated risk. The background risk of major birth defects and miscarriage for the indicated populations are unknown. However, the background risk in the U.S. general population of major birth defects is 2 to 4% and of miscarriage is 15 to 20% of clinically recognized pregnancies. No evidence of adverse developmental effects were seen in animal reproduction studies with rabeprazole administered during organogenesis at 13 and 8 times the human area under the plasma concentration-time curve (AUC) at the recommended dose for GERD, in rats and rabbits, respectively [see Data].

Changes in bone morphology were observed in offspring of rats treated with oral doses of a different PPI through most of pregnancy and lactation. When maternal administration was confined to gestation only, there were no effects on bone physeal morphology in the offspring at any age [see Data].

Data

Animal Data:

Embryo-fetal developmental studies have been performed in rats during organogenesis at intravenous doses of rabeprazole up to 50 mg/kg/day (plasma AUC of 11.8 mcghr/mL, about 13 times the human exposure at the recommended oral dose for GERD) and rabbits at intravenous doses up to 30 mg/kg/day (plasma AUC of 7.3 mcghr/mL, about 8 times the human exposure at the recommended oral dose for GERD) and have revealed no evidence of harm to the fetus due to rabeprazole.

Administration of rabeprazole to rats in late gestation and during lactation at an oral dose of 400 mg/kg/day (about 195-times the human oral dose based on mg/m 2) resulted in decreases in body weight gain of the pups.

A pre- and postnatal developmental toxicity study in rats with additional endpoints to evaluate bone development was performed with a different PPI at about 3.4 to 57 times an oral human dose on a body surface area basis. Decreased femur length, width and thickness of cortical bone, decreased thickness of the tibial growth plate, and minimal to mild bone marrow hypocellularity were noted at doses of this PPI equal to or greater than 3.4 times an oral human dose on a body surface area basis. Physeal dysplasia in the femur was also observed in offspring after in utero and lactational exposure to the PPI at doses equal to or greater than 33.6 times an oral human dose on a body surface area basis. Effects on maternal bone were observed in pregnant and lactating rats in a pre- and postnatal toxicity study when the PPI was administered at oral doses of 3.4 to 57 times an oral human dose on a body surface area basis. When rats were dosed from gestational day 7 through weaning on postnatal day 21, a statistically significant decrease in maternal femur weight of up to 14% (as compared to placebo treatment) was observed at doses equal to or greater than 33.6 times an oral human dose on a body surface area basis.

A follow-up developmental toxicity study in rats with further time points to evaluate pup bone development from postnatal day 2 to adulthood was performed with a different PPI at oral doses of 280 mg/kg/day (about 68 times an oral human dose on a body surface area basis) where drug administration was from either gestational day 7 or gestational day 16 until parturition. When maternal administration was confined to gestation only, there were no effects on bone physeal morphology in the offspring at any age.

8.4 pediatric use

The safety and effectiveness of rabeprazole sodium delayed-release tablets have been established in pediatric patients for adolescent patients 12 years of age and older for the treatment of symptomatic GERD. Use of rabeprazole sodium delayed-release tablets in this age group is supported by adequate and well controlled studies in adults and a multicenter, randomized, open-label, parallel-group study in 111 adolescent patients 12 to 16 years of age. Patients had a clinical diagnosis of symptomatic GERD, or suspected or endoscopically proven GERD and were randomized to either 10 mg or 20 mg once daily for up to 8 weeks for the evaluation of safety and efficacy. The adverse reaction profile in adolescent patients was similar to that of adults. The related reported adverse reactions that occurred in 2% of patients were headache (5%) and nausea (2%). There were no adverse reactions reported in these studies that were not previously observed in adults.

The safety and effectiveness of rabeprazole sodium delayed-release tablets have not been established in pediatric patients for:

  • Healing of Erosive or Ulcerative GERD
  • Maintenance of Healing of Erosive or Ulcerative GERD
  • Treatment of Symptomatic GERD
  • Healing of Duodenal Ulcers
  • Helicobacter pyloriEradication to Reduce the Risk of Duodenal Ulcer Recurrence
  • Treatment of Pathological Hypersecretory Conditions, Including Zollinger-Ellison Syndrome

Rabeprazole sodium delayed-release 20 mg tablets are not recommended for use in pediatric patients less than 12 years of age because the tablet strength exceeds the recommended dose for these patients [see DOSAGE AND ADMINISTRATION ( 2)].For pediatric patients 1 year to less than 12 years of age consider another rabeprazole formulation. The safety and effectiveness of a different dosage form and dosage strength of rabeprazole has been established in pediatric patients 1 to 11 years for the treatment of GERD.

Juvenile Animal Data

Studies in juvenile and young adult rats and dogs were performed. In juvenile animal studies rabeprazole sodium was administered orally to rats for up to 5 weeks and to dogs for up to 13 weeks, each commencing on Day 7 post-partum and followed by a 13-week recovery period. Rats were dosed at 5, 25, or 150 mg/kg/day and dogs were dosed at 3, 10, or 30 mg/kg/day. The data from these studies were comparable to those reported for young adult animals. Pharmacologically mediated changes, including increased serum gastrin levels and stomach changes, were observed at all dose levels in both rats and dogs. These observations were reversible over the 13-week recovery periods. Although body weights and/or crown-rump lengths were minimally decreased during dosing, no effects on the development parameters were noted in either juvenile rats or dogs.

When juvenile animals were treated for 28 days with a different PPI at doses equal to or greater than 34 times the daily oral human dose on a body surface area basis, overall growth was affected and treatment-related decreases in body weight (approximately 14%) and body weight gain, and decreases in femur weight and femur length were observed.

8.5 geriatric use

Of the total number of subjects (n=2009) in clinical studies of rabeprazole sodium delayed-release tablets, 19% were 65 years and over, while 4% were 75 years and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

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.

11 description

The active ingredient in rabeprazole sodium delayed-release tablets is rabeprazole sodium, 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 Hbenzimidazole sodium salt. It has an empirical formula of C 18H 20N 3NaO 3S and a molecular weight of 381.43. Rabeprazole sodium 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:

Image-01

Rabeprazole sodium is available for oral administration as delayed-release, enteric-coated tablets containing 20 mg of rabeprazole sodium.

Inactive ingredients of the 20 mg tablet are black iron oxide, carnauba wax, crospovidone, diacetylated monoglycerides, ethyl cellulose, hydroxypropyl cellulose, hypromellose phthalate, lecithin, light magnesium oxide, magnesium stearate, mannitol, polyethylene glycol, polyvinyl alcohol, shellac, sodium stearyl fumarate, talc, titanium dioxide and yellow iron oxide.

12 clinical pharmacology

12.1 mechanism of action

Rabeprazole belongs to a class of antisecretory compounds (substituted benzimidazole proton-pump inhibitors) that do not exhibit anticholinergic or histamine H 2-receptor antagonist properties, but suppress gastric acid secretion by inhibiting the gastric H +, K +ATPase at the secretory surface of the gastric parietal cell. Because this enzyme is regarded as the acid (proton) pump within the parietal cell, rabeprazole has been characterized as a gastric proton-pump inhibitor. Rabeprazole blocks the final step of gastric acid secretion.

In gastric parietal cells, rabeprazole is protonated, accumulates, and is transformed to an active sulfenamide. When studied in vitro, rabeprazole is chemically activated at pH 1.2 with a half-life of 78 seconds. It inhibits acid transport in porcine gastric vesicles with a half-life of 90 seconds.

12.2 pharmacodynamics

12.3 pharmacokinetics

After oral administration of 20 mg rabeprazole sodium delayed-release tablets, peak plasma concentrations (C max) of rabeprazole occur over a range of 2 to 5 hours (T max). The rabeprazole C maxand AUC are linear over an oral dose range of 10 mg to 40 mg. There is no appreciable accumulation when doses of 10 mg to 40 mg are administered every 24 hours; the pharmacokinetics of rabeprazole is not altered by multiple dosing.

12.4 microbiology

The following in vitrodata are available but the clinical significance is unknown.

Rabeprazole sodium, amoxicillin and clarithromycin as a three drug regimen has been shown to be active against most strains of Helicobacter pylori in vitroand in clinical infections [see INDICATIONS AND USAGE ( 1), CLINICAL STUDIES ( 14.5)].

13 nonclinical toxicology

14 clinical studies

15 references

  1. Clinical and Laboratory Standards Institute (CLSI). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved StandardTenth Edition. CLSI Document M07-A10, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania, 19087, USA 2015.

16 how supplied/storage and handling

Product: 50090-1424

NDC: 50090-1424-1 90 TABLET, DELAYED RELEASE in a BOTTLE

17 patient counseling information

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Acute Interstitial Nephritis

Advise the patient or caregiver to call the patient's healthcare provider immediately if they experience signs and/or symptoms associated with acute interstitial nephritis [see WARNINGS AND PRECAUTIONS ( 5.3)].

Clostridium difficile -Associated Diarrhea

Advise the patient or caregiver to immediately call the patient's healthcare provider if they experience diarrhea that does not improve [see WARNINGS AND PRECAUTIONS ( 5.4)].

Bone Fracture

Advise the patient or caregiver to report any fractures, especially of the hip, wrist or spine, to the patient's healthcare provider [see WARNINGS AND PRECAUTIONS ( 5.5)].

Cutaneous and Systemic Lupus Erythematosus

Advise the patient or caregiver to immediately call the patient's healthcare provider for any new or worsening of symptoms associated with cutaneous or systemic lupus erythematosus [see WARNINGS AND PRECAUTIONS ( 5.6)].

Cyanocobalamin (Vitamin B-12) Deficiency

Advise the patient or caregiver to report any clinical symptoms that may be associated with cyanocobalamin deficiency to the patient's healthcare provider if they have been receiving rabeprazole sodium delayed-release tablets for longer than 3 years [see WARNINGS AND PRECAUTIONS ( 5.7)].

Hypomagnesemia

Advise the patient or caregiver to report any clinical symptoms that may be associated with hypomagnesemia to the patient's healthcare provider, if they have been receiving rabeprazole sodium delayed-release tablets for at least 3 months [see WARNINGS AND PRECAUTIONS ( 5.8)].

Drug Interactions

Advise patients to report to their healthcare provider if they are taking rilpivirine-containing products [see CONTRAINDICATIONS ( 4)],warfarin, digoxin or high-dose methotrexate [see WARNINGS AND PRECAUTIONS ( 5.2, 5.8, 5.9)].

Administration

  • Swallow rabeprazole sodium delayed-release tablets whole. Do not chew, crush or split the tablets.
  • For the treatment of duodenal ulcers take rabeprazole sodium delayed-release tablets after a meal.
  • For Helicobacter pylorieradication 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.

The brands listed are trademarks of their respective owners and are not trademarks of Lupin Pharmaceuticals, Inc. The makers of these brands are not affiliated with and do not endorse Lupin Pharmaceuticals, Inc. or its products.

Manufactured for:

Lupin Pharmaceuticals, Inc.

Baltimore, Maryland 21202

United States

Manufactured by:

Lupin Limited

Goa 403722

INDIA

Revised: July 7, 2018 ID#: 255833

Spl medguide section

MEDICATION GUIDE

Rabeprazole Sodium (ra bep ra zole soe dee um)

Delayed-Release Tablets

Rx Only

Read the Medication Guide that comes with rabeprazole sodium delayed-release tablets before you start taking it and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking to your doctor about your medical condition or treatment.

What is the most important information I should know about rabeprazole sodium delayed-release tablets?

You should take rabeprazole sodium delayed-release tablets exactly as prescribed, at the lowest dose possible and for the shortest time needed.

Rabeprazole sodium delayed-release tablets may help your acid-related symptoms, but you could still have serious stomach problems.Talk with your doctor .

Rabeprazole sodium delayed-release tablets can cause serious side effects, including:

  • A type of kidney problem (acute interstitial nephritis).Some people who take proton pump inhibitor (PPI) medicines, including rabeprazole sodium delayed-release tablets, may develop a kidney problem called acute interstitial nephritis that can happen at any time during treatment with rabeprazole sodium delayed-release tablets. Call your doctor right away if you have a decrease in the amount that you urinate or if you have blood in your urine.
  • Diarrhea caused by an infection ( Clostridium difficile) in your intestines.Call your doctor right away if you have watery stools or, stomach pain that does not go away. You may or may not have a fever.
  • Bone fractures (hip, wrist, or spine).Bone fractures in the hip, wrist, or spine may happen in people who take multiple daily doses of PPI medicines and for a long period of time (a year or longer). Tell your doctor if you have a bone fracture, especially in the hip, wrist, or spine.
  • Certain types of lupus erythematosus.Lupus erythematosus is an autoimmune disorder (the body's immune cells attack other cells or organs in the body). Some people who take PPI medicines, including rabeprazole sodium delayed-release tablets, may develop certain types of lupus erythematosus or have worsening of the lupus they already have. Call your doctor right away if you have new or worsening joint pain or a rash on your cheeks or arms that gets worse in the sun.

Talk to your doctor about your risk of these serious side effects.

Rabeprazole sodium delayed-release tablet can have other serious side effects. See "What are the possible side effects of rabeprazole sodium delayed-release tablets?"

What are rabeprazole sodium delayed-release tablets?

Rabeprazole sodium delayed-release tablet is a prescription medicine called a proton pump inhibitor (PPI).

Rabeprazole sodium delayed-release tablet reduces the amount of acid in your stomach.

In adults, rabeprazole sodium delayed-release tablets are used for:

  • 8 weeks up to 16 weeks to heal acid-related damage to the lining of the esophagus (called erosive esophagitis or EE) and to relieve symptoms, such as heartburn pain.
  • maintaining healing of the esophagus and relief of symptoms related to EE. It is not known if rabeprazole sodium delayed-release tablet is safe and effective if used longer than 12 months (1 year).
  • up to 4 weeks to treat daytime and nighttime heartburn and other symptoms that happen with Gastroesophageal Reflux Disease (GERD).
  • up to 4 weeks for the healing and relief of symptoms of duodenal ulcers.
  • 7 days with certain antibiotic medicines to treat an infection and stomach (duodenal) ulcers caused by bacteria called H. pylori.
  • the long-term treatment of conditions where your stomach makes too much acid. This includes a rare condition called Zollinger-Ellison syndrome.

In adolescents 12 years of age and older,rabeprazole sodium delayed-release tablet is used for up to 8 weeks to treat symptoms of GERD.

It is not known if rabeprazole sodium delayed-release tablet is safe and effective in children less than 12 years of age for other uses. Rabeprazole sodium delayed-release tablets should not be used in children under 12 years of age.

Do not take rabeprazole sodium delayed-release tablets if you are:

  • allergic to rabeprazole, any other PPI medicine, or any of the ingredients in rabeprazole sodium delayed-release tablet. See the end of this Medication Guide for a complete list of ingredients.
  • taking a medicine that contains rilpivirine (EDURANT, COMPLERA, ODEFSEY) used to treat HIV-1 (Human Immunodeficiency Virus).

Before you take rabeprazole sodium delayed-release tablets, tell your doctor about all of your medical conditions, including if you:

  • have low magnesium levels in your blood.
  • have liver problems.
  • are pregnant or plan to become pregnant. It is not known if rabeprazole sodium delayed-release tablet can harm your unborn baby.
  • are breastfeeding or plan to breastfeed. It is not known if rabeprazole sodium passes into your breast milk. Talk to your doctor about the best way to feed your baby if you take rabeprazole sodium delayed-release tablet.

Tell your doctor about all the medicines you take,including prescription and over-the-counter medicines, vitamins, and herbal supplements. Especially tell your doctorif you take an antibiotic that contains clarithromycin or amoxicillin or if you take warfarin (COUMADIN, JANTOVEN), methotrexate (OTREXUP, RASUVO, TREXALL, XATMEP), digoxin (LANOXIN), or a water pill (diuretic).

How should I take rabeprazole sodium delayed-release tablets?

  • Take rabeprazole sodium delayed-release tablets exactly as prescribed.
  • Rabeprazole sodium delayed-release tablets are usually taken 1 time each day. Your doctor will tell you the time of day to take rabeprazole sodium delayed-release tablets, based on your medical condition.
  • Rabeprazole sodium delayed-release tablets can be taken with or without food. Your doctor will tell you whether to take this medicine with or without food based on your medical condition.
  • Swallow each rabeprazole sodium delayed-release tablet whole. Do not chew, crush, or split rabeprazole sodium delayed-release tablets. Tell your doctor if you cannot swallow tablets whole.
  • If you miss a dose of rabeprazole sodium delayed-release tablets, take it as soon as possible. If it is almost time for your next dose, you should not take the missed dose. You should take your next dose at your regular time. Do not take 2 doses at the same time.
  • If you take too much rabeprazole sodium delayed-release tablets, call your doctor or your poison control center at 1-800-222-1222 right away, or go to the nearest emergency room.
  • If your doctor prescribes antibiotic medicines with rabeprazole sodium delayed-release tablets, read the patient information that comes with the antibiotic medicines before you take them.

What are the possible side effects of rabeprazole sodium delayed-release tablets?

Rabeprazole sodium delayed-release tablets can cause serious side effects, including:

  • See "What is the most important information I should know about rabeprazole sodium delayed-release tablets?"
  • Interaction with warfarin.Taking warfarin with a PPI medicine may lead to an increased risk of bleeding and death. If you take warfarin, your doctor may check your blood to see if you have an increased risk of bleeding. If you take warfarin during treatment with rabeprazole sodium delayed-release tablets, tell your doctor right away if you have any signs or symptoms of bleeding, including:
    • pain, swelling or discomfort
    • headaches, dizziness, or weakness
    • unusual bruising (bruises that happen without known cause or that grow in size)
    • nosebleeds
    • bleeding gums
    • bleeding from cuts take a long time to stop
    • menstrual bleeding that is heavier than normal
    • pink or brown urine
    • red or black stools
    • coughing up blood
    • vomiting blood or vomit that looks like coffee grounds
  • Low vitamin B-12 levelsin the body can happen in people who have taken rabeprazole sodium delayed-release tablets for a long time (more than 3 years). Tell your doctor if you have symptoms of low vitamin B-12 levels, including shortness of breath, lightheadedness, irregular heartbeat, muscle weakness, pale skin, feeling tired, mood changes, and tingling or numbness in the arms and legs.
  • Low magnesium levels in the bodycan happen in people who have taken rabeprazole sodium delayed-release tablets for at least 3 months. Tell your doctor if you have symptoms of low magnesium levels, including seizures, dizziness, irregular heartbeat, jitteriness, muscle aches or weakness, and spasms of hands, feet or voice.
  • Stomach growths (fundic gland polyps).People who take PPI medicines for a long time have an increased risk of developing a certain type of stomach growths called fundic gland polyps, especially after taking PPI medicines for more than 1 year.

The most common side effects of rabeprazole sodium delayed-release tablets in adults include:pain, sore throat, gas, infection, and constipation.

The most common side effects of rabeprazole sodium delayed-release tablets in adolescents 12 years of age and older include:headache, diarrhea, nausea, vomiting, and stomach-area (abdomen) pain.

These are not all of the possible side effects of rabeprazole sodium delayed-release tablets. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store rabeprazole sodium delayed-release tablets?

Store rabeprazole sodium delayed-release tablets in a dry place at 25C (77F); excursions permitted to 15 to 30C (59 to 86F). Protect from moisture.

Keep rabeprazole sodium delayed-release tablets and all medicines out of the reach of children.

General Information about the safe and effective use of rabeprazole sodium delayed-release tablets

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use rabeprazole sodium delayed-release tablets for a condition for which it was not prescribed. Do not give rabeprazole sodium delayed-release tablets to other people, even if they have the same symptoms that you have. It may harm them.

You can ask your doctor or pharmacist for information about rabeprazole sodium delayed-release tablets that is written for health professionals.

What are the ingredients in rabeprazole sodium delayed-release tablets?

Active ingredient: rabeprazole sodium

Inactive ingredients:black iron oxide, carnauba wax, crospovidone, diacetylated monoglycerides, ethyl cellulose, hydroxypropyl cellulose, hypromellose phthalate, lecithin, light magnesium oxide, magnesium stearate, mannitol, polyethylene glycol, polyvinyl alcohol, shellac, sodium stearyl fumarate, talc, titanium dioxide and yellow iron oxide.

The brands listed are the trademarks of their respective owners and are not trademarks of Lupin Pharmaceuticals, Inc. The makers of these brands are not affiliated with and do not endorse Lupin Pharmaceuticals, Inc. or its products.

For more information, go to www.lupinpharmaceuticals.com or call the toll free number 1-800-399-2561.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Manufactured for:

Lupin Pharmaceuticals, Inc.

Baltimore, Maryland 21202

United States

Manufactured by:

Lupin Limited

Goa 403722

INDIA

Revised: July 7, 2018 ID#: 255819

Ingredients and appearance - Product information

Rabeprazole sodium tablet, delayed release- Rabeprazole sodium

Product information

Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC: 50090-1424
Route of Administration Oral

Active Ingredient/Active Moiety

Ingredient Name Strength
Rabeprazole sodium ( UNII: 3L36P16U4R)( Rabeprazole - UNII: 32828355LL ) 20 mgin 1

Inactive Ingredients

Ingredient Name Code
Carnauba wax ( UNII: R12CBM0EIZ)
Crospovidone, unspecified ( UNII: 2S7830E561)
Diacetylated monoglycerides ( UNII: 5Z17386USF)
Ethylcellulose, unspecified ( UNII: 7Z8S9VYZ4B)
Ferric oxide yellow ( UNII: EX438O2MRT)
Ferrosoferric oxide ( UNII: XM0M87F357)
Hydroxypropyl cellulose (1600000 wamw) ( UNII: RFW2ET671P)
Hypromellose phthalate (24% phthalate, 55 cst) ( UNII: 87Y6436BKR)
Lecithin, soybean ( UNII: 1DI56QDM62)
Magnesium oxide ( UNII: 3A3U0GI71G)
Magnesium stearate ( UNII: 70097M6I30)
Mannitol ( UNII: 3OWL53L36A)
Polyethylene glycol, unspecified ( UNII: 3WJQ0SDW1A)
Polyvinyl alcohol, unspecified ( UNII: 532B59J990)
Shellac ( UNII: 46N107B71O)
Sodium stearyl fumarate ( UNII: 7CV7WJK4UI)
Talc ( UNII: 7SEV7J4R1U)
Titanium dioxide ( UNII: 15FIX9V2JP)

Product Characteristics

Color YELLOW (yellow) Shape ROUND (biconvex)
Size 7 mm Score 1
Imprint Code L020

Packaging

# Item Code Package Description Marketing Start Date
1 NDC: 50090-1424-0 30 in 1 BOTTLE 2014/11/28
2 NDC: 50090-1424-1 90 in 1 BOTTLE 2014/11/28
3 NDC: 50090-1424-2 60 in 1 BOTTLE 2017/05/25

Marketing Information

Marketing Category Application Number or Monograph Citation Territorial Authority Marketing Start Date
ANDA ANDA078964 USA 2017/05/25

Labeler - A-S Medication Solutions( 830016429)

Establishment

Name ID/FEI Business Operations
A-S Medication Solutions 830016429 RELABEL( 50090-1424), REPACK( 50090-1424)

Rabeprazole sodium