RABERPRAZOLE SODIUM D/R tablet, delayed release

United States - English - NLM (National Library of Medicine)

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Active ingredient:
RABEPRAZOLE SODIUM (UNII: 3L36P16U4R) (RABEPRAZOLE - UNII:32828355LL)
Available from:
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Administration route:
ORAL
Prescription type:
PRESCRIPTION DRUG
Therapeutic indications:
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 Rabep
Product summary:
Rabeprazole sodium 20 mg is supplied as yellow colored, round, biconvex delayed-release tablets imprinted with '107' on one side in black ink and plain on other side. Bottles of 30 Bottles of 90 Bottles of 500 Bottles of 4000 100 Unit dose Tablets Store at 20° to 25°C (68° to 77°F), excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Protect from moisture.
Authorization status:
Abbreviated New Drug Application
Authorization number:
61919-225-60, 61919-225-90

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MEDICATION GUIDE

Rabeprazole sodium (ra-BEP-ra-zole SOE-dee-um) delayed-release tablets

What is the most important information I should know about r abeprazole 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 tablets can have other serious side effects. See "What are the possible

side effects of r abeprazole sodium delayed-release tablets?"

What are rabeprazole sodium delayed-release tablets?

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

Rabeprazole sodium delayed-release tablets 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 tablets are 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 tablets are used for up to 8

weeks to treat symptoms of GERD.

It is not known if rabeprazole sodium delayed-release tablets are 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 tablets. 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 tablets can

harm your unborn baby.

are breastfeeding or plan to breastfeed. It is not known if rabeprazole sodium delayed-release tablets passes

into your breast milk.

Talk to your doctor about the best way to feed your baby if you take rabeprazole sodium delayed-release

tablets.

Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines,

vitamins, and herbal supplements. Especially tell your doctor if 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 r abeprazole 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 prescribe 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:

ο pain, swelling or discomfort ο menstrual bleeding that is heavier than

ο headaches, dizziness, or weakness normal

ο unusual bruising (bruises that happen ο pink or brown urine

without known cause or that grow in size) ο red or black stools

ο nosebleeds ο coughing up blood

ο bleeding gums ο vomiting blood or vomit that looks like

ο bleeding from cuts take a long time to stop coffee grounds

Low vitamin B-12 levels in 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 your body can 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 adult 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 20° to 25°C (68° to 77°F), excursions

permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

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: diethyl phthalate, ethyl cellulose, hypromellose phthalate, magnesium oxide,

magnesium stearate, mannitol, povidone, sodium starch glycolate, talc, and titanium dioxide. Ferric oxide

yellow is the coloring agent for the tablet coating.

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

All brand names are the trademarks of their respective owners.

[Image]

Manufactured by:

TORRENT PHARMACEUTICALS LTD., Indrad-382 721, Dist. Mehsana, INDIA.

For:

TORRENT PHARMA INC., 150 Allen Road, Suite 102, Basking Ridge, NJ 07920.

8069704 Revised July 2018

Revised: 10/2020

Document Id: b1a80b01-f3f4-fd4b-e053-2995a90aff85

34391-3

Set id: 8f896469-4df5-599c-e053-2a95a90ac924

Version: 3

Effective Time: 20201014

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RABERPRAZOLE SODIUM D/R- raberprazole sodium d/r tablet, delayed release

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RABERPRAZOLE SODIUM D/R 20mg

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.

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

* 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.

Indication

Dosage of Rabeprazole Sodium delayed-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 1000 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

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.

Rabeprazole sodium delayed-release tablets are provided in one strength, 20 mg. The tablets are yellow

coloured, round, biconvex delayed-release tablet, imprinted with "107"on one side in black ink and plain

on other side.

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.

5.1 Presence of Gastric Malignancy

In adults, symptomatic response to therapy with rabeprazole sodium delayed-release tablets does not

preclude the presence of gastric malignancy. Consider additional follow-up and diagnostic testing in

adult patients who have a suboptimal response or an early symptomatic relapse after completing

treatment with a PPI.

5.2 Interaction with Warfarin

Steady state interactions of rabeprazole and warfarin have not been adequately evaluated in patients.

There have been reports of increased INR and prothrombin time in patients receiving a proton pump

inhibitor and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal

bleeding and even death. Patients treated with rabeprazole sodium delayed-release tablets and warfarin

concomitantly may need to be monitored for increases in INR and prothrombin time [see Drug

Interactions (7)].

5.3 Acute Interstitial Nephritis

Acute interstitial nephritis has been observed in patients taking PPIs including rabeprazole sodium.

Acute interstitial nephritis may occur at any point during PPI therapy and is generally attributed to an

idiopathic hypersensitivity reaction. Discontinue rabeprazole sodium if acute interstitial nephritis

develops [see Contraindications (4)].

5.4 Clostridium difficile-Associated Diarrhea

Published observational studies suggest that PPI therapy like rabeprazole sodium may be associated

with an increased risk of Clostridium difficile-associated diarrhea, especially in hospitalized patients.

This diagnosis should be considered for diarrhea that does not improve [see Adverse Reaction (6.2)].

Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition

being treated.

Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial

agents. For more information specific to antibacterial agents (clarithromycin and amoxicillin) indicated

for use in combination with rabeprazole sodium, refer to Warnings and Precautions sections of the

corresponding prescribing information.

5.5 Bone Fracture

Several published observational studies in adults suggest that PPI therapy may be associated with an

increased risk for osteoporosis-related fractures of the hip, wrist, or spine. The risk of fracture was

increased in patients who received high-dose, defined as multiple daily doses, and long-term PPI

therapy (a year or longer). Patients should use the lowest dose and shortest duration of PPI therapy

appropriate to the condition being treated. Patients at risk for osteoporosis-related fractures should be

managed according to established treatment guidelines [see Dosage and Administration (2), Adverse

Reactions (6.2)].

5.6 Cutaneous and Systemic Lupus Erythematosus

Cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE) have been reported in

patients taking PPIs, including rabeprazole. These events have occurred as both new onset and an

exacerbation of existing autoimmune disease. The majority of PPI-induced lupus erythematosus cases

were CLE.

The most common form of CLE reported in patients treated with PPIs was subacute CLE (SCLE) and

occurred within weeks to years after continuous drug therapy in patients ranging from infants to the

elderly. Generally, histological findings were observed without organ involvement.

Systemic lupus erythematosus (SLE) is less commonly reported than CLE in patients receiving PPIs. PPI

associated SLE is usually milder than non-drug induced SLE. Onset of SLE typically occurred within

days to years after initiating treatment primarily in patients ranging from young adults to the elderly. The

majority of patients presented with rash; however, arthralgia and cytopenia were also reported.

Avoid administration of PPIs for longer than medically indicated. If signs or symptoms consistent with

CLE or SLE are noted in patients receiving rabeprazole sodium, discontinue the drug and refer the

patient to the appropriate specialist for evaluation. Most patients improve with discontinuation of the PPI

alone in 4 to 12 weeks. Serological testing (e.g. ANA) may be positive and elevated serological test

results may take longer to resolve than clinical manifestations.

5.7 Cyanocobalamin (Vitamin B-12) Deficiency

Daily treatment with any acid-suppressing medications over a long period of time (e.g., longer than 3

years) may lead to malabsorption of cyanocobalamin (vitamin B-12) caused by hypo- or achlorhydria.

Rare reports of cyanocobalamin deficiency occurring with acid-suppressing therapy have been

reported in the literature. This diagnosis should be considered if clinical symptoms consistent with

cyanocobalamin deficiency are observed in patients treated with rabeprazole sodium delayed-release

tablets.

5.8 Hypomagnesemia

Hypomagnesemia, symptomatic and asymptomatic, has been reported rarely in patients treated with PPIs

for at least three months, in most cases after a year of therapy. Serious adverse events include tetany,

arrhythmias, and seizures. In most patients, treatment of hypomagnesemia required magnesium

replacement and discontinuation of the PPI.

For patients expected to be on prolonged treatment or who take PPIs with medications such as digoxin

or drugs that may cause hypomagnesemia (e.g., diuretics), healthcare professionals may consider

monitoring magnesium levels prior to initiation of PPI treatment and periodically [see Adverse

Reactions (6.2)].

5.9 Interaction with Methotrexate

Literature suggests that concomitant use of PPIs with methotrexate (primarily at high dose; see

methotrexate prescribing information) may elevate and prolong serum concentrations of methotrexate

and/or its metabolite, possibly leading to methotrexate toxicities. In high-dose methotrexate

administration, a temporary withdrawal of the PPI may be considered in some patients [see Drug

Interactions (7)].

5.10 Fundic Gland Polyps

PPI use is associated with an increased risk of fundic gland polyps that increases with long-term use,

especially beyond one year. Most PPI users who developed fundic gland polyps were asymptomatic and

fundic gland polyps were identified incidentally on endoscopy. Use the shortest duration of PPI therapy

appropriate to the condition being treated.

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)]

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 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 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=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 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.

Pediatric

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

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.

8.1 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/m2) 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.

8.2 Lactation

Risk Summary

Lactation studies have not been conducted to assess the presence of rabeprazole in human milk, the

effects of rabeprazole on the breastfed infant, or the effects of rabeprazole on milk production.

Rabeprazole is present in rat milk. The development and health benefits of breastfeeding should be

considered along with the mother's clinical need for rabeprazole sodium delayed-release tablets and any

potential adverse effects on the breastfed infant from rabeprazole sodium delayed-release tablets or

from the underlying maternal condition.

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 pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence

Treatment of Pathological Hypersecretory Conditions, Including Zollinger-Ellison Syndrome

Rabeprazole sodium delayed-release tablets 20 mg 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.

8.6 Hepatic Impairment

Administration of rabeprazole sodium delayed-release tablets to patients with mild to moderate hepatic

impairment (Child-Pugh Class A and B, respectively) resulted in increased exposure and decreased

elimination [see Clinical Pharmacology (12.3)]. No dosage adjustment is necessary in patients with mild

to moderate hepatic impairment. There is no information in patients with severe hepatic impairment

(Child-Pugh Class C). Avoid use of rabeprazole sodium delayed-release tablets in patients with severe

hepatic impairment; however, if treatment is necessary, monitor patients for adverse reactions [see

Warnings and Precautions (5), Adverse Reactions (6)].

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.

The active ingredient in rabeprazole sodium delayed-release tablets is rabeprazole sodium hydrate,

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]-1H–benzimidazole sodium salt. It has an

empirical formula of C18H20N3NaO3S and a molecular weight of 381.42. Rabeprazole sodium

hydrate, 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 hydrate, USP is a function of pH; it is rapidly degraded in acid media,

and is more stable under alkaline conditions. The structural figure is:

[structure]

Rabeprazole sodium hydrate, USP is available for oral administration as delayed-release, enteric-

coated tablets containing 20 mg of rabeprazole sodium hydrate, USP.

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