PACKAGE LABEL.PRINCIPAL DISPLAY PANEL - Bottle

NDC 68788-7657
Rx only
Rabeprazole Sodium
** Delayed-release Tablets**
** 20 mg**
** PHARMACIST: Dispense the Medication Guide**
** provided separately to each patient.**
AUROBINDO

Repackaged By: Preferred Pharmaceuticals Inc.

5 WARNINGS AND PRECAUTIONS

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 Tubulointerstitial Nephritis

Acute tubulointerstitial nephritis (TIN) has been observed in patients taking PPIs and may occur at any point during PPI therapy. Patients may present with varying signs and symptoms from symptomatic hypersensitivity reactions, to non-specific symptoms of decreased renal function (e.g., malaise, nausea, anorexia). In reported case series, some patients were diagnosed on biopsy and in the absence of extra-renal manifestations (e.g., fever, rash or arthralgia).

Discontinue rabeprazole sodium delayed-release tablets and evaluate patients with suspected acute TIN [see Contraindication (4)].

5.4 Clostridium difficile-Associated Diarrhea

Published observational studies suggest that PPI therapy like rabeprazole sodium delayed-release tablets 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 Reactions (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 delayed-release tablets, 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 Severe Cutaneous Adverse Reactions

Severe cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) have been reported in association with the use of PPIs [see Adverse Reactions (6.2)]. Discontinue rabeprazole at first signs or symptoms of severe cutaneous adverse reactions or other signs of hypersensitivity and consider further evaluation.

5.7 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 delayed-release tablets, 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.

5.8 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.

5.9 Hypomagnesemia and Mineral Metabolism

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. Hypomagnesemia may lead to hypocalcemia and/or hypokalemia and may exacerbate underlying hypocalcemia in at-risk patients. 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), health care professionals may consider monitoring magnesium levels prior to initiation of PPI treatment and periodically [see Adverse Reactions (6.2)].

Consider monitoring magnesium and calcium levels prior to initiation of rabeprazole and periodically while on treatment in patients with a preexisting risk of hypocalcemia (e.g., hypoparathyroidism). Supplement with magnesium and/or calcium as necessary. If hypocalcemia is refractory to treatment, consider discontinuing the PPI.

5.10 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)].

5.11 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.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

In an 88/104-week carcinogenicity study in CD-1 mice, rabeprazole at oral doses up to 100 mg/kg/day did not produce any increased tumor occurrence. The highest tested dose produced a systemic exposure to rabeprazole (AUC) of 1.40 mcg•hr/mL which is 1.6 times the human exposure (plasma AUC0-∞ = 0.88 mcg•hr/mL) at the recommended dose for GERD (20 mg/day). In a 28-week carcinogenicity study in p53+/- transgenic mice, rabeprazole at oral doses of 20, 60, and 200 mg/kg/day did not cause an increase in the incidence rates of tumors but produced gastric mucosal hyperplasia at all doses. The systemic exposure to rabeprazole at 200 mg/kg/day is about 17 to 24 times the human exposure at the recommended dose for GERD. In a 104-week carcinogenicity study in Sprague-Dawley rats, males were treated with oral doses of 5, 15, 30 and 60 mg/kg/day and females with 5, 15, 30, 60, and 120 mg/kg/day. Rabeprazole produced gastric enterochromaffin-like (ECL) cell hyperplasia in male and female rats and ECL cell carcinoid tumors in female rats at all doses including the lowest tested dose. The lowest dose (5 mg/kg/day) produced a systemic exposure to rabeprazole (AUC) of about 0.1 mcg•hr/mL which is about 0.1 times the human exposure at the recommended dose for GERD. In male rats, no treatment related tumors were observed at doses up to 60 mg/kg/day producing a rabeprazole plasma exposure (AUC) of about 0.2 mcg•hr/mL (0.2 times the human exposure at the recommended dose for GERD).

Rabeprazole was positive in the Ames test, the Chinese hamster ovary cell (CHO/HGPRT) forward gene mutation test, and the mouse lymphoma cell (L5178Y/TK+/–) forward gene mutation test. Its demethylated-metabolite was also positive in the Ames test. Rabeprazole was negative in the in vitro Chinese hamster lung cell chromosome aberration test, the in vivo mouse micronucleus test, and the in vivo and ex vivo rat hepatocyte unscheduled DNA synthesis (UDS) tests.

Rabeprazole at intravenous doses up to 30 mg/kg/day (plasma AUC of 8.8 mcg•hr/mL, about 10 times the human exposure at the recommended dose for GERD) was found to have no effect on fertility and reproductive performance of male and female rats.

17 PATIENT COUNSELING INFORMATION

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

Acute Tubulointerstitial Nephritis

Advise the patient or caregiver to call the patient’s healthcare provider immediately if they experience signs and/or symptoms associated with -acute tubulointerstitial 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)].

Severe Cutaneous Adverse Reactions

Advise the patient or caregiver to discontinue rabeprazole sodium delayed- release tablets and report any signs and symptoms of a severe cutaneous adverse reaction or other sign of hypersensitivity to the healthcare provider [see Warnings and Precautions (5.6)].

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 and Mineral Metabolism

Advise the patient or caregiver to report any clinical symptoms that may be associated with hypomagnesemia, hypocalcemia, hypokalemia and hyponatremia 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 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.

**Dispense with Medication Guide available at: **www.aurobindousa.com/medication-guides

The brands listed are trademarks of their respective owners and are not trademarks of Aurobindo Pharma Limited.

Distributed by:
Aurobindo Pharma USA, Inc.
279 Princeton-Hightstown Road
East Windsor, NJ 08520

Manufactured by:
Aurobindo Pharma Limited
Hyderabad–500 032, India

Revised: 08/2023

** Dispense with Medication Guide available at: **www.aurobindousa.com/medication-guides

**A type of kidney problem (acute tubulointerstitial nephritis).**Some people who take proton pump inhibitor (PPI) medicines, including rabeprazole sodium delayed-release tablets, may develop a kidney problem called acute tubulointerstitial 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. 

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. 

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).

have low magnesium levels, low calcium levels and low potassium 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 passes into your breast milk. 

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, 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.

**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

menstrual bleeding that is heavier than normal

unusual bruising (bruises that happen without known cause or that grow in size)

pink or brown urine

red or black stools

nosebleeds

bleeding gums

bleeding from cuts take a long time to stop

coughing up blood

vomiting blood or vomit that looks like 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 the 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.

**Severe skin reactions.**rabeprazole sodium delayed-release tablets can cause rare but serious skin reactions that may affect any part of your body. These serious skin reactions may need to be treated in a hospital and may be life threatening:  

Skin rash which may have blistering, peeling or bleeding on any part of your skin (including your lips, eyes, mouth, nose, genitals, hands or feet). 

You may also have fever, chills, body aches, shortness of breath, or enlarged lymph nodes.

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

Revised: 08/2023

Repackaged By: Preferred Pharmaceuticals Inc.

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.

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.