PANTOPRAZOLE SODIUM- pantoprazole sodium tablet, delayed release

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

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Active ingredient:
PANTOPRAZOLE SODIUM (UNII: 6871619Q5X) (PANTOPRAZOLE - UNII:D8TST4O562)
Available from:
NuCare Pharmaceuticals,Inc.
INN (International Name):
PANTOPRAZOLE SODIUM
Composition:
PANTOPRAZOLE 40 mg
Administration route:
ORAL
Prescription type:
PRESCRIPTION DRUG
Therapeutic indications:
Pantoprazole sodium delayed-release tablets are indicated for: Pantoprazole sodium delayed-release tablets are indicated in adults and pediatric patients five years of age and older for the short-term treatment (up to 8 weeks) in the healing and symptomatic relief of erosive esophagitis. For those adult patients who have not healed after 8 weeks of treatment, an additional 8-week course of pantoprazole sodium delayed-release tablets may be considered. Safety of treatment beyond 8 weeks in pediatric patients has not been established. Pantoprazole sodium delayed-release tablets are indicated for maintenance of healing of erosive esophagitis and reduction in relapse rates of daytime and nighttime heartburn symptoms in adult patients with GERD. Controlled studies did not extend beyond 12 months.   Pantoprazole sodium delayed-release tablets are indicated for the long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison syndrome. Pantoprazole sodium is contraindicated in patients w
Product summary:
Pantoprazole sodium delayed-release tablets, USP are supplied as 40 mg white to pale yellow colored, oval shape, biconvex, enteric-coated tablets, plain on one side and 97 printed with brown ink on the other side. They are available as follows: NDC 68071-1571-9 Bottles of 90 strong>Storage 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].
Authorization status:
Abbreviated New Drug Application
Authorization number:
68071-1571-9

NuCare Pharmaceuticals,Inc.

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MEDICATION GUIDE

Pantoprazole sodium (pan TOE pra zole SO-dee-um) delayed-release tablets, USP

Read this Medication Guide before you start taking pantoprazole sodium delayed-release tablets and each

time you get a refill. There may be new information. This information does not take the place of talking

with your doctor about your medical condition or your treatment.

What is the most important information I should know about pantoprazole sodium delayed-release

tablets?

Pantoprazole sodium delayed-release tablets may help your acid-related symptoms, but you could still

have seriousstomach problems. Talk with your doctor.

Pantoprazole 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 pantoprazole sodium delayed-release tablets, may develop a kidney problem called

acute interstitial nephritis that can happen at any time during treatment with Pantoprazole sodium

delayed-release tablets. Call your doctor if you have a decrease in the amount that you urinate or if you

have blood in your urine.

Diarrhea. Pantoprazole sodium delayed-release tablets may increase your risk of getting severe diarrhea.

This diarrhea may be caused by an infection ( Clostridiumdifficile) in your intestines.

Call your doctor right away if you have watery stool, stomach pain, and fever that does not go away.

Bone fractures. People who take multiple daily doses of PPI medicines for a long period of time (a year

or longer) may have an increased risk of fractures of the hip, wrist or spine. You should take pantoprazole

sodium delayed-release tablets exactly as prescribed, at the lowest dose possible for your treatment and

for the shortest time needed. Talk to your doctor about your risk of bone fracture if you take pantoprazole

sodium delayed-release tablets.

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

pantoprazole 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.

Pantoprazole sodium delayed-release tablets can have other serious side effects. See "What are the

possible side effects ofpantoprazole sodium delayed-release tablets?"

What are pantoprazole sodium delayed-release tablets?

Pantoprazole sodium delayed-release tablets are a prescription medicine called a proton pump inhibitor

(PPI).

Pantoprazole sodium delayed-release tablets reduce the amount of acid in your stomach.

Pantoprazole sodium delayed-release tablets are used in adults:

for up to 8 weeks to heal acid-related damage to the lining of the esophagus (erosive esophagitis or EE)

and to relieve symptoms caused by gastroesophageal reflux disease (GERD). If needed, your doctor may

decide to prescribe another 8 weeks of pantoprazole sodium delayed-release tablets.

to maintain the healing of acid-related damage to the lining of the esophagus and help prevent return of

heartburn symptoms caused by GERD. It is not known if pantoprazole sodium delayed-release tablets are

safe and effective if used longer than 12 months (1 year).

GERD happens when acid in your stomach backs up into the tube (esophagus) that connects your mouth

to your stomach. This may cause a burning feeling in your chest or throat, sour taste, or burping.

for the long-term treatment of conditions where your stomach makes too much acid. This includes a rare

condition called Zollinger-Ellison syndrome.

Pantoprazole sodium delayed-release tablets are used in children 5 years of age and older for up to 8

weeks to heal acid-related damage to the lining of the esophagus (erosive esophagitis or EE) caused by

GERD.

It is not known if pantoprazole sodium delayed-release tablets are safe if used longer than 8 weeks in

children. Pantoprazole sodium delayed-release tablets are not for use in children under 5 years of age.

Whoshouldnottakepantoprazolesodiumdelayed-releasetablets?

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

allergic to pantoprazole sodium or any of the other ingredients in pantoprazole sodium delayed-

release tablets. See the end of this Medication Guide for a complete list of ingredients in

pantoprazole sodium delayed-release tablets.

allergic to any proton pump inhibitor (PPI) medicine.

WhatshouldItellmydoctorbeforetakingpantoprazolesodiumdelayed-releasetablets?

Beforetakingpantoprazolesodiumdelayed-releasetablets, tellyourdoctorifyou:

have been told that you have low magnesium levels in your blood

have liver problems

have any other medical conditions

are pregnant or plan to become pregnant. It is not known if pantoprazole sodium delayed-release

tablets will harm your unborn baby.

are breastfeeding or plan to breastfeed. Pantoprazole may pass into your milk. You and your

doctor should decide if you will take pantoprazole sodium delayed-release tablets or breastfeed.

You should not do both. Talk with your doctor about the best way to feed your baby if you take

pantoprazole sodium delayed-release tablets.

> Tell your doctor about all of the medicines you take, including prescription and non-prescription drugs,

vitamins and herbal supplements. Pantoprazole sodium delayed-release tablets may affect how other

medicines work, and other medicines may affect how pantoprazole sodium delayed-release tablets work.

Especially tell your doctor if you take:

atazanavir (Reyataz)

nelfinavir (Viracept)

warfarin (Coumadin, Jantoven)

ketoconazole (Nizoral)

a product that contains iron

an antibiotic that contains ampicillin

methotrexate

mycophenolate mofetil (Cellcept)

Ask your doctor or pharmacist for a list of these medicines, if you are not sure.

Know the medicines that you take. Keep a list of them to show your doctor and pharmacist when you get

a new medicine.

HowshouldItakepantoprazolesodiumdelayed-releasetablets?

Take pantoprazole sodium delayed-release tablets exactly as prescribed by your doctor.

Do not change your dose or stop pantoprazole sodium delayed-release tablets without talking to

your doctor.

If you forget to take a dose of pantoprazole sodium delayed-release tablets, take it as soon as you

remember. If it is almost time for your next dose, do not take the missed dose. Take the next dose

at your regular time. Do not take two doses to try to make up for a missed dose.

If you take too much pantoprazole sodium delayed-release tablets, call your doctor right away or

go to the nearest hospital emergency room.

See the Instructions for Use at the end of this Medication Guide for detailed instructions about:

how to take pantoprazole sodium delayed-release tablets

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

Pantoprazole sodium delayed-release tablets may cause serious side effects, including:

See "What is the most important information I should know about pantoprazole sodium delayed-release

tablets?"

Vitamin B-12 deficiency. Pantoprazole sodium delayed-release tablets reduce the amount of acid in

your stomach. Stomach acid is needed to absorb vitamin B-12 properly. Talk with your doctor about the

possibility of vitamin B-12 deficiency if you have been on pantoprazole sodium delayed-release tablets

for a long time (more than 3 years).

Low magnesium levels in your body. This problem can be serious. Low magnesium can happen in some

people who take a PPI medicine for at least 3 months. If low magnesium levels happen, it is usually after

a year of treatment. You may or may not have symptoms of low magnesium.

Tell your doctor right away if you have any of these symptoms:

seizures

dizziness

abnormal or fast heartbeat

jitteriness

jerking movements or shaking (tremors)

muscle weakness

spasms of the hands and feet

cramps or muscle aches

spasm of the voice box

Your doctor may check the level of magnesium in your body before you start taking pantoprazole sodium

delayed-release tablets or during treatment; if you will be taking pantoprazole sodium delayed-release

tablets for a long period of time.

The most common side effects with pantoprazole sodium delayed-release tablets in adults include:

width="100%"> Headache Vomiting Diarrhea Gas Nausea Dizziness Stomach pain Pain in

your joints

The most common side effects with pantoprazole sodium delayed-release tablets in children include:

width="100%"> Upper respiratory infection Vomiting Headache Rash Fever Stomach pain

Diarrhea Other side effects:

Serious allergic reactions . Tell your doctor if you get any of the following symptoms with

pantoprazole sodium delayed-release tablets:

rash

face swelling

throat tightness

difficult breathing

Your doctor may stop pantoprazole sodium delayed-release tablets if these symptoms happen.

Tell your doctor about any side effects that bother you or that do not go away.

These are not all the possible side effects with pantoprazole sodium delayed-release tablets. For more

information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-

FDA-1088.

HowshouldIstorepantoprazolesodiumdelayed-releasetablets?

Store pantoprazole sodium delayed-release tablets 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 pantoprazole sodium delayed-release tablets and all medicines out of the reach of children.

GeneralInformationabout pantoprazole sodium delayed-release tablets

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not

use pantoprazole sodium delayed-release tablets for a condition for which it was not prescribed. Do not

give pantoprazole sodium delayed-release tablets to other people, even if they have the same symptoms

you have. It may harm them.

This Medication Guide summarizes the most important information about pantoprazole sodium delayed-

release tablets. For more information, ask your doctor. You can ask your doctor or pharmacist for

information that is written for healthcare professionals.

For more information, call 1-269-544-2299.

Whataretheingredientsinpantoprazolesodiumdelayed-releasetablets?

Activeingredient: pantoprazole sodium (sesquihydrate), USP

Inactiveingredientsinpantoprazolesodiumdelayed-releasetablets: calcium stearate, crospovidone,

hydroxypropyl cellulose, hypromellose, mannitol, methacrylic acid copolymer dispersion, propylene

glycol, sodium carbonate, talc, titanium dioxide, and triethyl citrate.

Instructions for Use

Pantoprazole sodium Delayed-Release Tablets:

You can take pantoprazole sodium delayed-release tablets with food or on an empty stomach.

Swallow pantoprazole sodium delayed-release tablets whole.

If you have trouble swallowing a pantoprazole sodium delayed-release 40 mg tablet, you can take

two 20 mg tablets instead.

Do not split, chew, or crush pantoprazole sodium delayed-release tablets.

Trademarks are the property of their respective owners.

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

This product's label may have been updated. For current full prescribing information, please visit

www.torrentpharma.com.

Manufactured by:

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

For:

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

8063066 Revised February 2017

Revised: 4/2019

Document Id: 86570209-c7a6-80e0-e053-2a91aa0a240b

34391-3

Set id: 55f2d95f-b922-3765-e054-00144ff88e88

Version: 2

Effective Time: 20190412

NuCare Pharmaceuticals,Inc.

PANTOPRAZOLE SODIUM- pantoprazole sodium tablet, delayed release

NuCare Pharmaceuticals,Inc.

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HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use PANTOPRAZOLE SODIUM delayed-release

tablets safely and effectively. See full prescribing information for PANTOPRAZOLE SODIUM delayed-release

tablets.

PANTOPRAZOLE SODIUM delayed-release tablets, for oral use

Initial U.S. approval: 2000

RECENT MAJOR CHANGES

Warnings and Precautions, Atrophic Gastritis removed (5.2) 10/2016

Warnings and Precautions, Cutaneous and Systemic Lupus

Erythematosus (5.5) 10/2016

INDICATIONS AND USAGE

Pantoprazole is a proton pump inhibitor indicated for the following:

Short-Term Treatment of Erosive Esophagitis Associated with Gastroesophageal Reflux Disease (GERD) ( 1.1)

Maintenance of Healing of Erosive Esophagitis ( 1.2)

Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome ( 1.3)

DOSAGE AND ADMINISTRATION

Indication

Dose

Frequency

Short-Term Treatment of Erosive Esophagitis Associated With GERD (2.1)

Adults

40 mg

Once Daily for up to 8 wks

Children (5 years and older)

≥ 15 kg to < 40 kg

20 mg

Once Daily for up to 8 wks

≥ 40 kg

40 mg

Maintenance of Healing of Erosive Esophagitis (2.1)

Adults

40 mg

Once Daily*

Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome (2.1)

Adults

40 mg

Twice Daily

Controlled studies did not extend beyond 12 months (2)

See full prescribing information for administration instructions (2)

DOSAGE FORMS AND STRENGTHS

Delayed-Release Tablets, 20 mg and 40 mg ( 3)

CONTRAINDICATIONS

Known hypersensitivity to any component of the formulation or to substituted benzimidazoles ( 4)

WARNINGS AND PRECAUTIONS

In adults, symptomatic response does not preclude presence of gastric malignancy. Consider additional follow-up and

diagnostic testing. (5.1)

Acute interstitial nephritis has been observed in patients taking PPIs. (5.2)

PPI therapy may be associated with increased risk of Clostridium difficile- associated diarrhea. (5.3)

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. (5.4)

Cutaneous and Systemic Lupus Erythematosus: Mostly cutaneous; new onset or exacerbation of existing disease;

discontinue pantoprazole and refer to specialist for evaluation (5.5)

Cyanocobalamin (vitamin B-12) Deficiency: Daily long-term use (e.g., longer than 3 years) may lead to malabsorption or

a deficiency of cyanocobalamin. (5.6)

Hypomagnesemia has been reported rarely with prolonged treatment with PPIs (5.7)

ADVERSE REACTIONS

The most frequently occurring adverse reactions are as follows: (6)

For adult use (>2%) are headache, diarrhea, nausea, abdominal pain, vomiting, flatulence, dizziness, and arthralgia. (6)

For pediatric use (>4%) are URI, headache, fever, diarrhea, vomiting, rash, and abdominal pain. (6)

To report SUSPECTED ADVERSE REACTIONS, contact Torrent Pharma Inc at 1-269-544-2299 or FDA at 1-

800-FDA-1088 or www.fda.gov/medwatch. (6)

DRUG INTERACTIONS

Do not co-administer with atazanavir or nelfinavir ( 7.1)

Concomitant warfarin use may require monitoring ( 7.2)

May interfere with the absorption of drugs where gastric pH is important for bioavailability (e.g. ketoconazole, ampicillin

esters, atazanavir, iron salts, erlotinib and mycophenolate mofetil) ( 7.4)

May produce false-positive urine screen for THC (7.5)

Methotrexate: Pantoprazole may increase serum level of methotrexate (7.6)

See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.

Revised: 2/2017

FULL PRESCRIBING INFORMATION: CONTENTS*

1 INDICATIONS AND USAGE

1.1 Short-Term Treatment of Erosive Esophagitis Associated With Gastroesophageal Reflux

Disease (GERD)

1.2 Maintenance of Healing of Erosive Esophagitis

1.3 Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Dosing Schedule

2.2 Administration Instructions

3 DOSAGE FORMS AND STRENGTHS

4 CONTRAINDICATIONS

5 WARNINGS AND PRECAUTIONS

5.1 Presence of Gastric Malignancy

5.2 Acute Interstitial Nephritis

5.3 Clostridium difficile-Associated Diarrhea

5.4 Bone Fracture

5.5 Cutaneous and Systemic Lupus Erythematosus

5.6 Cyanocobalamin (Vitamin B-12) Deficiency

5.7 Hypomagnesemia

5.8 Tumorigenicity

5.9 Interference with Urine Screen for THC

5.10 Concomitant Use of Pantoprazole with Methotrexate

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

6.2 Postmarketing Experience

7 DRUG INTERACTIONS

7.1 Interference with Antiretroviral Therapy

7.2 Coumarin Anticoagulants

7.3 Clopidogrel

7.4 Drugs for Which Gastric pH Can Affect Bioavailability

7.5 False Positive Urine Tests for THC

7.6 Methotrexate

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

8.3 Nursing Mothers

8.4 Pediatric Use

8.5 Geriatric Use

8.6 Gender

8.7 Patients with Hepatic Impairment

10 OVERDOSAGE

11 DESCRIPTION

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

12.2 Pharmacodynamics

12.3 Pharmacokinetics

12.4 Pharmacogenomics

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

13.2 Animal Toxicology and/or Pharmacology

14 CLINICAL STUDIES

14.1 Erosive Esophagitis (EE) Associated with Gastroesophageal Reflux Disease (GERD)

14.2 Long-Term Maintenance of Healing of Erosive Esophagitis

14.3 Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome

16 HOW SUPPLIED/STORAGE AND HANDLING

17 PATIENT COUNSELING INFORMATION

FULL PRESCRIBING INFORMATION

1 INDICATIONS AND USAGE

Pantoprazole sodium delayed-release tablets are indicated for:

1.1 Short-Term Treatment of Erosive Esophagitis Associated With Gastroesophageal Reflux

Disease (GERD)

Pantoprazole sodium delayed-release tablets are indicated in adults and pediatric patients five years of

age and older for the short-term treatment (up to 8 weeks) in the healing and symptomatic relief of

erosive esophagitis. For those adult patients who have not healed after 8 weeks of treatment, an

additional 8-week course of pantoprazole sodium delayed-release tablets may be considered. Safety of

treatment beyond 8 weeks in pediatric patients has not been established.

1.2 Maintenance of Healing of Erosive Esophagitis

Pantoprazole sodium delayed-release tablets are indicated for maintenance of healing of erosive

esophagitis and reduction in relapse rates of daytime and nighttime heartburn symptoms in adult patients

with GERD. Controlled studies did not extend beyond 12 months.

1.3 Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome

Pantoprazole sodium delayed-release tablets are indicated for the long-term treatment of pathological

hypersecretory conditions, including Zollinger-Ellison syndrome.

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Dosing Schedule

Sections or subsections omitted from the full prescribing information are not listed.

Pantoprazole sodium is supplied as delayed-release tablets. The recommended dosages are outlined in

Table 1.

Table 1: Recommended Dosing Schedule for Pantoprazole Sodium Delayed-Release Tablets

For adult patients who have not healed after 8 weeks of treatment, an additional 8-week course of pantoprazole

sodium delayed-release tablets may be considered.

Dosage regimens should be adjusted to individual patient needs and should continue for as long as clinically

indicated. Doses up to 24 0 mg daily have been administered.

*** Controlled studies did not extend beyond 12 months

Indication

Dose

Frequency

Short-Term Treatment of Erosive Esophagitis Associated With GERD

Adults

40 mg

Once daily for up to 8 weeks*

Children (5 years and older)

≥ 15 kg to < 40 kg

≥ 40 kg

20 mg

40 mg

Once daily for up to 8 weeks

Maintenance of Healing of Erosive Esophagitis

Adults

40 mg

Once daily***

Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome

Adults

40 mg

Twice daily**

2.2 Administration Instructions

Directions for method of administration are presented in Table 2.

Table 2: Administration Instructions

Formulation

Route

Ins tructions

Delayed-Release Tablets

Oral

Swallowed whole, with or without food

Pantoprazole sodium delayed-release tablets

Pantoprazole sodium delayed-release tablets should be swallowed whole, with or without food in the

stomach. If patients are unable to swallow a 40 mg tablet, two 20 mg tablets may be taken. Concomitant

administration of antacids does not affect the absorption of pantoprazole sodium delayed-release tablets.

3 DOSAGE FORMS AND STRENGTHS

Delayed-Release Tablets:

20 mg, white to pale yellow colored, oval shape, biconvex, enteric-coated tablets, plain on one side

and "96" printed with brown ink on the other side.

40 mg, white to pale yellow colored, oval shape, biconvex, enteric-coated tablets, plain on one side

and "1097" printed with brown ink on the other side.

4 CONTRAINDICATIONS

Pantoprazole sodium is contraindicated in patients with known hypersensitivity to any component of the

formulation or any substituted benzimidazole. Hypersensitivity reactions may include anaphylaxis,

anaphylactic shock, angioedema, bronchospasm, acute interstitial nephritis, and urticaria [see Adverse

Reactions (6)].

Patients should be cautioned that pantoprazole sodium delayed-release tablets should not be split, chewed, or

crushed.

5 WARNINGS AND PRECAUTIONS

5.1 Presence of Gastric Malignancy

In adults, symptomatic response to therapy with pantoprazole 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. In older

patients, also consider an endoscopy.

5.2 Acute Interstitial Nephritis

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

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

hypersensitivity reaction. Discontinue pantoprazole if acute interstitial nephritis develops [see

Contraindications (4)].

5.3 Clostridium difficile-Associated Diarrhea

Published observational studies suggest that PPI therapy like pantoprazole 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.

5.4 Bone Fracture

Several published observational studies suggest that proton pump inhibitor (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) and

Adverse Reactions (6.2)].

5.5 Cutaneous and Systemic Lupus Erythematosus

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

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

exacerbation of existing autoimmune disease. The majority of PPI-induced lupus erythematous 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 pantoprazole, 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.

5.6 Cyanocobalamin (Vitamin B-12) Deficiency

Generally, 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.

5.7 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), health care professionals may consider

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

6.2)].

5.8 Tumorigenicity

Due to the chronic nature of GERD, there may be a potential for prolonged administration of

pantoprazole. In long-term rodent studies, pantoprazole was carcinogenic and caused rare types of

gastrointestinal tumors. The relevance of these findings to tumor development in humans is unknown

[see Nonclinical Toxicology (13.1) ].

5.9 Interference with Urine Screen for THC

See Drug Interactions (7.5).

5.10 Concomitant Use of Pantoprazole with Methotrexate

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

methotrexate prescribing information) may elevate and prolong serum levels 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 (7.6)].

6 ADVERSE REACTIONS

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

Acute Interstitial Nephritis [see Warnings and Precautions (5.2)]

Clostridium difficile- Associated Diarrhea [see Warnings and Precautions (5.3)]

Bone Fracture [see Warnings and Precautions (5.4)]

Cutaneous and Systemic Lupus Erythematosus [see Warnings and Precautions (5.5)]

Cyanocobalamin (Vitamin B-12) Deficiency [see Warnings and Precautions (5.6)]

Hypomagnesemia [see Warnings and Precautions (5.7)]

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely 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 clinical practice.

Adults

Safety in nine randomized comparative US clinical trials in patients with GERD included 1,473 patients

on oral pantoprazole (20 mg or 40 mg), 299 patients on an H

-receptor antagonist, 46 patients on

another proton pump inhibitor, and 82 patients on placebo. The most frequently occurring adverse

reactions are listed in Table 3.

Table 3: Adverse Reactions Reported in Clinical Trials of Adult Patients with GERD at a

Frequency of > 2%

Pantoprazole

Comparators

Placebo

(n=1473)

(n=345)

(n=82)

Headache

12.2

12.8

Diarrhea

Nausea

Abdominal pain

Vomiting

Flatulence

Dizziness

Arthralgia

Additional adverse reactions that were reported for pantoprazole in clinical trials with a frequency of ≤

2% are listed below by body system:

Body as a Whole: allergic reaction, pyrexia, photosensitivity reaction, facial edema

Gastrointestinal: constipation, dry mouth, hepatitis

Hematologic: leukopenia, thrombocytopenia

Metabolic/Nutritional: elevated CK (creatine kinase), generalized edema, elevated triglycerides, liver

enzymes elevated

Musculoskeletal: myalgia

Nervous: depression, vertigo

Skin and Appendages: urticaria, rash, pruritus

Special Senses: blurred vision

Pediatric Patients

Safety of pantoprazole in the treatment of Erosive Esophagitis (EE) associated with GERD was

evaluated in pediatric patients ages 1 year through 16 years in three clinical trials. Safety trials involved

pediatric patients with EE; however, as EE is uncommon in the pediatric population, 249 pediatric

patients with endoscopically-proven or symptomatic GERD were also evaluated. All adult adverse

reactions to pantoprazole are considered relevant to pediatric patients. In patients ages 1 year through

16 years, the most commonly reported (> 4%) adverse reactions include: URI, headache, fever,

diarrhea, vomiting, rash, and abdominal pain.

For safety information in patients less than 1 year of age see Use in Specific Populations (8.4).

Additional adverse reactions that were reported for pantoprazole in pediatric patients in clinical trials

with a frequency of ≤ 4% are listed below by body system:

Body as a Whole: allergic reaction, facial edema

Gastrointestinal: constipation, flatulence, nausea

Metabolic/Nutritional: elevated triglycerides, elevated liver enzymes, elevated CK (creatine kinase)

Musculoskeletal: arthralgia, myalgia

Nervous: dizziness, vertigo

Skin and Appendages: urticaria

The following adverse reactions seen in adults in clinical trials were not reported in pediatric patients

in clinical trials, but are considered relevant to pediatric patients: photosensitivity reaction, dry mouth,

hepatitis, thrombocytopenia, generalized edema, depression, pruritus, leukopenia, and blurred vision.

Zollinger-Ellison Syndrome

In clinical studies of Zollinger-Ellison Syndrome, adverse reactions reported in 35 patients taking

pantoprazole 80 mg/day to 240 mg/day for up to 2 years were similar to those reported in adult patients

with GERD.

6.2 Postmarketing Experience

The following adverse reactions have been identified during postapproval use of pantoprazole.

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.

These adverse reactions are listed below by body system:

General Disorders and Administration Conditions: asthenia, fatigue, malaise

Hematologic: pancytopenia, agranulocytosis

Hepatobiliary Disorders: hepatocellular damage leading to jaundice and hepatic failure

Immune System Disorders: anaphylaxis (including anaphylactic shock), systemic lupus erythematosus

Infections and Infestations: Clostridium difficile associated diarrhea

Investigations: weight changes

Metabolism and Nutritional Disorders: hyponatremia, hypomagnesemia

Musculoskeletal Disorders: rhabdomyolysis, bone fracture

Nervous: ageusia, dysgeusia

Psychiatric Disorders: hallucination, confusion, insomnia, somnolence

Renal and Urinary Disorders: interstitial nephritis

Skin and Subcutaneous Tissue Disorders: severe dermatologic reactions (some fatal), including

erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis (TEN, some fatal), and

angioedema (Quincke's edema) and cutaneous lupus erythematosus

7 DRUG INTERACTIONS

7.1 Interference with Antiretroviral Therapy

Concomitant use of atazanavir or nelfinavir with proton pump inhibitors is not recommended. Co-

administration of atazanavir or nelfinavir with proton pump inhibitors is expected to substantially

decrease atazanavir or nelfinavir plasma concentrations and may result in a loss of therapeutic effect and

development of drug resistance.

7.2 Coumarin Anticoagulants

There have been postmarketing reports of increased INR and prothrombin time in patients receiving

proton pump inhibitors, including pantoprazole, and warfarin concomitantly. Increases in INR and

prothrombin time may lead to abnormal bleeding and even death. Patients treated with proton pump

inhibitors and warfarin concomitantly should be monitored for increases in INR and prothrombin time.

7.3 Clopidogrel

Concomitant administration of pantoprazole and clopidogrel in healthy subjects had no clinically

important effect on exposure to the active metabolite of clopidogrel or clopidogrel-induced platelet

inhibition [see Clinical Pharmacology (12.3)]. No dose adjustment of clopidogrel is necessary when

administered with an approved dose of pantoprazole.

7.4 Drugs for Which Gastric pH Can Affect Bioavailability

Due to its effects on gastric acid secretion, pantoprazole can reduce the absorption of drugs where

gastric pH is an important determinant of their bioavailability. Like with other drugs that decrease the

intragastric acidity, the absorption of drugs such as ketoconazole, ampicillin esters, atazanavir, iron

salts, erlotinib, and mycophenolate mofetil (MMF) can decrease.

Co-administration of pantoprazole 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 pantoprazole and

MMF. Use pantoprazole with caution in transplant patients receiving MMF [ see Clinical Pharmacology

(12.3)].

7.5 False Positive Urine Tests for THC

There have been reports of false positive urine screening tests for tetrahydrocannabinol (THC) in

patients receiving proton pump inhibitors. An alternative confirmatory method should be considered to

verify positive results.

7.6 Methotrexate

Case reports, published population pharmacokinetic studies, and retrospective analyses suggest that

concomitant administration of PPIs and methotrexate (primarily at high dose; see methotrexate

prescribing information) may elevate and prolong serum levels of methotrexate and/or its metabolite

hydroxymethotrexate. However, no formal drug interaction studies of Methotrexate with PPIs have been

conducted [see Warnings and Precautions (5.10)].

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Teratogenic Effects

Pregnancy Category B

Reproduction studies have been performed in rats at oral doses up to 88 times the recommended human

dose and in rabbits at oral doses up to 16 times the recommended human dose and have revealed no

evidence of impaired fertility or harm to the fetus due to pantoprazole. There are, however, no adequate

and well-controlled studies in pregnant women. Because animal reproduction studies are not always

predictive of human response, this drug should be used during pregnancy only if clearly needed [see

Nonclinical Toxicology (13.2)].

8.3 Nursing Mothers

Pantoprazole and its metabolites are excreted in the milk of rats. Pantoprazole excretion in human milk

has been detected in a study of a single nursing mother after a single 40 mg oral dose. The clinical

relevance of this finding is not known. Many drugs which are excreted in human milk have a potential

for serious adverse reactions in nursing infants. Based on the potential for tumorigenicity shown for

pantoprazole in rodent carcinogenicity studies, a decision should be made whether to discontinue

nursing or to discontinue the drug, taking into account the benefit of the drug to the mother.

8.4 Pediatric Use

The safety and effectiveness of pantoprazole for short-term treatment (up to eight weeks) of erosive

esophagitis (EE) associated with GERD have been established in pediatric patients 1 year through 16

years of age. Effectiveness for EE has not been demonstrated in patients less than 1 year of age. In

addition, for patients less than 5 years of age, there is no appropriate dosage strength in an age-

appropriate formulation available. Therefore, pantoprazole is indicated for the short-term treatment of

EE associated with GERD for patients 5 years and older. The safety and effectiveness of pantoprazole

for pediatric uses other than EE have not been established.

1 year through 16 years of age

Use of pantoprazole in pediatric patients 1 year through 16 years of age for short-term treatment (up to

eight weeks) of EE associated with GERD is supported by: a) extrapolation of results from adequate

and well-controlled studies that supported the approval of pantoprazole for treatment of EE associated

with GERD in adults, and b) safety, effectiveness, and pharmacokinetic studies performed in pediatric

patients [see Clinical Studies (14.1), and Clinical Pharmacology (12.3)].

Safety of pantoprazole in the treatment of EE associated with GERD in pediatric patients 1 through 16

years of age was evaluated in three multicenter, randomized, double-blind, parallel-treatment studies,

involving 249 pediatric patients, including 8 with EE (4 patients ages 1 year to 5 years and 4 patients 5

years to 11 years). The children ages 1 year to 5 years with endoscopically diagnosed EE (defined as an

endoscopic Hetzel-Dent score ≥ 2) were treated once daily for 8 weeks with one of two dose levels of

pantoprazole (approximating 0.6 mg/kg or 1.2 mg/kg). All 4 of these patients with EE were healed

(Hetzel-Dent score of 0 or 1) at 8 weeks. Because EE is uncommon in the pediatric population,

predominantly pediatric patients with endoscopically-proven or symptomatic GERD were also included

in these studies. Patients were treated with a range of doses of pantoprazole once daily for 8 weeks.

For safety findings see Adverse Reactions (6.1). Because these pediatric trials had no placebo, active

comparator, or evidence of a dose response, the trials were inconclusive regarding the clinical benefit

of pantoprazole for symptomatic GERD in the pediatric population. The effectiveness of pantoprazole

sodium delayed-release tablets for treating symptomatic GERD in pediatric patients has not been

established.

Although the data from the clinical trials support use of pantoprazole for the short-term treatment of EE

associated with GERD in pediatric patients 1 year through 5 years, there is no commercially available

dosage formulation appropriate for patients less than 5 years of age [see Dosage and Administration

(2)].

In a population pharmacokinetic analysis, clearance values in the children 1 to 5 years old with

endoscopically proven GERD had a median value of 2.4 L/h. Following a 1.2 mg/kg equivalent dose (15

mg for ≤ 12.5 kg and 20 mg for > 12.5 to < 25 kg), the plasma concentrations of pantoprazole were

highly variable and the median time to peak plasma concentration was 3 to 6 hours. The estimated AUC

for patients 1 to 5 years old was 37% higher than for adults receiving a single 40 mg tablet, with a

geometric mean AUC value of 6.8 µghr/mL.

Neonates to less than one year of age

Pantoprazole was not found to be effective in a multicenter, randomized, double-blind, placebo-

controlled, treatment-withdrawal study of 129 pediatric patients 1 through 11 months of age. Patients

were enrolled if they had symptomatic GERD based on medical history and had not responded to non-

pharmacologic interventions for GERD for two weeks. Patients received pantoprazole daily for four

weeks in an open-label phase, then patients were randomized in equal proportion to receive

pantoprazole treatment or placebo for the subsequent four weeks in a double-blind manner. Efficacy was

assessed by observing the time from randomization to study discontinuation due to symptom worsening

during the four-week treatment-withdrawal phase. There was no statistically significant difference

between pantoprazole and placebo in the rate of discontinuation.

In this trial, the adverse reactions that were reported more commonly (difference of ≥ 4%) in the treated

population compared to the placebo population were elevated CK, otitis media, rhinitis, and laryngitis.

In a population pharmacokinetic analysis, the systemic exposure was higher in patients less than 1 year

of age with GERD compared to adults who received a single 40 mg dose (geometric mean AUC was

103% higher in preterm infants and neonates receiving single dose of 2.5 mg of pantoprazole, and 23%

higher in infants 1 through 11 months of age receiving a single dose of approximately 1.2 mg/kg). In

these patients, the apparent clearance (CL/F) increased with age (median clearance: 0.6 L/hr, range: 0.03

to 3.2 L/hr).

These doses resulted in pharmacodynamic effects on gastric but not esophageal pH. Following once

daily dosing of 2.5 mg of pantoprazole in preterm infants and neonates, there was an increase in the mean

gastric pH (from 4.3 at baseline to 5.2 at steady-state) and in the mean % time that gastric pH was > 4

(from 60% at baseline to 80% at steady-state). Following once daily dosing of approximately 1.2 mg/kg

of pantoprazole in infants 1 through 11 months of age, there was an increase in the mean gastric pH

(from 3.1 at baseline to 4.2 at steady-state) and in the mean % time that gastric pH was > 4 (from 32% at

baseline to 60% at steady-state). However, no significant changes were observed in mean

intraesophageal pH or % time that esophageal pH was < 4 in either age group.

Because pantoprazole was not shown to be effective in the randomized, placebo-controlled study in this

age group, the use of pantoprazole for treatment of symptomatic GERD in infants less than 1 year of age

is not indicated.

8.5 Geriatric Use

In short-term US clinical trials, erosive esophagitis healing rates in the 107 elderly patients (≥ 65 years

old) treated with pantoprazole were similar to those found in patients under the age of 65. The incidence

rates of adverse reactions and laboratory abnormalities in patients aged 65 years and older were similar

to those associated with patients younger than 65 years of age.

8.6 Gender

Erosive esophagitis healing rates in the 221 women treated with pantoprazole sodium delayed-release

tablets in US clinical trials were similar to those found in men. In the 122 women treated long-term with

pantoprazole 40 mg or 20 mg, healing was maintained at a rate similar to that in men. The incidence rates

of adverse reactions were also similar for men and women.

8.7 Patients with Hepatic Impairment

Doses higher than 40 mg/day have not been studied in patients with hepatic impairment [see Clinical

Pharmacology (12.3)].

10 OVERDOSAGE

Experience in patients taking very high doses of pantoprazole (> 240 mg) is limited. Spontaneous post-

marketing reports of overdose are generally within the known safety profile of pantoprazole.

Pantoprazole is not removed by hemodialysis. In case of overdosage, treatment should be symptomatic

and supportive.

Single oral doses of pantoprazole at 709 mg/kg, 798 mg/kg, and 887 mg/kg were lethal to mice, rats, and

dogs, respectively. The symptoms of acute toxicity were hypoactivity, ataxia, hunched sitting, limb-

splay, lateral position, segregation, absence of ear reflex, and tremor.

11 DESCRIPTION

The active ingredient in pantoprazole sodium delayed-release tablets, USP is a substituted

benzimidazole, sodium 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridinyl) methyl] sulfinyl]- 1H-

benzimidazole sesquihydrate, a compound that inhibits gastric acid secretion. Its empirical formula is C

S x 1.5 H

O, with a molecular weight of 432.4. The structural formula is:

Pantoprazole sodium (sesquihydrate), USP is a white to off-white crystalline powder and is racemic.

Pantoprazole has weakly basic and acidic properties. Pantoprazole sodium (sesquihydrate), USP is

freely soluble in water, very slightly soluble in phosphate buffer at pH 7.4, and practically insoluble in

n-hexane.

The stability of the compound in aqueous solution is pH-dependent. The rate of degradation increases

with decreasing pH. At ambient temperature, the degradation half-life is approximately 2.8 hours at pH

5 and approximately 220 hours at pH 7.8.

Pantoprazole sodium is supplied as a delayed-release tablet, available in two strengths (20 mg and 40

mg).

Each pantoprazole sodium delayed-release tablet, USP contains 45.1 mg or 22.55 mg of pantoprazole

sodium (sesquihydrate), USP (equivalent to 40 mg or 20 mg pantoprazole, respectively) with the

following inactive ingredients: calcium stearate, crospovidone, hydroxypropyl cellulose,

hypromellose, mannitol, methacrylic acid copolymer dispersion, propylene glycol, sodium carbonate,

talc, titanium dioxide, and triethyl citrate. Pantoprazole sodium delayed-release tablets, USP, 20 mg and

40 mg meet USP dissolution test 3.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Pantoprazole is a proton pump inhibitor (PPI) that suppresses the final step in gastric acid production by

covalently binding to the (H

)-ATPase enzyme system at the secretory surface of the gastric

parietal cell. This effect leads to inhibition of both basal and stimulated gastric acid secretion,

irrespective of the stimulus. The binding to the (H

)-ATPase results in a duration of antisecretory

effect that persists longer than 24 hours for all doses tested (20 mg to 120 mg).

12.2 Pharmacodynamics

Antisecretory Activity

Under maximal acid stimulatory conditions using pentagastrin, a dose-dependent decrease in gastric acid

output occurs after a single dose of oral (20 to 80 mg) or a single dose of intravenous (20 to 120 mg)

pantoprazole in healthy volunteers. Pantoprazole given once daily results in increasing inhibition of

gastric acid secretion. Following the initial oral dose of 40 mg pantoprazole, a 51% mean inhibition

was achieved by 2.5 hours. With once-a-day dosing for 7 days, the mean inhibition was increased to

85%. Pantoprazole suppressed acid secretion in excess of 95% in half of the subjects. Acid secretion

had returned to normal within a week after the last dose of pantoprazole; there was no evidence of

rebound hypersecretion.

In a series of dose-response studies, pantoprazole, at oral doses ranging from 20 to 120 mg, caused

dose-related increases in median basal gastric pH and in the percent of time gastric pH was > 3 and > 4.

Treatment with 40 mg of pantoprazole produced significantly greater increases in gastric pH than the 20

mg dose. Doses higher than 40 mg (60, 80, 120 mg) did not result in further significant increases in

median gastric pH. The effects of pantoprazole on median pH from one double-blind crossover study

are shown in Table 4.

Table 4: Effect of Single Daily Doses of Oral Pantoprazole on Intragastric pH

Significantly different from placebo

Significantly different from 20 mg

––––––––––––––––––––––––––Median pH on day 7––––––––––––––––––––––––––––

Time

Placebo

20 mg

40 mg

80 mg

8 a.m. - 8 a.m.

(24 hours)

8 a.m. - 10 p.m.

(Daytime)

10 p.m. - 8 a.m.

(Nighttime)

Serum Gastrin Effects

Fasting serum gastrin levels were assessed in two double-blind studies of the acute healing of erosive

esophagitis (EE) in which 682 patients with gastroesophageal reflux disease (GERD) received 10, 20,

or 40 mg of pantoprazole for up to 8 weeks. At 4 weeks of treatment there was an increase in mean

gastrin levels of 7%, 35%, and 72% over pretreatment values in the 10, 20, and 40 mg treatment groups,

respectively. A similar increase in serum gastrin levels was noted at the 8-week visit with mean

increases of 3%, 26%, and 84% for the three pantoprazole dose groups. Median serum gastrin levels

remained within normal limits during maintenance therapy with pantoprazole sodium delayed-release

tablets.

In long-term international studies involving over 800 patients, a 2- to 3-fold mean increase from the

pretreatment fasting serum gastrin level was observed in the initial months of treatment with

pantoprazole at doses of 40 mg per day during GERD maintenance studies and 40 mg or higher per day

in patients with refractory GERD. Fasting serum gastrin levels generally remained at approximately 2 to

3 times baseline for up to 4 years of periodic follow-up in clinical trials.

Following short-term treatment with pantoprazole, elevated gastrin levels return to normal by at least 3

months.

Enterochromaffin-Like (ECL) Cell Effects

In 39 patients treated with oral pantoprazole 40 mg to 240 mg daily (majority receiving 40 mg to 80 mg)

for up to 5 years, there was a moderate increase in ECL-cell density, starting after the first year of use,

which appeared to plateau after 4 years.

In a nonclinical study in Sprague-Dawley rats, lifetime exposure (24 months) to pantoprazole at doses of

0.5 to 200 mg/kg/day resulted in dose-related increases in gastric ECL cell proliferation and gastric

neuroendocrine (NE)-cell tumors. Gastric NE-cell tumors in rats may result from chronic elevation of

serum gastrin concentrations. The high density of ECL cells in the rat stomach makes this species

highly susceptible to the proliferative effects of elevated gastrin concentrations produced by proton

pump inhibitors. However, there were no observed elevations in serum gastrin following the

administration of pantoprazole at a dose of 0.5 mg/kg/day. In a separate study, a gastric NE-cell tumor

without concomitant ECL-cell proliferative changes was observed in 1 female rat following 12 months

of dosing with pantoprazole at 5 mg/kg/day and a 9 month off-dose recovery [see Nonclinical Toxicology

(13.1)].

12.3 Pharmacokinetics

Pantoprazole sodium delayed-release tablets are prepared as enteric-coated tablets so that absorption of

pantoprazole begins only after the tablet leaves the stomach. Peak serum concentration (C

) and area

under the serum concentration time curve (AUC) increase in a manner proportional to oral and

intravenous doses from 10 mg to 80 mg. Pantoprazole does not accumulate, and its pharmacokinetics are

unaltered with multiple daily dosing. Following oral or intravenous administration, the serum

concentration of pantoprazole declines biexponentially, with a terminal elimination half-life of

approximately one hour.

In extensive metabolizers with normal liver function receiving an oral dose of the enteric-coated 40 mg

pantoprazole tablet, the peak concentration (C

) is 2.5 µg/mL; the time to reach the peak concentration

) is 2.5 h, and the mean total area under the plasma concentration versus time curve (AUC) is 4.8

µgh/mL (range 1.4 to 13.3 µgh/mL). Following intravenous administration of pantoprazole to extensive

metabolizers, its total clearance is 7.6 to 14.0 L/h, and its apparent volume of distribution is 11.0 to 23.6

Abs orption

After administration of a single or multiple oral 40 mg doses of pantoprazole sodium delayed-release

tablets, the peak plasma concentration of pantoprazole was achieved in approximately 2.5 hours, and C

was 2.5 µg/mL. Pantoprazole undergoes little first-pass metabolism, resulting in an absolute

bioavailability of approximately 77%. Pantoprazole absorption is not affected by concomitant

administration of antacids.

Administration of pantoprazole sodium delayed-release tablets with food may delay its absorption up to

2 hours or longer; however, the C

and the extent of pantoprazole absorption (AUC) are not altered.

Thus, pantoprazole sodium delayed-release tablets may be taken without regard to timing of meals.

Dis tribution

The apparent volume of distribution of pantoprazole is approximately 11.0 to 23.6 L, distributing mainly

in extracellular fluid. The serum protein binding of pantoprazole is about 98%, primarily to albumin.

Metabolis m

Pantoprazole is extensively metabolized in the liver through the cytochrome P450 (CYP) system.

Pantoprazole metabolism is independent of the route of administration (intravenous or oral). The main

metabolic pathway is demethylation, by CYP2C19, with subsequent sulfation; other metabolic pathways

include oxidation by CYP3A4. There is no evidence that any of the pantoprazole metabolites have

significant pharmacologic activity.

Elimination

After a single oral or intravenous dose of

C-labeled pantoprazole to healthy, normal metabolizer

volunteers, approximately 71% of the dose was excreted in the urine, with 18% excreted in the feces

through biliary excretion. There was no renal excretion of unchanged pantoprazole.

Geriatric

Only slight to moderate increases in pantoprazole AUC (43%) and C

(26%) were found in elderly

volunteers (64 to 76 years of age) after repeated oral administration, compared with younger subjects.

No dosage adjustment is recommended based on age.

Pediatric

The pharmacokinetics of pantoprazole were studied in children less than 16 years of age in four

randomized, open-label clinical trials in pediatric patients with presumed/proven GERD. Pantoprazole

sodium delayed-release tablets were studied in children older than 5 years.

In a population PK analysis, total clearance increased with increasing bodyweight in a non-linear

fashion. The total clearance also increased with increasing age only in children under 3 years of age.

Neonate through 5 years of age

See Use in Specific Populations (8.4).

Children and Adolescents 6 through 16 Years of Age

The pharmacokinetics of pantoprazole sodium delayed-release tablets were evaluated in children ages

6 through 16 years with a clinical diagnosis of GERD. The PK parameters following a single oral dose

of 20 mg or 40 mg of pantoprazole sodium delayed-release tablets in children ages 6 through 16 years

were highly variable (%CV ranges 40 to 80%). The geometric mean AUC estimated from population

PK analysis after a 40 mg pantoprazole sodium delayed-release tablet in pediatric patients was about

39% and 10% higher respectively in 6 to 11 and 12 to 16 year-old children, compared to that of adults

(Table 6).

Table 6: PK Parameters in Children and Adolescents 6 through 16 years with GERD receiving 40

mg pantoprazole sodium delayed-release tablets

6 to 11 years (n=12)

12 to 16 years (n=11)

(µg/mL)

AUC (µghr/mL)

CL/F (L/h)

Geometric mean values

Median values

Gender

There is a modest increase in pantoprazole AUC and C

in women compared to men. However,

weight-normalized clearance values are similar in women and men. No dosage adjustment is

recommended based on gender. In pediatric patients ages 1 through 16 years there were no clinically

relevant effects of gender on clearance of pantoprazole, as shown by population pharmacokinetic

analysis.

Renal Impairment

In patients with severe renal impairment, pharmacokinetic parameters for pantoprazole were similar to

those of healthy subjects. No dosage adjustment is necessary in patients with renal impairment or in

patients undergoing hemodialysis.

Hepatic Impairment

In patients with mild to severe hepatic impairment (Child-Pugh A to C cirrhosis), maximum pantoprazole

concentrations increased only slightly (1.5-fold) relative to healthy subjects. Although serum half-life

values increased to 7 to 9 hours and AUC values increased by 5- to 7-fold in hepatic-impaired patients,

these increases were no greater than those observed in CYP2C19 poor metabolizers, where no dosage

adjustment is warranted. These pharmacokinetic changes in hepatic-impaired patients result in minimal

drug accumulation following once-daily, multiple-dose administration. No dosage adjustment is needed

in patients with mild to severe hepatic impairment. Doses higher than 40 mg/day have not been studied in

hepatically impaired patients.

Drug-Drug Interactions

Pantoprazole is metabolized mainly by CYP2C19 and to minor extents by CYPs 3A4, 2D6, and 2C9. In in

vivo drug-drug interaction studies with CYP2C19 substrates (diazepam [also a CYP3A4 substrate] and

phenytoin [also a CYP3A4 inducer] and clopidogrel), nifedipine, midazolam, and clarithromycin

(CYP3A4 substrates), metoprolol (a CYP2D6 substrate), diclofenac, naproxen and piroxicam (CYP2C9

substrates), and theophylline (a CYP1A2 substrate) in healthy subjects, the pharmacokinetics of

pantoprazole were not significantly altered.

Clopidogrel: Clopidogrel is metabolized to its active metabolite in part by CYP2C19. In a crossover

clinical study, 66 healthy subjects were administered clopidogrel (300 mg loading dose followed

by 75 mg per day) alone and with pantoprazole (80 mg at the same time as clopidogrel) for 5 days.

On Day 5, the mean AUC of the active metabolite of clopidogrel was reduced by approximately 14%

(geometric mean ratio was 86%, with 90% CI of 79 to 93%) when pantoprazole was coadministered

with clopidogrel as compared to clopidogrel administered alone. Pharmacodynamic parameters were

also measured and demonstrated that the change in inhibition of platelet aggregation (induced by 5 μM

ADP) was correlated with the change in the exposure to clopidogrel active metabolite. The clinical

significance of this finding is not clear.

Mycophenolate Mofetil (MMF): Administration of pantoprazole 40 mg twice daily for 4 days and a

single 1000 mg dose of MMF approximately one hour after the last dose of pantoprazole to 12 healthy

subjects in a cross-over study resulted in a 57% reduction in the C

and 27% reduction in the AUC

of MPA. Transplant patients receiving approximately 2000 mg per day of MMF (n=12) were compared

to transplant patients receiving approximately the same dose of MMF and pantoprazole 40 mg per day

(n=21). There was a 78% reduction in the C

and a 45% reduction in the AUC of MPA in patients

receiving both pantoprazole and MMF.

In vivo studies also suggest that pantoprazole does not significantly affect the kinetics of the following

drugs (cisapride, theophylline, diazepam [and its active metabolite, desmethyldiazepam], phenytoin,

warfarin, metoprolol, nifedipine, carbamazepine, midazolam, clarithromycin, naproxen, piroxicam, and

oral contraceptives [levonorgestrel/ethinyl estradiol]). Dosage adjustment of these drugs is not

necessary when they are coadministered with pantoprazole. In other in vivo studies, digoxin, ethanol,

glyburide, antipyrine, caffeine, metronidazole, and amoxicillin had no clinically relevant interactions

with pantoprazole.

Based on studies evaluating possible interactions of pantoprazole with other drugs, no dosage

adjustment is needed with concomitant use of the following: theophylline, cisapride, antipyrine,

caffeine, carbamazepine, diazepam (and its active metabolite, desmethyldiazepam), diclofenac, naproxen,

piroxicam, digoxin, ethanol, glyburide, an oral contraceptive (levonorgestrel/ethinyl estradiol),

metoprolol, nifedipine, phenytoin, warfarin, midazolam, clarithromycin, metronidazole, or amoxicillin.

There was also no interaction with concomitantly administered antacids.

There have been postmarketing reports of increased INR and prothrombin time in patients receiving

proton pump inhibitors, including pantoprazole, and warfarin concomitantly [see Drug Interactions (7.2)].

Although no significant drug-drug interactions have been observed in clinical studies, the potential for

significant drug-drug interactions with more than once-daily dosing with high doses of pantoprazole

has not been studied in poor metabolizers or individuals who are hepatically impaired.

Other Effects

In a clinical pharmacology study, pantoprazole 40 mg given once daily for 2 weeks had no effect on the

levels of the following hormones: cortisol, testosterone, triiodothyronine (T

), thyroxine (T

thyroid-stimulating hormone (TSH), thyronine-binding protein, parathyroid hormone, insulin, glucagon,

renin, aldosterone, follicle-stimulating hormone, luteinizing hormone, prolactin, and growth hormone.

In a 1-year study of GERD patients treated with pantoprazole 40 mg or 20 mg, there were no changes

from baseline in overall levels of T

, and TSH.

12.4 Pharmacogenomics

CYP2C19 displays a known genetic polymorphism due to its deficiency in some subpopulations (e.g.,

approximately 3% of Caucasians and African-Americans and 17% to 23% of Asians are poor

metabolizers). Although these subpopulations of pantoprazole poor metabolizers have elimination half-

life values of 3.5 to 10.0 hours in adults, they still have minimal accumulation (≤ 23%) with once-daily

dosing. For adult patients who are CYP2C19 poor metabolizers, no dosage adjustment is needed.

Similar to adults, pediatric patients who have the poor metabolizer genotype of CYP2C19 (CYP2C19

*2/*2) exhibited greater than a 6-fold increase in AUC compared to pediatric extensive (CYP2C19

*1/*1) and intermediate (CYP2C19 *1/*x) metabolizers. Poor metabolizers exhibited approximately 10-

fold lower apparent oral clearance compared to extensive metabolizers.

For known pediatric poor metabolizers, a dose reduction should be considered.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

In a 24-month carcinogenicity study, Sprague-Dawley rats were treated orally with doses of 0.5 to 200

mg/kg/day, about 0.1 to 40 times the exposure on a body surface area basis of a 50 kg person dosed at

40 mg/day. In the gastric fundus, treatment at 0.5 to 200 mg/kg/day produced enterochromaffin-like

(ECL) cell hyperplasia and benign and malignant neuroendocrine cell tumors in a dose-related manner. In

the forestomach, treatment at 50 and 200 mg/kg/day (about 10 and 40 times the recommended human dose

on a body surface area basis) produced benign squamous cell papillomas and malignant squamous cell

carcinomas. Rare gastrointestinal tumors associated with pantoprazole treatment included an

adenocarcinoma of the duodenum at 50 mg/kg/day and benign polyps and adenocarcinomas of the gastric

fundus at 200 mg/kg/day. In the liver, treatment at 0.5 to 200 mg/kg/day produced dose-related increases

in the incidences of hepatocellular adenomas and carcinomas. In the thyroid gland, treatment at 200

mg/kg/day produced increased incidences of follicular cell adenomas and carcinomas for both male and

female rats.

In a 24-month carcinogenicity study, Fischer 344 rats were treated orally with doses of 5 to 50

mg/kg/day, approximately 1 to 10 times the recommended human dose based on body surface area. In the

gastric fundus, treatment at 5 to 50 mg/kg/day produced enterochromaffin-like (ECL) cell hyperplasia

and benign and malignant neuroendocrine cell tumors. Dose selection for this study may not have been

adequate to comprehensively evaluate the carcinogenic potential of pantoprazole.

In a 24-month carcinogenicity study, B6C3F1 mice were treated orally with doses of 5 to 150

mg/kg/day, 0.5 to 15 times the recommended human dose based on body surface area. In the liver,

treatment at 150 mg/kg/day produced increased incidences of hepatocellular adenomas and carcinomas

in female mice. Treatment at 5 to 150 mg/kg/day also produced gastric-fundic ECL cell hyperplasia.

A 26-week p53 +/- transgenic mouse carcinogenicity study was not positive.

Pantoprazole was positive in the in vitro human lymphocyte chromosomal aberration assays, in one of

two mouse micronucleus tests for clastogenic effects, and in the in vitro Chinese hamster ovarian

cell/HGPRT forward mutation assay for mutagenic effects. Equivocal results were observed in the in

vivo rat liver DNA covalent binding assay. Pantoprazole was negative in the in vitro Ames mutation

assay, the in vitro unscheduled DNA synthesis (UDS) assay with rat hepatocytes, the in vitro AS52/GPT

mammalian cell-forward gene mutation assay, the in vitro thymidine kinase mutation test with mouse

lymphoma L5178Y cells, and the in vivo rat bone marrow cell chromosomal aberration assay.

There were no effects on fertility or reproductive performance when pantoprazole was given at oral

doses up to 500 mg/kg/day in male rats (98 times the recommended human dose based on body surface

area) and 450 mg/kg/day in female rats (88 times the recommended human dose based on body surface

area).

13.2 Animal Toxicology and/or Pharmacology

Studies in neonatal/juvenile and adult rats and dogs were performed. The data from these studies

revealed that animals in both age groups respond to pantoprazole in a similar manner. Gastric alterations,

including increased stomach weights, increased incidence of eosinophilic chief cells in adult and

neonatal/juvenile rats, and atrophy of chief cells in adult rats and in neonatal/juvenile dogs, were

observed in the fundic mucosa of stomachs in repeated-dose studies. Decreases in red cell mass

parameters, increases in cholesterol and triglycerides, increased liver weight, enzyme induction, and

hepatocellular hypertrophy were also seen in repeated-dose studies in rats and/or dogs. Full to partial

recovery of these effects were noted in animals of both age groups following a recovery period.

Reproductive Toxicology Studies

Reproduction studies have been performed in rats at oral doses up to 450 mg/kg/day (88 times the

recommended human dose based on body surface area) and rabbits at oral doses up to 40 mg/kg/day (16

times the recommended human dose based on body surface area) and have revealed no evidence of

impaired fertility or harm to the fetus due to pantoprazole.

14 CLINICAL STUDIES

Pantoprazole sodium delayed-release tablets were used in the following clinical trials.

14.1 Erosive Esophagitis (EE) Associated with Gastroesophageal Reflux Disease (GERD)

Adult Patients

A US multicenter, double-blind, placebo-controlled study of pantoprazole 10 mg, 20 mg, or 40 mg once

daily was conducted in 603 patients with reflux symptoms and endoscopically diagnosed EE of grade 2

or above (Hetzel-Dent scale). In this study, approximately 25% of enrolled patients had severe EE of

grade 3, and 10% had grade 4. The percentages of patients healed (per protocol, n = 541) in this study

are shown in Table 7.

Table 7: Erosive Esophagitis Healing Rates (Per Protocol)

(p < 0.001) pantoprazole versus placebo

(p < 0.05) versus 10 mg or 20 mg pantoprazole

(p < 0.05) versus 10 mg pantoprazole

––––––––––––––– Pantoprazole –––––––––––––––

Placebo

Week

10 mg daily

(n = 153)

20 mg daily

(n = 158)

40 mg daily

(n = 162)

(n = 68)

45.6%

66.0%

58.4%

83.5 %

75.0%

92.6%

14.3%

39.7%

In this study, all pantoprazole treatment groups had significantly greater healing rates than the placebo

group. This was true regardless of H. pylori status for the 40 mg and 20 mg pantoprazole treatment

groups. The 40 mg dose of pantoprazole resulted in healing rates significantly greater than those found

with either the 20 mg or 10 mg dose.

A significantly greater proportion of patients taking pantoprazole 40 mg experienced complete relief of

daytime and nighttime heartburn and the absence of regurgitation, starting from the first day of treatment,

compared with placebo. Patients taking pantoprazole consumed significantly fewer antacid tablets per

day than those taking placebo.

Pantoprazole 40 mg and 20 mg once daily were also compared with nizatidine 150 mg twice daily in a

US multicenter, double-blind study of 243 patients with reflux symptoms and endoscopically diagnosed

EE of grade 2 or above. The percentages of patients healed (per protocol, n = 212) are shown in Table

Table 8: Erosive Esophagitis Healing Rates (Per Protocol)

(p < 0.001) pantoprazole versus nizatidine

–––––––––––– Pantoprazole ––––––––––––

Nizatidine

Week

20 mg daily

(n = 72)

40 mg daily

(n = 70)

150 mg twice daily

(n = 70)

61.4%

79.2%

64.0%

82.9%

22.2%

41.4%

Once-daily treatment with pantoprazole 40 mg or 20 mg resulted in significantly superior rates of

healing at both 4 and 8 weeks compared with twice-daily treatment with 150 mg of nizatidine. For the 40

mg treatment group, significantly greater healing rates compared to nizatidine were achieved regardless

of the H. pylori status.

A significantly greater proportion of the patients in the pantoprazole treatment groups experienced

complete relief of nighttime heartburn and regurgitation, starting on the first day and of daytime

heartburn on the second day, compared with those taking nizatidine 150 mg twice daily. Patients taking

pantoprazole consumed significantly fewer antacid tablets per day than those taking nizatidine.

Pediatric Patients Ages 5 Years through 16 Years

The efficacy of pantoprazole in the treatment of EE associated with GERD in pediatric patients ages 5

years through 16 years is extrapolated from adequate and well-conducted trials in adults, as the

pathophysiology is thought to be the same. Four pediatric patients with endoscopically diagnosed EE

were studied in multicenter, randomized, double-blind, parallel-treatment trials. Children with

endoscopically diagnosed EE (defined as an endoscopic Hetzel-Dent score ≥ 2) were treated once daily

for 8 weeks with one of two dose levels of pantoprazole (20 mg or 40 mg). All 4 patients with EE were

healed (Hetzel-Dent score of 0 or 1) at 8 weeks.

14.2 Long-Term Maintenance of Healing of Erosive Esophagitis

Two independent, multicenter, randomized, double-blind, comparator-controlled trials of identical

design were conducted in adult GERD patients with endoscopically confirmed healed erosive

esophagitis to demonstrate efficacy of pantoprazole in long-term maintenance of healing. The two US

studies enrolled 386 and 404 patients, respectively, to receive either 10 mg, 20 mg, or 40 mg of

pantoprazole sodium delayed-release tablets once daily or 150 mg of ranitidine twice daily. As

demonstrated in Table 9, pantoprazole 40 mg and 20 mg were significantly superior to ranitidine at

every timepoint with respect to the maintenance of healing. In addition, pantoprazole 40 mg was

superior to all other treatments studied.

Table 9: Long-Term Maintenance of Healing of Erosive Gastroesophageal Reflux Disease

(GERD Maintenance): Percentage of Patients Who Remained Healed

Pantoprazole

20 mg daily

Pantoprazole

40 mg daily

Ranitidine

150 mg twice daily

Study 1

n = 75

n = 74

n = 75

Month 1

Month 3

Month 6

Month 12

Study 2

n = 74

n = 88

n = 84

Month 1

Month 3

(p < 0.05 vs. ranitidine)

(p < 0.05 vs. pantoprazole 20 mg)

Note: pantoprazole 10 mg was superior (p < 0.05) to ranitidine in Study 2, but not Study 1.

Month 6

Month 12

Pantoprazole 40 mg was superior to ranitidine in reducing the number of daytime and nighttime

heartburn episodes from the first through the twelfth month of treatment. Pantoprazole 20 mg,

administered once daily, was also effective in reducing episodes of daytime and nighttime heartburn in

one trial, as presented in Table 10.

Table 10: Number of Episodes of Heartburn (mean ± SD)

Pantoprazole

40 mg daily

Ranitidine

150 mg twice daily

Month 1

Daytime

Nighttime

5.1 ± 1.6

3.9 ± 1.1

18.3 ± 1.6

11.9 ± 1.1

Month 12

Daytime

Nighttime

2.9 ± 1.5

2.5 ± 1.2

17.5 ± 1.5

13.8 ± 1.3

14.3 Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome

In a multicenter, open-label trial of 35 patients with pathological hypersecretory conditions, such as

Zollinger-Ellison syndrome, with or without multiple endocrine neoplasia-type I, pantoprazole

successfully controlled gastric acid secretion. Doses ranging from 80 mg daily to 240 mg daily

maintained gastric acid output below 10 mEq/h in patients without prior acid-reducing surgery and

below 5 mEq/h in patients with prior acid-reducing surgery.

Doses were initially titrated to the individual patient needs, and adjusted in some patients based on the

clinical response with time [see Dosage and Administration (2)]. Pantoprazole was well tolerated at

these dose levels for prolonged periods (greater than 2 years in some patients).

16 HOW SUPPLIED/STORAGE AND HANDLING

Pantoprazole sodium delayed-release tablets, USP are supplied as 40 mg white to pale yellow colored,

oval shape, biconvex, enteric-coated tablets, plain on one side and 97 printed with brown ink on the

other side.

They are available as follows:

NDC 68071-1571-9 Bottles of 90

strong>Storage

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].

17 PATIENT COUNSELING INFORMATION

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

Adverse Reactions

Hypersensitivity Reactions [see Contraindications (4)]

Acute Interstitial Nephritis [see Warnings and Precautions (5.2)]

Clostridium difficile -Associated Diarrhea [see Warnings and Precautions (5.3)]

(p < 0.001 vs. ranitidine, combined data from the two US studies)

Bone Fracture [see Warnings and Precautions (5.4)]

Cutaneous and Systemic Lupus Erythematosus [see Warnings and Precautions (5.5)]

Cyanocobalamin (Vitamin B-12) Deficiency [see Warnings and Precautions (5.6)]

Hypomagnesemia [see Warnings and Precautions (5.7)]

Drug Interactions

Instruct patients to inform their healthcare provider of any other medications they are currently taking,

including over-the-counter medications.

Administration

Caution patients that pantoprazole sodium delayed-release tablets should not be split, crushed, or

chewed.

Tell patients that pantoprazole sodium delayed-release tablets should be swallowed whole, with or

without food in the stomach.

Let patients know that concomitant administration of antacids does not affect the absorption of

pantoprazole sodium delayed-release tablets.

This product's label may have been updated. For current full prescribing information, please visit

www.torrentpharma.com

Manufactured by:

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

For:

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

8063043 Revised February 2017

MEDICATION GUIDE

Pantoprazole sodium (pan TOE pra zole SO-dee-um) delayed-release tablets, USP

Read this Medication Guide before you start taking pantoprazole sodium delayed-release tablets and

each time you get a refill. There may be new information. This information does not take the place of

talking with your doctor about your medical condition or your treatment.

What is the most important information I should know about pantoprazole sodium delayed-

release tablets?

Pantoprazole sodium delayed-release tablets may help your acid-related symptoms, but you

could still have seriousstomach problems. Talk with your doctor.

Pantoprazole 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 pantoprazole sodium delayed-release tablets, may develop a kidney problem

called acute interstitial nephritis that can happen at any time during treatment with Pantoprazole sodium

delayed-release tablets. Call your doctor if you have a decrease in the amount that you urinate or if you

have blood in your urine.

Diarrhea. Pantoprazole sodium delayed-release tablets may increase your risk of getting severe

diarrhea. This diarrhea may be caused by an infection ( Clostridiumdifficile) in your intestines.

Call your doctor right away if you have watery stool, stomach pain, and fever that does not go away.

Bone fractures. People who take multiple daily doses of PPI medicines for a long period of time (a

year or longer) may have an increased risk of fractures of the hip, wrist or spine. You should take

pantoprazole sodium delayed-release tablets exactly as prescribed, at the lowest dose possible for your

treatment and for the shortest time needed. Talk to your doctor about your risk of bone fracture if you

take pantoprazole sodium delayed-release tablets.

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

pantoprazole 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.

Pantoprazole sodium delayed-release tablets can have other serious side effects. See "What are the

possible side effects ofpantoprazole sodium delayed-release tablets?"

What are pantoprazole sodium delayed-release tablets?

Pantoprazole sodium delayed-release tablets are a prescription medicine called a proton pump inhibitor

(PPI).

Pantoprazole sodium delayed-release tablets reduce the amount of acid in your stomach.

Pantoprazole sodium delayed-release tablets are used in adults:

for up to 8 weeks to heal acid-related damage to the lining of the esophagus (erosive esophagitis or

EE) and to relieve symptoms caused by gastroesophageal reflux disease (GERD). If needed, your

doctor may decide to prescribe another 8 weeks of pantoprazole sodium delayed-release tablets.

to maintain the healing of acid-related damage to the lining of the esophagus and help prevent return of

heartburn symptoms caused by GERD. It is not known if pantoprazole sodium delayed-release tablets

are safe and effective if used longer than 12 months (1 year).

GERD happens when acid in your stomach backs up into the tube (esophagus) that connects your mouth

to your stomach. This may cause a burning feeling in your chest or throat, sour taste, or burping.

for the long-term treatment of conditions where your stomach makes too much acid. This includes a

rare condition called Zollinger-Ellison syndrome.

Pantoprazole sodium delayed-release tablets are used in children 5 years of age and older for up to 8

weeks to heal acid-related damage to the lining of the esophagus (erosive esophagitis or EE) caused by

GERD.

It is not known if pantoprazole sodium delayed-release tablets are safe if used longer than 8 weeks in

children. Pantoprazole sodium delayed-release tablets are not for use in children under 5 years of age.

Whos houldnottakepantoprazoles odiumdelayed-releas etablets ?

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

allergic to pantoprazole sodium or any of the other ingredients in pantoprazole sodium delayed-

release tablets. See the end of this Medication Guide for a complete list of ingredients in

pantoprazole sodium delayed-release tablets.

allergic to any proton pump inhibitor (PPI) medicine.

Whats houldItellmydoctorbeforetakingpantoprazoles odiumdelayed-releas etablets ?

Beforetakingpantoprazolesodiumdelayed-releasetablets, tellyourdoctorifyou:

have been told that you have low magnesium levels in your blood

have liver problems

have any other medical conditions

are pregnant or plan to become pregnant. It is not known if pantoprazole sodium delayed-release

tablets will harm your unborn baby.

are breastfeeding or plan to breastfeed. Pantoprazole may pass into your milk. You and your doctor

should decide if you will take pantoprazole sodium delayed-release tablets or breastfeed. You

should not do both. Talk with your doctor about the best way to feed your baby if you take

pantoprazole sodium delayed-release tablets.

> Tell your doctor about all of the medicines you take, including prescription and non-prescription

drugs, vitamins and herbal supplements. Pantoprazole sodium delayed-release tablets may affect how

other medicines work, and other medicines may affect how pantoprazole sodium delayed-release tablets

work.

Especially tell your doctor if you take:

atazanavir (Reyataz)

nelfinavir (Viracept)

warfarin (Coumadin, Jantoven)

ketoconazole (Nizoral)

a product that contains iron

an antibiotic that contains ampicillin

methotrexate

mycophenolate mofetil (Cellcept)

Ask your doctor or pharmacist for a list of these medicines, if you are not sure.

Know the medicines that you take. Keep a list of them to show your doctor and pharmacist when you get

a new medicine.

Hows houldItakepantoprazoles odiumdelayed-releas etablets ?

Take pantoprazole sodium delayed-release tablets exactly as prescribed by your doctor.

Do not change your dose or stop pantoprazole sodium delayed-release tablets without talking to

your doctor.

If you forget to take a dose of pantoprazole sodium delayed-release tablets, take it as soon as you

remember. If it is almost time for your next dose, do not take the missed dose. Take the next dose at

your regular time. Do not take two doses to try to make up for a missed dose.

If you take too much pantoprazole sodium delayed-release tablets, call your doctor right away or go

to the nearest hospital emergency room.

See the Instructions for Use at the end of this Medication Guide for detailed instructions about:

how to take pantoprazole sodium delayed-release tablets

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

Pantoprazole sodium delayed-release tablets may cause serious side effects, including:

See "What is the most important information I should know about pantoprazole sodium delayed-

release tablets?"

Vitamin B-12 deficiency. Pantoprazole sodium delayed-release tablets reduce the amount of acid in

your stomach. Stomach acid is needed to absorb vitamin B-12 properly. Talk with your doctor about the

possibility of vitamin B-12 deficiency if you have been on pantoprazole sodium delayed-release tablets

for a long time (more than 3 years).

Low magnesium levels in your body. This problem can be serious. Low magnesium can happen in

some people who take a PPI medicine for at least 3 months. If low magnesium levels happen, it is

usually after a year of treatment. You may or may not have symptoms of low magnesium.

Tell your doctor right away if you have any of these symptoms:

seizures

dizziness

abnormal or fast heartbeat

jitteriness

jerking movements or shaking (tremors)

muscle weakness

spasms of the hands and feet

cramps or muscle aches

spasm of the voice box

Your doctor may check the level of magnesium in your body before you start taking pantoprazole

sodium delayed-release tablets or during treatment; if you will be taking pantoprazole sodium delayed-

release tablets for a long period of time.

The most common side effects with pantoprazole sodium delayed-release tablets in adults include:

width="100%"> Headache Vomiting Diarrhea Gas Nausea Dizziness Stomach pain Pain in

your joints

The most common side effects with pantoprazole sodium delayed-release tablets in children include:

width="100%"> Upper respiratory infection Vomiting Headache Rash Fever Stomach pain

Diarrhea Other side effects:

Serious allergic reactions . Tell your doctor if you get any of the following symptoms with

pantoprazole sodium delayed-release tablets:

rash

face swelling

throat tightness

difficult breathing

Your doctor may stop pantoprazole sodium delayed-release tablets if these symptoms happen.

Tell your doctor about any side effects that bother you or that do not go away.

These are not all the possible side effects with pantoprazole sodium delayed-release tablets. For more

information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-

FDA-1088.

Hows houldIs torepantoprazoles odiumdelayed-releas etablets ?

Store pantoprazole sodium delayed-release tablets 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 pantoprazole sodium delayed-release tablets and all medicines out of the reach of children.

GeneralInformationabout pantoprazole sodium delayed-release tablets

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not

use pantoprazole sodium delayed-release tablets for a condition for which it was not prescribed. Do not

give pantoprazole sodium delayed-release tablets to other people, even if they have the same symptoms

you have. It may harm them.

This Medication Guide summarizes the most important information about pantoprazole sodium delayed-

This Medication Guide summarizes the most important information about pantoprazole sodium delayed-

release tablets. For more information, ask your doctor. You can ask your doctor or pharmacist for

information that is written for healthcare professionals.

For more information, call 1-269-544-2299.

Whataretheingredients inpantoprazoles odiumdelayed-releas etablets ?

Activeingredient: pantoprazole sodium (sesquihydrate), USP

Inactiveingredientsinpantoprazolesodiumdelayed-releasetablets: calcium stearate, crospovidone,

hydroxypropyl cellulose, hypromellose, mannitol, methacrylic acid copolymer dispersion, propylene

glycol, sodium carbonate, talc, titanium dioxide, and triethyl citrate.

Instructions for Use

Pantoprazole sodium Delayed-Release Tablets:

You can take pantoprazole sodium delayed-release tablets with food or on an empty stomach.

Swallow pantoprazole sodium delayed-release tablets whole.

If you have trouble swallowing a pantoprazole sodium delayed-release 40 mg tablet, you can take

two 20 mg tablets instead.

Do not split, chew, or crush pantoprazole sodium delayed-release tablets.

Trademarks are the property of their respective owners.

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

This product's label may have been updated. For current full prescribing information, please visit

www.torrentpharma.com.

Manufactured by:

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

For:

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

8063066 Revised February 2017

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

PANTOPRAZOLE SODIUM

pantoprazole sodium tablet, delayed release

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:6 8 0 71-1571(NDC:136 6 8 -429 )

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

PANTO PRAZO LE SO DIUM (UNII: 6 8 716 19 Q5X) (PANTOPRAZOLE - UNII:D8 TST4O56 2)

PANTOPRAZOLE

40 mg

Inactive Ingredients

Ingredient Name

Stre ng th

CALCIUM STEARATE (UNII: 776 XM70 47L)

CRO SPO VIDO NE (UNII: 6 8 40 19 6 0 MK)

HYDRO XYPRO PYL CELLULO SE ( 16 0 0 0 0 0 WAMW) (UNII: RFW2ET6 71P)

HYPRO MELLO SE 2 9 10 ( 3 MPA.S) (UNII: 0 VUT3PMY8 2)

MANNITO L (UNII: 3OWL53L36 A)

METHACRYLIC ACID - ETHYL ACRYLATE CO PO LYMER ( 1:1) TYPE A (UNII: NX76 LV5T8 J)

PRO PYLENE GLYCO L (UNII: 6 DC9 Q16 7V3)

SO DIUM CARBO NATE DECAHYDRATE (UNII: LS50 5BG22I)

TALC (UNII: 7SEV7J4R1U)

TITANIUM DIO XIDE (UNII: 15FIX9 V2JP)

TRIETHYL CITRATE (UNII: 8 Z9 6 QXD6 UM)

Product Characteristics

Color

white (white to pale yello w)

S core

no sco re

S hap e

OVAL (o val shaped, bico nvex)

S iz e

11mm

NuCare Pharmaceuticals,Inc.

Flavor

Imprint Code

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:6 8 0 71-1571-9

9 0 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 8 /0 4/20 17

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA0 9 0 0 74

0 1/20 /20 11

Labeler -

NuCare Pharmaceuticals,Inc. (010632300)

Establishment

Name

Ad d re s s

ID/FEI

Busine ss Ope rations

NuCare Pharmaceuticals,Inc.

0 10 6 3230 0

re la be l(6 8 0 71-1571)

Revised: 4/2019

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