PANTOPRAZOLE SODIUM tablet, delayed release

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PANTOPRAZOLE SODIUM (UNII: 6871619Q5X) (PANTOPRAZOLE - UNII:D8TST4O562)
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PANTOPRAZOLE SODIUM
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PANTOPRAZOLE 40 mg
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ORAL
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Pantoprazole Sodium Delayed-Release Tablets, USP are indicated for: Pantoprazole is 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 (EE). For those adult patients who have not healed after 8 weeks of treatment, an additional 8-week course of Pantoprazole may be considered. Safety of treatment beyond 8 weeks in pediatric patients has not been established. Pantoprazole is indicated for maintenance of healing of EE 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 is indicated for the long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison (ZE) Syndrome. - Pantoprazole is contraindicated in patients with known hypersensitivity to any component of the formulation or any substituted benzimidazole. Hypersensitivity reactions may includ
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Product: 63739-564 NDC: 63739-564-10 10 TABLET, DELAYED RELEASE in a BLISTER PACK / 10 in a BOX, UNIT-DOSE
Tình trạng ủy quyền:
Abbreviated New Drug Application
Số ủy quyền:
63739-564-10

PANTOPRAZOLE SODIUM- pantoprazole sodium tablet, delayed release

McKesson Corporation dba SKY Packaging

----------

MEDICATION GUIDE

Pantoprazole (pan-TOE-pruh-zole) Sodium Delayed-Release Tablets, USP

CIA77568N Rev. 05/2019

What is the most important information I should know about Pantoprazole?

You should take Pantoprazole exactly as prescribed, at the lowest dose possible and for the shortest time

needed.

Pantoprazole may help your acid-related symptoms, but you could still have serious stomach problems. Talk

with your doctor.

Pantoprazole 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, may develop a kidney problem called acute interstitial

nephritis that can happen at any time during treatment with Pantoprazole. 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 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 Pantoprazole, may develop certain types of lupus erythematosus or have worsening of the

lupus they already have. Call your doctor right away if you have new or worsening joint pain or a

rash on your cheeks or arms that gets worse in the sun.

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

Pantoprazole can have other serious side effects. See “What are the possible side effects of Pantoprazole?”

What is Pantoprazole?

A prescription medicine called a proton pump inhibitor (PPI) used to reduce the amount of acid in your

stomach.

In adults, Pantoprazole is used for:

up to 8 weeks for the healing and symptom relief of acid-related damage to the lining of the

esophagus (called erosive esophagitis or EE). Your doctor may prescribe another 8 weeks of

Pantoprazole in patients whose EE does not heal.

maintaining healing of EE and to help prevent the return of heartburn symptoms caused by GERD. It

is not known if Pantoprazole is safe and effective when used longer than 12 months for this purpose.

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

condition called Zollinger-Ellison Syndrome.

In children 5 years of age and older, Pantoprazole is used for:

up to 8 weeks for the healing and symptom relief of EE.

It is not known if Pantoprazole is safe if used longer than 8 weeks in children.

Pantoprazole is not for use in children under 5 years of age.

It is not known if Pantoprazole is safe and effective in children for treatement other than EE.

Do not take Pantoprazole if you are:

allergic to pantoprazole sodium, any other PPI medicine, or any of the ingredients in Pantoprazole.

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

taking a medicine that contains rilpivirine (EDURANT, COMPLERA, ODEFSEY, JULUCA) used

to treat HIV-1 (Human Immunodeficiency Virus).

Before taking Pantoprazole, tell your doctor about all of your medical conditions, including if you:

have low magnesium levels in your blood.

are pregnant or plan to become pregnant. Pantoprazole may harm your unborn baby. Tell your doctor

if you become pregnant or think you may be pregnant during treatment with Pantoprazole.

are breastfeeding or plan to breastfeed. Pantoprazole can pass into your breast milk. Talk with your

doctor about the best way to feed your baby if you take Pantoprazole.

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

vitamins and herbal supplements. Especially tell your doctor if you take methotrexate (Otrexup, Rasuvo,

Trexall, XATMEP), digoxin (LANOXIN), or a water pill (diuretic).

How should I take Pantoprazole?

Take Pantoprazole exactly as prescribed by your doctor.

Pantoprazole delayed-release tablets (Pantoprazole tablets):

Do not split, chew, or crush Pantoprazole tablets.

Swallow Pantoprazole tablets whole, with or without food.

Tell your doctor if you are not able to swallow your Pantoprazole tablet.

You may use antacids while taking Pantoprazole tablets.

If you miss a dose of Pantoprazole, take it as soon as possible. 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 2 doses at the same

time.

If you take too much Pantoprazole, call your doctor or your poison control center at 1-800-222-1222

right away or go to the nearest emergency room.

What are the possible side effects of Pantoprazole?

Pantoprazole can cause serious side effects, including:

See “What is the most important information I should know about Pantoprazole?”

Low vitamin B-12 levels in your body can happen in people who have taken Pantoprazole for a long

time (more than 3 years). Tell your doctor if you have symptoms of low vitamin B-12 levels,

including shortness of breath, lightheadedness, irregular heartbeat, muscle weakness, pale skin,

feeling tired, mood changes, and tingling or numbness in the arms and legs.

Low magnesium levels in your body can happen in people who have taken Pantoprazole for at least 3

months. Tell your doctor if you have symptoms of low magnesium levels, including seizures,

dizziness, irregular heartbeat, jitteriness, muscle aches or weakness, and spasms of hands, feet or

voice.

Stomach growths (fundic gland polyps). People who take PPI medicines for a long time have an

increased risk of developing a certain type of stomach growths called fundic gland polyps, especially

after taking PPI medicines for more than 1 year.

The most common side effects of Pantoprazole in adults include: headache, diarrhea, nausea, stomach-area

(abdominal) pain, vomiting, gas, dizziness, and joint pain.

The most common side effects of Pantoprazole in children include: upper respiratory infection, headache,

fever, diarrhea, vomiting, rash, and stomach-area (abdominal) pain.

These are not all the possible side effects of Pantoprazole. Call your doctor for medical advice about side

effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store Pantoprazole?

Store Pantoprazole at room temperature between 59° to 86°F (15° to 30°C).

Keep Pantoprazole and all medicines out of the reach of children.

General information about the safe and effective use of Pantoprazole.

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

Pantoprazole for a condition for which it was not prescribed. Do not give Pantoprazole to other people, even

if they have the same symptoms that you have. It may harm them. You can ask your doctor or pharmacist for

information about Pantoprazole that is written for health professionals.

What are the ingredients in Pantoprazole?

Active ingredient: pantoprazole sodium sesquihydrate

Inactive ingredients in Pantoprazole Sodium Delayed-Release Tablets: crospovidone, glyceryl dibehenate,

hypromellose, lactose monohydrate, methacrylic acid copolymer dispersion, talc, titanium dioxide, and

triethyl citrate. The 20 mg tablets also contains black iron oxide, isopropyl alcohol, and propylene glycol.

For more information, call 1-844-834-0530.

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

This product's label may have been updated. For more information, call 1-844-834-0530.

Distributed by:

Lannett Company, Inc.

Philadelphia, PA 19136

CIA77568N

Rev. 05/2019

All brand names are the trademarks of their respective owners.

Revised: 11/2020

Document Id: b4680d1b-1c5e-5040-e053-2a95a90a0e00

34391-3

Set id: a0141135-3f83-49ba-b50c-31f353bf42f4

Version: 13

Effective Time: 20201118

McKesson Corporation dba SKY Packaging

PANTOPRAZOLE SODIUM- pantoprazole sodium tablet, delayed release

McKesson Corporation dba SKY Packaging

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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, Fundic Gland Polyps ( 5.9)

06/2018

INDICATIONS AND USAGE

Pantoprazole is a proton pump inhibitor (PPI) 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 (ZE) Syndrome ( 1.3)

DOSAGE AND ADMINISTRATION

Indic atio n

Do se

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

See full prescribing information for administration instructions

DOSAGE FORMS AND STRENGTHS

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

CONTRAINDICATIONS

Patients with known hypersensitivity to any component of the formulation or to substituted benzimidazoles ( 4)

Patients receiving rilpivirine-containing products ( 4, 7)

WARNINGS AND PRECAUTIONS

Gastric Malignancy: In adults, symptomatic response does not preclude presence of gastric malignancy. Consider

additional follow-up and diagnostic testing. ( 5.1)

Acute Interstitial Nephritis: Observed in patients taking PPIs. ( 5.2)

Clostridium difficile-Associated Diarrhea: 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)

Controlled studies did not extend beyond 12 months

Hypomagnesemia: Reported rarely with prolonged treatment with PPIs. ( 5.7)

Fundic Gland Polyps: Risk increases with long-term use, especially beyond one year. Use the shortest duration of

therapy. ( 5.9)

ADVERSE REACTIONS

Most common adverse reactions are:

For adult use (>2%): headache, diarrhea, nausea, abdominal pain, vomiting, flatulence, dizziness, and arthralgia. ( 6.1)

For pediatric use (>4%): URI, headache, fever, diarrhea, vomiting, rash, and abdominal pain. ( 6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Lannett Company, Inc. at 1-844-834-0530 or FDA at 1-

800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS

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

USE IN SPECIFIC POPULATIONS

Pregnancy: Based on animal data, may cause fetal harm. ( 8.1)

See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.

Revised: 9/2019

FULL PRESCRIBING INFORMATION: CONTENTS*

RECENT MAJOR CHANGES

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 (ZE) 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 Fundic Gland Polyps

5.10 Interference with Investigations for Neuroendocrine Tumors

5.11 Interference with Urine Screen for THC

5.12 Concomitant Use of Pantoprazole with Methotrexate

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

6.2 Postmarketing Experience

7 DRUG INTERACTIONS

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

8.2 Lactation

8.4 Pediatric Use

8.5 Geriatric Use

10 OVERDOSAGE

11 DESCRIPTION

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

12.2 Pharmacodynamics

12.3 Pharmacokinetics

12.5 Pharmacogenomics

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

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, USP are indicated for:

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

Disease (GERD)

Pantoprazole is 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 (EE). For those

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

Pantoprazole 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 is indicated for maintenance of healing of EE 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 (ZE) Syndrome

Pantoprazole is indicated for the long-term treatment of pathological hypersecretory conditions,

including Zollinger-Ellison (ZE) Syndrome.

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Dosing Schedule

Pantoprazole is supplied as delayed-release tablets. The recommended dosages are outlined in Table 1.

Table 1: Recommended Dosing Schedule for Pantoprazole

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

Indication

Dos e

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

20 mg

Once daily for up to 8 weeks

≥ 40 kg

40 mg

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 for each dosage form are presented in Table 2.

Table 2: Administration Instructions

Formulation

Route

Instructions

Delayed-Release Tablets Oral

Swallowed whole, 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

take the next dose at the regular scheduled time. Do not take 2 doses at the same time.

Pantoprazole Sodium Delayed-Release Tablets

Swallow Pantoprazole Sodium Delayed-Release Tablets whole, with or without food in the stomach.

For patients 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

T ablets.

3 DOSAGE FORMS AND STRENGTHS

Delayed-Release Tablets:

40 mg, white oval biconvex tablets debossed with "17" on one side

20 mg, white oval biconvex tablets imprinted in black ink with "KU" on one side and "180" on the

other side

4 CONTRAINDICATIONS

Pantoprazole 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)].

Proton pump inhibitors (PPIs), including Pantoprazole, are contraindicated with rilpivirine-

containing products [see Drug Interactions ( 7)].

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

may be considered.

Controlled studies did not extend beyond 12 months

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.

*

Do not split, chew, or crush Pantoprazole Sodium Delayed-Release Tablets.

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 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)].

5.5 Cutaneous and Systemic Lupus Erythematosus

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

patients taking PPIs, including pantoprazole sodium. 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 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.

5.10 Interference with Investigations for Neuroendocrine Tumors

Serum chromogranin A (CgA) levels increase secondary to drug-induced decreases in gastric acidity.

The increased CgA level may cause false positive results in diagnostic investigations for

neuroendocrine tumors. Healthcare providers should temporarily stop Pantoprazole treatment at least 14

days before assessing CgA levels and consider repeating the test if initial CgA levels are high. If serial

tests are performed (e.g. for monitoring), the same commercial laboratory should be used for testing, as

reference ranges between tests may vary [see Clinical Pharmacology ( 12.2)] .

5.11 Interference with Urine Screen for THC

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

patients receiving PPIs, including Pantoprazole [see Drug Interactions ( 7)].

5.12 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 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)]

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)]

Fundic Gland Polyps [see Warnings and Precautions ( 5.9)]

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 PPI, 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

(n=1473)

Comparators

(n=345)

Placebo

(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 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 (ZE) Syndrome

In clinical studies of ZE 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:

Gastrointestinal Disorders: fundic gland polyps

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, toxic epidermal necrolysis (TEN, some fatal), angioedema

(Quincke’s edema) and cutaneous lupus erythematosus

7 DRUG INTERACTIONS

Table 4 includes drugs with clinically important drug interactions and interaction with diagnostics when

administered concomitantly with Pantoprazole and instructions for preventing or managing them.

Consult the labeling of concomitantly used drugs to obtain further information about interactions with

PPIs.

Table 4: Clinically Relevant Interactions Affecting Drugs Co-Administered with Pantoprazole and

Interactions with Diagnostics

Antiretrovirals

Clinical Impact:

The effect of PPIs on antiretroviral drugs is variable. The

clinical importance and the mechanisms behind these

interactions are not always known.

Decreased exposure of some antiretroviral drugs (e.g.,

rilpivirine atazanavir, and nelfinavir) when used

concomitantly with pantoprazole may reduce antiviral effect

and promote the development of drug resistance.

Increased exposure of other antiretroviral drugs (e.g.,

saquinavir) when used concomitantly with pantoprazole may

increase toxicity of the antiretroviral drugs.

There are other antiretroviral drugs which do not result in

clinically relevant interactions with pantoprazole.

Intervention:

Rilpivirine-containing products: Concomitant use with

Pantoprazole is contraindicated [see Contraindications ( 4)]. See

prescribing information.

Atazanavir: See prescribing information for atazanavir for

dosing information.

Nelfinavir: Avoid concomitant use with Pantoprazole. See

prescribing information for nelfinavir.

Saquinavir: See the prescribing information for saquinavir and

monitor for potential saquinavir toxicities.

Other antiretrovirals: See prescribing information.

Warfarin

Clinical Impact:

Increased INR and prothrombin time in patients receiving PPIs,

including pantoprazole, and warfarin concomitantly. Increases

in INR and prothrombin time may lead to abnormal bleeding and

even death.

Intervention:

Monitor INR and prothrombin time. Dose adjustment of

warfarin may be needed to maintain target INR range. See

prescribing information for warfarin.

Clopidogrel

Clinical Impact:

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)].

Intervention:

No dose adjustment of clopidogrel is necessary when

administered with an approved dose of Pantoprazole.

Methotrexate

Clinical Impact:

Concomitant use of PPIs with methotrexate (primarily at high

dose) may elevate and prolong serum concentrations of

methotrexate and/or its metabolite hydroxymethotrexate,

Clinical Impact:

possibly leading to methotrexate toxicities. No formal drug

interaction studies of high-dose methotrexate with PPIs have

been conducted [see Warnings and Precautions ( 5.12)].

Intervention:

A temporary withdrawal of Pantoprazole may be considered in

some patients receiving high-dose methotrexate.

Drugs Dependent on Gastric pH for

Absorption (e.g., iron salts, erlotinib,

dasatinib, nilotinib, mycophenolate

mofetil, ketoconazole/itraconazole)

Clinical Impact:

Pantoprazole can reduce the absorption of other drugs due to

its effect on reducing intragastric acidity.

Intervention:

Mycophenolate mofetil (MMF): Co-administration of

pantoprazole sodium 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 [see Clinical Pharmacology ( 12.3)] . 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 the prescribing information for other drugs dependent on

gastric pH for absorption.

Interactions with Investigations of

Neuroendocrine Tumors

Clinical Impact:

CgA levels increase secondary to PPI-induced decreases in

gastric acidity. The increased CgA level may cause false

positive results in diagnostic investigations for

neuroendocrine tumors [see Warnings and Precautions ( 5.10),

Clinical Pharmacology ( 12.2)].

Intervention:

Temporarily stop Pantoprazole treatment at least 14 days

before assessing CgA levels and consider repeating the test if

initial CgA levels are high. If serial tests are performed (e.g.

for monitoring), the same commercial laboratory should be

used for testing, as reference ranges between tests may vary.

False Positive Urine Tests for THC

Clinical Impact:

There have been reports of false positive urine screening tests

for tetrahydrocannabinol (THC) in patients receiving PPIs [see

Warnings and Precautions ( 5.11)].

Intervention:

An alternative confirmatory method should be considered to

verify positive results.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

Available data from published observational studies did not demonstrate an association of major

malformations or other adverse pregnancy outcomes with pantoprazole.

In animal reproduction studies, no evidence of adverse development outcomes was observed with

pantoprazole. Reproduction studies have been performed in rats at oral doses up to 450 mg/kg/day

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