DEXILANT- dexlansoprazole capsule, delayed release

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

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Active ingredient:
DEXLANSOPRAZOLE (UNII: UYE4T5I70X) (DEXLANSOPRAZOLE - UNII:UYE4T5I70X)
Available from:
A-S Medication Solutions
Administration route:
ORAL
Prescription type:
PRESCRIPTION DRUG
Therapeutic indications:
DEXILANT is indicated in patients 12 years of age and older for healing of all grades of erosive esophagitis (EE) for up to eight weeks. DEXILANT is indicated in patients 12 years of age and older to maintain healing of EE and relief of heartburn for up to six months in adults and 16 weeks in patients 12 to 17 years of age. DEXILANT is indicated in patients 12 years of age and older for the treatment of heartburn associated with symptomatic non-erosive gastroesophageal reflux disease (GERD) for four weeks. - DEXILANT is contraindicated in patients with known hypersensitivity to any component of the formulation [see Description (11)] . Hypersensitivity reactions, including anaphylaxis have been reported [see Adverse Reactions (6.1, 6.2)]. Acute interstitial nephritis (AIN) has been reported with other proton pump inhibitors (PPIs), including lansoprazole of which dexlansoprazole is the R-enantiomer. - PPIs, including DEXILANT, are contraindicated with rilpivirine-containing products [see Drug Interactions (7)
Product summary:
Product: 50090-4374 NDC: 50090-4374-0 90 CAPSULE, DELAYED RELEASE in a BOTTLE
Authorization status:
New Drug Application
Authorization number:
50090-4374-0

A-S Medication Solutions

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MEDICATION GUIDE

DEXILANT (decks-i-launt)

(dexlansoprazole)

delayed-release capsules, for oral use

Read this Medication Guide before you start taking DEXILANT and each time you get a refill. There may

be new information. This information does not take the place of talking to your doctor about your medical

condition or your treatment.

What is the most important information that I should know about DEXILANT?

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

with your doctor.

DEXILANT can cause serious side effects, including:

A type of kidney problem (acute interstitial nephritis). Some people who take proton pump inhibitor

(PPI) medicines, including DEXILANT, may develop a kidney problem called acute interstitial

nephritis, that can happen at any time during treatment with PPI medicines. 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. DEXILANT may increase your risk of getting severe diarrhea. This diarrhea may be

caused by an infection (Clostridium difficile) 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

DEXILANT 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 DEXILANT.

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 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.

DEXILANT can have other serious side effects. See "What are the possible side effects of DEXILANT?"

What is DEXILANT?

DEXILANT is a prescription medicine called a proton pump inhibitor (PPI). DEXILANT reduces the

amount of acid in your stomach.

DEXILANT is used in people 12 years of age and older:

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

esophagitis or EE)

MEDICATION GUIDE

DEXILANT (decks-i-launt)

(dexlansoprazole)

delayed-release capsules, for oral use

for up to 6 months in adults and up to 16 weeks in children 12 to 17 years of age to continue healing

of erosive esophagitis and relief of heartburn

for 4 weeks to treat heartburn related to gastroesophageal reflux disease (GERD)

GERD happens when acid from your stomach enters 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.

It is not known if DEXILANT is safe and effective in children under 12 years of age.

DEXILANT is not effective for symptoms of GERD in children under 1 year of age.

Who should not take DEXILANT?

Do not take DEXILANT if you:

are allergic to dexlansoprazole or any of the other ingredients in DEXILANT. See the end of this

Medication Guide for a complete list of ingredients in DEXILANT.

are taking a medicine that contains rilpivirine (EDURANT, COMPLERA) used to treat HIV-1

(Human Immunodeficiency Virus)

What should I tell my doctor before taking DEXILANT?

Before you take DEXILANT, tell your doctor if you:

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. DEXILANT may harm your unborn baby. Talk to your

doctor about the possible risks to an unborn baby if DEXILANT is taken during pregnancy.

are breastfeeding or plan to breastfeed. It is not known if DEXILANT passes into your breast milk or

if it will affect your baby or your breast milk. Talk to your doctor about the best way to feed your

baby if you take DEXILANT.

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

vitamins, and herbal supplements. DEXILANT may affect how other medicines work, and other medicines

may affect how DEXILANT works. Especially tell your doctor if you take methotrexate (Otrexup, Rasuvo,

Trexall).

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

new medicine.

How should I take DEXILANT?

Take DEXILANT exactly as prescribed by your doctor.

Do not change your dose or stop taking DEXILANT without talking to your doctor first.

MEDICATION GUIDE

DEXILANT (decks-i-launt)

(dexlansoprazole)

delayed-release capsules, for oral use

Take DEXILANT with or without food.

Swallow DEXILANT whole. Do not chew the capsules or the granules that are in the capsules.

If you have trouble swallowing a whole capsule, you can open the capsule and take the contents in

applesauce. See the "Instructions for Use" at the end of this Medication Guide for instructions on

how to take DEXILANT with applesauce.

See the "Instructions for Use" at the end of this Medication Guide for instructions on how to mix and

give DEXILANT with water using an oral syringe or through a nasogastric tube.

If you miss a dose of DEXILANT, take it as soon as you remember. If it is almost time for your next

dose, do not take the missed dose. Take your next dose at your regular time. Do not take 2 doses at

the same time to make up for the missed dose.

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

right away or go to the nearest hospital emergency room.

What are the possible side effects of DEXILANT?

DEXILANT may cause serious side effects, including:

See "What is the most important information I should know about DEXILANT?"

Vitamin B12 deficiency. DEXILANT reduces the amount of acid in your stomach. Stomach acid is

needed to absorb Vitamin B12 properly. Talk with your doctor about the possibility of Vitamin B12

deficiency if you have been on DEXILANT 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 develop 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 DEXILANT, or during

treatment, if you will be taking DEXILANT for a long period of time.

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 growth called fundic gland polyps, especially

after taking PPI medicines for more than 1 year.

The most common side effects of DEXILANT in adults include:

MEDICATION GUIDE

DEXILANT (decks-i-launt)

(dexlansoprazole)

delayed-release capsules, for oral use

diarrhea

stomach pain

nausea

common cold

vomiting

The most common side effects of DEXILANT in children 12 to 17 years of age include:

headache

stomach pain

diarrhea

pain or swelling (inflammation) in your mouth, nose or throat

Other side effects:

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

rash

face swelling

throat tightness

difficulty breathing

Your doctor may stop DEXILANT if these symptoms happen.

Tell your doctor if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of DEXILANT. 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.

How should I store DEXILANT?

Store DEXILANT at room temperature between 68°F to 77°F (20°C to 25°C).

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

General information about the safe and effective use of DEXILANT

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

DEXILANT for a condition for which it was not prescribed. Do not give DEXILANT 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 DEXILANT. If you would like

MEDICATION GUIDE

DEXILANT (decks-i-launt)

(dexlansoprazole)

delayed-release capsules, for oral use

more information, talk with your doctor. You can ask your doctor or pharmacist for information about

DEXILANT that is written for health professionals.

For more information, go to www.DEXILANT.com or call 1-877-825-3327.

What are the ingredients in DEXILANT?

Active ingredient: dexlansoprazole.

Inactive ingredients: sugar spheres, magnesium carbonate, sucrose, low-substituted hydroxypropyl cellulose,

titanium dioxide, hydroxypropyl cellulose, hypromellose 2910, talc, methacrylic acid copolymers,

polyethylene glycol 8000, triethyl citrate, polysorbate 80, and colloidal silicon dioxide. The capsule shell is

made of hypromellose, carrageenan and potassium chloride. Based on the capsule shell color, blue contains

FD&C Blue No. 2 aluminum lake; gray contains black ferric oxide; and both contain titanium dioxide.

Revised: 7/2019

Document Id: fea2c2d8-b224-4f52-9549-9ad84e8bfb1e

34391-3

Set id: cad21e6f-7ae1-4fd2-ae36-ea256c3e6eaf

Version: 1

Effective Time: 20190726

A-S Medication Solutions

DEXILANT- dexlansoprazole capsule, delayed release

A-S Medication Solutions

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HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use DEXILANT safely and effectively. See full

prescribing information for DEXILANT.

DEXILANT (dexlansoprazole) delayed-release capsules, for oral use

Initial U.S. Approval: 1995 (lansoprazole)

RECENT MAJOR CHANGES

Warnings and Precautions

Fundic Gland Polyps (5.10)

06/2018

INDICATIONS AND USAGE

DEXILANT is a proton pump inhibitor (PPI) indicated in patients 12 years of age and older for:

Healing of all grades of erosive esophagitis (EE). (1.1)

Maintenance of healed EE and relief of heartburn. (1.2)

Treatment of symptomatic non-erosive gastroesophageal reflux disease (GERD). (1.3)

DOSAGE AND ADMINISTRATION

Recommended dosage in patients 12 years of age and older:

See full prescribing information for complete dosing information for DEXILANT by indication and age group and

dosage adjustment in patients with hepatic impairment. (2.1, 2.2)

Administration Instructions (2.3):

Take without regard to food.

Swallow whole; do not chew.

See full prescribing information for alternative administration options.

DOSAGE FORMS AND STRENGTHS

Delayed-release capsules: 30 mg and 60 mg. (3)

CONTRAINDICATIONS

Patients with known hypersensitivity to any component of the formulation. (4)

Patients receiving rilpivirine-containing products. (4, 7)

WARNINGS AND PRECAUTIONS

Gastric Malignancy: In adults, symptomatic response with DEXILANT does not preclude the 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. (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 DEXILANT and refer to specialist for evaluation. (5.5)

Cyanocobalamin (Vitamin B12) Deficiency: Daily long-term use (e.g., longer than 3 years) may lead to malabsorption or

a deficiency of cyanocobalamin. (5.6)

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

Interactions with Investigations for Neuroendocrine Tumors: Increases in intragastric pH may result in

hypergastrinemia and enterochromaffin-like cell hyperplasia and increased chromogranin A levels which may interfere

with diagnostic investigations for neuroendocrine tumors. (5.8, 7)

Interaction with Methotrexate: Concomitant use with PPIs may elevate and/or prolong serum concentrations of

methotrexate and/or its metabolite, possibly leading to toxicity. With high-dose methotrexate administration, consider a

temporary withdrawal of DEXILANT. (5.9, 7)

Fundic Gland Polyps: Risk increases with long-term use, especially beyond 1 year. Use the shortest duration of therapy.

(5.10)

ADVERSE REACTIONS

The most common adverse reactions are:

Adults (≥2%): diarrhea, abdominal pain, nausea, upper respiratory tract infection, vomiting, and flatulence. (6.1)

Patients 12 to 17 years of age (≥5%): headache, abdominal pain, diarrhea, nasopharyngitis, and oropharyngeal pain.

(6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Takeda Pharmaceuticals at 1-877-TAKEDA-7 (1-877-

825-3327) 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 adverse effects on fetal bone growth and development. (8.1)

Pediatrics: Based on data with lansoprazole, DEXILANT is not effective in patients with symptomatic GERD 1 month to

less than 1 year of age and nonclinical studies have demonstrated adverse effects in juvenile rats. (8.4)

See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.

Revised: 7/2019

FULL PRESCRIBING INFORMATION: CONTENTS*

1 INDICATIONS AND USAGE

1.1 Healing of Erosive Esophagitis

1.2 Maintenance of Healed Erosive Esophagitis and Relief of Heartburn

1.3 Treatment of Symptomatic Non-Erosive Gastroesophageal Reflux Disease

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Dosage in Patients 12 Years of Age and Older

2.2 Dosage Adjustment in Patients with Hepatic Impairment for the Healing of Erosive Esophagitis

2.3 Important Administration Information

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 B12) Deficiency

5.7 Hypomagnesemia

5.8 Interactions with Investigations for Neuroendocrine Tumors

5.9 Interaction with Methotrexate

5.10 Fundic Gland Polyps

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

8.6 Hepatic Impairment

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 Healing of Erosive Esophagitis in Adults

14.2 Maintenance of Healed Erosive Esophagitis and Relief of Heartburn in Adults

14.3 Treatment of Symptomatic Non-Erosive GERD in Adults

14.4 Pediatric GERD

16 HOW SUPPLIED/STORAGE AND HANDLING

17 PATIENT COUNSELING INFORMATION

FULL PRESCRIBING INFORMATION

1 INDICATIONS AND USAGE

1.1 Healing of Erosive Esophagitis

DEXILANT is indicated in patients 12 years of age and older for healing of all grades of erosive

esophagitis (EE) for up to eight weeks.

1.2 Maintenance of Healed Erosive Esophagitis and Relief of Heartburn

DEXILANT is indicated in patients 12 years of age and older to maintain healing of EE and relief of

heartburn for up to six months in adults and 16 weeks in patients 12 to 17 years of age.

1.3 Treatment of Symptomatic Non-Erosive Gastroesophageal Reflux Disease

DEXILANT is indicated in patients 12 years of age and older for the treatment of heartburn associated

with symptomatic non-erosive gastroesophageal reflux disease (GERD) for four weeks.

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Dosage in Patients 12 Years of Age and Older

Table 1. Recommended DEXILANT Capsules Dosage Regimen by Indication in

Patients 12 Years of Age and Older

Indication

Dosage of DEXILANT

Caps ules

Duration

Healing of EE

One 60 mg capsule once daily.

Up to 8 weeks.

Maintenance of Healed EE and

Relief of Heartburn

One 30 mg capsule once daily.

Controlled studies did not

extend beyond 6 months in

adults and 16 weeks in patients

12 to 17 years of age.

Symptomatic Non-Erosive

GERD

One 30 mg capsule once daily.

4 weeks.

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

2.2 Dosage Adjustment in Patients with Hepatic Impairment for the Healing of Erosive

Es ophagitis

For patients with moderate hepatic impairment (Child-Pugh Class B), the recommended dosage is 30 mg

DEXILANT once daily for up to eight weeks. DEXILANT is not recommended in patients with severe

hepatic impairment (Child-Pugh Class C) [see Use in Specific Populations (8.6)].

2.3 Important Administration Information

Take without regard to food.

Missed doses: If a dose is missed, administer as soon as possible. However, if the next scheduled

dose is due, do not take the missed dose, and take the next dose on time. Do not take two doses at one

time to make up for a missed dose.

Swallow whole; do not chew.

For patients who have trouble swallowing capsules, DEXILANT capsules can be opened and

administered with applesauce as follows:

1. Place one tablespoonful of applesauce into a clean container.

2. Open capsule.

3. Sprinkle intact granules on applesauce.

4. Swallow applesauce and granules immediately. Do not chew granules. Do not save the

applesauce and granules for later use.

Alternatively, the capsule can be administered with water via oral syringe or nasogastric (NG) tube.

Administration with Water in an Oral Syringe

1. Open the capsule and empty the granules into a clean container with 20 mL of water.

2. Withdraw the entire mixture into a syringe.

3. Gently swirl the syringe in order to keep granules from settling.

4. Administer the mixture immediately into the mouth. Do not save the water and granule mixture for

later use.

5. Refill the syringe with 10 mL of water, swirl gently, and administer.

6. Refill the syringe again with 10 mL of water, swirl gently, and administer.

Administration with Water via a NG Tube (≥16 French)

1. Open the capsule and empty the granules into a clean container with 20 mL of water.

2. Withdraw the entire mixture into a catheter-tip syringe.

3. Swirl the catheter-tip syringe gently in order to keep the granules from settling, and immediately

inject the mixture through the NG tube into the stomach. Do not save the water and granule

mixture for later use.

4. Refill the catheter-tip syringe with 10 mL of water, swirl gently, and flush the tube.

5. Refill the catheter-tip syringe again with 10 mL of water, swirl gently, and administer.

3 DOSAGE FORMS AND STRENGTHS

DEXILANT delayed-release capsules

30 mg: strength is an opaque, blue and gray capsule imprinted with "TAP" and "30".

60 mg: strength is an opaque, blue capsule imprinted with "TAP" and "60".

4 CONTRAINDICATIONS

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

formulation [see Description (11)]. Hypersensitivity reactions, including anaphylaxis have been

reported [see Adverse Reactions (6.1, 6.2)]. Acute interstitial nephritis (AIN) has been reported with

other proton pump inhibitors (PPIs), including lansoprazole of which dexlansoprazole is the R-

enantiomer.

PPIs, including DEXILANT, are contraindicated with rilpivirine-containing products [see Drug

Interactions (7)].

5 WARNINGS AND PRECAUTIONS

5.1 Presence of Gastric Malignancy

In adults, symptomatic response to therapy with DEXILANT 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 lansoprazole. Acute

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

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

Contraindications (4)].

5.3 Clostridium difficile-Associated Diarrhea

Published observational studies suggest that PPI therapy like DEXILANT 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

conditions 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. These events have occurred as both new onset and an exacerbation of existing

autoimmune disease. The majority of PPI-induced lupus erythematosus cases were CLE.

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

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

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

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

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

within days to years after initiating treatment primarily in patients ranging from young adults to the

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

reported.

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

CLE or SLE are noted in patients receiving DEXILANT, discontinue the drug and refer the patient to

the appropriate specialist for evaluation. Most patients improve with discontinuation of the PPI alone in

four 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 B12) Deficiency

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

three years) may lead to malabsorption of cyanocobalamin (Vitamin B12) caused by hypo- or

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

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

with cyanocobalamin deficiency are observed in patients treated with DEXILANT.

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), healthcare professionals may consider

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

(6.2)].

5.8 Interactions 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 dexlansoprazole 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 Drug Interactions (7), Clinical Pharmacology

(12.2)].

5.9 Interaction with Methotrexate

Literature suggests that concomitant use of PPIs with methotrexate (primarily at high dose) 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)].

5.10 Fundic Gland Polyps

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

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

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

appropriate to the condition being treated.

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 B12) Deficiency [see Warnings and Precautions (5.6)]

Hypomagnesemia [see Warnings and Precautions (5.7)]

Fundic Gland Polyps [see Warnings and Precautions (5.10)]

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 practice.

Adults

The safety of DEXILANT was evaluated in 4548 adult patients in controlled and single-arm clinical

trials, including 863 patients treated for at least six months and 203 patients treated for one year. Patients

ranged in age from 18 to 90 years (median age 48 years), with 54% female, 85% Caucasian, 8% Black,

4% Asian, and 3% other races. Six randomized controlled clinical trials were conducted for the

treatment of EE, maintenance of healed EE, and symptomatic GERD, which included 896 patients on

placebo, 455 patients on DEXILANT 30 mg, 2218 patients on DEXILANT 60 mg, and 1363 patients on

lansoprazole 30 mg once daily.

Common Adverse Reactions

The most common adverse reactions (>2%) that occurred at a higher incidence for DEXILANT than

placebo in the controlled studies are presented in Table 2.

Table 2. Common Adverse Reactions in Controlled Studies in Adults

Adverse Reaction

Placebo

(N=896)

%

DEXILANT

30 mg

(N=455)

%

DEXILANT

60 mg

(N=2218)

%

DEXILANT

Total

(N=2621)

%

Lans oprazole

30 mg

(N=1363)

%

Diarrhea

Abdominal Pain

Nausea

Upper Respiratory Tract

Infection

Vomiting

Flatulence

Adverse Reactions Resulting in Discontinuation

In controlled clinical studies, the most common adverse reaction leading to discontinuation from

DEXILANT was diarrhea (0.7%).

Less Common Adverse Reactions

Other adverse reactions that were reported in controlled studies at an incidence of less than 2% are

listed below by body system:

Blood and Lymphatic System Disorders: anemia, lymphadenopathy

Cardiac Disorders: angina, arrhythmia, bradycardia, chest pain, edema, myocardial infarction, palpitation,

tachycardia

Ear and Labyrinth Disorders: ear pain, tinnitus, vertigo

Endocrine Disorders: goiter

Eye Disorders: eye irritation, eye swelling

Gastrointestinal Disorders: abdominal discomfort, abdominal tenderness, abnormal feces, anal

discomfort, Barrett's esophagus, bezoar, bowel sounds abnormal, breath odor, colitis microscopic,

colonic polyp, constipation, dry mouth, duodenitis, dyspepsia, dysphagia, enteritis, eructation,

esophagitis, gastric polyp, gastritis, gastroenteritis, gastrointestinal disorders, gastrointestinal

hypermotility disorders, GERD, GI ulcers and perforation, hematemesis, hematochezia, hemorrhoids,

impaired gastric emptying, irritable bowel syndrome, mucus stools, oral mucosal blistering, painful

defecation, proctitis, paresthesia oral, rectal hemorrhage, retching

General Disorders and Administration Site Conditions: adverse drug reaction, asthenia, chest pain, chills,

feeling abnormal, inflammation, mucosal inflammation, nodule, pain, pyrexia

Hepatobiliary Disorders: biliary colic, cholelithiasis, hepatomegaly

Immune System Disorders: hypersensitivity

Infections and Infestations: candida infections, influenza, nasopharyngitis, oral herpes, pharyngitis,

sinusitis, viral infection, vulvo-vaginal infection

Injury, Poisoning and Procedural Complications: falls, fractures, joint sprains, overdose, procedural

pain, sunburn

Laboratory Investigations: ALP increased, ALT increased, AST increased, bilirubin

decreased/increased, blood creatinine increased, blood gastrin increased, blood glucose increased,

blood potassium increased, liver function test abnormal, platelet count decreased, total protein

increased, weight increase

Metabolism and Nutrition Disorders: appetite changes, hypercalcemia, hypokalemia

Musculoskeletal and Connective Tissue Disorders: arthralgia, arthritis, muscle cramps, musculoskeletal

pain, myalgia

Nervous System Disorders: altered taste, convulsion, dizziness, headaches, migraine, memory impairment,

paresthesia, psychomotor hyperactivity, tremor, trigeminal neuralgia

Psychiatric Disorders: abnormal dreams, anxiety, depression, insomnia, libido changes

Renal and Urinary Disorders: dysuria, micturition urgency

Reproductive System and Breast Disorders: dysmenorrhea, dyspareunia, menorrhagia, menstrual disorder

Respiratory, Thoracic and Mediastinal Disorders: aspiration, asthma, bronchitis, cough, dyspnea, hiccups,

hyperventilation, respiratory tract congestion, sore throat

Skin and Subcutaneous Tissue Disorders: acne, dermatitis, erythema, pruritus, rash, skin lesion, urticaria

Vascular Disorders: deep vein thrombosis, hot flush, hypertension

Additional adverse reactions that were reported in a long-term single-arm trial and were considered

related to DEXILANT by the treating physician included: anaphylaxis, auditory hallucination, B-cell

lymphoma, bursitis, central obesity, cholecystitis acute, dehydration, diabetes mellitus, dysphonia,

epistaxis, folliculitis, gout, herpes zoster, hyperlipidemia, hypothyroidism, increased neutrophils,

MCHC decrease, neutropenia, rectal tenesmus, restless legs syndrome, somnolence, tonsillitis.

Pediatrics

The safety of DEXILANT was evaluated in controlled and single-arm clinical trials including 166

pediatric patients,12 to 17 years of age for the treatment of symptomatic non-erosive GERD, healing of

EE, maintenance of healed EE and relief of heartburn [see Clinical Studies (14.4)].

The adverse reaction profile was similar to that of adults. The most common adverse reactions that

occurred in ≥5% of patients were headache, abdominal pain, diarrhea, nasopharyngitis and

oropharyngeal pain.

Other Adverse Reactions

See the full prescribing information for lansoprazole for other adverse reactions not observed with

DEXILANT.

6.2 Postmarketing Experience

The following adverse reactions have been identified during post-approval of DEXILANT. Because

these reactions are reported voluntarily from a population of uncertain size, it is not always possible to

reliably estimate their frequency or establish a causal relationship to drug exposure.

Blood and Lymphatic System Disorders: autoimmune hemolytic anemia, idiopathic thrombocytopenic

purpura

Ear and Labyrinth Disorders: deafness

Eye Disorders: blurred vision

Gastrointestinal Disorders: oral edema, pancreatitis, fundic gland polyps

General Disorders and Administration Site Conditions: facial edema

Hepatobiliary Disorders: drug-induced hepatitis

Immune System Disorders: anaphylactic shock (requiring emergency intervention), exfoliative dermatitis,

Stevens-Johnson syndrome, toxic epidermal necrolysis (some fatal)

Infections and Infestations: Clostridium difficile-associated diarrhea

Metabolism and Nutrition Disorders: hypomagnesemia, hyponatremia

Musculoskeletal System Disorders: bone fracture

Nervous System Disorders: cerebrovascular accident, transient ischemic attack

Renal and Urinary Disorders: acute renal failure

Respiratory, Thoracic and Mediastinal Disorders: pharyngeal edema, throat tightness

Skin and Subcutaneous Tissue Disorders: generalized rash, leukocytoclastic vasculitis

7 DRUG INTERACTIONS

Tables 3 and 4 include drugs with clinically important drug interactions and interaction with diagnostics

when administered concomitantly with DEXILANT and instructions for preventing or managing them.

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

PPIs.

Table 3. Clinically Relevant Interactions Affecting Drugs Co-Administered with DEXILANT 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 dexlansoprazole

may reduce antiviral effect and promote the development of drug

resistance.

Increased exposure of other antiretroviral drugs (e.g., saquinavir) when

used concomitantly with dexlansoprazole may increase toxicity of the

antiretroviral drugs.

There are other antiretroviral drugs which do not result in clinically

relevant interactions with dexlansoprazole.

Rilpivirine-containing products: Concomitant use with DEXILANT is

contraindicated [see Contraindications (4)]. See prescribing information.

Intervention:

Atazanavir: See prescribing information for atazanavir for dosing information.

Nelfinavir: Avoid concomitant use with DEXILANT. 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 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.

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, possibly leading to methotrexate toxicities.

No formal drug interaction studies of high-dose methotrexate with PPIs have

been conducted [see Warnings and Precautions (5.9)].

Intervention:

A temporary withdrawal of DEXILANT may be considered in some patients

receiving high-dose methotrexate.

Digoxin

Clinical Impact:

Potential for increased exposure of digoxin.

Intervention:

Monitor digoxin concentrations. Dose adjustment of digoxin may be needed

to maintain therapeutic drug concentrations. See prescribing information for

digoxin.

Drugs Dependent on Gastric pH for Absorption (e.g., iron salts, erlotinib, dasatinib, nilotinib,

mycophenolate mofetil, ketoconazole/itraconazole)

Clinical Impact:

Dexlansoprazole can reduce the absorption of other drugs due to its effect on

reducing intragastric acidity.

Intervention:

Mycophenolate mofetil (MMF): Co-administration of PPIs in healthy subjects

and in transplant patients receiving MMF has been reported to reduce the

exposure to the active metabolite, mycophenolic acid (MPA), possibly due to

a decrease in MMF solubility at an increased gastric pH. The clinical

relevance of reduced MPA exposure on organ rejection has not been

established in transplant patients receiving DEXILANT and MMF. Use

DEXILANT with caution in transplant patients receiving MMF.

See the prescribing information for other drugs dependent on gastric pH for

absorption.

Tacrolimus

Clinical Impact:

Potentially increased exposure of tacrolimus, especially in transplant patients

who are intermediate or poor metabolizers of CYP2C19.

Intervention:

Monitor tacrolimus whole blood trough concentrations. Dose adjustment of

tacrolimus may be needed to maintain therapeutic drug concentrations. See

prescribing information for tacrolimus.

Interactions with Investigations of Neuroendocrine Tumors

Clinical Impact:

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 (5.8),

Clinical Pharmacology (12.2)].

Temporarily stop DEXILANT treatment at least 14 days before assessing

Intervention:

CgA levels and consider repeating the test if initial CgA levels are high. If

serial tests are performed (e.g., for monitoring), the same commercial

laboratory should be used for testing, as reference ranges between tests may

vary.

Interaction with Secretin Stimulation Test

Clinical Impact:

Hyper-response in gastrin secretion in response to secretin stimulation test,

falsely suggesting gastrinoma.

Intervention:

Temporarily stop DEXILANT treatment at least 30 days before assessing to

allow gastrin levels to return to baseline [see Clinical Pharmacology (12.2)].

False Positive Urine Tests for THC

Clinical Impact:

There have been reports of false positive urine screening tests for

tetrahydrocannabinol (THC) in patients receiving PPIs.

Intervention:

An alternative confirmatory method should be considered to verify positive

results.

Table 4. Clinically Relevant Interactions Affecting DEXILANT When Co-Administered with

Other Drugs and Substances

CYP2C19 or CYP3A4 Inducers

Clinical Impact:

Decreased exposure of dexlansoprazole when used concomitantly with

strong inducers [see Clinical Pharmacology (12.3)].

Intervention:

St. John's Wort, rifampin: Avoid concomitant use with DEXILANT.

Ritonavir-containing products: See prescribing information.

CYP2C19 or CYP3A4 Inhibitors

Clinical Impact:

Increased exposure of dexlansoprazole is expected when used concomitantly

with strong inhibitors [see Clinical Pharmacology (12.3)].

Intervention:

Voriconazole: See prescribing information.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

There are no studies with dexlansoprazole use in pregnant women to inform a drug-associated risk.

Dexlansoprazole is the R-enantiomer of lansoprazole, and published observational studies of

lansoprazole use during pregnancy did not demonstrate an association of adverse pregnancy-related

outcomes with lansoprazole (see Data).

In animal reproduction studies, oral administration of lansoprazole to rats during organogenesis through

lactation at 1.8 times the maximum recommended human dexlansoprazole dose produced reductions in

the offspring in femur weight, femur length, crown-rump length and growth plate thickness (males only)

on postnatal Day 21 (see Data). These effects were associated with reduction in body weight gain.

Advise pregnant women of the potential risk to a fetus.

The estimated background risk of major birth defects and miscarriage for the indicated population is

unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In

the U.S. general population, the estimated background risk of major birth defects and miscarriage in

clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Data

Human Data

Dexlansoprazole is the R-enantiomer of lansoprazole. Available data from published observational

studies failed to demonstrate an association of adverse pregnancy-related outcomes and lansoprazole

use. Methodological limitations of these observational studies cannot definitely establish or exclude

any drug-associated risk during pregnancy. In a prospective study by the European Network of

Teratology Information Services, outcomes from a group of 62 pregnant women administered median

daily doses of 30 mg of lansoprazole were compared to a control group of 868 pregnant women who

did not take any PPIs. There was no difference in the rate of major malformations between women

exposed to PPIs and the control group, corresponding to a Relative Risk (RR)=1.04, [95% Confidence

Interval (CI) 0.25-4.21]. In a population-based retrospective cohort study covering all live births in

Denmark from 1996 to 2008, there was no significant increase in major birth defects during analysis of

first trimester exposure to lansoprazole in 794 live births. A meta-analysis that compared 1,530 pregnant

women exposed to PPIs in at least the first trimester with 133,410 unexposed pregnant women showed

no significant increases in risk for congenital malformations or spontaneous abortion with exposure to

PPIs (for major malformations Odds Ratio (OR)=1.12, [95% CI 0.86-1.45] and for spontaneous

abortions OR=1.29, [95% CI 0.84-1.97]).

Animal Data

An embryo-fetal development study conducted in rabbits at oral dexlansoprazole doses up to 30

mg/kg/day (approximately nine times the maximum recommended human dexlansoprazole dose [60

mg/day] based on body surface area) during organogenesis showed no effects on fetuses due to

dexlansoprazole. In addition, embryo-fetal development studies performed in rats with oral lansoprazole

at doses up to 150 mg/kg/day (40 times the recommended human lansoprazole dose based on body

surface area) during organogenesis and in rabbits with oral lansoprazole at doses up to 30 mg/kg/day

(16 times the recommended human lansoprazole dose based on body surface area) during organogenesis

revealed no effects on fetuses due to lansoprazole.

A pre- and postnatal developmental toxicity study in rats with additional endpoints to evaluate bone

development was performed with lansoprazole at oral doses of 10 to 100 mg/kg/day (0.2 to 1.8 times

the maximum recommended human dexlansoprazole dose of 60 mg based on dexlansoprazole AUC [area

under the plasma concentration-time curve]) administered during organogenesis through lactation.

Maternal effects observed at 100 mg/kg/day (1.8 times the maximum recommended human

dexlansoprazole dose of 60 mg based on dexlansoprazole AUC) included increased gestation period,

decreased body weight gain during gestation, and decreased food consumption. The number of

stillbirths was increased at this dose, which may have been secondary to maternal toxicity. Body weight

of pups was reduced at 100 mg/kg/day starting on postnatal Day 11. Femur weight, femur length, and

crown-rump length were reduced at 100 mg/kg/day on postnatal Day 21. Femur weight was still

decreased in the 100 mg/kg/day group at age 17 to 18 weeks. Growth plate thickness was decreased in

the 100 mg/kg/day males on postnatal Day 21, and was increased in the 30 and 100 mg/kg/day males at

age 17 to 18 weeks. The effects on bone parameters were associated with reduction in body weight

gain.

8.2 Lactation

Risk Summary

There is no information regarding the presence of dexlansoprazole in human milk, the effects on the

breastfed infant, or the effects on milk production. However, lansoprazole and its metabolites are

present in rat milk. The developmental and health benefits of breastfeeding should be considered along

with the mother's clinical need for DEXILANT and any potential adverse effects on the breastfed child

from DEXILANT or from the underlying maternal condition.

8.4 Pediatric Use

The use of DEXILANT is not recommended for the treatment of symptomatic GERD in pediatric

patients one month to less than one year of age because lansoprazole (the racemic mixture) was not

shown to be effective in a multicenter, double-blind controlled trial, and nonclinical studies with

lansoprazole have demonstrated an adverse effect of heart valve thickening and bone changes.

The safety and effectiveness of DEXILANT have not been established in pediatric patients less than 12

years of age. DEXILANT is not recommended in pediatric patients less than 12 years of age.

Nonclinical studies in juvenile rats with lansoprazole have demonstrated an adverse effect of heart

valve thickening and bone changes at lansoprazole doses higher than the maximum recommended

equivalent human dose, as described below in Juvenile Animal Toxicity Data.

The safety and effectiveness of DEXILANT have been established in pediatric patients 12 to 17 years

of age for the healing of all grades of EE, the maintenance of healed EE and relief of heartburn, and

treatment of heartburn associated with symptomatic non-erosive GERD.

Use of DEXILANT in this age group is supported by evidence from adequate and well-controlled

studies of DEXILANT in adults with additional safety, efficacy and pharmacokinetic data in pediatric

patients 12 to 17 years of age [see Dosage and Administration (2.1), Adverse Reactions (6.1), Clinical

Pharmacology (12.3), and Clinical Studies (14.1, 14.2, 14.3, and 14.4)].

The adverse reaction profile in patients 12 to 17 years of age was similar to adults.

Juvenile Animal Toxicity Data

In a juvenile rat study, adverse effects on bone growth and development and heart valves were observed

at lansoprazole doses higher than the maximum recommended equivalent human dose.

An eight-week oral toxicity study with a four-week recovery phase was conducted in juvenile rats with

lansoprazole administered from postnatal Day 7 (age equivalent to neonatal humans) through 62 (age

equivalent to approximately 14 years in humans) at doses of 40 to 500 mg/kg/day.

Heart valve thickening occurred at a lansoprazole dose of 500 mg/kg/day (approximately three to five

times the expected dexlansoprazole exposure in pediatric patients less than 12 years of age based on

AUC). Heart valve thickening was not observed at the next lower dose (250 mg/kg/day) and below. The

findings trended towards reversibility after a four-week drug-free recovery period. The relevance of

heart valve thickening in this study to pediatric patients less than 12 years of age is unknown. These

findings are not relevant for patients 12 years of age and older. No effects on heart valves were

observed in a 13-week intravenous toxicity study of lansoprazole in adolescent rats (approximately 12

years human age equivalence) at systemic exposures similar to those achieved in the eight-week oral

toxicity study in juvenile (neonatal) rats.

In the eight-week oral toxicity study of lansoprazole, doses equal to or greater than 100 mg/kg/day

produced delayed growth, with impairment of weight gain observed as early as postnatal Day 10 (age

equivalent to neonatal humans). At the end of treatment, the signs of impaired growth at 100 mg/kg/day

and higher included reductions in body weight (14% to 44% compared to controls), absolute weight of

multiple organs, femur weight, femur length and crown-rump length. Femoral growth plate thickness

was reduced only in males and only at the 500 mg/kg/day dose. The effects related to delayed growth

persisted through the end of the 4-week recovery period. Longer term data were not collected.

8.5 Geriatric Use

Of the total number of patients (n=4548) in clinical studies of DEXILANT, 11% of patients were aged

65 years and over, while 2% were 75 years and over. No overall differences in safety or effectiveness

were observed between these patients and younger patients and other reported clinical experience has

not identified significant differences in responses between geriatric and younger patients, but greater

sensitivity of some older individuals cannot be ruled out [see Clinical Pharmacology (12.3)].

8.6 Hepatic Impairment

No dosage adjustment for DEXILANT is necessary for patients with mild hepatic impairment (Child-

Pugh Class A).

In a study of adult patients with moderate hepatic impairment (Child-Pugh Class B) who received a

single dose of 60 mg DEXILANT, there was a significant increase in systemic exposure of

dexlansoprazole compared to healthy subjects with normal hepatic function [see Clinical Pharmacology

(12.3)]. Therefore, for patients with moderate hepatic impairment (Child-Pugh Class B), dosage

reduction is recommended for the healing of EE [see Dosage and Administration (2.2)].

No studies have been conducted in patients with severe hepatic impairment (Child-Pugh Class C); the

use of DEXILANT is not recommended for these patients [see Dosage and Administration (2.2)].

10 OVERDOSAGE

There have been no reports of significant overdose with DEXILANT. Multiple doses of DEXILANT

120 mg and a single dose of DEXILANT 300 mg did not result in death or other severe adverse events.

However, serious adverse events of hypertension have been reported in association with twice daily

doses of DEXILANT 60 mg. Non-serious adverse reactions observed with twice daily doses of

DEXILANT 60 mg include hot flashes, contusion, oropharyngeal pain, and weight loss.

Dexlansoprazole is not expected to be removed from the circulation by hemodialysis.

In the event of over-exposure, treatment should be symptomatic and supportive.

If over-exposure occurs, call your poison control center at 1-800-222-1222 for current information on

the management of poisoning or over-exposure.

11 DESCRIPTION

The active ingredient in DEXILANT (dexlansoprazole) delayed-release capsules, a proton pump

inhibitor, is (+)-2-[(R)-{[3-methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl] methyl} sulfinyl]-1H-

benzimidazole, a compound that inhibits gastric acid secretion. Dexlansoprazole is the R-enantiomer of

lansoprazole (a racemic mixture of the R- and S-enantiomers). Its empirical formula is:

H F N O S, with a molecular weight of 369.36. Dexlansoprazole has the following chemical

structure:

Dexlansoprazole is a white to nearly white crystalline powder which melts with decomposition at

140°C. Dexlansoprazole is freely soluble in dimethylformamide, methanol, dichloromethane, ethanol,

and ethyl acetate; and soluble in acetonitrile; slightly soluble in ether; and very slightly soluble in water;

and practically insoluble in hexane.

Dexlansoprazole is stable when exposed to light. Dexlansoprazole is more stable in neutral and alkaline

conditions than acidic conditions.

Dexlansoprazole is supplied for oral administration as a dual delayed-release formulation in capsules.

The capsules contain dexlansoprazole in a mixture of two types of enteric-coated granules with

different pH-dependent dissolution profiles [see Clinical Pharmacology (12.3)].

DEXILANT delayed-release capsules are available in two dosage strengths: 30 and 60 mg, per

capsule. Each capsule contains enteric-coated granules consisting of dexlansoprazole (active

ingredient) and the following inactive ingredients: sugar spheres, magnesium carbonate, sucrose, low-

substituted hydroxypropyl cellulose, titanium dioxide, hydroxypropyl cellulose, hypromellose 2910,

talc, methacrylic acid copolymers, polyethylene glycol 8000, triethyl citrate, polysorbate 80, and

colloidal silicon dioxide. The components of the capsule shell include the following inactive

ingredients: hypromellose, carrageenan and potassium chloride. Based on the capsule shell color, blue

contains FD&C Blue No. 2 aluminum lake; gray contains black ferric oxide; and both contain titanium

dioxide.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Dexlansoprazole belongs to a class of antisecretory compounds, the substituted benzimidazoles, that

suppress gastric acid secretion by specific inhibition of the (H , K )-ATPase at the secretory surface

of the gastric parietal cell. Because this enzyme is regarded as the acid (proton) pump within the

parietal cell, dexlansoprazole has been characterized as a gastric proton-pump inhibitor, in that it blocks

the final step of acid production.

12.2 Pharmacodynamics

Antisecretory Activity

The effects of DEXILANT 60 mg (n=20) or lansoprazole 30 mg (n=23) once daily for five days on 24

hour intragastric pH were assessed in healthy subjects in a multiple-dose crossover study. The results

are summarized in Table 5.

Table 5. Effect on 24 Hour Intragastric pH on

Day 5 After Administration of DEXILANT or

Lans oprazole

DEXILANT

60 mg

Lans oprazole

30 mg

Mean Intragastric pH

4.55

4.13

% Time Intragastric pH >4 (hours)

(17 hours)

(14 hours)

Serum Gastrin Effects

The effect of dexlansoprazole on serum gastrin concentrations was evaluated in approximately 3460

patients in clinical trials up to eight weeks and in 1023 patients for up to six to 12 months. The mean

fasting gastrin concentrations increased from baseline during treatment with 30 and 60 mg DEXILANT.

In patients treated for more than six months, mean serum gastrin levels increased during approximately

the first three months of treatment and were stable for the remainder of treatment. Mean serum gastrin

levels returned to pre-treatment levels within one month of discontinuation of treatment.

Increased gastrin causes enterochromaffin-like cell hyperplasia and increased serum CgA levels. The

increased CgA levels may cause false positive results in diagnostic investigations for neuroendocrine

tumors [see Warnings and Precautions (5.8)].

Enterochromaffin-Like Cell (ECL) Effects

There were no reports of ECL cell hyperplasia in gastric biopsy specimens obtained from 653 patients

treated with DEXILANT 30, 60, or 90 mg for up to 12 months.

During lifetime exposure of rats dosed daily with up to 150 mg/kg/day of lansoprazole, marked

hypergastrinemia was observed followed by ECL cell proliferation and formation of carcinoid tumors,

especially in female rats [see Nonclinical Toxicology (13.1)].

Cardiac Electrophysiology

At a dose five times the maximum recommended dose, dexlansoprazole does not prolong the QT

interval to any clinically relevant extent.

12.3 Pharmacokinetics

The dual delayed-release formulation of DEXILANT results in a dexlansoprazole plasma

concentration-time profile with two distinct peaks; the first peak occurs one to two hours after

administration, followed by a second peak within four to five hours (see Figure 1). Dexlansoprazole is

eliminated with a half-life of approximately one to two hours in healthy subjects and in patients with

symptomatic GERD. No accumulation of dexlansoprazole occurs after multiple, once daily doses of

DEXILANT 30 or 60 mg although mean AUC and C

values of dexlansoprazole were slightly

higher (less than 10%) on Day 5 than on Day 1.

Figure 1: Mean Plasma Dexlansoprazole Concentration – Time Profile Following Oral

Administration of 30 or 60 mg DEXILANT Once Daily for 5 Days in Healthy Adult Subjects

The pharmacokinetics of dexlansoprazole are highly variable, with percent coefficient of variation

(%CV) values for C

, AUC, and CL/F of greater than 30% (see Table 6).

Table 6. Mean (%CV) Pharmacokinetic Parameters for

Adult Subjects on Day 5 After Administration of

DEXILANT

Dos e

(mg)

C

(ng/mL)

AUC

(ng·h/mL)

CL/F

(L/h)

658 (40%)

(N=44)

3275 (47%)

(N=43)

11.4 (48%)

(N=43)

1397 (51%)

(N=79)

6529 (60%)

(N=73)

11.6 (46%)

(N=41)

Absorption

After oral administration of DEXILANT 30 or 60 mg to healthy subjects and symptomatic GERD

patients, mean C

and AUC values of dexlansoprazole increased approximately dose proportionally

(see Figure 1).

max

24

When granules of DEXILANT 60 mg are mixed with water and dosed via NG tube or orally via

syringe, the bioavailability (C

and AUC) of dexlansoprazole was similar to that when DEXILANT

60 mg was administered as an intact capsule [see Dosage and Administration (2.3)].

Effect on Food

In food-effect studies in healthy subjects receiving DEXILANT under various fed conditions compared

to fasting, increases in C

ranged from 12 to 55%, increases in AUC ranged from 9 to 37%, and T

varied (ranging from a decrease of 0.7 hours to an increase of three hours) [see Dosage and

Administration (2.3)].

Distribution

Plasma protein binding of dexlansoprazole ranged from 96 to 99% in healthy subjects and was

independent of concentration from 0.01 to 20 mcg/mL. The apparent volume of distribution (V /F) after

multiple doses in symptomatic GERD patients was 40 L.

Elimination

Metabolism

Dexlansoprazole is extensively metabolized in the liver by oxidation, reduction, and subsequent

formation of sulfate, glucuronide and glutathione conjugates to inactive metabolites. Oxidative

metabolites are formed by the cytochrome P450 (CYP) enzyme system including hydroxylation mainly

by CYP2C19, and oxidation to the sulfone by CYP3A4.

CYP2C19 is a polymorphic liver enzyme which exhibits three phenotypes in the metabolism of

CYP2C19 substrates: extensive metabolizers (*1/*1), intermediate metabolizers (*1/mutant) and poor

metabolizers (mutant/mutant). Dexlansoprazole is the major circulating component in plasma regardless

of CYP2C19 metabolizer status. In CYP2C19 intermediate and extensive metabolizers, the major plasma

metabolites are 5-hydroxy dexlansoprazole and its glucuronide conjugate, while in CYP2C19 poor

metabolizers dexlansoprazole sulfone is the major plasma metabolite.

Excretion

Following the administration of DEXILANT, no unchanged dexlansoprazole is excreted in urine.

Following the administration of [

C] dexlansoprazole to six healthy male subjects, approximately

50.7% (standard deviation (SD): 9.0%) of the administered radioactivity was excreted in urine and

47.6% (SD: 7.3%) in the feces. Apparent clearance (CL/F) in healthy subjects was 11.4 to 11.6 L/hour,

respectively, after five days of 30 or 60 mg once daily administration.

Specific Populations

Age: Pediatric Population

The pharmacokinetics of dexlansoprazole in patients under the age of 12 years have not been studied.

Patients 12 to 17 Years of Age

The pharmacokinetics of dexlansoprazole were studied in 36 patients 12 to 17 years of age with

symptomatic GERD in a multi-center trial. Patients were randomized to receive DEXILANT 30 or 60

mg once daily for seven days. The dexlansoprazole mean C

and AUC in patients 12 to 17 years of

age were 105 and 88%, respectively, compared to those observed in adults at the 30 mg dose, and were

81 and 78%, respectively, at the 60 mg dose (see Tables 6 and 7).

Table 7. Mean (%CV) Pharmacokinetic Parameters in Patients 12 to 17

Years of Age with Symptomatic GERD on Day 7 After Administration of

DEXILANT Once Daily for 7 Days

Dos e

C

(ng/mL)

AUC

(ng·h/mL)

CL/F

(L/h)

max

tau

30 mg

(N=17)

(53)

2886

(47)

12.8

(48)

60 mg

(N=18)

1136

(51)

5120

(58)

15.3

(49)

Age: Geriatric Population

The terminal elimination half-life of dexlansoprazole is significantly increased in geriatric subjects

compared to younger subjects (2.2 and 1.5 hours, respectively). Dexlansoprazole exhibited higher

systemic exposure (AUC) in geriatric subjects (34% higher) than younger subjects [see Use in Specific

Populations (8.5)].

Sex

In a study of 12 male and 12 female healthy subjects who received a single dose of DEXILANT 60 mg,

females had higher systemic exposure (AUC) (43% higher) than males. This difference in exposure

between males and female does not represent a significant safety concern.

Renal Impairment

Dexlansoprazole is extensively metabolized in the liver to inactive metabolites, and no parent drug is

recovered in the urine following an oral dose of dexlansoprazole. Therefore, the pharmacokinetics of

dexlansoprazole are not expected to be altered in patients with renal impairment, and no studies were

conducted in patients with renal impairment. In addition, the pharmacokinetics of lansoprazole were not

clinically different in patients with mild, moderate or severe renal impairment compared to healthy

subjects with normal renal function.

Hepatic Impairment

In a study of 12 patients with moderate hepatic impairment (Child-Pugh Class B) who received a single

dose of 60 mg DEXILANT, the systemic exposure (AUC) of bound and unbound dexlansoprazole was

approximately two times greater compared to subjects with normal hepatic function. This difference in

exposure was not due to a difference in protein binding. No studies have been conducted in patients with

severe hepatic impairment (Child-Pugh Class C) [see Dosage and Administration (2.2), Use in Specific

Populations (8.6)].

Drug-Drug Interactions

Effect of Dexlansoprazole on Other Drugs

Cytochrome P 450 Interactions

Dexlansoprazole is metabolized, in part, by CYP2C19 and CYP3A4 [see Clinical Pharmacology (12.3)].

In vitro studies have shown that dexlansoprazole is not likely to inhibit CYP isoforms 1A1, 1A2, 2A6,

2B6, 2C8, 2C9, 2D6, 2E1 or 3A4. As such, no clinically relevant interactions with drugs metabolized

by these CYP enzymes would be expected. Furthermore, in vivo studies showed that DEXILANT did

not have an impact on the pharmacokinetics of co-administered phenytoin (CYP2C9 substrate) or

theophylline (CYP1A2 substrate). The subjects' CYP1A2 genotypes in the drug-drug interaction study

with theophylline were not determined. Although in vitro studies indicated that DEXILANT has the

potential to inhibit CYP2C19 in vivo, an in vivo drug-drug interaction study in mainly CYP2C19 extensive

and intermediate metabolizers has shown that DEXILANT does not affect the pharmacokinetics of

diazepam (CYP2C19 substrate).

Clopidogrel

Clopidogrel is metabolized to its active metabolite in part by CYP2C19. A study of healthy subjects

who were CYP2C19 extensive metabolizers, receiving once daily administration of clopidogrel 75 mg

alone or concomitantly with DEXILANT 60 mg (n=40), for nine days was conducted. The mean AUC

of the active metabolite of clopidogrel was reduced by approximately 9% (mean AUC ratio was 91%,

with 90% CI of 86 to 97%) when DEXILANT was co-administered compared to administration of

clopidogrel alone. Pharmacodynamic parameters were also measured and demonstrated that the change

in inhibition of platelet aggregation (induced by 5 mcM ADP) was related to the change in the exposure

to clopidogrel active metabolite. The effect on exposure to the active metabolite of clopidogrel and on

clopidogrel-induced platelet inhibition is not considered clinically important.

Effect of Other Drugs on Dexlansoprazole

Because dexlansoprazole is metabolized by CYP2C19 and CYP3A4, inducers and inhibitors of these

enzymes may potentially alter exposure of dexlansoprazole.

12.5 Pharmacogenomics

Effect of CYP2C19 Polymorphism on Systemic Exposure of Dexlansoprazole

Systemic exposure of dexlansoprazole is generally higher in intermediate and poor metabolizers. In

male Japanese subjects who received a single dose of DEXILANT 30 or 60 mg (N=2 to 6

subjects/group), mean dexlansoprazole C

and AUC values were up to two times higher in

intermediate compared to extensive metabolizers; in poor metabolizers, mean C

was up to four times

higher and mean AUC was up to 12 times higher compared to extensive metabolizers. Though such

study was not conducted in Caucasians and African Americans, it is expected dexlansoprazole exposure

in these races will be affected by CYP2C19 phenotypes as well.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

The carcinogenic potential of dexlansoprazole was assessed using lansoprazole studies. In two 24

month carcinogenicity studies, Sprague-Dawley rats were treated orally with lansoprazole at doses of 5

to 150 mg/kg/day, about one to 40 times the exposure on a body surface (mg/m ) basis of a 50 kg person

of average height [1.46 m body surface area (BSA)] given the recommended human dose of

lansoprazole 30 mg/day.

Lansoprazole produced dose-related gastric ECL cell hyperplasia and ECL cell carcinoids in both male

and female rats [see Clinical Pharmacology (12.2)].

In rats, lansoprazole also increased the incidence of intestinal metaplasia of the gastric epithelium in

both sexes. In male rats, lansoprazole produced a dose-related increase of testicular interstitial cell

adenomas. The incidence of these adenomas in rats receiving doses of 15 to 150 mg/kg/day (four to 40

times the recommended human lansoprazole dose based on BSA) exceeded the low background

incidence (range = 1.4 to 10%) for this strain of rat.

In a 24 month carcinogenicity study, CD-1 mice were treated orally with lansoprazole doses of 15 to

600 mg/kg/day, two to 80 times the recommended human lansoprazole dose based on BSA.

Lansoprazole produced a dose-related increased incidence of gastric ECL cell hyperplasia. It also

produced an increased incidence of liver tumors (hepatocellular adenoma plus carcinoma). The tumor

incidences in male mice treated with 300 and 600 mg lansoprazole/kg/day (40 to 80 times the

recommended human lansoprazole dose based on BSA) and female mice treated with 150 to 600 mg

lansoprazole/kg/day (20 to 80 times the recommended human lansoprazole dose based on BSA)

exceeded the ranges of background incidences in historical controls for this strain of mice.

Lansoprazole treatment produced adenoma of rete testis in male mice receiving 75 to 600 mg/kg/day (10

to 80 times the recommended human lansoprazole dose based on BSA).

A 26 week p53 (+/-) transgenic mouse carcinogenicity study of lansoprazole was not positive.

Lansoprazole was positive in the Ames test and the in vitro human lymphocyte chromosomal aberration

assay. Lansoprazole was not genotoxic in the ex vivo rat hepatocyte unscheduled DNA synthesis (UDS)

test, the in vivo mouse micronucleus test or the rat bone marrow cell chromosomal aberration test.

Dexlansoprazole was positive in the Ames test and in the in vitro chromosome aberration test using

Chinese hamster lung cells. Dexlansoprazole was negative in the in vivo mouse micronucleus test.

The potential effects of dexlansoprazole on fertility and reproductive performance were assessed using

lansoprazole studies. Lansoprazole at oral doses up to 150 mg/kg/day (40 times the recommended human

lansoprazole dose based on BSA) was found to have no effect on fertility and reproductive performance

of male and female rats.

14 CLINICAL STUDIES

14.1 Healing of Erosive Esophagitis in Adults

Two multi-center, double-blind, active-controlled, randomized, eight week studies were conducted in

patients with endoscopically confirmed EE. Severity of the disease was classified based on the Los

Angeles Classification Grading System (Grades A-D). Patients were randomized to one of the

following three treatment groups: DEXILANT 60 mg once daily, DEXILANT 90 mg once daily or

lansoprazole 30 mg once daily. Patients who were H. pylori positive or who had Barrett's Esophagus

and/or definite dysplastic changes at baseline were excluded from these studies. A total of 4092

patients were enrolled and ranged in age from 18 to 90 years (median age 48 years) with 54% male.

Race was distributed as follows: 87% Caucasian, 5% Black and 8% Other. Based on the Los Angeles

Classification, 71% of patients had mild EE (Grades A and B) and 29% of patients had moderate to

severe EE (Grades C and D) before treatment.

The studies were designed to test non-inferiority. If non-inferiority was demonstrated then superiority

would be tested. Although non-inferiority was demonstrated in both studies, the finding of superiority in

one study was not replicated in the other.

The proportion of patients with healed EE at Week 4 or 8 is presented below in Table 8.

Table 8. EE Healing Rates

in Adults: All Grades

Study

Number of

Patients (N)

Treatment

Group

(daily)

Week 4

%

Healed

Week 8

%

Healed

(95% CI) for the Treatment

Difference

(DEXILANT–

Lansoprazole) by Week 8

CI = Confidence interval

1

DEXILANT 60

(-1.5, 6.1)

Lansoprazole 30

2

DEXILANT 60

(2.2, 10.5)

Lansoprazole 30

DEXILANT 90 mg once daily was studied and did not provide additional clinical benefit over

DEXILANT 60 mg once daily.

14.2 Maintenance of Healed Erosive Esophagitis and Relief of Heartburn in Adults

*

Based on crude rate estimates, patients who did not have endoscopically documented healed EE and

prematurely discontinued were considered not healed.

Patients with at least one post-baseline endoscopy.

Primary efficacy endpoint.

Demonstrated non-inferiority to lansoprazole.

A multi-center, double-blind, placebo-controlled, randomized study was conducted in patients who

successfully completed an EE study and showed endoscopically confirmed healed EE. Maintenance of

healing and symptom resolution over a six month period was evaluated with DEXILANT 30 or 60 mg

once daily compared to placebo. A total of 445 patients were enrolled and ranged in age from 18 to 85

years (median age 49 years), with 52% female. Race was distributed as follows: 90% Caucasian, 5%

Black and 5% Other.

Sixty six percent of patients treated with 30 mg of DEXILANT remained healed over the six month time

period as confirmed by endoscopy (see Table 9).

Table 9. Maintenance Rates

of Healed EE at Month 6 in

Adults

Number of

Patients

(N)

Treatment Group

(daily)

Maintenance Rate

(%)

DEXILANT 30 mg

66.4

Placebo

14.3

DEXILANT 60 mg once daily was studied and did not provide additional clinical benefit over

DEXILANT 30 mg once daily.

The effect of DEXILANT 30 mg on maintenance of relief of heartburn was also evaluated. Upon entry

into the maintenance study, a majority of patients' baseline heartburn severity was rated as none.

DEXILANT 30 mg demonstrated a statistically significantly higher percent of 24 hour heartburn-free

periods compared to placebo over the six month treatment period (see Table 10). The majority of patients

treated with placebo discontinued due to relapse of EE between Month 2 and Month 6.

Table 10. Median Percentage of 24 Hour Heartburn-Free Periods of the Maintenance

of Healed EE Study in Adults

Overall Treatment

Month 1

Month 6

Treatment

Group

(daily)

N

Heartburn-

Free 24

hour

Periods

(%)

N

Heartburn-

Free 24

hour

Periods

(%)

N

Heartburn-

Free 24

hour

Periods

(%)

DEXILANT

30 mg

96.1

96.7

98.3

Placebo

28.6

28.6

73.3

14.3 Treatment of Symptomatic Non-Erosive GERD in Adults

A multi-center, double-blind, placebo-controlled, randomized, four week study was conducted in

patients with a diagnosis of symptomatic non-erosive GERD made primarily by presentation of

symptoms. These patients who identified heartburn as their primary symptom, had a history of heartburn

for six months or longer, had heartburn on at least four of seven days immediately prior to

*

Based on crude rate estimates, patients who did not have

endoscopically documented relapse and prematurely discontinued

were considered to have relapsed.

Patients with at least one post-baseline endoscopy

Statistically significant vs placebo

*

Secondary efficacy endpoint

Statistically significant vs placebo

randomization and had no esophageal erosions as confirmed by endoscopy. However, patients with

symptoms which were not acid-related may not have been excluded using these inclusion criteria.

Patients were randomized to one of the following treatment groups: DEXILANT 30 mg daily, 60 mg

daily, or placebo. A total of 947 patients were enrolled and ranged in age from 18 to 86 years (median

age 48 years) with 71% female. Race was distributed as follows: 82% Caucasian, 14% Black and 4%

Other.

DEXILANT 30 mg provided statistically significantly greater percent of days with heartburn-free 24

hour periods over placebo as assessed by daily diary over four weeks (see Table 11). DEXILANT 60

mg once daily was studied and provided no additional clinical benefit over DEXILANT 30 mg once

daily.

Table 11. Median Percentages of 24 Hour Heartburn-Free Periods

During the 4 Week Treatment Period of the Symptomatic Non-Erosive

GERD Study in Adults

N

Treatment Group

(daily)

Heartburn-Free 24

hour Periods

(%)

DEXILANT 30 mg

54.9

Placebo

18.5

A higher percentage of patients on DEXILANT 30 mg had heartburn-free 24 hour periods compared to

placebo as early as the first three days of treatment and this was sustained throughout the treatment

period (percentage of patients on Day 3: DEXILANT 38% vs placebo 15%; on Day 28: DEXILANT

63% vs placebo 40%).

14.4 Pediatric GERD

Use of DEXILANT in patients 12 to 17 years of age is supported by evidence from adequate and well-

controlled studies of DEXILANT capsules in adults, with additional safety, efficacy, and

pharmacokinetic data from studies performed in pediatric patients.

Healing of EE, Maintenance of Healed EE and Relief of Heartburn

In a multi-center, 36 week trial, 62 patients 12 to 17 years of age with a documented history of GERD

for at least three months and endoscopically-proven erosive esophagitis (EE) were enrolled to evaluate

the healing of EE, maintenance of healed EE and relief of heartburn, followed by an additional 12 weeks

without treatment. The median age was 15 years, with males accounting for 61% of the patients. Based

on the Los Angeles Classification Grading Scale, 97% of patients had mild EE (Grades A and B), and

3% of patients had moderate to severe EE (Grades C and D) before treatment.

In the first eight weeks, 62 patients were treated with DEXILANT 60 mg once daily to evaluate the

healing of EE. Of the 62 patients, 58 patients completed the eight week trial, and 51 (88%) patients

achieved healing of EE, as confirmed by endoscopy, over eight weeks of treatment (see Table 12).

Table 12. Healing of EE at Week 8 in Pediatric Patients 12 to 17 Years of

Age

DEXILANT 60 mg

Proportion of randomized patients

healed

n (%)

95% CI

51/62 (82%)

(70, 91)

Statistically significant vs placebo

Proportion of evaluable patients

healed

n (%)

95% CI

51/58 (88%)

(77, 95)

After the initial eight weeks of treatment, all 51 patients with healed EE were randomized to receive

treatment with DEXILANT 30 mg or placebo, once daily for an additional 16 weeks to evaluate

maintenance of healing and symptom resolution. Maintenance of healing was assessed by endoscopy at

Week 24. Of the 51 patients randomized, 13 patients discontinued early. Of these, five patients did not

undergo post-baseline endoscopy. Eighteen of 22 (82%) evaluable patients treated with DEXILANT 30

mg remained healed over the 16 week treatment period as confirmed by endoscopy, compared with 14

of 24 (58%) in placebo (see Table 13).

Table 13. Maintenance of Healed EE at Week 24 in Pediatric Patients 12

to 17 Years of Age

DEXILANT 30

mg

Placebo

Proportion of randomized patients who

maintained healing of EE

n (%)

95% Cl

18/25 (72%)

(51, 88)

14/26 (54%)

(33, 73)

Proportion of evaluable patients who

maintained healing of EE

n (%)

95% Cl

18/22 (82%)

(60, 95)

14/24 (58%)

(37, 78)

Relief of heartburn was assessed in randomized patients during the 16 week maintenance period. The

median percentage of 24 hour heartburn-free periods was 87% for those receiving DEXILANT 30 mg

compared to 68% for those receiving placebo.

Out of the 32 patients who maintained healing of EE at the end of the 16 week maintenance period, 27

patients (16 treated with DEXILANT and 11 treated with placebo during the double-blind phase) were

followed for an additional 12 weeks without therapy. Twenty four of the 27 patients completed the 12

week follow-up period. One patient required treatment with acid suppression therapy.

Treatment of Symptomatic Non-Erosive GERD

In a single-arm, open-label, multi-center trial, 104 pediatric patients 12 to 17 years of age with

symptomatic non-erosive GERD were treated with DEXILANT 30 mg once daily, for four weeks to

evaluate safety and effectiveness. Patients had a documented history of GERD symptoms for at least

three months prior to screening, reported heartburn on at least three out of seven days during screening,

and had no esophageal erosions as confirmed by endoscopy. The median age was 15 years, with

females accounting for 70% of the patients. During the four week treatment period, the median

percentage of 24 hour heartburn free periods was 47%.

16 HOW SUPPLIED/STORAGE AND HANDLING

Product: 50090-4374

Reported are the exact confidence limits.

Includes only patients who underwent post-baseline endoscopy.

*

Following eight weeks of initial therapy and 16 weeks of maintenance therapy.

Reported are the exact confidence limits.

Includes patients with at least one post-baseline endoscopy.

Product: 50090-4374

NDC: 50090-4374-0 90 CAPSULE, DELAYED RELEASE in a BOTTLE

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for

Use).

Adverse Reactions

Advise patients to report to their healthcare provider if they experience any signs or symptoms

consistent with:

Hypersensitivity Reactions [see Contraindications (4)]

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 B12) Deficiency [see Warnings and Precautions (5.6)]

Hypomagnesemia [see Warnings and Precautions (5.7)]

Drug Interactions

Advise patients to report to their healthcare provider if they are taking rilpivirine-containing products

[see Contraindications (4)] or high-dose methotrexate [see Warnings and Precautions (5.9)].

Pregnancy

Advise a pregnant woman of the potential risk to a fetus. Advise females of reproductive potential to

inform their healthcare provider of a known or suspected pregnancy [see Use in Specific Populations

(8.1)].

Administration

Take without regard to food.

Missed doses: If a dose is missed, administer as soon as possible. However, if the next scheduled

dose is due, do not take the missed dose, and take the next dose on time. Do not take two doses at one

time to make up for a missed dose.

Swallow whole; do not chew.

Can be opened and sprinkled on applesauce for patients who have trouble swallowing the capsule.

Alternatively, the capsule can be administered with water via oral syringe or NG tube, as described

in the Instructions for Use.

MEDICATION GUIDE

DEXILANT (decks-i-launt)

(dexlans oprazole)

delayed-release capsules, for oral use

Read this Medication Guide before you start taking DEXILANT and each time you get a refill. There

may be new information. This information does not take the place of talking to your doctor about your

medical condition or your treatment.

What is the most important information that I should know about DEXILANT?

DEXILANT may help your acid-related symptoms, but you could still have serious stomach

problems. Talk with your doctor.

DEXILANT can cause serious side effects, including:

A type of kidney problem (acute interstitial nephritis). Some people who take proton pump

inhibitor (PPI) medicines, including DEXILANT, may develop a kidney problem called acute

interstitial nephritis, that can happen at any time during treatment with PPI medicines. 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. DEXILANT may increase your risk of getting severe diarrhea. This diarrhea may be

caused by an infection (Clostridium difficile) 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

DEXILANT 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 DEXILANT.

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

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.

DEXILANT can have other serious side effects. See "What are the possible side effects of

DEXILANT?"

What is DEXILANT?

DEXILANT is a prescription medicine called a proton pump inhibitor (PPI). DEXILANT reduces the

amount of acid in your stomach.

DEXILANT is used in people 12 years of age and older:

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

esophagitis or EE)

for up to 6 months in adults and up to 16 weeks in children 12 to 17 years of age to continue healing

of erosive esophagitis and relief of heartburn

for 4 weeks to treat heartburn related to gastroesophageal reflux disease (GERD)

GERD happens when acid from your stomach enters 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.

It is not known if DEXILANT is safe and effective in children under 12 years of age.

DEXILANT is not effective for symptoms of GERD in children under 1 year of age.

Who should not take DEXILANT?

Do not take DEXILANT if you:

are allergic to dexlansoprazole or any of the other ingredients in DEXILANT. See the end of this

Medication Guide for a complete list of ingredients in DEXILANT.

are taking a medicine that contains rilpivirine (EDURANT, COMPLERA) used to treat HIV-1

(Human Immunodeficiency Virus)

What should I tell my doctor before taking DEXILANT?

Before you take DEXILANT, tell your doctor if you:

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. DEXILANT may harm your unborn baby. Talk to your

doctor about the possible risks to an unborn baby if DEXILANT is taken during pregnancy.

are breastfeeding or plan to breastfeed. It is not known if DEXILANT passes into your breast milk

or if it will affect your baby or your breast milk. Talk to your doctor about the best way to feed

your baby if you take DEXILANT.

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

medicines, vitamins, and herbal supplements. DEXILANT may affect how other medicines work, and

other medicines may affect how DEXILANT works. Especially tell your doctor if you take

methotrexate (Otrexup, Rasuvo, Trexall).

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

a new medicine.

How should I take DEXILANT?

Take DEXILANT exactly as prescribed by your doctor.

Do not change your dose or stop taking DEXILANT without talking to your doctor first.

Take DEXILANT with or without food.

Swallow DEXILANT whole. Do not chew the capsules or the granules that are in the capsules.

If you have trouble swallowing a whole capsule, you can open the capsule and take the contents in

applesauce. See the "Instructions for Use" at the end of this Medication Guide for instructions on

how to take DEXILANT with applesauce.

See the "Instructions for Use" at the end of this Medication Guide for instructions on how to mix

and give DEXILANT with water using an oral syringe or through a nasogastric tube.

If you miss a dose of DEXILANT, take it as soon as you remember. If it is almost time for your next

dose, do not take the missed dose. Take your next dose at your regular time. Do not take 2 doses at

the same time to make up for the missed dose.

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

1222 right away or go to the nearest hospital emergency room.

What are the possible side effects of DEXILANT?

DEXILANT may cause serious side effects, including:

See "What is the most important information I should know about DEXILANT?"

Vitamin B12 deficiency. DEXILANT reduces the amount of acid in your stomach. Stomach acid is

needed to absorb Vitamin B12 properly. Talk with your doctor about the possibility of Vitamin B12

deficiency if you have been on DEXILANT 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 develop 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 DEXILANT, or

during treatment, if you will be taking DEXILANT for a long period of time.

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 growth called fundic gland polyps,

especially after taking PPI medicines for more than 1 year.

The most common side effects of DEXILANT in adults include:

diarrhea

stomach pain

nausea

common cold

vomiting

The most common side effects of DEXILANT in children 12 to 17 years of age include:

headache

stomach pain

diarrhea

pain or swelling (inflammation) in your mouth, nose or throat

Other side effects:

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

DEXILANT:

rash

face swelling

throat tightness

difficulty breathing

Your doctor may stop DEXILANT if these symptoms happen.

Tell your doctor if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of DEXILANT. 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.

How should I store DEXILANT?

Store DEXILANT at room temperature between 68°F to 77°F (20°C to 25°C).

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

General information about the safe and effective use of DEXILANT

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

use DEXILANT for a condition for which it was not prescribed. Do not give DEXILANT 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 DEXILANT. If you would

like more information, talk with your doctor. You can ask your doctor or pharmacist for information

about DEXILANT that is written for health professionals.

For more information, go to www.DEXILANT.com or call 1-877-825-3327.

What are the ingredients in DEXILANT?

Active ingredient: dexlansoprazole.

Inactive ingredients: sugar spheres, magnesium carbonate, sucrose, low-substituted hydroxypropyl

cellulose, titanium dioxide, hydroxypropyl cellulose, hypromellose 2910, talc, methacrylic acid

copolymers, polyethylene glycol 8000, triethyl citrate, polysorbate 80, and colloidal silicon dioxide.

The capsule shell is made of hypromellose, carrageenan and potassium chloride. Based on the capsule

shell color, blue contains FD&C Blue No. 2 aluminum lake; gray contains black ferric oxide; and both

contain titanium dioxide.

INSTRUCTIONS FOR USE

DEXILANT (decks-i-launt)

(dexlans oprazole)

delayed-release capsules, for oral use

Taking DEXILANT with applesauce:

1. Place 1 tablespoon of applesauce into a clean container.

2. Carefully open the capsule and sprinkle the granules onto the applesauce.

3. Swallow the applesauce and granules right away. Do not chew the granules. Do not save the

applesauce and granules for later use.

Giving DEXILANT with water using an oral syringe:

1. Place 20 mL of water into a clean container.

2. Carefully open the capsule and empty the granules into the container of water.

3. Use an oral syringe to draw up the water and granule mixture.

4. Gently swirl the oral syringe to keep the granules from settling.

5. Place the tip of the oral syringe in your mouth. Give the medicine right away. Do not save the water

and granule mixture for later use.

6. Refill the syringe with 10 mL of water and swirl gently. Place the tip of the oral syringe in your

mouth and give the medicine that is left in the syringe.

7. Repeat step 6.

Giving DEXILANT with water through a nasogastric tube (NG tube):

For people who have an NG tube that is size 16 French or larger, DEXILANT may be given as

follows:

1. Place 20 mL of water into a clean container.

2. Carefully open the capsule and empty the granules into the container of water.

3. Use a 60 mL catheter-tip syringe to draw up the water and granule mixture.

4. Gently swirl the catheter-tip syringe to keep the granules from settling.

5. Connect the catheter-tip syringe to the NG tube.

6. Give the mixture right away through the NG tube that goes into the stomach. Do not save the water

and granule mixture for later use.

7. Refill the catheter-tip syringe with 10 mL of water and swirl gently. Flush the NG tube with the

water.

8. Repeat step 7.

How should I store DEXILANT?

Store DEXILANT at room temperature between 68°F to 77°F (20°C to 25°C).

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

This Medication Guide and Instructions for Use have been approved by the U.S. Food and Drug

Administration.

Distributed by:

Takeda Pharmaceuticals America, Inc.

Deerfield, IL 60015

Revised: June 2018

DEXILANT is a trademark of Takeda Pharmaceuticals U.S.A., Inc. registered with the U.S. Patent and

Trademark Office.

All other trademark names are the property of their respective owners.

©2009 – 2018 Takeda Pharmaceuticals America, Inc.

DEX006 R30

dexlans oprazole

DEXILANT

dexlansoprazole capsule, delayed release

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:50 0 9 0 -4374(NDC:6 476 4-175)

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

DEXLANSO PRAZO LE (UNII: UYE4T5I70 X) (DEXLANSOPRAZOLE - UNII:UYE4T5I70 X)

DEXLANSOPRAZOLE

6 0 mg

Inactive Ingredients

Ingredient Name

Stre ng th

Metha crylic Acid - Methyl Metha cryla te Co po lymer ( 1:1) (UNII: 74G4R6 TH13)

Metha crylic Acid - Methyl Metha cryla te Co po lymer ( 1:2 ) (UNII: 5KY6 8 S2577)

Metha crylic Acid - Ethyl Acryla te Co po lymer ( 1:1) Type A (UNII: NX76 LV5T8 J)

ma g nesium ca rbo na te (UNII: 0 E53J9 27NA)

sucro se (UNII: C151H8 M554)

lo w-substituted hydro xypro pyl cellulo se, unspecified (UNII: 216 5RE0 K14)

tita nium dio xide (UNII: 15FIX9 V2JP)

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

HYPRO MELLO SE 2 9 10 ( 6 MPA.S) (UNII: 0 WZ8 WG20 P6 )

ta lc (UNII: 7SEV7J4R1U)

po lyethylene g lyco l 8 0 0 0 (UNII: Q6 6 2QK8 M3B)

triethyl citra te (UNII: 8 Z9 6 QXD6 UM)

po lyso rba te 8 0 (UNII: 6 OZP39 ZG8 H)

silico n dio xide (UNII: ETJ7Z6 XBU4)

ca rra g eena n (UNII: 5C6 9 YCD2YJ)

po ta ssium chlo ride (UNII: 6 6 0 YQ9 8 I10 )

a luminum o xide (UNII: LMI26 O6 9 33)

FD&C Blue No . 2 (UNII: L0 6 K8 R7DQK)

STARCH, CO RN (UNII: O8 232NY3SJ)

A-S Medication Solutions

Product Characteristics

Color

BLUE (o paque)

S core

no sco re

S hap e

CAPSULE

S iz e

18 mm

Flavor

Imprint Code

TAP;6 0

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:50 0 9 0 -4374-0

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

0 6 /20 /20 19

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

NDA0 2228 7

0 4/12/20 10

Labeler -

A-S Medication Solutions (830016429)

Establishment

Name

Ad d re s s

ID/FEI

Busine ss Ope rations

A-S Medicatio n So lutio ns

8 30 0 16 429

RELABEL(50 0 9 0 -4374)

Revised: 7/2019

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