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: C 16 H 14 F 3 N 3 O 2 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 . 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 (or FD&C Blue No. 2 aluminum lake); gray contains black ferric oxide; and both contain titanium dioxide. Chemical Structure

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). Maintenance of healed EE and relief of heartburn. Treatment of symptomatic non-erosive gastroesophageal reflux disease (GERD)

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

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

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.

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". Delayed-release capsules: 30 mg and 60 mg.

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. Administration Instructions : Take without regard to food. Swallow whole; do not chew. See full prescribing information for alternative administration options

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 Capsules 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

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

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: Place one tablespoonful of applesauce into a clean container. Open capsule. Sprinkle intact granules on applesauce. 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 Open the capsule and empty the granules into a clean container with 20 mL of water. Withdraw the entire mixture into a syringe. Gently swirl the syringe in order to keep granules from settling. Administer the mixture immediately into the mouth. Do not save the water and granule mixture for later use. Refill the syringe with 10 mL of water, swirl gently, and administer. Refill the syringe again with 10 mL of water, swirl gently, and administer. Administration with Water via a NG Tube (≥16 French) Open the capsule and empty the granules into a clean container with 20 mL of water. Withdraw the entire mixture into a catheter-tip syringe. 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. Refill the catheter-tip syringe with 10 mL of water, swirl gently, and flush the tube. Refill the catheter-tip syringe again with 10 mL of water, swirl gently, and administer.

Gastric Malignancy : In adults, symptomatic response with DEXILANT does not preclude the presence of gastric malignancy. Consider additional follow-up and diagnostic testing. Acute Tubulointerstitial Nephritis : Discontinue treatment and evaluate patients. Clostridium difficile -Associated Diarrhea : PPI therapy may be associated with increased risk. 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. Severe Cutaneous Adverse Reactions: Discontinue at the first signs or symptoms of severe cutaneous adverse reactions or other signs of hypersensitivity and consider further evaluation. Cutaneous and Systemic Lupus Erythematosus : Mostly cutaneous; new onset or exacerbation of existing disease; discontinue DEXILANT and refer to specialist for evaluation. Cyanocobalamin (Vitamin B12) Deficiency : Daily long-term use (e.g., longer than 3 years) may lead to malabsorption or a deficiency of cyanocobalamin. Hypomagnesemia and Mineral Metabolism : Reported rarely with prolonged treatment with PPIs. 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. ( 5.9 , 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. ( 5.10 , 7 ) Fundic Gland Polyps : Risk increases with long-term use, especially beyond 1 year. Use the shortest duration of therapy. Risk of Heart Valve Thickening in Pediatric Patients Less than Two Years of Age : DEXILANT is not recommended in pediatric patients less than 2 years of age. ( 5.12 , 8.4 ) 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

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

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

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

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

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 nondrug 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

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

Hypomagnesemia and Mineral Metabolism Hypomagnesemia, symptomatic and asymptomatic, has been reported rarely in patients treated with PPIs for at least three months, in most cases after a year of therapy. Serious adverse events include tetany, arrhythmias, and seizures. Hypomagnesemia may lead to hypocalcemia and/or hypokalemia and may exacerbate underlying hypocalcemia in at-risk patients. In most patients, treatment of hypomagnesemia required magnesium replacement and discontinuation of the PPI. For patients expected to be on prolonged treatment or who take PPIs with medications such as digoxin or drugs that may cause hypomagnesemia (e.g., diuretics), health care professionals may consider monitoring magnesium levels prior to initiation of PPI treatment and periodically . Consider monitoring magnesium and calcium levels prior to initiation of DEXILANT and periodically while on treatment in patients with a preexisting risk of hypocalcemia (e.g., hypoparathyroidism). Supplement with magnesium and/or calcium as necessary. If hypocalcemia is refractory to treatment, consider discontinuing the PPI

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

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

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

Risk of Heart Valve Thickening in Pediatric Patients Less Than Two Years of Age DEXILANT is not recommended in pediatric patients less than two years of age. Nonclinical studies in juvenile rats with lansoprazole have demonstrated an adverse effect of heart valve thickening. Dexlansoprazole is the R-enantiomer of lansoprazole .

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 Coadministered 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. Intervention: Rilpivirine-containing products : Concomitant use with DEXILANT is contraindicated . See prescribing information. 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 . 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): Coadministration 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 . Intervention: Temporarily stop DEXILANT treatment at least 14 days before assessing CgA levels and consider repeating the test if initial CgA levels are high. If serial tests are performed (e.g., for monitoring), the same commercial laboratory should be used for testing, as reference ranges between tests may vary. Interaction with Secretin Stimulation Test Clinical Impact: Hyper-response in gastrin secretion in response to secretin stimulation test, falsely suggesting gastrinoma. Intervention: Temporarily stop DEXILANT treatment at least 30 days before assessing to allow gastrin levels to return to baseline . False Positive Urine Tests for THC Clinical Impact: There have been reports of false positive urine screening tests for tetrahydrocannabinol (THC) in patients receiving PPIs. Intervention: An alternative confirmatory method should be considered to verify positive results. Table 4. Clinically Relevant Interactions Affecting DEXILANT When Coadministered with Other Drugs and Substances CYP2C19 or CYP3A4 Inducers Clinical Impact: Decreased exposure of dexlansoprazole when used concomitantly with strong inducers . 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 . Intervention: Voriconazole : See prescribing information. See full prescribing information for a list of clinically important drug interactions.