Dexlansoprazole Drug Information

Recommended Dosage in Patients 12 Years of Age and Older

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 dexlansoprazole delayed-release capsules once daily for up to eight weeks. Dexlansoprazole delayed-release capsule 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, dexlansoprazole delayed-release 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 pellets on applesauce. 4.

Swallow applesauce and pellets immediately. Do not chew pellets. Do not save the applesauce and pellets 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 pellets 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 pellets from settling. 4. Administer the mixture immediately into the mouth. Do not save the water and pellet mixture for later use. 5.

Refill the syringe with 10 mL of water, swirl gently, and administer. 6. Administration with Water via a NG Tube (≥16 French) 1. Refill the catheter-tip syringe with 10 mL of water, swirl gently, and flush the tube. 5.

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 dexlansoprazole 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. Common Adverse Reactions The most common adverse reactions (>2%) that occurred at a higher incidence for dexlansoprazole than placebo in the controlled studies are presented in Table 2. s Resulting in Discontinuation In controlled clinical studies, the most common adverse reaction leading to discontinuation from dexlansoprazole 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 dexlansoprazole 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 dexlansoprazole 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. 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 dexlansoprazole.

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of dexlansoprazole. 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, SJS/TEN (some fatal), DRESS, AGEP, erythema multiforme Infections and Infestations: Clostridium difficile-associated diarrhea Metabolism and Nutrition Disorders: hypomagnesemia, hypocalcemia, hypokalemia, hyponatremia Musculoskeletal System Disorders: bone fracture Nervous System Disorders: cerebrovascular accident, transient ischemic attack Renal and Genitourinary Disorders: acute renal failure, erectile dysfunction Respiratory, Thoracic and Mediastinal Disorders: pharyngeal edema, throat tightness Skin and Subcutaneous Tissue Disorders: generalized rash, leukocytoclastic vasculitis

Tables 3 and 4 include drugs with clinically important drug interactions and interaction with diagnostics when administered concomitantly with dexlansoprazole 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 Dexlansoprazole and Interactions with Diagnostics Antiretrovirals Clinical Impact: The effect of PPIs on antiretroviral drugs is variable. Intervention: Rilpivirine-containing products: Concomitant use with dexlansoprazole is contraindicated. See prescribing information.

No formal drug interaction studies of high-dose methotrexate with PPIs have been conducted. The increased CgA level may cause false positive results in diagnostic investigations for neuroendocrine tumors. Temporarily stop dexlansoprazole treatment at least 30 days before assessing to allow gastrin levels to return to baseline.

Decreased exposure of dexlansoprazole when used concomitantly with strong inducers. Intervention: St. 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.

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 the 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 US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 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,. 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, and for spontaneous abortions OR=1.29, ).

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 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 ) 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.

Pediatric Use The safety and effectiveness of dexlansoprazole have been established in pediatric patients 12 years 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 dexlansoprazole in this age group is supported by evidence from adequate and well-controlled studies of dexlansoprazole in adults with additional safety, efficacy and pharmacokinetic data in pediatric patients 12 to 17 years of age. The adverse reaction profile in patients 12 to 17 years of age was similar to adults.

The safety and effectiveness of dexlansoprazole have not been established in pediatric patients less than 12 years of age. Dexlansoprazole is not recommended in pediatric patients less than two years of age. Nonclinical studies in juvenile rats treated with lansoprazole (the racemic mixture) have demonstrated adverse effects of heart valve thickening and bone changes at dexlansoprazole exposures which are expected to be similar to or higher than the dexlansoprazole exposure in pediatric patients one year to two years of age, as described below in Juvenile Animal Toxicity Data.

The use of dexlansoprazole is not recommended for the treatment of symptomatic GERD in pediatric patients one month to less than one year of age because lansoprazole was not shown to be effective in a multicenter, double-blind controlled trial. Juvenile Animal Toxicity Data Heart Valve Thickening In two oral toxicity studies, thickening of the mitral heart valve occurred in juvenile rats treated with lansoprazole. Heart valve thickening was observed primarily with oral dosing initiated on postnatal Day 7 (age equivalent to neonatal humans) and postnatal Day 14 (human age equivalent of approximately one year) at doses of 250 mg/kg/day and higher (at postnatal Day 7 and postnatal Day 14 respectively, 2.5 and 1.8 times the expected dexlansoprazole exposure based on AUC in pediatric patients one year to two years of age).

The treatment durations associated with heart valve thickening ranged from 5 days to 8 weeks. The findings reversed or trended towards reversibility after a 4-week drug-free recovery period. The incidence of heart valve thickening after initiation of dosing on postnatal Day 21 (human age equivalent of approximately two years) was limited to a single rat (1/24) in groups given 500 mg/kg/day for 4 or 8 weeks (2.1 times the expected dexlansoprazole exposure based on AUC in pediatric patients one year to two years of age).

Based on the low incidence of heart valve thickening in 21-day old rats and the equivalent human age, the risk of heart valve injury does not appear to be relevant to patients two years of age and older. Bone Changes In an eight-week oral toxicity study of lansoprazole in juvenile rats with dosing initiated on postnatal Day 7, doses equal to or greater than 100 mg/kg/day (dexlansoprazole exposure based on AUC approximately equal to that in pediatric patients one year to two years of age) 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 four-week recovery period. Longer term data were not collected.

• Dexlansoprazole delayed-release capsules are contraindicated in patients with known hypersensitivity to any component of the formulation. Hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute tubulointerstitial nephritis and urticaria.
• PPIs, including dexlansoprazole delayed-release capsules, are contraindicated with rilpivirine-containing products.
• Patients with known hypersensitivity to any component of the formulation.
• Patients receiving rilpivirine-containing products.

There have been no reports of significant overdose with dexlansoprazole. Multiple doses of dexlansoprazole 120 mg and a single dose of dexlansoprazole 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 dexlansoprazole 60 mg.

Nonserious adverse reactions observed with twice daily doses of dexlansoprazole 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.