LANSOPRAZOLE 30MG CAPS 28'S

Indications/Uses Healing of Erosive Esophagitis: Dexlansoprazole (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: Dexlansoprazole (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: Dexlansoprazole (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. 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 (Dexilant) once daily for up to eight weeks. Dexlansoprazole (Dexilant) is not recommended in patients with severe hepatic impairment (Child-Pugh Class C) [see Hepatic Impairment under Precautions]. 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 (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. Overdosage There have been no reports of significant overdose with Dexlansoprazole (Dexilant). Multiple doses of Dexlansoprazole (Dexilant) 120 mg and a single dose of Dexlansoprazole (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 Dexlansoprazole (Dexilant) 60 mg. Nonserious adverse reactions observed with twice daily doses of Dexlansoprazole (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. Administration May be taken with or without food: Swallow whole. For patients w/ swallowing difficulties, open cap & sprinkle contents in 1 tbsp applesauce. Swallow immediately, do not chew. Alternatively, empty contents in 20 mL water & administer using oral syringe or via a nasogastric tube (≥16 French). Contraindications Dexlansoprazole (Dexilant) is contraindicated in patients with known hypersensitivity to any component of the formulation [see Description]. Hypersensitivity reactions, may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute tubulointerstitial nephritis and urticaria [see Precautions and Adverse Reactions]. PPIs, including Dexlansoprazole (Dexilant), are contraindicated with rilpivirine-containing products [see Interactions]. Special Precautions Presence of Gastric Malignancy: In adults, symptomatic response to therapy with Dexlansoprazole (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 Dexlansoprazole (Dexilant) and evaluate patients with suspected acute TIN [see Contraindications]. Clostridium difficile-Associated Diarrhea: Published observational studies suggest that PPI therapy like Dexlansoprazole (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]. 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 [see Dosage & Administration and Adverse Reactions]. 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 Dexlansoprazole (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 Dexlansoprazole (Dexilant). 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]. 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 Interactions and Pharmacology under Actions]. 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 Interactions]. 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: Dexlansoprazole (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 [see Use in Children as follows]. Hepatic Impairment: No dosage adjustment for Dexlansoprazole (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 Dexlansoprazole (Dexilant), there was a significant increase in systemic exposure of dexlansoprazole compared to healthy subjects with normal hepatic function [see Pharmacology under Actions]. Therefore, for patients with moderate hepatic impairment (Child-Pugh Class B), dosage reduction is recommended for the healing of EE [see Dosage & Administration]. No studies have been conducted in patients with severe hepatic impairment (Child-Pugh Class C); the use of Dexlansoprazole (Dexilant) is not recommended for these patients [see Dosage & Administration]. Use in Children: The safety and effectiveness of Dexlansoprazole (Dexilant) 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 (Dexilant) in this age group is supported by evidence from adequate and well-controlled studies of Dexlansoprazole (Dexilant) 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 [see Dosage & Administration, Adverse Reactions, Pharmacology: Clinical Studies under Actions]. The safety and effectiveness of Dexlansoprazole (Dexilant) have not been established in pediatric patients less than 12 years of age. Dexlansoprazole (Dexilant) is not recommended in pediatric patients less than two years of age [see Precautions]. 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 in Juvenile Animal Toxicity Data as follows. The use of Dexlansoprazole (Dexilant) 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. Use in the Elderly: Of the total number of patients (n=4548) in clinical studies of Dexlansoprazole (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 Pharmacology under Actions]. Use In Pregnancy & Lactation 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 as follows). 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 as follows). 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 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. 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 Dexlansoprazole (Dexilant) and any potential adverse effects on the breastfed child from Dexlansoprazole (Dexilant) or from the underlying maternal condition. Adverse Reactions The following serious adverse reactions are described as follows and elsewhere in labeling: Acute Tubulointerstitial Nephritis [see Precautions]; Clostridium difficile-Associated Diarrhea [see Precautions]; Bone Fracture [see Precautions]; Cutaneous and Systemic Lupus Erythematosus [see Precautions]; Cyanocobalamin (Vitamin B12) Deficiency [see Precautions]; Hypomagnesemia [see Precautions]; Fundic Gland Polyps [see Precautions]; Risk of Heart Valve Thickening in Pediatric Patients Less than Two Years of Age [see Precautions]. 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 (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 Dexlansoprazole (Dexilant) 30 mg, 2218 patients on Dexlansoprazole (Dexilant) 60 mg, and 1363 patients on lansoprazole 30 mg once daily.