Dexilant

Name: Dexilant

What is Dexilant (Dexlansoprazole)?

Dexilant is the brand name of dexlansoprazole, a prescription drug used to treat gastroesophageal reflux disease or GERD.

GERD is a condition that causes stomach acid to enter the esophagus, the tube connecting your mouth to your stomach. People who have GERD will notice a burning feeling in their chests or throats, a sour taste, or burping.

Dexilant is a proton pump inhibitor, which relies on a dual delayed-release action (combining two different types of granules in one pill) to reduce the acid in your stomach. The first release of medicine occurs within an hour of taking it; the second hits four to five hours later.

The drug is prescribed to adults for up to 8 weeks to heal acid-related damage in the lining of the esophagus, known as erosive esophagitis. Your treatment may be ongoing for up to 6 months in order to continue the healing process and relieve heartburn. In addition, your doctor may prescribe Dexilant for a four-week period to treat heartburn-related GERD.

In addition to the uses listed on the labeling, your doctor may prescribe Dexilant to treat stomach ulcers. Never use this medicine for any off-label purposes unless directed by your doctor.

Dexilant Warnings

Dexilant is designed to treat those 18 and over. It’s unknown if this drug is safe or effective in those under 18.

Dexilant can cause a serious allergic reaction. If you are using Dexilant and develop a rash, throat tightness, difficulty breathing, or notice that your face is swelling, you need to let your doctor know right away.

Dexilant may increase your risk of severe diarrhea. Let your physician know immediately if you have stomach pain, a watery stool, or a fever that doesn’t go away.

Taking multiple daily doses of a proton pump inhibitor like Dexilant for a year or longer, may increase your risk of hip, wrist, or spine fractures. In addition, people who take this medicine may experience low magnesium levels.

If your heartburn is accompanied by unexplained weight loss, lightheadedness, sweating or dizziness as well as chest, jaw, arm and shoulder pain — especially in conjunction with shortness of breath or unusual sweating — see your doctor right away.

Be sure to tell your doctor if you have a history of liver disease. You should also mention any products you are taking that contain iron, ketoconazole, tacrolimus or methotrexate, as well as drugs like ampicillin (Principen), atazanavir (Reyataz), erlotinib (Tarceva) and digoxin (Digox and Lanoxin).

If you are currently using warfarin (Jantoven or Coumadin) and Dexilant together, you may need to be monitored closely since serious problems could occur.

Pregnancy and Dexilant

It’s unknown how this medication affects pregnant or breastfeeding women, so tell your doctor if you are pregnant or breastfeeding or plan to become pregnant or breastfeed.

Dexilant Dosage

Once you begin taking Dexilant, don't stop taking it or change the dose without first consulting your doctor.

The recommended dose of Dexilant for those with erosive esophagitis is 60 milligrams (mg) once a day for up to eight weeks, and 30 mg once a day to maintain the healing thereafter. If you have liver problems, your doctor may adjust this dose.

The recommended dose for those with GERD-associated heartburn is 30 mg once a day for four weeks.

You can take Dexilant with or without food, but if your symptoms occur after a meal, your doctor may tell you to take it before the same meal to get the best results. Don't crush the capsule or chew it, just swallow it.

In the event you have problems swallowing, open the capsule and sprinkle the contents into one tablespoon of applesauce and swallow it right away without chewing it. Never prepare the mixture ahead of time, since it may destroy the drug's effectiveness.

Ask your doctor for detailed instructions if you are using a syringe or if you have a stomach tube.

It's best to take antacids 30 to 60 minutes before Dexilant. If you are using sucralfate (Carafate), take Dexilant at least 30 minutes beforehand.

Dexilant Overdose

If you believe you may have overdosed on Dexilant go to the emergency room right away or contact a poison control center at 1-800-222-1222.

Missed Dose of Dexilant

If you miss a dose of Dexilant, take it as soon as you remember. If it's almost time for your next dose, wait until your next schedule dose. Don't "double up" to make up for your missed dose.

Dexilant Usage

  • Take Dexilant exactly as prescribed by your doctor.
  • Do not change your dose or stop taking Dexilant without talking to your doctor first.
  • You can take Dexilant with or without food.
  • Swallow Dexilant capsules whole.
  • If you have trouble swallowing Dexilant capsules whole, you may take or give them as follows:
  1. Take Dexilant with applesauce
    • Place 1 tablespoon of applesauce into a clean container.
    • Carefully open the capsule and sprinkle the granules onto the applesauce.
    • Swallow the applesauce and granules right away. Do not chew the granules. Do not save the applesauce and granules for later use.
  2. Take Dexilant with water using an oral (by mouth) syringe
    • Place 20 mL of water into a clean container.
    • Carefully open the capsule and empty the granules into the container of water.
    • Use an oral syringe to draw up the water and granule mixture.
    • Gently swirl the syringe to keep the granules from settling.
    • Give the mixture into the mouth right away. Do not save the water and granule mixture for later use.
    • Refill the syringe with 10 mL of water and swirl gently. Give the water into the mouth.
    • Repeat the previous step.
  3. For people who have a nasogastric (NG) tube that is size 16 French or larger, Dexilant may be given as follows:
    • Place 20 mL of water into a clean container.
    • Carefully open the capsule and empty the granules into the container of water.
    • Use a 60 mL catheter-tip syringe to draw up the water and granule mixture.
    • Gently swirl the syringe to keep the granules from settling.
    • Connect the catheter-tip syringe to the nasogastric tube.
    • Give the mixture right away through the nasogastric tube into the stomach. Do not save the water and granule mixture for later use.
    • Refill the syringe with 10 mL of water and swirl gently. Flush the nasogastric tube with the water.
    • Repeat repeat the previous step.

If you miss a dose, take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and take your next dose at the regular time. Do not take two doses of Dexilant at the same time.

 

How should I take Dexilant (dexlansoprazole)?

Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Take this medicine with a full glass of water.

Dexlansoprazole may be taken with or without food.

Do not crush, chew, break, or open a delayed-release capsule. Swallow it whole.

If you are unable to swallow a delayed-release capsule whole: Open the capsule and sprinkle the medicine into a spoonful of applesauce. Swallow this mixture right away without chewing. Do not save the mixture for later use. Discard the empty capsule.

To heal erosive esophagitis and relieve heartburn, dexlansoprazole is usually given for up to 6 months in adults, and for 4 to 16 weeks in children ages 12 through 17. Follow your doctor's dosing instructions very carefully.

Take this medicine for the full prescribed length of time. Your symptoms may improve before the condition is fully treated.

This medicine can cause unusual results with certain medical tests. Tell any doctor who treats you that you are using dexlansoprazole.

Dexlansoprazole can also cause you to have a false positive drug screening test. If you provide a urine sample for drug screening, tell the laboratory staff that you are taking dexlansoprazole.

Call your doctor if your symptoms do not improve, or if they get worse while using dexlansoprazole.

If you use dexlansoprazole for longer than 3 years, you could develop a vitamin B-12 deficiency. Talk to your doctor about how to manage this condition if you develop it.

Store at room temperature away from moisture and heat.

Commonly used brand name(s)

In the U.S.

  • Dexilant
  • Dexilant SoluTab
  • Kapidex

Available Dosage Forms:

  • Capsule, Delayed Release
  • Tablet Disintegrating, Delayed Release

Therapeutic Class: Gastric Acid Secretion Inhibitor

Pharmacologic Class: Proton Pump Inhibitor

What are some side effects that I need to call my doctor about right away?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of low magnesium levels like mood changes, muscle pain or weakness, muscle cramps or spasms, seizures, shakiness, not hungry, very bad upset stomach or throwing up, or a heartbeat that does not feel normal.
  • Signs of kidney problems like unable to pass urine, change in how much urine is passed, blood in the urine, or a big weight gain.
  • Dizziness or passing out.
  • A fast heartbeat.
  • Bone pain.
  • Fever.
  • This medicine may raise the chance of a very bad form of diarrhea called Clostridium difficile (C diff)-associated diarrhea. Call your doctor right away if you have stomach pain or cramps, very loose or watery stools, or bloody stools. Do not try to treat loose stools without first checking with your doctor.
  • A very bad skin reaction (Stevens-Johnson syndrome/toxic epidermal necrolysis) may happen. It can cause very bad health problems that may not go away, and sometimes death. Get medical help right away if you have signs like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in your mouth, throat, nose, or eyes.

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.
Intervention: Rilpivirine-containing products: Concomitant use with Dexilant is contraindicated [see Contraindications (4)]. 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 [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)].
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 [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.

Use in specific populations

Pregnancy

Risk Summary

There are no studies with dexlansoprazole use in pregnant women to inform a drug-associated risk. In animal reproduction studies, no effects on embryo-fetal development were observed with the administration of oral dexlansoprazole to rabbits during organogenesis at doses up to nine times the maximum recommended human dose (MRHD) (based on body surface area) or with administration of oral lansoprazole to rats and rabbits during organogenesis at doses up to 40 and 16 times the MRHD (based on body surface area), respectively [see Data].

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Data

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.

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 [see Data]. 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.

Data

When [14C] lansoprazole was administered orally at 2 mg/kg to lactating rats 14 days after parturition, milk collected at 0.5, 2 and 6 hours after the lansoprazole dose contained 2 to 6 fold higher concentrations of radioactivity than plasma. Almost all of the radioactivity was determined to be from lansoprazole metabolites.

Pediatric Use

The safety and effectiveness of Dexilant capsules have been established in pediatric patients 12 to 17 years of age for the healing of all grades of EE. The safety and effectiveness of Dexilant capsules have been established in pediatric patients 12 to 17 years of age for 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 capsules 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.

The safety and effectiveness of Dexilant have not been established in pediatric patients less than 12 years of age.

The use of Dexilant is not recommended for symptomatic non-erosive GERD in pediatric patients less than one year of age because studies in this class of drugs have not demonstrated efficacy.

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)].

Hepatic Impairment

No dosage adjustment for Dexilant capsules 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 60 mg Dexilant capsule, 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 capsules is not recommended for these patients [see Dosage and Administration (2.2)].

Dexilant - Clinical Pharmacology

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.

Pharmacodynamics

Antisecretory Activity

The effects of Dexilant capsules 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 Lansoprazole
Dexilant
60 mg capsules
Lansoprazole
30 mg
Mean Intragastric pH
4.55 4.13
% Time Intragastric pH >4 (hours)
71
(17 hours)
60
(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 Dexilant 30 and 60 mg capsules. 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 capsules 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.

Pharmacokinetics

The dual delayed-release formulation of Dexilant capsules 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 capsules although mean AUCt and Cmax 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 Capsules Once Daily for 5 Days in Healthy Adult Subjects

The pharmacokinetics of dexlansoprazole are highly variable, with percent coefficient of variation (CV%) values for Cmax, 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 Capsules
Dose
(mg)
Cmax
(ng/mL)
AUC24
(ng∙h/mL)
CL/F
(L/h)
30 658 (40%)
(N=44)
3275 (47%)
(N=43)
11.4 (48%)
(N=43)
60 1397 (51%)
(N=79)
6529 (60%)
(N=73)
11.6 (46%)
(N=41)

Absorption

After oral administration of Dexilant 30 or 60 mg capsules to healthy subjects and symptomatic GERD patients, mean Cmax and AUC values of dexlansoprazole increased approximately dose proportionally (see Figure 1).

When granules of Dexilant 60 mg capsules are mixed with water and dosed via NG tube or orally via syringe, the bioavailability (Cmax 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 capsules under various fed conditions compared to fasting, increases in Cmax ranged from 12 to 55%, increases in AUC ranged from 9 to 37%, and Tmax 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 (Vz/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 capsules, no unchanged dexlansoprazole is excreted in urine. Following the administration of [14C] 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 capsules once daily for seven days. The dexlansoprazole mean Cmax 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 Capsules Once Daily for 7 Days
Dose
(mg)
Cmax
(ng/mL)
AUCtau
(ng∙h/mL)
CL/F
(L/h)
30
(N=17)
691
(53)
2886
(47)
12.8
(48)
60
(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 oral dose of Dexilant 60 mg capsules, 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 oral dose of 60 mg Dexilant capsules, 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 capsules (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.

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 capsules (N=2 to 6 subjects/group), mean dexlansoprazole Cmax and AUC values were up to two times higher in intermediate compared to extensive metabolizers; in poor metabolizers, mean Cmax 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.

How Supplied/Storage and Handling

Dexilant delayed-release capsules, 30 mg, are opaque, blue and gray with TAP and "30" imprinted on the capsule and supplied as:

NDC Number Size
64764-171-11 Unit dose package of 100
64764-171-30 Bottle of 30
64764-171-90 Bottle of 90
64764-171-19 Bottle of 1000

Dexilant delayed-release capsules, 60 mg, are opaque, blue with TAP and "60" imprinted on the capsule and supplied as:

NDC Number Size
64764-175-11 Unit dose package of 100
64764-175-30 Bottle of 30
64764-175-90 Bottle of 90
64764-175-19 Bottle of 1000

Store at 20 to 25°C (68 to 77°F); excursions permitted to 15 to 30°C (59 to 86°F) [see USP Controlled Room Temperature].

PRINCIPAL DISPLAY PANEL - 60 mg Capsule Bottle Label

NDC 64764-175-30

Rx only
30 Capsules

Dexilant
dexlansoprazole
delayed release
capsules

Dispense the
accompanying
Medication Guide
to each patient.

60 mg

Dexilant 
dexlansoprazole capsule, delayed release
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:64764-171
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
dexlansoprazole (dexlansoprazole) dexlansoprazole 30 mg
Inactive Ingredients
Ingredient Name Strength
Methacrylic Acid - Methyl Methacrylate Copolymer (1:1)  
Methacrylic Acid - Methyl Methacrylate Copolymer (1:2)  
Methacrylic Acid - Ethyl Acrylate Copolymer (1:1) Type A  
magnesium carbonate  
sucrose  
low-substituted hydroxypropyl cellulose, unspecified  
titanium dioxide  
hydroxypropyl cellulose (1200000 mw)  
HYPROMELLOSE 2910 (6 MPA.S)  
talc  
polyethylene glycol 8000  
triethyl citrate  
polysorbate 80  
silicon dioxide  
carrageenan  
potassium chloride  
ferric oxide red  
aluminum oxide  
FD&C Blue No. 2  
STARCH, CORN  
Product Characteristics
Color BLUE (opaque) , GRAY (opaque) Score no score
Shape CAPSULE Size 16mm
Flavor Imprint Code TAP;30
Contains     
Packaging
# Item Code Package Description
1 NDC:64764-171-30 30 CAPSULE, DELAYED RELEASE in 1 BOTTLE
2 NDC:64764-171-90 90 CAPSULE, DELAYED RELEASE in 1 BOTTLE
3 NDC:64764-171-19 1000 CAPSULE, DELAYED RELEASE in 1 BOTTLE
4 NDC:64764-171-11 10 BLISTER PACK in 1 CARTON
4 10 CAPSULE, DELAYED RELEASE in 1 BLISTER PACK
5 NDC:64764-171-01 5 BLISTER PACK in 1 TRAY
5 4 CAPSULE, DELAYED RELEASE in 1 BLISTER PACK
6 NDC:64764-171-00 7 CAPSULE, DELAYED RELEASE in 1 BOTTLE
7 NDC:64764-171-03 1 BOTTLE in 1 CARTON
7 5 CAPSULE, DELAYED RELEASE in 1 BOTTLE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA022287 04/12/2010
Dexilant 
dexlansoprazole capsule, delayed release
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:64764-175
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
dexlansoprazole (dexlansoprazole) dexlansoprazole 60 mg
Inactive Ingredients
Ingredient Name Strength
Methacrylic Acid - Methyl Methacrylate Copolymer (1:1)  
Methacrylic Acid - Methyl Methacrylate Copolymer (1:2)  
Methacrylic Acid - Ethyl Acrylate Copolymer (1:1) Type A  
magnesium carbonate  
sucrose  
low-substituted hydroxypropyl cellulose, unspecified  
titanium dioxide  
hydroxypropyl cellulose (1200000 mw)  
HYPROMELLOSE 2910 (6 MPA.S)  
talc  
polyethylene glycol 8000  
triethyl citrate  
polysorbate 80  
silicon dioxide  
carrageenan  
potassium chloride  
aluminum oxide  
FD&C Blue No. 2  
STARCH, CORN  
Product Characteristics
Color BLUE (opaque) Score no score
Shape CAPSULE Size 18mm
Flavor Imprint Code TAP;60
Contains     
Packaging
# Item Code Package Description
1 NDC:64764-175-30 30 CAPSULE, DELAYED RELEASE in 1 BOTTLE
2 NDC:64764-175-90 90 CAPSULE, DELAYED RELEASE in 1 BOTTLE
3 NDC:64764-175-19 1000 CAPSULE, DELAYED RELEASE in 1 BOTTLE
4 NDC:64764-175-11 10 BLISTER PACK in 1 CARTON
4 10 CAPSULE, DELAYED RELEASE in 1 BLISTER PACK
5 NDC:64764-175-01 5 BLISTER PACK in 1 TRAY
5 4 CAPSULE, DELAYED RELEASE in 1 BLISTER PACK
6 NDC:64764-175-00 7 CAPSULE, DELAYED RELEASE in 1 BOTTLE
7 NDC:64764-175-02 30 CAPSULE, DELAYED RELEASE in 1 BOTTLE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA022287 04/12/2010
Labeler - Takeda Pharmaceuticals America, Inc. (830134016)
Registrant - Takeda Pharmaceuticals America, Inc. (830134016)
Establishment
Name Address ID/FEI Operations
Packaging Coordinators, LLC 078567231 LABEL(64764-171, 64764-175), PACK(64764-171, 64764-175)
Establishment
Name Address ID/FEI Operations
Takeda Ireland Ltd. 988980314 ANALYSIS(64764-171, 64764-175), MANUFACTURE(64764-171, 64764-175)
Revised: 08/2017   Takeda Pharmaceuticals America, Inc.
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