DEXILANT is indicated in adults and in adolescents aged 12 to 17 years for the following:
- Treatment of erosive reflux oesophagitis
- Maintenance of healed erosive reflux oesophagitis and maintenance of relief of heartburn
- Short-term treatment of heartburn and acid regurgitation associated with symptomatic nonerosive
gastro-oesophageal reflux disease (GORD)

Posology
- Treatment of erosive reflux oesophagitis
Adults and adolescents aged 12 to 17 years - The recommended dose is 60 mg once daily for
4 weeks. In patients not fully healed within this time, the treatment may be continued at the
same dose for another 4 weeks.
- Maintenance of healed erosive reflux oesophagitis and maintenance of relief of heartburn
Adults - The recommended dose is 30 mg once daily for up to 6 months in patients where
prolonged acid suppression is needed.
Adolescents aged 12 to 17 years - The recommended dose is 30 mg once daily. Current
evidence does not support a specific treatment period time. A decision should be taken by the
clinician on a case by case basis.
- Symptomatic non-erosive gastro-oesophageal reflux disease (GORD)
Adults and adolescents aged 12 to 17 years - The recommended dose is 30 mg once daily for up
to 4 weeks.
Special populations
Elderly
Due to reduced clearance of dexlansoprazole in the elderly an adjustment of dose may be necessary
based on individual requirements. A daily dose of 60 mg should not be exceeded in the elderly unless
there are compelling clinical indications (see section 5.2).
Renal impairment
No dosage adjustment is necessary for patients with renal impairment (see section 5.2).
Hepatic impairment
No dosage adjustment is necessary for patients with mild hepatic impairment. Patients with moderate
hepatic impairment should be kept under regular supervision and a maximum daily dose of 30 mg
should be considered. No studies have been conducted in patients with severe hepatic impairment (see
sections 4.4 and 5.2), the use of dexlansoprazole is not recommended for these patients.
Paediatric population
Adolescents aged 12 to 17 years
Treatment of erosive reflux oesophagitis
The posology of DEXILANT in adolescents aged 12 to 17 years is the same as in adults.
Maintenance of healed erosive reflux oesophagitis and maintenance of relief of heartburn
The dose of DEXILANT in adolescents aged 12 to 17 years is the same as in adults.
Symptomatic non-erosive gastro-oesophageal reflux disease (GORD)
The posology of DEXILANT in adolescents aged 12 to 17 years is the same as in adults.
Children under 12 years of age
The safety and efficacy of DEXILANT in children under 12 years of age have not been established.
No data are available.
Method of administration
Oral use.
Capsules should be swallowed whole with liquid. They can be taken with or without food (see section
5.2).
Capsules may also be opened and granules mixed with one tablespoon apple sauce for administration.
After preparing the mixture, the medicinal product should be administered immediately.
Granules should not be chewed.

The possibility of malignant gastric tumour should be excluded when using DEXILANT because
dexlansoprazole can mask the symptoms and delay the diagnosis.
Co-administration of dexlansoprazole is not recommended with HIV protease inhibitors for which
absorption is dependent on acidic intragastric pH, such as atazanavir or nelfinavir, due to significant
reduction in their bioavailability (see section 4.5).
Dexlansoprazole should be used with caution in patients with moderate hepatic dysfunction.
Dexlansoprazole is not recommended for patients with severe hepatic impairment (see sections 4.2
and 5.2).
Decreased gastric acidity due to any means, including proton pump inhibitors (PPIs) such as
dexlansoprazole, increases gastric counts of bacteria normally present in the gastrointestinal tract.
Treatment with PPIs may lead to slightly increased risk of gastrointestinal infections such as
Salmonella, Campylobacter and Clostridium difficile.
Because of limited safety data for patients on treatment for longer than 1 year, regular review of the
treatment and a thorough risk/benefit assessment should regularly be performed in these patients.
Severe hypomagnesaemia has been reported in patients treated with PPIs like dexlansoprazole for at
least three months, in most cases for a year. Serious manifestations of hypomagnesaemia such as
fatigue, delirium, convulsions, dizziness and ventricular arrhythmia can occur but they may begin
insidiously and be overlooked. In most affected patients, hypomagnesaemia improved after
magnesium replacement and discontinuation of the PPI. For patients expected to be on prolonged
treatment or who take PPIs with digoxin or medicinal products that may cause hypomagnesaemia (e.g.
diuretics), health care professionals should consider measuring magnesium levels before starting PPI
treatment and periodically during treatment.
Influence on Vitamin B-12 Absorption
Dexlansoprazole, as all acid-blocking medicines, may reduce the absorption of vitamin B-12
(cyanocobalamin) due to hypo- or achlorhydria. This should be considered in patients with reduced
body stores or risk factors for reduced vitamin B-12 absorption on long-term therapy or if respective
clinical symptoms are observed.
Very rarely cases of colitis have been reported in patients taking lansoprazole. Similar effects could
be expected with dexlansoprazole. Therefore, in the case of severe and/or persistent diarrhoea,
discontinuation of therapy should be considered.
Proton pump inhibitors, especially if used in high doses and over long durations (>1 year), may
modestly increase the risk of hip, wrist and spine fracture, predominantly in the elderly or in the
presence of other recognised risk factors. Observational studies suggest that proton pump inhibitors
may increase the overall risk of fracture by 10–40%. Some of this increase may be due to other risk
factors. Patients at risk of osteoporosis should receive care according to current clinical guidelines
and they should have an adequate intake of vitamin D and calcium.
When given together with PPIs, methotrexate levels have been reported to increase in some patients.
In high dose methotrexate administration a temporary withdrawal of dexlansoprazole may need to be
considered.
As DEXILANT contains sucrose, patients with rare hereditary problems of fructose intolerance,
glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicinal
product.
Subacute cutaneous lupus erythematosus (SCLE)
Proton pump inhibitors are associated with very infrequent cases of SCLE. If lesions occur, especially
in sun-exposed areas of the skin, and if accompanied by arthralgia, the patient should seek medical
help promptly and the health care professional should consider stopping DEXILANT. SCLE after
previous treatment with a proton pump inhibitor may increase the risk of SCLE with other proton
pump inhibitors.
Interference with laboratory tests
Increased Chromogranin A (CgA) level may interfere with investigations for neuroendocrine tumours.
To avoid this interference, DEXILANT treatment should be stopped for at least 5 days before CgA
measurements (see section 5.1). If CgA and gastrin levels have not returned to reference range after
initial measurement, measurements should be repeated 14 days after cessation of proton pump
inhibitor treatment.

Interaction studies have only been performed in adults.
Effects of other medicinal products on dexlansoprazole
CYP2C19 and CYP3A4 have been shown to be involved in the metabolism of dexlansoprazole.
Medicinal products which inhibit CYP2C19
Inhibitors of CYP2C19 (such as fluvoxamine) would likely increase the systemic exposure of
dexlansoprazole.
Medicinal products which induce CYP2C19 and CYP3A4
Enzyme inducers affecting CYP2C19 and CYP3A4 such as rifampicin, and St John’s wort
(Hypericum perforatum) may reduce the plasma concentrations of dexlansoprazole.
Others
Sucralfate/Antacids
Sucralfate/Antacids may decrease the bioavailability of dexlansoprazole. Therefore dexlansoprazole
should be taken at least 1 hour after taking these drugs.
Effects of dexlansoprazole on other medicinal products
Medicinal products with pH dependent absorption
Dexlansoprazole may interfere with the absorption of medicinal products where gastric pH is critical
to bioavailability.
HIV protease inhibitors
Co-administration of dexlansoprazole is not recommended with HIV protease inhibitors for which
absorption is dependent on acidic intragastric pH, such as atazanavir or nelfinavir; due to significant
reduction in their bioavailability (see section 4.4).
Ketoconazole, itraconazole and erlotinib
The absorption of ketoconazole, itraconazole and erlotinib from the gastrointestinal tract is enhanced
by the presence of gastric acid. Administration of dexlansoprazole may result in sub-therapeutic
concentrations of ketoconazole, itraconazole and erlotinib, and the combination should be avoided.
Digoxin
Co-administration of dexlansoprazole and digoxin may lead to increased digoxin plasma levels. The
plasma levels of digoxin should therefore be monitored and the dose of digoxin adjusted if necessary
when initiating and ending dexlansoprazole treatment.
Medicinal products metabolised by P450 enzymes
In vitro studies have shown that DEXILANT is not likely to inhibit CYP isoforms 1A1, 1A2, 2A6,
2B6, 2C8, 2C9, 2D6, 2E1 or 3A4. As such, no clinically relevant interactions with medicinal products
metabolised by these CYP enzymes would be expected. Furthermore, in vivo studies showed that
DEXILANT did not have an impact on the pharmacokinetics of coadministered 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 demonstrated that
DEXILANT has the potential to inhibit CYP2C19, an in vivo drug-drug interaction study in mainly
CYP2C19 extensive and intermediate metabolisers has shown that DEXILANT does not affect the
pharmacokinetics of diazepam (CYP2C19 substrate).
Tacrolimus
Co-administration of dexlansoprazole may increase the plasma concentrations of tacrolimus (a
CYP3A and P-glycoprotein [P-gp] substrate), especially in transplant patients who are intermediate or
poor metabolisers of CYP2C19. Monitoring of tacrolimus plasma concentrations is advised when
concomitant treatment with dexlansoprazole is initiated or ended.
Warfarin
In a study, co-administration of DEXILANT and warfarin did not result in any significant differences
in the pharmacokinetics of warfarin or International Normalised Ratio (INR) compared to
administration of warfarin with placebo. However, there have been reports of increased INR and
prothrombin time in patients receiving PPIs and warfarin concomitantly. Patients treated with PPIs
and warfarin concomitantly may need to be monitored for increases in INR and prothrombin time,
especially when initiating or ending concomitant treatment.
Clopidogrel
A study has shown that concomitant administration of dexlansoprazole (60 mg once daily) and
clopidogrel 75 mg to healthy volunteers resulted in a reduction in the exposure to the active
metabolite of clopidogrel (approximately 9% decrease in AUC and 27% decrease in Cmax).
Co-administration of dexlansoprazole had no clinically meaningful effect on pharmacodynamics of
clopidogrel. No dose adjustment of clopidogrel is necessary when administered with an approved
dose of DEXILANT.
Methotrexate
Case reports, published population pharmacokinetic studies, and retrospective analyses suggest that
concomitant administration of PPIs and methotrexate (primarily at high dose; see methotrexate
prescribing information) may elevate and prolong serum levels of methotrexate and/or its metabolite
hydroxymethotrexate possibly leading to methotrexate toxicities. Therefore, in settings where highdose
methotrexate is used a temporary withdrawal of dexlansoprazole may need to be considered.
However, no formal drug interaction studies of high-dose methotrexate with PPIs have been
conducted.
Medicinal products transported by P-glycoprotein
Lansoprazole has been observed to inhibit the transport protein, P-gp in vitro. Similar effects could be
expected with dexlansoprazole. The clinical relevance of this is unknown.
Others
No clinically significant interactions of dexlansoprazole with nonsteroidal anti-inflammatory drugs
have been demonstrated, although no formal interactions studies have been performed.

Pregnancy
There are no or limited amount of data from the use of dexlansoprazole in pregnant women. Animal
studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see
section 5.3). As a precautionary measure, it is preferable to avoid the use of DEXILANT during
pregnancy.
Breastfeeding
It is not known whether dexlansoprazole is excreted in human breast milk. Animal studies have shown
excretion of lansoprazole in milk.
A risk to the newborns/infants cannot be excluded. A decision must be made whether to discontinue
breast-feeding or to discontinue/abstain therapy taking into account the benefit of breast-feeding for
the child and the benefit of therapy for the woman.
Fertility
There was no evidence of impaired fertility following the administration of lansoprazole in animal
studies (see section 5.3). Similar results could be expected with dexlansoprazole.

Adverse drug reactions such as dizziness, vertigo, visual disturbances and somnolence may occur (see
section 4.8). Under these conditions the ability to react may be decreased.

Summary of the safety profile
Adults
DEXILANT at doses of 30, 60, or 90 mg has been evaluated for safety in clinical studies in patients
treated for up to 1 year. In these clinical studies, adverse reactions associated with treatment with
DEXILANT were mostly mild or moderate, with an overall incidence similar to placebo and
lansoprazole. The most commonly reported adverse reactions were diarrhoea, abdominal pain,
headache, nausea, abdominal discomfort, flatulence and constipation. The incidence of these adverse
reactions was not affected by gender, age, or race.
Tabulated list of adverse reactions
Adverse reactions reported for DEXILANT (30 mg, 60 mg or 90 mg) in clinical studies and postmarketing
experience are listed below as MedDRA preferred term by system organ class and absolute
frequency. Frequencies are defined as: very common (≥ 1/10); common (≥ 1/100 to < 1/10);
uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); not known
(cannot be estimated from the available data). Within each frequency grouping, adverse reactions are
presented in order of decreasing seriousness.

Description of selected adverse reactions
Diarrhoea and abdominal pain
In the Phase 3 clinical studies, the most commonly reported adverse reaction was diarrhoea (excluding
infective diarrhoea), the majority of which were non serious. Overall, few subjects (2.4%)
prematurely discontinued due to an adverse reaction while receiving dexlansoprazole therapy. The
most common (≥ 0.5%) adverse reactions leading to premature discontinuation were diarrhoea,
gastrointestinal and abdominal pains. Initial onset of diarrhoea and abdominal pain was independent
of the duration of exposure, and the majority of these events were mild to moderate in severity. There
were no apparent dose-related trends observed across dexlansoprazole doses for the incidence of these
events.
Hypersensitivity
There have been post-marketing cases reporting serious hypersensitivity reactions. Hypersensitivity
reactions were more frequently reported in females (74%). The majority of the serious cases were
managed with steroids and/or antihistamines and withdrawal of the medicinal product. Severe
reactions of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) were reported in
few patients.
Haemolytic anaemia
There have been few serious post-marketing reports of haemolytic anaemia after approximately four
to seven months on dexlansoprazole 60 mg therapy.
Paediatric population
The safety profile for adolescents aged 12 to 17 years is similar to adults. In clinical studies of 166
adolescent patients, the only adverse reaction that occurred in more than one patient was abdominal
pain. Additional adverse reactions, which occurred in one patient each, included diarrhoea, urticaria,
dry mouth and headache.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare
professionals are asked to report any suspected adverse reactions via the national pharmacovigilance
and drug safety centre (NPC)

The effects of overdose of dexlansoprazole in humans are not known (although the acute toxicity is
likely to be low) and, consequently, instruction for treatment cannot be given.
There have been no reports of significant overdose of DEXILANT. Multiple doses of DEXILANT
120 mg and a single dose of DEXILANT 300 mg did not result in death or other severe adverse
events. Serious adverse reactions of hypertension have been reported in association with twice daily
doses of DEXILANT 60 mg. Non-serious adverse reactions observed with twice daily doses of
DEXILANT 60 mg include hot flushes, contusion, oropharyngeal pain, and weight loss.
In the case of suspected overdose the patient should be monitored. Dexlansoprazole is not
significantly eliminated by haemodialysis. If necessary, gastric emptying, charcoal and symptomatic
therapy is recommended.

Pharmacotherapeutic group: Proton pump inhibitors, ATC code: A02BC06
Mechanism of action
Dexlansoprazole is the R-enantiomer of lansoprazole. It is a gastric PPI. It inhibits the final stage of
gastric acid formation by inhibiting the activity of H+/K+ ATPase of the parietal cells in the stomach.
The inhibition is dose-dependent and reversible, and the effect applies to both basal and stimulated
secretion of gastric acid. Dexlansoprazole is concentrated in the parietal cells and becomes active in
their acidic environment, whereupon it reacts with the sulphydryl group of H+/K+ATPase causing
inhibition of the enzyme activity.
Pharmacodynamic effects
Antisecretory activity
The antisecretory activity of DEXILANT has been studied in healthy subjects taking dexlansoprazole
60 mg or lansoprazole 30 mg once daily for five days. The average intragastric pH was 4.55 for
DEXILANT and 4.13 for lansoprazole. The average percentage of time throughout the day in which
the intragastric pH is maintained above 4 was 71% (17 hours) with DEXILANT and 60% (14 hours)
with lansoprazole.
Serum gastrin effect
The effect of DEXILANT on serum gastrin concentrations was evaluated in patients in clinical trials
up to 12 months. The mean fasting gastrin concentrations increased from baseline during treatment
with DEXILANT 30 mg and 60 mg doses. In patients treated for more than 6 months, mean serum
gastrin levels increased during approximately the first 3 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.
Please contact the relevant competent authority.
During treatment with antisecretory medicinal products, serum gastrin increases in response to the
decreased acid secretion. Also CgA increases due to decreased gastric acidity. The increased CgA
level may interfere with investigations for neuroendocrine tumours.
Available published evidence suggests that proton pump inhibitors should be discontinued between 5
days and 2 weeks prior to CgA measurements. This is to allow CgA levels that might be spuriously
elevated following PPI treatment to return to reference range.
Enterochromaffin-Like Cell (ECL) Effects
There were no reports of ECL cell hyperplasia in gastric biopsy specimens obtained from patients
treated with DEXILANT 30 mg, 60 mg or 90 mg for up to 12 months.
Effect on Cardiac Repolarisation
A study was conducted to assess the potential of DEXILANT to prolong the QT/QTc interval in
healthy adult subjects. DEXILANT doses of 90 mg or 300 mg did not delay cardiac repolarisation
compared to placebo. The positive control (moxifloxacin) produced statistically significantly greater
mean maximum and time-averaged QT/QTc intervals compared to placebo.
Clinical efficacy and safety
Treatment of erosive reflux oesophagitis
Two multi-center, double-blind, active-controlled, randomised, 8-week studies were conducted in
patients with endoscopically confirmed erosive reflux oesophagitis. Severity of the disease was
classified based on the Los Angeles Classification Grading System (Grades A-D). Patients were
randomised to one of the following three treatment groups: DEXILANT 60 mg daily, DEXILANT
90 mg daily or lansoprazole 30 mg daily. A total of 4092 patients were enrolled and ranged in age
from 18 to 90 years (median age 48 years) with 54% male. Based on the Los Angeles Classification,
71% of patients had Grades A and B erosive reflux oesophagitis (mild) and 29% of patients had
Grades C and D erosive reflux oesophagitis (moderate to severe) before treatment.
By the life-table method of analysis DEXILANT 60 mg healed 92.3% to 93.1% of patients versus
86.1% to 91.5% for lansoprazole 30 mg after 8 weeks of treatment (primary). Non-inferiority was
demonstrated in both studies. Statistical superiority was not established using log-rank tests.
After 4 weeks of treatment (secondary), the healing rates by the life-table method were 77.0% to
80.1% versus 76.5% to 77.0% for lansoprazole 30 mg.
The life-table healing rates at Week 8 for patients with moderate to severe erosive reflux oesophagitis
(secondary) were 88.9% and 74.5% for DEXILANT 60 mg and lansoprazole 30 mg, respectively, in
the first study. The difference was statistically significant (p=0.011). In the second study, the Week 8
life-table healing rates were 87.6% and 87.7% for DEXILANT 60 mg and lansoprazole 30 mg,
respectively, and were not statistically significantly different.
DEXILANT 90 mg was studied and did not provide additional clinical benefit over DEXILANT
60 mg.
Maintenance of healed erosive reflux oesophagitis
A multi-center, double-blind, placebo-controlled, randomised study was conducted in patients who
successfully completed an erosive reflux oesophagitis study and showed endoscopically confirmed
healed erosive reflux oesophagitis. Maintenance of healing and symptom relief over a six-month
period were evaluated with DEXILANT 30 mg or 60 mg once daily compared to placebo. A total of
445 patients were enrolled and ranged in age from 18 to 85 years (median age 49 years), with 52%
female.
By the life-table method, DEXILANT 30 mg and 60 mg demonstrated statistically significantly higher
rates of maintenance of healed erosive reflux oesophagitis (74.9% and 82.5%, respectively) than
placebo (27.2%) at Month 6 (p<0.00001).
For patients with more severe grades of erosive reflux oesophagitis (Grades C or D) before healing,
DEXILANT 30 mg and 60 mg also achieved statistically significantly higher 6-month maintenance
rates than placebo by the life-table method.
DEXILANT 30 mg and 60 mg achieved statistically significantly (p<0.00001) greater percentages of
heartburn relief during the study treatment period. The median percentages of 24-hour heartburn-free
days were 96.1%, 90.9% and 28.6% for DEXILANT 30 mg, 60 mg and placebo, respectively. The
median percentages of nights without heartburn were 98.9%, 96.2% and 71.7% for DEXILANT
30 mg, 60 mg and placebo, respectively.
In a second study (N=451) of DEXILANT 60 mg and 90 mg versus placebo, DEXILANT 60 mg
showed similar results to the first study in the maintenance of healed erosive reflux oesophagitis and
heartburn relief. DEXILANT 90 mg did not provide additional clinical benefit over DEXILANT
60 mg.
Symptomatic non-erosive GORD
A multi-center, double-blind, placebo-controlled, randomised, 4-week study was conducted in patients
with a diagnosis of symptomatic GORD made primarily by presentation of symptoms. These patients
who identified heartburn as their primary symptom, had a history of heartburn for 6 months or longer,
had heartburn on at least 4 of 7 days immediately prior to randomisation and had no esophageal
erosions as confirmed by endoscopy. However, patients with symptoms which were not acid-related
may not have been excluded using these inclusion criteria. Patients were randomised to one of the
following treatment groups: DEXILANT 30 mg daily, 60 mg daily, or placebo. A total of 947 patients
were enrolled and ranged in age from 18 to 86 years (median age 48 years) with 71% female.
DEXILANT 30 mg provided statistically significantly greater percent of days with heartburn-free
24-hour periods and percent of nights without heartburn (respectively 54.9% and 80.8%) over placebo
(respectively 18.5% and 51.7%) as assessed by daily diary over 4 weeks. A higher percentage of
patients on DEXILANT 30 mg had heartburn-free 24-hour periods compared to placebo through
4 weeks of treatment. DEXILANT 60 mg was studied and provided no additional clinical benefit over
DEXILANT 30 mg.
A second multi-center, double blind, placebo-controlled, randomised, 4-week study was conducted in
patients with a history of nocturnal heartburn and GORD associated sleep disturbances on at least 3 of
7 nights immediately prior to randomisation. Patients were randomised to receive DEXILANT 30 mg
or placebo daily. A total of 305 patients were enrolled and ranged in age from 18 to 66 years (median
age 45 years) with 63.9% female. DEXILANT 30 mg provided statistically significantly greater
percent of nights without heartburn (73.1%) over placebo (35.7%) as assessed by daily diary over
4 weeks.
A third multi-center, single blind study enrolled 178 patients with a history of symptomatic GORD.
Patients whose symptoms were well-controlled during a run-in period while taking a PPI other than
DEXILANT twice a day subsequently received blinded DEXILANT 30 mg (morning) and placebo
(evening) for 6 weeks. Well-controlled was defined as having a weekly average of ≤1 episode of
heartburn during the last 4 weeks of both the 6 week run-in and treatment periods. A total of
142 patients were included in the analysis. Ages ranged from 22 to 90 years (median age 53 years)
with 56% female. After switching from twice daily PPI therapy to once daily DEXILANT 30 mg,
88% of patients’ heartburn remained well-controlled.
Paediatric population
Treatment of erosive reflux oesophagitis, maintenance of healed erosive reflux oesophagitis and relief
of heartburn
In a multi-center, 24-week study, 62 adolescents with a documented history of GORD for at least 3
months and endoscopically-proven erosive reflux oesophagitis were treated with DEXILANT 60 mg
once daily, for 8 weeks to evaluate safety and effectiveness. Patients ranged in age from 12 to 17
years (median age 15 years) with 61% being male. Based on the Los Angeles Classification Grading
Scale, 96.8% of the erosive reflux oesophagitis patients had mild erosive reflux oesophagitis (Grades
A and B), and 3.2% of patients had moderate to severe erosive reflux oesophagitis (Grades C and D)
before treatment. The erosive reflux oesophagitis healing rate in adolescents was 87.9%, which is
similar to adults, for up to 8 weeks of treatment.
After the initial 8 weeks of treatment, patients with endoscopically confirmed healed erosive reflux
oesophagitis were randomised to receive treatment with DEXILANT 30 mg or placebo, once daily for
an additional 16 weeks. Eighty-two percent of patients treated with 30 mg of DEXILANT remained
healed over the four-month treatment period as confirmed by endoscopy versus 58% for placebo.
During the 16-week maintenance period, the median percentage of 24-hour heartburn-free periods was
86.6% for those receiving DEXILANT 30 mg compared to 68.1% for those receiving placebo.
The results for maintenance of healing and relief of heartburn were similar to adults.
Symptomatic non-erosive GORD
In an uncontrolled, open-label, multi-center study, 104 adolescents with symptomatic non-erosive
GORD were treated with DEXILANT 30 mg once daily, for 4 weeks to evaluate safety and
effectiveness. Patients had a documented history of GORD symptoms for at least 3 months prior to
screening, reported heartburn on at least three out of seven days during screening, and had no
oesophageal erosions as confirmed by endoscopy. Patients ranged in age from 12 to 17 years (median
age 15 years) with 70% being female. During the 4-week treatment period, the median percentage of
24-hour heartburn-free periods was 47.3% which was similar to adults.

The formulation of DEXILANT utilising dual delayed release technology results in a dexlansoprazole
plasma concentration-time profile with two distinct peaks; the first peak occurs 1 to 2 hours after
administration, followed by a second peak within 4 to 5 hours.
Absorption
After oral administration of DEXILANT 30 mg or 60 mg to healthy subjects, mean Cmax and AUC
values of dexlansoprazole increased approximately dose proportionally. Peak plasma levels occur
within 4 to 6 hours.
Distribution
Plasma protein binding of dexlansoprazole ranged from 96.1% to 98.8% in healthy subjects and was
independent of concentration from 0.01 to 20 mcg per mL. The apparent volume of distribution after
multiple doses in symptomatic GORD patients was 40.3 L.
Biotransformation
Dexlansoprazole is extensively metabolised 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
metabolisers (*1/*1), intermediate metabolisers (*1/mutant) and poor metabolisers (mutant/mutant).
Systemic exposure of dexlansoprazole is generally higher in intermediate and poor metabolisers.
Dexlansoprazole is the major circulating component in plasma, regardless of CYP2C19 metaboliser
status. In CYP2C19 intermediate and extensive metabolisers, the major plasma metabolites are
5-hydroxy dexlansoprazole and its glucuronide conjugate, while in CYP2C19 poor metabolisers
dexlansoprazole sulfone is the major plasma metabolite.
Elimination
Following the administration of DEXILANT, no unchanged dexlansoprazole is excreted in urine.
Following the administration of [14C] dexlansoprazole to healthy male subjects, approximately 50.7%
of the administered radioactivity was excreted in urine and 47.6% in the feces. Apparent clearance in
healthy subjects was 11.4 to 11.6 L/h, respectively, after 5-days of 30 or 60 mg once daily
administration.
Linearity/non-linearity
Following a single and multiple daily dexlansoprazole 30 to 120 mg doses to healthy subjects, mean
dexlansoprazole Cmax and AUC values increased approximately dose proportionally over the entire
dose range. The pharmacokinetics of dexlansoprazole was both dose- and time-independent, with an
estimated terminal elimination half-life of approximately 1 to 2 hours. Therefore, little or no active
substance accumulation was observed for dexlansoprazole after once daily doses of dexlansoprazole,
as evidenced by similar Cmax and AUC values after a single and multiple once-daily doses at steadystate.
Effect of food
DEXILANT can be taken without regard to food or the timing of food. In food-effect studies in
healthy subjects receiving DEXILANT, increases in Cmax ranged from 12% to 55% and increases in
AUC ranged from 9% to 37% under various fed conditions compared to fasting. However, no relevant
differences with regard to intragastric pH were observed. An additional study showed that
administration of 60 mg DEXILANT prior to consumption of breakfast, lunch, dinner or an evening
snack did not have an effect on dexlansoprazole exposure, or a clinically relevant effect on 24-hour
intragastric pH control.
Special patient populations
Elderly
In a study of male and female healthy subjects who received a single oral dose of DEXILANT 60 mg,
the terminal elimination half-life of dexlansoprazole was statistically significantly longer in elderly
subjects compared to younger subjects (2.23 and 1.5 hours, respectively). In addition, dexlansoprazole
exhibited higher systemic exposure (AUC) in elderly subjects (34.5% higher) than younger subjects.
These differences were not clinically relevant. A daily dose of 60 mg should not be exceeded in the
elderly unless there are compelling clinical indications.
Renal impairment
Dexlansoprazole is extensively metabolised in the liver to inactive metabolites, and no parent active
substance 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 subjects with renal impairment (see section 4.4).
Hepatic impairment
In a study of patients with moderately impaired hepatic function who received a single oral dose of
DEXILANT 60 mg, plasma exposure (AUC) of bound and unbound dexlansoprazole in the hepatic
impairment group was approximately 2 times greater compared to subjects with normal hepatic
function. This difference in exposure was not due to a difference in protein binding between the two
liver function groups. No adjustment for DEXILANT is necessary for patients with mild hepatic
impairment. DEXILANT 30 mg should be considered for patients with moderate hepatic impairment.
No studies have been conducted in patients with severe hepatic impairment, the use of
dexlansoprazole is not recommended for these patients (see section 4.4).
Paediatric population
The pharmacokinetics of dexlansoprazole were studied in 36 patients with symptomatic GORD aged
12 to 17 years in a multi-center study. Patients were randomised to receive DEXILANT 30 mg or 60
mg once daily for 7 days. In adolescents, dexlansoprazole mean Cmax was 81% to 105% of the adult
mean Cmax value, mean AUC was 78% to 88% of the adult mean AUC value, and mean CL/F was
112% to 132% of the adult mean CL/F value. Overall, dexlansoprazole pharmacokinetics in patients
aged 12 to 17 years were similar to those observed in healthy adults.
Gender
In a study of male and female healthy subjects who received a single oral dose of DEXILANT 60 mg,
females had higher (42.8%) systemic exposure (AUC) than males. No dosage adjustment is necessary
in patients based on gender.

Non-clinical data reveal no special hazard for humans based on conventional studies of safety
pharmacology, repeated dose toxicity, genotoxicity, toxicity to reproduction and development.
Lansoprazole is a racemic mixture of R- and S-enantiomers. Following administration of lansoprazole
in humans and animals, the major component circulating in plasma is dexlansoprazole, the Renantiomer
of lansoprazole. Therefore, the carcinogenic potential of dexlansoprazole was assessed
using existing lansoprazole studies.
In rat carcinogenicity studies, lansoprazole produced dose-related gastric ECL cell hyperplasia and
ECL cell carcinoids associated with hypergastrinaemia due to inhibition of acid secretion. Intestinal
metaplasia was also observed, as were Leydig cell hyperplasia and benign Leydig cell tumours in the
testes. After 18 months of treatment retinal atrophy was observed. This was not observed in monkeys,
dogs, or mice.
In mouse carcinogenicity studies dose-related gastric ECL cell hyperplasia developed as well as liver
tumours and adenoma of rete testis.
The clinical relevance of these findings is unknown.
Lansoprazole was positive in the Ames test and the in vitro human lymphocyte chromosomal
aberration assay. Lansoprazole was not genotoxic in the ex vivo rat hepatocyte unscheduled DNA
synthesis (UDS) test, the in vivo mouse micronucleus test, or the rat bone marrow cell chromosomal
aberration test.
Dexlansoprazole was positive in the Ames test and in the in vitro chromosome aberration test using
Chinese hamster lung cells. Dexlansoprazole was negative in the in vivo mouse micronucleus test.
A reproduction study conducted in rabbits at oral dexlansoprazole doses up to approximately 9 times
the maximum recommended human dexlansoprazole dose (60 mg per day), based on body surface
area (BSA), revealed no evidence of harm to the fetus due to dexlansoprazole. In addition,
reproduction studies performed in pregnant rats with oral lansoprazole at doses up to 40 times the
recommended human lansoprazole dose, based on BSA, and in pregnant rabbits at oral lansoprazole
doses up to 16 times the recommended human lansoprazole dose, based on BSA, revealed no evidence
of impaired fertility or harm to the fetus due to lansoprazole.

Capsule content
Silica, colloidal anhydrous
Hydroxypropylcellulose
Hypromellose
Low-substituted hydroxypropyl cellulose
Magnesium carbonate, heavy
Methacrylic acid-ethyl acrylate copolymer (1:1) dispersion 30 per cent (Methacrylic acid units, Ethyl
acrylate units, Sodium laurilsulfate, Polysorbate 80)
Methacrylic acid-methyl methacrylate copolymer (1:1)
Methacrylic acid-methyl methacrylate copolymer (1:2)
Macrogol 8000
Polysorbate 80
Sucrose
Sugar spheres (Sucrose, Corn starch)
Talc
Titanium dioxide (E171)
Triethyl citrate
Capsule shell 30 mg
Carrageenan (E407)
Titanium dioxide (E171)
Hypromellose
Potassium chloride
Water, purified
Indigotine (E132)
Iron oxide, black (E172)

Printing ink
Iron oxide, red (E172)
Iron oxide, yellow (E172)
Indigotine (E132)
Carnauba wax
17
Shellac
Glycerol mono-oleate

NA

Do not store above 30°C.

DEXILANT 30 mg: PVC/PE/polychlorotrifluoroethylene (PCTFE) - aluminium blister packs
containing 14, 28, 56 or 98 capsules.
Not all pack sizes may be marketed.

No special requirements.