MICRO LABS LIMITED, INDIA

SUMMARY OF PRODUCT CHARACTERISTICS

ESOMEPRAZOLE TABLETS 20 mg (ESOFAG-20)

SUMMARY OF PRODUCT CHARACTERISTICS

1. NAME OF THE MEDICINAL PRODUCT

1.1 Product Name:
Esomeprazole Tablets

1.2 Strength
20 mg

2. QUALITATIVE AND QUANTITATIVE COMPOSITION:

Each Enteric-coated tablet contains:
Esomeprazole Magnesium Trihydrate BP equivalent to Esomeprazole…. 20mg

3. PHARMACEUTIAL FORM
Tablets

4. CLINICAL PARTICULAR
4.1 Indication:
Esomeprazole tablets are indicated in adults for:
Gastroesophageal Reflux Disease (GERD)
– Treatment of erosive reflux esophagitis.
Prolonged treatment after i.v. induced prevention of rebleeding of peptic ulcers.
Treatment of Zollinger Ellison Syndrome
Esomeprazole tablets are indicated in adolescents from the age of 12 years for:
Gastroesophageal Reflux Disease (GERD)
- Treatment of erosive reflux esophagitis

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ESOMEPRAZOLE TABLETS 20 mg (ESOFAG-20)

4.2 Posology and method of Administration:

Posology
Adults
Gastroesophageal Reflux Disease (GERD)
- Treatment of erosive reflux esophagitis
40 mg once daily for 4 weeks
An additional 4 weeks treatment is recommended for patients in whom esophagitis has not
healed or who have persistent symptoms.
Prolonged treatment after i.v. induced prevention of rebleeding of peptic ulcers.
40 mg once daily for 4 weeks after i.v. induced prevention of rebleeding of peptic ulcers.
Treatment of Zollinger Ellison Syndrome
The recommended initial dosage is Esomeprazole 40 mg twice daily. The dosage should then be
individually adjusted and treatment continued as long as clinically indicated. Based on the
clinical data available, the majority of patients can be controlled on doses between 80 to 160 mg
esomeprazole daily. With doses above 80 mg daily, the dose should be divided and given twice
daily.
Special Populations
Renal impairment
Dose adjustment is not required in patients with impaired renal function. Due to limited
experience in patients with severe renal insufficiency, such patients should be treated with
caution.
Hepatic impairment
Dose adjustment is not required in patients with mild to moderate liver impairment. For patients
with severe liver impairment, a maximum dose of 20 mg Esomeprazole should not be exceeded.
Elderly
Dose adjustment is not required in the elderly.
Paediatric population
Adolescents from the age of 12 years
Gastroesophageal Reflux Disease (GERD)

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ESOMEPRAZOLE TABLETS 20 mg (ESOFAG-20)

- Treatment of erosive reflux esophagitis

40 mg once daily for 4 weeks
An additional 4 weeks treatment is recommended for patients in whom esophagitis has not
healed or who have persistent symptoms.
Children below the age of 12 years
For posology in patient’s aged 1 to 11 references is made to the Esomeprazole sachet SmPC.

Method of administration
The tablets should be swallowed whole with liquid. The tablets should not be chewed or crushed.
For patients who have difficulty in swallowing, the tablets can also be dispersed in half a glass of
non-carbonated water. No other liquids should be used as the enteric coating may be dissolved.
Stir until the tablets disintegrate and drink the liquid with the pellets immediately or within 30
minutes. Rinse the glass with half a glass of water and drink. The pellets must not be chewed or
crushed.
For patients who cannot swallow, the tablets can be dispersed in non-carbonated water and
administered through a gastric tube. It is important that the appropriateness of the selected
syringe and tube is carefully tested.

4.3 Contraindication:
Hypersensitivity to the active substance, to substituted benzimidazoles or to any of the excipients
listed in section 6.1.
Esomeprazole should not be used concomitantly with nelfinavir

4.4 Warning and Precaution:

In the presence of any alarm symptom (e.g. significant unintentional weight loss, recurrent
vomiting, dysphagia, hematemesis or melaena) and when gastric ulcer is suspected or present,
malignancy should be excluded, as treatment with Esomeprazole may alleviate symptoms and
delay diagnosis.
Long term use

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ESOMEPRAZOLE TABLETS 20 mg (ESOFAG-20)

Patients on long-term treatment (particularly those treated for more than a year) should be kept
under regular surveillance.
On demand treatment
Patients on on-demand treatment should be instructed to contact their physician if their
symptoms change in character.

Helicobacter pylori eradication

When prescribing esomeprazole for eradication of Helicobacter pylori, possible drug interactions
for all components in the triple therapy should be considered. Clarithromycin is a potent inhibitor
of CYP3A4 and hence contraindications and interactions for clarithromycin should be
considered when the triple therapy is used in patients concurrently taking other drugs
metabolised via CYP3A4 such as cisapride.
Gastrointestinal infections
Treatment with proton pump inhibitors may lead to slightly increased risk of gastrointestinal
infections such as Salmonella and Campylobacter.
Absorption of vitamin B12
Esomeprazole, as all acid-blocking medicines, may reduce the absorption of vitamin B12
(cyanocobalamin) due to hypo- or achlorhydria. This should be considered in patients with
reduced body stores or risk factors for reduced vitamin B12 absorption on long-term therapy.
Hypomagnesaemia
Severe hypomagnesaemia has been reported in patients treated with proton pump inhibitors
(PPIs) like esomeprazole for at least three months, and in most cases for a year. Serious
manifestations of hypomagnesaemia such as fatigue, tetany, 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 drugs that
may cause hypomagnesaemia (e.g. diuretics), healthcare professionals should consider
measuring magnesium levels before starting PPI treatment and periodically during treatment.

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Risk of fracture
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
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.
Sub acute 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
Esomeprazole. SCLE after previous treatment with a proton pump inhibitor may increase the risk
of SCLE with other proton pump inhibitors.

Combination with other medicinal products

Co-administration of esomeprazole with atazanavir is not recommended. If the combination of
atazanavir with a proton pump inhibitor is judged unavoidable, close clinical monitoring is
recommended in combination with an increase in the dose of atazanavir to 400 mg with 100 mg
of ritonavir; esomeprazole 20 mg should not be exceeded.
Esomeprazole is a CYP2C19 inhibitor. When starting or ending treatment with esomeprazole,
the potential for interactions with drugs metabolised through CYP2C19 should be considered.
An interaction is observed between clopidogrel and esomeprazole. The clinical relevance of this
interaction is uncertain. As a precaution, concomitant use of esomeprazole and clopidogrel
should be discouraged.
When prescribing esomeprazole for on demand therapy, the implications for interactions with
other pharmaceuticals, due to fluctuating plasma concentrations of esomeprazole should be
considered.

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ESOMEPRAZOLE TABLETS 20 mg (ESOFAG-20)

This medicinal product contains lactose. Patients with rare hereditary problems of galactose
intolerance, the Lapp-lactase deficiency or glucose-galactose malabsorption should not take this
medicinal product.

Interference with laboratory tests

Increased Chromogranin A (CgA) level may interfere with investigations for neuroendocrine
tumours. To avoid this interference, esomeprazole treatment should be stopped for at least 5 days
before CgA measurements. 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.

4.5 Interaction with other medicinal product and other forms of interactions:
Effects of esomeprazole on the pharmacokinetics of other drugs
Protease inhibitors
Omeprazole has been reported to interact with some protease inhibitors. The clinical importance
and the mechanisms behind these reported interactions are not always known. Increased gastric
pH during omeprazole treatment may change the absorption of the protease inhibitors. Other
possible interaction mechanisms are via inhibition of CYP2C19.

For atazanavir and nelfinavir, decreased serum levels have been reported when given together
with omeprazole and concomitant administration is not recommended. Co-administration of
omeprazole (40 mg once daily) with atazanavir 300 mg/ritonavir 100 mg to healthy volunteers
resulted in a substantial reduction in atazanavir exposure (approximately 75% decrease in AUC,
Cmax and Cmin). Increasing the atazanavir dose to 400 mg did not compensate for the impact of
omeprazole on atazanavir exposure. The co-administration of omeprazole (20 mg qd) with
atazanavir 400 mg/ritonavir 100 mg to healthy volunteers resulted in a decrease of approximately
30% in the atazanavir exposure as compared with the exposure observed with atazanavir 300
mg/ritonavir 100 mg qd without omeprazole 20 mg qd. Co-administration of omeprazole (40 mg
qd) reduced mean nelfinavir AUC, Cmax and Cmin by 36–39 % and mean AUC, Cmax and Cmin for

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the pharmacologically active metabolite M8 was reduced by 75-92%. Due to the similar
Pharmacodynamic effects and pharmacokinetic properties of omeprazole and esomeprazole,
concomitant administration with esomeprazole and atazanavir is not recommended and
concomitant administration with esomeprazole and nelfinavir is contraindicated.

For saquinavir (with concomitant ritonavir), increased serum levels (80-100%) have been
reported during concomitant omeprazole treatment (40 mg qd). Treatment with omeprazole 20
mg qd had no effect on the exposure of darunavir (with concomitant ritonavir) and amprenavir
(with concomitant ritonavir). Treatment with esomeprazole 20 mg qd had no effect on the
exposure of amprenavir (with and without concomitant ritonavir). Treatment with omeprazole 40
mg qd had no effect on the exposure of lopinavir (with concomitant ritonavir).

Methotrexate
When given together with PPIs, methotrexate levels have been reported to increase in some
patients. In high-dose methotrexate administration a temporary withdrawal of esomeprazole may
need to be considered.

Tacrolimus
Concomitant administration of esomeprazole has been reported to increase the serum levels of
tacrolimus. A reinforced monitoring of tacrolimus concentrations as well as renal function
(creatinine clearance) should be performed, and dosage of tacrolimus adjusted if needed.

Medicinal products with pH dependent absorption

Gastric acid suppression during treatment with esomeprazole and other PPIs might decrease or
increase the absorption of medicinal products with a gastric pH dependent absorption. As with
other medicinal products that decrease intragastric acidity, the absorption of medicinal products
such as ketoconazole, itraconazole and erlotinib can decrease and the absorption of digoxin can
increase during treatment with esomeprazole. Concomitant treatment with omeprazole (20 mg
daily) and digoxin in healthy subjects increased the bioavailability of digoxin by 10% (up to 30%

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in two out of ten subjects). Digoxin toxicity has been rarely reported. However, caution should
be exercised when esomeprazole is given at high doses in elderly patients. Therapeutic drug
monitoring of digoxin should then be reinforced.

Medicinal products metabolised by CYP2C19

Esomeprazole inhibits CYP2C19, the major esomeprazole-metabolising enzyme. Thus, when
esomeprazole is combined with drugs metabolised by CYP2C19, such as diazepam, citalopram,
imipramine, clomipramine, phenytoin etc., the plasma concentrations of these drugs may be
increased and a dose reduction could be needed. This should be considered especially when
prescribing esomeprazole for on-demand therapy.

Diazepam
Concomitant administration of 30 mg esomeprazole resulted in a 45% decrease in clearance of
the CYP2C19 substrate diazepam.

Phenytoin
Concomitant administration of 40 mg esomeprazole resulted in a 13% increase in trough plasma
levels of phenytoin in epileptic patients. It is recommended to monitor the plasma concentrations
of phenytoin when treatment with esomeprazole is introduced or withdrawn.

Voriconazole
Omeprazole (40 mg once daily) increased voriconazole (a CYP2C19 substrate) Cmax and AUC
by 15% and 41%, respectively

Cilostazol
Omeprazole as well as esomeprazole act as inhibitors of CYP2C19. Omeprazole, given in doses
of 40 mg to healthy subjects in a cross-over study, increased Cmax and AUC for cilostazol by
18% and 26% respectively, and one of its active metabolites by 29% and 69% respectively.

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ESOMEPRAZOLE TABLETS 20 mg (ESOFAG-20)

Cisapride
In healthy volunteers, concomitant administration of 40 mg esomeprazole resulted in a 32%
increase in area under the plasma concentration-time curve (AUC) and a 31% prolongation of
elimination half-life (t1/2) but no significant increase in peak plasma levels of cisapride. The
slightly prolonged QTc interval observed after administration of cisapride alone, was not further
prolonged when cisapride was given in combination with esomeprazole.

Warfarin
Concomitant administration of 40 mg esomeprazole to warfarin-treated patients in a clinical trial
showed that coagulation times were within the accepted range. However, post-marketing, a few
isolated cases of elevated INR of clinical significance have been reported during concomitant
treatment. Monitoring is recommended when initiating and ending concomitant esomeprazole
treatment during treatment with warfarin or other coumarine derivatives.
Clopidogrel
Results from studies in healthy subjects have shown a pharmacokinetic (PK)/ Pharmacodynamic
(PD) interaction between clopidogrel (300 mg loading dose/75 mg daily maintenance dose) and
esomeprazole (40 mg p.o. Daily) resulting in decreased exposure to the active metabolite of
clopidogrel by an average of 40% and resulting in decreased maximum inhibition of (ADP
induced) platelet aggregation by an average of 14%.
When clopidogrel was given together with a fixed dose combination of esomeprazole 20 mg +
ASA 81 mg compared to clopidogrel alone in a study in healthy subjects there was a decreased
exposure by almost 40% of the active metabolite of clopidogrel. However, the maximum levels
of inhibition of (ADP induced) platelet aggregation in these subjects were the same in the
clopidogrel and the clopidogrel + the combined (esomeprazole + ASA) product groups.
Inconsistent data on the clinical implications of a PK/PD interaction of esomeprazole in terms of
major cardiovascular events have been reported from both observational and clinical studies. As
a precaution concomitant use of clopidogrel should be discouraged.

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Investigated medicinal products with no clinically relevant interaction

Amoxicillin and quinidine
Esomeprazole has been shown to have no clinically relevant effects on the pharmacokinetics of
amoxicillin or quinidine.

Naproxen or rofecoxib
Studies evaluating concomitant administration of esomeprazole and either naproxen or rofecoxib
did not identify any clinically relevant pharmacokinetic interactions during short-term studies.
Effects of other medicinal products on the pharmacokinetics of esomeprazole

Medicinal products which inhibit CYP2C19 and/or CYP3A4

Esomeprazole is metabolised by CYP2C19 and CYP3A4. Concomitant administration of
esomeprazole and a CYP3A4 inhibitor, clarithromycin (500 mg b.i.d.), resulted in a doubling of
the exposure (AUC) to esomeprazole. Concomitant administration of esomeprazole and a
combined inhibitor of CYP2C19 and CYP3A4 may result in more than doubling of the
esomeprazole exposure. The CYP2C19 and CYP3A4 inhibitor voriconazole increased
omeprazole AUC by 280%. A dose adjustment of esomeprazole is not regularly required in
either of these situations. However, dose adjustment should be considered in patients with severe
hepatic impairment and if long-term treatment is indicated.

Medicinal products which induce CYP2C19 and/or CYP3A4

Drugs known to induce CYP2C19 or CYP3A4 or both (such as rifampicin and St. John's wort)
may lead to decreased esomeprazole serum levels by increasing the esomeprazole metabolism.

Paediatric population
Interaction studies have only been performed in adults.

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4.6 Pregnancy and Lactation:

Pregnancy
Clinical data on exposed pregnancies with Esomeprazole are insufficient. With the neither
racemic mixture omeprazole data on a larger number of exposed pregnancies stemmed from
epidemiological studies indicate no malformative nor foetotoxic effects. Animal studies with
esomeprazole do not indicate direct or indirect harmful effects with respect to embryonal/foetal
development. Animal studies with the racemic mixture do not indicate direct or indirect harmful
effects with respect to pregnancy, parturition or postnatal development. Caution should be
exercised when prescribing to pregnant women.
A moderate amount of data on pregnant women (between 300-1000 pregnancy outcomes)
indicates no malformative or foeto/neonatal toxicity of esomeprazole.
Animal studies do not indicate direct or indirect harmful effects with respect to reproductive
toxicity.

Lactation
It is not known whether esomeprazole is excreted in human breast milk. There is insufficient
information on the effects of esomeprazole in new-borns/infants. Esomeprazole should not be
used during breast-feeding.

Fertility
Animal studies with the racemic mixture omeprazole, given by oral administration do not
indicate effects with respect to fertility.

4.7 Effect on the ability to drive and use machines:

Esomeprazole has minor influence on the ability to drive and use machines. Adverse reactions
such as dizziness (uncommon) and blurred vision (rare) has been reported. If affected patients
should not drive or use machines.

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4.8 Undesirable effects:

Summary of the safety profile
Headache, abdominal pain, diarrhoea and nausea are among those adverse reactions that have
been most commonly reported in clinical trials (and also from post-marketing use). In addition,
the safety profile is similar for different formulations, treatment indications, age groups and
patient populations. No dose-related adverse reactions have been identified.

Tabulated list of adverse reactions

The following adverse drug reactions have been identified or suspected in the clinical trials
programme for esomeprazole and post-marketing. None was found to be dose-related. The
reactions are classified according to frequency 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).
System Organ Class Frequency Undesirable Effect

Blood and lymphatic system Rare Leukopenia, thrombocytopenia

disorders Very rare Agranulocytosis, pancytopenia

Immune system disorders Rare Hypersensitivity reactions e.g. fever,

angioedema and anaphylactic
reaction/shock

Metabolism and nutrition disorders Uncommon Peripheral oedema

Rare Hyponatraemia

Not known Hypomagnesaemia; severe

hypomagnesaemia can correlate with
hypocalcaemia. Hypomagnesaemia may
also be associated with hypokalaemia.

Psychiatric disorders Uncommon Insomnia

Rare Agitation, confusion, depression

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Very rare Aggression, hallucinations

Nervous system disorders Common Headache

Uncommon Dizziness, paraesthesia, somnolence

Rare Taste disturbance

Eye disorders Rare Blurred vision

Ear and labyrinth disorders Uncommon Vertigo

Respiratory, thoracic and mediastinal Rare Bronchospasm

disorders

Gastrointestinal disorders Common Abdominal pain, constipation,

diarrhoea, flatulence, nausea/vomiting,
fundic gland polyps (benign)

Uncommon Dry mouth

Rare Stomatitis, gastrointestinal candidiasis

Not known Microscopic colitis

Hepatobiliary disorders Uncommon Increased liver enzymes

Rare Hepatitis with or without jaundice

Very rare Hepatic failure, encephalopathy in

patients with pre-existing liver disease

Skin and subcutaneous tissue Uncommon Dermatitis, pruritus, rash, urticaria

disorders Rare Alopecia, photosensitivity

Very rare Erythema multiforme, Stevens-Johnson

syndrome, toxic epidermal necrolysis
(TEN)

Not known Sub acute cutaneous lupus

erythematosus

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Musculoskeletal and connective Uncommon Fracture of the hip, wrist or spine

tissue disorders Rare Arthralgia, myalgia

Very rare Muscular weakness

Renal and urinary disorders Very rare Interstitial nephritis; in some patients
renal failure has been reported
concomitantly.

Reproductive system and breast Very rare Gynaecomastia

disorders

General disorders and administration Rare Malaise, increased sweating

site conditions

4.9 Overdosage:
There is very limited experience to date with deliberate overdose. The symptoms described in
connection with 280 mg were gastrointestinal symptoms and weakness. Single doses of 80 mg
esomeprazole were uneventful. No specific antidote is known. Esomeprazole is extensively
plasma protein bound and is therefore not readily dialyzable. As in any case of overdose,
treatment should be symptomatic and general supportive measures should be utilized.

5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamics:
Pharmacotherapeutic group: Drugs for acid-related disorders proton pump inhibitors
ATC code: A02B C05
Esomeprazole is the S-isomer of omeprazole and reduces gastric acid secretion through a specific
targeted mechanism of action. It is a specific inhibitor of the acid pump in the parietal cell. Both
the R- and S-isomer of omeprazole have similar pharmacodynamics activity.
Mechanism of action

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Esomeprazole is a weak base and is concentrated and converted to the active form in the highly
acidic environment of the secretory canaliculi of the parietal cell, where it inhibits the enzyme
H+K+-ATPase – the acid pump and inhibits both basal and stimulated acid secretion.

5.2 Pharmacokinetic Properties:

Absorption
Esomeprazole is acid labile and is administered orally as enteric-coated granules. In vivo
conversion to the R-isomer is negligible. Absorption of esomeprazole is rapid, with peak plasma
levels occurring approximately 1-2 hours after dose. The absolute bioavailability is 64% after a
single dose of 40 mg and increases to 89% after repeated once daily administration. For 20 mg
esomeprazole the corresponding values are 50% and 68%, respectively.
Food intake both delays and decreases the absorption of esomeprazole although this has no
significant influence on the effect of esomeprazole on intragastric acidity.

Distribution
The apparent volume of distribution at steady state in healthy subjects is approximately 0.22 l/kg
body weight. Esomeprazole is 97% plasma protein bound.

Biotransformation
Esomeprazole is completely metabolised by the cytochrome P450 system (CYP). The major part
of the metabolism of esomeprazole is dependent on the polymorphic CYP2C19, responsible for
the formation of the hydroxy- and desmethyl metabolites of esomeprazole. The remaining part is
dependent on another specific isoform, CYP3A4, responsible for the formation of esomeprazole
sulphone, the main metabolite in plasma.

Elimination
The parameters below reflect mainly the pharmacokinetics in individuals with a functional
CYP2C19 enzyme, extensive metabolisers.

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Total plasma clearance is about 17 l/h after a single dose and about 9 l/h after repeated
administration. The plasma elimination half-life is about 1.3 hours after repeated once daily
dosing. Esomeprazole is completely eliminated from plasma between doses with no tendency for
accumulation during once-daily administration.
The major metabolites of esomeprazole have no effect on gastric acid secretion. Almost 80% of
an oral dose of esomeprazole is excreted as metabolites in the urine, the remainder in the faeces.
Less than 1% of the parent drug is found in urine.

Linearity/non-linearity
The pharmacokinetics of esomeprazole has been studied in doses up to 40 mg b.i.d. The area
under the plasma concentration-time curve increases with repeated administration of
esomeprazole. This increase is dose-dependent and results in a more than dose proportional
increase in AUC after repeated administration. This time- and dose-dependency is due to a
decrease of first pass metabolism and systemic clearance probably caused by an inhibition of the
CYP2C19 enzyme by esomeprazole and/or its sulphone metabolite.

Special patient populations

Poor metabolisers
Approximately 2.9 ±1.5% of the population lack a functional CYP2C19 enzyme and are called
poor metabolisers. In these individuals the metabolism of esomeprazole is probably mainly
catalysed by CYP3A4. After repeated once daily administration of 40 mg esomeprazole, the
mean area under the plasma concentration-time curve was approximately 100% higher in poor
metabolisers than in subjects having a functional CYP2C19 enzyme (extensive metabolisers).
Mean peak plasma concentrations were increased by about 60%. These findings have no
implications for the posology of esomeprazole.
Gender
Following a single dose of 40 mg esomeprazole the mean area under the plasma concentration-
time curve is approximately 30% higher in females than in males. No gender difference is seen

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after repeated once daily administration. These findings have no implications for the posology of
esomeprazole.
Hepatic impairment
The metabolism of esomeprazole in patients with mild to moderate liver dysfunction may be
impaired. The metabolic rate is decreased in patients with severe liver dysfunction resulting in a
doubling of the area under the plasma concentration-time curve of esomeprazole. Therefore, a
maximum of 20 mg should not be exceeded in patients with severe dysfunction. Esomeprazole or
its major metabolites do not show any tendency to accumulate with once daily dosing.
Renal impairment
No studies have been performed in patients with decreased renal function. Since the kidney is
responsible for the excretion of the metabolites of esomeprazole but not for the elimination of the
parent compound, the metabolism of esomeprazole is not expected to be changed in patients with
impaired renal function.
Elderly
The metabolism of esomeprazole is not significantly changed in elderly subjects (71-80 years of
age).
Paediatric population
Adolescents 12-18 years:
Following repeated dose administration of 20 mg and 40 mg esomeprazole, the total exposure
(AUC) and the time to reach maximum plasma concentration (tmax) in 12 to 18 year-olds was
similar to that in adults for both esomeprazole doses.

5.3 Preclinical safety data

Non-clinical data reveal no special hazard for humans based on conventional studies of safety
pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to
reproduction and development. Adverse reactions not observed in clinical studies, but seen in
animals at exposure levels similar to clinical exposure levels and with possible relevance to
clinical use were as follows:

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Carcinogenicity studies in the rat with the racemic mixture have shown gastric ECL-cell
hyperplasia and carcinoids. These gastric effects in the rat are the result of sustained, pronounced
hypergastrinaemia secondary to reduced production of gastric acid and are observed after long-
term treatment in the rat with inhibitors of gastric acid secretion.

6. PHARMACEUTICAL PARTICULARS:
6.1 List of Excipients:
Esofag 20
Microcrystalline cellulose BP
Maize starch BP
Lactose BP (Monohydrate)
Crosspovidone BP
Anhydrous Disodium Hydrogen Phosphate BP
Magnesium stearate BP
Hypromellose BP (15 CPS)
Titanium dioxide BP
Polyethylene glycol 4000 USP
Talc BP
Methcrylic acid copolymer (E-L10055)
Dibutyl phthalate
Ferric Oxide (RED)
Polyethylene Glycol 6000

6.2 Incompatibilities:
No major incompatibilities are known.

6.3 Shelf Life:

36 months from the date of manufacturing

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6.4 Special Storage Conditions:

Store below 30°C. Keep out of reach of children.

6.5 Nature and Contents of container:

Alu/Alu Pack of 10 Tablets, such a 3 blisters are packed in Outer carton along with Pack Insert.

6.6 Special Precautions for disposal and other handlings:

Not applicable.

7. Marketing Authorization Holder:

Micro labs limited
31, Race course road
Bangalore-560001
INDIA

8. Marketing Authorization Numbers

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9. Date of first authorization

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10. Date of revision of the text

Oct 2019

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