Esomeprazole Magnesium
capsules
Read all of this leaflet carefully before you start taking this
medicine because it contains important information for you.
* Keep this leaflet. You may need to read it again.
* If you have any further questions, ask your doctor or
pharmacist.
* This medicine has been prescribed for you only.
Do not pass it on to others. It may harm them, even if their
signs of illness are the same as yours.
* If you get any side effects talk to your doctor or pharmacist.
This includes any possible side effects not listed in this leaflet.
See section 4.
This is a medicament:
- A medicament is a product which
affects your health and its consumption
contrary to instructions is dangerous for
you.
- Follow strictly the doctor's prescription,
the method of use and the instructions of
the pharmacist who sold the
medicament.
- The doctor and the pharmacist are the
experts in medicine, their benefits and
risks.
- Do not by yourself interrupt the period
of treatment prescribed.
- Do not repeat the same prescription
without consulting your doctor.
- Keep all medicaments out of reach of
children.
Council of Arab Health Ministers
Union of Arab pharmacists
1.DESCRIPTION
ESOFLUX is a capsule containing enteric coated pellets.
2. COMPOSITION
Each capsule contains:
-40 mg of Esomeprazole Magnesium Trihydrate present in 470,6mg of
enteric coated pellets.
Excipients: Hypromellose E5, Polysorbate 80 (Tween-80), Sodium
Hydroxide, Purified Talc, Titanium dioxide, Methacrylic Acid & Ethyl
Acrylate copolymer (Type C) L30D, Diethyl phthalate.
3. THERAPEUTIC INDICATIONS
ESOFLUX is indicated in adults (18 years of age and above) for
treatment of conditions where a reduction in gastric acid secretion is
required such as:
• Treatment of gastroesophageal reflux disease (GERD)
• Risk reduction of NSAID-associated gastric ulcer
• H. pylori eradication to reduce the risk of duodenal ulcer recurrence
• Pathological hypersecretory conditions, including Zollinger-Ellison
syndrome
4. MECHANISM OF ACTION AND PHARMACODYNAMIC EFFECTS
Esomeprazole magnesium (a substituted benzimidazole), reduces
gastric acid secretion through a highly targeted mechanism of
action.
Esomeprazole accumulates in the acidic environment of the parietal
cells after absorption, where it is converted into the active form. This
active sulphenamide specifically binds the H+ , K+ -ATPase (proton
pump), to block the final step in acid production by the parietal cells,
thus reducing gastric acidity.
Esomeprazole is effective in the inhibition of both basal acid secretion
and stimulated acid secretion.
5. PHARMACOKINETICS
Absorption
ESOFLUX Capsules contain an enteric-coated pellet formulation of
esomeprazole. After oral administration peak plasma levels (Cmax)
occur at approximately 1.5 hours (Tmax). The Cmax increases
proportionally when the dose is increased, and there is a three-fold
increase in the area under the plasma concentration-time curve
(AUC) from 20 to 40 mg. At repeated once daily dosing with 40 mg,
the systemic bioavailability is approximately 90% compared to 64%
after a single dose of 40 mg. The mean exposure (AUC) to esomepra-
zole increases from 4.32 µmol*hr/L on day 1 to 11.2 µmol*hr/L on day 5
after 40 mg once daily dosing.
The AUC after administration of a single 40 mg dose of ESOFLUX
capsules is decreased by 43% to 53% after food intake compared to
fasting conditions. ESOFLUX should be taken at least one hour before
meals.
Distribution
Esomeprazole is 97% bound to plasma proteins. Plasma protein binding
is constant over the concentration range of 2 to 20 µmol/L. The
apparent volume of distribution at steady state in healthy volunteers is
approximately 16 L.
Metabolism
Esomeprazole is extensively metabolized in the liver by the cytochrome
P450 (CYP) enzyme system. The metabolites of esomeprazole lack
antisecretory activity. The major part of esomeprazole’s metabolism is
dependent upon the CYP 2C19 isoenzyme, which forms the hydroxy
and desmethyl metabolites.
The remaining amount is dependent on CYP 3A4 which forms the
sulphone metabolite. CYP 2C19 isoenzyme exhibits polymorphism in
the metabolism of esomeprazole, since some 3% of Caucasians and 15
to 20% of Asians lack CYP 2C19 and are termed Poor Metabolizers. At
steady state, the ratio of AUC in Poor Metabolizers to AUC in the rest of
the population (Extensive Metabolizers) is approximately 2. Following
administration of equimolar doses, the S- and R-isomers are
metabolized differently by the liver, resulting in higher plasma levels of
the S- than of the R-isomer.
Excretion
The plasma elimination half-life of esomeprazole is approximately 1 to
1.5 hours. Less than 1% of parent drug is excreted in the urine.
Approximately 80% of an oral dose of esomeprazole is excreted as
inactive metabolites in the urine, and the remainder is found as
inactive metabolites in the feces.
6. CONTRAINDICATIONS
• in patients who are hypersensitive to esomeprazole or to any
ingredient in the formulation.
• with co-administration of rilprivirine due to significant decrease in
rilpivirine exposure and loss of therapeutic effect
7. DOSAGE AND ADMINISTRATION
Gastroesophageal Reflux Disease (GERD)
For Adults: ESOFLUX 40 mg Once daily for 4 to 8 weeks
For 12 to 17 years: ESOFLUX 40 mg Once daily for up to 8 weeks
Risk Reduction of NSAID-Associated Gastric Ulcer
ESOFLUX 40 mg Once daily for up to 6 months
H. pylori Eradication (Triple Therapy)
ESOFLUX 40 mg Once daily for 10 days
Amoxicillin 1000 mg Twice daily for 10 days
Clarithromycin 500 mg Twice daily for 10 days
Pathological Hypersecretory Conditions
ESOFLUX 40 mg Twice daily
Patients with severe liver impairment-do not exceed dose of 20 mg.
8. WARNINGS AND PRECAUTIONS
• Symptomatic response does not preclude the presence of gastric
malignancy.
• Atrophic gastritis has been noted with long-term omeprazole therapy
• Acute interstitial nephritis has been observed in patients taking PPIs.
• Cyanocobalamin (vitamin B-12) Deficiency: Daily long-term use (e.g.,
longer than 3 years) may lead to malabsorption or a deficiency of
cyanocobalamin.
• PPI therapy may be associated with increased risk of Clostridium
difficile associated diarrhea.
• Bone Fracture: Long-term and multiple daily dose PPI therapy may be
associated with an increased risk for osteoporosis-related fractures of
the hip, wrist or spine.
• Hypomagnesemia has been reported rarely with prolonged
treatment with PPIs.
• Avoid concomitant use of ESOFLUX with St John’s Wort or rifampin due
to the potential reduction in esomeprazole levels.
• Interactions with diagnostic investigations for Neuroendocrine
Tumors: Increases in intragastric pH may result in hypergastrinemia
and enterochromaffin-like cell hyperplasia and increased
chromogranin A levels which may interfere with diagnostic
investigations for neuroendocrine tumors.
9. SPECIFIC PATIENT POPULATIONS
Renal Insufficiency: No dose adjustment is required.
Hepatic Insufficiency: No dose adjustment is required for patients
with mild to moderate hepatic impairment. The daily doses of 20 mg
in patients with severe hepatic impairment should not, as a rule, be
exceeded.
Elderly Patients: No dose adjustment is required.
Pregnant Women: There are no adequate or well-controlled studies
in pregnant women. Therefore, the safety of ESOFLUX in pregnancy
has not been established. ESOFLUX should not be administered to
pregnant women unless the expected benefits outweigh the
potential risks. Pregnancy Category B
Nursing Women: It has not been investigated whether or not
esomeprazole is excreted in human breast milk. No studies in
lactating women have been performed. Precaution should be
exercised because many drugs can be excreted in human milk.
Esomeprazole is the Sisomer of omeprazole, which is secreted in
breast milk. Therefore, ESOFLUX should not be given to nursing
mothers unless its use is considered essential.
10. DRUG INTERRACTIONS
Esomeprazole is extensively metabolized in the liver by CYP2C19 and
CYP3A4.
• May affect plasma levels of antiretroviral drugs – use with
atazanavir and nelfinavir is not recommended; if saquinavir is used
with ESOFLUX, monitor for toxicity and consider saquinavir dose
reduction.
• May interfere with drugs for which gastric pH affects bioavailability
(e.g., ketoconazole, iron salts, erlotinib, digoxin and mycophenolate
mofetil). Patients treated with ESOFLUX and digoxin may need to be
monitored for digoxin toxicity.
• Combined inhibitor of CYP 2C19 and 3A4 may raise esomeprazole
levels.
• Clopidogrel: ESOFLUX decreases exposure to the active metabolite
of clopidogrel.
• May increase systemic exposure of cilostazol and an active
metabolite. Consider dose reduction.
• Tacrolimus: ESOFLUX may increase serum levels of tacrolimus
• Methotrexate: ESOFLUX may increase serum levels of methotrexate.
11. ADVERSE REACTIONS
Most common adverse reactions:
• Adults (≥ 18 years) (incidence > 1%) are headache, diarrhea, nausea,
flatulence, abdominal pain, constipation, and dry mouth
• Pediatric (12 to 17 years) (incidence > 2%) are headache, diarrhea,
abdominal pain, nausea, and somnolence.
12. STORAGE CONDITION
Store below 30° C. Protect from light.
Keep in original pack in intact condition.
Date of Revision: March 13, 2025
PI021/01
Marketing Authorisation Holder,
Manufacturer
30 capsules Reg. N°: 19725/1
