Stadnex 20/40

Esomeprazole.

STADNEX 20 GASTRO-RESISTANT CAPSULES 20MG: Esomeprazole 20 mg (as esomeprazole (magnesium dihydrate) pellets).
STADNEX 40 GASTRO-RESISTANT CAPSULES 40MG: Esomeprazole 40 mg (as esomeprazole (magnesium dihydrate) pellets).
Excipients/Inactive Ingredients: Component of pellets: Sugar spheres, mannitol, sodium carbonate, talc, titanium dioxide, hypromellose, disodium hydrogen orthophosphate, sodium lauryl sulfate, hypromellose phthalate, cetyl alcohol.
Component of capsule: Gelatin, Azorubine (Carm), FD&C blue 1, FD&C red 3, titanium dioxide.
Printing ink (White SB-0007P): Shellac, dehydrate alcohol, isopropyl alcohol, butyl alcohol, propylene glycol, sodium hydroxide, povidone, titanium dioxide.

Adults: Gastroesophageal Reflux Disease (GORD): Treatment of erosive reflux esophagitis; Long-term management of patients with healed esophagitis to prevent relapse; Symptomatic treatment of gastroesophageal reflux disease (GORD).
In combination with appropriate antibacterial therapeutic regimens for the eradication of Helicobacter pylori and: Healing of Helicobacter pylori associated duodenal ulcer and prevention of relapse of peptic ulcers in patients with Helicobacter pylori associated ulcers.
Patients requiring continued NSAID therapy: Healing of gastric ulcers associated with NSAID therapy; Prevention of gastric and duodenal ulcers associated with NSAID therapy, in patients at risk.
Prolonged treatment after IV induced prevention of re-bleeding of peptic ulcers.
Treatment of Zollinger Ellison Syndrome.
Adolescents from the age of 12 years: Gastroesophageal Reflux Disease (GORD): Treatment of erosive reflux esophagitis; Long-term management of patients with healed esophagitis to prevent relapse; Symptomatic treatment of gastroesophageal reflux disease (GORD).
In combination with antibiotics in treatment of duodenal ulcer caused by Helicobacter pylori.

Administration: The capsules should be swallowed whole with some water. The capsules should not be chewed or crushed.
Dosage: Adults: Gastroesophageal Reflux Disease (GORD): 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.
Long-term management of patients with healed esophagitis to prevent relapse: 20 mg once daily.
Symptomatic treatment of gastroesophageal reflux disease (GORD): 20 mg once daily in patients without esophagitis. If symptom control has not been achieved after 4 weeks, the patient should be further investigated. Once symptoms have resolved, subsequent symptom control can be achieved using 20 mg once daily. An on-demand regimen taking 20 mg once daily, when needed, can be used. In NSAID treated patients at risk of developing gastric and duodenal ulcers, subsequent symptom control using an on-demand regimen is not recommended.
In combination with appropriate antibacterial therapeutic regimens for the eradication of Helicobacter pylori and: Healing of Helicobacter pylori associated duodenal ulcer and prevention of relapse of peptic ulcers in patients with Helicobacter pylori associated ulcers: 20 mg of esomeprazole with 1 g amoxicillin and 500 mg clarithromycin, all twice daily for 7 days.
Patients requiring continued NSAID therapy: Healing of gastric ulcers associated with NSAID therapy: The usual dose is 20 mg once daily. The treatment duration is 4-8 weeks.
Prevention of gastric and duodenal ulcers associated with NSAID therapy in patients at risk: 20 mg once daily.
Prolonged treatment after IV induced prevention of re-bleeding of peptic ulcers: 40 mg once daily for 4 weeks after IV 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: Impaired renal function: 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.
Impaired hepatic function: 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 of esomeprazole should not be exceeded.
Elderly: Dose adjustment is not required in the elderly.
Adolescents from the age of 12 years: Gastroesophageal Reflux Disease (GORD): 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.
Long-term management of patients with healed esophagitis to prevent relapse: 20 mg once daily.
Symptomatic treatment of gastroesophageal reflux disease (GORD): 20 mg once daily in patients without esophagitis. If symptom control has not been achieved after 4 weeks, the patient should be further investigated. Once symptoms have resolved, subsequent symptom control can be achieved using 20 mg once daily.
Treatment of duodenal ulcer caused by Helicobacter pylori: When selecting appropriate combination therapy, consideration should be given to official national, regional and local guidance regarding bacterial resistance, duration of treatment (most commonly 7 days but sometimes up to 14 days), and appropriate use of antibacterial agents. The treatment should be supervised by a specialist.
The posology recommendation is: 30 - 40 kg: Combination with two antibiotics: Esomeprazole 20 mg, amoxicillin 750 mg and clarithromycin 7.5 mg/kg body weight are all administered together twice daily for one week.
> 40 kg: Combination with two antibiotics: Esomeprazole 20 mg, amoxicillin 1 g and clarithromycin 500 mg are all administered together twice daily for one week.
Children below the age of 12 years: Esomeprazole should not be used in children younger than 12 years since no data is available.

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 utilised.

Hypersensitivity to the active substance, substituted benzimidazoles or to any of the excipients in the formula.
Esomeprazole should not be used concomitantly with nelfinavir.

In the presence of any alarm symptom (e.g. significant unintentional weight loss, recurrent vomiting, dysphagia, haematemesis or melaena) and when gastric ulcer is suspected or present, malignancy should be excluded, as treatment with esomeprazole may alleviate symptoms and delay diagnosis.
Stadnex contains sucrose. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.
Long term use: 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 active substance 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 medicinal products metabolised via CYP3A4 such as cisapride.
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: Hypomagnesemia, symptomatic and asymptomatic, has been reported rarely in patients treated with PPIs for at least three months, in most cases after a year of therapy. Serious adverse events include tetany, arrhythmias, and seizures. In most patients, treatment of hypomagnesemia required magnesium replacement and discontinuation of the PPI.
For patients expected to be on prolonged treatment or who take PPIs with medications such as digoxin or drugs that may cause hypomagnesemia (e.g., diuretics), health care professionals may consider monitoring magnesium levels prior to initiation of PPI treatment and periodically.
Inhibition CYP2C19 inhibition: 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 omeprazole. The clinical relevance of this interaction is uncertain. As a precaution, concomitant use of esomeprazole and clopidogrel should be discouraged.
Gastrointestinal tract infections: Decreased gastric acidity due to any means, including proton pump inhibitors, increases gastric counts of bacteria normally present in the gastrointestinal tract. Treatment with proton pump inhibitors may lead to slightly increased risk of gastrointestinal infections such as Salmonella and Campylobacter and possibly Clostridium difficile.
Concomitant use of Proton Pump Inhibitors (PPIs) with Methotrexate: Literature suggests that concomitant use of PPIs with methotrexate (primarily at high dose) may elevate and prolong serum levels of methotrexate and/or its metabolite, possibly leading to methotrexate toxicities. A temporary withdrawal of the PPI may be considered in some patients receiving treatments with high dose methotrexate.
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. 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.
Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated.
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.
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 Stadnex. SCLE after previous treatment with a proton pump inhibitor may increase the risk of SCLE with other proton pump inhibitors.
Effects on ability to drive and use machines: Esomeprazole has minor influence on the ability to drive or use machines. Adverse reactions such as dizziness (uncommon) and blurred vision (rare) has been reported. If affected patients should not drive or use machines.

Pregnancy: Clinical data on exposed pregnancies with esomeprazole are insufficient. With the racemic mixture omeprazole data on a larger number of exposed pregnancies from epidemiological studies indicate no malformative nor foetotoxic effect.
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.
Lactation: It is unknown whether esomeprazole/metabolites are excreted in human milk. There is insufficient information on the effects of esomeprazole in newborns/infants. Esomeprazole should not be used during breast-feeding.

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.
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).
Blood and lymphatic system disorders: Rare: Leukopenia, thrombocytopenia.
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.
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 disorders: Rare: Bronchospasm.
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 disorders: Uncommon: Dermatitis, pruritus, rash, urticaria.
Rare: Alopecia, photosensitivity.
Very rare: Erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN).
Not known: Subacute cutaneous lupus erythematosus.
Musculoskeletal and connective tissue disorders: Uncommon: Fracture of the hip, wrist or spine.
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 disorders: Very rare: Gynaecomastia.
General disorders and administration site conditions: Rare: Malaise, increased sweating.

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. Co-administration of omeprazole (40 mg once daily) reduced mean nelfinavir AUC, Cmax, and Cmin and mean AUC, Cmax, and Cmin for the pharmacologically active metabolite M8 was reduced. 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 once daily). Treatment with omeprazole 20 mg once daily had no effect on the exposure of darunavir (with concomitant ritonavir) and amprenavir (with concomitant ritonavir). Treatment with esomeprazole 20 mg once daily had no effect on the exposure of amprenavir (with and without concomitant ritonavir). Treatment with omeprazole 40 mg once daily had no effect on the exposure of lopinavir (with concomitant ritonavir).
Methotrexate: Case reports, published population pharmacokinetic studies, and retrospective analyses suggest that concomitant administration of PPIs and methotrexate (primarily at high dose) may elevate and prolong serum levels of methotrexate and/or its metabolite hydroxymethotrexate. However, no formal drug interaction studies of methotrexate with PPIs have been conducted.
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: The absorption of medicinal products such as ketoconazole, itraconazole and erlotinib can decrease and the absorption of digoxin can increase during treatment with esomeprazole. 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 metabolizing enzyme. Thus, when esomeprazole is combined with active substances metabolised by CYP2C19, such as diazepam, citalopram, imipramine, clomipramine, phenytoin etc., the plasma concentrations of these active substances 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 of esomeprazole resulted in a 45% decrease in clearance of the CYP2C19 substrate diazepam.
Phenytoin: Concomitant administration of 40 mg of 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 AUCt 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.
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 (t½) 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.
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 AUCt 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.

Store in a well-closed container, in a dry place. Protect from light.
Do not store above 30°C.

Antacids, Antireflux Agents & Antiulcerants

A02BC05 - esomeprazole ; Belongs to the class of proton pump inhibitors. Used in the treatment of peptic ulcer and gastro-oesophageal reflux disease (GERD).

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