Descrizione Clinica
ESOMENAR 20 mg GastroResisting tablets
active principles
A gastroresistant tablet contains 20 mg of esomeprazole (equivalent to 21.75 mg of esomeprazole magnesium dihydrate). Excipient with known effects: Each tablet contains no more than 5.65 mg of sucrose.For the complete list of excipients, see paragraph 6.1.Eccepienti
Microgranuli: Copolymer of methacrylic acrylic acrylate (1: 1) 30% dispersion, talc, triethylcitrate, 3cps, sugar spheres, magnesium stearate, hydroxypropil cellulose, Glycerol monostearate 40-55, polysorbate 80. Tablet core: Microcrystalline cellulose, Povidone K29 / 32, Macrogol 6000, CRUSPOVIDONE TYPE A, sodium stearil fumarate. Tablet coating: Ipromellosa, titanium dioxide (E171), Macrogol / PEG 400, red oxide iron (E172), yellow oxide iron (E172).Therapeutic indications
ESOMENAR is indicated in adults for short-term treatment of reflux symptoms (eg pyrosis and rigurgito acid).Contraindications
Hypersensitivity to the active ingredient, to benzimidazolic substitutes or to any of the excipients listed in the paragraph 6.1. Esomeprazole should not be used in conjunction with Nelfinavir (see section 4.5).Dosage
Dosage: The recommended dose is 20 mg of esomeprazole (one tablet) a day. You may need to take the tablets for 2-3 consecutive days to get the improvement of symptoms. The duration of the treatment is up to 2 weeks. Once the complete disappearance of the symptoms has been obtained, the treatment must be interrupted. If you do not get the resolution of symptoms within 2 weeks of continuous treatment, the patient must consult a doctor. Special populations. . Pediatric population: There is no indication for specific use of Esomenar in the pediatric population under the age of 18 in the indication: "Short term treatment of reflux symptoms (eg pyrosis and rigurgito acid)". Impairment of renal function: In patients with compromised renal function, no dose adjustment is required. Due to the limited experience in patients with serious renal failure, these patients must be treated with caution (see section 5.2). Hepatic function impaired: In patients with mild to moderate hepatic impairment, no dose adjustment is required. However, patients with severe hepatic impairment must be recommended by a doctor before taking Esomenar (see section 4.4 and 5.2). Elderly (≥65 years): In the elderly there is no dose adjustment. Mode of administration: The tablets must be whole ingested with half a glass of water. The tablets should not be chewed or crushed. For patients who have injury difficulties, tablets can be dispersed in half a glass of non-carbonated water. No other liquid must be used as the enteric coating can dissolve. Mix until the tablet has not disintegrated and drink water with granules immediately or within 30 minutes. Rinse the glass filling it in half of water and drink. Granules must not be chewed or crushed.Storage
Do not store at a temperature above 30 ° C.Warnings
Patients must be educated to consult a doctor if: - they have a significant loss of non-intentional weight, recurring vomiting, dysphagia, hematemesis or Melena and when the presence of a gastric ulcer is suspected or is confirmed. Malignant ulcer nature must be excluded as esomeprazole therapy could alleviate symptoms and delay diagnosis. - They had a previous gastric ulcer or gastrointestinal surgical interventions. - They were in continuous symptomatic treatment of dyspepsia or pyrosis for 4 or more weeks. - They have jaundice or severe liver disease. - They are over 55 years old with new or recently changed symptoms. Patients with recurrent long-term symptoms of dyspepsia or pyrosis must consult their doctor at regular intervals. Patients over the age of 55 who take daily treatments for dyspexia and pyrosis without a prescription, must inform the doctor or pharmacist. Patients should not take Esomenar as a long-term preventive drug. Treatment with proton pump inhibitors (IPP) can lead to a slight increase in gastrointestinal infections such as Salmonella and Campylobacter , and possibly also from Clostridium difficult in hospitalized patients (see paragraph 5.1). Patients should consult their doctor before taking this medicine if they must be subjected to endoscopy or urea breath test. Combination with other medicines: concomitant administration of esomeprazole with Atazanavir is not recommended (see section 4.5). If the Association of Atazanavir is inevitable with a proton pump inhibitor, a close monitoring is recommended in association with an increase in the dose of Atazanavir at 400 mg with 100 mg of ritonavir. The dose of esomeprazole must not exceed 20 mg. Esomeprazole, like all acid-blocking medicines, can reduce the absorption of vitamin B12 (cyanocobalamin) due to hypo- or aclory. This must be taken into consideration in patients with reduced body reserves or risk factors for reduced absorption of vitamin B12 in long-term therapy. Esomeprazole is a CYP2C19 inhibitor. When starting or ending the treatment with esomeprazole, it is necessary to consider the possibility of interactions with medicinal products metabolized through the CYP2C19. An interaction between Clopidogrel and Esomeprazole was observed (see section 4.5). The clinical relevance of that interaction is not certain. As a precaution, the concomitant use of esomeprazole and clopidogrel must be discouraged. Patients should not take another IPP or H2 antagonist in conjunction. The severe hypomagnesemia was reported in patients treated with proton pump inhibitors (IPP), such as esomeprazole, for at least 3 months, and in most cases after 1 year of therapy. Serious manifestations of hypomagnesemia, such as fatigue, tetania, delirium, convulsions, dizziness and ventricular arrhythmia can insorcely arise and be underestimated. In most affected patients, hypomagnesemia improves after magnesium intake and suspension of the administration of the proton pump inhibitors. For patients who are expected to have to take for a long time or taking proton pump inhibitors (IPP) with digoxin or drugs that can cause hypomagnesemia (for example, diuretics), healthcare professionals must take into consideration Monitoring of magnesium levels before starting treatment with proton pump inhibitors and periodically during treatment. Lupus erythematosus Subacuto skin (LECS): Protonic pump inhibitors are associated with extremely infrequent cases of LECS. In the presence of injuries, especially on the skin parts exposed to sunlight, and if accompanied by arthralgia, the patient must immediately contact the doctor and the healthcare operator must evaluate the opportunity to interrupt treatment with Esomernar. The appearance of LECS following a treatment with a proton pump inhibitor can increase the risk of the onset of LECS with other proton pump inhibitors. Interference with laboratory exams: An increased level of chromogranin A (CGA) can interfere with diagnostic exams for neuroendocrine tumors. To avoid this interference, the treatment with Esomenar must be suspended for at least five days before the CGA measurements (see section 5.1). If the CGA and gastrin levels have not returned within the reference range after the initial measurement, the measurements should be repeated 14 days after the treatment interruption with proton pump inhibitor. Sucrose: This product contains sucrose. Patients suffering from hereditary problems of fructose intolerance, glucose-galactose malabsorption or lack of sucrase -isomaltase should not take this medicine.Interactions
Interaction studies have been carried out only in adults. Effects of Esomeprazole on the pharmacokinetics of other medicines: Since esomeprazole is an omeprazole enantiomer it is advisable to consider the interactions observed with omeprazole. Proteases' inhibitors: it has been reported that omeprazole interacts with some protease inhibitors. Clinical importance and mechanisms behind these referring interactions are not always known. The increase in gastric pH during treatment with omeprazole can change the absorption of protease inhibitors. Other possible interaction mechanisms take place via CYP 2C19 inhibition. For Atazanavir and Nelphinavir, serum levels have been reported reduced when administered with omeprazole and concomitant administration is not recommended. Concomitant administration of omeprazole (40 mg once a day) with Atazanavir 300 mg / ritonavir 100 mg at healthy volunteers gave rise to a substantial reduction in exposure to the Atazanavir (reduction of approximately 75% of AUC, Cmax and Cmin). The increase in the dose of Atazanavir at 400 mg did not offset the impact of homeprazole on the exposure to the Atazanavir. Concomitant administration of omeprazole (20 mg once a day) with Atazanavir 400 mg / ritonavir 100 mg in healthy volunteers gave rise to a reduction of about 30% of the exposure to the Altazanavir respect At the exposure observed with Atazanavir 300 mg / ritonavir 100 mg once a day without omeprazole 20 mg once a day. Concomitant administration of omeprazole (40 mg once a day) has reduced AUC, Cmax and Cmin medium of the Nelphinavir of 36-39% and AUC, Cmax and Cmin medium of pharmacologically active M8 metabolite were reduced by 75-92%. For the Saquinavir (in conjunction with the Ritonavir), increases in serum levels were reported (80-100%) during concomitant treatment with omeprazole (40 mg once a day). Treatment with omeprazole 20 mg once a day had no effect on exposure to Darunavir (in conjunction with Ritonavir) and to amprenavir (in conjunction with ritonavir). The treatment with Esomeprazole 20 mg once a day had no effect on the exposure to the amprenavir (with or without ritonavir in conjunction). Treatment with omeprazole 40 mg once a day had no effects on exposure to Lopinavir (in conjunction with Ritonavir). Due to the pharmacodynamic effects and similar pharmacokinetic properties of omeprazole and exomeprazole, concomitant administration of Esomeprazole and Atazanavir is not recommended and concomitant administration of Esomeprazole and Nelphinavir is contraindicated. Methotrexate: It has been reported that the levels of methotrexate, when administered together with proton pump inhibitors, increased in some patients. In case of high doses, high doses can be considered to be considered a temporary suspension of esomeprazole. Tacrolimus: It has been reported that concomitant administration of esomeprazole increases serum levels of tacrolimus. A reinforced monitoring of tacrolimus concentrations must be performed, as well as renal function (creatinine clearance), and the tacrolimus dosage adjusted, if necessary. Medicines with pH-dependent absorption: The suppression of gastric acidity during treatment with esomeprazole and other IPP can reduce or increase the absorption of medicines with addicted to gastric pH. As noted with other medicines that reduce intragastrical acidity, the absorption of medicines such as ketoconazole, itraconazole and erlotinib can decrease while digoxy absorption can increase during treatment with Esomeprazole. Concomitant treatment with omeprazole (20 mg / day) and digoxin in healthy subjects increases the bioavailability of 10% digoxin (up to 30% in two out of ten subjects). The toxicity of digoxin has rarely been reported. However, caution is recommended in case of administration of high doses of esomeprazole in elderly patients. It is also recommended to follow a close therapeutic monitoring of digoxin. Medicines metabolized by CYP2C19: The esomeprazole inhibits the CYP2C19, the main metabolic enzyme esomeprazole. So when esomeprazole is associated with other medicines metabolised through the CYP2C19, such as warfarin, phenytoin, citalopram, imipramine, clomipramine, diazepam, etc., le Plasmatic concentrations of these medicines may be increased and a dose reduction may be needed. In the case of the clopidogrel, a pro-format transformed into its active metabolite from the CYP2C19, the plasma concentration of the active metabolite could be reduced. Warfarin: Concomitant administration of 40 mg of esomeprazole in patients treated with Warfarin in clinical trials showed that coagulation times returned to the interval interval. However, after the marketing of the drug, some isolated cases of a clinically relevant increase in RF have been reported during concomitant treatment. Monitoring is recommended when you start or end the concomitant treatment with esomeprazole during Warfarin treatment or other coumarin derivatives. Clopidogrel: The results of studies in healthy subjects showed a pharmacokinetic interaction (PK) / pharmacodynamics (PD) between Clopidogrel (loading dose of 300 mg / dose of maintenance of 75 mg / day) and esomeprazole (40 mg per OS per day) which gave rise to a reduced exposure to the active metabolite of Clopidogrel on average by 40% and to a reduced maximum inhibition of platelet aggregation (ADP-induced) on average of 14%. In a study in healthy subjects, when Clopidogrel was administered together with a fixed doses of Esomeprazole 20 mg + acetylsalicylicylic acid 81 mg, there was reduced exposure of at least 40% of the Active clopidrogrel metabolite with respect to clopidogrel in monotherapy. However the maximum levels of papillary inhibition (ADP-induced) in these subjects was the same for groups treated with Clopidogrel and Clopidogrel + the association (esomeprazole + acid Acetylsalicylic). Unconscious data on the clinical implications of this PK / PD interaction in terms of major cardiovascular events have been reported both in observational and clinical studies. As a precautionary measure, the concomitant use of Clopidogrel must be discouraged. Phenytoin: Concomitant administration of 40 mg of Esomeprazole caused an increase of 13% of the plasma valley values of phenytoin in epileptic patients. It is recommended to monitor the plasma concentrations of phenytoin when the treatment with esomeprazole is introduced or suspended. Voriconazole: Omeprazole (40 mg once a day) has increased Cmax and AUCτ of voriconazole (a CYP2C19 substrate) respectively 15% and 41%. Cilostazolo: Omeprazole as well as esomeprazole act as CYP2C19 inhibitors. Omeprazole, administered in 40 mg doses in healthy subjects in a studio with cross-over design, has increased Cmax and auc of cilostazole respectively 18% and 26% respectively, and one of its metabolites active respectively by 29% and 69%. Cisapride: In healthy volunteers, concomitant administration of 40 mg of Esomeprazole gave rise to a 32% increase in the area under the concentration / time curve (AUC) and an extension of 31% of the elimination half-life (t½) But no significant increase in the maximum plasma levels of Cisapride. The slight extension of the QTC interval observed after the administration of cisapride in monotherapy was not further extended when the cisapride was administered in association with esomeprazole. Diazepam: Concomitant administration of 30 mg of Esomeprazole caused a 45% reduction in the CYP2C19 substrate default clearance. Medicines designed with unelevant clinical interactions. Amoxicillin and quinidine: Esomeprazole showed clinically relevant effects on amoxicillin or quinidine pharmacokinetics. NaproSene and Rofecoxib: Assessment studies of concomitant administration of Esomeprazole with NaproSene or Rofecoxib have not identified any clinically relevant pharmacokinetic interaction during short-term studies. Effects of other medicines on the pharmacokinetics of esomeprazole. Medicines CYP2C19 and / or CYP3A4 inhibitors: Esomeprazole is metabolized by CYP2C19 and CYP3A4. Concomitant administration of esomeprazole and a CYP3A4 inhibitor, clarithromycin (500 mg twice a day) gave rise to a doubling of the exhibition (AUC) to exomeprazole. Concomitant administration of Esomeprazole and a combined CYP2C19 and CYP3A4 inhibitor can give rise to exposure to exomeprazole more than doubled. Voriconazole, CYP2C19 and CYP3A4 inhibitor increased the AUCτ of 280% homeprazole. In any of these situations a dose adjustment of Esomeprazole is regularly requested. However, a dose adjustment must be taken into account in patients with severe hepatic impairment and if long-term treatment is indicated. Medicines that induce CYP2C19 and / or CYP3A4: medicines notoriously able to induce CYP2C19 or CYP3A4 or both (such as rifampicin and grass of San Giovanni) can determine one Reduction of serum esomeprazole levels by increasing the metabolism of exomeprazole.Effects
Safety profile summary: headache, abdominal pain, diarrhea and nausea are among the adverse reactions most commonly reported in clinical trials (and also by use after marketing). Furthermore, the security profile is similar to the different formulations, treatment indications, age groups and patient population. No adverse reactions related to the dose have been identified. The adverse reactions listed below were identified or suspected during clinical trials conducted with esomeprazole and after marketing. The reactions are classified according to the frequency (very common ≥1 / 10), (common ≥1 / 100, <1/10), (not common ≥1 / 1000, <1/100), (rare ≥1 / 10,000, <1 / 1,000), (Very rare <1 / 10,000), not known (frequency cannot be defined based on the data available).| Bemolyfopoiet system diseases | Rare | Leucopenia, thrombocytopenia |
| Very rare | Agranulocytosis, Pancitopenia | |
| Immune system disorders | Rare | Hypersensitivity reactions, p.es. fever, Angioedema and Anaphylactic Reaction / Shock |
| Metabolism and nutrition disorders | Uncommon | Peripheral edema |
| Rare | Hyponatremia | |
| Not known | Hypomagnesemia (see paragraph 4.4.) The severe hypomagnesemia can be related to hypocalcemia. The hypomagnesemia can also be related to hypopotassemia. | |
| Psychiatric disorders | Uncommon | Insomnia |
| Rare | Agitation, confusion, depression | |
| Very rare | Aggressiveness, hallucinations | |
| Nervous system pathologies | Common | Headache |
| Uncommon | Dizziness, paresthesia, drowsiness | |
| Rare | Taste alterations | |
| Eye pathologies | Rare | Blurred vision |
| Ear and labyrinth pathologies | Uncommon | Dizziness |
| Respiratory, thoracic and mediastinic pathologies | Rare | Bronchospasm |
| Gastrointestinal disorders | Common | Abdominal pain, constipation, diarrhea, flatulence, nausea / vomiting, polyps of the jay Fordica (Benigni) |
| Uncommon | Dry mouth | |
| Rare | Stomatitis, gastrointestinal candidiasis | |
| Non-note frequency | Microscopic colitis | |
| Hepatobiliary disorders | Uncommon | Increased liver enzymes |
| Rare | Hepatitis with or without jaundice | |
| Very rare | Hepatic impairment, encephalopathy in patients with pre-existing liver disease | |
| Cute and subcutaneous fabric pathologies | Uncommon | Dermatitis, itching, rash, urticaria |
| Rare | Alopecia, photosensitivity | |
| Very rare | Multiform erythema, Stevens-Johnson syndrome, toxic epidermal necrolisi (TEN) | |
| Not known | Lupus Eritematosus Subacuto skin (see section 4.4) | |
| Musculoskeletal system diseases and connective tissue | Uncommon | Fracture of the hip, wrist or spine (see paragraph 4.4.) |
| Rare | Artralgia, myalgia | |
| Very rare | Muscle weakness | |
| Renal and urinary disorders | Very rare | Interstitial nephritis; In some patients concomitant renal failure was reported |
| Pathologies of the reproductive and breast apparatus | Very rare | Gynecomastia |
| Systemic disorders and conditions relating to the administration site | Rare | Malay, increase in sweating |
Overdose
Experience on intentional overdose is currently very limited. The symptoms described in relation to 280 mg were gastrointestinal symptoms and weakness. Single doses of 80 mg of esomeprazole have been lacking with consequences. No specific antidote is known. Esomeprazole binds extensively to plasma proteins and therefore is not quickly dialyable. As in any case of overdose, the treatment must be symptomatic and general support measures must be used.Pregnancy
: With regard to esomeprazole, clinical data on exposed pregnancies are insufficient. With racemic mix, omeprazole, data from epidemiological studies on a greater number of exposed pregnancies do not indicate malformation or fetotoxic effects. Animal studies with esomeprazole do not indicate direct or indirect harmful effects on embryo/fetal development. Animal studies with racemic mixture do not indicate direct or indirect harmful effects on pregnancy, childbirth or post-natal development. For precautionary purposes, it is preferable to avoid the use of ESOMENAR during pregnancy.Nursing:
It is not known whether esomeprazole is excreted in breast milk. No studies have been conducted on nursing women. Therefore ESOMENAR should not be used during breastfeeding.Source: Farmadati
