NEXIUM CONTROL 7CPR GASTR 20MG

NEXIUM CONTROL 20 MG COMPRESENT

active ingredients

Each gastrorous tablet contains 20 mg of esomeprazole (such as magnesium trihydrate). Excipient (i) with known effects Each gastrorous tablet contains 28 mg of sucrose. For the full list of excipients, see paragraph 6.1.

Excellent

Monostearate glycerol 40-55 Idorssipropylcellulose Ipromellose 2910 (6 mPa s) Iron red-brown oxide (E 172) Iron yellow oxide (E 172) Magnesium stearate Metacrilic acid copolymerized etylacrilate (1:1) dispersion to 30% Cellulose microcrystalline Synthetic paraffin Macrogol 6000 Polysorbate 80 Crospovidone

Therapeutic indications

Nexium Control is indicated in adults for short-term treatment of reflux symptoms (e.g. pyrosis and acid regurgitation).

Contraindications

Hypersensitivity to the active ingredient, benzimidazolec substitutes or any of the excipients listed in the paragraph 6.1. Esomeprazole should not be used in conjunction with nelfinavir (see paragraph 4.5).

Population

Population The recommended dose is 20 mg of esomeprazole (one tablet) per day. It may be necessary to take tablets for 2-3 consecutive days to obtain better symptoms. The duration of treatment is up to 2 weeks. Once the complete disappearance of symptoms is achieved, treatment must be stopped. If you do not get the symptoms resolution within 2 weeks of continuous treatment, the patient should consult a doctor. Special populations Patients with renal compromise Dose adjustment is not necessary in patients with compromised kidney function. Given the limited experience in patients with severe kidney failure, these patients must be treated with caution (see paragraph 5.2). Patients with liver impairment Dose adjustment is not necessary in patients with mild or moderate liver impairment. However, patients with severe liver impairment should be advised by a doctor before taking Nexium Control (see paragraph 4.4 and 5.2). Senior Patients (≥65 years) Dose adjustment is not necessary in elderly patients. Pediatric population There is no indication for a specific use of Nexium Control in the pediatric population under 18 years of age for the indication “ short-term treatment of reflux symptoms (e.g. pyrosis and acid regurgitation). Method of administration The tablets should be swallowed whole with half a glass of water. Tablets should not be chewed or crushed. Alternatively, the tablet can be dispersed in half a glass of non-carbonated water. Other liquids should not be used as the gastro-resistant coating could dissolve. The water must be mixed until it is dispersed. The liquid with granules must be drunk immediately or within 30 minutes. The glass must be rinsed with half a glass of water and drinking water. Granules should not be chewed or crushed.

Conservation

Store in the original blister to protect the medicine from moisture.

Warnings

General Patients should be trained to consult a doctor if: • They have significant non-intentional weight loss, recurring vomiting, dysphagia, ematemesis or melena and when suspected or confirmed the presence of a gastric ulcer, the malignant nature of the ulcer must be excluded as therapy with esomeprazole could relieve symptoms and delay diagnosis. • They had a previous gastric ulcer or gastrointestinal surgery. • They have been in continuous symptomatic treatment of dyspepsia or pyrosis for 4 or more weeks. • They have ittero or severe liver disease. • They are older than 55 years old with new or newly changed symptoms. Patients with recurrent long-term symptoms of dyspepsia or pyrosis, should consult their doctor at regular intervals. Patients over 55 years of age who daily take treatment for dyspepsia and pirosis without a prescription, should inform the doctor or pharmacist. Patients should not take Nexium Control as a long-term preventive drug. Treatment with protonic pump inhibitors (IPP) can lead to a slight increase in the risk of gastrointestinal infections such as those from Salmonella and Campylobacter, and possibly even from Clostridium difficult in hospitalized patients (see paragraph 5.1). Patients should consult their physician before taking this medicine if they must be subjected to endoscopy or urea breath test. Combine with other medicines Co-administration of esomeprazole and atazanavir is not recommended (see paragraph 4.5). If the association of atazanavir with a protonic pump inhibitor is considered inevitable, close clinical monitoring is recommended in association with an increase in atazanavir dose to 400 mg with 100 mg ritonavir. The dose of 20 mg of esomeprazole should not be exceeded. Esomeprazole is a CYP2C19 inhibitor. At the beginning or end of treatment with esomeprazole, the potential interaction with metabolized medicines from CYP2C19 must be considered. An interaction between clopidogrel and esomeprazole has been observed. The clinical relevance of this interaction is uncertain. The use of esomeprazole with chlopidogrel must be discouraged (see paragraph 4.5). Patients should not take another IPP or H at the same time₂ antagonist. Interference with laboratory exams An increased level of Chromogranin A (CgA) can interfere with diagnostic tests for neuroendocrine tumors. To avoid such interference, Nexium Control should be suspended for at least 5 days before CgA measurements (see paragraph 5.1). If the levels of CgA and gastrin are not returned within the reference range after initial measurement, it is necessary to repeat the measurements 14 days after the interruption of treatment with protonic pump inhibitor. Subacute cutaneous erythematose lupus (LECS) Protonic pump inhibitors are associated with extremely infrequent cases of LECS. In the presence of injuries, especially on the skin parts exposed to the sun rays, and if accompanied by artralgia, the patient must immediately contact the doctor and the healthcare provider must assess the opportunity to stop treatment with Nexium Control. The appearance of LECS following a treatment with a protonic pump inhibitor can increase the risk of LECS onset with other protonic pump inhibitors. Sucrose This medicine contains sugar balls (saccharose). Patients suffering from rare hereditary problems of fructose intolerance, glucose-galactose mal absorption or sucrasis-isomaltase failure should not take this medicinale.Sodio This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e. essentially ‘without sodium’.

Interactions

Interaction studies were carried out only in adults. Esomeprazole influence on pharmacokinetics of other medicines Since esomeprazole is an omeprazole enantiomer it is advisable to consider the interactions observed with omeprazole. Protease inhibitors Interactions between omeprazole and some protease inhibitors have been reported. Clinical relevance and mechanisms of such interactions are not always known. An increase in gastric pH during treatment with omeprazole may change the absorption of protease inhibitors. Other possible interaction mechanisms occur through CYP2C19 inhibition. For atazanavir and nelfinavir, a decrease in serum levels was reported when administered with omeprazole and concomitant administration is not recommended. Co-administration of omeprazole (40 mg once a day) with atazanavir 300 mg/ritonavir 100 mg in healthy volunteers results in a substantial reduction in exposure to atazanavir (a decrease of about 75% of the AUC, C_max and C_min). An increase in the dose of atazanavir at 400 mg does not compensate for the impact of homorazole on exposure to atazanavir. Co-administration of omeprazole (20 mg once a day) with atazanavir 400 mg/ritonavir 100 mg in healthy volunteers resulted in a decrease of about 30% of exposure to atazanavir compared to exposure observed with atazanavir 300 mg/ritonavir 100 mg once a day without omeprazole 20 mg once a day. Co-administration of omeprazole (40 mg once a day) reduced UAA, C_max and the C_min average of infinavir of 36-39% and UAC, C_max and the C_min average drug metabolite M8 was reduced by 75-92%. Due to pharmacodynamic effects and similar pharmacokinetic properties of omeprazole and esomeprazole, concurrent administration of esomeprazole and atazanavir is not recommended and concomitant administration of esomeprazole and infinavir is contraindicated (see paragraph 4.3 and 4.4). Increased serum levels (80-100%) of saquinavir (in co-administration with ritonavir) were reported during the concomitant treatment with omeprazole (40 mg once a day). Treatment with omeprazole 20 mg once a day had no effect on the exposure of darunavir (in co-administration with ritonavir) and amprenavir (in co-administration with ritonavir). Treatment with esomeprazole 20 mg once a day had no effects on amprenavir exposure (with and without ritonavir co-administration). Treatment with omeprazole 40 mg once a day had no effects on lopinavir exposure (in co-administration with ritonavir). Metotress In some patients it has been reported that metotressate levels increase if administered along with IPP. In the presence of high doses of metotressate, it may be necessary to consider the temporary suspension of esomeprazole.Tacrolimus There has been an increase in serum levels of tacrolimus with the concomitant administration of esomeprazole and tacrolimus. Strengthened monitoring of tacrolimus concentrations as well as renal function (cancerance of creatinine), and the dose of tacrolimus adjusted if necessary. Medicines with pH-dependent absorption The suppression of gastric acidity during treatment with esomeprazole and other IPPs may decrease or increase the absorption of medicines with gastric pH dependent absorption. The absorption of oral medications such as ketoconazole, itraconazole and erlotinib may decrease during treatment with esomeprazole and digoxin absorption may increase during treatment with esomeprazole. Concurrent treatment with omeprazole (20 mg per day) and digoxin in healthy subjects increased the bioavailability of 10% (up to 30% in two of the ten subjects). It has rarely been reported toxicity to digoxin. However, caution should be given when esomeprazole is given at high doses to elderly patients. Monitoring the therapeutic effect of digoxin must therefore be reinforced. Metabolized medicines from CYP2C19 Esomeprazole inhibits CYP2C19, the main metabolizing enzyme esomeprazole. So when esomeprazole is associated with other metabolized medicines through CYP2C19, such as warfarin, phenytoine, citalopram, imipramine, chlomipramine, diazepam, etc., plasma concentrations of these medicines could be increased and a dose reduction could be required. In the case of chlopidogrel, a pharmaco transformed into its active metabolite by CYP2C19, the plasma concentration of active metabolite could be reduced. Warfarin Concurrent administration of 40 mg of esomeprazole to patients in treatment with warfarin in a clinical study showed that coagulation times remained within a normal range. However, after the marketing of the product, during the concomitant treatment, some isolated cases of increase of INR values of clinical relevance were reported. Monitoring is recommended at the beginning and end of the concurrent treatment with esomeprazole during treatment with warfarin or other cumarinic derivatives. Clopidogrel Results from studies in healthy volunteers showed a pharmacokinetic interaction (PK)/pharmacodynamics (PD) between chlopidogrel (load dose 300 mg/ daily maintenance dose 75 mg) and esomeprazole (40 mg per oral per day) resulting in a decreased exposure to the active metabolite of chlopidogrel equal to 40%, and resulting in a decrease in peak inhibition. In a study in healthy subjects, a decrease of almost 40% of exposure to active chlopidogrel metabolite was observed when a fixed combination of esomeprazole dose 20 mg + acetylsalicylic acid 81 mg and chlopidogrel was administered, compared to clopidogrel alone. However, in these subjects the maximum levels of inhibition of platelet aggregation (induced ADP) were equal in both groups. Non-unique data from observational and clinical studies have been reported on the clinical implications of this PK/PD interaction in terms of higher cardiovascular events. Precautionaryly, the concomitant use of esomeprazole and clopidogrel must be discouraged. Fenitoin Concurrent administration of 40 mg of esomeprazole leads to an increase of 13% of the minimum plasma levels of phenytoin in epileptic patients. It is recommended to monitor the plasma concentrations of phenytoin when you start or suspend treatment with esomeprazole. Voriconazole Omeprazole (40 mg once a day) increased C_max and the UACτ of voriconazole (a substrate of CYP2C19), respectively 15% and 41%. Cilostazola Omeprazole as well as esomeprazole act as CYP2C19 inhibitors. Omeprazole, administered at doses of 40 mg in healthy subjects in a cross over study, increased C_max and the AUC of 18% and 26% respectively, and one of its active metabolites of 29% and 69% respectively. Cisapride In healthy volunteers, the concurrent administration of 40 mg of esomeprazole led to an increase of 32% of the area under the plasma/time concentration curve (AUC) and an extension of 31% of the elimination half-life (t_1/2) but not a significant increase in cysapride plasma concentration peaks. The slight extension of the QTc range observed after administration of cisapride alone, is not further prolonged when cysapride is administered in combination with esomeprazole. Diazepam Concurrent administration of 30 mg of esomeprazole resulted in a reduction of 45% of diazepam clearance, substrate of CYP2C19. Medicinal products studied with non-relevant clinical interactions Amoxicillin and chinidine It has been shown that hesomeprazole has no clinical effects relevant to the pharmacokinetics of amoxicillin and kinidine. Naprossene or rofecoxib Studies for the evaluation of concomitant administration of esomeprazole with naprossene or rofecoxib have not evidenced any clinically relevant pharmacokinetic interaction in short-term studies. Influence of other medicines on pharmacokinetics of hesomeprazole CYP2C19 and/or CYP3A4 inhibitor medicines Esomeprazole is metabolized through CYP2C19 and CYP3A4. Concurrent treatment of esomeprazole with a CYP3A4 inhibitor, clarithromycin (500 mg twice daily)b.i.d.)), involves double exposure (AUC) to hesomeprazole. Concurrent administration of esomeprazole and a combined inhibitor of CYP2C19 and CYP3A4 can lead to more than doubled esomeprazole exposure. Voriconazole, inhibitor of the CYP2C19 and CYP3A4, raises the AUCτ of the oomeprazole by 280%. An adaptation of the dose of esomeprazole is not regularly required in both above mentioned situations. However, a dose adjustment should be taken into account in patients with severe liver impairment and if long-term treatment is indicated. Medicines that induce CYP2C19 and/or CYP3A4 Drugs known for the induction of CYP2C19 or CYP3A4 or both (such as the rifamp and herb of St. John (Hypericum perforatum)) can lead to a decrease in the serum levels of esomeprazole for the increase in the metabolism of esomeprazole.

Effects

Summary of security profile Headache, abdominal pain, diarrhea and nausea are among the most commonly reported adverse reactions in clinical trials (and also use after marketing). In addition, the safety profile is similar to the different formulations, treatment indications, age groups and patient population. No adverse reactions related to the dose have been identified. Table of adverse reactions The following adverse reactions were identified or suspected during clinical trials conducted with esomeprazole and after marketing. The reactions were classified according to the MedDRA Convention on Frequency: very common (>1/10); common (≥1/100,   Town Not common Rare Very rare Notable Emolinfopoietic system pathologies     leucopenia, trombocytope-nia agranulocytosis, pancitopenia   Immune system disorders     hypersensitivity reactions such as fever, angioedema and anaphylactic reaction/shock     Disorders of metabolism and nutrition   peripheral edema hyponatriemia   hypomagnese-my; severe hypomagnese-my may correlate to hypocalcemia; hypomagnese-my can also lead to hypokaliemia Psychiatric disorders   insomnia agitation, confusion, depression aggressiveness, hallucinations   Diseases of the nervous system headache dizziness, paresthesia, drowsiness taste disorders     Pathologies of the eye     sight blurring     Ear and labyrinth pathologies   dizziness       Respiratory, chest and mediastinic pathologies     bronchospasmo     Gastrointestinal diseases addomina-le pain, constipation-ne, diarrhea, flatulence, nausea/ vomiting, polyps of the fungus gland (drinks) dry mouth stomatitis, candid gastrointestinal   microscopic colitis Hepatobiliary diseases   the value of liver enzymes hepatitis with or without jaundice liver failure, liver encephalopathy in patients with pre-existing liver disease   Pathologies of skin and subcutaneous tissue   dermatitis, itching, rash, hives alopecia, photosensitivity multiform erythema, Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN) lupus erythematous subacute skin (see paragraph 4.4) Diseases of musculoskeletal system and connective tissue     artralgia, mialgia muscle weakness   Kidney and urinary pathologies       interstitial nephritis   Pathologies of the reproductive apparatus and of the breast       gynecomastia   Systemic pathologies and conditions for administration     disease, increased sweating     Reporting of suspicious adverse reactions The reporting of suspicious adverse reactions that occur after the authorization of the medicinal product is important, as it allows continuous monitoring of the benefit/risk ratio of the medicinal product. Healthcare workers are required to report any suspected adverse reaction through the national reporting system reported in Annex V.

Overdosing

There is currently a very limited experience on intentional overdose. The symptoms described in relation to taking 280 mg were gastrointestinal symptoms and weakness. Single doses of 80 mg of esomeprazole did not cause consequences. A specific antidote is not known. Esomeprazole is widely linked to plasma proteins and is therefore not fast dialysable. Treatment should be symptomatic and support measures should generally be used.

Pregnancy

A modest amount of data on pregnant women (between 300-1,000 pregnancy outcomes) indicates the absence of malformations or fetus/neonatal toxicity of esomeprazole. Animal studies show no direct or indirect harmful effects in relation to reproductive toxicity (see paragraph 5.3). For precautionary purposes, it is preferable to avoid the use of Nexium Control during pregnancy.

Food

It is not known whether hesomeprazole/his metabolites are excreted in breast milk. There is no sufficient information on the effects of esomeprazole in infants/infators. Esomeprazole should not be used during lactation.

Fertility

Studies of animals with the racemic mixture of omeprazole, administered by mouth do not highlight effects on fertility.

Source: Farmadati