Inexium drug Dosage, Side Effects, Interactions

Inexium drug >>> generic drug of the Therapeutic class: Gastro-Entero – Hepatology
active ingredients: Esomeprazole

Important to know about Inexium?

Inexium (Esomeprazole) 40 mg gastro-resistant tablet is used in the treatment of the following diseases:

• The treatment of reflux erosive esophagitis when stomach acid rises up to the esophagus and causes pain, inflammation and burns.
• Excess acid in the stomach due to Zollinger-Ellison syndrome.
• Continuation of the treatment after prevention with intravenous Inexium (Esomeprazole) of the haemorrhagic recurrence of a peptic ulcer.

Inexium indication and Uses

Inexium Dosage

adults

Gastroesophageal reflux disease (GERD):

• Treatment of erosive reflux oesophagitis 40 mg once a day for 4 weeks.
• An additional treatment of 4 weeks is recommended in patients whose esophagitis is not healed or whose symptoms persist.

Treatment of Zollinger-Ellison syndrome

The recommended starting dose is 40 mg twice daily. The dosage should be adjusted individually and treatment continued as long as clinically necessary. Based on the available clinical data, the majority of patients are controlled with doses between 80 and 160 mg deomeprazole daily. For dosages above 80 mg daily, the daily dose should be divided and given in 2 doses.

Continuing treatment after intravenous prevention of haemorrhagic recurrence of peptic ulcer

40 mg once daily for 4 weeks after intravenous prevention of haemorrhagic recurrence of peptic ulcer.

Special populations

Renal failure

• No dosage adjustment is necessary in case of renal insufficiency.
• Due to limited experience in patients with severe renal impairment, the use of dInexium (Esomeprazole) should be cautious in these patients.

Hepatic insufficiency

No dose adjustment is necessary in patients with mild to moderate hepatic impairment. The maximum dose of 20 mg of INInexium (Esomeprazole) should not be exceeded in patients with severe hepatic impairment.

Elderly

• No dose adjustment in the elderly.

Pediatric population

• Teenagers from the age of 12

Gastroesophageal reflux disease (GERD):

• Treatment of reflux erosive oesophagitis 40 mg once a day for 4 weeks.
• An additional 4-week treatment is recommended in patients whose osteoarthritis is not healed or whose symptoms persist.

Children under 12 years

• Inexium (Esomeprazole) should not be used in children under 12 years of age in the absence of available data.
• For the dosage of patients aged 1 to 11 years, refer to the SPINE dInexium (Esomeprazole) sachet.

Administration mode

• The tablets should be swallowed whole with a drink. They must not be chewed or chewed.
• In patients who have difficulty swallowing, the tablets can also be dispersed in half a glass of non-carbonated water. No other liquid should be used as the gastroenteric coating may be dissolved. Stir until tablets break and drink solution with granules immediately or within 30 minutes. Rinse the glass with half a glass of water and drink it. Granules should not be chewed or chewed.
• For patients who can not swallow, the tablets can be dispersed in non-aerated water and administered by gastric tube.
• It is important to make sure beforehand and thoroughly that the chosen probe and syringe are appropriate.
• For preparation and administration by gastric tube.

Contraindications

Known hypersensitivity to esomeprazole, to benzimidazole derivatives or to any of the ingredients.

•  Esomeprazole, like other proton pump inhibitors, should not be administered with atazanavir ( see section Interactions with other medicinal products and other forms of interactions ).
• Esomeprazole must not be used concomitantly with nelfinavir (see section Interactions with other medicinal products and other forms of interactions ).

How it works Inexium

Pharmacotherapeutic group: Drugs for acidity disorders, PROTON INHIBITORS, ATC code: A02B C05

• Esomeprazole is the S- isomer of omeprazole and decreases acidic gastric secretion by a specifically targeted mechanism of action. It is a specific inhibitor of the proton pump at the level of the parietal cell. Both R and S isomers of omeprazole have similar pharmacodynamic activity.

Action mechanism

• Esomeprazole is a weak base. It is concentrated and converted into an active form in the acidic environment of secretory canaliculi of parietal cells, where it inhibits the enzyme H + K + -ATPase (the proton pump), basal acid secretion and stimulated acid secretion.

Pharmacodynamic effects

• After an oral dose of 20 and 40 mg of esomeprazole, the onset of anti-secretory effect occurs within one hour. After repeated administration of 20 mg of esomeprazole once daily for 5 days, the maximum flow rate obtained after acid stimulation by pentagastrin is reduced on average by 90% in the 5 ^th day, 6 to 7 hours after dosing.
• After 5 days of oral doses of 20 mg and 40 mg of esomeprazole, an intragastric pH greater than 4 was maintained for an average of 13 and 17 hours in 24 hours in patients with symptomatic gastroesophageal reflux. The percentages of patients with pH> 4, for at least 8, 12 and 16 hours are respectively 76%, 54% and 24% with 20 mg of esomeprazole and 97%, 92% and 56% with 40 mg esomeprazole.
• Using the area under the curve (AUC) as a parameter reflecting plasma concentration, a relationship between acid gastric secretion inhibition and area under the curve (AUC) has been demonstrated.
• Healing of reflux esophagitis with esomeprazole 40 mg was achieved in approximately 78% of patients after 4 weeks of treatment and in 93% of patients after 8 weeks of treatment.
• One week of treatment with esomeprazole 20 mg twice daily with appropriate antibiotics results in eradication of Helicobacter pylori in approximately 90% of patients.
• After a week-long eradication treatment, it is not necessary to continue anti-secretory monotherapy to obtain healing and disappearance of symptoms in uncomplicated duodenal ulcer.
• In a randomized, double-blind, placebo-controlled clinical trial, patients with endoscopically-confirmed gastroduodenal ulcer bleeding (Forrest Ia, Ib, IIa, or IIb, for 9%, 43%, 38%, and 10%, respectively) were randomized to receive Inexium (Esomeprazole) solution for infusion (n = 375) or placebo (n = 389). After endoscopic hemostasis, patients received either 80 mg of esomeprazole as a 30-minute intravenous infusion followed by a continuous infusion of 8 mg / h for 72 hours, or a placebo. After the initial 72-hour period, all patients received Inexium (Esomeprazole) 40 mg orally open for 27 days to reduce acid secretion. The occurrence of haemorrhagic recurrence within 3 days was 5.9% in the group treated with Inexium (Esomeprazole), compared to 10.3% in the placebo group.
• During antisecretory treatment, serum gastrin concentration increases in response to reduced acid gastric secretion. CgA also increases because of the decrease in gastric acidity. Increased levels of CgA may interfere with test results for neuroendocrine tumors. Data from the literature indicate that treatment with a proton pump inhibitor should be stopped at least 5 days prior to CgA measurement. If the concentrations of CgA and gastrin have not normalized after 5 days, measurements should be repeated 14 days after discontinuation of esomeprazole.
• An increase in the number of ECL cells in relation to the increase in serum gastrin concentrations was observed in both children and adults treated with esomeprazole in the long term. The results are considered to have no clinical significance.
• During long-term treatment with anti-secretory drugs, gastric glandular cysts have been reported with a slightly increased frequency. These changes are a physiological consequence of pronounced inhibition of acid secretion: they are benign and appear reversible.
• The reduction of gastric acid secretion whatever the cause, especially that induced by proton pump inhibitors (PPIs) increases in the stomach the amount of bacteria normally present in the digestive tract. PPI treatment may slightly increase the risk of gastrointestinal infections caused by germs such as Salmonella and Campylobacterand possibly due to Clostridium difficile in hospitalized patients.

Clinical efficiency

• In two studies versus ranitidine, used as an active comparator, improved efficacy with Inexium (Esomeprazole) has been demonstrated in the healing of gastric ulcers in patients treated with NSAIDs, including selective COX-2 inhibitors.
• In two placebo-controlled studies, used as a comparator, improved efficacy with Inexium (Esomeprazole) has been demonstrated in the prevention of peptic ulcers in patients treated with NSAIDs (age> 60 years and / or history of ulcer), including selective COX-2.

Pediatric population

• In a study in a pediatric population (children younger than 1 year to 17 years) with GERD receiving long-term PPI treatment, 61% of children had low levels of ECL cell hyperplasia without significance. clinically known and without development of atrophic gastritis or carcinoid tumors.

Inexium Side Effects

– This is most often:

• diarrhea
• vomiting
• abdominal pain
• rash, Quincke’s edema.

– Also reported a few cases of:

• Digestive manifestations: As with other broad-spectrum antibiotics, rare cases of enterocolitis with bloody diarrhea have been reported as well as rare cases of pseudomembranous colitis
• Hepatobiliary manifestations: moderate elevation of ASAT and ALAT transaminases
• allergic reactions: rash, itching, hives, anaphylactic shock

cutaneous manifestations: various eruptions, localized bullous eruption, erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis

• headache,
• feelings of dizziness
• renal manifestations: mild increase in creatinine
•  haematological manifestations: decreased hemoglobin, thrombocytopenia, neutropenia and eosinophilia, exceptional agranulocytosis.

Inexium Interactions

Effects of esomeprazole on the pharmacokinetics of other drugs

Protease inhibitors

• Interactions between omeprazole and some protease inhibitors have been reported. The clinical significance and mechanism of these interactions are not always known. The increase in gastric pH observed with omeprazole treatment may alter the absorption of protease inhibitors. There are other mechanisms of interactions that occur via inhibition of CYP 2C19.
• For atazanavir and nelfinavir, decreased plasma concentrations have been reported when combined with omeprazole; Concomitant administration of omeprazole and these drugs is therefore not recommended. Omeprazole (40 mg once daily) administered in combination with atazanavir 300 mg with ritonavir 100 mg in healthy volunteers resulted in a substantial decrease in plasma levels of atazanavir (approximately a 75% decrease ASC, Cmax and Cmin). The increase in dosage of atazanavir to 400 mg did not offset the effect of omeprazole on the plasma concentrations of atazanavir.
• The combination of omeprazole (20 mg once daily) with atazanavir 400 mg / ritonavir 100 mg in healthy volunteers decreased the exposure to atazanavir by approximately 30% compared to the exposure observed with Atazanavir 300 mg / ritonavir 100 mg once daily administered alone.
• The association of omeprazole (40 mg once daily), decreased by 36-39% the mean AUC, C max and C _min of nelfinavir and 75-92% of the mean AUC, C _maxand C _min of its pharmacologically active metabolite M8.
• Due to the similarity of the pharmacodynamic and pharmacokinetic effects of omeprazole and esomeprazole, concomitant administration of esomeprazole and atazanavir is not recommended (see Warnings and Precautions for Use section ) .   and concomitant administration of esomeprazole and nelfinavir is contraindicated.
• For saquinavir (in combination with ritonavir), an increase in plasma concentration (80-100%) has been reported in association with omeprazole (40 mg once daily).
•  Treatment with omeprazole 20 mg once daily did not affect exposure to darunavir (ritonavir-associated) or amprenavir (ritonavir-associated).
• Treatment with esomeprazole 20 mg once daily did not affect exposure to amprenavir (with or without ritonavir).
•  Treatment with omeprazole 40 mg once daily did not affect exposure to lopinavir (ritonavir-associated).

methotrexate

• An increase in methotrexate concentrations has been observed in some patients when concomitant administration of methotrexate with proton pump inhibitors (PPIs). When administering high doses of methotrexate, temporary discontinuation of esomeprazole may be necessary.

tacrolimus

• An increase in serum tacrolimus concentrations has been observed when co-administered with esomeprazole. Enhanced monitoring of tacrolimus concentrations and renal function (creatinine clearance) should be performed, and the dosage of tacrolimus should be adjusted if necessary.

Drugs whose absorption is pH dependent

• Inhibition of acidity e gastric during treatment with esomeprazole and other PPIs might decrease or increase the absorption of drugs if it is dependent on the gastric pH.
• As with other drugs that decrease intragastric acidity, the absorption of certain drugs, such as ketoconazole, itraconazole and erlotinib, may be decreased while the absorption of drugs such as digoxin may increase during treatment by esomeprazole.
• Concomitant treatment with omeprazole (20 mg daily) and digoxin in healthy subjects increased the bioavailability of digoxin by 10% (up to 30% in two of the ten subjects).
• The toxicity of digoxin has been reported rarely. However, special attention should be paid when esomeprazole is given in high doses in elderly patients. Therapeutic monitoring of digoxin should be strengthened.

Drugs metabolised by CYP2C19

• Esomeprazole inhibits CYP2C19, the major metabolizing enzyme of esomeprazole. Therefore, when co-administered with drugs metabolized by CYP2C19, such as diazepam, citalopram, imipramine, clomipramine, phenytoin, etc., the plasma concentrations of these drugs may be increased and dose reduction may be necessary.
• This should be particularly taken into account when esomeprazole is prescribed for on-demand treatment.

diazepam

• Concomitant administration of 30 mg esomeprazole results in a 45% decrease in the clearance of diazepam metabolized by CYP2C19.

phenytoin

• Co-administration of 40 mg esomeprazole leads to a 13% increase in plasma phenytoin concentrations in epileptic patients. It is recommended to monitor the plasma concentrations of phenytoin when starting or stopping treatment with esomeprazole.

voriconazole

• Omeprazole (for the 40 mg dose once daily) resulted in increased plasma concentrations of voriconazole (a CYP2C19 substrate), with Cmax and AUC t   increased by 15 and 41% respectively.

cilostazol

• Like omeprazole, esomeprazole is an inhibitor of CYP2C19. In a crossover study, omeprazole, administered at a healthy dose of 40 mg, increased cilax and cilostazol AUC by 18% and 26%, respectively, and one of its active metabolites. 29% and 69% respectively.

cisapride

• In healthy volunteers, concomitant administration of 40 mg esomeprazole and cisapride results in a 32% increase in plasma AUC and a 31% prolongation of half-life. elimination (t1 / 2) without a significant increase in the plasma peak of cisapride.
• The slight prolongation of QTc observed after cisapride alone is not increased when concomitant administration of cisapride with esomeprazole. (see section Warnings and precautions for use ).

warfarin

• A clinical trial has shown that during the administration of 40 mg esomeprazole in patients treated with warfarin, clotting times remain within normal range. However, since marketing, a few clinically significant cases of INR elevation have been reported during concomitant treatment.
•  Monitoring is recommended at initiation and at the end of concomitant treatment of esomeprazole with warfarin or other coumarin derivatives.

clopidogrel

• The results of studies in healthy subjects showed a pharmacokinetic (PK) / pharmacodynamic (PD) interaction between clopidogrel (loading dose 300 mg / maintenance dose 75 mg daily) and esomeprazole (40 mg / day orally), resulting in approximately 40% decrease in exposure to the active metabolite of clopidogrel and approximately 14% decrease in maximal inhibition of platelet aggregation (ADP-induced).
• In a study in healthy subjects, a decrease in the exposure of approximately 40% of the active metabolite of clopidogrel was observed when taking a fixed combination of esomeprazole 20 mg and acetylsalicylic acid (ASA). mg with clopidogrel in comparison with clopidogrel alone. However, the maximum levels of inhibition of platelet aggregation (ADP-induced) in these patients were identical in the clopidogrel group and the clopidogrel + fixed combination group (esomeprazole + acetylsalicylic acid).
• Conflicting data on the clinical consequences of a PK / PD interaction of esomeprazole in terms of major cardiovascular events were observed from both observational and clinical studies. As a precaution, concomitant use of clopidogrel should be discouraged.

Drugs studied without clinically significant interaction

Amoxicillin and quinidine

• Esomeprazole has no clinically significant effect on the pharmacokinetics of amoxicillin, or quinidine.

Naproxen or rofecoxib

• Short-term studies evaluating co-administration of esomeprazole with naproxen or rofecoxib have not shown a clinically significant pharmacokinetic interaction.

Effects of other drugs on the pharmacokinetics of esomeprazole

Drugs that inhibit CYP2C19 and / or CYP3A4

• Esomeprazole is metabolized by CYP2C19 and CYP3A4.
• Co-administration of esomeprazole with a CYP3A4 inhibitor, clarithromycin (500 mg twice daily), leads to a doubling of the area under the curve (AUC) of esomeprazole.
• Concomitant administration of esomeprazole and a combination inhibitor of CYP2C19 and CYP3A4 may result in an increase of more than twice the Cmax and AUC of esomeprazole.
• Voriconazole, an inhibitor of CYP2C19 and CYP3A4, resulted in an increase in AUC t of omeprazole by 280%.
• Systematic dose adjustment of esomeprazole is not required in either of these situations.
• However, dose adjustment should be considered in patients with severe hepatic impairment, and if long-term therapy is indicated.

Drugs that 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 serum esomeprazole levels by increasing the metabolism of esomeprazole.

Pediatric population

• Interaction studies have only been performed in adults.

Inexium Warnings and Precautions

In the presence of any of the following alarm symptoms (such as significant and involuntary weight loss, repeated vomiting, dysphagia, hematemesis or melena) or if there is suspicion or presence of a gastric ulcer, the possibility of a malignant lesion should be excluded as Inexium (Esomeprazole) may reduce symptoms and delay the diagnosis.

Long-term use

• Patients receiving maintenance treatment (and, more specifically, those treated for more than one year) should be followed regularly.

On demand processing

• Patients with on-demand treatment should be advised of the need to contact their doctor if their symptoms change.

Eradication of Helicobacter pylori

• In the case of prescription of lesomeprazole for eradication of Helicobacter pylori , the possible drug interactions of all components of the treatment should be taken into consideration.
• Clarithromycin is a potent inhibitor of CYP3A4 and therefore contraindications and clarithromycin interactions should be considered when treatment with concomitant use of drugs that are metabolised by CYP3A4, such as cisapride.

Gastrointestinal infections

• IPP treatment may slightly increase the risk of gastrointestinal infections caused by germs such as Salmonellaand Campylobacter .

Absorption of vitamin B12

• Like all drugs aimed at decreasing the secretion of gastric acids, lesomeprazole can decrease the absorption of vitamin B12 (cyanocobalamin) due to hypohydrochloride or lachlorhydria. This should be taken into account during long-term treatment in patients with a reduced vitamin B12 reserve or risk factors leading to decreased absorption of vitamin B12.

hypomagnesemia

• Severe hypomagnesemic cases have been reported in patients treated with proton pump inhibitors (PPIs) such as esomeprazole for at least three months, and in most cases for one year. Hypomagnesemia can manifest itself in serious clinical signs such as fatigue, tetany, delirious flushes, convulsions, dizziness, ventricular arrhythmia, but it can start insidiously and go unnoticed. In most patients, hypomagnesemia improved after magnesium supplementation and discontinuation of PPI.
• In patients requiring prolonged therapy or when PPIs are combined with digoxin or with drugs that may induce hypomagnesaemia (eg diuretics), blood magnesium levels should be considered by health professionals before starting treatment with IPP and regularly during treatment.

Risk of fractures

• Proton pump inhibitors, particularly if they are used in high doses over a prolonged period (> 1 year), may moderately increase the risk of hip, wrist and vertebral fractures, mainly in elderly or elderly patients.
• in the presence of other identified risk factors. Observational studies suggest that proton pump inhibitors can increase the overall risk of fracture by 10-40%. This increase may be due in part to other risk factors.
• Patients at risk of osteoporosis should be managed according to the recommendations in force and receive appropriate vitamin D and calcium intake.

Subacute cutaneous lupus erythematosus (LECS)

• Inhibitors of the proton pump are associated with very occasional cases of LECS. If lesions develop, especially on the skin areas exposed to the sun, and if they are accompanied by arthralgia, the patient must consult a doctor quickly and the health professional must consider stopping Inexium (Esomeprazole).
• The occurrence of LECS after treatment with a proton pump inhibitor may increase the risk of LECS with other proton pump inhibitors.

Association with other medicines

• The combination of lesomeprazole with latazanavir is not recommended (see section 4.5). If the combination of latazanavir with a proton pump inhibitor is considered essential, close clinical monitoring is recommended, together with an increase in the dose of 400 mg datazanavir with 100 mg ritonavir; a maximum dose of 20 mg deomeprazole should not be exceeded.
• Lesomeprazole is an inhibitor of CYP2C19. At the beginning or end of treatment with omeprazole, the risk of interactions with drugs metabolized by CYP2C19 should be considered. An interaction between clopidogrel and lesomeprazole has been observed (see section 4.5). The clinical relevance of this interaction is uncertain. As a precaution, the concomitant use of deomeprazole and clopidogrel should be discouraged.
• If deomeprazole treatment is prescribed on demand, the impact on interactions with other drugs should be taken into account due to fluctuations in plasma concentrations of lesomeprazole.

Sucrose

• This medicine contains sucrose. This medicine is contraindicated in patients with fructose intolerance, glucose or galactose malabsorption syndrome or sucrase-isomaltase deficiency.

Drive and use machines

• Esomeprazole has a minor influence on the ability to drive and use machines. Side effects such as dizziness (uncommon) and blurred vision (rare) have been reported .
• Affected patients should not drive or use machinery.

PREGNANCY / BREAST FEEDING / FERTILITY

Pregnancy

• Due to the expected benefit, the use of cefpodoxime may be considered during pregnancy if needed, despite insufficient clinical and animal data.

Breast-feeding

• The passage into breast milk is low and the amounts ingested are well below therapeutic doses. As a result, breastfeeding is possible when taking this antibiotic.
• However, discontinue breastfeeding (or medication) if diarrhea, candidiasis or rash occurs in infants.

What should I do if I miss a dose?

• Take it as soon as possible. However, if you are near the time of taking the next dose, do not take the dose you have forgotten, but continue your treatment normally.
• Do not take a double dose to make up for the dose you forgot to take.

What is  Forms and Composition?

• 20 mg gastro-resistant film-coated tablet (oblong, biconvex, engraved “20 mg” on one side and “A / EH” on the other side, light pink):   Boxes of 7, 14 and 28, under platelets.
• Hospital model: Box of 50, under pads. 40 mg gastroresistant film-coated tablet (oblong, biconvex, engraved “40 mg” on one side and “A / EI” on the other side, pink):   Boxes of 14 and 28, under blisters. Hospital model: Box of 50, under pads.

• Excipients (common): glycerol monostearate (40-55), hydroxypropylcellulose, hypromellose, red-brown iron oxide E 172, yellow iron oxide E 172 (cp at 20 mg only), magnesium stearate, methacrylic acid copolymer and ethyl acrylate (1: 1) 30% dispersion, microcrystalline cellulose, synthetic paraffin, macrogol 6000, polysorbate 80, crospovidone, sodium stearyl fumarate, neutral microgranules (sucrose and corn starch), talc, titanium E 171, triethyl citrate.
• Excipient (s) with known effect: sucrose (28 mg / day to 20 mg, 30 mg / day to 40 mg).

NOT’s

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general information:

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Additional information:

• General explanation about dealing with the medicine: how to take the medicine, the doses and times of it, the start and duration of its effectiveness, the recommended diet during the period of taking the medicine, the method of storage and storage, recommendations in cases for forgetting the dose and instructions to stop taking the drug and take additional doses.

Special warnings:

• For pregnant and breastfeeding women, the elderly, boys and drivers, and use before surgery.

Side effects:

• It treats possible side effects and drug interactions that require attention and its effect on continuous use.
• The information contained in this medicine is based on medical literature, but it is not a substitute for consulting a doctor.