Nexilok 20 20mg Gastro-resistant tablets

NEXILOK is indicated for:

Temporary, short-term relief of heartburn and hyperacidity.

Posology:

The recommended dose is 20 mg (one tablet) daily, for a maximum treatment period of 14 days. The duration of treatment is up to 2 weeks. Once complete relief of symptoms has occurred, treatment should be discontinued. If no symptom relief is obtained within 14 days of continuous treatment, the patient should be instructed to consult a doctor.

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 (see section 5.2).
• Impaired hepatic function: Dose adjustment is not required in patients with mild to moderate liver impairment. For patients with severe liver impairment, a maximum daily dose of 20 mg NEXILOK should be used (see sections 4.4 and 5.2).
• Elderly: Dose adjustment is not required in the elderly.
• Paediatric population: There is no experience with NEXILOK in the paediatric population below 18 years of age.

Method of administration:

The tablets should be swallowed whole with liquid. The tablets should not be chewed or crushed. The tablets can also be dispersed in half a glass of non-carbonated water. No other liquids should be used. Stir until the tablets disintegrate and drink the liquid with the pellets immediately or within 30 minutes. Rinse the glass with half a glass of water and drink. The pellets must not be chewed or crushed. For patients who cannot swallow, the tablets can be dispersed in non-carbonated water and administered through a gastric tube.

• Known hypersensitivity to esomeprazole, substituted benzimidazoles or to any other constituents of NEXILOK (see section 6.1).
• Concomitant administration of NEXILOK with atazanavir or nelfinavir (see section 4.5).

General:

Patients should be instructed to consult a doctor if:

• They have significant unintentional weight loss, recurrent vomiting, dysphagia, haematemesis or melaena and when gastric ulcer is suspected or present, malignancy should be excluded, as the treatment with NEXILOK may alleviate the symptoms of malignant ulcers and can thus delay diagnosis.
• They have had previous gastric ulcer of gastrointestinal surgery.
• They have been on continuous symptomatic treatment of indigestion or heartburn for 4 or more weeks.
• They have jaundice or severe liver disease.
• They are aged over 55 years with new or recently changed symptoms.

Patients with long-term recurrent symptoms of indigestion or heartburn should see their doctor at regular intervals. Patients over 55 years taking any non-prescription indigestion or heartburn remedy on a daily basis should inform their pharmacist or doctor.

Patients should not take NEXILOK as a long-term preventative medicine: Treatment with proton pump inhibitors such as NEXILOK may lead to slightly increased risk of gastric intestinal infections such as Salmonella and Campylobacter and possibly Clostridium difficile (see section 5.1). PPI therapy like esomeprazole as contained in NEXILOK may be associated with an increased risk of Clostridium difficile associated with watery diarrhoea, stomach pain and fever, especially in hospitalised patients. Patient should consult their doctor before taking this medicine if they are due to have an endoscopy or urea breath test.

Subacute cutaneous lupus erythematosus (SCLE): Proton pump inhibitors are associated with very infrequent cases of subacute cutaneous lupus erythematosus (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 healthcare professional should consider stopping NEXILOK. SCLE after previous treatment with a proton pump inhibitor may increase the risk of SCLE with other proton pump inhibitors.

Combination with other medicines: Co-administration of esomeprazole, as contained in NEXILOK, with atazanavir and nelfinavir is contraindicated (see section 4.3) and clopidogrel (see section 4.5). NEXILOK is a CYP2C19 inhibitor. When starting or ending treatment with NEXILOK, the potential for interactions with medicines metabolised through CYP2C19 should be considered.

Renal failure: Interstitial nephritis may progress to chronic renal inflammation and renal failure as it is not necessarily reversed when treatment is discontinued.

Interference with laboratory tests: Increased Chromagranin A (CgA) level may interfere with investigations for neuroendocrine tumours. To avoid this interference, NEXILOK treatment should be stopped for at least 5 days before CgA measurements (see section 5.1). If CgA and gastrin levels have not returned to reference range after initial measurements, it should be repeated 14 days after cessation of proton pump inhibitor treatment.

Sucrose: NEXILOK contains sugar (sucrose). Patients with rare hereditary conditions such as fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take NEXILOK. Sucrose may have an effect on the glycaemic control of patients with diabetes mellitus.

Sodium: This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially u2018sodium-freeu2019.

Interaction studies have only been performed in adults.

Effects of NEXILOK on the pharmacokinetics of other medicines:

As esomeprazole, contained in NEXILOK, is one enantiomer of omeprazole it is reasonable to advise about interactions reported with omeprazole.

Protease inhibitors: Increased gastric pH during omeprazole treatment may change the absorption of the protease inhibitors. Other possible interaction mechanisms are via inhibition of CYP2C19.

Atazanavir & nelfinavir: Esomeprazole, contained in NEXILOK, decreases the concentration of atazanavir and nelfinavir. Co-administration of NEXILOK and atazanavir or nelfinavir is contraindicated (see section 4.3).

For saquinavir (with concomitant ritonavir), increased serum levels (80 - 100 %) have been reported during concomitant omeprazole treatment (40 mg once a day). Treatment with omeprazole 20 mg once a day had no effect on the exposure of darunavir (with concomitant ritonavir) and amprenavir (with concomitant ritonavir). Treatment with esomeprazole 20 mg, as contained in NEXILOK, once a day had no effect on the exposure of amprenavir (with and without concomitant ritonavir). Treatment with omeprazole 40 mg once a day had no effect on the exposure of lopinavir (with concomitant ritonavir).

Methotrexate: When given together with proton pump inhibitors (PPIu2019s) such as NEXILOK, methotrexate levels have been reported to increase in some patients. In high-dose methotrexate administration a temporary withdrawal of NEXILOK may need to be considered.

Tacrolimus: Concomitant administration of esomeprazole as in NEXILOK 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.

Medicines with pH dependent absorption: The decreased intragastric acidity during treatment with NEXILOK might increase or decrease the absorption of medicines if the mechanism of absorption is influenced by gastric acidity. The absorption of ketoconazole, itraconazole and erlotinib can decrease and the absorption of digoxin can increase during treatment with NEXILOK. Caution should be exercised when NEXILOK is given at high doses in elderly patients. Therapeutic monitoring of digoxin should be reinforced.

Medicines metabolised by CYP2C19: Esomeprazole, contained in NEXILOK, inhibits CYP2C19, the major esomeprazole metabolising enzyme. Thus, when NEXILOK is combined with medicines metabolised by CYP2C19, such as diazepam, citalopram, imipramine, clomipramine, phenytoin etc., the plasma concentrations of these medicines may be increased and a dose reduction could be needed. This should be considered especially when prescribing NEXILOK for on demand therapy.

Diazepam: Concomitant administration of 30 mg esomeprazole resulted in a 45 % decrease in clearance of the CYP2C19 substrate diazepam.

Phenytoin: Concomitant administration of 40 mg esomeprazole resulted in a 13 % increase in trough plasma levels of phenytoin in epileptic patients; dose adjustment was not required.

Voriconazole: Omeprazole (40 mg once daily) increased voriconazole (a CYP2C19 substrate) C max and AUC 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 C max and AUC for cilostazol by 18 % and 26 % respectively, and one of its active metabolites by 29 % and 69 % respectively.

Warfarin: Concomitant administration of 40 mg NEXILOK to warfarin-treated patients showed that, despite a slight elevation in the trough plasma concentration of the less potent R-isomer of warfarin, the coagulation times were within the accepted range. However, as with all patients receiving warfarin, monitoring is recommended during concomitant treatment with NEXILOK.

Clopidogrel: Studies in healthy subjects have shown that concomitant use of clopidogrel and esomeprazole resulted in decreased plasma concentrations of the active metabolite of clopidogrel and a reduction in platelet inhibition. An increase in cardiovascular events has also been reported. Concomitant use of NEXILOK and clopidogrel should be avoided.

Cisapride: In healthy volunteers, concomitant administration of 40 mg NEXILOK resulted in a 32 % increase in area under the plasma concentration-time curve (AUC) and a 31 % prolongation of elimination half-life (tu00bd) but no significant increase in peak plasma levels of cisapride. This interaction did not alter the influence of cisapride on cardiac electrophysiology.

Effects of other medicines on the pharmacokinetics of NEXILOK: Medicines which inhibit CYP2C19 and/or CYP3A4: NEXILOK is metabolised by CYP2C19 and CYP3A4. Concomitant administration of NEXILOK and a CYP3A4 inhibitor, clarithromycin (500 mg twice daily), resulted in a doubling of the exposure (AUC) to esomeprazole, contained in NEXILOK. Dose adjustment of NEXILOK is not required. Medicines which induce CYP2C19 and/or CYP3A4: Medicines known to induce CYP2C19 or CYP3A4 or both (such as rifampicin and St. John's Wort (Hypericum perforatum)) may lead to decreased esomeprazole serum levels by increasing the esomeprazole metabolism.

Pregnancy: Safety during pregnancy has not been established.

Breastfeeding: Safety during lactation has not been established.

Fertility: Reported animal studies with the racemic mixture omeprazole, given by oral administration do not indicate effects with respect to fertility.

NEXILOK may cause somnolence, dizziness and blurred vision. As concentration may be impaired, patients should be advised to exercise caution when driving or operating machinery (see section 4.8).

a. 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.

b. Tabulated summary of adverse reactions:

Infections and infestations: Less frequent Clostridium difficile associated diarrhoea

Blood and lymphatic system disorders: Less frequent Leukopenia, thrombocytopenia Frequency unknown Agranulocytosis, pancytopenia

Immune system disorders: Less frequent Hypersensitivity reactions e.g. angioedema and anaphylactic reaction/shock

Metabolism and nutrition disorders: Less frequent Peripheral oedema, hyponatraemia Frequency unknown Hypomagnesaemia, severe hypomagnesaemia can correlate with hypocalcaemia. Hypomagnesaemia may also be associated with hypokalaemia.

Psychiatric disorders: Less frequent Insomnia, agitation, reversible confusional state, depression Frequency unknown Aggression, hallucinations

Nervous system disorders: Frequent Headache Less frequent Dizziness, paraesthesia, somnolence Frequency unknown Taste disturbance

Eye disorders: Less frequent Blurred vision

Ear and labyrinth disorders: Less frequent Vertigo

Respiratory, thoracic and mediastinal disorders: Less frequent Bronchospasm

Gastrointestinal disorders: Frequent Abdominal pain, constipation, diarrhoea, flatulence, nausea/vomiting Less frequent Dry mouth, stomatitis, gastrointestinal candidiasis Frequency unknown Microscopic colitis

Hepato-biliary disorders: Less frequent Increased liver enzymes, hepatitis with or without jaundice Frequency unknown Hepatic encephalopathy, hepatic failure

Skin and subcutaneous tissue disorders: Frequent Skin rashes Less frequent Dermatitis, pruritus, rash, urticaria, alopecia, bullous eruption, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN), photosensitivity Frequency unknown Subacute cutaneous lupus erythematosus (see section 4.4)

Musculoskeletal and connective tissue disorders: Less frequent Arthralgia, myalgia, fracture of hip, wrist or spine or muscular weakness

Renal and urinary disorders: Less frequent Interstitial nephritis Frequency unknown Renal failure

Reproductive system and breast disorders: Less frequent Gynaecomastia

General disorders and administration site conditions: Less frequent Malaise, hyperhidrosis, fatigue

Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare providers are requested to report any suspected adverse drug reactions to SAHPRA via the Med Safety APP (Medsafety X SAHPRA) and eReporting platform (who-umc.org) found on SAHPRA website.

The symptoms described in connection with deliberate NEXILOK overdose (limited experience of doses in excess of 280 mg/day) are transient. No specific antidote is known. Esomeprazole contained in NEXILOK is extensively plasma protein bound and is therefore not readily dialysable. As in any case of overdose, treatment should be symptomatic and general supportive measures should be utilised.