Nexipraz Otc 30 mg Gastric-resistant tablets

NEXIPRAZ OTC tablets are 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.
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 NEXIPRAZ OTC should be used.
Elderly
Dose adjustment is not required in the elderly.
Paediatric population
There is no experience with NEXIPRAZ OTC 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 any other constituents of NEXIPRAZ OTC.
• Co-administration with atazanavir and nelfinavir (see section 4.5).

General:
Patients should be instructed to consult a doctor if:
u2022 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 treatment with NEXIPRAZ OTC may alleviate symptoms and delay diagnosis.
u2022 They have had previous gastric ulcer or gastrointestinal surgery.
u2022 They have been on continuous symptomatic treatment of indigestion or heartburn for 4 or more weeks.
u2022 They have jaundice or severe liver disease.
u2022 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 Nexipraz OTC as a long-term preventative medicine: Treatment with proton pump inhibitors may lead to slightly increased risk of gastric intestinal infections such as Salmonella and Campylobacter. PPI therapy like esomeprazole as in NEXIPRAZ OTC may be associated with an increased risk of Clostridium difficile associated with watery diarrhoea, stomach pain and fever, especially in hospitalised patients.
Patients should consult their doctor before taking this medicinal product if they are due to have an endoscopy or urea breath test.
Subacute cutaneous lupus erythematosus (SCLE)
Proton pump inhibitors are associated with 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 NEXIPRAZ OTC 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 with atazanavir, nelfinavir and clopidogrel is contraindicated (see section 4.3 and 4.5). Esomeprazole is a CYP2C19 inhibitor. When starting or ending treatment with esomeprazole, the potential for interactions with medicines metabolised through CYP2C19 should be considered. Patients should not take another PPI or H2 antagonist concomitantly.
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 Chromogranin A (CgA) level may interfere with investigations for neuroendocrine tumours. To avoid this interference, NEXIPRAZ OTC 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 should be repeated 14 days after cessation of proton pump inhibitor treatment.
Sucrose
NEXIPRAZ OTC contains sugar (sucrose). Patients with rare hereditary conditions such as fructose intolerance, glucose-galactose mal-absorption or sucrase-isomaltase insufficiency should not take NEXIPRAZ OTC. Sucrose may have an effect on the glycaemic control of patients with diabetes mellitus.

Interaction studies have only been performed in adults
Effects of NEXIPRAZ OTC on the pharmacokinetics of other medicines
As esomeprazole 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 decreases the concentration of atazanavir and nelfinavir. Co-administration of NEXIPRAZ OTC and atazanavir or nelfinavir is contra-indicated (see section 4.3).
Methotrexate
When given together with PPIs in NEXIPRAZ OTC methotrexate levels have been reported to increase in some patients. In high-dose methotrexate administration a temporary withdrawal of NEXIPRAZ OTC may need to be considered.
Tacrolimus
Concomitant administration of esomeprazole as in NEXIPRAZ OTC 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 NEXIPRAZ OTC, 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 NEXIPRAZ OTC. Caution should be exercised when NEXIPRAZ OTC is given at high doses in elderly patients. Therapeutic monitoring of digoxin should be reinforced.
Medicines metabolised by CYP2C19
Esomeprazole inhibits CYP2C19, the major esomeprazole metabolising enzyme. Thus, when esomeprazole 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 NEXIPRAZ OTC 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 esomeprazole 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 NEXIPRAZ OTC.
Clopidogrel
Studies in healthy subjects have shown that concomitant use of esomeprazole and clopidogrel resulted in reduced 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 NEXIPRAZ OTC and clopidogrel should be avoided.
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 (t1/2) 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 esomeprazole:
Medicines which inhibit CYP2C19 and/or CYP3A4 Esomeprazole is metabolised by CYP2C19 and CYP3A4. Concomitant administration of esomeprazole and a CYP3A4 inhibitor, clarithromycin (500 mg twice daily), resulted in a doubling of the exposure (AUC) to esomeprazole. Dose adjustment of NEXIPRAZ OTC 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 breastfeeding 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.

NEXIPRAZ OTC 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).

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.
Tabulated list of adverse reactions
Table 1
MedDRA System Organ Class
Frequent Less Frequent Frequency Unknown
Infections and infestations
Clostridium difficile associated diarrhoea.
Blood and the lymphatic system disorders
Leukopenia, thrombocytopenia, Agranulocytosis, Pancytopenia.
Immune system disorders
Hypersensitivity reactions e.g. angioedema, anaphylactic reaction.
Metabolism and nutrition disorders
Hyponatraemia, Peripheral oedema Hypomagnesaemia Severe hypomagnesaemia can correlate with hypocalcaemia, hypomagnesaemia may also be associated with hypokalaemia.
Nervous system disorders
Headache Dizziness, somnolence paraesthesia Taste disturbance
Psychiatric disorders
Insomnia, reversible confusional state, agitation, depression. Aggression Hallucinations.
Eye disorders
Blurred vision
Ear and labyrinth disorders
Vertigo
Respiratory, thoracic and mediastinal disorders
Bronchospasm
Gastric-intestinal disorders
Abdominal pain, diarrhoea, flatulence, nausea / vomiting, constipation Dry mouth, stomatitis, taste disturbances, gastric-intestinal candidiasis Microscopic colitis
Hepato - biliary disorders
Increased liver enzymes, hepatitis with or without jaundice. Hepatic encephalopathy, hepatic failure
Skin and subcutaneous tissue disorders
Skin rashes Dermatitis, pruritus, urticaria, alopecia, bullous eruption, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN), photosensitivity Subacute cutaneous lupus erythematosus
Musculoskeletal connective tissue and bone disorders
Arthralgia, myalgia, fracture of hip, wrist or spine or muscular weakness.
Renal and urinary disorders
Interstitial nephritis Renal failure
Reproductive system and breast disorders
Gynaecomastia
General disorders and administration site condition
Fatigue, increased sweating, malaise
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. Health care providers are asked to report any suspected adverse reactions to SAHPRA via the u201c6.04 Adverse Drug Reactions Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8.

The symptoms described in connection with deliberate NEXIPRAZ OTC overdose (limited experience of doses in excess of 280 mg/day) are transient. No specific antidote is known. Esomeprazole 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.