Source: Health Products Regulatory Authority (ZA) Revision Year: 2021 Publisher: Dr. Reddys Laboratories (Pty) Ltd., Block B, 204 Rivonia Road, Morningside, Sandton 2057
Hypersensitivity to omeprazole or to any of the other ingredients of OMEZ.
Safety in pregnancy and lactation has not been established.
OMEZ must not be used concomitantly with nelfinavir.
Co-administration of atazanavir with OMEZ is not recommended.
In the presence of any alarm symptom (e.g. significant unintentional weight loss, recurrent vomiting, dysphagia, haematemesis or melena) and when gastric ulcer is suspected or present, malignancy should be excluded, as treatment may alleviate symptoms and delay diagnosis.
Hepatic impairment may require a reduction in dose (see Section 4.2).
The long-term safety of OMEZ in patients with renal and/or hepatic impairment has not been established.
There is very limited experience with the use of OMEZ in children.
Some children with chronic illnesses may require long-term treatment although it is not recommended.
Co-administration of atazanavir with proton pump inhibitors is not recommended (see Section 4.3). If the combination of atazanavir with OMEZ is judged unavoidable, close clinical monitoring (e.g. virus load) is recommended in combination with an increase in the dose of atazanavir to 400 mg with 100 mg of ritonavir; omeprazole 20 mg should not be exceeded.
OMEZ, as all acid-blocking medicines, may reduce the absorption of vitamin B12 (cyanocobalamin) due to hypo- or achlorhydria. This should be considered in patients with reduced body stores or risk factors for reduced vitamin B12 absorption on long-term therapy.
OMEZ is a CYP2C19 inhibitor. When starting or ending treatment with omeprazole, the potential for interactions with drugs metabolised through CYP2C19 should be considered. An interaction is observed between clopidogrel and OMEZ (see Section 4.5). The clinical relevance of this interaction is uncertain. As a precaution, concomitant use of OMEZ and clopidogrel should be discouraged.
OMEZ, especially if used in high doses and over long durations (>1 year), may modestly increase the risk of hip, wrist and spine fracture, predominantly in the elderly or in presence of other recognised risk factors. Observational studies suggest that proton pump inhibitors may increase the overall risk of fracture by 10 to 40 %. Some of this increase may be due to other risk factors. Patients at risk of osteoporosis should receive care according to current clinical guidelines and they should have an adequate intake of vitamin D and calcium.
Severe hypomagnesaemia has been reported in patients treated with proton pump inhibitors (PPIs) like OMEZ for at least three months, and in most cases for a year. Serious manifestations of hypomagnesaemia such as fatigue, tetany, delirium, convulsions, dizziness and ventricular arrhythmia can occur but they may begin insidiously and be overlooked. In most affected patients, hypomagnesaemia improved after magnesium replacement and discontinuation of the OMEZ.
For patients expected to be on prolonged treatment or who take OMEZ with digoxin or drugs that may cause hypomagnesaemia (e.g. diuretics), healthcare professionals should consider measuring magnesium levels before starting OMEZ treatment and periodically during treatment.
Proton pump inhibitor (PPI) therapy like OMEZ is associated with very 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 OMEZ. SCLE after previous treatment with OMEZ may increase the risk of SCLE with other proton pump inhibitors.
Increased Chromogranin A (CgA) level may interfere with investigations for neuroendocrine tumours. To avoid this interference, OMEZ treatment should be stopped for at least 5 days before CgA measurements. If CgA and gastrin levels have not returned to reference range after initial measurement, measurements should be repeated 14 days after cessation of OMEZ treatment.
During long-term treatment gastric glandular cysts have been reported in increased frequency. These physiological changes result from pronounced inhibition of gastric acid secretion. Decreased gastric acidity increases gastric counts of bacteria normally present in the gastro-intestinal tract.
Treatment with OMEZ may lead to an increased risk of gastro-intestinal infections such as Salmonella, Campylobacter, or C. difficile.
Proton pump inhibitor (PPI) therapy like OMEZ may be associated with an increased risk of Clostridium difficile associated diarrhoea (CDAD), especially in hospitalised patients.
This diagnosis should be considered for diarrhoea that does not improve (see Section 4.8).
Patients should use the lowest dose and shortest duration of OMEZ therapy appropriate to the condition being treated.
Acute Tubulointerstitial Nephritis (TIN) has been observed in patients taking PPIs and may occur at any point during PPI therapy. TIN is characterised by an inflammatory reaction within the tubulointerstitial space of the kidney. Acute interstitial inflammatory reactions are associated with damage to the tubulointerstitium, leading to acute kidney injury. TIN may be drug-related, infectious, systemic, autoimmune, genetic, and idiopathic with the most common cause being related to a medication or drug exposure.
Patients may present with varying signs and symptoms from symptomatic hypersensitivity reactions to non-specific symptoms of decrease renal function (e.g., malaise, nausea, anorexia). In reported case series, some patients were diagnosed on biopsy and in the absence of extrarenal manifestations (e.g., fever rash or arthralgia). Discontinue OMEZ and evaluate patients with suspected acute TIN.
As in all long-term treatments, especially when exceeding a treatment period of 1 year, patients should be kept OMEZ contains mannitol which, on rare occasions, may cause hypersensitivity reactions and may have a laxative effect.
Clopidogrel is metabolised to its active metabolite in part by CYP2C19. Co-administration of clopidogrel with omeprazole, an inhibitor of CYP2C19, reduces the pharmacological activity of clopidogrel given concomitantly or 12 hours apart. Concomitant use of medicines that inhibit the activity of this enzyme may result in reduced plasma concentrations of the active metabolite of clopidogrel and a reduction in platelet inhibition.
OMEZ is metabolised via the hepatic P450 cytochrome enzyme system, which may affect the metabolism of other medications metabolised by these enzymes, when given concomitantly.
The elimination of diazepam, warfarin and phenytoin may be prolonged when OMEZ is given concomitantly. Monitoring of INR and phenytoin serum levels is recommended and dosage reductions may be necessary when OMEZ is given concomitantly.
There may be interactions with other medicines, which are also metabolised via the cytochrome P450 enzyme system.
Concomitant treatment with omeprazole (20 mg daily) and digoxin in healthy subjects increased the bioavailability of digoxin by 10%. Digoxin toxicity has been rarely reported. However caution should be exercised when omeprazole is given at high doses in elderly patients. Therapeutic drug monitoring of digoxin should then be reinforced (see Section 4.4).
In case of co-administration with OMEZ, the plasma levels of nelfinavir and atazanavir are decreased. Concomitant administration of OMEZ with nelfinavir is contraindicated (see Section 4.3). Co-administration of OMEZ (40 mg once daily) reduced mean nelfinavir exposure by ca. 40% and the mean exposure of the pharmacologically active metabolite M8 was reduced by ca. 75 to 90%. The interaction may also involve CYP2C19 inhibition. Concomitant administration of omeprazole with atazanavir is not recommended. Concomitant administration of OMEZ (40 mg once daily) and atazanavir 300 mg/ritonavir 100 mg to healthy volunteers resulted in a 75% decrease of the atazanavir exposure. Increasing the atazanavir dose to 400 mg did not compensate for the impact of omeprazole on atazanavir exposure. The co-administration of OMEZ (20 mg once daily) with atazanavir 400 mg/ritonavir 100 mg to healthy volunteers resulted in a decrease of approximately 30% in the atazanavir exposure as compared to atazanavir 300 mg/ritonavir 100 mg once daily.
Concomitant administration of OMEZ 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.
When given together with OMEZ, methotrexate levels have been reported to increase in some patients. In high-dose methotrexate administration a temporary withdrawal of omeprazole may need to be considered.
The absorption of posaconazole, erlotinib, ketoconazole and itraconazole is significantly reduced and thus clinical efficacy may be impaired. For posaconazole and erlotinib concomitant use should be avoided.
Safety in pregnancy and lactation has not been established (see Section 4.3).
OMEZ may lead to drowsiness and impaired concentration that may be aggravated by the simultaneous intake of alcohol or other central nervous system depressants. Patients should be advised, particularly at the initiation of therapy, against taking charge of vehicles or machinery or performing potentially hazardous tasks where loss of concentration could lead to accidents.
Frequency not known: Clostridium-difficile-associated diarrhoea
Less frequent: Leucopenia, thrombocytopenia, agranulocytosis, pancytopenia
Less frequent: Gynaecomastia
Less frequent: Hyponatraemia, hypomagnesaemia.
Less frequent: Reversible mental confusion, agitation, aggression, depression and hallucinations (predominantly in severely ill patients)
Frequent: Headache (severe enough to cause discontinuation in some patients)
Less frequent: Dizziness, somnolence, insomnia, parasthaesias
Less frequent: Blurred vision
Less frequent: Peripheral oedema
Less frequent: Bronchospasm
Frequent: Diarrhoea (severe enough to require discontinuation of therapy in some patients), constipation, abdominal pain or colic, nausea, vomiting, flatulence, gastric glandular cysts, fundic gland polyps (benign)
Less frequent: Dry mouth, stomatitis, oesophageal candidiasis, taste disturbances
Frequency unknown: microscopic colitis
Less frequent: Raised liver enzymes, hepatitis with or without jaundice, hepatic encephalopathy
Less frequent: Skin rash, urticaria, pruritus, photosensitivity, bullous eruption, toxic epidermal necrolysis, StevensJohnson syndrome, alopecia, erythema multiforme
Less frequent: Asthenia, arthralgia, myalgia, bone fracture
Less frequent: Interstitial nephritis
Less frequent: Hypersensitivity reactions (e.g. fever, angioedema, bronchospasm, interstitial nephritis)
Less frequent: Malaise
Reporting suspected adverse reactions after authorisation of the medicine is important. Health care providers are asked to report any suspected adverse reactions to SAHPRA via the “6.04 Adverse Drug Reactions Reporting Form”, found online under SAHPRA’s publications: https://www.sahpra.org.za/Publications/Index/8.
Not applicable.
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