It occurs as a white to off-white lyophilization powder in vial.

NAME AND STRENGTH OF ACTIVE INGREDIENT

Each vial contains 42.6 mg Omeprazole Sodium equivalent to Omeprazole…………40 mg.

MECHANISMS OF ACTION

Omeprazole reversibly reduces gastric acid secretion by specifically inhibiting the gastric enzyme H+ /K+ -ATPase proton pump in the parietal cell.

SUMMARY OF PHARMACOKINETICS

Omeprazole Sodium is absorbed rapidly. Omeprazole Sodium is 95% bound to plasma proteins. It is entirely metabolized, mainly in the liver, about 80% of the metabolites are excreted in urine and the remainder in feces. 

PHARMACODYNAMICS

During treatment with antisecretory medicinal products, serum gastrin increases in response to the decreased acid secretion. Also Chromogranin A (CgA) increases due to decreased gastric acidity. The increased CgA level may interfere with investigations for neuroendocrine tumours. Available published evidence suggests that proton pump inhibitors (PPIs) should be discontinued between 5 days and 2 weeks prior to CgA measurements. This is to allow CgA levels that might be spuriously elevated following PPI treatment to return to reference range.

TOXICOLOGY (BRIEF)

To date there has been no experience with deliberate overdosage, nor has there been any indication that it has acute toxic effects in human.

INDICATIONS

Alternative therapy for the following conditions which cannot be treated effectively with oral medication: duodenal ulcer, gastric ulcer, ulcerative oesophagitis and Zollinger-Ellison syndrome.

CONTRAINDICATIONS

Omeprazole is contraindicated in patients with known hypersensitivity to the drug or any ingredient in the formulation. 

SIDE EFFECTS AND ADVERSE REACTIONS

It is generally well tolerated and adverse reactions have generally been mild and reversible. The following have been reported as adverse events in clinical trials or reported from routine use but in many cases a relationship to treatment with omeprazole has not been established.

Skin rash, urticaria and pruritus have been reported, usually resolving after discontinuation of treatment. In addition, photosensitivity, bullous eruption, erythema multiforme, StevensJohnson syndrome, toxic epidermal necrolysis, angioedema and alopecia have been reported in isolated cases.

Diarrhea and headache have been reported and may be severe enough to require discontinuation of therapy in a small number of patients. In the majority of cases, the symptoms resolved after discontinuation of therapy.

Other gastrointestinal reactions include constipation, nausea/vomiting, flatulence and abdominal pain. Dry mouth, stomatitis and candidiasis have been reported as isolated cases. Paraesthesia has been reported. Dizziness, light-headedness and feeling faint have been associated with treatment, but all usually resolve on cessation of therapy. Somnolence, insomnia and vertigo have been reported rarely. Reversible mental confusion, agitation, depression and hallucinations have occurred predominantly in severely ill patients.

Arthritic and myalgic symptoms have been reported and have usually resolved when therapy is stopped.

In isolated cases, the following have been reported: blurred vision, taste disturbance, aggression, peripheral oedema, hyponatraemia, increased sweating, gynaecomastia, impotence, leucopenia, thrombocytopenia, agranulocytosis, pancytopenia, anaphylactic shock, malaise, fever, bronchospasm, encephalopathy in patients with pre-existing severe liver disease, hepatitis with or without jaundice, rarely hepatic failure and interstitial nephritis which has resulted in acute renal failure. 
Isolated cases of irreversible visual impairment have been reported in critically ill patients who have received the product, particularly at high doses, however no causal relationship has been established.

Increase in liver enzymes has been observed rarely. 

PRECAUTIONS AND WARNINGS

Before giving omeprazole to patients with gastric ulcers, the possibility of malignancy should be excluded since omeprazole may mask symptoms and delay diagnosis.
Omeprazole inhibits the metabolism of some drugs metabolized by the hepatic cytochrome P-450 enzyme system and may increase plasma concentrations of diazepam, phenytoin, and warfarin.
Patients with impaired hepatic function show a markedly increased bioavailability, a reduced total plasma clearance and up to a four-fold prolongation of the elimination half-life. However urinary recovery over 96 hours remains unchanged, indicating no accumulation of omeprazole or its metabolites. A daily dose of 10-20 mg may be sufficient for patients with impaired hepatic disease.

There are no adequate or well-controlled studies in pregnant women. Omeprazole should only be given to pregnant women if its use is considered essential.

Although omeprazole is excreted at low concentrations in the milk of lactating female rats, it is not known if omeprazole or its metabolites appear in human breast milk. Therefore it is recommended that omeprazole not be used during breast-feeding. 

Hypomagnesaemia, symptomatic and asymptomatic, has been reported rarely in patients treated with PPIs for at least three months, in most cases after a year of therapy. 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 PPIs.

For patients expected to be on prolonged treatment or who take PPIs with medications such as digoxin or drugs that may cause hypomagnesaemia (e.g. diuretics), health care professionals may consider monitoring magnesium levels prior to initiation of PPI treatment and periodically. 

Several published observational studies suggest that PPI therapy may be associated with an increased overall risk for osteoporosis-related fractures of the hip, wrist, or spine. The risk of fracture was increased in patients who received high-dose, defined as multiple daily doses, and long-term PPI therapy (a year or longer), predominantly in the elderly or in presence of other recognized risk factors. Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. Patients at risk for osteoporosis-related fractures should be managed according to established treatment guidelines and they should have an adequate intake of Vitamin D and calcium.

Literature suggests that concomitant use of PPIs with methotrexate (primarily at high dose; see methotrexate prescribing information) may elevate and prolong serum levels of methotrexate and/or its metabolite, possibly leading to methotrexate toxicities. In high-dose methotrexate administration a temporary withdrawal of the PPI may be considered in some patients.

Cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE) CLE and SLE have been reported in patients taking PPIs. These events have occurred as both new onset and an exacerbation of existing autoimmune disease. The majority of PPI-induced lupus erythematosus cases were CLE. The most common form of CLE reported in patients treated with PPIs was subacute CLE (SCLE) and occurred within weeks to years after continuous drug therapy in patients ranging from infants to the elderly. Generally, histological findings were observed without organ involvement. 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 Omezol Lyo Injection 40 mg. SCLE after previous treatment with a PPI may increase the risk of SCLE with other PPI. Systemic lupus erythematosus (SLE) is less commonly reported than CLE in patients receiving PPIs. PPI associated SLE is usually milder than non-drug induced SLE. Onset of SLE typically occurred within days to years after initiating treatment primarily in patients ranging from young adults to the elderly. The majority of patients presented with rash; however, arthralgia and cytopenia were also reported. Avoid administration of PPIs for longer than medically indicated. If signs or symptoms consistent with CLE or SLE are noted in patients receiving Omezol Lyo-Injection, discontinue the drug and refer the patient to the appropriate specialist for evaluation. Most patients improve with discontinuation of the PPI alone in 4 to 12 weeks. Serological testing (e.g., Antinuclear antibody) may be positive and elevated serological test results may take longer to resolve than clinical manifestations. 

Increased CgA level may interfere with investigations for neuroendocrine tumours. If the patient(s) are due to have a test on Chromogranin A level, Omezol Lyo Injection 40 mg treatment should be stopped for at least 5 days before CgA measurements to avoid this interference (see PHARMACODYNAMICS). If CgA and gastrin levels have not returned to reference range after initial measurement, measurements should be repeated 14 days after cessation of PPI treatment.

Patients on PPI treatment (particularly those treated for long term) should be kept under regular surveillance.

Daily treatment with any acid-suppressing medications over a long period of time (e.g., longer than 3 years) may lead to malabsorption of cyanocobalamin (Vitamin B12) caused by hypo- or achlorhydria. Rare reports of cyanocobalamin deficiency occurring with acidsuppressing therapy have been reported in the literature. This diagnosis should be considered if clinical symptoms consistent with cyanocobalamin deficiency are observed.