GENERIC NAME OF THE MEDICINAL PRODUCT:

Omeprazole for Injection 40mg (PRILOSID) Taj Pharma

QUALITATIVE AND QUANTITATIVE COMPOSITION:

Each vial of Omeprazole for Injection 40mg (PRILOSID) Taj Pharma contains:
Omeprazole sodium equivalent to
Omeprazole 40mg
Excipients q.s.

THERAPEUTIC INDICATIONS:

Treatment of duodenal ulcers, gastric ulcers, Zollinger-Ellison syndrome, in combination with appropriate antibiotics for symptomatic gastro-oesophageal reflux disease, symptomatic gastro-oesophageal reflux disease, reflux oesophagitisHelicobacter pylori (H. pylori) eradication in peptic ulcer disease, NSAID-associated gastric and duodenal ulcers, Prevention of relapse of duodenal ulcers, Prevention of relapse of gastric ulcers, NSAID-associated gastric and duodenal ulcers in patients at risk.

Omeprazole for Injection 40mg (Prilosid) Taj Pharma

Overview

INTRODUCTION

Prilosid 40mg Injection is a medicine which reduces the amount of acid produced in your stomach. It is used to treat heartburn, acid reflux and problems in your food pipe. It is also used to prevent and treat stomach ulcers.

You should take Prilosid 40mg Injection as your doctor advises. The dose will depend on what you are being treated for, but it should be the lowest dose for the shortest amount of time needed to treat your condition. It should be given as an injection into the vein by a healthcare professional. It may take up to a few weeks to work properly but your doctor will tell you how long you need to be taking it for. You should keep on taking it as prescribed even if your symptoms disappear quickly. If you are taking this medicine for a long time, your doctor may carry out regular tests to check your levels of magnesium which can fall with this medicine.

Common side effects include headache, constipation or diarrhoea, stomach pain and feeling or being sick. These tend to be mild but talk to your doctor if they bother you or do not go away. The risk of side effects may increase the longer you take this medicine. Serious side effects are rare, but some need immediate medical attention. Ask your doctor what these are. You may be more likely to have a broken bone if you take it for a long time. It is best to avoid foods that seem to make your symptoms worse, such as rich, spicy and fatty foods. It also helps to cut down on caffeinated drinks, such as tea, coffee and cola, as well as alcohol.

Prilosid 40mg Injection is not suitable for some people. Before taking this medicine, you need to tell your doctor if you have severe liver problems, are taking medicines for HIV, have had an allergic reaction to similar medicines in the past or have osteoporosis. Alcohol does not interfere with the way pantoprazole works. However, drinking alcohol makes your stomach produce more acid than normal. This medicine can make you feel dizzy, sleepy, or affect your vision. If this happens, do not drive, cycle or use machinery or tools until you feel better. It is not usually recommended during pregnancy and breastfeeding.

USES OF PRILOSID POWDER FOR INJECTION

  • Gastroesophageal reflux disease (Acid reflux)
  • Peptic ulcer disease

SIDE EFFECTS OF PRILOSID POWDER FOR INJECTION

Common
  • Headache
  • Stomach pain
  • Nausea
  • Flatulence
  • Diarrhea
  • Injection site reactions (pain, swelling, redness)
  • Dryness in mouth
  • Dizziness

HOW TO USE PRILOSID POWDER FOR INJECTION

Your doctor or nurse will give you this medicine. Kindly do not self administer.

HOW PRILOSID POWDER FOR INJECTION WORKS

Prilosid 40mg Injection is a proton pump inhibitor (PPI). It works by reducing the amount of acid in the stomach which helps in relief of acid related indigestion and heartburn.

SAFETY ADVICE

warnings

Alcohol

CAUTION
Caution is advised when consuming alcohol with Prilosid 40mg Injection. Please consult your doctor.
warnings

Pregnancy

CONSULT YOUR DOCTOR
Prilosid 40mg Injection may be unsafe to use during pregnancy. Although there are limited studies in humans, animal studies have shown harmful effects on the developing baby. Your doctor will weigh the benefits and any potential risks before prescribing it to you. Please consult your doctor.
warnings

Breastfeeding

CONSULT YOUR DOCTOR
Prilosid 40mg Injection is probably unsafe to use during breastfeeding. Limited human data suggests that the drug may pass into the breastmilk and harm the baby.
warnings

Driving

UNSAFE
Prilosid 40mg Injection may cause side effects which could affect your ability to drive.
Prilosid 40mg Injection may cause dizziness and visual disturbances. This may affect your driving ability.
warnings

Kidney

SAFE IF PRESCRIBED
Prilosid 40mg Injection is safe to use in patients with kidney disease. No dose adjustment of Prilosid 40mg Injection is recommended.
warnings

Liver

CAUTION
Prilosid 40mg Injection should be used with caution in patients with severe liver disease. Dose adjustment of Prilosid 40mg Injection may be needed. Please consult your doctor.
A lower dose may be advised in patients with liver disease and who have to take this medicine for a long time.

WHAT IF YOU FORGET TO TAKE PRILOSID POWDER FOR INJECTION?

If you miss a dose of Prilosid 40mg Injection, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular schedule. Do not double the dose.

Omeprazole for Injection 40mg (Prilosid) Taj Pharma

  1. Name of the medicinal product

Omeprazole for Injection 40mg (PRILOSID) Taj Pharma

  1. Qualitative and quantitative composition

Each vial of Omeprazole for Injection 40mg (PRILOSID) Taj Pharma contains:

Omeprazole sodium equivalent to
Omeprazole.       40mg
Excipients             q.s.

  1. Pharmaceutical form

Powder for solution for infusion.

The powder for solution for infusion is a white to almost white powder.

The reconstituted solution has a pH of about 9-10.5.

The osmolarity of the solution reconstituted with100 ml of 5 % glucose solution is about 0.297Osmol/kg.

The osmolarity of the solution reconstituted with 100 ml of 0.9 % saline is about 0.282 Osmol/kg

  1. Clinical particulars

4.1 Therapeutic indications

Omeprazole for intravenous use is indicated as an alternative to oral therapy for the following indications i.e.

Adults

  • Treatment of duodenal ulcers
  • Prevention of relapse of duodenal ulcers
  • Treatment of gastric ulcers
  • Prevention of relapse of gastric ulcers
  • In combination with appropriate antibiotics, Helicobacter pylori (H. pylori) eradication in peptic ulcer disease
  • Treatment of NSAID-associated gastric and duodenal ulcers
  • Prevention of NSAID-associated gastric and duodenal ulcers in patients at risk
  • Treatment of reflux oesophagitis
  • Long-term management of patients with healed reflux oesophagitis
  • Treatment of symptomatic gastro-oesophageal reflux disease
  • Treatment of Zollinger-Ellison syndrome

4.2 Posology and method of administration

Posology

Alternative to oral therapy

In patients where the use of oral medicinal products is inappropriate, Omeprazole IV 40 mg once daily is recommended. In patients with Zollinger-Ellison Syndrome the recommended initial dose of Omeprazole given intravenously is 60 mg daily. Higher daily doses may be required and the dose should be adjusted individually. When doses exceed 60 mg daily, the dose should be divided and given twice daily.

Omeprazole is to be administered in an intravenous infusion for 20-30 minutes.

For instructions on reconstitution of the product before administration, see section 6.6.

Special populations

Impaired renal function

Dose adjustment is not needed in patients with impaired renal function (see section 5.2).

Impaired hepatic function

In patients with impaired hepatic function a daily dose of 10-20 mg may be sufficient (see section 5.2).

Elderly (> 65 years old)

Dose adjustment is not needed in the elderly (see section 5.2).

Paediatric patients

There is limited experience with Omeprazole for intravenous use in children.

Method of administration

Omeprazole for intravenous is to be administered in an intravenous infusion for 20-30 minutes. After reconstitution the solution is colourless, clear, practically free from visible particles.

4.3 Contraindications

Hypersensitivity to omeprazole, substituted benzimidazoles or to any of the excipients.

Omeprazole like other proton pump inhibitors (PPIs) should not be used concomitantly with nelfinavir (see section 4.5).

4.4 Special warnings and precautions for use

In the presence of any alarm symptoms (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.

Co-administration of atazanavir with proton pump inhibitors is not recommended (see section 4.5). If the combination of atazanavir with a proton pump inhibitor 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.

Omeprazole, as all acid-blocking medicinal products, 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.

Omeprazole is a CYP2C19 inhibitor. When starting or ending treatment with omeprazole, the potential for interactions with medicinal products metabolised through CYP2C19 should be considered. An interaction is observed between clopidogrel and omeprazole (see section 4.5). The clinical relevance of this interaction is uncertain. As a precaution, concomitant use of omeprazole and clopidogrel should be discouraged.

Treatment with proton pump inhibitors may lead to slightly increased risk of gastrointestinal infections such as Salmonella and Campylobacter (see section 5.1).

Severe hypomagnesaemia has been reported in patients treated with proton pump inhibitors like omeprazole 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 proton pump inhibitor.

For patients expected to be on prolonged treatment or who take proton pump inhibitors with digoxin or medicinal products that may cause hypomagnesaemia (e.g., diuretics), health care professionals should consider measuring magnesium levels before starting proton pump inhibitor treatment and periodically during treatment.

Proton pump inhibitors, 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 10–40%. 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.

Subacute cutaneous lupus erythematosus (SCLE)

Proton pump inhibitors are 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 omeprazole for intravenous. SCLE after previous treatment with a proton pump inhibitor may increase the risk of SCLE with other proton pump inhibitors.

Interference with laboratory tests

Increased Chromogranin A (CgA) level may interfere with investigations for neuroendocrine tumours. To avoid this interference, omeprazole for intravenous 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 measurement, measurements should be repeated 14 days after cessation of proton pump inhibitor treatment.

As in all long-term treatments, especially when exceeding a treatment period of 1 year, patients should be kept under regular surveillance.

4.5 Interaction with other medicinal products and other forms of interaction

Effects of omeprazole on the pharmacokinetics of other active substances

Active substances with pH dependent absorption

The decreased intragastric acidity during treatment with omeprazole might increase or decrease the absorption of active substances with a gastric pH dependent absorption.

Nelfinavir, atazanavir

The plasma levels of nelfinavir and atazanavir are decreased in case of co-administration with omeprazole.

Concomitant administration of omeprazole with nelfinavir is contraindicated (see section 4.3).

Co-administration of omeprazole (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. 75-90%. The interaction may also involve CYP2C19 inhibition.

Concomitant administration of omeprazole with atazanavir is not recommended (see section 4.4).

Concomitant administration of omeprazole (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 omeprazole (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.

Digoxin

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.

Clopidogrel

In a crossover clinical study, clopidogrel (300 mg loading dose followed by 75 mg/day) alone and with omeprazole (80 mg at the same time as clopidogrel) were administered for 5 days. The exposure to the active metabolite of clopidogrel was decreased by 46% (Day 1) and 42% (Day 5) when clopidogrel and omeprazole were administered together. Mean inhibition of platelet aggregation (IPA) was diminished by 47% (24 hours) and 30% (Day 5) when clopidogrel and omeprazole were administered together. In another study it was shown that administering clopidogrel and omeprazole at different times did not prevent their interaction that is likely to be driven by the inhibitory effect of omeprazole on CYP2C19. Inconsistent data on the clinical implications of this PK/PD interaction in terms of major cardiovascular events have been reported from observational and clinical studies.

Other active substances

The absorption of posaconazole, erlotinib, ketoconazol and itraconazol is significantly reduced and thus clinical efficacy may be impaired. For posaconazol and erlotinib concomitant use should be avoided.

Active substances metabolised by CYP2C19

Omeprazole is a moderate inhibitor of CYP2C19, the major omeprazole metabolising enzyme. Thus, the metabolism of concomitant active substances also metabolised by CYP2C19, may be decreased and the systemic exposure to these substances increased. Examples of such medicinal products are R-warfarin and other vitamin K antagonists, cilostazol, diazepam and phenytoin.

Cilostazol

Omeprazole, given in doses of 40 mg to healthy subjects in a cross-over study, increased Cmax and AUC for cilostazol by 18% and 26% respectively, and one of its active metabolites by 29% and 69% respectively.

Phenytoin

Monitoring phenytoin plasma concentration is recommended during the first two weeks after initiating omeprazole treatment and, if a phenytoin dose adjustment is made, monitoring and a further dose adjustment should occur upon ending omeprazole treatment.

Unknown mechanism

Saquinavir

Concomitant administration of omeprazole with saquinavir/ritonavir resulted in increased plasma levels up to approximately 70% for saquinavir associated with good tolerability in HIV-infected patients.

Tacrolimus

Concomitant administration of omeprazole 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.

Effects of other active substances on the pharmacokinetics of omeprazole

Inhibitors of CYP2C19 and/or CYP3A4

Since omeprazole is metabolised by CYP2C19 and CYP3A4, active substances known to inhibit CYP2C19 or CYP3A4 (such as clarithromycin and voriconazole) may lead to increased omeprazole serum levels by decreasing omeprazole’s rate of metabolism. Concomitant voriconazole treatment resulted in more than doubling of the omeprazole exposure. As high doses of omeprazole have been well-tolerated adjustment of the omeprazole dose is not generally required. However, dose adjustment should be considered in patients with severe hepatic impairment and if long-term treatment is indicated.

Inducers of CYP2C19 and/or CYP3A4

Active substances known to induce CYP2C19 or CYP3A4 or both (such as rifampicin and St John’s wort) may lead to decreased omeprazole serum levels by increasing omeprazole’s rate of metabolism.

4.6 Pregnancy and lactation

Results from three prospective epidemiological studies (more than 1000 exposed outcomes) indicate no adverse events of omeprazole on pregnancy or on the health of the foetus/newborn child. Omeprazole can be used during pregnancy.

Omeprazole is excreted in breast milk but is not likely to influence the child when therapeutic doses are used.

4.7 Effects on ability to drive and use machines

Omeprazole is not likely to affect the ability to drive or use machines. Adverse reactions such as dizziness and visual disturbances may occur (see section 4.8). If affected, patients should not drive or operate machinery.

4.8 Undesirable effects

Summary of the safety profile

The most common adverse events (1-10% of patients) are headache, abdominal pain, constipation, diarrhoea, flatulence and nausea/vomiting.

Tabulated list of adverse reactions

The following adverse reactions have been identified or suspected in the clinical trials programme for omeprazole and post-marketing. None was found to be dose-related. Adverse reactions listed below are classified according to frequency and System Organ Class (SOC). Frequency categories are defined according to the following convention: Very common (≥1/10), Common (≥1/100 to <1/10), Uncommon (≥1/1,000 to <1/100), Rare (≥1/10,000 to <1/1,000), Very rare (<1/10,000), Not known (cannot be estimated from the available data).

SOC/frequencyAdverse reaction
Blood and lymphatic system disorders
Rare:Leukopenia, thrombocytopenia
Very rare:Agranulocytosis, pancytopenia
Immune system disorders
Rare:Hypersensitivity reactions e.g. fever, angioedema and anaphylactic reaction/shock
Metabolism and nutrition disorders
Rare:Hyponatraemia
Very rare:Hypomagnesaemia (see section 4.4).
Psychiatric disorders
Uncommon:Insomnia
Rare:Agitation, confusion, depression
Very rare:Aggression, hallucinations
Nervous system disorders
Common:Headache
Uncommon:Dizziness, paraesthesia, somnolence
Rare:Taste disturbance
Eye disorders
Rare:Blurred vision
Ear and labyrinth disorders
Uncommon:Vertigo
Respiratory, thoracic and mediastinal disorders
Rare:Bronchospasm
Gastrointestinal disorders
Common:Abdominal pain, constipation, diarrhoea, flatulence, nausea/vomiting, fundic gland polyps (benign)
Rare:Dry mouth, stomatitis, gastrointestinal candidiasis, microscopic colitis
Hepatobiliary disorders
Uncommon:Increased liver enzymes
Rare:Hepatitis with or without jaundice
Very rare:Hepatic failure, encephalopathy in patients with pre-existing liver disease
Skin and subcutaneous tissue disorders
Uncommon:Dermatitis, pruritus, rash, urticaria
Rare:Alopecia, photosensitivity
Very rare:Erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN)
Not known:Subacute cutaneous lupus erythematosus (see section 4.4)
Musculoskeletal and connective tissue disorders
Uncommon:Fracture of the hip, wrist or spine (see section 4.4)
Rare:Arthralgia, myalgia
Very rare:Muscular weakness
Renal and urinary disorders
Rare:Interstitial nephritis
Reproductive system and breast disorders
Very rare:Gynaecomastia
General disorders and administration site conditions
Uncommon:Malaise, peripheral oedema
Rare:Increased sweating

Irreversible visual impairment has been reported in isolated cases of critically ill patients who have received omeprazole intravenous injection, especially at high doses, but no causal relationship has been established.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.

4.9 Overdose

There is limited information available on the effects of overdoses of omeprazole in humans. In the literature, doses of up to 560 mg have been described, and occasional reports have been received when single oral doses have reached up to 2,400 mg omeprazole (120 times the usual recommended clinical dose). Nausea, vomiting, dizziness, abdominal pain, diarrhoea and headache have been reported. Also apathy, depression and confusion have been described in single cases.

The symptoms described have been transient, and no serious outcome has been reported. The rate of elimination was unchanged (first order kinetics) with increased doses. Treatment, if needed, is symptomatic.

Intravenous doses of up to 270 mg on a single day and up to 650 mg over a three-day period have been given in clinical trials without any dose-related adverse reactions.

  1. Pharmacological properties

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Drugs for acid related disorders, Proton pump inhibitors, Mechanism of action

Omeprazole, a racemic mixture of two enantiomers reduces gastric acid secretion through a highly targeted mechanism of action. It is a specific inhibitor of the acid pump in the parietal cell. It is rapidly acting and provides control through reversible inhibition of gastric acid secretion with once-daily dosing.

Omeprazole is a weak base and is concentrated and converted to the active form in the highly acidic environment of the intracellular canaliculi within the parietal cell, where it inhibits the enzyme H+, K+-ATPase – the acid pump. This effect on the final step of the gastric acid formation process is dose-dependent and provides for highly effective inhibition of both basal acid secretion and stimulated acid secretion, irrespective of stimulus.

Pharmacodynamic effects

All pharmacodynamic effects observed can be explained by the effect of omeprazole on acid secretion.

Effect on gastric acid secretion

Intravenous omeprazole produces a dose dependent inhibition of gastric acid secretion in humans. In order to immediately achieve a similar reduction of intragastric acidity as after repeated dosing with 20 mg orally, a first dose of 40 mg intravenously is recommended. This results in an immediate decrease in intragastric acidity and a mean decrease over 24 hours of approximately 90% for both IV injection and IV infusion.

The inhibition of acid secretion is related to the area under the plasma concentration-time curve (AUC) of omeprazole and not to the actual plasma concentration at a given time.

No tachyphylaxis has been observed during treatment with omeprazole.

Effect on H. pylori

  1. pylori is associated with peptic ulcer disease, including duodenal and gastric ulcer disease. H. pylori is a major factor in the development of gastritis. H. pylori together with gastric acid are major factors in the development of peptic ulcer disease. H. pylori is a major factor in the development of atrophic gastritis which is associated with an increased risk of developing gastric cancer.

Eradication of H. pylori with omeprazole and antimicrobials is associated with high rates of healing and long-term remission of peptic ulcers.

Other effects related to acid inhibition

During long-term treatment gastric glandular cysts have been reported in a somewhat increased frequency. These changes are a physiological consequence of pronounced inhibition of acid secretion, are benign and appear to be reversible.

Decreased gastric acidity due to any means including proton pump inhibitors, increases gastric counts of bacteria normally present in the gastrointestinal tract. Treatment with acid-reducing medicinal products may lead to slightly increased risk of gastrointestinal infections such as Salmonella and Campylobacter.

During treatment with antisecretory medicinal products, serum gastrin increases in response to the decreased acid secretion. Also 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 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.

5.2 Pharmacokinetic properties

Distribution

The apparent volume of distribution in healthy subjects is approximately 0.3 l/kg body weight. Omeprazole is 97% plasma protein bound.

Metabolism:

Omeprazole is completely metabolised by the cytochrome P450 system (CYP). The major part of its metabolism is dependent on the polymorphically expressed CYP2C19, responsible for the formation of hydroxyomeprazole, the major metabolite in plasma. The remaining part is dependent on another specific isoform, CYP3A4, responsible for the formation of omeprazole sulphone. As a consequence of high affinity of omeprazole to CYP2C19, there is a potential for competitive inhibition and metabolic drug-drug interactions with other substrates for CYP2C19. However, due to low affinity to CYP3A4, omeprazole has no potential to inhibit the metabolism of other CYP3A4 substrates. In addition, omeprazole lacks an inhibitory effect on the main CYP enzymes.

Approximately 3% of the Caucasian population and 15–20% of Asian populations lack a functional CYP2C19 enzyme and are called poor metabolisers. In such individuals the metabolism of omeprazole is probably mainly catalysed by CYP3A4. After repeated once-daily administration of 20 mg omeprazole, the mean AUC was 5 to 10 times higher in poor metabolisers than in subjects having a functional CYP2C19 enzyme (extensive metabolisers). Mean peak plasma concentrations were also higher, by 3 to 5 times. These findings have no implications for the posology of omeprazole.

Excretion

Total plasma clearance is about 30-40 l/h after a single dose. The plasma elimination half-life of omeprazole is usually shorter than one hour both after single and repeated once-daily dosing. Omeprazole is completely eliminated from plasma between doses with no tendency for accumulation during once-daily administration. Almost 80% of a dose of omeprazole is excreted as metabolites in the urine, the remainder in the faeces, primarily originating from bile secretion.

Linearity/non-linearity

The AUC of omeprazole increases with repeated administration. This increase is dose-dependent and results in a non-linear dose-AUC relationship after repeated administration. This time- and dose-dependency is due to a decrease of first pass metabolism and systemic clearance probably caused by an inhibition of the CYP2C19 enzyme by omeprazole and/or its metabolites (e.g. the sulphone).

No metabolite has been found to have any effect on gastric acid secretion.

Special populations

Impaired hepatic function

The metabolism of omeprazole in patients with liver dysfunction is impaired, resulting in an increased AUC. Omeprazole has not shown any tendency to accumulate with once-daily dosing.

Impaired renal function

The pharmacokinetics of omeprazole, including systemic bioavailability and elimination rate, are unchanged in patients with reduced renal function.

Elderly

The metabolism rate of omeprazole is somewhat reduced in elderly subjects (75-79 years of age).

5.3 Preclinical safety data

Gastric ECL-cell hyperplasia and carcinoids have been observed in life-long studies in rats treated with omeprazole. These changes are the result of sustained hypergastrinaemia secondary to acid inhibition. Similar findings have been made after treatment with H2-receptor antagonists, proton pump inhibitors and after partial fundectomy. Thus, these changes are not from a direct effect of any individual active substance.

  1. Pharmaceutical particulars

6.1 List of excipients

Sodium hydroxide (for pH adjustment)

Disodium edetate

6.2 Incompatibilities

Omeprazole powder for solution for infusion should not be mixed with other medicinal products than those mentioned in section 6.6.

6.3 Shelf life

Powder for solution for infusion: 2 years.

Reconstituted solution: Chemical and physical in-use stability has been demonstrated for 12 hours when dissolved in NaCl 0.9% solution and for 6 hours in 5% glucose when reconstituted under controlled aseptic conditions and stored below 25°C.

Chemical and physical in-use stability has also been demonstrated for 24 hours at 2-8°C in both NaCl 0.9% solution and 5% glucose.

From a microbiological point of view, the product should be used immediately.

If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8 °C, unless reconstitution has taken place in controlled and aseptic conditions.

6.4 Special precautions for storage

Powder for solution for infusion: do not store above 25°C. Keep vials in the outer carton in order to protect from light.

For storage conditions of the reconstituted medicinal product, see section 6.3.

6.5 Nature and contents of container

10 ml colourless glass vial Type I with a red bromobutyl rubber stopper, and an aluminium cramping cap with polypropylene cap

Pack sizes: 1, 5, 10 or 20 vials.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

The entire contents of each vial is to be dissolved in approximately 5 ml and then immediately diluted to 100 ml. Sodium chloride 9 mg/ml (0.9%) solution for infusion or glucose 50 mg/ml (5%) solution for infusion must be used. The stability of omeprazole is influenced by the pH of the solution for infusion, which is why no other solvent or quantities should be used for dilution.

Preparation

  1. With a syringe draw 5 ml of infusion solution from the 100 ml infusion bottle or bag.
  2. Add this volume to the vial with the freeze-dried omeprazole, mix thoroughly making sure all omeprazole is dissolved.
  3. Draw the omeprazole solution back into the syringe.
  4. Transfer the solution into the infusion bag or bottle.
  5. Repeat steps 1-4 to make sure all omeprazole is transferred from the vial into the infusion bag or bottle.

Alternative preparation for infusions in flexible containers

  1. Use a double-ended transfer needle and attach to the injection membrane of the infusion bag. Connect the other needle-end from the vial with freeze-dried omeprazole.
  2. Dissolve the omeprazole substance by pumping the infusion solution back and forward between the infusion bag and the vial.
  3. Make sure all omeprazole is dissolved.

The solution for infusion is to be administered in an intravenous infusion for 20-30 minutes. After reconstitution the solution is colourless, clear, practically free from visible particles.

Any unused product or waste material should be disposed of in accordance with local requirements.

7. Manufactured in India By:
TAJ PHARMACEUTICALS LTD.
Survey No. 506, At: Palli,
Sachana- Kalyanpura Road,
TAL-KADI, DIST- MEHSANA,
Palli, 382165, GUJARAT

Omeprazole for Injection 40mg (PRILOSID) Taj Pharma

Package leaflet: Information for the user

Powder for solution for infusion

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

  • Keep this leaflet. You may need to read it
  • If you have any further questions, ask your doctor, pharmacist or
  • This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as
  • If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section
What is in this leaflet
  1. What Omeprazole is and what it is used for
  2. What you need to know before Omeprazole is given to you
  3. How Omeprazole will be given
  4. Possible side effects
  5. How to store Omeprazole
  6. Contents of the pack and other information
1.  What Omeprazole is and what it is used for 

Omeprazole powder for solution for infusion contains the active substance omeprazole. It belongs to a  group of medicines called ‘proton pump inhibitors’. They work by reducing the amount of acid that your stomach produces.

Omeprazole powder for solution for infusion can be used as an alternative to oral therapy.

What you need to know before Omeprazole is given to you

You must not be given Omeprazole:

  • if you are allergic to omeprazole or any of the other ingredients of this medicine (listed in section 6).
  • if you are allergic to other proton pump inhibitor medicines (e.g. pantoprazole, lansoprazole, rabeprazole, esomeprazole).
  • if you are taking a medicine containing nelfinavir (used for HIV infection).
Warnings and precautions

Talk to your doctor, pharmacist or nurse before you are given Omeprazole, if:

  • You have ever had a skin reaction after treatment with a medicine similar to  Omeprazole that reduces stomach acid
  • You are due to have a specific blood test (Chromogranin A).

 

Omeprazole may hide the symptoms of other diseases. Therefore, if any of the following happen to you before you are given Omeprazole or after you are given it, talk to your doctor straight away:

  • You lose a lot of weight for no reason and have problems swallowing
  • You get stomach pain or indigestion
  • You begin to vomit food or blood
  • You pass black stools (blood-stained faeces)
  • You experience severe or persistent diarrhoea, as Omeprazole has been associated with a small increase in infectious diarrhoea
  • You have severe liver
If you get a rash on your skin, especially in areas exposed to the sun tell your doctor as soon as you can, as you may need to stop your treatment with Omeprazole. Remember to also  mention  any  other ill-effects like pain in your joints.
Monitoring Tests

If you take Omeprazole on a long-term basis (longer than 1 year) your  doctor will probably  keep you  under regular surveillance. You should report any new and exceptional symptoms and circumstances whenever you see your doctor.

Taking a proton pump inhibitor like Omeprazole, especially over a period of more than one year, may slightly  increase your risk of fracture of the hip, wrist or spine. Tell your doctor if you have osteoporosis   or if you are taking corticosteroids (which can increase the risk of osteoporosis).

Other medicines and Omeprazole

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.  This is because Omeprazole can affect the way some medicines work and some medicines can have an effect on Omeprazole.

You must not be given Omeprazole if you are taking a medicine containing nelfinavir (used to treat HIV infection).

Tell your doctor or pharmacist if you are taking any of the following medicines:
  • Ketoconazole, itraconazole, posaconazole or voriconazole (used to treat infections caused by a fungus)
  • Digoxin (used to treat heart problems)
  • Diazepam (used to treat anxiety, relax muscles or in epilepsy)
  • Phenytoin (used in epilepsy). If you are taking phenytoin, your doctor will need to monitor you  when you start or stop taking Omeprazole
  • Medicines that are used to thin your blood, such as warfarin or other vitamin K blockers. Your doctor may need to monitor you when you start or stop taking Omeprazole
  • Rifampicin (used to treat tuberculosis)
  • Atazanavir (used to treat HIV infection)
  • Tacrolimus (in cases of organ transplantation)
  • St John’s wort (Hypericum perforatum) (used to treat mild depression)
  • Cilostazol (used to treat intermittent claudication)
  • Saquinavir (used to treat HIV infection)
  • Clopidogrel (used to prevent blood clots (thrombi))
  • Erlotinib (used to treat cancer)
  • Methotrexate (a chemotherapy medicine used in high doses to treat cancer) –  if you are taking a  high dose of methotrexate, your doctor may temporarily stop your Omeprazole

If your doctor has prescribed the antibiotics amoxicillin and clarithromycin as well as Omeprazole to treat ulcers caused by Helicobacter pylori infection, it is very  important that you tell your doctor about any   other medicines you are taking.

If you are going into hospital for any other tests, talk to your doctor as you may need to stop taking this medicine for a short while.

Pregnancy and breast-feeding Pregnancy

Before you are given Omeprazole, tell your doctor if you are pregnant or trying to get pregnant. Your

doctor will decide whether you can be given Omeprazole during this time.

Breast-feeding

Omeprazole is excreted in breast milk but is not likely to influence the child when therapeutic doses are used. Your doctor will decide whether you can take Omeprazole if you are breastfeeding.

Driving and using machines

Omeprazole is not likely to affect your ability to drive or use any tools or machines. Side effects such as dizziness and visual disturbances may occur (see section 4). If affected, you should not drive or operate machinery.

Important information about some of the ingredients of Omeprazole

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially “sodium free”.

2.  How Omeprazole will be given: 
  • Omeprazole can be given to adults including the elderly
  • There is limited experience with Omeprazole for intravenous use in
Being given Omeprazole:
  • Omeprazole will be given to you by a doctor who will decide how much you need
  • The medicine will be given to you as an infusion into one of your
If you are given more Omeprazole than you should

If you think you have been given too much Omeprazole, talk to your doctor straight away.

3.  Possible side effects 

Like all medicines, this medicine can cause side effects, although not everybody gets them.

If you notice any of the following rare but serious side effects, stop using Omeprazole and contact a doctor immediately:
  • Sudden wheezing, swelling of your lips, tongue and throat or body, rash, fainting or difficulties to swallow (severe allergic reaction)
  • Reddening of the skin with blisters or peeling. There may also be severe blisters and bleeding in the lips, eyes, mouth, nose and genitals. This could be ‘Stevens-Johnson syndrome’ or ‘toxic epidermal necrolysis’
  • Yellow skin, dark urine and tiredness which can be symptoms of liver

Other side effects include:

Common side effects (may affect up to 1 in 10 people):
Headache
  • Effects on your stomach or gut: diarrhoea, stomach pain, constipation, wind (flatulence), benign polyps in the stomach
  • Feeling sick (nausea) or being sick (vomiting).
Uncommon side effects (may affect up to 1 in 100 people):
  • Swelling of the feet and ankles
  • Disturbed sleep (insomnia)
  • Dizziness, tingling feelings such as “pins and needles”, feeling sleepy
  • Spinning feeling (vertigo)
  • Changes in blood tests that check how the liver is working
  • Skin rash, lumpy rash (hives) and itchy skin
  • Generally feeling unwell and lacking energy
  • Fracture of the hip, wrist or
Rare side effects (may affect up to 1 in 1,000 people):
  • Blood problems such as a reduced number of white cells or platelets. This can cause weakness, bruising or make infections more likely
  • Allergic reactions, sometimes very severe, including swelling of the lips, tongue and throat, fever, wheezing
  • Low levels of sodium in the This may cause weakness, being sick (vomiting) and cramps
  • Feeling agitated, confused or depressed
  • Taste changes
  • Eyesight problems such as blurred vision
  • Suddenly feeling wheezy or short of breath (bronchospasm)
  • Dry mouth
  • An inflammation of the inside of the mouth
  • An infection called “thrush” which can affect the gut and is caused by a fungus
  • Liver problems, including jaundice which can cause yellow skin, dark urine, and tiredness
  • Hair loss (alopecia)
  • Skin rash on exposure to sunshine
  • Joint pains (arthralgia) or muscle pains (myalgia)
  • Severe kidney problems (interstitial nephritis)
  • Increased sweating
  • Inflammation in the gut (leading to diarrhoea).
Very rare side effects (may affect up to 1 in 10,000 people):
  • Changes in blood count including agranulocytosis (lack of white blood cells)
  • Aggression
  • Seeing, feeling or hearing things that are not there (hallucinations)
  • Severe liver problems leading to liver failure and inflammation of the brain
  • Sudden onset of a severe rash or blistering or peeling skin. This may be associated with a high fever and joint pains (Erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis)
  • Muscle weakness
  • Enlarged breasts in
Not known side effects (frequency cannot be estimated from the available data):
  • Rash, possibly with pain in the joints
  • If you are on Omeprazole for more than three months it is possible that the levels of magnesium in your blood may fall. Low levels of magnesium can be seen as fatigue, involuntary muscle contractions, disorientation, convulsions, dizziness, increased heart rate. If you get any of these symptoms, please tell your doctor promptly. Low levels of magnesium can also lead to a reduction in potassium or calcium levels in the blood. Your doctor may decide to perform regular blood tests   to monitor your levels of

Irreversible visual impairment has been reported in isolated cases of critically ill patients  who  have received Omeprazole intravenous injection, especially at high doses, but no causal relationship has been established.

Omeprazole may in very rare cases affect the white blood cells leading to immune deficiency. If you have  an infection with symptoms such as fever with a severely reduced general condition or fever with  symptoms of a local infection such as pain in the neck, throat or mouth or difficulties in urinating, you   must consult your doctor as soon as possible so that a lack of white blood cells (agranulocytosis) can be ruled out by a blood test. It is important for you to give information about your medicine at this time.

Do not be concerned by this list of possible side effects. You may not get any of them

4.  How to store Omeprazole

 Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the vial and on the box. The expiry date refers to the last day of that month.

Before opening: Do not store above 25°C. Store in the original package in order to protect from light.

After reconstitution:

Chemical and physical in-use stability has been demonstrated for 12 hours after reconstitution in 0.9% sodium chloride and for 6 hours after reconstitution in 5% glucose at 25°C.

However, from a microbiological point of view, the product should be used immediately after  reconstitution.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

Contents of the pack and other information What Omeprazole contains

The active substance is omeprazole. Each vial of powder contains 42.5 mg of omeprazole sodium  equivalent to 40 mg of omeprazole.

The other ingredients are: Disodium edetate, sodium hydroxide.

What Omeprazole looks like and contents of the pack

This medicine is available as a powder for solution for infusion in a 6 ml vial. A box contains 5 or 10    vials.

7. Manufactured in India By:
TAJ PHARMACEUTICALS LTD.
Survey No. 506, At: Palli,
Sachana- Kalyanpura Road,
TAL-KADI, DIST- MEHSANA,
Palli, 382165, GUJARAT