Drug Class Description
Proton pump inhibitors (PPIs).

Generic Name
omeprazole sodium

Drug Description
Each vial of powder for solution for infusion contains Omeprazole Sodium 42.6 mg equivalent to Omeprazole 40 mg.

Presentation
Powder for solution for infusion.

Indications
Prophylaxis of acid aspiration.In patients who are unable to take oral therapy for the shortterm treatment (up to 5 days) of reflux oesophagitis, duodenal and benign gastric ulcers, including those complicating NSAID therapy e.g. perioperative use.

Adult Dosage
DosageAdults onlyProphylaxis of acid aspiration: Losec 40 mg given as an intravenous infusion to be completed one hour before surgery.Treatment in patients where oral therapy is inappropriate e.g. in severely ill patients with either reflux oesophagitis, duodenal ulcer or gastric ulcer: Losec 40 mg given as an intravenous infusion once daily is recommended for up to 5 days.The i.v. infusion produces an immediate decrease in intragastric acidity and a mean decrease over 24 hours of approximately 90%.Clinical experience in ZollingerEllison syndrome is limited.AdministrationLosec powder for solution for infusion is for intravenous administration only and must not be given by any other route.Losec powder for solution for infusion should only be dissolved in either 100 ml normal saline for infusion or 100 ml 5% dextrose for infusion. No other solutions for i.v. infusion should be used.After reconstitution from a microbiological point of view, use immediately (i.e. within 3 hours) and any unused portion should be discarded.The duration of administration should be 20–30 minutes.Use in the elderlyDosage adjustment is not necessary.Use in childrenThere is limited experience of use in children.Impaired renal functionDose adjustment is not required in patients with impaired renal function.Impaired hepatic functionAs half-life is increased in patients with impaired hepatic function, the dose requires adjustment and a daily dose of 10 mg–20 mg may be sufficient.

Child Dosage
Limited experience of use in children.

Contra Indications
Known hypersensitivity to omeprazole or to any of the other constituents of the formulation.Omeprazole like other PPIs should not be administered with atazanavir

Special Precautions
Due to the decreased intragastric acidity, the absorption of ketoconazole or itraconazole may be reduced during omeprazole therapy as it is during treatment with other acid secretion inhibitors.As omeprazole is metabolised in the liver through cytochrome P450 it can prolong the elimination of diazepam, phenytoin, warfarin and other vitamin K antagonists, which are in part substrates for this enzyme.Monitoring of patients receiving phenytoin, is recommended and a reduction of the phenytoin dose may be necessary . However, concomitant treatment with Losec 20 mg orally daily did not change the blood concentration of phenytoin in patients on continuous treatment with phenytoin. In patients receiving warfarin or other vitamin K antagonists, monitoring of INR is recommended and a reduction of the warfarin (or other vitamin K antagonist) dose may be necessary. Concomitant treatment with Losec 20 mg orally daily did not change coagulation time in patients on continuous treatment with warfarin.Plasma concentrations of omeprazole and clarithromycin are increased during concomitant oral administration. There is no interaction with metronidazole or amoxicillin. These antimicrobials are used together with omeprazole for eradication of Helicobacter pylori .There is no evidence of an interaction with phenacetin, theophylline, caffeine, propranolol, metoprolol, ciclosporin, lidocaine, quinidine, estradiol, or antacids when Losec is given orally. The absorption of Losec given orally is not affected by alcohol or food.There is no evidence of an interaction with piroxicam, diclofenac or naproxen, this is considered useful when patients are required to continue these treatments.Simultaneous treatment with omeprazole and digoxin in healthy subjects led to a 10% increase in the bioavailability of digoxin as a consequence of the increased intragastric pH.Interaction with other drugs also metabolised via the cytochrome P450 system cannot be excluded.Co-administration of omeprazole (40mg once daily) with atazanavir 300 mg/ritonavir 100mg to healthy volunteers resulted in a substantial reduction in atazanavir exposure (approximately 75% decrease in AUC, Cmax, and Cmin). Increasing the atazanavir dose to 400mg did not compensate for the impact of omeprazole on atazanavir exposure. PPIs including omeprazole should not be co-administered with atazanavir.Concomitant administration of omeprazole and tacrolimus may increase the serum levels of tacrolimus.Concomitant administration of omeprazole and a CYP2C19 and CYP3A4 inhibitor, voriconazole, resulted in more than doubling of the omeprazole exposure. Omeprazole (40 mg once daily) increased voriconazole (a CYP2C19 substrate) Cmax and AUCτ by 15% and 41%, respectively. A dose adjustment of omeprazole is not regularly required in either of these situations. However, dose adjustment should be considered in patients with severe hepatic impairment and if long-term treatment is indicated.

Interactions
Due to the decreased intragastric acidity, the absorption of ketoconazole or itraconazole may be reduced during omeprazole therapy as it is during treatment with other acid secretion inhibitors.As omeprazole is metabolised in the liver through cytochrome P450 it can prolong the elimination of diazepam, phenytoin, warfarin and other vitamin K antagonists, which are in part substrates for this enzyme.Monitoring of patients receiving phenytoin, is recommended and a reduction of the phenytoin dose may be necessary . However, concomitant treatment with Losec 20 mg orally daily did not change the blood concentration of phenytoin in patients on continuous treatment with phenytoin. In patients receiving warfarin or other vitamin K antagonists, monitoring of INR is recommended and a reduction of the warfarin (or other vitamin K antagonist) dose may be necessary. Concomitant treatment with Losec 20 mg orally daily did not change coagulation time in patients on continuous treatment with warfarin.Plasma concentrations of omeprazole and clarithromycin are increased during concomitant oral administration. There is no interaction with metronidazole or amoxicillin. These antimicrobials are used together with omeprazole for eradication of Helicobacter pylori .There is no evidence of an interaction with phenacetin, theophylline, caffeine, propranolol, metoprolol, ciclosporin, lidocaine, quinidine, estradiol, or antacids when Losec is given orally. The absorption of Losec given orally is not affected by alcohol or food.There is no evidence of an interaction with piroxicam, diclofenac or naproxen, this is considered useful when patients are required to continue these treatments.Simultaneous treatment with omeprazole and digoxin in healthy subjects led to a 10% increase in the bioavailability of digoxin as a consequence of the increased intragastric pH.Interaction with other drugs also metabolised via the cytochrome P450 system cannot be excluded.Co-administration of omeprazole (40mg once daily) with atazanavir 300 mg/ritonavir 100mg to healthy volunteers resulted in a substantial reduction in atazanavir exposure (approximately 75% decrease in AUC, Cmax, and Cmin). Increasing the atazanavir dose to 400mg did not compensate for the impact of omeprazole on atazanavir exposure. PPIs including omeprazole should not be co-administered with atazanavirConcomitant administration of omeprazole and tacrolimus may increase the serum levels of tacrolimus.Concomitant administration of omeprazole and a CYP2C19 and CYP3A4 inhibitor, voriconazole, resulted in more than doubling of the omeprazole exposure. Omeprazole (40 mg once daily) increased voriconazole (a CYP2C19 substrate) Cmax and AUCτ by 15% and 41%, respectively. A dose adjustment of omeprazole is not regularly required in either of these situations. However, dose adjustment should be considered in patients with severe hepatic impairment and if long-term treatment is indicated.

Adverse Reactions
Losec is 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.The following definitions of frequencies are used:Common > 1/100Uncommon > 1/1000 and < 1/100Rare < 1/1000 CommonCentral and peripheral nervous systemHeadacheGastrointestinalDiarrhoea, constipation, abdominal pain, nausea/vomiting and flatulenceUncommonCentral and peripheral nervous systemDizziness, paraesthesia, lightheadedness, feeling faint, somnolence, insomnia and vertigoHepaticIncreased liver enzymesSkinRash, dermatitis and/or pruritus, urticariaOtherMalaiseRareCentral and peripheral nervous systemReversible mental confusion, agitation, aggression, depression and hallucinations, predominantly in severely ill patientsEndocrineGynaecomastiaGastrointestinalDry mouth, stomatitis and gastrointestinal candidiasisHaematologicalLeukopenia, thrombocytopenia, agranulocytosis and pancytopeniaHepaticEncephalopathy in patients with preexisting severe liver disease; hepatitis with or without jaundice, hepatic failure increased liver enzymesMusculoskeletalArthritic and myalgic symptoms and muscular weaknessReproductive system and breast disordersImpotenceSkinPhotosensitivity, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN), alopeciaOtherHypersensitivity reactions e.g. angioedema, fever, bronchospasm, interstitial nephritis and anaphylactic shock. Increased sweating, peripheral oedema, blurred vision, taste disturbance and hyponatraemiaIsolated cases of irreversible visual impairment have been reported in critically ill patients who have received Losec Intravenous Injection, particularly at high doses, however no causal relationship has been established.

Manufacturer
AstraZeneca

Drug Availability
(POM)

Updated
22 November 2011