Omepradex EC

Omepradex EC

omeprazole

Manufacturer:

Dexcel Pharma/AmediusTec

Distributor:

Apex Pharma Marketing
Full Prescribing Info
Contents
Omeprazole.
Description
Omepradex EC also contains the following excipients: Lactose monohydrate, sodium starch glycollate, sodium stearate, sodium stearyl fumarate, hydroxypropyl methylcellulose (HPMC) acetate succinate, brownish pink colour [which contains propylene glycol, titanium dioxide (E-171), red iron oxide (E-172), hypromellose and yellow iron oxide (E172)], talc, triethyl citrate, monoethanolamine, sodium lauryl sulphate and traces of carnauba wax.
Action
Pharmacotherapeutic Group: Proton pump inhibitor (substance reducing gastric acid secretion). ATC Code: A02B C01.
Pharmacology: Pharmacodynamics: Omeprazole is a substituted benzimidazole. Omeprazole is a racemate of 2 active enantiomers. The secretion of hydrochloric acid in the stomach is inhibited by omeprazole through its specific effect on the proton pump in the parietal cells. The effect on acid secretion is reversible. Omeprazole is a weak base, which is concentrated and converted into active form in the acidic environment in the parietal cell, where it inhibits H+, K+-ATPase ie, the final step in production of the gastric acid. The inhibition is dose-dependent, and affects both basal and stimulated acid secretion, irrespective of the type of stimulation.
Omeprazole does not affect cholinergic or histaminergic receptors.
Like treatment with H2-receptor blockers, treatment with omeprazole results in reduced acidity in the stomach and thus, an increase in gastrin in proportion to the reduction in acidity. The gastrin increase is reversible. During long-term treatment, the frequency of glandular cysts in the stomach may increase. These changes are physiological and a consequence of the inhibition of acid secretion. They are benign and reversible.
Decreased gastric acidity with proton pump inhibitors or other acid-inhibiting agents, increases the amount of bacteria normally present in the gastrointestinal tract, where such treatment may lead to a slightly increased risk of gastrointestinal infections eg, Salmonella and Campylobacter.
No other pharmacodynamic effects of clinical significance, other than those due to the effect of omeprazole on acid secretion, have been found.
The effect on acid secretion is directly correlated to the area under the plasma concentration curve (AUC), but not to the actual plasma concentration of omeprazole. Oral administration of Omepradex EC produces a reduction in hydrochloric acid secretion within 2 hrs after administration. With repeated treatment once daily, the full effect is obtained within 3-5 days. The degree of acidity measured over 24 hrs in duodenal ulcer patients is then reduced on average by 80%, and the reduction in pentagastrin-stimulated hydrochloric acid production is approximately 70% 24 hrs after administration. The secretion-inhibiting effect is characterised by its long duration, and has subsided after approximately 5 days from the end of treatment.
Pharmacokinetics: Absorption: The absorption of omeprazole takes place in the small intestine and is usually completed within 3-6 hrs. The bioavailability of omeprazole after repeated oral administration is approximately 60%. Binding to plasma proteins is approximately 95% and the volume of distribution is 0.3 L/kg.
Metabolism: Omeprazole is metabolised completely, mainly in the liver. Mainly the enzymes CYP2C19 and CYP3A4 catalyse the metabolism. Identified metabolites are the sulphone, the sulphide and hydroxyl-omeprazole, which have no significant effect on the acid secretion. Total plasma clearance is 0.3-0.6 L/min. Omeprazole inhibits its own CYP2C19 catalysed metabolism. Therefore, the bioavailability of omeprazole increases with approximately 50% during multiple-dose treatment compared to single dose.
Elimination: The half-life (t½) in plasma in the elimination phase is approximately 40 min (30-90 min) after multiple doses. Approximately 80% of the metabolites are excreted via the urine and the remainder in the faeces.
Patient Factors: The bioavailability of omeprazole is not changed significantly in elderly patients or patients with impaired renal function. In patients with impaired liver function, the bioavailability increases. Clearance is greatly reduced in these patients.
Toxicology: Preclinical Safety Data: Gastric enterochromaffin-like (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 drug.
Indications/Uses
Treatment of duodenal and gastric ulcers, NSAID-associated gastric and duodenal ulcers or erosions, reflux oesophagitis, symptomatic gastroesophageal reflux disease, acid-related dyspepsia, Zollinger-Ellison syndrome.
Dosage/Direction for Use
Duodenal Ulcer: Recommended Dose: Patients with an Active Duodenal Ulcer: 20 mg once daily. Symptom resolution is rapid and in most patients, healing occurs within 2 weeks. For those patients who may not be fully healed after the initial course, healing usually occurs during a further 2-week treatment period.
Patients with Poorly Responsive Duodenal Ulcer: Two 20-mg tablets once daily is recommended and healing is usually achieved within 4 weeks.
Gastric Ulcer: Recommended Dose: 20 mg once daily. Symptom resolution is rapid and in most patients, healing occurs within 4 weeks. For those patients who may not be fully healed after the initial course, healing usually occurs during a further 4-week treatment period.
Patients with Poorly Responsive Gastric Ulcer: Two 20-mg tablets once daily is recommended and healing is usually achieved within 8 weeks.
Prevention of Relapse in Patients with Poorly Responsive Gastric Ulcer: Recommended Dose: 20 mg once daily. If needed, the dose can be increased to 40 mg once daily.
NSAID-Associated Ulcers, Duodenal Ulcers or Gastroduodenal Erosions: Patients with or without Continued NSAID Treatment: Recommended Dose: 20 mg once daily. Symptom resolution is rapid and in most patients, healing occurs within 4 weeks. For those patients who may not be fully healed after the initial course, healing usually occurs during a further 4-week treatment period.
Prevention of NSAID-Associated Gastric Ulcers, Duodenal ulcers, Gastroduodenal Erosions and Dyspeptic Symptoms: Recommended Dose: 20 mg once daily.
Reflux Oesophagitis: Recommended Dose: 20 mg once daily. Symptom resolution is rapid and in most patients, healing occurs within 4 weeks. For those patients who may not be fully healed after the initial course, healing usually occurs during a further 4-week treatment period.
Patients with Severe Reflux Oesophagitis: Two 20-mg tablets once daily is recommended and healing is usually achieved within 8 weeks.
Severe Reflux Oesophagitis: Children ≥1 year: Recommended Dose for Healing: 10-20 kg Body Weight: 10 mg once daily; >20 kg body weight: 20 mg once daily.
If needed, the dosage may be increased to 20 mg and 40 mg, respectively. The duration of treatment in these patients should be between 2-8 weeks.
Symptomatic Gastroesophageal Reflux Disease: Recommended Dose: 20 mg daily.
If symptom control has not been achieved after 4-week treatment with 20 mg daily, further investigation is recommended.
Acid-Related Dyspepsia: In the relief of symptoms in patients with epigastric pain/discomfort with or without heartburn, the recommended dosage is 20 mg once daily.
Zollinger-Ellison Syndrome: In patients with Zollinger-Ellison syndrome, the dosage should be individually adjusted and treatment continued as long as is clinically indicated. Recommended Initial Dose: 60 mg daily. All patients with severe disease and inadequate response to other therapies have been effectively controlled and >90% of the patients maintained on doses of 20-120 mg daily. When doses exceed 80 mg daily, the dose should be divided and given twice daily.
Renal Impairment: Dose adjustment is not needed in patients with impaired renal function.
Hepatic Impairment: As bioavailability and plasma t½ of omeprazole are increased in patients with impaired hepatic function, a daily dose of 10-20 mg may be sufficient.
Elderly: Dose adjustment is not needed in the elderly.
Administration: Omepradex EC is recommended to be given in the morning and swallowed whole with ½ a glass of water. The tablet must not be chewed or crushed. Omepradex EC should be taken before food on empty stomach.
Overdosage
Probably low acute toxicity, 320-800 mg to adults resulted in low intoxication, 560 mg to adults resulted in moderate intoxication.
Symptoms: Dizziness, apathy, headache, confusion, blood vessel dilatation, tachycardia. Nausea, vomiting, flatulence, diarrhoea. (See also Adverse Reactions.)
Treatment: If necessary, gastric lavage, charcoal. Symptomatic therapy.
Contraindications
Known hypersensitivity to omeprazole. Like other active proton pump inhibitors, omeprazole must not be used together with atazanavir (see Interactions).
Special Precautions
Suspected ulcer-disease must be verified objectively at an early stage in the anamnesis by means of x-ray or endoscopy in order to avoid inadequate treatment.
If ≥1 of the following alarm symptoms occur, malignancy should be excluded, as treatment can mask symptoms and delay diagnosis: Significant unintentional weight loss, repeated vomiting, dysphagia, haematemesis or melaena.
Clostridium Difficile-associated Diarrhoea: Published observational studies suggest that proton pump inhibitor (PPI) therapy like Omepradex EC tablet 20 mg 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 Adverse Reactions). Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. Clostridium difficile-associated diarrhoea has been reported with use of nearly all antibacterial agents. For more information specific to antibacterial agents (clarithromycin and amoxicillin) indicated for use in combination with Omepradex EC, see Precautions.
Bone Fracture: Several published observational studies suggest that PPI therapy may be associated with an increased 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 (≥1 year). 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 (see Dosage and Administration and Adverse Reactions).
Hypomagnesaemia: Hypomagnesaemia, symptomatic and asymptomatic, has been reported rarely in patients treated with PPIs for at least 3 months, in most cases after a year of therapy. Serious adverse events include tetany, arrhythmias and seizures. In most patients, treatment of hypomagnesaemia required magnesium replacement and discontinuation of the PPI.
For patients expected to be on prolonged treatment or who take PPIs with medications eg digoxin or drugs that may cause hypomagnesaemia (eg, diuretics), health care professionals may consider monitoring magnesium levels prior to initiation of PPI treatment and periodically.
Literature suggests that concomitant use of PPIs with methotrexate [primarily at high dose (see Dosage and Adminstration)] 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 (see Drug Interactions).
Effects on the Ability to Drive or Operate Machinery: Omepradex EC is not likely to affect the ability to drive or use machines.
Use in pregnancy & lactation: As with most drugs, Omepradex EC should not be given during pregnancy and lactation unless its use is considered essential. Results from 3 prospective epidemiological studies indicate no adverse effects of omeprazole on pregnancy or on the health of the fetus/newborn child.
Omeprazole is excreted in breast milk. Influence, if any, on the child is unknown.
Use In Pregnancy & Lactation
As with most drugs, Omepradex EC should not be given during pregnancy and lactation unless its use is considered essential. Results from 3 prospective epidemiological studies indicate no adverse effects of omeprazole on pregnancy or on the health of the fetus/newborn child.
Omeprazole is excreted in breast milk. Influence, if any, on the child is unknown.
Adverse Reactions
The most common symptoms that were reported in clinical trials with omeprazole have been gastrointestinal eg, diarrhoea, nausea and constipation, and also headache, each in 1-3%.
Adverse effects are listed by organ system and frequency with the following convention: Common (>1/100, <1/100), less common (>1/1000, <1/100), rare (>1/10,000, <1/1000).
General: Common: Headache. Less Common: Fatigue. Rare: Increased sweating, peripheral oedema, hyponatraemia, hypersensitivity reactions eg, angioedema, fever and anaphylactic shock.
Blood: Rare: Leucopenia, thrombocytopenia, agranulocytosis, pancytopenia.
Endocrine: Rare: Gynaecomastia.
Gastrointestinal: Common: Diarrhoea, nausea/vomiting, constipation, abdominal pain, flatulence. Rare: Dry mouth, taste disturbances, stomatitis, candidiasis.
Skin: Less Common: Rash, pruritus, urticaria, dermatitis. Rare: Hair loss, photosensitivity, erythema multiforme.
Liver: Less Common: Change in liver function tests. Rare: Encephalopathy in patients with severe hepatic disease, hepatitis with or without jaundice, liver failure.
Respiratory Tract: Rare: Bronchospasms.
Musculoskeletal: Rare: Arthralgia, myalgia, muscle weakness.
Neurological: Less Common: Paraesthesia, dizziness, drowsiness.
Psychiatric: Less Common: Sleep disturbance. Rare: Reversible confusion, agitation, depression, aggression and hallucinations, especially in severely ill patients.
Genito-Urinary: Rare: Interstitial nephritis.
Eyes: Rare: Blurred vision.
Isolated cases of Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported, but a relationship with omeprazole could not be established.
In clinical trials, an increased frequency of adverse reactions involving the central nervous system (especially headache) and gastrointestinal adverse reactions have been observed when omeprazole was given together with clarithromycin.
During post-approval use of omeprazole, cases of Clostridium difficile-associated diarrhoea and bone fractures have been reported (frequency unknown).
Drug Interactions
Effects of Omeprazole on the Pharmacokinetics of Other Drugs: The following combination with Omepradex EC should be avoided: Ketoconazole and itraconazole.
Omeprazole might influence the absorption of other drugs due to its effect on the gastric pH. The dissolution of ketoconazole tablets in the stomach is adversely affected if the pH of the gastric juice increases as a result of drug treatment (antacids, secretion-inhibiting agents, sucralfate). This leads to ineffective plasma concentrations of ketoconazole. During concomitant administration of omeprazole and itraconazole, the plasma concentration and area under the curve (AUC) of itraconazole are reduced by approximately 65%, probably as a result of poorer absorption, which is dependent on pH.
Omeprazole inhibits the enzyme CYP2C19 and therefore, increased plasma levels of other drugs (diazepam, warfarin, phenytoin) metabolized via this enzyme might be expected. Monitoring is recommended during initiation or withdrawal of omeprazole in patients being treated with phenytoin, warfarin or other vitamin K antagonist.
During concomitant administration of clarithromycin or erythromycin and omeprazole, the plasma concentrations of omeprazole were increased. The plasma concentrations of omeprazole are not influenced during concomitant administration with amoxicillin or metronidazole.
Concomitant administration of omeprazole (40 mg once daily) and atazanavir 300 mg/ritonavir 100 mg to healthy volunteers resulted in a marked reduction in total atazanavir exposure (approximately 75% reduction of AUC, Cmax and Cmin). An increase in the atazanavir dose to 400 mg did not compensate for the effect that omeprazole had on atazanavir exposure. Proton pump inhibitors including omeprazole should therefore not be administered concomitantly with atazanavir (see Contraindications).
Concomitant administration of omeprazole and tacrolimus may increase the serum levels of tacrolimus. Monitoring of the plasma tacrolimus concentration is recommended when treatment with omeprazole is being initiated or discontinued. Omeprazole (40 mg daily) increased the Cmax and AUC of voriconazole (CYP2C19 substrate) by 15% and 41%, respectively.
Effects of Other Drugs on the Pharmacokinetics of Omeprazole: Drugs inhibiting the enzymes CYP2C19 or CYP3A (HIV protease inhibitors, ketoconazole, itraconazole) might increase the plasma concentrations of omeprazole. Voriconazole increases the AUC of omeprazole by 280%. In cases of concomitant treatment, an adjustment of the omeprazole dose should be considered for patients with considerable impaired hepatic function and in cases of long-term treatment.
Case reports, published population pharmacokinetic studies and retrospective analyses suggest that concomitant administration of PPIs and methotrexate (primarily at high doses) may elevate and prolong serum levels of methotrexate and/or its metabolite hydroxymethotrexate. However, no formal drug interaction studies of methotrexate with PPIs have been conducted (see Precautions).
No interactions between omeprazole and antacids, theophylline, caffeine, quinidine, lidocaine, propranolol, metoprolol or ethanol have been detected.
Storage
Store below 25°C.
ATC Classification
A02BC01 - omeprazole ; Belongs to the class of proton pump inhibitors. Used in the treatment of peptic ulcer and gastro-oesophageal reflux disease (GERD).
Presentation/Packing
EC tab 20 mg (brownish-pink, capsule-shaped) x 14's, 28's.
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