Zomep

Omeprazole sodium.

Each vial contains: Sterile Omeprazole (as sodium) 40 mg.
Each ampoule contains: 0.9% Sodium Chloride Solution for injection 10 mL.
Color: A white or almost white, crystalline powder.
Solubility: Freely soluble in water.
pH for 2% solution in water: 9.0-12.0.
Chemical formula: C₁₁H₁₈N₃NaO₃S₁H₂O.
Molecular weight: 385.4 g/mol.

Pharmacology: Pharmacokinetics: Omeprazole is rapidly but variably absorbed after oral doses. Absorption is not significantly affected by food. Omeprazole is acid-labile and the pharmacokinetics of the various formulations developed to improve oral bioavailability may vary. The absorption of omeprazole also appears to be dose- dependent, increasing the dosage above 40 mg has been reported to increase the plasma concentration in a non-linear fashion because of saturable first-pass hepatic metabolism. In addition, bioavailability is higher after long-term use. Bioavailability of omeprazole may be increased in elderly patients, in some ethnic groups such as Chinese, and in patients with hepatic impairment, but is not markedly affected in patients with renal impairment. On absorption, omeprazole is almost completely metabolized in the liver, primarily by the cytochrome P450 isoenzyme CYP2C19 to form hydroxy omeprazole, and to a small extent by CYP3A4 to form Omeprazole sulfone. The metabolites are inactive and are excreted mostly in the urine and to a lesser extent in bile. The elimination half-life from plasma is reported to be about 0.5 to 3 hours. Omeprazole is about 95% bound to plasma proteins.
Metabolism: The major enzyme involved in omeprazole metabolism is cytochrome P450 isoenzyme CYP2C19. This enzyme is polymorphically expressed and individuals who are deficient in the enzyme are poor metabolizers of Omeprazole. This occurs in about 3% of Caucasians and 15% of Chinese, Japanese and Koreans. These individuals have markedly higher plasma concentrations of Omeprazole and they may require dosage adjustment. Some Omeprazole is metabolized by CYP3A4 and some by CYP206 to form desmethylomeprazole.

Used in the treatment of duodenal ulcer, gastric ulcer, non-steroidal anti-inflammatory drug-associated gastric and duodenal ulcers or erosions, Helicobacter pylori eradication in peptic ulcer disease, reflux esophagitis, symptomatic gastroesophageal reflux disease, acid-related dyspepsia, Zollinger­ Ellison syndrome and patients considered to be at risk of aspiration of gastric contents during general anesthesia/acid aspiration prophylaxis.

Omeprazole sodium may be given in a short-term basis by intravenous infusion, in a usual dose equivalent to 40 mg of the base over period of 20-30 minutes. It may also be given by slow intravenous injection. Higher intravenous doses have been given to patients with Zollinger-Ellison syndrome.
Directions for Reconstitution and Storage of Reconstituted Product: Omeprazole sodium may be given on a short-term basis by intravenous infusion, in a usual dose equivalent to 40 mg of the base over period of 20-30 minutes. It may also be given by slow intravenous injection. Higher intravenous doses have been given to patients with Zollinger-Ellison syndrome.

The major clinical features were drowsiness, headache (possibly due to a metabolite) and tachycardia. Both patients recovered uneventfully without specific treatment.

Hypersensitivity to Omeprazole, substituted benzimidazoles or to any of the excipients. Omeprazole like other proton pump inhibitors (PPls) should not be used concomitantly with nelfinavir.

Before giving Omeprazole or other proton pump inhibitors to patients with gastric ulcers the possibility of malignancy should be excluded since these drugs may mask symptoms and delay diagnosis. Omeprazole and other proton pump inhibitors should be used with caution in hepatic impairment and dose adjustment maybe required.
Gastric carcinoma: Proton pump inhibitors relieve dyspeptic symptoms associated with gastric carcinoma and can therefore delay its diagnosis. In addition, there is some evidence that they may also endoscopically "heal" early gastric carcinoma so that the diagnosis is missed. Consequently, some commentators recommend that proton pump inhibitors, should not be prescribed for symptom control before endoscopy in patients at risk for gastric carcinoma.
Helicobacter infection: Treatment with proton pump inhibitors may cause false-negative results in the urea breath test for Helicobacter pylori infection. In one study in patients with H. pylori infection, 4 weeks of treatment with Lanzoprazole 30 mg daily caused 33% of patients to have negative urea breath tests. The breath test became positive again in all patients within 2 weeks of stopping lanzoprazole therapy. In a similar study, 52% of patients had negative urea breathe tests for H. pylori while receiving Omeprazole 20 mg daily, and the breath test became positive again in all patients within 2 to 5 days of stopping treatment. The manufacturers of the urea breath test for H. pylori recommend that it should not be performed for at least 2 weeks after stopping treatment with an antisecretory drug.
Hepatic impairment: In patients with cirrhosis, an increase in omeprazole bioavailability and elimination half-life has been reported.
Pregnancy: Proton-pump inhibitors are not generally licensed for use during pregnancy, but a meta-analysis of 1 of 5 studies of exposure to proton pump inhibitors during the first trimester, involving 593 exposed infants found the relative risks of major abnormalities associated with such exposure to be only 1.18 with a 95% confidence interval ranging from 0.72 to 1.94. Metanalysis of exposure to Omeprazole (from 4 studies only) gave a relative risk of 1.05 (95% confidence interval 0.59 to 1.85). It was concluded that exposure to proton pump inhibitors and Omeprazole in particular, did not pose an important teratogenic risk.

Proton pump inhibitors are generally well tolerated, and adverse effects are relatively infrequent. The adverse effects reported most often with Omeprazole and other proton pump inhibitors have been headache, diarrhea, and skin rashes, they have sometimes been severe enough to require stopping treatment. Other effects include pruritic, dizziness, fatigue, constipation, nausea and vomiting, flatulence, abdominal pain, arthralgia and myalgia, urticaria, and dry mouth. Isolated cases of photosensitivity, bullous eruption, erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis have occurred. Hypersensitivity reactions, including fever, bronchospasm, angioedema and anaphylaxis have been reported.
Effects on the Central Nervous System include occasional insomnia, somnolence and vertigo; reversible confusional states, agitation, depression, and hallucinations have occurred in severely ill patients. Raised liver enzymes, and isolated cases of hepatitis, jaundice, hepatic failure and hepatic encephalopathy have been reported. Other adverse effects reported rarely include paraesthesia, blurred vision, alopecia, stomatitis, increased sweating, taste disturbances, peripheral oedema, malaise, hyponatraemia, blood disorders, (including agranulocytosis, leucopenia and thrombocytopenia), gynaecomastia, impotence and interstitial nephritis. Proton pump inhibitors may increase the risk of gastrointestinal infections because of their acid suppressive effects. Early toxicological studies identified carcinoid-like tumors of the gastric mucosa in the rats given very high doses of Omeprazole over long periods.

Omeprazole and other proton pump inhibitors are metabolized by the cytochrome P450 system, primarily by isoenzyme CYP2C19, and to smaller extent by CY3A4. Inhibitors or inducers of these isoenzymes may affect exposure to Omeprazole and other proton pump inhibitors. In turn, proton pump inhibitors may alter the metabolism of some drugs metabolized by these enzymes. Omeprazole may prolong the elimination of diazepam, phenytoin and warfarin. Omeprazole and other proton pump inhibitors can reduce the absorption of drugs such as dasatinib, ketoconazole and itraconazole, whose absorption is dependent on an acid gastric pH. With voriconazole, the plasma concentration of both drugs maybe increased. Other proton pump inhibitors may be similarly affected by voriconazole. Omeprazole and other proton pump inhibitors should not be used with atazanavir, as it substantially reduces exposure to atazanavir. Omeprazole is metabolized primarily by the cytochrome P450 isoenzyme YP2C19 and therefor may interact with Diazepam. Some metabolism of phenytoin, tolbutamide, and the R-enantiomer of warfarin also takes place by CYP2C19, but the effect seen have been minor. Although some induction of CYP1 A2, which metabolizes caffeine and theophylline, has been reported this does not appear to be clinically significant. While some consider the effect of Omeprazole on CYP3A4 activity to be insignificant, others have noted an increasing body of evidence that competitive inhibition of intestinal CYP3A4 by Omeprazole may affect the first ­pass metabolism of a number of drugs. A review concluded that, while Omeprazole and possibly Esomeprazole have a considerable potential for drug interactions, Lansoprazole, Pantoprazole and Rabeprazole are associated with a lower incidence of drug interactions.
Clarithromycin: Clarithromycin inhibits the metabolism of Omeprazole mediated by the cytochrome P450 isoenzyme CYP3A4. The interaction may contribute to the benefits of combined therapy for Helicobacter pylori infection.
Fluvoxamine: Omeprazole and other proton pump inhibitors are metabolized mainly by cytochrome P450 isoenzyme CYP2C19, which shows genetically determined polymorphism, yielding extensive metabolizers and poor metabolizers.
Fluvoxamine increased exposure to omeprazole, lanzoprazole and rabeprazole in patients who are extensive metabolizers, but had no effect on pharmacokinetic parameters in poor metabolizers. Dose reductions may need to be considered in patients treated with fluvoxamine and proton pump inhibitors.

Store at temperatures not exceeding 30°C. Protect from light.

Antacids, Antireflux Agents & Antiulcerants

A02BC01 - omeprazole ; Belongs to the class of proton pump inhibitors. Used in the treatment of peptic ulcer and gastro-oesophageal reflux disease (GERD).

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