RISEK Omeprazole 20mg Capsule 1's

Indications/Uses

Treatment of symptomatic gastroesophageal disease (GERD) without esophagitis; healing of erosive esophagitis; maintenance of healed erosive esophagitis; gastric and duodenal ulcer.
Risek: Treatment and prophylaxis of NSAID-associated ulceration; eradication of Helicobacter pylori infection associated with peptic ulcer disease; Zollinger-Ellison syndrome; dyspepsia and prophylaxis of acid aspiration.

Dosage/Direction for Use

Risek: Adults: Recommended Oral Dose: Symptomatic Gastroesophageal Reflux Disease (GERD) without Esophagitis: 20 mg daily for up to 4 weeks.
Erosive Esophagitis and Accompanying GERD Symptoms: 20 mg daily for 4-8 weeks.
Maintenance Healing of Erosive Esophagitis: 20 mg daily.
Children: GERD: Dose Range: 0.7-1.4 mg/kg body weight daily up to a maximum daily dose of 40 mg for 4-12 weeks.
Gastric and Duodenal Ulcer: 20 mg single daily dose orally or 40 mg in severe cases is given. Treatment is continued for 4 weeks for duodenal ulcer and 8 weeks for gastric ulcer. When appropriate, a dose of 10-20 mg once daily may be given for maintenance.
NSAID-Associated Ulceration: A dose of 20 mg daily, which may also be used for prophylaxis in patients with a previous history of gastroduodenal lesions who require continued NSAID treatment.
Helicobacter pylori Eradication: 40 mg daily may be combined with antibacterials in dual therapy or 20 mg twice daily may be combined with antibacterials in triple therapy. Omeprazole alone may be continued for a further 2-8 weeks.
Zollinger-Ellison Syndrome: Initial Recommended Dose: 60 mg orally once daily, adjusted as required. The majority of patients are effectively controlled by doses in the range of 20-120 mg daily, but doses of up to 120 mg 3 times daily have been used. Daily doses >80 mg should be administered in divided doses.
Dyspepsia: Usual Dose: 10 or 20 mg daily orally for 2-4 weeks.
Prophylaxis of Acid Aspiration: Also used for the prophylaxis of acid aspiration during general anesthesia in a dose of 40 mg in the evening before surgery and a further 40 mg 2-6 hrs before the procedure.
Hepatic Impairment: Maximum Daily Dose: 20 mg is recommended for patients with impaired hepatic function.
Vial: GERD, Peptic Ulcer Disease, Treatment and Prophylaxis of NSAID-Associated Ulceration: 40 mg IV once daily.
Zollinger-Ellison Syndrome: Initial Dose: 60 mg IV daily. Higher daily doses may be required and the dose should be adjusted individually. Doses >60 mg should be given twice daily.
Prophylaxis of Acid Aspiration: 40 mg IV to be completed 1 hr before surgery.
Hepatic Impairment: 10-20 mg daily may be sufficient or as directed by a physician.
Risek Insta: Recommended dosing given in the following table. (See Table.)

Since both 20 mg and 40 mg oral suspension sachets contain the same amount of sodium bicarbonate (1680 mg), 2 sachets of Risek Insta 20 mg are not equivalent to 1 sachet of Risek Insta 40 mg; therefore two 20 mg sachets should not be substituted for 1 sachet Risek Insta 40 mg.
Administration: Risek: Capsule: Risek is given orally which should be swallowed whole and not crushed or chewed.
IV: Risek vial should be given as an IV infusion (over a period of 20-30 min). The contents of 1 vial must be dissolved in at least 100 mL of normal saline or 100 mL of 5% dextrose in IV chamber.
Preparation: With a syringe, draw 5 mL of infusion solution from the infusion bag. Add the infusion solution to the lyophilized powder of omeprazole in the vial. Mix thoroughly, making sure all the powder is dissolved. Draw the omeprazole solution back into the syringe. Transfer the solution into the infusion bag. Repeat the previous steps to make sure all the powder is transferred from the vial into the infusion bag.
Riske Insta: Risek Insta should be taken on an empty stomach at least 1 hr before a meal.
Direction for Reconstitution: Empty the sachet contents into a small cup containing 15-30 mL (1-2 tbsp) of water to form suspension. Stir well and drink immediately. Refill cup with water and drink. Do not use other liquids or food.

Overdosage

Risek Insta: In doses ranged up to 2400 mg, manifestations were variable, but included confusion, drowsiness, blurred vision, tachycardia, nausea, vomiting, diaphoresis, flushing, headache, dry mouth and other adverse reactions similar to those seen in normal clinical experience. No specific antidote for omeprazole overdosage is known.
Omeprazole is extensively protein bound and is, therefore, not readily dialyzable. In the event of overdosage, treatment should be symptomatic and supportive. In addition, a sodium bicarbonate overdose may cause hypocalcemia, hypokalemia, hypernatremia and seizures.

Administration

Should be taken on an empty stomach: Take 30 min-1 hr before meals. Swallow whole, do not chew/crush.

Contraindications

Risek: Hypersensitivity to any of the components of Risek or to substituted benzimidazoles.
Risek Insta: Hypersensitivity to omeprazole or to any of the excipients of Risek Insta. Sodium bicarbonate is contraindicated in patients with metabolic alkalosis and hypocalcemia.

Special Precautions

Risek: When gastric ulcer is suspected, the possibility of malignancy should be excluded as treatment may alleviate symptoms and delay diagnosis. Prior to initiation of dual or triple therapy, the physician should consider the patient with known hypersensitivity reactions to penicillin, macrolides and other antibiotics.
Hepatic Impairment: Consideration should be given to reducing the dose of omeprazole in patients with impaired hepatic function as bioavailability and t_½ can increase.
Risek Insta: Symptomatic response to therapy with omeprazole does not preclude the presence of gastric malignancy.
Atrophic gastritis has been noted occasionally in gastric corpus biopsies from patients treated long-term with omeprazole.
Omeprazole powder for oral suspension contains sodium in the form of sodium bicarbonate. This should be taken into consideration for patients on a sodium-restricted diet.
Sodium bicarbonate should be used with caution in patients with Bartter's syndrome, hypokalemia, respiratory alkalosis and problems with acid-base balance.
Long-term administration of bicarbonate with calcium or milk can cause milk-alkali syndrome.
Use in Pregnancy: There are no adequate or well-controlled studies in pregnant women. Omeprazole should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Use in Lactation: Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from omeprazole, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Risek: It is not known whether omeprazole is excreted in human milk
Risek Insta: Omeprazole is excreted in human milk. In addition, sodium bicarbonate should be used with caution in nursing mothers.

Use In Pregnancy & Lactation

Use in Pregnancy: There are no adequate or well-controlled studies in pregnant women. Omeprazole should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Use in Lactation: Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from omeprazole, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Risek: It is not known whether omeprazole is excreted in human milk
Risek Insta: Omeprazole is excreted in human milk. In addition, sodium bicarbonate should be used with caution in nursing mothers.

Adverse Reactions

Risek: Risek is well-tolerated and the adverse reactions have generally been mild and reversible.
Central and Peripheral Nervous System: Common: Headache. Uncommon: Dizziness, paresthesia, somnolence, insomnia, vertigo. Rare: Reversible mental confusion, agitation, aggression, depression and hallucinations, predominantly in severely ill patients.
Gastrointestinal: Common: Diarrhea, constipation, abdominal pain, nausea, vomiting and flatulence. Rare: Dry mouth, stomatitis and gastrointestinal candidiasis.
Hepatic: Uncommon: Increased liver enzymes.
Endocrine: Rare: Gynecomastia.
Hematological: Rare: Leukopenia, thrombocytopenia, agranulocytosis and pancytopenia.
Skin: Uncommon: Rash and/or pruritus, urticaria.
Others: Uncommon: Malaise.
Gastroduodenal carcinoids have been reported in patients with Zollinger-Ellison syndrome on long-term treatment with omeprazole.
Risek Insta: The following adverse reactions were reported: Body as a Whole: Allergic reactions eg, rarely anaphylaxis, fever, pain, fatigue, malaise and abdominal swelling.
Cardiovascular: Chest pain or angina, tachycardia, bradycardia, palpitation, elevated blood pressure and peripheral edema.
Gastrointestinal: Pancreatitis (sometimes fatal), anorexia, irritable colon, flatulence, fecal discoloration, esophageal candidiasis, mucosal atrophy of the tongue, dry mouth and stomatitis. During treatment with omeprazole, gastric fundic gland polyps have been noted rarely. These polyps are benign and appear to be reversible when treatment is discontinued.
Hepatic: Mild and rarely marked elevations of liver function tests [ALT (SGPT), AST (SGOT), g-glutamyl transpeptidase, alkaline phosphatase and bilirubin (jaundice)]. In rare instances, overt liver disease has occurred, including hepatocellular, cholestatic or mixed hepatitis, liver necrosis (sometimes fatal), hepatic failure (sometimes fatal) and hepatic encephalopathy.
Metabolic/Nutritional: Hyponatremia, hypoglycemia and weight gain.
Musculoskeletal: Muscle cramps, myalgia, muscle weakness, joint and leg pain.
Nervous System/Psychiatric: Psychic disturbances eg, depression, agitation, aggression, hallucinations, confusion, insomnia, nervousness, tremors, apathy, somnolence, anxiety, dream abnormalities, vertigo, paresthesia and hemifacial dysesthesia.
Respiratory: Epistaxis and pharyngeal pain.
Skin: Rash and rarely, cases of severe generalized skin reactions eg, toxic epidermal necrolysis (TEN; sometimes fatal), Stevens-Johnson syndrome and erythema multiforme (some severe); purpura and/or petechiae (sometimes with rechallenge); skin inflammation, urticaria, angioedema, pruritus, photosensitivity, alopecia, dry skin and hyperhydrosis.
Special Senses: Tinnitus and taste perversion.
Ocular: Blurred vision, ocular irritation, dry eye syndrome, optic atrophy, anterior ischemic optic neuropathy, optic neuritis and double vision.
Urogenital: Interstitial nephritis (sometimes with positive rechallenge), urinary tract infection, microscopic pyuria, urinary frequency, elevated serum creatinine, proteinuria, hematuria, glycosuria, testicular pain and gynecomastia.
Hematologic: Rare instances of pancytopenia, agranulocytosis (sometimes fatal), thrombocytopenia, neutropenia, leukopenia, anemia, leukocytosis and hemolytic anemia have been reported.
Additional adverse reactions that could be caused by sodium bicarbonate, include metabolic alkalosis, seizures and tetany.

Drug Interactions

Risek: Commonly with the use of other inhibitors of acid secretion or antacids, the absorption of ketoconazole and itraconazole can be decreased due to decreased intragastric acidity during treatment with omeprazole.
Omeprazole inhibits CYP2C19. Thus, when omeprazole is combined with drugs metabolized by CYP2C19 eg, diazepam, citalopram, imipramine, clomipramine, phenytoin, etc, the plasma concentrations of these drugs may be increased and a dose reduction could be needed.
Risek Insta: Omeprazole can prolong the elimination of diazepam, warfarin and phenytoin, drugs that are metabolized by oxidation in the liver.
There have been reports of increased international normalized ratio (INR) and prothrombin time in patients receiving proton-pump inhibitors eg, omeprazole and warfarin concomitantly. Increase in INR and prothrombin time may lead to abnormal bleeding and even death. Patients treated with proton-pump inhibitors and warfarin may need to be monitored for increase in INR and prothrombin time.
Although in normal subjects, no interaction with theophylline or propranolol was found, there have been clinical reports of interaction with other drugs metabolized via the cytochrome P-450 system (eg, cyclosporine, disulfiram, benzodiazepines). Patients should be monitored to determine if it is necessary to adjust the dosage of these drugs when taken concomitantly with omeprazole.
Because of its profound and long-lasting inhibition of gastric acid secretion, it is theoretically possible that omeprazole may interfere with absorption of drugs where gastric pH is an important determinant of their bioavailability (eg, ketoconazole, ampicillin esters and iron salts).
Concomitant administration of omeprazole and atazanavir has been reported to reduce the plasma levels of atazanavir.
Concomitant administration of omeprazole and tacrolimus may increase the serum levels of tacrolimus.
Co-administration of omeprazole and clarithromycin have resulted in increase of plasma levels of omeprazole, clarithromycin and 14-hydroxyclarithromycin.

Caution For Usage

Risek: Incompatibilities: No other drugs should be mixed with reconstituted Risek IV infusion.
Special Precautions: The lyophilized powder for infusion must be dissolved in saline for infusion 100 mL or 5% dextrose for infusion 100 mL.

Storage

Store at temperatures not exceeding 30°C. Protect from sunlight and moisture.
Shelf-Life: Risek: Six (6) hrs for an infusion prepared in 5% dextrose and 12 hrs for an infusion prepared in normal saline.
Risek Insta: 24 months.

Action

Pharmacotherapeutic Group: Omeprazole, a substituted benzimidazole, is a proton-pump inhibitor that inhibits gastric acid secretion.
Pharmacology: Mechanism of Action: Omeprazole reduces gastric acid secretion through a unique mechanism of action. Omeprazole belongs to a new class of antisecretory compounds, the substituted benzimidazoles that do not exhibit anticholinergic or histamine antagonistic properties. It inhibits secretion of gastric acid by irreversibly blocking the enzyme system of hydrogen/potassium adenosine triphosphate (H⁺/K⁺ ATPase), the proton pump of the gastric parietal cell. This effect is dose-related and leads to inhibition of both basal and stimulated acid secretion irrespective of the stimulus.
Pharmacokinetics: Absorption and Distribution: Risek: Risek capsule is acid-labile and administered orally as enteric-coated pellets in capsules. Omeprazole is rapidly but variably absorbed following oral administration, with peak plasma levels of omeprazole occurring within 0.5-3.5 hrs. Absorption of omeprazole is not affected by food and also appears to be dose dependent. Increasing the dosage >40 mg has been reported to increase the plasma concentrations in a nonlinear fashion because of saturable first-pass metabolism. Absorption is higher after long-term administration.
The systemic bioavailability of omeprazole is approximately 35%. After repeated once-daily administration, the bioavailability increases to about 60%. The plasma protein-binding of omeprazole is about 95%.
Risek Insta: Omeprazole is acid-labile and is administered orally on an empty stomach 1 hr prior to a meal. The absorption of omeprazole is rapid, with mean peak plasma levels being 1954 ng/mL (33%) occurring at about 30 min (range 10-90 min) after a single-dose or repeated-dose administration. Absolute bioavailability of omeprazole powder for oral suspension is about 30-40% at doses 20-40 mg due in large part to presystemic metabolism. When powder for oral suspension is administered 1 hr after a meal, the omeprazole area under the concentration-time curve (AUC) is reduced by approximately 24% relative to administered 1 hr prior to meal.
Omeprazole is bound to plasma proteins. Protein-binding is approximately 95%.
Metabolism and Excretion: Following 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 CYP3A to form omeprazole sulfone. These metabolites are inactive and excreted mostly in the urine and to a lesser extent in the bile. The majority of the dose (about 77%) is eliminated in the urine and the remainder recoverable in the feces.
Risek: The elimination half-life (t_½) from plasma following oral administration is reported to be about 0.5-3 hrs. The elimination t_½ from plasma following IV administration is approximately 40 min to 3 hrs. The total plasma clearance is 0.3-0.6 L/min. There is no change in t_½ during treatment.
Risek Insta: The mean plasma omeprazole half-life (t_½) is approximately 1 hr (ranging from 0.4-3.2 hrs) and the total body clearance is 500-600 mL/min.
Special Population: Pediatric: Risek: Available data from children (≥1 year) suggest that the pharmacokinetics within the recommended doses are similar to those in adults. At steady-state, lower plasma levels of omeprazole were seen in some children.
There is limited experience with omeprazole administered IV in children.
Risek Insta: The pharmacokinetics of omeprazole has not been studied in patients <18 years.
Geriatric: Risek: The bioavailability of omeprazole may be increased in elderly patients.
In elderly patients, the volume of distribution (V_d) is slightly decreased as compared to healthy patients. Dose adjustment is not needed in the elderly.
Risek Insta: The elimination rate of omeprazole was somewhat decreased in the elderly and bioavailability was increased. Omeprazole was 76% bioavailable when a single oral dose of omeprazole 40 mg (buffered solution) was administered to healthy elderly subjects, versus 58% in young subjects given the same dose. The plasma clearance of omeprazole was 250 mL/min (about ½ that of young subjects) and its plasma half-life (t½) averaged 1 hr, similar to that of young healthy subjects.
Renal Insufficiency: Risek: The systemic bioavailability of omeprazole is not significantly altered in patients with reduced renal function. The V_d in patients with reduced renal function is similar to that seen in healthy patients. Therefore, dose adjustment is not required.
Risek Insta: In patients with chronic renal impairment, whose creatinine clearance (CrCl) ranged between 10 and 62 mL/min/1.73 m², the disposition of omeprazole from a buffered solution was very similar to that in healthy subjects, although there was a slight increase in bioavailability. Because urinary excretion is a primary route of excretion of omeprazole metabolites, their elimination slowed in proportion to the decreased CrCl.
Hepatic Insufficiency: Risek: The area under the plasma concentration-time curve (AUC) is increased in patients with impaired liver function, but no tendency to accumulation of omeprazole has been found.
The V_d is slightly decreased, while the plasma t_½ of omeprazole is increased.
Risek Insta: In patients with chronic hepatic disease, the bioavailability of omeprazole from a buffered solution increased to approximately 100% and the mean plasma t_½ of the drug increased to nearly 3 hrs compared to the mean t½ of 1 hr in normal subjects. Plasma clearance averaged 70 mL/min, compared to a value of 500-600 mL/min in normal subject.

MedsGo Class

Antacids, Antireflux Agents & Antiulcerants