Risek (+sodium bicarbonate)

Uses

Duodenal Ulcer: Omeprazole & Sodium bicarbonate is used for short-term treatment of active duodenal ulcer. Most patients heal within four weeks. Some patients may require an additional four weeks of therapy. Gastric Ulcer: Omeprazole & Sodium bicarbonate is used for short-term treatment (4-8 weeks) of active benign gastric ulcer. Treatment Of Gastroesophageal Reflux Disease (GERD):

• Symptomatic GERD: Omeprazole & Sodium bicarbonate is used for the treatment of heartburn and other symptoms associated with GERD for up to 4 weeks.
• Erosive Esophagitis: Omeprazole & Sodium bicarbonate is used for the short-term treatment (4-8 weeks) of erosive esophagitis which has been diagnosed by endoscopy. The efficacy of Omeprazole & Sodium bicarbonate used for longer than 8 weeks in these patients has not been established. If a patient does not respond to 8 weeks of treatment, it may be helpful to give up to an additional 4 weeks of treatment. If there is recurrence of erosive esophagitis or GERD symptoms (e.g., heartburn), additional 4-8 week courses of Omeprazole & Sodium bicarbonate may be considered.

Maintenance Of Healing Of Erosive Esophagitis: Omeprazole & Sodium bicarbonate is used to maintain healing of erosive esophagitis. Controlled studies do not extend beyond 12 months.

Reduction Of Risk of Upper Gastrointestinal Bleeding In Critically Ill Patients (40mg oral suspension only): Omeprazole & Sodium bicarbonate Powder for Oral Suspension 40 mg/1680 mg is used for the reduction of risk of upper GI bleeding in critically ill patients. [See Clinical Studies, Reduction of Risk of Upper Gastrointestinal Bleeding in Critically Ill Patients]

Risek (+sodium bicarbonate) is also used to associated treatment for these conditions: Ankylosing Spondylitis (AS), Duodenal Ulcer, Erosive Esophagitis, Gastric Ulcer, Gastro-esophageal Reflux Disease (GERD), Healing, Heartburn, Helicobacter Pylori Infection, NSAID Associated Gastric Ulcers, Osteoarthritis (OA), Rheumatoid Arthritis, Zollinger-Ellison Syndrome, Hypersecretory conditions, Multiple endocrine adenomasAcid indigestion, Barbiturate intoxication, Breast Cancer, Constipation, Dental Decay, Duodenal Ulcer, Dyspepsia, Gastro-esophageal Reflux Disease (GERD), Gingival Bleeding, Heartburn, Helicobacter Infections, Hyperkalemia, Ischaemia, Metabolic Acidosis, Myocardial Infarction, Plaque, Dental, Pruritis of the skin, Skin Irritation, Upset stomach, Zollinger-Ellison Syndrome, Abdominal bloating, Benign, active Gastric Ulcer, Methyl alcohol poisoning, Prophylaxis of Contrast-induced nephropathy, Salicylate poisoning, Severe Diarrhea, Swelling of the gums, Bowel preparation therapy

How Risek (+sodium bicarbonate) works

Hydrochloric acid (HCl) secretion into the gastric lumen is a process regulated mainly by the H(+)/K(+)-ATPase of the proton pump , expressed in high quantities by the parietal cells of the stomach. ATPase is an enzyme on the parietal cell membrane that facilitates hydrogen and potassium exchange through the cell, which normally results in the extrusion of potassium and formation of HCl (gastric acid) .

Omeprazole is a member of a class of antisecretory compounds, the substituted benzimidazoles, that stop gastric acid secretion by selective inhibition of the H+/K+ ATPase enzyme system. Proton-pump inhibitors such as omeprazole bind covalently to cysteine residues via disulfide bridges on the alpha subunit of the H+/K+ ATPase pump, inhibiting gastric acid secretion for up to 36 hours . This antisecretory effect is dose-related and leads to the inhibition of both basal and stimulated acid secretion, regardless of the stimulus .

Mechanism of H. pylori eradication

Peptic ulcer disease (PUD) is frequently associated with Helicobacter pylori bacterial infection (NSAIDs) . The treatment of H. pylori infection may include the addition of omeprazole or other proton pump inhibitors as part of the treatment regimen , . H. pylori replicates most effectively at a neutral pH . Acid inhibition in H. pylori eradication therapy, including proton-pump inhibitors such as omeprazole, raises gastric pH, discouraging the growth of H.pylori . It is generally believed that proton pump inhibitors inhibit the urease enzyme, which increases the pathogenesis of H. pylori in gastric-acid related conditions .

Sodium bicarbonate is a systemic alkalizer, which increases plasma bicarbonate, buffers excess hydrogen ion concentration, and raises blood pH, thereby reversing the clinical manifestations of acidosis. It is also a urinary alkalizer, increasing the excretion of free bicarbonate ions in the urine, thus effectively raising the urinary pH. By maintaining an alkaline urine, the actual dissolution of uric acid stones may be accomplished. Sodium bicarbonate acts as an antacid and reacts chemically to neutralize or buffer existing quantities of stomach acid but has no direct effect on its output. This action results in increased pH value of stomach contents, thus providing relief of hyperacidity symptoms. [PharmGKB]

Dosage

Risek (+sodium bicarbonate) dosage

Since both the 20 mg and 40 mg capsules contain the same amount of sodium bicarbonate (1100 mg), two capsules of 20 mg are not equivalent to one capsule of 40 mg; therefore, two 20 mg capsules should not be substituted for one capsule 40 mg.

Short-Term Treatment of Active Duodenal Ulcer:20 mg Once daily for 4 weeks

Benign Gastric Ulcer: 40 mg Once daily for 4-8 weeks

Symptomatic GERD (with no esophageal erosions): 20 mg Once daily for up to 4 weeks

Erosive Esophagitis: 20 mg Once daily for 4-8 weeks

Maintenance of Healing of Erosive Esophagitis: 20 mg Once daily

Reduction of Risk of Upper Gastrointestinal Bleeding in Critically Ill Patients (40 mg oral suspension only): 40 mg initially followed by 40 mg 6-8 hours later and 40 mg daily thereafter for 14 days

Should be taken on an empty stomach. Take at least 1 hr before a meal.

Side Effects

Abdominal pain, asthenia, constipation, diarrhea, flatulence, nausea, vomiting, acid regurgitation, headache

Toxicity

Oral acute (LD50): 4000 mg/kg (mouse), 2210 mg/kg (rat) .

Overdose

Symptoms of overdose include confusion, drowsiness, blurred vision, tachycardia, nausea, diaphoresis, flushing, headache, and dry mouth.

Carcinogenesis and mutagenesis

In 24-month studies in rats, a dose-related significant increase in gastric carcinoid tumors and ECL cell hyperplasia was seen in male and female animals. Carcinoid tumors have also been found in rats treated with a fundectomy or long-term treatment with other proton pump inhibitors, or high doses of H2-receptor antagonists .

Omeprazole showed positive clastogenic effects in an in vitro human lymphocyte chromosomal aberration study, in one of two in vivo mouse micronucleus tests, and in an in vivo bone marrow cell chromosomal aberration test. Omeprazole tested negative in the in vitro Ames test, an in vitro mouse lymphoma cell forward mutation assay, and an in vivo rat liver DNA damage assay .

The use in breastfeeding

Limited data indicate that omeprazole may be present in human milk. There is currently no information on the effects of omeprazole on the breastfed infant or production of milk. The benefits of breastfeeding should be considered along with the level of need for omeprazole and any potential adverse effects on the breastfed infant from omeprazole .

Effects on fertility

Effects of omeprazole at oral doses up to 138 mg/kg/day in rats (about 34 times an oral human dose) was found to have no impact on fertility and reproductive performance .

Precaution

Patients on Na-restricted diet; Bartter's syndrome, hypokalemia, resp alkalosis, problems with acid-base balance. Severe hepatic impairment. Lactation. Childn & adolescents <18 yr.

Interaction

Diazepam, warfarin, phenytoin, drugs metabolized by oxidation in the liver, cyclosporine, disulfiram, benzodiazepines, ketoconazole, ampicillin esters, Fe salts, atazanavir, tacrolimus, clarithromycin.

Volume of Distribution

Approximately 0.3 L/kg, corresponding to the volume of extracellular water .

Elimination Route

Omeprazole delayed-release capsules contain an enteric-coated granule formulation of omeprazole (because omeprazole is acid-labile), so that absorption of omeprazole begins only after the granules exit the stomach .

Absorption of omeprazole occurs rapidly, with peak plasma concentrations of omeprazole achieved within 0.5-3.5 hours .

Absolute bioavailability (compared with intravenous administration) is approximately 30-40% at doses of 20-40 mg, largely due to pre-systemic metabolism. The bioavailability of omeprazole increases slightly upon repeated administration of omeprazole delayed-release capsules .

Half Life

0.5-1 hour (healthy subjects, delayed-release capsule)
Approximately 3 hours (hepatic impairment)

Clearance

Healthy subject (delayed release capsule), total body clearance 500 - 600 mL/min

Geriatric plasma clearance: 250 mL/min

Hepatic impairment plasma clearance: 70 mL/min

Elimination Route

After a single dose oral dose of a buffered solution of omeprazole, negligible (if any) amounts of unchanged drug were excreted in urine. Most of the dose (about 77%) was eliminated in urine as at least six different metabolites. Two metabolites were identified as hydroxyomeprazole and the corresponding carboxylic acid. The remainder of the dose was found in the feces. This suggests significant biliary excretion of omeprazole metabolites. Three metabolites have been identified in the plasma, the sulfide and sulfone derivatives of omeprazole, and hydroxyomeprazole. These metabolites possess minimal or no antisecretory activity .

Pregnancy & Breastfeeding use

Pregnancy Category C. Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.

Contraindication

Metabolic alkalosis & hypocalcemia. Pregnancy.

Acute Overdose

If alkalosis results, the bicarbonate should be stopped and the patient managed according to the degree of alkalosis present. 0.9% sodium chloride injection intravenous may be given; potassium chloride also may be indicated if there is hypokalemia. Severe alkalosis may be accompanied by hyperirritability or tetany and these symptoms may be controlled by calcium gluconate. An acidifying agent such as ammonium chloride may also be indication in severe alkalosis.

Storage Condition

Store in a cool (below 30° C) and dry place, protected from light and moisture.

Store in a cool & dry place protected from light. Keep out of reach of children.

Innovators Monograph

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