warnings and cautions
5 WARNINGS AND PRECAUTIONS Concomitant Gastric Malignancy: Symptomatic response to therapy with Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets does not preclude the presence of gastric malignancy ( 5.1 ) Atrophic Gastritis: Has been observed in gastric corpus biopsies from patients treated long-term with omeprazole ( 5.2 ) Buffer Content: Contains sodium bicarbonate. ( 5.3 ) PPI therapy may be associated with increased risk of Clostridium difficile associated diarrhea. ( 5.4 ) Bone Fracture: Long-term and multiple daily dose PPI therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist, or spine. ( 5.5 ) Diminished anti-platelet activity of clopidogrel due to impaired CYP2C19 function by 80 mg omeprazole ( 5.6 ) Hypomagnesemia has been reported rarely with prolonged treatment with PPIs ( 5.7 ) Avoid concomitant use of Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets with St John's Wort or rifampin due to the potential reduction in omeprazole concentrations ( 5.8 , 7.2 ) Interactions with diagnostic investigations for Neuroendocrine Tumors: Increases in intragastric pH may result in hypergastrinemia and enterochromaffin-like cell hyperplasia and increased Choromogranin A levels which may interfere with diagnostic investigations for neuroendocrine tumors. ( 5.9 , 12.2 ) 5.1 Concomitant Gastric Malignancy Symptomatic response to therapy with omeprazole does not preclude the presence of gastric malignancy. 5.2 Atrophic Gastritis Atrophic gastritis has been noted occasionally in gastric corpus biopsies from patients treated long-term with omeprazole. 5.3 Buffer Content Each 20 mg and 40 mg Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablet contains 750 mg (9 mEq) of sodium bicarbonate (equivalent to 209 mg of Na+) and 343 mg (12 mEq) of magnesium hydroxide (equivalent to 143 mg of Mg2+). Sodium Bicarbonate Because Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets contains sodium bicarbonate, it should be used with caution in patients with Bartter's syndrome, hypokalemia, hypocalcemia, respiratory and metabolic alkalosis, and problems with acid-base balance. Long-term administration of bicarbonate with calcium or milk can cause milk-alkali syndrome. The sodium content of this product should be taken into consideration when administering to patients on a sodium-restricted diet or at risk of developing congestive heart failure (CHF). Chronic use of sodium bicarbonate may lead to systemic alkalosis and increased sodium intake can produce edema and weight increase. Magnesium Hydroxide Because Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets contains magnesium hydroxide, it should be used with caution in elderly and in patients with renal impairment or renal disease due to increased risk of developing hypermagnesemia and magnesium toxicity. Magnesium hydroxide should not be used in patients with renal failure unless serum magnesium levels are being closely monitored. Hypermagnesemia has been reported in infants whose mothers were using magnesium-containing antacid products chronically in high doses. 5.4 Clostridium difficile associated diarrhea Published observational studies suggest that PPI therapy like Omprezole/Sodium Bicarbonate/Magnesium Hydroxide tablets may be associated with an increased risk of Clostridium difficile associated diarrhea, especially in hospitalized patients. This diagnosis should be considered for diarrhea that does not improve. [See Adverse Reactions ( 6.2 )] Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. 5.5 Bone Fracture Several published observational studies suggest that proton pump inhibitor (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 (a year or longer). 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 the established treatment guidelines. [See Dosage and Administration ( 2 ) and Adverse Reactions ( 6.2 )] 5.6 Diminished Anti-platelet Activity of clopidogrel due to Impaired CYP2C19 Function by Omeprazole Clopidogrel is a prodrug. Inhibition of platelet aggregation by clopidogrel is entirely due to an active metabolite. The metabolism of clopidogrel to its active metabolite can be impaired by use with concomitant medications, such as omeprazole, that interfere with CYP2C19 activity. Avoid concomitant use of clopidogrel and omeprazole. Co-administration of clopidogrel with 80 mg omeprazole, a proton pump inhibitor that is an inhibitor of CYP2C19, reduces the pharmacological activity of clopidogrel if given concomitantly or if given 12 hours apart [ see Drug Interactions ( 7 ) ]. 5.7 Hypomagnesemia Hypomagnesemia, symptomatic and asymptomatic, has been reported rarely in patients treated with PPIs for at least three months, in most cases after a year of therapy. Serious adverse events include tetany, arrhythmias, and seizures. In most patients, treatment of hypomagnesemia required magnesium replacement and discontinuation of the PPI. For patients expected to be on prolonged treatment or who take PPIs with medications such as digoxin or drugs that may cause hypomagnesemia (e.g., diuretics), health care professionals may consider monitoring magnesium levels prior to initiation of PPI treatment and periodically. [See Adverse Reactions ( 6.2 )] 5.8 Concomitant use of omeprazole with St John's Wort or rifampin Drugs which induce CYP2C19 or CYP3A4 (such as St John's Wort or rifampin) can substantially decrease omeprazole concentrations. [See Drug Interactions ( 7.2 )] Avoid concomitant use of omeprazole with St John's Wort or rifampin. 5.9 Interactions with Investigations for Neuroendocrine Tumors Serum chromogranin A (CgA) levels increase secondary to drug-induced decreases in gastric acidity. The increased CgA level may cause false positive results in diagnostic investigations for neuroendocrine tumors. Providers should temporarily stop omeprazole treatment before assessing CgA levels and consider repeating the test if initial CgA levels are high. If serial tests are performed (e.g. for monitoring), the same commercial laboratory should be used for testing, as reference ranges between tests may vary.