warnings and cautions
5 WARNINGS AND PRECAUTIONS Concomitant Gastric Malignancy: Symptomatic response to therapy with ZEGERID 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 ) 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. ( 5.4 ) Diminished anti-platelet activity of clopidogrel due to impaired CYP2C19 function by 80 mg omeprazole ( 5.5 ) Hypomagnesemia has been reported rarely with prolonged treatment with PPIs ( 5.6 ) 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 ZEGERID Capsule contains 1100 mg (13 mEq) of sodium bicarbonate. The total content of sodium in each capsule is 304 mg. Each packet of ZEGERID Powder for Oral Suspension contains 1680 mg (20 mEq) of sodium bicarbonate (equivalent to 460 mg of Na+). The sodium content of ZEGERID products should be taken into consideration when administering to patients on a sodium restricted diet. Because ZEGERID products contain sodium bicarbonate, they should be used with caution in patients with Bartter's syndrome, hypokalemia, hypocalcemia, and problems with acid-base balance. Long-term administration of bicarbonate with calcium or milk can cause milk-alkali syndrome. Chronic use of sodium bicarbonate may lead to systemic alkalosis and increased sodium intake can produce edema and weight increase. 5.4 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 )] 5.5 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 ) ]. 5.6 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 )] 5.7 Concomitant use of Zegerid with Methotrexate Literature suggests that concomitant use of PPIs with methotrexate (primarily at high dose; see methotrexate prescribing information) 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 ( 7.7 )