Rabeprazole - Warnings and Precautions

5 WARNINGS AND PRECAUTIONS Gastric Malignancy : In adults, symptomatic response to therapy with rabeprazole does not preclude the presence of gastric malignancy.

Consider additional follow-up and diagnostic testing .

Use with Warfarin : Monitor for increases in INR and prothrombin time ( 5.2 , 7 ).

Acute Tubulointerstitial Nephritis : Discontinue treatment and evaluate patients .

Clostridium difficile- Associated Diarrhea : PPI therapy may be associated with increased risk of .

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 .

Severe Cutaneous Adverse Reactions : Discontinue at the first signs or symptoms of severe cutatneous adverse reactions or other signs of hypersensitivity and consider further evaluation .

Cutaneous and Systemic Lupus Erythematosus : Mostly cutaneous, new onset or exacerbation of existing disease; discontinue rabeprazole sodium delayed-release tablets and refer to specialist for evaluation .

Cyanocobalamin (Vitamin B-12) Deficiency : Daily long-term use (e.g., longer than 3 years) may lead to malabsorption or a deficiency of cyanocobalamin .

Hypomagnesemia and Mineral Metabolism : Reported rarely with prolonged treatment with PPIs .

Interaction with Methotrexate : Concomitant use with PPIs may elevate and/or prolong serum concentrations of methotrexate and/or its metabolite, possibly leading to toxicity.

With high dose methotrexate administration, consider a temporary withdrawal of rabeprazole sodium delayed-release tablets ( 5.10 , 7 ).

Fundic Gland Polyps : Risk increases with long-term use, especially beyond one year.

Use the shortest duration of therapy .

5.1 Presence of Gastric Malignancy In adults, symptomatic response to therapy with rabeprazole sodium delayed-release tablets does not preclude the presence of gastric malignancy.

Consider additional follow-up and diagnostic testing in adult patients who have a suboptimal response or an early symptomatic relapse after completing treatment with a PPI.

5.2 Interaction with Warfarin Steady state interactions of rabeprazole and warfarin have not been adequately evaluated in patients.

There have been reports of increased INR and prothrombin time in patients receiving a proton pump inhibitor and warfarin concomitantly.

Increases in INR and prothrombin time may lead to abnormal bleeding and even death.

Patients treated with rabeprazole sodium delayed-release tablets and warfarin concomitantly may need to be monitored for increases in INR and prothrombin time [see Drug Interactions ] .

5.3 Acute Tubulointerstitial Nephritis Acute tubulointerstitial nephritis (TIN) has been observed in patients taking PPIs and may occur at any point during PPI therapy.

Patients may present with varying signs and symptoms from symptomatic hypersensitivity reactions, to non-specific symptoms of decreased renal function (e.g., malaise, nausea, anorexia).

In reported case series, some patients were diagnosed on biopsy and in the absence of extra-renal manifestations (e.g., fever, rash or arthralgia).

Discontinue rabeprazole sodium and evaluate patients with suspected acute TIN [see Contraindication ].

5.4 Clostridium difficile -Associated Diarrhea Published observational studies suggest that PPI therapy like rabeprazole sodium may be associated with an increased risk of Clostridium difficile -associated diarrhea, especially in hospitalized patients.