Esomeprazole magnesium - Warnings and Precautions

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

Consider additional follow-up and diagnostic testing. • Acute Tubulointerstitial Nephritis : Discontinue treatment and evaluate patients. • Clostridium difficile -Associated Diarrhea : PPI therapy may be associated with increased risk. • 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 cutaneous 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 esomeprazole magnesium delayed-release capsules and refer to specialist for evaluation. • Interaction with Clopidogrel : Avoid concomitant use of esomeprazole magnesium delayed-release capsules. • 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 St.

John’s Wort or Rifampin : Avoid concomitant use of esomeprazole magnesium delayed-release capsules. ( 5.10 , 7 ) • I nteractions with Diagnostic Investigations for Neuroendocrine Tumors : Increased chromogranin A (CgA) levels may interfere with diagnostic investigations for neuroendocrine tumors, temporarily stop esomeprazole magnesium delayed-release capsules are at least 14 days before assessing CgA levels. ( 5.11 , 12.2 ) • 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 temporary withdrawal of esomeprazole magnesium delayed-release capsules. ( 5.12 , 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 esomeprazole magnesium delayed-release capsules 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.

In older patients, also consider an endoscopy.

5.2 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 esomeprazole magnesium delayed-release capsules and evaluate patients with suspected acute TIN [see Contraindications ] .

5.3 Clostridium difficile -Associated Diarrhea Published observational studies suggest that PPI therapy like esomeprazole magnesium delayed-release capsules 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 ] .

Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated.

Clostridium difficile -associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents.

For more information specific to antibacterial agents (clarithromycin and amoxicillin) indicated for use in combination with esomeprazole magnesium delayed-release capsules, refer to Warnings and Precautions section of the corresponding prescribing information.

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 established treatment guidelines [see Dosage and Administration and Adverse Reactions ] .

5.5 Severe Cutaneous Adverse Reactions Severe cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) have been reported in association with the use of PPIs [see Adverse Reactions ] .

Discontinue esomeprazole magnesium delayed-release capsules at the first signs or symptoms of severe cutaneous adverse reactions or other signs of hypersensitivity and consider further evaluation.

5.6 Cutaneous and Systemic Lupus Erythematosus Cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE) have been reported in patients taking PPIs, including esomeprazole.

These events have occurred as both new onset and an exacerbation of existing autoimmune disease.