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U.S. Department of Health and Human Services

Safety

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Prevpac (Lansoprazole 30 mg delayed-release, Amoxicillin 500 mg capsules and Clarithromycin 500 mg tablets)

Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)

 

November 2013

Summary View

CONTRAINDICATIONS

  • history of severe hypersensitivity reactions (e.g.,anaphylaxis or Stevens-Johnson syndrome) to amoxicillin or other beta-lactam antibiotics (e.g., penicillins and cephalosporins) is a contraindication.
  • Clarithromycin should not be given to patients with history of QT prolongation or ventricular cardiac arrhythmia, including torsades de pointes.
  • Clarithromycin should not be used concomitantly with HMG-CoA reductase inhibitors (statins) that are extensively metabolized by CYP3A4 (lovastatin or simvastatin), due to the increased risk of myopathy, including rhabdomyolysis.

WARNINGS

Acute Hypersensitivity Reactions
  • In the event of severe acute hypersensitivity reactions, such as anaphylaxis, Stevens-Johnson Syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms (DRESS), and Henoch-Schonlein purpura PREVPAC should be discontinued immediately and appropriate treatment should be urgently initiated.
QT Prolongation
  • Clarithromycin has been associated with prolongation of the QT interval and infrequent cases of arrhythmia…
Gastric Malignancy
  • Symptomatic response to therapy with lansoprazole does not preclude the presence of gastric malignancy.
Oral Hypoglycemic Agents/Insulin
  • The concomitant use of clarithromycin and oral hypoglycemic agents and/or insulin can result in significant hypoglycemia…
Oral Anticoagulants
  • There is a risk of serious hemorrhage and significant elevations in INR and prothrombin time when clarithromycin is co-administered with warfarin. INR and prothrombin times should be frequently monitored while patients are receiving clarithromycin and oral anticoagulants concurrently.
HMG-CoA Reductase Inhibitors (statins)
  • Concomitant use of clarithromycin with lovastatin or simvastatin is contraindicated (see CONTRAINDICATIONS) as these statins are extensively metabolized by CYP3A4, and concomitant treatment with clarithromycin increases their plasma concentration, which increases the risk of myopathy, including rhabdomyolysis…
Concomitant use of Prevpac with Methotrexate
  • Literature suggests that concomitant use of Proton Pump Inhibitors (PPI) 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 hign dose methotrexate administration, a temporary withdrawal of PREVPAC may be considered in some patients.
  • In addition, published observational studies suggest that PPI therapy maybe associated with an increase risk of CDAD, especially in hospitalized patients.
Adverse Reactions with Long-term PPI Use:
  • Bone Fracture: Several published observational studies suggest that 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).
  • 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.

ADVERSE REACTIONS

  • Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
  • The following post-marketing adverse reaction from the labeling for clarithromycin are provided for information:
    • drug rash with eosinophilia and systemic symptoms (DRESS), Henoch-Schonlein Purpura
    • myalgia and hemorrhage
    • depression
  • There have been cases of rhabdomyolysis reported with clarithromycin use. In some cases, clarithromycin was administered concomitantly with other drugs known to be associated with rhabdomyolysis (such as statins, fibrates, colchicine or allopurinol)…
  • Prevacid is not removed from the circulation by hemodialysis. In one reported overdose, a patient consumed 600 mg of PREVACID with no adverse reaction. Oral PREVACID doses up to 5000 mg/kg in rats (approximately 650 times the recommended human dose of 60 mg/day based on BSA) and in mice (about 338 times the recommended human dose of 60 mg/day based on BSA) did not produce deaths or any clinical signs.