NEODOSE

INDICATIONS

• Thromboprophylaxis: Antiplatelet agent for the prophylaxis of thrombotic events. Has been used successfully for the prophylaxis of thrombosis in cardiac disease and cardiac conditions associated with a high risk for arterial thrombosis

FDA APPROVED INDICATION

Not FDA approved in pediatric patients

CONTRAINDICATIONS

Contraindicated in patients with active, pathological bleeding (eg, peptic ulcer or intracranial hemorrhage). Bleeding risk is increased with the concomitant use of clopidogrel, NSAIDs or warfarin. In one pediatric clinical study (n=17), significant intracranial hemorrhage was reported in 25% of pediatric patients (n=2/9) when clopidogrel was used concomitantly with aspirin. In another study (n=46), 1 case each of severe epistaxis and gastrointestinal bleeding was reported in the 2 children receiving concomitant warfarin and clopidogrel therapy. There was 1 report of massive upper GI bleeding in a child on concomitant clopidogrel, low-dose aspirin, and warfarin in another study (n=15). Thrombotic thrombocytopenic purpura, some cases fatal, has been reported.

PRECAUTIONS

• Administration:
  • Nasogastric administration in critically ill patients after cardiopulmonary resuscitation increases risk of impaired clopidogrel bioavailability.
• Concomitant Use:
  • Avoid with omeprazole or esomeprazole: in a subgroup analysis (n=49) of the Platelet Inhibition in Children On cLOpidogrel (PICOLO) trial, clopidogrel plus a proton pump inhibitor reduced platelet inhibition and reduced the numbers of responders.
  • Etravirine not recommended.
• Discontinuation:
  • Premature discontinuation may increase risk of cardiovascular events, including stent thrombosis, myocardial infarction, and death, particularly in patients undergoing percutaneous coronary intervention; restart as soon as possible when temporary discontinuation is required.
• Hematologic:
  • Thrombotic thrombocytopenic purpura, with some cases fatal, has been reported.
  • Bleeding risk is increased with use.
• Immunologic:
  • Hypersensitivity reactions (including angioedema or hematologic reaction) has been reported, including patients with a history of hypersensitivity or hematologic reaction to other thienopyridines.
• Surgery:
  • Interrupt use 5 days prior to elective surgery with major risk of bleeding, when possible.

ADVERSE EFFECTS

Bleeding and thrombotic thrombocytopenic purpura are the most common hematological adverse events. Anemia, neutropenia, and leukopenia have also been reported.

BLACK BOX WARNING

The effectiveness of clopidogrel hydrogen sulfate results from its antiplatelet activity, which is dependent on its conversion to an active metabolite by the cytochrome P450 (CYP) system, principally CYP2C19. Clopidogrel hydrogen sulfate at recommended doses forms less of the active metabolite and so has a reduced effect on platelet activity in patients who are homozygous for nonfunctional alleles of the CYP2C19 gene, (termed “CYP2C19 poor metabolizers”). Tests are available to identify patients who are CYP2C19 poor metabolizers. Consider use of another platelet P2Y12 inhibitor in patients identified as CYP2C19 poor metabolizers.

ADMINISTRATION

May be given without regard to feedings

MONITORING

Measure bleeding time prior to therapy initiation and 3 to 7 days after therapy initiation to assess drug efficacy. Platelet aggregation assay studies may be useful in some patients to evaluate response . Monitor hematological parameters closely during the first few months of therapy and every 2 to 3 months in patients on long-term therapy.