Transdermal Tirofiban

Transdermal Aggrastat


In vivo proof of principle for transdermal tirofiban was recently established in studies conducted under Medicure International, Inc.'s research and development collaboration with 4P Therapeutics, Inc. (Alpharetta, GA). 4P Therapeutics, a world leader in the research and development of novel transdermal products. The transdermal tirofiban development program is now focusing on refining the delivery approach in preparation for initial human studies. Medicure and its's subsidiaries hold worldwide rights to transdermal tirofiban.

Market Applications

Upstream treatment for Acute Coronary Syndromes (current AGGRASTAT® indication)

AGGRASTAT (IV tirofiban) is indicated and guideline recommended for the treatment of acute coronary syndrome (ACS), including patients who are to be managed medically and those undergoing PTCA or atherectomy. Upon admission to hospital ACS patients sometimes receive tirofiban, or another GP IIb/IIIa inhibitor, for up to 72 hours. Transdermal tirofiban has the potential to replace IV administration in this setting and to provide an easier, more efficient way to begin treatment early. It may also provide an opportunity for prehospital administration of tirofiban.

Transdermal Tirofiban

Medicure is currently developing a transdermal delivery formulation of its lead drug AGGRASTAT (tirofiban HCl). This development program is an important part of Medicure's life cycle management strategy for AGGRASTAT. Drugs in the Glycoprotein IIb/IIIa inhibitor class, including tirofiban, are currently only available in intravenous form.

Transdermal delivery has several benefits over intravenous delivery to offer patients and optimize patient care, including:

  • Patient preference (non-invasive)

  • Ease of administration

  • Possible reduction in hospital length-of-stay

  • Potential for new indications

Bridging Oral Antiplatelet Drugs

Upstream treatment for Acute Coronary Syndromes (current AGGRASTAT indication)

Dual antiplatelet therapy (ASA & clopidogrel) is often prescribed to patients who receive coronary stent implantation for one year following the procedure. The antiplatelet effect of these oral agents is not reversible and, due to the resulting risk of bleeding, administration needs to be discontinued up to five days prior to surgery of any kind. During this five-day period, the patient is at an increased risk of having a cardiovascular event, including myocardial infarction (heart attack), because they are not protected by any antiplatelet medication.

In contrast to the non-reversible effect of oral agents, tirofiban's antiplatelet effect wears off very quickly and therefore can be used to provide antiplatelet protection to within as little as 4 hours prior to surgery. Transdermal tirofiban delivery could be desirable in this application as patients may not be required to remain in hospital awaiting their surgery, as they are required to for intravenous infusion of tirofiban. This treatment approach is often referred to as 'bridging therapy' and there are currently no antiplatelet agents on the market that are indicated or approved by the FDA for this use. An estimated 4-8% of patients need to undergo surgery within a year of coronary stent implantation.

Updated Indication

AGGRASTAT is indicated to reduce the rate of thrombotic cardiovascular events (combined endpoint of death, myocardial infarction, or refractory ischemia/repeat cardiac procedure) in patients with non-ST elevation acute coronary syndrome (NSTE-ACS).

Transdermal tirofiban (also referred to and trademarked as Aggraderm) is an experimental product and is not approved by the FDA.

Warnings and Precautions

  • AGGRASTAT can cause serious bleeding. If bleeding cannot be controlled discontinue AGGRASTAT.

  • Thrombocytopenia: Discontinue AGGRASTAT and heparin

Adverse Reactions

  • Bleeding is the most commonly reported adverse reaction