CDSCO Panel rejects Lupin FDC of Tranexamic Acid and Mefenamic Acid

This came in accordance with Lupin's proposal, which included a bioequivalence study protocol and a waiver request for a Phase III clinical trial (CT) study.

Tranexamic Acid is an anti-fibrinolytic. It works by preventing the breakdown of blood clots to control excessive bleeding during periods. Tranexamic acid is a synthetic derivative of lysine that exerts antifibrinolytic effects by blocking lysine binding sites on plasminogen molecules, inhibiting the interaction of plasminogen with formed plasmin and fibrin.

Tranexamic acid competitively and reversibly inhibits the activation of plasminogen via binding at several distinct sites, including four or five low-affinity sites and one high-affinity site, the latter of which is involved in its binding to fibrin. The binding of plasminogen to fibrin induces fibrinolysis - by occupying the necessary binding sites tranexamic acid prevents this dissolution of fibrin, thereby stabilizing the clot and preventing hemorrhage.

Mefenamic Acid is a non-steroidal anti-inflammatory drug (NSAID) which blocks the production of certain chemical messengers (prostaglandins) that cause pain and inflammation (redness and swelling). In animal studies, meclofenamic acid was found to inhibit prostaglandin synthesis and to compete for binding at the prostaglandin receptor site. In vitro meclofenamic acid was found to be an inhibitor of human leukocyte 5-lipoxygenase activity. These properties may be responsible for the anti-inflammatory action of meclofenamic acid. There is no evidence that meclofenamic acid alters the course of the underlying disease.

At the recent SEC meeting for Analgesics and Rheumatology held on 23.06.2022, the expert panel reviewed the proposal to conduct Phase III clinical trial of fixed-dose combination of Tranexamic Acid plus Mefenamic acid in detail.

After detailed deliberation, the committee opined that

1. Mefenamic Acid 375mg ER is not approved internationally.

2. Firm did not present any rational, published literature from peer reviewed journal for the FDC in proposed doses.

Finally, based on the protocol presented by Lupin the expert panel did not recommend the FDC Tranexamic Acid and Mefenamic Acid.