Tranexamic acid formulations with reduced adverse effects

Abstract

Tranexamic acid formulated in an oral dosage form with at least one agent that decreases tranexamic acid release in the stomach. Such formulations minimize nausea, vomiting, and other adverse gastric effects that may accompany tranexamic acid therapy, for example, to treat heavy menstrual bleeding. One embodiment is an extended release formulation with waxes, polymers, etc. that prevent a bolus release of tranexamic acid in the stomach. An alternative embodiment is a delayed release formulation with polymers that prevent release of tranexamic acid in the acid environment of the stomach and delay its release until the formulation reaches the less acid environment of the intestines. Such formulations enhance patient compliance with therapy because adverse effects of tranexamic acid therapy are reduced.

Description

FIELD OF THE INVENTION [0001] The invention is directed to therapeutic oral tranexamic acid formulations that minimize or eliminate undesirable side effects. BACKGROUND [0002] Tranexamic acid (trans-4-(aminomethyl) cyclohexanecarboxylic acid, Cyklokapron® (Pfizer) is an antifibrinolytic agent. That is, it helps to prevent lysis or dissolution of a fibrin clot which forms in the normal physiologic process of hemostasis. Its mechanism of action is as a competitive inhibitor of plasminogen activation, and as a noncompetitive inhibitor of plasmin; both plasminogen and plasmin are activators of fibrinolyis and active clot-lysing agents. Tranexamic acid thus helps to stabilize fibrin clots, which in turn maintains coagulation and helps to control bleeding. [0003] Tranexamic acid is used to control excess bleeding, for example, excess bleeding that occurs during dental procedures in hemophiliacs and for heavy bleeding during menstruation (menorrhagia). Women suffering from menorrhagia are ...

AI Technical Summary

Benefits of technology

[0004] Formulations of tranexamic acid which minimize or eliminate the undesirable gastrointestinal side effects in patients on oral tranexamic acid therapy, e.g. women treated for menorrhagia (heavy menstrual bleeding), by modifying the release characteristics of tranexamic acid are disclosed. One embodiment is an extended release formulation, also termed a controlled release formulation, formulated so that the release of tranexamic acid from the dosage form occurs in an extended or controlled fashion to prevent a bolus of tranexamic acid being introduced into the stomach and available for dissolution in the gastric contents. An alternative embodiment is a delayed release formulation. Delayed release dosage forms are formulated to minimize or prevent the dissolution of the drug in the stomach. The release of tranexamic acid is delayed until the dosage form exits the stomach and reaches the small intestine. Both extended release dosage forms and delayed release dosage forms are termed modified release dosage forms. Such modified release formulations reduce the concentration of tranexamic acid dissolved in the stomach contents. The beneficial effect of this reduced tranexamic acid concentration is to lower the amount of tranexamic acid in the gastric contents so that there are fewer gastric adverse effects with tranexamic acid therapy. This reduction in gastric adverse effects results in improved patient compliance with therapy, because patients will not intentionally miss taking a dose to avoid these adverse side effects. Physicians will also be more likely to initiate and maintain tranexamic acid treatment for their patients because of the reduced patient complaints.

Problems solved by technology

However, this treatment may cause adverse gastrointestinal reactions, including nausea, vomiting, diarrhea, and cramping, etc.

These gastrointestinal side effects are due to the quantity of tranexamic acid introduced into the stomach with each dose, as well as the large quantity of excipients used in tablet formulation that are introduced into the stomach.

Such side effects, in addition to the cramping, bloating, pain, and other symptoms that may accompany menses, are undesirable, and a formulation of tranexamic acid is needed which will reduce or eliminate these side effects.