Orenitram is an oral formulation of Treprostinil, a potent vasodilator used to treat patients with Pulmonary Arterial Hypertension to improve exercise ability and delay clinical worsening. Treprostinil is chemically known as (1R,2R,3aS,9aS)-[[2,3,3a,4,9,9a-hexahydro-2-hydroxy-1-[(3S)-3-hydroxyoctyl]-1H-benz[f]inden-5-yl] oxy]acetic acid) and is a synthetic form of the lipid molecule prostacyclin (also called prostaglandin, denoted as PGI2), belonging to the class of eicosanoids. This formulation, manufactured by United Therapeutics, was approved by the US FDA in December 2013, making it the first oral formulation of prostacyclin to be approved for use in any form of disease.
How Orenitram Works
Being a potent prostacyclin analogue, treprostinil is involved in vasodilation of pulmonary and systemic arterial vascular beds and inhibition of platelet aggregation and clotting. It does so by increasing the amount of cyclic adenosine monophosphate (cAMP), which in turn balances the excess amount of calcium released in the cytosol. When balanced, the calcium ions ensure dephosphorylation of enzymes which are crucial to muscle contraction. This leads to smooth muscle relaxation and vasodilation.
The FDA approval for Orenitram came shortly after results from the successful primary efficacy study with Orenitram titled FREEDOM-M were released. These showed that orenitram, when compared against a placebo, showed considerable improvements in the 6-min walk distance (6MWD) of as much as 23 metres, on being administered twice daily among patients. Though the effect of the drug in this trial was small, as it was the sole vasodilator used, yet, the safety and tolerability studies showed that it was well-tolerated among adults (though no concrete data has been presented for children below 16 years of age).
The most common side effects for Orenitram included headache, nausea, irritation and diarrhea. The tablets are to be taken twice daily along with food, but the total dosage might be divided into three times daily as well. Mostly available in four strengths of 0.125 mg, 0.25 mg, 1 mg and 2.5 mg, the doses should be adjusted according to the patient’s tolerance, by increasing by factors of 0.25 or 0.5 mg twice daily, for every 3 to 4 days. After the initial dose of 0.25 mg every 12 hours with food, the mean dose should be increased to 3.5 mg orally every 12 hours with food. Patients with liver or kidney diseases or those planning to conceive a child or are pregnant, should undergo expert consultation before taking the drug.
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