Treprostinil

Brand Names: Sterile Diluent For Treprostinil

Drug Class: Prostacycline Vasodilator

Overview

11 DESCRIPTION Treprostinil Injection is a sterile solution of treprostinil formulated for subcutaneous or intravenous administration. Treprostinil injection is supplied in 20 mL multidose vials in four strengths, containing 20 mg, 50 mg, 100 mg, or 200 mg (1 mg/mL, 2.5 mg/mL, 5 mg/mL or 10 mg/mL) of treprostinil. Each mL also contains 5.

Mechanism of Action

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action The major pharmacologic actions of treprostinil are direct vasodilation of pulmonary and systemic arterial vascular beds, and inhibition of platelet aggregation. 12.2 Pharmacodynamics In animals, the vasodilatory effects reduce right and left ventricular afterload and increase cardiac output and stroke volume. Other studies have shown that treprostinil causes a dose-related negative inotropic and lusitropic effect. No major effects on cardiac conduction have been observed. Treprostinil produces vasodilation and tachycardia. Single doses of treprostinil up to 84 mcg by inhalation produce modest and short-lasting effects on QTc, but this is apt to be an artifact of the rapidly changing heart rate.

Indications

  • 1 INDICATIONS AND USAGE Treprostinil injection is a prostacyclin vasodilator indicated for: Treatment of pulmonary arterial hypertension (PAH; WHO Group 1) to diminish symptoms associated with exercise. Studies establishing effectiveness included patients with NYHA Functional Class II-IV symptoms and etiologies of idiopathic or heritable PAH (58%), PAH associated with congenital systemic-to-pulmonary shunts (23%), or PAH associated with connective tissue diseases (19%). ( 1.1 ) Patients who require transition from epoprostenol, to reduce the rate of clinical deterioration.

Common Doses

  • 0.004 mg
  • 0.000001 mg
  • 0.002 mL

Dosage

2 DOSAGE AND ADMINISTRATION PAH WHO Group 1 in patients with NYHA Class II-IV symptoms : Initial dose for patients new to prostacyclin infusion therapy: 1.25 ng/kg/min; increase based on clinical response (increments of 1.25 ng/kg/min per week for the first 4 weeks of treatment, later 2.5 ng/kg/min per week). Avoid abrupt cessation. ( 2.2 , 2.4 ) Mild to moderate hepatic insufficiency: Decrease initial dose to 0.625 ng/kg/min. Severe hepatic insufficiency: No studies performed. ( 2.

Contraindications

  • 4 CONTRAINDICATIONS None None

Side Effects

  • 6 ADVERSE REACTIONS The following adverse reactions are discussed elsewhere in labeling: Infections associated with intravenous administration [see Warnings and Precautions (5.1) ] . Most common adverse reactions (incidence >3%) reported in clinical studies with treprostinil injection: subcutaneous infusion site pain and reaction, headache, diarrhea, nausea, jaw pain, vasodilatation, edema, and hypotension. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Dr. Reddy’s Laboratories Inc., at 1-888-375-3784 or contact FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.

Interactions

  • 7 DRUG INTERACTIONS Treprostinil injection dosage adjustment may be necessary if inhibitors or inducers of CYP2C8 are added or withdrawn. ( 7.1 ) 7.1 Effect of CYP2C8 Inhibitors and Inducers on Treprostinil Dose adjustment of treprostinil may be necessary when co-administered with CYP2C8 inducers or inhibitors. Human pharmacokinetic studies with an oral formulation of treprostinil (treprostinil diolamine) indicated that co-administration of the cytochrome P450 (CYP) 2C8 enzyme inhibitor gemfibrozil increases exposure (both C max and AUC) to treprostinil.