CardioSource WorldNews - Page 4

Can’t wait to read the latest news in cardiology? Go online at ACC.org/CSWN! BRIEF SUMMARY The following is a brief summary of the full prescribing information for Orenitram® (treprostinil) ExtendedRelease Tablets. Please review the full prescribing information before prescribing Orenitram. INDICATIONS AND USAGE Orenitram is indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to improve exercise capacity. The study that established effectiveness included predominately patients with WHO functional class II-III symptoms and etiologies of idiopathic or heritable PAH (75%) or PAH associated with connective tissue disease (19%). When used as the sole vasodilator, the effect of Orenitram on exercise is about 10% of the deficit, and the effect, if any, on a background of another vasodilator is probably less than this. CONTRAINDICATIONS Severe hepatic impairment (Child Pugh Class C). WARNINGS AND PRECAUTIONS Worsening PAH Sympt mptoms upon Abrupt Withdrawal — Abrupt discontinuation or sudden large reductions in dosage of Orenitram may result in worsening of PAH symptoms. Risk of Blee Bleed ding—Orenitram ng inhibits platelet aggregation and increases the risk of bleeding. Use in Patients with Blind-end Pouches—The tablet shell does not dissolve. In patients with diverticulosis, Orenitram tablets can lodge in a diverticulum. ADVERSE REACTIONS Clinical Trials Experience—Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical Table 1. Adverse Reactions with Rates at Least 5% Higher on Orenitram Monotherapy than on Placebo Treatment (%) Reaction Orenitram (N=151) Placebo (N=77) Headache 63% 19% Diarrhea 30% 16% Nausea 30% 18% Flushing 15% 6% Pain in jaw 11% 4% Pain in extremity 14% 8% Hypokalemia 9% 3% Abdominal discomfort 6% 0% The safety of Orenitram was also evaluated in an open-label study transitioning patients from Remodulin. The safety profile during this study was similar to that observed in the three pivotal studies. DRUG INTERACTIONS Antihypertensive Agents or Other Vasodilator— Vasodilator Concomitant administration of Orenitram with diuretics, antihypertensive agents or other vasodilators increases the risk of symptomatic hypotension. Anticoagulants Anticoagulants—Treprostinil inhibits platelet aggregation; there is increased risk of bleeding, particularly among patients receiving anticoagulants. —Co-administration of Orenitram and the CYP2C8 enzyme inhibitor exposure to treprostinil. Reduce the starting dose of Orenitram to 0.125 mg BID and use 0.125 mg BID increments every 3 to 4 days. Effect of Other Drugs on Orenitram—Based Orenitram on human pharmacokinetic studies, no dose adjustment of Orenitram is recommended when coadministered or esomeprazole. observed in clinical practice. In a 12-week placebocontrolled monotherapy study (Study 1; WHO Group 1; functional class II-III), the most commonly reported adverse reactions that occurred in patients receiving Orenitram included: headache, diarrhea, nausea and flushing. Table 1 lists the adverse reactions that occurred at a rate on Orenitram at least 5% higher than on placebo. Orenitram patients in Table 1 for Study 1 (N = 151) had access to 0.25 mg tablets at randomization. Approximately 91% of such patients experienced an adverse reaction, but only 4% discontinued therapy for an adverse reaction (compared to 3% receiving placebo). The overall discontinuation rate for any reason was 17% for active and 14% for placebo. Orenitram was studied in a long-term, open-label extension study in which 824 patients were dosed for a mean duration of approximately 2 years. About 70% of patients continued treatment with Orenitram for at least a year. The mean dose was 4.2 mg BID at one year. The adverse reactions were similar to those observed in the placebo-controlled trials. Warfarin—A drug interaction study was carried out with Remodulin co-administered with warfarin (25 mg/day) in healthy volunteers. There was no the pharmacokinetics of treprostinil. Additionally, or pharmacodynamics of warfarin. The pharmacokinetics of R- and S- warfarin and the international normalized ratio (INR) in healthy subjects given a single 25 mg dose of warfarin were treprostinil at an infusion rate of 10 ng/kg/min. delivery were seen in animal studies. Nursing Mothers—It Mothers is not known whether treprostinil is excreted in human milk or absorbed systemically after ingestion. Because many drugs are excreted in human milk, choose Orenitram or breastfeeding. Pediatric Use patients have not been established. Geriatric Use—Clinical studies of Orenitram did years and over to determine whether they respond selection for an elderly patient should be cautious, hepatic or cardiac function, and of concomitant disease or other drug therapy. Patients with Hepatic Impairment—Plasma Impairment clearance of treprostinil is reduced in patients with hepatic therefore be at increased risk of dose-dependent adverse reactions because of an increase in systemic exposure. Titrate slowly in patients with hepatic exposed to greater systemic concentrations relativ