Orenitram -Extended-Release Tablets

CONTRAINDICATIONS

• Avoid use of Orenitram in patients with severe hepatic impairment (Child Pugh Class C) due to increases in systemic exposure.

WARNINGS AND PRECAUTIONS

• Abrupt discontinuation or sudden large reductions in dosage of Orenitram may result in worsening of PAH symptoms.
• The Orenitram tablet shell does not dissolve. In patients with diverticulosis, Orenitram tablets can lodge in a diverticulum.

ADVERSE REACTIONS

• In the 12-week, placebo-controlled, monotherapy study, and an event-driven, placebo-controlled, combination therapy study, adverse reactions that occurred at rates at least 5% higher on Orenitram than on placebo included headache, diarrhea, nausea, vomiting, flushing, pain in jaw, pain in extremity, hypokalemia, abdominal discomfort, and upper abdominal pain.

DRUG INTERACTIONS

• Co-administration of Orenitram and the CYP2C8 enzyme inhibitor gemfibrozil increases exposure to treprostinil; therefore, Orenitram dosage reduction may be necessary in these patients.

SPECIFIC POPULATIONS

• Animal reproductive studies with Orenitram have shown an adverse effect on the fetus. There are no adequate and well-controlled studies with Orenitram in pregnant women.
• It is not known whether treprostinil is excreted in human milk or if it affects the breastfed infant or milk production.
• Safety and effectiveness of Orenitram in pediatric patients have not been established.
• Use of Orenitram in patients aged 65 years and over demonstrated slightly higher absolute and relative adverse event rates compared to younger patients. Caution should be used when selecting a dose for geriatric patients.
• There is a marked increase in the systemic exposure to treprostinil in hepatically impaired patients.