Transitioning from Remodulin to Orenitram
Estimate a comparable total daily dose of Orenitram using the equation below
Determine the transition plan
Decrease Remodulin dose while simultaneously increasing Orenitram dose*
Continue to titrate Orenitram as needed while monitoring for tolerability
- The dose of Remodulin can be reduced up to 30 ng/kg/min/day and the dose of Orenitram simultaneously increased up to 6 mg/day (2 mg TID), if tolerated.1
When transitioning stable patients from Remodulin (parenteral treprostinil) to Orenitram (oral treprostinil), the following equation can be used to estimate a comparable total daily dose of Orenitram:Orenitram total daily dose (mg) = 0.0072 x Remodulin daily dose (ng/kg/min) x weight (kg)1
Transition Study: Remodulin (treprostinil) injection to oral Orenitram (treprostinil)
In a multicenter, open-label, noncontrolled transition study:Orenitram showed no clinically significant changes in 6MWD or hemodynamics at week 241,2
Study design: A 24-week, multicenter, open-label, inpatient study enrolled 33 WHO Group 1 patients on stable doses of IV/SC treprostinil as well as background therapy with a PDE-5i and/or ERA. Patients were WHO FC I or II and hemodynamically stable at baseline, with a cardiac index >2.2 L/m2, RAP <11 mm Hg, and PVR <10 Wood units. The primary endpoint of the study was the safety and tolerability of the transition.1
- Successful transition was defined as a patient no longer taking Remodulin at week 4 and maintaining Orenitram treatment at week 24 with consistent 6MWD and hemodynamics1
Without a control group, data from this long-term study must be interpreted cautiously
- In the TID patient cohort (n=23), the median Orenitram total daily dose at week 24 was 43.9 mg (15.8 to 75.0)* compared with a median Remodulin dose prior to transition of 60 ng/kg/min (27 to 111)2
- Adverse events were similar to those observed in the placebo-controlled trials2
- Data for Orenitram TID cohort excludes data from 1 patient who discontinued the study prior to week 24.2
Important Safety Information
- 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.
- 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.
- Co-administration of Orenitram and the CYP2C8 enzyme inhibitor gemfibrozil increases exposure to treprostinil; therefore, Orenitram dosage reduction may be necessary in these patients.
- 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.
Orenitram is a prostacyclin mimetic indicated for treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to delay disease progression and to improve exercise capacity. The studies that established effectiveness included predominately patients with WHO functional class II-III symptoms and etiologies of idiopathic or heritable PAH (66%) or PAH associated with connective tissue disease (26%).
6MWD=6-minute walk distance; ERA=endothelin receptor antagonist; FC=functional class; IV=intravenous; PDE-5i=phosphodiesterase type 5 inhibitor; PVR=pulmonary vascular resistance; RAP=right atrial pressure; SC=subcutaneous; TID=3 times daily; WHO=World Health Organization.
References: 1. Orenitram [package insert]. Research Triangle Park, NC: United Therapeutics Corporation; 2019. 2. Chakinala MM, Feldman JP, Rischard F, et al. Transition from parenteral to oral treprostinil in pulmonary arterial hypertension. J Heart Lung Transplant. 2017;36:193-201.