Indications: Treprostinil (Tyvaso®) is indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to improve exercise ability.
Mechanism: Treprostinil (Tyvaso®) is a prostacyclin analogue. The major pharmacologic actions of treprostinil are direct vasodilation of pulmonary and systemic arterial vascular beds and inhibition of platelet aggregation.
Dosing: Use only with the Tyvaso Inhalation System, undiluted, as supplied. A single inhalation delivers approximately 6 mcg of treprostinil. Administer in 4 separate treatment sessions each day, approximately four hours apart, during waking hours.
- Initial dosage: 3 breaths [18 mcg] per treatment session. If 3 breaths are not tolerated, reduce to 1 or 2 breaths.
- Dosage should be increased by an additional 3 breaths at approximately 1-2 week intervals, if tolerated.
- Titrate to target maintenance dosage of 9 breaths or 54 mcg per treatment session as tolerated.
Efficacy: TRIUMPH I, was a 12-week, randomized, double-blind, placebo-controlled multi-center study of patients with PAH. The study population included 235 clinically stable subjects with pulmonary arterial hypertension (WHO Group 1), nearly all with NYHA Class III (98%) symptoms who were receiving either bosentan (an endothelin receptor antagonist) or sildenafil (a phosphodiesterase-5 inhibitor) for at least three months prior to study initiation. These patients were administered either placebo or treprostinil (Tyvaso®) in four daily treatment sessions with a target dose of 9 breaths (54 mcg) per session over the course of the 12-week study.
The primary efficacy endpoint of the trial was the change in six-minute walk distance (6MWD) relative to baseline at 12 weeks. 6MWD was measured at peak exposure (between 10 and 60 minutes after dosing), and 3-5 hours after bosentan or 0.5-2 hours after sildenafil. Patients receiving treprostinil (Tyvaso®) had a placebo-corrected median change from baseline in peak 6MWD of 20 meters at Week 12 (p<0.001) (Figure
1). 6MWD measured at trough exposure (defined as measurement of 6MWD at least 4 hours after dosing)
improved by 14 meters.
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Adverse Events:
Most common adverse reactions (≥ 10%) include cough, headache, nausea, dizziness, flushing, throat irritation, pharyngolaryngeal pain and diarrhea.
Warnings:
- Safety and efficacy have not been established in patients with significant underlying lung disease (such as asthma or chronic obstructive pulmonary disease).
- In patients with low systemic arterial pressure, treprostinil (Tyvaso®) may cause symptomatic hypotension.
- Treprostinil (Tyvaso®) may increase the risk of bleeding, particularly in patients receiving anticoagulants.
- Treprostinil (Tyvaso®) dosage adjustments may be necessary if inhibitors or inducers of CYP2C8 are added or withdrawn.
- Hepatic or renal insufficiency may increase exposure and decrease tolerability.
Contraindications: none
Metabolism/Drug interactions: Treprostinil (Tyvaso®) is substantially metabolized by the liver, primarily by CYP2C8. Concomitant diuretics, antihypertensives or other vasodilators may increase the risk of systemic hypotension.
Access Program: Product only available through specialty pharmacy with an accompanying Rx and patient enrollment form.
Patient Enrollment form: http://www.remodulin.com/downloads/Franchisereferralforminteractive7-18-2011.pdf
Full US Prescribing Information can be found here: http://www.tyvaso.com/Content/docs/Tyvaso_PI_2013-04-30.pdf
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