TYVASO DPI
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TYVASO DPI (TYVASO DPI).
Treprostinil is a prostacyclin analog that directly causes vasodilation of pulmonary and systemic arterial vascular beds, inhibits platelet aggregation, and suppresses smooth muscle proliferation.
| Metabolism | Primarily hepatic metabolism via CYP2C8 and CYP2C19 to inactive metabolites; also undergoes spontaneous hydrolysis. |
| Excretion | Renal: 6-9% as unchanged treprostinil; biliary/fecal: ~70% as metabolites; total clearance: 20-40 L/h. |
| Half-life | Terminal half-life: 1.4-2.0 hours; clinical context: supports continuous dosing for sustained pulmonary arterial hypertension effect. |
| Protein binding | 91-93% bound, primarily to albumin. |
| Volume of Distribution | Approximately 1.2 L/kg (range 0.6-1.8 L/kg); clinical meaning: moderate distribution indicating tissue binding. |
| Bioavailability | Inhalation: ~70% (relative to IV); oral: ≤10% (negligible for inhaled route). |
| Onset of Action | Inhalation: 15-30 minutes (based on hemodynamic response). |
| Duration of Action | Approximately 3-6 hours; clinical notes: dosing requires 3-4 times daily due to short effect. |
Inhalation powder: 16 mcg (1 capsule) via Tyvaso DPI inhaler four times daily (QID) with approximately 4-hour intervals during waking hours. Titrate as tolerated to target dose of 64 mcg (4 capsules) QID.
| Dosage form | POWDER |
| Renal impairment | No dose adjustment required for renal impairment. Pharmacokinetics not significantly altered; specific GFR thresholds not established. |
| Liver impairment | Child-Pugh Class A, B, C: No dose adjustment recommended. Exposure may increase, but clinical significance unknown; monitor for adverse effects. |
| Pediatric use | Safety and efficacy not established in pediatric patients (<18 years). No dosing recommendations available. |
| Geriatric use | No specific dose adjustment recommended. Limited data in patients ≥65 years; no geriatric-specific differences in safety or efficacy identified. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TYVASO DPI (TYVASO DPI).
| Breastfeeding | No data on presence in human milk, effect on breastfed infant, or milk production. M/P ratio unknown. Caution recommended due to potential for vasodilation and hypotension in the infant. Generally avoid breastfeeding during therapy. |
| Teratogenic Risk | Pregnancy Category B (pre-2015). No adequate and well-controlled studies in pregnant women. In animal studies, inhaled treprostinil at up to 73 times the human exposure (based on AUC) resulted in no fetal harm. However, due to potential for uterine relaxation and hypotension, use only if clearly needed. Risk in first trimester is theoretical; second and third trimesters may have increased risk of preterm labor and fetal distress from maternal hypotension. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
["Hypersensitivity to treprostinil or any excipient in the formulation","Concomitant use with strong CYP2C8 inhibitors or inducers without dose adjustment","Active bleeding disorders (relative contraindication due to antiplatelet effects)"]
| Precautions | ["Risk of hypotension: Monitor blood pressure; dose reduction if symptomatic hypotension occurs.","Use in patients with hepatic impairment: Dose adjustment required in moderate to severe impairment.","Use in patients with renal impairment: No significant dose adjustment needed, but monitor for fluid retention.","Withdrawal syndrome: Abrupt discontinuation may cause rebound worsening of PAH symptoms.","Potential for bleeding: Treprostinil inhibits platelet aggregation; use caution in patients with bleeding risk or on anticoagulants."] |
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| Fetal Monitoring | Monitor maternal vital signs, especially blood pressure and heart rate, for hypotension and syncope. Fetal monitoring (nonstress test, biophysical profile) may be considered in third trimester. Assess for signs of pulmonary hypertension exacerbation. |
| Fertility Effects | No human data on fertility effects. In animal studies, no impairment of fertility observed in male or female rats at inhaled treprostinil doses up to 900 mcg/kg/day (approximately 73 times human exposure). |