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. |
| Molecular Weight | 506.6 |
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 | Insufficient human data; animal studies show fetal harm at high doses. Use only if benefit outweighs risk. |
| 2nd trimester | Insufficient human data; potential for fetal harm based on animal studies. Consider alternative therapy. |
| 3rd trimester | Insufficient human data; potential for fetal harm. May cause uterine relaxation and affect labor. Use only if clearly needed. |
Clinical note
Comprehensive clinical and safety monograph for TYVASO DPI (TYVASO DPI).
| Placental transfer | Treprostinil crosses the placenta in rats; significant placental transfer is expected based on molecular weight and lipophilicity. |
| Breastfeeding | No human data on excretion in breast milk; based on molecular weight and protein binding, excretion is likely minimal but unknown. Use with caution in nursing mothers. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
History of hypersensitivity to treprostinil or any excipients
| 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. |
| Food/Dietary | No specific food interactions have been reported for treprostinil. However, grapefruit juice may theoretically affect drug metabolism via CYP2C8 inhibition, though data are lacking; caution is advised. |
Loading safety data…
| Lactation Rating |
| L3 (Moderately Safe) |
| 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. |
| 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). |
| Clinical Pearls | Tyvaso DPI (treprostinil) is a prostacyclin analogue for pulmonary arterial hypertension (PAH). Unlike continuous subcutaneous or intravenous treprostinil, the dry powder inhaler offers a more convenient inhaled route, but requires proper inhaler technique to ensure dose delivery. Monitor for common side effects such as cough, headache, and throat irritation. Abrupt discontinuation may worsen PAH. Dose titration is necessary to achieve optimal effect. Avoid use in patients with a known hypersensitivity to treprostinil or sulfobutylether beta-cyclodextrin. |
| Patient Advice | Use the Tyvaso DPI inhaler exactly as prescribed; do not increase or skip doses without consulting your doctor. · Clean the inhaler regularly according to the instructions to prevent clogging or infection. · Report any new or worsening symptoms such as chest pain, shortness of breath, or bleeding (hemoptysis) immediately. · Do not stop treatment suddenly, as this could cause a sudden worsening of your condition. · Store the inhaler cartridges at room temperature away from moisture and heat. |