TYVASO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TYVASO (TYVASO).
Treprostinil is a prostacyclin analogue that directly vasodilates pulmonary and systemic arterial beds and inhibits platelet aggregation. It binds to IP receptors, increasing cAMP in smooth muscle cells, leading to vasodilation.
| Metabolism | Treprostinil is extensively metabolized in the liver via oxidation (CYP2C8 major, CYP2C9 minor) and glucuronidation. Five metabolites are formed, with minimal activity. |
| Excretion | Treprostinil is primarily eliminated via hepatic metabolism; urinary excretion of unchanged drug is negligible (approximately 4%). Biliary/fecal excretion accounts for the majority of elimination (around 70% as metabolites). |
| Half-life | The terminal elimination half-life of treprostinil (Tyvaso) is approximately 4 hours following inhalation and 4.5 hours after subcutaneous administration. This half-life supports a four-times-daily dosing regimen for the inhaled formulation to maintain therapeutic plasma concentrations. |
| Protein binding | Treprostinil is highly protein bound, approximately 91% bound to human plasma proteins, primarily albumin. |
| Volume of Distribution | The volume of distribution (Vd) of treprostinil is approximately 14 L/kg, indicating extensive distribution into tissues beyond the plasma compartment. |
| Bioavailability | Inhaled treprostinil has an absolute bioavailability of approximately 64% relative to subcutaneous administration. For the subcutaneous route, bioavailability is considered complete (100%) as it is administered parenterally. |
| Onset of Action | Following oral inhalation, the onset of clinical effect (improvement in exercise capacity and hemodynamics) is typically observed within 30 to 60 minutes after administration. |
| Duration of Action | The duration of clinical effect after a single inhaled dose is approximately 3 to 4 hours, necessitating dosing four times daily (every 4 hours during waking hours) to maintain efficacy. |
Inhalation solution: 0.6 mg/mL, 1.74 mg/2.9 mL via the Tyvaso Inhalation System. Administer 3 breaths (approximately 72 mcg per breath) per treatment session, 4 times daily, with at least 4 hours between doses. May increase to 9 breaths per session if tolerated. Maximum dose: 9 breaths (approximately 216 mcg) 4 times daily.
| Dosage form | SOLUTION |
| Renal impairment | No dose adjustment required for renal impairment. Not studied in patients on dialysis. |
| Liver impairment | Mild hepatic impairment (Child-Pugh A): No dose adjustment. Moderate to severe impairment (Child-Pugh B or C): Not studied; use caution and consider dose reduction if needed. |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment recommended; elderly patients may have greater sensitivity and should be titrated slowly. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TYVASO (TYVASO).
| Breastfeeding | It is not known whether treprostinil is excreted in human milk. In animal studies, treprostinil was excreted in the milk of lactating rats. The M/P ratio is unknown. Due to the potential for serious adverse reactions in nursing infants from treprostinil, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. |
| Teratogenic Risk | Tyvaso (treprostinil) is a prostacyclin analog. There are no adequate and well-controlled studies in pregnant women. In animal studies, treprostinil administered during organogenesis resulted in increased post-implantation loss and decreased fetal viability at doses ≥ 30 times the recommended human dose. Based on animal data, there is potential risk of developmental toxicity, including malformations and fetal death. In humans, the drug should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Known hypersensitivity to treprostinil or any excipients.","Patients with hepatic impairment (Child-Pugh Class C) should not receive oral treprostinil."]
| Precautions | ["Risk of hypotension: monitor blood pressure, especially in patients with low systemic arterial pressure.","Abrupt discontinuation may lead to worsening pulmonary hypertension symptoms.","Use with caution in patients with hepatic impairment due to reduced clearance.","May increase bleeding risk, especially in patients with risk factors for hemorrhage.","Infusion site reactions (pain, erythema, induration) are common with subcutaneous infusion."] |
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| Fetal Monitoring | Monitor maternal blood pressure and heart rate for hypotension and tachycardia. Monitor for signs of fluid overload or edema. Fetal monitoring includes regular ultrasound to assess fetal growth and amniotic fluid volume, as well as fetal heart rate monitoring, especially if signs of placental insufficiency develop. Additionally, monitor for signs of bleeding, as treprostinil inhibits platelet aggregation. In late pregnancy, assess for preterm labor and placental abruption. |
| Fertility Effects | In animal studies, treprostinil did not affect male or female fertility at doses up to 32 times the human dose. However, based on its vasodilatory and antiplatelet effects, there is a theoretical risk of altered uterine blood flow or implantation. Human data are lacking. Use with caution in women of reproductive potential. |