Drug Guide
Treprostinil
Classification
Therapeutic: Pulmonary hypertension agent
Pharmacological: Prostacyclin analogue and vasodilator
FDA Approved Indications
- Pulmonary arterial hypertension (PAH) to improve exercise capacity and delay disease progression
Mechanism of Action
Treprostinil is a prostacyclin analogue that induces vasodilation by activating prostacyclin receptors, leading to increased cyclic AMP in vascular smooth muscle cells, resulting in vasodilation and inhibition of platelet aggregation.
Dosage and Administration
Adult: Dose individualized based on response, starting typically at 1.25 ng/kg/min via continuous IV infusion (Remodulin); inhaled doses vary, titrated to clinical response (Tyvaso); inhalation dosing for Tyvaso Dpi is usually 3 breaths (54 mcg) four times daily, titrated as tolerated.
Pediatric: Use is not well established; dosing is individualized based on clinical response and tolerability.
Geriatric: Use with caution; dose adjustments may be necessary based on renal and hepatic function.
Renal Impairment: No specific adjustments indicated; monitor closely.
Hepatic Impairment: Use with caution; consider dose adjustments.
Pharmacokinetics
Absorption: Inhaled treprostinil is absorbed through the pulmonary epithelium; intravenous infusion provides 100% bioavailability.
Distribution: Widely distributed; volume of distribution approximately 0.7 L/kg.
Metabolism: Primarily hepatic via CYP2C8, CYP2C9, and glucuronidation pathways.
Excretion: Metabolites primarily excreted via urine; small amount excreted unchanged.
Half Life: Approximately 4.5 hours.
Contraindications
- Hypersensitivity to treprostinil or excipients.
Precautions
- Use with caution in patients at risk of bleeding, with liver impairment, or hypotension.
- Closely monitor for infusion site infections or complications (for IV use).
- Inhaled treprostinil should be used cautiously in patients with airway disease.
Adverse Reactions - Common
- Headache (Common)
- Flushing (Common)
- Jaw pain (Common)
- Nausea (Common)
- Hypotension (Common)
Adverse Reactions - Serious
- Hypotension causing syncope (Serious)
- Sepsis or infusion site infection (Remodulin) (Serious)
- Bleeding (Serious)
Drug-Drug Interactions
- Other vasodilators may have additive hypotensive effects.
- CYP2C8 inhibitors (e.g., gemfibrozil) may increase treprostinil levels.
Drug-Food Interactions
- No well-established food interactions.
Drug-Herb Interactions
- Limited data; caution with herbs affecting bleeding or blood pressure.
Nursing Implications
Assessment: Monitor blood pressure, infusion site, and patient response to therapy.
Diagnoses:
- Risk for bleeding
- Risk for hypotension
- Impaired tissue integrity at infusion site
Implementation: Administer as prescribed; monitor for adverse effects; ensure proper infusion site care.
Evaluation: Assess for improved exercise tolerance and symptom relief; monitor for adverse reactions.
Patient/Family Teaching
- Take medications exactly as prescribed.
- Report signs of bleeding, severe headache, or hypotension.
- For inhaled forms, use inhaler correctly and store properly.
- Avoid abrupt discontinuation; consult provider before stopping therapy.
Special Considerations
Black Box Warnings:
- Risk of sudden decrease in blood pressure and infusion site infections with IV form.
Genetic Factors: No specific genetic markers influencing response identified.
Lab Test Interference: No significant interference with routine labs.
Overdose Management
Signs/Symptoms: Severe hypotension, dizziness, flushing, syncope.
Treatment: Supportive care; discontinue treprostinil; provide IV fluids; vasopressors if needed.
Storage and Handling
Storage: Store in a refrigerator at 2°C to 8°C (36°F to 46°F). Protect from light.
Stability: Stable for specified period as per manufacturer; consult packaging.