TreprostinilRx

Trade Names: Remodulin (injection); Tyvaso (inhalation); Orenitram (oral)

Synonyms: Prostacyclin, PGI2

Drug Class: Prostaglandin

Preparations:
Injection: 1-, 2.5-, 5-, 10 mg/ml
Inhalation: 0.6 mg/ml with Tyvaso inhalation system
Oral: 0.125-, 0.25-, 1-, 2.5 mg tablets

Dose: Injection (subcutaneous or IV infusion): 1.25 ng/kg/minute initially and titrated slowly in small increments at approximately weekly intervals. Administered by a pump as a continuous subcutaneous injection or intravenous infusion through a central line.
Inhalation: 3 breaths (18 mcg) per treatment session, administer in 4 separate sessions approximately 4 hours apart during waking hours. Dose is titrated according to adverse effects and response.
Oral: Initially 0.25 mg every 12 hours; dose is titrated according to adverse effects and response.

Indications: Pulmonary arterial hypertension

Mechanism of Action: Is a synthetic analog of prostacyclin, a potent vasodilator that also decreases platelet aggregation.

Contraindications: Hypersensitivity

Precautions: Sudden discontinuation of drug can cause rebound pulmonary hypertension. Initiation and maintenance requires specialized cardiopulmonary monitoring and expertise. Increased risk of bleeding. May prolong QT interval.

Monitoring: Monitor closely for clinical response, adverse effects, pump dysfunction and adherence to therapy.

Pregnancy Risk: C

Adverse Effects
Common: Injections  site reactions (subQ route), flushing, tachycardia, GI side effects (nausea, vomiting, diarrhea, cramps), dizziness, headache, jaw pain, tremor
Less common: Hypotension, syncope, angina, edema, rash, anemia, central line infection (IV infusion route)

Drug Interactions:
Vasodilators or antihypertensive drugs: Treprostinil may potentiate hypotensive effects
Gemfibrozil and other cytochrome P450  2C8 (CYP2C8) inhibitors: Increased treprostinil concentrations

Patient Instructions: IV and subQ therapy requires wearing a pump, and self-administration of drug. Dose titration is required. Do not discontinue the drug suddenly.

Comments: Treprostinil is only prescribed by physicians expert in the management of pulmonary hypertension, generally cardiologists or pulmonologists with a special interest in pulmonary hypertension.

Clinical Pharmacology: Hepatic metabolism in part by CYP2C8, half-life 4 hours. Oral bioavailability of tablet is 17% with maximum concentrations 4-6 h after administration.

Cost: $$$$$

BIBLIOGRAPHY

Skoro-Sajer N. Optimal use of treprostinil in pulmonary arterial hypertension:a guide to the correct use of different formulations. Drugs 2012;72:2351-63. PMID:23231023.