treprostinil

Contraindicated in:

Known hypersensitivity;
Moderate or severe hepatic impairment (PO only).

Use Cautiously in:

Renal impairment;
Hepatic impairment (dose ↓ recommended in mild to moderate hepatic impairment [for parenteral] and mild hepatic impairment [PO]);
Pulmonary disease (inhalation only);
Diverticulosis (PO only) (tablet shell does not dissolve);
OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
Lactation: Safety not established in breastfeeding;
Pedi: Safety and effectiveness not established in children ≤16 yr (parenteral) or children <18 yr (inhalation and PO).

Adv. Reactions/Side Effects ⬆ ⬇

CV: edema, hypotension

Derm: rash, pruritus, flushing

F and E: hypokalemia

GI: diarrhea, nausea

Hemat: bleeding

Local: infusion site pain/reaction

MS: jaw pain

Neuro: headache, dizziness

Resp: cough (inhalation only), bronchospasm (inhalation only), dyspnea (inhalation only)

Interactions ⬆ ⬇

Drug-drug:

↑risk of hypotension with antihypertensives, diuretics, or vasodilators.
Effects may be ↑ by CYP2C8 inhibitors, including gemfibrozil.
Effects may be ↓ by CYP2C8 inducers, includingrifampin.
Risk of bleeding may be ↑ by concurrent use of anticoagulants.

Availability ⬆ ⬇

(Generic available)

Extended-release tablets (Orenitram): 0.125 mg; 0.25 mg; 1 mg; 2.5 mg; 5 mg
Solution for injection (Remodulin): 1 mg/mL; 2.5 mg/mL; 5 mg/mL; 10 mg/mL
Solution for oral inhalation (Tyvaso): 0.6 mg/mL
Dry powder for inhalation (Tyvaso DPI): 16 mcg/cartridge; 32 mcg/cartridge; 48 mcg/cartridge; 64 mcg/cartridge

Route/Dosage ⬆ ⬇

SC IV (Adults ): Naive to prostacyclin therapy: 1.25 ng/kg/min; may ↓ to 0.625 ng/kg/min if intolerance occurs. Increments of no more than 1.25 ng/kg/min may be made weekly for the first 4 wk and then no more than 2.5 ng/kg/min weekly for the remainder of therapy. Avoid abrupt discontinuation or rapid ↓ in dosing; Patients requiring transition from epoprostenol: Initiate at 10% of current epoprostenol dose; ↑ dose as epoprostenol dose is ↓.
PO (Adults ): 0.25 mg every 12 hr with food; may ↑ by 0.25–0.5 mg every 12 hr every 3–4 days to achieve optimal clinical response (max dose = 21 mg every 12 hr); Concomitant gemfibrozil therapy: ↓initial dose to 0.125 mg every 12 hr; may ↑ by 0.125 mg every 12 hr every 3–4 days to achieve optimal clinical response.
Inhaln (Adults ): Solution for inhalation: 3 breaths (18 mcg) 4 times daily (administered every 4 hr while awake); may ↑ by 3 breaths/treatment every 1–2 wk until target dose of 9 breaths (54 mcg) 4 times daily (administered every 4 hr while awake) is achieved. Dry powder inhaler: 16 mcg 4 times daily (administered every 4 hr while awake); ↑ by 16 mcg/treatment every 1–2 wk until target dose of 48–64 mcg 4 times daily (administered every 4 hr while awake) is achieved.

Hepatic Impairment

SC IV (Adults ): Mild or moderate hepatic impairment: ↓initial dose to 0.625 ng/kg/min (using ideal body weight).

Hepatic Impairment

PO (Adults ): Mild hepatic impairment: ↓in initial dose to 0.125 mg every 12 hr; may ↑ by 0.125 mg every 12 hr every 3–4 days to achieve optimal clinical response.

US Brand Names ⬆ ⬇

Orenitram, Remodulin, Tyvaso, Tyvaso DPI

Action ⬆ ⬇

Treprostinil is a prostacyclin that produces direct vasodilation of pulmonary and systemic arterial vascular beds.
Also inhibits platelet aggregation.

Therapeutic effects:

Decreased exercise-associated symptoms and delayed disease progression.

Classifications ⬆ ⬇

Therapeutic Classification: vasodilators

Pharmacologic Classification: prostacyclins

Pharmacokinetics ⬆ ⬇

Absorption: IV administration results in complete bioavailability. Rapidly and completely (near 100%) absorbed following SUBQ administration; 64–72% absorbed after oral inhalation; 17% absorbed after oral administration.

Distribution: Well distributed to extravascular tissues.

Protein Binding: 91%.

Metabolism/Excretion: Primarily metabolized by the liver via the CYP2C8 isoenzyme; metabolites are renally excreted; minimal excretion of unchanged drug in urine.

Half-Life: SUBQ: 4 hr Dry powder inhalation: 27–50 min.

Time/Action Profile ⬆ ⬇

(clinical improvement)

ROUTE	ONSET	PEAK	DURATION
SUBQ/IV	unknown	1 wk	unknown
Inhaln (soln)	unknown	unknown	unknown
Inhaln (dry powder)	unknown	unknown	unknown
PO	unknown	unknown	unknown

Patient/Family Teaching ⬆ ⬇

Instruct patient to take treprostinil as directed. Advise patient to read Patient Information before starting therapy and with each Rx refill in case of changes.
Instruct patient to inform health care professional if headache, nausea, vomiting, restlessness, anxiety, or infusion site reactions occur.
Inform patient and family that therapy may be required for years to control disease.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if planning to breastfeed.
PO: Instruct patient to take treprostinil as directed. Take missed tablets as soon as remembered with food. If two or more doses missed, must restart titration at lowest dose. Do not stop therapy abruptly; may result in worsening of symptoms.
Inform patient that empty shell of tablet may appear in stool; this is of no concern.
IV: Instruct patient on insertion of catheter and use of pump. Patient must have immediate access to a backup infusion pump and SUBQ infusion sets to prevent potential interruptions in drug delivery.
SC: Inform patient that subsequent disease management may require an alternative form of IV therapy.
Inhaln: For solution for inhalation, train patient in dosing, Tyvaso device set up, operation, cleaning, and maintenance, according to the instructions for use. Obtain access to a backup Tyvaso device to avoid potential interruptions in drug delivery due to equipment malfunction. If a scheduled treatment session is missed or interrupted, resume therapy as soon as possible. Avoid skin and eye contact with solution.
Inhaln: For use of dry powder inhaler, instruct the patient to store inhaler with the mouthpiece attached and empty and to wipe the outside of the inhaler with a clean, dry cloth only, if needed; do not rinse or wash the inhaler. Advise the patient to throw away the used inhaler after 7 days of use into the regular household trash.

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Indications ⬇

Contraind./Precautions ⬆ ⬇