treprostinil (parenteral)

tre-PROSS-ti-nil

Therapeutic Classification: vasodilators

Pharmacologic Classification: prostacyclins

REMS

IV: SC: Pulmonary arterial hypertension (WHO Group I).
Pulmonary arterial hypertension in patients requiring transition from epoprostenol.
Inhaln: PO: Pulmonary arterial hypertension (WHO Group I).

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 in patients with pulmonary arterial hypertension.

Absorption: Rapidly and completely (near 100%) absorbed following subcut administration; bioavailability after inhalation is 64–72%; bioavailability after oral administration is 17%.

Distribution: Unknown.

Protein Binding: 91%.

Metabolism/Excretion: Extensively metabolized by the liver (by CYP2C8), metabolites are renally excreted; minimal excretion of unchanged drug in urine.

Half-Life: 4 hr.

(clinical improvement)

ROUTE	ONSET	PEAK	DURATION
Subcut/IV	unknown	1 wk	unknown
Inhaln	unknown	unknown	unknown
PO	unknown	unknown	unknown

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 inhalation and IV) and mild hepatic impairment (PO); data not available for severe hepatic insufficiency (for inhalation and IV));
Pulmonary disease (inhalation only);
Diverticulosis (PO only) (tablet shell does not dissolve);
Avoid abrupt discontinuation or rapid dose reduction;
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).

CNS: headache, dizziness

CV: vasodilation, hypotension, edema

Derm: rash, pruritus, flushing

F and E: hypokalemia

GI: diarrhea, nausea

Hemat: bleeding

Local: infusion site pain/reaction

MS: jaw pain

Resp: cough

Drug-drug:

↑risk of hypotension with antihypertensives, diuretics, or vasodilators.
Effects may be ↑ by gemfibrozil.
Effects may be ↓ by rifampin.
Risk of bleeding may be ↑ by concurrent use of anticoagulants.

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.

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.
Inhaln (Adults ): 3 breaths (18 mcg) 4 times daily; may ↑ by 3 breaths/treatment every 1–2 wk until target dose of 9 breaths (54 mcg) 4 times daily is achieved.

(Generic available)

Extended-release tablets: 0.125 mg; 0.25 mg; 1 mg; 2.5 mg; 5 mg
Solution for injection: 1 mg/mL; 2.5 mg/mL; 5 mg/mL; 10 mg/mL
Solution for oral inhalation: 0.6 mg/mL

Monitor patient for signs of improvement in pulmonary arterial hypertension (decrease in dyspnea, increased exercise tolerance) periodically during therapy.
IV: Assess patient for infusion site reactions (pain, erythema, induration, rash) during therapy.
Inhaln: Monitor BP during therapy. May cause hypotension.

Treprostinil should be used only by clinicians experienced in the treatment of pulmonary arterial hypertension. Initiation of therapy should be in a setting equipment and personnel for monitoring and emergency treatment.
- Assess patient's ability to accept and administer treprostinil, and insert and care for infusion system prior to initiating therapy.
- Dose should be increased for lack of improvement or worsening in symptoms, or decreased for excessive side effects or infusion site reactions.
- Subcut route is preferred to ↓ risk of blood stream infections. IV route may be used if subcut route is not tolerated due to severe site pain or reaction.
- Avoid abrupt withdrawal or large dose reductions; may result in worsening of symptoms of pulmonary arterial hypertension.
Transitioning from Subcut or IV Route to PO: Decrease Subcut or IV dose up to 30 ng/kg/min per day while simultaneously increasing PO dose up to 6 mg per day (2 mg 3 times daily) if tolerated.
PO: Administer with food every 12 hr for twice daily dosing and every 8 hrs for three time daily dosing. Swallow tablets whole; do not crush, break, or chew. Do not take a tablet that is damaged or broken.
- If therapy must be PO interrupted, consider temporary subcut or IV infusion. May use implantable IV infusion pump using same dose as external infusion pump.
SC: Administer without diluting solution via a self-inserted subcut catheter and an infusion pump designed for subcut drug delivery. During use, a single syringe can be administered up to 72 hr. A single vial should be used for up to 14 days after initial introduction into vial. Do not administer solutions that are discolored or contain particulate matter. Refer to manufacturer's instructions.
Rate: Subcutaneous infusion rate (using undiluted treprostinil) may be calculated with the following formula: Undiluted subcut or IV infusion rate (mL/hr) = [Dose (ng/kg/min) ×weight (kg) ×0.00006]/treprostinil vial strength (mg/mL).
Rate: Administer via infusion set with in-line 0.22 or 0.2 micron pore size filter. IV infusion rate (using undiluted treprostinil) may be calculated with the following formula: Undiluted subcut or IV infusion rate (mL/hr) = [Dose (ng/kg/min) ×weight (kg) ×0.00006]/treprostinil vial strength (mg/mL).
Inhaln: Use only with the Tyvaso Inhalation System. Administer undiluted, as supplied. Solution is clear and colorless to slightly yellow. Do not administer solutions that are discolored or contain particulate matter. Do not mix with other medications. Single breath delivers approximately 6 mcg of treprostinil. Administer in 4 separate treatments each day approximately four hours apart, during waking hours. If initial 3 breaths are not tolerated, may decrease to 1 or 2 breaths. One ampule of Tyvaso contains a sufficient volume of medication for all 4 treatment sessions in a single day. Prior to first treatment session, twist top off a single ampule and squeeze entire contents into medicine cup. Cap device and store upright with remaining medication inside between each of the 4 daily treatment sessions. Discard medicine cup and any remaining medication at end of each day and clean device according to instructions.

IV Administration:

Continuous Infusion: Administer via a surgically placed indwelling central venous catheter, using an infusion pump designed for intravenous drug delivery or implantable infusion pump. If clinically necessary, a temporary peripheral intravenous cannula, preferably placed in a large vein, may be used for short-term administration. Use of a peripheral IV infusion for more than a few hours increases risk of thrombophlebitis.Diluent: 50–100 mL of sterile water for injection, 0.9% NaCl, Sterile Diluent for Flolan or Sterile Diluent for Eproprostenol Sodium. Do not administer solutions that are discolored or contain particulate matter.Concentration: Amount of diluent and concentration is calculated based on dose needed, patient, weight, and volume of reservoir. Diluted solutions are stable for up to 48 hr in concentrations as low as 0.004 mg/mL at room temperature. Refer to manufacturer's instructions.

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.
Advise female patients to notify health care professional if pregnancy is planned or suspected and or if planning to breastfeed during therapy.
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 subcut 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: Train patient in dosing, Tyvaso device set up, operation, cleaning, and maintenance, according to the instructions for use. Obtain access to a back-up 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.

Improved exercise tolerance in patients with pulmonary arterial hypertension.

treprostinil (parenteral): Remodulin,

treprostinil (inhalation): Tyvaso,

treprostinil (oral): Orenitram

Activity intolerance(Indications)
Deficient knowledge, Relate med(Patient/Family Teaching)

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Action ⬆ ⬇

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Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇

Interactions ⬆ ⬇

Route/Dosage ⬆ ⬇

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Assessment ⬆ ⬇

Implementation ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

Evaluation/Desired Outcomes ⬆ ⬇

US Brand Names ⬆ ⬇

Pot. Nursing Diagnoses ⬆