Treprostinil Sodium
Pronouncation: (tre-PROST-in-il SO-dee-um)Class: Aggregation inhibitor, Vasodilator
Trade Names:
Remodulin
- Injection 1 mg/mL
- Injection 2.5 mg/mL
- Injection 5 mg/mL
- Injection 10 mg/mL
Pharmacology
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Treprostinil directly vasodilates pulmonary and systemic arterial vascular beds and inhibits platelet aggregation.
Pharmacokinetics
Absorption
Relatively rapid and complete absorption after subcutaneous infusion; absolute bioavailability approximately 100%. Steady state achieved in approximately 10 h.
Distribution
Vd approximately 14 L; 91% bound to plasma proteins.
Metabolism
Substantially metabolized by liver; 5 metabolites identified but biological activity and metabolic fate unknown.
Elimination
Biphasic elimination; terminal t ½ approximately 4 h. Approximately 79% excreted in urine, 4% as unchanged drug; approximately 13% excreted in feces. Cl approximately 30 L/h.
Special Populations
Hepatic Function ImpairmentCl reduced up to 80% in patients with hepatic function impairment. C max increased 2‐fold in patients with mild impairment and 4‐fold in patients with moderate impairment.
Indications and Usage
Treatment of pulmonary arterial hypertension (PAH) in patients with New York Heart Association (NYHA) class II to IV symptoms to diminish symptoms associated with exercise; to diminish the rate of clinical deterioration in patients requiring transition from epoprostenol.
Contraindications
Standard considerations.
Dosage and Administration
Adults and Children 17 yr of age and olderSubcutaneous or IV infusion Initial dose: 1.25 ng/kg/min; reduce to 0.625 ng/kg/min if initial dose not tolerated. Titrate dose in increments of no more than 1.25 ng/kg/min/wk for first 4 wk, then by no more than 2.5 ng/kg/min/wk to establish dose at which PAH symptoms are improved, while minimizing excessive pharmacologic adverse reactions. Little experience with doses higher than 40 ng/kg/min.
Hepatic Function ImpairmentReduce initial dose to 0.625 ng/kg/min in patients with mild to moderate hepatic function impairment and increase dose cautiously.
Transition from EpoprostenolAdults and Children 17 yr of age and older
IV Initiate the infusion of treprostinil and increase it while simultaneously decreasing the dose of IV epoprostenol. This transition should take place in a hospital with constant observation. During transition, treprostinil is initiated at 10% of current epoprostenol dose and then escalated as epoprostenol dose is decreased. The transition is as follows: Step 1- Epoprostenol dose is unchanged and treprostinil dose is 10% of epoprostenol dose. Step 2- Administer 80% of starting epoprostenol dose and treprostinil dose is 30% of starting epoprostenol dose. Step 3- Administer 60% of starting epoprostenol dose and treprostinil dose is 50% of starting epoprostenol dose. Step 4- Administer 40% of starting epoprostenol dose and treprostinil dose is 70% of starting epoprostenol dose. Step 5- Administer 20% of starting epoprostenol dose and treprostinil dose is 90% of starting epoprostenol dose. Step 6- Administer 5% of starting epoprostenol dose and treprostinil dose is 110% of starting epoprostenol dose. Step 7- Administer 0% of starting epoprostenol dose and treprostinil dose is 110% of starting epoprostenol dose plus additional 5% to 10% increments as needed.
General Advice
- For subcutaneous or IV infusion only. IV infusion is for those who are not able to tolerate subcutaneous infusion (severe site pain or reaction).
- Administer as supplied (undiluted) for subcutaneous infusion. Administer via self-inserted subcutaneous catheter, using an infusion pump designed for subcutaneous drug delivery.
- Calculate subcutaneous infusion rate using the following formula: subcutaneous infusion rate = (dose [ng/kg/min] × weight [kg] × 0.00006)/treprostinil vial strength 1 mg per mL.
- For IV infusion, dilute with sterile water for injection or sodium chloride 0.9% injection for IV infusion. Administer via surgically placed indwelling central venous catheter, using an infusion pump designed for IV drug delivery.
- First, calculate diluted IV treprostinil concentration using following formula: diluted IV treprostinil concentration = (dose [ng/kg/min] × weight [kg] × 0.00006)/IV infusion rate (mL/min); then calculate amount of treprostinil injection needed using following formula: amount of treprostinil injection (mL) = (diluted IV concentration [mg/mL]/treprostinil vial strength [mg/mL]) × total volume of diluted treprostinil solution in reservoir (mL).
- Add calculated amount of treprostinil injection to reservoir along with sufficient volume of sterile water for injection or sodium chloride 0.9% to achieve desired total volume in reservoir.
Storage/Stability
Store vials at controlled room temperature (59° to 86°F). Discard any unused solution 30 days following initial entry into vial. During use, a single reservoir (syringe) of undiluted treprostinil can be administered for up to 72 h at 98.6°F; diluted treprostinil can be administered for up to 48 h at 98.6°F. A single vial should be used for no more than 30 days after initial introduction into the vial.
Drug Interactions
AnticoagulantsSince treprostinil inhibits platelet aggregation, the risk of bleeding may be increased.
Antihypertensives, diuretics, vasodilatorsReduction in BP associated with these agents may be exacerbated by treprostinil.
Laboratory Test Interactions
None well documented.
Adverse Reactions
Cardiovascular
Vasodilatation (11%); hypotension (4%).
CNS
Headache (27%); dizziness (9%).
Dermatologic
Rash (14%); pruritus (8%); macular or papular rashes (postmarketing).
GI
Diarrhea (25%); nausea (22%).
Local
Infusion-site pain (85%); infusion-site reaction (83%); arm swelling, hematoma, pain, paresthesias (potentially related to mode of infusion).
Miscellaneous
Jaw pain (13%); edema (9%); cellulitis (postmarketing).
Precautions
Pregnancy
Category B .
Lactation
Undetermined.
Children
Safety and efficacy not established in children younger than 17 yr of age.
Elderly
Dose selection should be cautious, reflecting the higher frequency of decreased hepatic, renal, or cardiac function, and of comorbidity.
Renal Function
Use with caution.
Hepatic Function
Use with caution.
Abrupt withdrawal
Avoid abrupt withdrawal or sudden large dose reductions because of risk of worsening of PAH symptoms.
Initiating therapy
Initiate therapy in a setting with adequate personnel and equipment for physiological monitoring and emergency care.
Overdosage
Symptoms
Diarrhea, flushing, headache, hypotension, nausea, vomiting.
Patient Information
- Advise patient that medication is administered as a continuous infusion through a catheter using an infusion pump and that therapy will be needed for a prolonged period of time, possibly years.
- Advise patient or caregiver that medication initially will be prepared by health care provider and administered in health care setting while the dose is being adjusted to provide optimal benefit.
- For home infusion, ensure that patient understands how to store, prepare, and administer the medication using the infusion pump, and dispose of used equipment and supplies.
- Ensure that patient has immediate access to back-up infusion pump and infusion sets at all times, and knows how to change equipment if necessary.
- Advise patient that dose may be adjusted periodically by health care provider to maintain optimal benefit or to manage adverse reactions. Caution patient not to stop the infusion or change the dose unless advised by health care provider.
- Advise patient that if medication needs to be discontinued, it will be slowly withdrawn unless safety concerns (eg, rash) require a more rapid withdrawal.
- Advise patient or caregiver to immediately inform health care provider if injection-site pain or reaction, skin rash, itching, worsening shortness of breath, fatigue, or chest pain occur during treatment.
- Advise patient or caregiver to report persistent headache, diarrhea, dizziness, or any other bothersome or unexplained sensation or feeling.
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