TreprostinilU.S. Brand Names: Remodulin�(r)
Synonyms: Treprostinil Sodium
Generic Available: No
Use: Treatment of pulmonary arterial hypertension (PAH) in patients with NYHA Class II-IV symptoms to decrease exercise-associated symptoms
Pregnancy Risk Factor: B
Pregnancy Implications: No concerns identified in animal studies. Safety and efficacy for use during pregnancy have not been established; use caution.
Lactation: Excretion in breast milk unknown/use caution
Contraindications: Hypersensitivity to treprostinil or any component of formulation
Warnings/Precautions: Use caution in hepatic insufficiency, dose modification may be warranted; use caution in renal impairment; abrupt withdrawal/large dosage reductions may worsen symptoms of PAH. Safety and efficacy have not been established in patients  16 years of age.
Adverse Reactions: >10%: Cardiovascular: Vasodilation (11%) Central nervous system: Headache (27%) Dermatologic: Rash (14%) Gastrointestinal: Diarrhea (25%), nausea (22%) Local: Infusion site pain (SubQ 85%, may improve after several months of therapy); infusion site reaction (SubQ 83%) Miscellaneous: Jaw pain (13%) 1% to 10%: Cardiovascular: Edema (9%), hypotension (4%) Central nervous system: Dizziness (9%) Dermatologic: Pruritus (8%)
Overdosage/Toxicology: Symptoms of overdose are extensions of the known pharmacological effects: Flushing, headache, hypotension, nausea, vomiting, diarrhea. Dosage reduction will likely coincide with symptom resolution. Treatment is otherwise supportive.
Drug Interactions: Anticoagulants: Treprostinil inhibits platelet aggregation. Concomitant use with anticoagulants may increase the risk of bleeding. Antiplatelet agents: Treprostinil inhibits platelet aggregation. Concomitant use with antiplatelet agents may increase the risk of bleeding. NSAIDs: Treprostinil inhibits platelet aggregation. Concomitant use with NSAIDs may increase the risk of bleeding. Salicylates: Treprostinil inhibits platelet aggregation. Concomitant use with salicylates may increase the risk of bleeding.
Stability: Store at 25°C (77°F). Product does not need dilution prior to SubQ use. For I.V. infusion, dilute in SWFI or NS to a final volume of either 50 mL or 100 mL (dependent on system reservoir and calculated dose). Stability for up to 48 hours has been shown for concentrations as low as 4000 ng/mL. Contents of a single-reservoir syringe of treprostinil can be administered up to 72 hours at 37°C; diluted solutions can be used up to 48 hours at 37°C. Contents of a vial should not be used past 30 days after the initial needle access into the vial.
Mechanism of Action: Treprostinil is a direct dilator of both pulmonary and systemic arterial vascular beds; also inhibits platelet aggregation.
Pharmacodynamics/Kinetics: Absorption: SubQ: Rapidly and completely Distribution: 14 L/70 kg lean body weight Protein binding: 91% Metabolism: Hepatic (enzymes unknown); forms metabolites Bioavailability: 100% Half-life elimination: Terminal: 2-4 hours Excretion: Urine (4% as unchanged drug; 64% as metabolites); feces (13%)
Dosage: SubQ or I.V. infusion: Adults: PAH: Initial: 1.25 ng/kg/minute continuous; if dose cannot be tolerated, reduce to 0.625 ng/kg/minute. Increase at rate not >1.25 ng/kg/minute per week for first 4 weeks, and not >2.5 ng/kg/minute per week for remainder of therapy. Limited experience with doses >40 ng/kg/minute. Note: Dose must be carefully and individually titrated (symptom improvement with minimal adverse effects). Avoid abrupt withdrawal. Elderly: Limited experience in patients >65 years; refer to adult dosing; use caution Dosage adjustment in renal impairment: No specific dosage adjustment recommended; use with caution. Dosage adjustment in hepatic impairment: Mild to moderate: Initial: 0.625 ng/kg/minute; increase with caution. Severe: No data available.
Administration: I.V. infusion: Solution must be diluted prior to use and administered by continuous infusion using an indwelling catheter and infusion pump. I.V. use is recommended when SubQ infusion is not tolerated. Infusion site reactions may be helped by moving the infusion site every 3 days, local application of topical hot and cold packs, topical or oral analgesics. Injection site pain and erythema may improve after several months of therapy. SubQ infusion: Administer via continuous SubQ infusion using an appropriately-designed infusion pump. Patients must be assessed regarding their ability to manage such a delivery system.
Monitoring Parameters: Dyspnea, fatigue, activity tolerance
Dietary Considerations: Sodium chloride content of solution for injection: 1 mg/mL, 2.5 mg/mL, and 5 mg/mL each contain sodium chloride 5.3 mg/mL 10 mg/mL contains sodium chloride 4 mg/mL
Dental Health: Effects on Dental Treatment: No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions: No information available to require special precautions
Mental Health: Effects on Mental Status: May cause headache
Mental Health: Effects on Psychiatric Treatment: Nausea and diarrhea are common, these effects may be additive with concurrent use of SSRIs, lithium, or valproate. Treprostinil inhibits platelet aggregation. Concomitant use with SSRIs which possess some antiplatelet activity may increase the risk of bleeding.
Dosage Forms: Injection, solution: 1 mg/mL (20 mL) [contains sodium chloride 5.3 mg/mL]; 2.5 mg/mL (20 mL) [contains sodium chloride 5.3 mg/mL]; 5 mg/mL (20 mL) [contains sodium chloride 5.3 mg/mL]; 10 mg/mL (20 mL) [contains sodium chloride 4 mg/mL]
References: Badesch DB, Abman SH, Ahearn GS, et al, "Medical Therapy for Pulmonary Arterial Hypertension: ACCP Evidence-Based Clinical Practice Guidelines,"Chest, 2004, 126(1 Suppl):35-62, Gildea TR, Arroliga AC, and Minai OA, "Treatments and Strategies to Optimize the Comprehensive Management of Patients With Pulmonary Arterial Hypertension,"Cleve Clin J Med, 2003, 70(Suppl 1):18-27. McLaughlin VV, Gaine SP, Barst RJ, et al, "Efficacy and Safety of Treprostinil: An Epoprostenol Analog for Primary Pulmonary Hypertension,"J Cardiovasc Pharmacol, 2003, 41(2):293-9. Rubin LJ and American College of Chest Physicians, "Diagnosis and Management of Pulmonary Arterial Hypertension: ACCP Evidence-Based Clinical Practice Guidelines,"Chest, 2004, 126(1 Suppl):4-6.
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