treprostinil SC

Action and Spectrum

Actions and spectrum: 

• Vasodilation: treprostinil promotes the smooth muscle cells relaxation in the walls of blood vessels, causing vasodilation. This effect helps to reduce pulmonary vascular resistance and systemic vascular resistance, improving blood flow and reducing the workload on the heart. 
• Pulmonary arterial hypertension (PAH) treatment: treprostinil SC is primarily indicated for the treatment of PAH. By dilating the pulmonary arteries, treprostinil SC improves pulmonary hemodynamics, increases exercise capacity, and reduces symptoms associated with PAH, such as shortness of breath and fatigue. 
• Improved exercise tolerance: By dilating blood vessels and reducing pulmonary vascular resistance, treprostinil SC enhances exercise tolerance in individuals with PAH. It allows for better blood flow to the lungs and improves oxygenation during physical activity. 

The spectrum of treprostinil SC is primarily focused on the treatment of PAH. It is not used for other conditions outside the scope of PAH treatment. However, it is important to note that the specific use and indications of treprostinil SC may vary depending on country-specific approvals and prescribing guidelines. Therefore, it is essential to consult with a healthcare professional for accurate information on the appropriate use and indications of treprostinil SC. 

Drug Interaction

Adverse Reaction

None

Black Box Warning

Black Box Warning: 

there is no specific black box warning associated with subcutaneous treprostinil. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• Hypersensitivity: treprostinil is contraindicated in individuals who have a known hypersensitivity or allergic reaction to treprostinil or any of its components. 
• Pulmonary Veno-Occlusive Disease (PVOD): treprostinil is contraindicated in patients with PVOD, a condition characterized by occlusion of small veins in the lungs. Administration of treprostinil in individuals with PVOD can further worsen the condition. 
• Severe Bleeding Disorders: treprostinil should not be used in individuals with severe bleeding disorders or active bleeding, as it can increase the risk of bleeding. 
• Decompensated Heart Failure: treprostinil is contraindicated in individuals with decompensated heart failure, where the heart is unable to adequately pump blood. 
• Pulmonary Arterial Hypertension (PAH) Associated with Idiopathic Pulmonary Fibrosis (IPF): treprostinil is contraindicated in patients with PAH associated with IPF, a condition characterized by progressive scarring of lung tissue.

Caution: 

• Pulmonary Edema: treprostinil may cause fluid retention, which can lead to pulmonary edema. Close monitoring of fluid balance, symptoms of fluid overload, and regular assessment of heart and lung function is important during treprostinil therapy. 
• Coagulation Disorders: treprostinil may increase the risk of bleeding, particularly in patients with coagulation disorders or taking anticoagulant medications. Caution should be exercised when using treprostinil in such individuals, and regular monitoring of bleeding parameters is recommended. 
• Hepatic Impairment: treprostinil is primarily metabolized in the liver, and caution should be exercised when using treprostinil in patients with hepatic impairment. Dose adjustments or close monitoring may be necessary in these individuals. 
• Renal Impairment: Although treprostinil is mainly cleared by the liver, there is limited information available with severe renal impairment. Caution should be exercised when using treprostinil in individuals with significant renal dysfunction. 
• Drug Interactions: treprostinil may interact with other medications, including those that affect platelet function or anticoagulant therapy. It is important to inform healthcare professionals about all the medications being taken, including over-the-counter drugs and herbal supplements, to avoid potential interactions. 
• Infusion Site Reactions: treprostinil subcutaneous infusion can cause local infusion site reactions, such as pain, erythema, swelling, and inflammation. Proper infusion site care and rotation can help minimize the occurrence of these reactions.

Comorbidities: 

• Cardiovascular Disease: Individuals with underlying cardiovascular conditions, such as CAD, CHF, or significant valvular disease, may require close monitoring when initiating treprostinil therapy. treprostinil’s vasodilatory effects can affect cardiac function, and careful assessment of cardiac status is important. 
• Renal Impairment: Patients with renal impairment may require dose adjustments or closer monitoring during treprostinil therapy. The clearance of treprostinil and its metabolites may be affected in individuals with impaired renal function. 
• Hepatic Impairment: treprostinil is primarily metabolized in the liver, so individuals with hepatic impairment may require dose adjustments or close monitoring. Hepatic function should be assessed before initiating treprostinil therapy. 
• Bleeding Disorders: treprostinil can increase the risk of bleeding due to its antiplatelet effects. Patients with a history of bleeding disorders or those taking anticoagulant medications may require careful monitoring of bleeding parameters. 
• Thyroid Dysfunction: treprostinil may affect thyroid hormone levels. Individuals with pre-existing thyroid dysfunction, such as hypothyroidism or hyperthyroidism, may need periodic monitoring of thyroid function during treatment. 

Pregnancy / Lactation

Pregnancy consideration: US FDA pregnancy category: Not assigned 

Lactation: Excreted into human milk: Unknown  

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.   
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

treprostinil is a analogue of prostacyclin that plays a role in vasodilation and inhibition of platelet aggregation. The mechanism of action of treprostinil involves binding to the prostacyclin receptor (IP receptor) on smooth muscle cells in blood vessels, leading to activation of cyclic adenosine monophosphate (cAMP) signaling pathways. 

• Vasodilation: treprostinil causes smooth muscles relaxation in the walls of blood vessels, leading to dilation of pulmonary and systemic arteries and veins. This reduces resistance to blood flow and improves blood circulation. 
• Inhibition of platelet aggregation: treprostinil inhibits platelet aggregation and adhesion, reducing the risk of blood clot formation. 
• Anti-inflammatory effects: treprostinil has anti-inflammatory properties, which can help to reduce inflammation and tissue damage in conditions such as pulmonary arterial hypertension (PAH). 
• Antiproliferative effects: treprostinil inhibits the proliferation of smooth muscle cells in blood vessels, which is important in conditions where excessive cell growth and remodeling of blood vessels occur, such as in PAH.

Pharmacodynamics: 

• Vasodilation: treprostinil acts as a potent vasodilator, primarily targeting the pulmonary arterial bed. It binds to prostacyclin receptors on vascular smooth muscle cells, leading to the activation of adenylate cyclase and subsequent increase in cyclic adenosine monophosphate (cAMP) levels. Elevated cAMP levels promote smooth muscle relaxation, resulting in vasodilation of both pulmonary and systemic arteries. This reduces pulmonary vascular resistance and improves blood flow in the pulmonary circulation. 
• Inhibition of Platelet Aggregation: treprostinil exerts antiplatelet effects by increasing intracellular cAMP levels in platelets. Elevated cAMP levels inhibit platelet activation, reducing their ability to aggregate and form blood clots. This antiplatelet effect helps prevent thrombus formation and maintains blood flow within the pulmonary arteries. 
• Anti-Remodeling Effects: treprostinil has been shown to inhibit vascular smooth muscle cell proliferation and reduce the production of endothelin-1, a potent vasoconstrictor. These actions contribute to the prevention of vascular remodeling and the thickening of pulmonary arterial walls associated with conditions such as pulmonary arterial hypertension (PAH). 
• Hemodynamic Effects: treprostinil SC administration improves hemodynamic parameters in patients with PAH. It decreases pulmonary arterial pressure, reduces pulmonary vascular resistance, and improves cardiac output. These effects result in improved exercise capacity, reduced symptoms of PAH, and potentially enhanced survival. 

Pharmacokinetics: 

Absorption 

treprostinil is administered subcutaneously using a continuous infusion pump, allowing for sustained release into the bloodstream. The drug is readily absorbed at the injection site and enters the systemic circulation. 

Distribution 

treprostinil has a high plasma protein binding capacity, primarily binding to albumin. It distributes throughout the body, including the pulmonary arteries, where it exerts its vasodilatory effects. 

Metabolism 

treprostinil undergoes rapid metabolism in the liver, primarily through glucuronidation, mediated by the enzyme UDP-glucuronosyltransferase (UGT). This metabolic pathway leads to the formation of inactive metabolites, such as treprostinil glucuronide. These metabolites are less pharmacologically active than the parent compound. 

Elimination and excretion 

The elimination of treprostinil and its metabolites primarily occurs via renal excretion. The inactive metabolites, including treprostinil glucuronide, are eliminated in the urine. The elimination half-life of treprostinil is relatively short, approximately 4 hours. 

Adminstartion

Administration: 

• Preparation: The treprostinil solution or concentrate may involve dilution with an appropriate sterile diluent, as specified in the product labeling. 
• Catheter Placement: A subcutaneous catheter is inserted into a suitable site on the patient’s body. Common sites include the abdomen, thigh, or upper arm. The catheter is secured in place to prevent dislodgement. 
• Infusion Pump Setup: An infusion pump specifically designed for subcutaneous administration is used to deliver treprostinil. The pump is designed to deliver a continuous and controlled infusion rate based on the prescribed dosage. 
• Priming: The infusion line and catheter are primed to remove any air bubbles and ensure proper drug delivery. Priming is done according to the manufacturer’s instructions to ensure accurate dosing. 
• Initiation and Titration: The treprostinil infusion is started at a low initial dose as prescribed by the healthcare professional. The dosage is gradually increased over time based on the patient’s response and tolerability, following the recommended titration schedule. 
• Ongoing Monitoring: Close monitoring of the patient is essential during treprostinil therapy. This includes regular assessment of vital signs, monitoring of infusion site for any signs of infection or irritation, and evaluation of clinical response to therapy. The infusion pump should be checked regularly to ensure proper functioning. 
• Maintenance and Adjustment: treprostinil SC therapy is typically continued on a long-term basis. The dosage is adjusted periodically based on the patient’s clinical status, exercise tolerance, and any adverse effects. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: treprostinil SC 

Pronounced: (tre-PROS-ti-nil ess-SEE)  

Why do we use treprostinil SC? 

• Treatment of PAH: treprostinil SC is a prostacyclin analog that acts as a potent vasodilator in the pulmonary arteries. It helps to reduce pulmonary vascular resistance and improve exercise capacity in patients with PAH. It is indicated for the long-term treatment of PAH to improve symptoms and delay disease progression. 
• Functional Class Improvement: treprostinil SC therapy aims to improve the functional class of patients with PAH. It may help to relieve symptoms such as shortness of breath, fatigue, and exercise intolerance. Improvement in functional class allows for a better quality of life and increased ability to perform daily activities. 
• Delaying Disease Progression: treprostinil SC has been shown to slow down the progression of PAH and reduce the risk of hospitalization associated with the condition. It can help in preserving cardiac function and preventing further deterioration of the pulmonary vasculature. 
• Combination Therapy: treprostinil SC may be used in combination with other PAH-specific therapies, such as endothelin receptor antagonists, phosphodiesterase-5 inhibitors, or soluble guanylate cyclase stimulators. Combination therapy can have a synergistic effect, leading to better clinical outcomes in patients with PAH.