greater systemic concentrations relative to patients with normal hepatic or renal function Use caution in patients with low arterial blood pressure (may produce symptomatic hypotension) Do not take oral tablets with alcohol; faster release of treprostinil from the tablet may occur The tablet shell does not dissolve and can lodge in a diverticulum in patients with diverticulosis Abrupt withdrawal may worsen pulmonary arterial hypertension symptoms Inhibits platelet aggregation and increases risk of bleeding; use caution in patients receiving concurrent anticoagulant/antiplatelet therapy Indwelling central venous catherer associated with serious blood stream infections; use this method only in patients intolerant to the SC therapy Experienced personnel required to administer therapy Drug interactions overview Dosage adjustment may be necessary if CYP2C8 inhibitors (eg, atazanavir, gemfibrozil, ritonavir) or inducers (eg, carbamazepine, phenobarbital, phenytoin, rifampin ) are added or withdrawn Pregnancy Limited case reports of treprostinil insufficient to inform a drug-associated risk of adverse developmental outcomes; however, there are risks to mother and fetus associated with pulmonary arterial hypertension associated with an increased risk of maternal and fetal mortality; in animal studies, no adverse reproductive and developmental effects observed Animal data Animal reproductive studies have shown an adverse effect on fetus; in rats, administration to pregnant rats during period of organogenesis at doses greater than or equal to 10 mg/kg/day (approximately 15 times the human exposure at the dose of 3.5 mg BID on an AUC basis) resulted in decreased pregnancy rate, increased post-implantation loss, and decreased fetal viability and growth In rabbits, teratogenicity and decreased fetal viability and growth were observed at doses greater than or equal to 1.5 mg/kg/day (approximately 7 times the human exposure at dose of 3.5 mg BID on an AUC basis) Lactation There are no data on presence of treprostinil in human milk, effects on breastfed infant, or on milk productionPregnancy Categories A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk. B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available. Mechanism of Action Peripheral prostacyclin vasodilator of both pulmonary and systemic arterial vascular bed; decreases ventricular afterload; also inhibits platelet aggregation Absorption Bioavailability: ~ 100% (SC infusion) Peak plasma time: ~10 hr (SC infusion) Concentrations in patients treated with an average dose of 9.3 ng/kg/min SC were ~2000 ng/L Distribution Protein bound: 91% Vd: 14 L/70 kg (ideal body weight) Metabolism Metabolized by liver, primarily by CYP2C8 Metabolites: HU1-HU5 Elimination Half-life: ~4 hr Total body clearance: 30 L/hr (based on 70 kg person) Excretion: Urine (79%); feces (13%) Five metabolites were detected in the urine (10-16%) and representing 64% of the dose administered SC/IV Preparation Visually inspect for particulate matter and discoloration prior to administration Administer by SC or IV infusion only Refer to Remodulin prescribing information for dosing calculations SC/IV Administration SC infusion Treprostinil is preferably infused SC, but can be administered by a central IV line if the SC route is not tolerated because of severe site pain or reaction Administer SC by continuous infusion, via a SC catheter, using an infusion pump designed for SC drug delivery Infusion pump should be adjustable to ~0.002 mL/hour, have occlusion/no delivery, low battery, programming error and motor malfunction alarms, have delivery accuracy of ±6% or better, be positive pressure-driven, and have a reservoir made of polyvinyl chloride, polypropylene or glass Alternatively, use an infusion pump cleared for use with treprostinil Avoid potential interruptions in drug delivery, the patient must have immediate access to a backup infusion pump and SC infusion sets External IV infusion pump Administer IV by continuous infusion via a surgically placed indwelling central venous catheter using an external infusion pump designed for IV drug delivery If clinically necessary, a temporary peripheral IV 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 the risk of thrombophlebitis Infusion pump should have occlusion/no delivery, low battery, programming error and motor malfunction alarms, have delivery accuracy of ±6% or better of the hourly dose, be positive pressure driven, and have a reservoir made of polyvinyl chloride, polypropylene or glass Alternatively, use an infusion pump cleared for use with treprostinil To avoid potential interruptions in drug delivery, patient must have immediate access to a backup infusion pump and infusion sets Use infusion sets with an in-line 0.22 or 0.2 micron pore size filter Implantable IV infusion pump Use an implantable IV infusion pump approved for use with treprostinil (eg, Implantable System for Remodulin [ISR]) Refer to the pump manufacturer’s manual for specific instructions regarding preparation, programing, implantation, and refilling If infusion is stopped and then restarted within a few hours after discontinuing it, may use the same rate; interruptions for long periods may require retitration Oral Administration (Extended-release Tablets) Administer with food Swallow tablets whole; do not chew, crush, or split Avoid abrupt discontinuation; when discontinuing, reduce dose by 0.5-1 mg/day increments Missed doses If 1 dose is missed, take the missed dose as soon as possible, with food If ≥2 doses are missed, restart at a lower dose and retitrate Storage Tablets Store at 25°C (77°F); excursions are permitted between 15-30°C (59-86°F) SC/IV Unopened vials Store at 25°C (77°F), with excursions permitted to 2-30°C (36-86°F) A single vial should be used for ≤30 days after the initial introduction into the vial Diluted solutions Sterile diluents for Remodulin: Store at room temperature for up to 14 days and can be used within 48 hr at 40°C Sterile water for injection or 0.9% NaCl: Store at room temperature for up to 4 hr or 24 hr refrigerated and can be used within 48 hr at 40°C No images available for this drug. No images available for this drug.Print Patient Educationtreprostinil inhalation TREPROSTINIL SOLUTION - INHALATION (tre-PROST-i-nil) COMMON BRAND NAME(S): Tyvaso USES: This medication is used to treat a type of high blood pressure in the lungs (pulmonary arterial hypertension). Treprostinil helps to increase your ability to exercise and improves symptoms such as shortness of breath and tiredness. It works by relaxing and widening the blood vessels (arteries) in the lungs and other parts of the body so that blood can flow more easily. This medication belongs to a class of drugs known as vasodilators. HOW TO USE: Read the Patient Information leaflet available from your pharmacist. This medication comes in a plastic container called an ampule. Follow the manufacturer's instructions on how to prepare each dose. This product is used with a special breathing device (nebulizer). Consult your doctor, pharmacist or respiratory therapist on how to inhale this medication properly with this equipment. Make sure you understand how to properly clean the nebulizer to prevent infections. If you have any questions, consult your health care professional.Before using, check this product visually for particles or discoloration. If either is present, do not use the liquid. Do not mix with other inhaled medications in the nebulizer.Inhale this medication by mouth as directed by your doctor, usually 4 times daily during waking hours, at least 4 hours apart. Do not drink the solution. Do not get this medication on the skin or in your eye. If this happens, rinse the area with water. The dosage is based on your medical condition and response to treatment.Use this medication regularly to get the most benefit from it. To help you remember, use it at the same times each day.To avoid missing doses, be sure to have a back-up nebulizer in case your regular device stops working properly.Tell your doctor if your condition does not improve or if it worsens. SIDE EFFECTS: Cough, headache, throat irritation, nausea, flushing, dizziness, or jaw/muscle/bone pain may occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly. Fainting is another common side effect. If fainting does occur, get medical help right away.To reduce the risk of dizziness and lightheadedness, get up slowly when rising from a sitting or lying position.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Tell your doctor right away if you have any serious side effects, including: unusual bleeding/bruising.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345. PRECAUTIONS: Before using treprostinil, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: low blood pressure, liver problems, bleeding problems, other breathing problems (such as asthma, chronic obstructive pulmonary disease-COPD).This drug may make you dizzy. Alcohol or marijuana (cannabis) can make you more dizzy. Do not drive, use machinery, or do anything that needs alertness until you can do it safely. Limit alcoholic beverages. Talk to your doctor if you are using marijuana (cannabis).Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.It is unknown if this drug passes into breast milk. Consult your doctor before breast-feeding. DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval. OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: severe dizziness, fainting. NOTES: Do not share this medication with others.Lab and/or medical tests (such as blood pressure) may be done while you are using this medication. Keep all medical and lab appointments. Consult your doctor for more details. MISSED DOSE: If you miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Use your next dose at the regular time. Do not double the dose to catch up. STORAGE: Store at room temperature away from light and moisture. Once the foil pack is opened, the ampules should be used within 7 days. After an ampule has been opened, discard any unused solution at the end of the day. Do not store in the bathroom. Keep all medications away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company. Information last revised December 2022. Copyright(c) 2023 First Databank, Inc. IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or