AdultPediatricDosage Forms & Strengths inhalation solution 600mcg/mL ~6mcg delivered for single breath inhaled inhalation dry powder 16mcg/cartridge 32mcg/cartridge 48mcg/cartridge 64mcg/cartridge Single-dose cartridges administered with Tyvaso DPI inhaler Pulmonary Arterial Hypertension Indicated for treatment of pulmonary arterial hypertension (PAH; WHO Group 1) to improve exercise ability Solution for inhalation Initial 18 mcg (3 breaths) per treatment session QID If 3 breaths not tolerated, decrease to 1-2 breaths and later increase to 3 breaths as tolerated Maintenance If tolerated, increase by 3 breaths/dose (18 mcg) q1-2Weeks Target maintenance: 54 mcg (9 breaths) per treatment session QID If adverse effects preclude titration to target dose, continue at highest tolerated dose If effects diminish over minimum recommended dosing interval of 4 hr, treatment timing can be adjusted for planned activities Dry powder for inhalation Initial 16 mcg inhaled per treatment session QID (~4 hr apart during waking hours) Maintenance Increase dosage by 16 mcg/treatment session at ~1- to 2-week intervals Target maintenance: 48-64 mcg/treatment session If prescribed dose >64 mcg/treatment session, >1 cartridge needed per session If adverse effects preclude titration, continue at highest tolerated dose Pulmonary Hypertension Associated with ILD Indicated for treatment of pulmonary hypertension associated with interstitial lung disease (PH-ILD; WHO Group 3) to improve exercise ability Solution for inhalation Initial 18 mcg (3 breaths) per treatment session QID If 3 breaths not tolerated, decrease to 1-2 breaths and later increase to 3 breaths as tolerated Maintenance If tolerated, increase by 3 breaths/dose (18 mcg) q1-2Weeks Target maintenance: 54 mcg (9 breaths) per treatment session QID If adverse effects preclude titration to target dose, continue at highest tolerated dose If effects diminish over minimum recommended dosing interval of 4 hr; treatment timing can be adjusted for planned activities Dry powder for inhalation Initial 16 mcg inhaled per session QID (~4 hr apart during waking hours) Maintenance Increase dosage by 16 mcg/treatment session at ~1- to 2-week intervals Target maintenance: 48-64 mcg/treatment session If prescribed dose >64 mcg/treatment session, >1 cartridge needed per session If adverse effects preclude titration, continue at highest tolerated dose Dosage Modifications Renal impairment No dose adjustments required in patients with renal impairment Drug is not cleared by dialysis Hepatic impairment Uptitrate dose slowly Plasma clearance may be reduced with hepatic insufficiency (reduced up to 80% with SC administration) Patients with hepatic insufficiency may be at increased risk of dose-dependent adverse reactions owing to increased systemic exposure <18 years: Safety and efficacy not established >10% Cough (54%) Headache (41%) Throat irritation/pharyngolaryngeal pain (25%) Nausea (19%) Flushing (15%) 1-10% Syncope (6%) Postmarketing Reports Angioedema Contraindications None Cautions Efficacy of treprostinil inhaled has not been established in patients with significant underlying lung disease (eg, asthma or chronic obstructive pulmonary disease); monitor patients with acute pulmonary infections to detect any worsening of lung disease and loss of drug effect May produce symptomatic hypotension in patients with low systemic arterial pressure Titrate slowly in patients with hepatic or renal insufficiency Inhibits platelet aggregation and increases the risk of bleeding Bronchospasm As with other inhaled prostaglandins, therapy may cause acute bronchospasm Patients with asthma or chronic obstructive pulmonary disease (COPD), or other bronchial hyperreactivity, are at increased risk for bronchospasm Ensure that such patients are treated optimally for reactive airway disease prior to and during treatment Drug interaction overview Oral treprostinil is a CYP2C8 substrate It is unclear if systemic exposure of treprostinil by the inhalation route are altered by inhibitors or inducers of CYP2C8 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) Clinical considerations Pulmonary arterial hypertension is associated with an increased risk of maternal and fetal mortality Lactation Data are not available regarding presence in human milk, effects on breastfed infants, or effects 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 Prostacyclin analog; elicits direct vasodilation of both pulmonary and systemic arterial vascular beds; decreases ventricular afterload; also inhibits platelet aggregation Absorption Bioavailability: ~64% (18 mcg inhalation); ~72% (36 mcg inhalation) Peak plasma concentration: 0.91-1.3 ng/mL (54 mcg inhalation) Peak plasma time: 0.12-0.25 hr (54 mcg inhalation) AUC: 0.81-0.97 ng·hr/mL (54 mcg inhalation) Distribution Protein bound: 91% Vd: 14 L/70 kg IBW (parenteral infusion) Metabolism Substantially metabolized by the liver, primarily by CYP2C8 Elimination Half-life (SC): 4 hr Excretion (SC): Urine 79%; feces 13% Incompatibilities Solution or dry powder for inhalation Do not mix with other medications in the inhalation system Compatibility with other medications has not been studied Oral Inhalation Preparation Solution for inhalation Only use with Tyvaso Inhalation System, which consists of an ultrasonic, pulsed delivery device and its accessories Follow instructions for operating inhalation system and for device cleaning after last daily treatment session Avoid potential interruptions in drug delivery because of equipment malfunction, by having a back-up inhalation system device Prepare inhalation system for use each day according to instructions for use One ampule of treprostinil contains a sufficient volume of medication for all 4 treatment sessions/day Before first treatment session, twist the top off a single ampule and squeeze entire contents into medicine cup Between each treatment session, cap device and store upright with remaining medication inside At end of each day, discard medicine cup and any remaining medication Oral Inhalation Administration Solution for inhalation Avoid skin or eye contact; rinse with water if contact occurs Do not orally ingest Inhale orally via Tyvaso Inhalation System in 4 daily treatment session ~4 hr apart during waking hours Each session will take 2-3 minutes Missed dose: Take as soon as possible and adjust remainder of daily scheduled doses to be 4 hr apart Dry powder for inhalation Administered using a single inhalation per cartridge Administer in 4 separate, equally spaced treatment sessions/day, during waking hours (~4 hr apart) Missed dose: Resume therapy as soon as possible at the usual dose Between each treatment session, store with mouthpiece attached and empty Wipe outside of inhaler with clean, dry cloth only, if needed Do not rinse or wash; always keep inhaler dry After 7 days of use, throw away used inhaler into regular household trash Storage Solution for inhalation Store ampules in foil packs at 25ºC (77ºF); excursions are permitted between 15-30ºC (59-86ºF); protect from light Once foil pack is opened, ampules should be used within 7 days Following transfer of solution to inhalation device, solution should remain in device for ≤24 hr; discard unused portion Dry powder for inhalation If refrigerated, cartridges and inhaler should be at room temperature for 10 minutes before use Inhaler Store at 2-25ºC (36-77ºF); excursions permitted Can be used for up to 7 days from the date of first use After 7 days of use, discard inhaler and replaced with a new inhaler Unopened blister strip cartridges Refrigerate at 2-8ºC (36-46ºF) until expiration date, OR Use within 5 weeks at 20-25ºC (68-77ºF), excursions permitted to 15-30ºC (59-86ºF) Opened blister strip cartridges Do not put blister strip back into refrigerator after being opened or stored at room temperature Use within 3 days at 20-25ºC (68-77ºF), excursions permitted to 15-30ºC (59-86ºF) No images available for this drug. No images available for this drug.A Patient Handout is not currently available for this monograph.Print FormularyPatient DiscountsAdding plans allows you to compare formulary status to other drugs in the same class.To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.Create Your List of PlansAdding plans allows you to:View the formulary and any restrictions for each plan.Manage and view all your plans together – even plans in different states.Compare formulary status to other drugs in the same class.Access your plan list on any device – mobile or desktop. The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information. View explanations for tiers and restrictions Tier Description 1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs. 2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs. 3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs. 4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products. 5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products. 6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products. NC NOT COVERED – Drugs that are not covered by the plan. Code Definition PA Prior Authorization Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription. 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