Drug Facts
Composition & Profile
Identifiers & Packaging
16 HOW SUPPLIED/STORAGE AND HANDLING Tyvaso (treprostinil) inhalation solution is supplied in 2.9 mL clear LDPE ampules packaged as 4 ampules in a foil pouch. Tyvaso is a clear colorless to slightly yellow solution containing 1.74 mg treprostinil per ampule at a concentration of 0.6 mg/mL. Ampules of Tyvaso are stable until the date indicated when stored in the unopened foil pouch at 20-25°C (68-77°F) with excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature]. Once the foil pack is opened, ampules should be used within 7 days. Because Tyvaso is light-sensitive, unopened ampules should be stored in the foil pouch. One ampule of Tyvaso should be used each day in the Tyvaso Inhalation System. After a Tyvaso ampule is opened and transferred to the medicine cup, the solution should remain in the device for no more than 1 day (24 hours). Any remaining solution should be discarded at the end of the day. Tyvaso Inhalation System Starter Kit containing a 28-ampule carton of Tyvaso (7 foil pouches each containing four 2.9 mL ampules; each ampule contains 1.74 mg treprostinil [0.6 mg per mL]) and the Tyvaso Inhalation System. (NDC 66302-206-01) Tyvaso Inhalation System Refill Kit containing a 28-ampule carton of Tyvaso (7 foil pouches each containing four 2.9 mL ampules; each ampule contains 1.74 mg treprostinil [0.6 mg per mL]) and accessories. (NDC 66302-206-02) Tyvaso 4 Pack Carton with 1 foil pouch containing four 2.9 mL ampules. Each ampule contains 1.74 mg treprostinil (0.6 mg per mL). (NDC 66302-206-03) Tyvaso Inhalation System Institutional Starter Kit containing a 4-ampule carton of Tyvaso (1 foil pouch containing four 2.9 mL ampules; each ampule contains 1.74 mg treprostinil [0.6 mg per mL]) and the Tyvaso Inhalation System. (NDC 66302-206-04); PRINCIPAL DISPLAY PANEL - 4 Ampule Pouch Carton TYVASO ® (treprostinil) INHALATION SOLUTION Treprostinil 1.74 mg / 2.9 mL (0.6 mg/mL) Four 2.9 mL ampules For oral inhalation use only See package insert and Instructions For Use manual for dosage and administration Principal Display Panel - 4 Ampule Pouch Carton; PRINCIPAL DISPLAY PANEL - 28 Ampule Pouch Carton TYVASO ® (treprostinil) INHALATION SOLUTION Treprostinil 1.74 mg / 2.9 mL (0.6 mg/mL) Seven foil pouches each containing four 2.9 mL ampules For oral inhalation use only See package insert and Instructions For Use manual for dosage and administration. PRINCIPAL DISPLAY PANEL - 28 Ampule Pouch Carton; PRINCIPAL DISPLAY PANEL - Patient Starter Kit TYVASO Inhalation System Patient Starter Kit TYVASO ® (treprostinil) INHALATION SOLUTION Treprostinil 1.74 mg/2.9 mL (0.6 mg/mL) TYVASO is for oral inhalation use only and is intended for administration with the TYVASO Inhalation System. See package insert and Instructions for Use manual for dosage and administration. CONTENTS QTY CONTENTS QTY + 28 ampule carton of TYVASO (seven foil pouches, each containing four 2.9 mL ampules) 1 + AC wall plugs 2 + TYVASO Inhalation Device 2 + Water level cup 1 + TYVASO Inhalation System Instructions for Use manual 1 + Plugs for storage between treatment sessions 2 + Treatment Tracker 1 + Carrying case 1 + Sets of Dome assembly, Inhalation piece, Mouthpiece, and 2 Filter shells 2 + Distilled water carrier 1 + Medicine cups 32 + Filter membranes 65 Each ampule of TYVASO contains: treprostinil 1.74 mg. Each ampule also contains 18.9 mg sodium chloride, 18.3 mg sodium citrate dihydrate, 0.6 mg sodium hydroxide, 11.7 mg 1N hydrochloric acid, and water for injection. Hydrochloric acid and sodium hydroxide may have been added to adjust pH. + One new ampule should be used each day. Each ampule of TYVASO (once opened and transferred to the medicine cup) should remain in the device for no more than 1 day. Any remaining TYVASO and the medicine cup should be discarded at the end of each day. + Once a foil pouch is opened, use ampules within 7 days. + Store unused ampules of TYVASO in the foil pouch until use, protected from light. + Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Patient Starter Kit For Single Patient Use Only. Keep out of the reach of children. NDC 66302-206-01 Rx only Manufactured by United Therapeutics Corporation Research Triangle Park, NC 27709 United Therapeutics CORPORATION 102129 Rev. 01/2024 PRINCIPAL DISPLAY PANEL - Patient Starter Kit; PRINCIPAL DISPLAY PANEL - Refill Kit TYVASO Inhalation System Refill Kit TYVASO ® (treprostinil) INHALATION SOLUTION Treprostinil 1.74 mg/2.9 mL (0.6 mg/mL) TYVASO is for oral inhalation use only and is intended for administration with the TYVASO Inhalation System. See package insert and Instructions for Use manual for dosage and administration. CONTENTS QTY CONTENTS QTY + 28 ampule carton of TYVASO (seven foil pouches each containing four 2.9 mL ampules) 1 + Filter membranes 65 + Set of Dome assembly, Inhalation piece, Mouthpiece, and 2 Filter shells 1 + Plugs for storage between treatment sessions 2 + Medicine cups 32 + Treatment Tracker 1 Each ampule of TYVASO contains: treprostinil 1.74 mg. Each ampule also contains 18.9 mg sodium chloride, 18.3 mg sodium citrate dihydrate, 0.6 mg sodium hydroxide, 11.7 mg 1N hydrochloric acid, and water for injection. Hydrochloric acid and sodium hydroxide may have been added to adjust pH. + One new ampule should be used each day. Each ampule of TYVASO (once opened and transferred to the medicine cup) should remain in the device for no more than 1 day. Any remaining TYVASO and the medicine cup should be discarded at the end of each day. + Once a foil pouch is opened, use ampules within 7 days. + Store unused ampules of TYVASO in the foil pouch until use, protected from light. + Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Keep out of the reach of children. NDC 66302-206-02 Rx only Manufactured for United Therapeutics Corporation Research Triangle Park, NC 27709 United Therapeutics CORPORATION 102136 Rev. 01/2024 LOT XXXXXXX EXP YYYY-MMM GTIN XXXXXXXXXXXXXX S/N XXXXXXXXXXXX PRINCIPAL DISPLAY PANEL - Refill Kit; PRINCIPAL DISPLAY PANEL - Institutional Starter Kit TYVASO Inhalation System Institutional Starter Kit TYVASO ® (treprostinil) INHALATION SOLUTION Treprostinil 1.74 mg/2.9 mL (0.6 mg/mL) TYVASO is for oral inhalation use only and is intended for administration with the TYVASO Inhalation System. See package insert and Instructions for Use manual for dosage and administration. CONTENTS QTY CONTENTS QTY + 4 ampule carton of TYVASO (one foil pouch containing four 2.9 mL ampules) 1 + AC wall plugs 2 + TYVASO Inhalation Device 2 + Water level cup 1 + TYVASO Inhalation System Instructions for Use manual 1 + Plugs for storage between treatment sessions 2 + Treatment Tracker 1 + Carrying case 1 + Sets of Dome assembly, Inhalation piece, Mouthpiece, and 2 Filter shells 2 + Distilled water carrier 1 + Medicine cups 32 + Filter membranes 65 Each ampule of TYVASO contains: treprostinil 1.74 mg. Each ampule also contains 18.9 mg sodium chloride, 18.3 mg sodium citrate dihydrate, 0.6 mg sodium hydroxide, 11.7 mg 1N hydrochloric acid, and water for injection. Hydrochloric acid and sodium hydroxide may have been added to adjust pH. + One new ampule should be used each day. Each ampule of TYVASO (once opened and transferred to the medicine cup) should remain in the device for no more than 1 day. Any remaining TYVASO and the medicine cup should be discarded at the end of each day. + Once a foil pouch is opened, use ampules within 7 days. + Store unused ampules of TYVASO in the foil pouch until use, protected from light. + Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Institutional Starter Kit For Single Patient Use Only. Keep out of the reach of children. NDC 66302-206-04 Rx only Manufactured by United Therapeutics Corporation Research Triangle Park, NC 27709 United Therapeutics CORPORATION 102130 Rev. 01/2024 PRINCIPAL DISPLAY PANEL - Institutional Starter Kit
- 16 HOW SUPPLIED/STORAGE AND HANDLING Tyvaso (treprostinil) inhalation solution is supplied in 2.9 mL clear LDPE ampules packaged as 4 ampules in a foil pouch. Tyvaso is a clear colorless to slightly yellow solution containing 1.74 mg treprostinil per ampule at a concentration of 0.6 mg/mL. Ampules of Tyvaso are stable until the date indicated when stored in the unopened foil pouch at 20-25°C (68-77°F) with excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature]. Once the foil pack is opened, ampules should be used within 7 days. Because Tyvaso is light-sensitive, unopened ampules should be stored in the foil pouch. One ampule of Tyvaso should be used each day in the Tyvaso Inhalation System. After a Tyvaso ampule is opened and transferred to the medicine cup, the solution should remain in the device for no more than 1 day (24 hours). Any remaining solution should be discarded at the end of the day. Tyvaso Inhalation System Starter Kit containing a 28-ampule carton of Tyvaso (7 foil pouches each containing four 2.9 mL ampules; each ampule contains 1.74 mg treprostinil [0.6 mg per mL]) and the Tyvaso Inhalation System. (NDC 66302-206-01) Tyvaso Inhalation System Refill Kit containing a 28-ampule carton of Tyvaso (7 foil pouches each containing four 2.9 mL ampules; each ampule contains 1.74 mg treprostinil [0.6 mg per mL]) and accessories. (NDC 66302-206-02) Tyvaso 4 Pack Carton with 1 foil pouch containing four 2.9 mL ampules. Each ampule contains 1.74 mg treprostinil (0.6 mg per mL). (NDC 66302-206-03) Tyvaso Inhalation System Institutional Starter Kit containing a 4-ampule carton of Tyvaso (1 foil pouch containing four 2.9 mL ampules; each ampule contains 1.74 mg treprostinil [0.6 mg per mL]) and the Tyvaso Inhalation System. (NDC 66302-206-04)
- PRINCIPAL DISPLAY PANEL - 4 Ampule Pouch Carton TYVASO ® (treprostinil) INHALATION SOLUTION Treprostinil 1.74 mg / 2.9 mL (0.6 mg/mL) Four 2.9 mL ampules For oral inhalation use only See package insert and Instructions For Use manual for dosage and administration Principal Display Panel - 4 Ampule Pouch Carton
- PRINCIPAL DISPLAY PANEL - 28 Ampule Pouch Carton TYVASO ® (treprostinil) INHALATION SOLUTION Treprostinil 1.74 mg / 2.9 mL (0.6 mg/mL) Seven foil pouches each containing four 2.9 mL ampules For oral inhalation use only See package insert and Instructions For Use manual for dosage and administration. PRINCIPAL DISPLAY PANEL - 28 Ampule Pouch Carton
- PRINCIPAL DISPLAY PANEL - Patient Starter Kit TYVASO Inhalation System Patient Starter Kit TYVASO ® (treprostinil) INHALATION SOLUTION Treprostinil 1.74 mg/2.9 mL (0.6 mg/mL) TYVASO is for oral inhalation use only and is intended for administration with the TYVASO Inhalation System. See package insert and Instructions for Use manual for dosage and administration. CONTENTS QTY CONTENTS QTY + 28 ampule carton of TYVASO (seven foil pouches, each containing four 2.9 mL ampules) 1 + AC wall plugs 2 + TYVASO Inhalation Device 2 + Water level cup 1 + TYVASO Inhalation System Instructions for Use manual 1 + Plugs for storage between treatment sessions 2 + Treatment Tracker 1 + Carrying case 1 + Sets of Dome assembly, Inhalation piece, Mouthpiece, and 2 Filter shells 2 + Distilled water carrier 1 + Medicine cups 32 + Filter membranes 65 Each ampule of TYVASO contains: treprostinil 1.74 mg. Each ampule also contains 18.9 mg sodium chloride, 18.3 mg sodium citrate dihydrate, 0.6 mg sodium hydroxide, 11.7 mg 1N hydrochloric acid, and water for injection. Hydrochloric acid and sodium hydroxide may have been added to adjust pH. + One new ampule should be used each day. Each ampule of TYVASO (once opened and transferred to the medicine cup) should remain in the device for no more than 1 day. Any remaining TYVASO and the medicine cup should be discarded at the end of each day. + Once a foil pouch is opened, use ampules within 7 days. + Store unused ampules of TYVASO in the foil pouch until use, protected from light. + Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Patient Starter Kit For Single Patient Use Only. Keep out of the reach of children. NDC 66302-206-01 Rx only Manufactured by United Therapeutics Corporation Research Triangle Park, NC 27709 United Therapeutics CORPORATION 102129 Rev. 01/2024 PRINCIPAL DISPLAY PANEL - Patient Starter Kit
- PRINCIPAL DISPLAY PANEL - Refill Kit TYVASO Inhalation System Refill Kit TYVASO ® (treprostinil) INHALATION SOLUTION Treprostinil 1.74 mg/2.9 mL (0.6 mg/mL) TYVASO is for oral inhalation use only and is intended for administration with the TYVASO Inhalation System. See package insert and Instructions for Use manual for dosage and administration. CONTENTS QTY CONTENTS QTY + 28 ampule carton of TYVASO (seven foil pouches each containing four 2.9 mL ampules) 1 + Filter membranes 65 + Set of Dome assembly, Inhalation piece, Mouthpiece, and 2 Filter shells 1 + Plugs for storage between treatment sessions 2 + Medicine cups 32 + Treatment Tracker 1 Each ampule of TYVASO contains: treprostinil 1.74 mg. Each ampule also contains 18.9 mg sodium chloride, 18.3 mg sodium citrate dihydrate, 0.6 mg sodium hydroxide, 11.7 mg 1N hydrochloric acid, and water for injection. Hydrochloric acid and sodium hydroxide may have been added to adjust pH. + One new ampule should be used each day. Each ampule of TYVASO (once opened and transferred to the medicine cup) should remain in the device for no more than 1 day. Any remaining TYVASO and the medicine cup should be discarded at the end of each day. + Once a foil pouch is opened, use ampules within 7 days. + Store unused ampules of TYVASO in the foil pouch until use, protected from light. + Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Keep out of the reach of children. NDC 66302-206-02 Rx only Manufactured for United Therapeutics Corporation Research Triangle Park, NC 27709 United Therapeutics CORPORATION 102136 Rev. 01/2024 LOT XXXXXXX EXP YYYY-MMM GTIN XXXXXXXXXXXXXX S/N XXXXXXXXXXXX PRINCIPAL DISPLAY PANEL - Refill Kit
- PRINCIPAL DISPLAY PANEL - Institutional Starter Kit TYVASO Inhalation System Institutional Starter Kit TYVASO ® (treprostinil) INHALATION SOLUTION Treprostinil 1.74 mg/2.9 mL (0.6 mg/mL) TYVASO is for oral inhalation use only and is intended for administration with the TYVASO Inhalation System. See package insert and Instructions for Use manual for dosage and administration. CONTENTS QTY CONTENTS QTY + 4 ampule carton of TYVASO (one foil pouch containing four 2.9 mL ampules) 1 + AC wall plugs 2 + TYVASO Inhalation Device 2 + Water level cup 1 + TYVASO Inhalation System Instructions for Use manual 1 + Plugs for storage between treatment sessions 2 + Treatment Tracker 1 + Carrying case 1 + Sets of Dome assembly, Inhalation piece, Mouthpiece, and 2 Filter shells 2 + Distilled water carrier 1 + Medicine cups 32 + Filter membranes 65 Each ampule of TYVASO contains: treprostinil 1.74 mg. Each ampule also contains 18.9 mg sodium chloride, 18.3 mg sodium citrate dihydrate, 0.6 mg sodium hydroxide, 11.7 mg 1N hydrochloric acid, and water for injection. Hydrochloric acid and sodium hydroxide may have been added to adjust pH. + One new ampule should be used each day. Each ampule of TYVASO (once opened and transferred to the medicine cup) should remain in the device for no more than 1 day. Any remaining TYVASO and the medicine cup should be discarded at the end of each day. + Once a foil pouch is opened, use ampules within 7 days. + Store unused ampules of TYVASO in the foil pouch until use, protected from light. + Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Institutional Starter Kit For Single Patient Use Only. Keep out of the reach of children. NDC 66302-206-04 Rx only Manufactured by United Therapeutics Corporation Research Triangle Park, NC 27709 United Therapeutics CORPORATION 102130 Rev. 01/2024 PRINCIPAL DISPLAY PANEL - Institutional Starter Kit
Overview
Tyvaso is a sterile formulation of treprostinil, a prostacyclin mimetic, intended for administration by oral inhalation using the Tyvaso Inhalation System. Tyvaso is supplied in 2.9 mL low density polyethylene (LDPE) ampules, containing 1.74 mg treprostinil (0.6 mg/mL). Each ampule also contains 18.9 mg sodium chloride, 18.3 mg sodium citrate dihydrate, 0.58 mg sodium hydroxide, 11.7 mg 1 N hydrochloric acid, and water for injection. Sodium hydroxide and hydrochloric acid may be added to adjust pH between 6.0 and 7.2. Treprostinil is (1 R ,2 R ,3a S ,9a S )-[[2,3,3a,4,9,9a-hexahydro-2-hydroxy-1-[(3 S )-3-hydroxyoctyl]-1 H -benz[ f ]inden-5-yl]oxy]acetic acid. Treprostinil has a molecular weight of 390.52 and a molecular formula of C 23 H 34 O 5 . The structural formula of treprostinil is: Chemical Structure
Indications & Usage
Tyvaso is a prostacyclin mimetic indicated for the treatment of: Pulmonary arterial hypertension (PAH; WHO Group 1) to improve exercise ability. Studies establishing effectiveness predominately included patients with NYHA Functional Class III symptoms and etiologies of idiopathic or heritable PAH (56%) or PAH associated with connective tissue diseases (33%). ( 1.1 ) Pulmonary hypertension associated with interstitial lung disease (PH-ILD; WHO Group 3) to improve exercise ability. The study establishing effectiveness predominately included patients with etiologies of idiopathic interstitial pneumonia (IIP) (45%) inclusive of idiopathic pulmonary fibrosis (IPF), combined pulmonary fibrosis and emphysema (CPFE) (25%), and WHO Group 3 connective tissue disease (22%). ( 1.2 ) 1.1 Pulmonary Arterial Hypertension Tyvaso is indicated for the treatment of pulmonary arterial hypertension (PAH; WHO Group 1) to improve exercise ability. Studies establishing effectiveness predominately included patients with NYHA Functional Class III symptoms and etiologies of idiopathic or heritable PAH (56%) or PAH associated with connective tissue diseases (33%). The effects diminish over the minimum recommended dosing interval of 4 hours; treatment timing can be adjusted for planned activities. While there are long-term data on use of treprostinil by other routes of administration, nearly all controlled clinical experience with inhaled treprostinil has been on a background of bosentan (an endothelin receptor antagonist) or sildenafil (a phosphodiesterase type 5 inhibitor). The controlled clinical experience was limited to 12 weeks in duration [see Clinical Studies (14) ] . 1.2 Pulmonary Hypertension Associated with ILD Tyvaso is indicated for the treatment of pulmonary hypertension associated with interstitial lung disease (PH-ILD; WHO Group 3) to improve exercise ability. The study establishing effectiveness predominately included patients with etiologies of idiopathic interstitial pneumonia (IIP) (45%) inclusive of idiopathic pulmonary fibrosis (IPF), combined pulmonary fibrosis and emphysema (CPFE) (25%), and WHO Group 3 connective tissue disease (22%) [see Clinical Studies (14) ] .
Dosage & Administration
Use only with the Tyvaso Inhalation System. ( 2.1 ) Administer undiluted, as supplied. A single breath of Tyvaso delivers approximately 6 mcg of treprostinil. ( 2.1 ) Administer in 4 separate treatment sessions each day approximately 4 hours apart, during waking hours. ( 2.1 ) Initial dosage: 3 breaths (18 mcg) per treatment session. If 3 breaths are not tolerated, reduce to 1 or 2 breaths. ( 2.1 ) Dosage should be increased by an additional 3 breaths per treatment session at approximately 1- to 2-week intervals, if tolerated. ( 2.1 ) Titrate to target maintenance doses of 9 to 12 breaths per treatment session, 4 times daily. ( 2.1 ) 2.1 Usual Dosage in Adults Tyvaso is intended for oral inhalation using the Tyvaso Inhalation System, which consists of an ultrasonic, pulsed delivery device and its accessories. Tyvaso is dosed in 4 separate, equally spaced treatment sessions per day, during waking hours. Each treatment session will take 2 to 3 minutes. The treatment sessions should be approximately 4 hours apart. Initial Dosage: Therapy should begin with 3 breaths of Tyvaso (18 mcg of treprostinil) per treatment session 4 times daily. If 3 breaths are not tolerated, reduce to 1 or 2 breaths and subsequently increase to 3 breaths, as tolerated. Maintenance Dosage: Dosage should be increased by an additional 3 breaths per treatment session, 4 times daily at approximately 1- to 2-week intervals. Studies establishing effectiveness in patients with PAH and PH-ILD have used target doses of 9 to 12 breaths per treatment session, 4 times daily. If adverse effects preclude titration to target dose, Tyvaso should be continued at the highest tolerated dose. If a scheduled treatment session is missed or interrupted, therapy should be resumed as soon as possible at the usual dose. 2.2 Administration Tyvaso must be used only with the Tyvaso Inhalation System. Patients should follow the instructions for use for operation of the Tyvaso Inhalation System and for daily cleaning of the device components after the last treatment session of the day. To avoid potential interruptions in drug delivery because of equipment malfunction, patients should have access to a back-up Tyvaso Inhalation System device. Do not mix Tyvaso with other medications in the Tyvaso Inhalation System. Compatibility of Tyvaso with other medications has not been studied. The Tyvaso Inhalation System should be prepared for use each day according to the instructions for use. One ampule of Tyvaso contains a sufficient volume of medication for all 4 treatment sessions in a single day. Prior to the first treatment session, the patient should twist the top off a single Tyvaso ampule and squeeze the entire contents into the medicine cup. Between each of the 4 daily treatment sessions, the device should be capped and stored upright with the remaining medication inside. At the end of each day, the medicine cup and any remaining medication must be discarded. The device must be cleaned each day according to the instructions for use. Avoid skin or eye contact with Tyvaso solution. Do not orally ingest the Tyvaso solution.
Warnings & Precautions
Tyvaso may cause symptomatic hypotension. ( 5.1 ) Tyvaso inhibits platelet aggregation and increases the risk of bleeding. ( 5.2 ) Tyvaso dosage adjustments may be necessary if inhibitors or inducers of CYP2C8 are added or withdrawn. ( 5.3 , 7.3 ) May cause bronchospasm: Patients with a history of hyperreactive airway disease may be more sensitive. ( 5.4 ) 5.1 Risk of Symptomatic Hypotension Treprostinil is a pulmonary and systemic vasodilator. In patients with low systemic arterial pressure, treatment with Tyvaso may produce symptomatic hypotension. 5.2 Risk of Bleeding Tyvaso inhibits platelet aggregation and increases the risk of bleeding. 5.3 Effect of Other Drugs on Treprostinil Co-administration of a cytochrome P450 (CYP) 2C8 enzyme inhibitor (e.g., gemfibrozil) may increase exposure (both C max and AUC) to treprostinil. Co-administration of a CYP2C8 enzyme inducer (e.g., rifampin) may decrease exposure to treprostinil. Increased exposure is likely to increase adverse events associated with treprostinil administration, whereas decreased exposure is likely to reduce clinical effectiveness [see Drug Interactions (7.3) and Clinical Pharmacology (12.3) ] . 5.4 Bronchospasm Like other inhaled prostaglandins, Tyvaso 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 with Tyvaso Inhalation Solution.
Contraindications
None. None. ( 4 )
Adverse Reactions
The following potential adverse reactions are described in Warnings and Precautions (5): - Decrease in systemic blood pressure [see Warnings and Precautions (5.1) ] . - Bleeding [see Warnings and Precautions (5.2) ] . Most common adverse reactions (≥4%) are cough, headache, nausea, dizziness, flushing, throat irritation, pharyngolaryngeal pain, diarrhea, and syncope. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact United Therapeutics Corp. at 1-866-458-6479 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Pulmonary Arterial Hypertension In a 12-week, placebo-controlled study (TRIUMPH I) of 235 patients with PAH (WHO Group 1 and nearly all NYHA Functional Class III), the most commonly reported adverse reactions on Tyvaso included cough and throat irritation, headache, gastrointestinal effects, muscle, jaw or bone pain, dizziness, flushing, and syncope. Table 1 lists the adverse reactions that occurred at a rate of at least 4% and were more frequent in patients treated with Tyvaso than with placebo. Table 1: Adverse Events in ≥4% of PAH Patients Receiving Tyvaso and More Frequent More than 3% greater than placebo than Placebo in TRIUMPH I Adverse Event Treatment n (%) Tyvaso n=115 Placebo n=120 Cough 62 (54) 35 (29) Headache 47 (41) 27 (23) Throat Irritation / Pharyngolaryngeal Pain 29 (25) 17 (14) Nausea 22 (19) 13 (11) Flushing 17 (15) 1 (<1) Syncope 7 (6) 1 (<1) The safety of Tyvaso was also studied in a long-term, open-label extension study in which 206 patients were dosed for a mean duration of 2.3 years, with a maximum exposure of 5.4 years. Eighty-nine percent (89%) of patients achieved the target dose of 9 breaths, 4 times daily. Forty-two percent (42%) achieved a dose of 12 breaths, 4 times daily. The adverse events during this chronic dosing study were qualitatively similar to those observed in the 12-week placebo-controlled trial. In a prospective, observational study comparing patients taking Tyvaso (958 patient-years of exposure) and a control group (treatment with other approved therapies for PAH; 1094 patient-years), Tyvaso was associated with a higher rate of cough (16.2 vs. 10.9 per 100 patient-years), throat irritation (4.5 vs. 1.2 per 100 pt-years), nasal discomfort (2.6 vs. 1.3 per 100 pt-years), and hemoptysis (2.5 vs. 1.3 per 100 pt-years) compared to the control group. Pulmonary Hypertension Associated with ILD In a 16-week, placebo-controlled study (INCREASE) of 326 patients with PH-ILD (WHO Group 3), adverse reactions were similar to the experience in studies of PAH. 6.2 Post-Marketing Experience The adverse reaction of angioedema has been identified during the post-approval use of Tyvaso. Because this reaction is reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate the frequency or establish a causal relationship to drug exposure.
Drug Interactions
7.1 Bosentan In a human pharmacokinetic study conducted with bosentan (250 mg/day) and an oral formulation of treprostinil (treprostinil diolamine), no pharmacokinetic interactions between treprostinil and bosentan were observed. 7.2 Sildenafil In a human pharmacokinetic study conducted with sildenafil (60 mg/day) and an oral formulation of treprostinil (treprostinil diolamine), no pharmacokinetic interactions between treprostinil and sildenafil were observed. 7.3 Effect of Cytochrome P450 Inhibitors and Inducers In vitro studies of human hepatic microsomes showed that treprostinil does not inhibit cytochrome P450 (CYP) isoenzymes CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A. Additionally, treprostinil does not induce cytochrome P450 isoenzymes CYP1A2, CYP2B6, CYP2C9, CYP2C19, and CYP3A. Human pharmacokinetic studies with an oral formulation of treprostinil (treprostinil diolamine) indicated that co-administration of the cytochrome P450 (CYP) 2C8 enzyme inhibitor, gemfibrozil, increases exposure (both C max and AUC) to treprostinil. Co-administration of the CYP2C8 enzyme inducer, rifampin, decreases exposure to treprostinil. It is unclear if the safety and efficacy of treprostinil by the inhalation route are altered by inhibitors or inducers of CYP2C8 [see Warnings and Precautions (5.3) ] . 7.4 Effect of Other Drugs on Treprostinil Drug interaction studies have been carried out with treprostinil (oral or subcutaneous) co-administered with acetaminophen (4 g/day), warfarin (25 mg/day), and fluconazole (200 mg/day), respectively, in healthy volunteers. These studies did not show a clinically significant effect on the pharmacokinetics of treprostinil. Treprostinil does not affect the pharmacokinetics or pharmacodynamics of warfarin. The pharmacokinetics of R- and S- warfarin and the international normalized ratio (INR) in healthy subjects given a single 25 mg dose of warfarin were unaffected by continuous subcutaneous infusion of treprostinil at an infusion rate of 10 ng/kg/min.
Storage & Handling
Ampules of Tyvaso are stable until the date indicated when stored in the unopened foil pouch at 20-25°C (68-77°F) with excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature]. Once the foil pack is opened, ampules should be used within 7 days. Because Tyvaso is light-sensitive, unopened ampules should be stored in the foil pouch. One ampule of Tyvaso should be used each day in the Tyvaso Inhalation System. After a Tyvaso ampule is opened and transferred to the medicine cup, the solution should remain in the device for no more than 1 day (24 hours). Any remaining solution should be discarded at the end of the day. Tyvaso Inhalation System Starter Kit containing a 28-ampule carton of Tyvaso (7 foil pouches each containing four 2.9 mL ampules; each ampule contains 1.74 mg treprostinil [0.6 mg per mL]) and the Tyvaso Inhalation System. (NDC 66302-206-01) Tyvaso Inhalation System Refill Kit containing a 28-ampule carton of Tyvaso (7 foil pouches each containing four 2.9 mL ampules; each ampule contains 1.74 mg treprostinil [0.6 mg per mL]) and accessories. (NDC 66302-206-02) Tyvaso 4 Pack Carton with 1 foil pouch containing four 2.9 mL ampules. Each ampule contains 1.74 mg treprostinil (0.6 mg per mL). (NDC 66302-206-03) Tyvaso Inhalation System Institutional Starter Kit containing a 4-ampule carton of Tyvaso (1 foil pouch containing four 2.9 mL ampules; each ampule contains 1.74 mg treprostinil [0.6 mg per mL]) and the Tyvaso Inhalation System. (NDC 66302-206-04)
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