TYVASO DPI- treprostinil inhalant TYVASO DPI- treprostinil kit

Tyvaso DPI by

Drug Labeling and Warnings

Tyvaso DPI by is a Prescription medication manufactured, distributed, or labeled by United Therapeutics Corporation. Drug facts, warnings, and ingredients follow.

Drug Details [pdf]

• HIGHLIGHTS OF PRESCRIBING INFORMATION

  These highlights do not include all the information needed to use TYVASO DPI safely and effectively. See full prescribing information for TYVASO DPI.
  
  TYVASO DPI® (treprostinil) inhalation powder, for oral inhalation use
  Initial U.S. Approval: 2002

  INDICATIONS AND USAGE

  Tyvaso DPI is a prostacyclin mimetic indicated for the treatment of:

  • Pulmonary arterial hypertension (PAH; WHO Group 1) to improve exercise ability. Studies with Tyvaso 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 with Tyvaso 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)

  DOSAGE AND ADMINISTRATION

  • Use only with the Tyvaso DPI Inhaler. (2.1)
  • Administer using a single inhalation per cartridge. (2.1)
  • Administer in 4 separate treatment sessions each day approximately 4 hours apart, during waking hours. (2.1)
  • Initial dosage: one 16 mcg cartridge per treatment session. (2.2)
  • Dosage should be increased by an additional 16 mcg per treatment session at approximately 1- to 2-week intervals, if tolerated. (2.2)
  • Titrate to target maintenance doses of 48 mcg to 64 mcg per treatment session, 4 times daily. (2.2)

  DOSAGE FORMS AND STRENGTHS

  Inhalation powder: Single-dose plastic cartridges containing 16 mcg, 32 mcg, 48 mcg, 64 mcg, or 80 mcg of treprostinil as a dry powder formulation. (3)

  CONTRAINDICATIONS

  None. (4)

  WARNINGS AND PRECAUTIONS

  • Tyvaso DPI may cause symptomatic hypotension. (5.1)
  • Tyvaso DPI inhibits platelet aggregation and increases the risk of bleeding. (5.2)
  • Tyvaso DPI dosage adjustments may be necessary if inhibitors or inducers of CYP2C8 are added or withdrawn.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)

  ADVERSE REACTIONS

  Most common adverse reactions (≥4%) are cough, headache, throat irritation/pharyngolaryngeal pain, nausea, flushing, dyspnea, and syncope. (6.1)

  
  

  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.

  See 17 for PATIENT COUNSELING INFORMATION.

  Revised: 10/2024

• Table of Contents

  FULL PRESCRIBING INFORMATION: CONTENTS*

  1 INDICATIONS AND USAGE

  1.1 Pulmonary Arterial Hypertension

  1.2 Pulmonary Hypertension Associated with ILD

  2 DOSAGE AND ADMINISTRATION

  2.1 Administration

  2.2 Usual Dosage in Adults

  3 DOSAGE FORMS AND STRENGTHS

  4 CONTRAINDICATIONS

  5 WARNINGS AND PRECAUTIONS

  5.1 Risk of Symptomatic Hypotension

  5.2 Risk of Bleeding

  5.3 Effect of Other Drugs on Treprostinil

  5.4 Bronchospasm

  6 ADVERSE REACTIONS

  6.1 Clinical Trials Experience

  7 DRUG INTERACTIONS

  7.1 Bosentan

  7.2 Sildenafil

  7.3 Effect of Cytochrome P450 Inhibitors and Inducers

  7.4 Effect of Other Drugs on Treprostinil

  8 USE IN SPECIFIC POPULATIONS

  8.1 Pregnancy

  8.2 Lactation

  8.4 Pediatric Use

  8.5 Geriatric Use

  8.6 Patients with Hepatic Insufficiency

  8.7 Patients with Renal Impairment

  10 OVERDOSAGE

  11 DESCRIPTION

  11.1 Tyvaso DPI Cartridges

  12 CLINICAL PHARMACOLOGY

  12.1 Mechanism of Action

  12.2 Pharmacodynamics

  12.3 Pharmacokinetics

  13 NONCLINICAL TOXICOLOGY

  13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

  13.2 Animal Toxicology and/or Pharmacology

  14 CLINICAL STUDIES

  14.1 Pulmonary Arterial Hypertension (WHO Group 1) (TRIUMPH I)

  14.2 Long-term Treatment of PAH

  14.3 Pulmonary Hypertension Associated with ILD (WHO Group 3)

  16 HOW SUPPLIED/STORAGE AND HANDLING

  17 PATIENT COUNSELING INFORMATION

  * Sections or subsections omitted from the full prescribing information are not listed.

1 INDICATIONS AND USAGE

1.1 Pulmonary Arterial Hypertension

Tyvaso DPI is indicated for the treatment of pulmonary arterial hypertension (PAH; WHO Group 1) to improve exercise ability. Studies with Tyvaso 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 clinical experience with inhaled treprostinil has been on a background of an endothelin receptor antagonist (ERA) and/or a phosphodiesterase type 5 (PDE-5) inhibitor. The controlled clinical experience with Tyvaso was limited to 12 weeks in duration [see Clinical Studies (14)].

1.2 Pulmonary Hypertension Associated with ILD

Tyvaso DPI is indicated for the treatment of pulmonary hypertension associated with interstitial lung disease (PH-ILD; WHO Group 3) to improve exercise ability. The study with Tyvaso 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 (14.3)].

2 DOSAGE AND ADMINISTRATION

2.1 Administration

Use Tyvaso DPI only with the Tyvaso DPI Inhaler. Tyvaso DPI is administered using a single inhalation per cartridge. Administer Tyvaso DPI in 4 separate, equally spaced treatment sessions per day, during waking hours. The treatment sessions should be approximately 4 hours apart.

If the prescribed dose is higher than 80 mcg per treatment session, more than 1 cartridge will be needed per session. Patients should follow the instructions for use for operation and care of the Tyvaso DPI Inhaler.

Do not use the Tyvaso DPI Inhaler with other medications.

Between each of the 4 daily treatment sessions, store the Tyvaso DPI Inhaler with the mouthpiece attached and empty. Wipe the outside of the inhaler with a clean, dry cloth only, if needed. Do not rinse or wash the Tyvaso DPI Inhaler; always keep the inhaler dry. After 7 days of use, throw away the used Tyvaso DPI Inhaler into regular household trash.

2.2 Usual Dosage in Adults

Initial Dosage:

Tyvaso DPI therapy should begin with one 16 mcg cartridge per treatment session, 4 times daily.

Maintenance Dosage:

Increase dosage by an additional 16 mcg per treatment session at approximately 1- to 2-week intervals. The target maintenance dosage is usually 48 mcg to 64 mcg per session.

If adverse effects preclude titration, continue Tyvaso DPI at the highest tolerated dose.

If a scheduled treatment session is missed, resume therapy as soon as possible at the usual dose.

Dosage for Transition from Tyvaso® (treprostinil) Inhalation Solution:

The following regimens of Tyvaso DPI and Tyvaso give similar exposure:

Tyvaso DPI Cartridge Strength	Tyvaso Number of Breaths
16 mcg	≤5 (≤30 mcg)
32 mcg	6 to 7 (36 to 42 mcg)
48 mcg	8 to 10 (48 to 60 mcg)
64 mcg	11 to 13 (66 to 78 mcg)
80 mcg	14 to 15 (84 to 90 mcg)

3 DOSAGE FORMS AND STRENGTHS

Inhalation powder: Single-dose plastic cartridges containing 16 mcg, 32 mcg, 48 mcg, 64 mcg, or 80 mcg of treprostinil as a dry powder formulation.

4 CONTRAINDICATIONS

None.

5 WARNINGS AND PRECAUTIONS

5.1 Risk of Symptomatic Hypotension

Treprostinil is a pulmonary and systemic vasodilator. In patients with low systemic arterial pressure, treatment with Tyvaso DPI may produce symptomatic hypotension.

5.2 Risk of Bleeding

Tyvaso DPI 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 Cmax 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 DPI 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 DPI.

6 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)].

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

Tyvaso DPI

In a 3-week, open-label, single-sequence, safety and tolerability study (BREEZE) conducted in 51 patients on stable doses of Tyvaso Inhalation Solution who switched to a corresponding dose of Tyvaso DPI, the most commonly reported adverse events on Tyvaso DPI during the 3-week treatment phase included cough, headache, dyspnea, and nausea. Patient tolerability, as assessed by incidence of new adverse events following transition to Tyvaso DPI, was consistent with the expected known safety profile of Tyvaso Inhalation Solution. Table 1 lists the adverse events that occurred at a rate of at least 4%.

Table 1: Adverse Events in ≥4% of PAH Patients Receiving Tyvaso DPI in BREEZE (Treatment Phase)

Adverse Event	Tyvaso DPI (n=51) n (%)
	Cough	18 (35.3)
Headache	8 (15.7)
Dyspnea	4 (7.8)
Nausea	3 (5.9)

The safety of Tyvaso DPI was also studied in an extension phase of the study in which 49 patients were dosed for a duration of 43 patient-years. Fifty-nine percent (59%) of patients achieved a dose of 64 mcg, 4 times daily or higher. The adverse events during this long-term, extension phase were similar to those observed in the 3-week treatment phase.

Tyvaso Inhalation Solution

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 Inhalation Solution included cough and throat irritation, headache, gastrointestinal effects, muscle, jaw or bone pain, dizziness, flushing, and syncope. Table 2 lists the adverse reactions that occurred at a rate of at least 4% and were more frequent in patients treated with Tyvaso Inhalation Solution than with placebo.

Table 2: Adverse Events in ≥4% of PAH Patients Receiving Tyvaso Inhalation Solution and More Frequent* than Placebo in TRIUMPH I

Adverse Event	Treatment n (%)
	Tyvaso Inhalation Solution n=115	Placebo n=120
* More than 3% greater than placebo
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)

Pulmonary Hypertension Associated with ILD

In a 16-week, placebo-controlled study (INCREASE) of 326 patients with PH-ILD (WHO Group 3), adverse reactions on Tyvaso Inhalation Solution were similar to the experience in studies of PAH.

7 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 Cmax 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.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

Limited case reports of treprostinil use in pregnant women are insufficient to inform a drug-associated risk of adverse developmental outcomes. However, there are risks to the mother and the fetus associated with pulmonary arterial hypertension (see Clinical Considerations). In animal studies, no adverse reproductive and developmental effects were seen for treprostinil at ≥8 and ≥134 times the human exposure when based on Cmax and AUC, respectively, following a single, inhaled 64 mcg dose of treprostinil inhalation powder.

The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Clinical Considerations

Disease-associated maternal and embryo-fetal risk

Pulmonary arterial hypertension is associated with an increased risk of maternal and fetal mortality.

Data

Animal reproduction studies have been conducted with treprostinil via continuous subcutaneous administration and with treprostinil diolamine administered orally. In studies with orally administered treprostinil diolamine, no adverse effect doses for fetal viability/growth, fetal development (teratogenicity), and postnatal development were determined in rats. In pregnant rats, no evidence of harm to the fetus was observed following oral administration of treprostinil diolamine at the highest dose tested (20 mg/kg/day), which represents about 129 and 1366 times the human exposure, when based on Cmax and AUC, respectively, following a single, inhaled 64 mcg dose of treprostinil inhalation powder. In pregnant rabbits, external fetal and soft tissue malformations and fetal skeletal malformation occurred. The dose at which no adverse effects were seen (0.5 mg/kg/day) represents about 8 and 134 times the human exposure, when based on Cmax and AUC, respectively, following a single, inhaled 64 mcg dose of treprostinil inhalation powder. No treprostinil treatment-related effects on labor and delivery were seen in animal studies. Animal reproduction studies are not always predictive of human response.

8.2 Lactation

Risk Summary

There are no data on the presence of treprostinil in human milk, the effects on the breastfed infant, or the effects on milk production.

8.4 Pediatric Use

Safety and effectiveness in pediatric patients have not been established. Clinical studies of inhaled treprostinil did not include patients younger than 18 years to determine whether they respond differently from older patients.

8.5 Geriatric Use

Across clinical studies used to establish the effectiveness of Tyvaso Inhalation Solution in patients with PAH and PH-ILD, 268 (47.8%) patients aged 65 years and over were enrolled. The treatment effects and safety profile observed in geriatric patients were similar to younger patients. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of hepatic, renal, or cardiac dysfunction, and of concomitant diseases or other drug therapy.

8.6 Patients with Hepatic Insufficiency

Plasma clearance of treprostinil, delivered subcutaneously, was reduced up to 80% in subjects with mild-to-moderate hepatic insufficiency. Uptitrate slowly when treating patients with hepatic insufficiency because of the risk of an increase in systemic exposure which may lead to an increase in dose-dependent adverse effects. Treprostinil has not been studied in patients with severe hepatic insufficiency [see Clinical Pharmacology (12.3)].

8.7 Patients with Renal Impairment

No dose adjustments are required in patients with renal impairment. Treprostinil is not cleared by dialysis [see Clinical Pharmacology (12.3)].

10 OVERDOSAGE

In general, symptoms of overdose with inhaled treprostinil include flushing, headache, hypotension, nausea, vomiting, and diarrhea. Provide general supportive care until the symptoms of overdose have resolved.

11 DESCRIPTION

11.1 Tyvaso DPI Cartridges

Tyvaso DPI consists of single-dose plastic cartridges filled with a white powder containing 1% of treprostinil, a prostacyclin mimetic, which is intended for administration by oral inhalation using the Tyvaso DPI Inhaler only. Treprostinil is adsorbed onto carrier particles consisting of fumaryl diketopiperazine (FDKP). Each cartridge contains 16 mcg, 32 mcg, 48 mcg, 64 mcg, or 80 mcg of treprostinil with approximate fill weights of 1.6 mg, 3.2 mg, 4.8 mg, 6.4 mg, or 8.0 mg of Tyvaso DPI, respectively.

Treprostinil is (1R,2R,3aS,9aS)-[[2,3,3a,4,9,9a-hexahydro-2-hydroxy-1-[(3S)-3-hydroxyoctyl]-1H-benz[f]inden-5-yl]oxy]acetic acid. Treprostinil has a molecular weight of 390.52 and a molecular formula of C23H34O5.

The structural formula of treprostinil is:

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Treprostinil is a prostacyclin analogue. The major pharmacologic actions of treprostinil are direct vasodilation of pulmonary and systemic arterial vascular beds and inhibition of platelet aggregation.

12.2 Pharmacodynamics

In a clinical trial of 240 healthy volunteers, single doses of Tyvaso Inhalation Solution 54 mcg (the target maintenance dose per session) and 84 mcg (supratherapeutic inhalation dose) prolonged the corrected QTc interval by approximately 10 ms. The QTc effect dissipated as the concentration of treprostinil decreased.

12.3 Pharmacokinetics

Absorption

Treprostinil plasma exposure data were obtained from a 6-treatment, 6-period, 6-sequence, crossover study of Tyvaso DPI and Tyvaso Inhalation Solution in healthy volunteers. The mean Cmax for the 16, 48, and 64 mcg doses of Tyvaso DPI were 0.39, 1.11, and 1.33 ng/mL, respectively, with corresponding median Tmax of 0.17 hr. The mean AUC0-5hr for the 16, 48, and 64 mcg doses of Tyvaso DPI were 0.275, 0.774, and 0.964 hr∙ng/mL, respectively.

Treprostinil systemic exposure (AUC0-5hr and Cmax) of Tyvaso DPI post-inhalation was approximately proportional to the doses administered (16 to 64 mcg).

Distribution

Following parenteral infusion, the steady state volume of distribution (Vss) of treprostinil is approximately 14 L/70 kg ideal body weight.

In vitro treprostinil is 91% bound to human plasma proteins over the 330 to 10,000 mcg/L concentration range.

Elimination

With a single dose of Tyvaso DPI, the mean terminal half-life of treprostinil ranged from 27 to 50 minutes.

Metabolism: Treprostinil is substantially metabolized by the liver, primarily by CYP2C8. Metabolites are excreted in urine (79%) and feces (13%) over 10 days. Five apparently inactive metabolites were detected in the urine, each accounting for 10 to 15% of the dose administered. Four of the metabolites are products of oxidation of the 3-hydroxyloctyl side chain and one is a glucuroconjugated derivative (treprostinil glucuronide).

Excretion: Of subcutaneously administered treprostinil, only 4% is excreted unchanged in urine.

Specific Populations

Hepatic Insufficiency

Plasma clearance of treprostinil, delivered subcutaneously, was reduced up to 80% in subjects presenting with mild-to-moderate hepatic insufficiency. Treprostinil has not been studied in patients with severe hepatic insufficiency [see Use in Specific Populations (8.6)].

Renal Impairment

In patients with severe renal impairment requiring dialysis (n=8), administration of a single 1 mg dose of orally administered treprostinil pre- and post-dialysis resulted in AUC0-inf that was not significantly altered compared to healthy subjects [see Use in Specific Populations (8.7)].

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

A 2-year rat carcinogenicity study was performed with treprostinil inhalation at target doses of 5.26, 10.6, and 34.1 mcg/kg/day. There was no evidence for carcinogenic potential associated with treprostinil inhalation in rats at systemic exposure levels up to 36 times the clinical exposure at the 64 mcg dose of treprostinil inhalation powder. In vitro and in vivo genetic toxicology studies did not demonstrate any mutagenic or clastogenic effects of treprostinil. Treprostinil sodium did not affect fertility or mating performance of male or female rats given continuous subcutaneous infusions at rates of up to 450 ng treprostinil/kg/min. In this study, males were dosed from 10 weeks prior to mating and through the 2-week mating period. Females were dosed from 2 weeks prior to mating until gestational day 6.

Oral administration of treprostinil diolamine to Tg.rasH2 mice at 0, 5, 10, and 20 mg/kg/day in males and 0, 3, 7.5, and 15 mg/kg/day in females daily for 26 weeks did not significantly increase the incidence of tumors.

Treprostinil diolamine was tested in vivo in a rat micronucleus assay and did not induce an increased incidence of micronucleated polychromatic erythrocytes.

13.2 Animal Toxicology and/or Pharmacology

In a 2-year rat study with treprostinil inhalation solution at target doses of 5.26, 10.6, and 34.1 mcg/kg/day, there were more deaths (11) in the mid- and high-dose treprostinil groups during the first 9 weeks of the study, compared to 1 in control groups. At the high-dose level, males showed a higher incidence of inflammation in teeth and preputial gland, and females showed higher incidences of inflammation and urothelial hyperplasia in the urinary bladder. The exposures in rats at mid- and high-dose levels were about 14 and 36 times, respectively, the clinical exposure at the 64 mcg dose of treprostinil inhalation powder.

14 CLINICAL STUDIES

14.1 Pulmonary Arterial Hypertension (WHO Group 1) (TRIUMPH I)

TRIUMPH I, was a 12-week, randomized, double-blind, placebo-controlled, multicenter study of patients with PAH (NCT00147199). The study population included 235 clinically stable subjects with PAH (WHO Group 1), nearly all with NYHA Class III (98%) symptoms who were receiving either bosentan (an endothelin receptor antagonist) or sildenafil (a phosphodiesterase-5 inhibitor) for at least 3 months prior to study initiation. Concomitant therapy also could have included anticoagulants, other vasodilators (e.g., calcium channel blockers), diuretics, oxygen, and digitalis, but not a prostacyclin. These patients were administered either placebo or Tyvaso Inhalation Solution in 4 daily treatment sessions with a target dose of 9 breaths (54 mcg) per session over the course of the 12-week study. Patients were predominately female (82%), had the origin of PAH as idiopathic/heritable (56%), secondary to connective tissue diseases (33%) or secondary to HIV or previous use of anorexigens (12%); bosentan was the concomitant oral medication in 70% of those enrolled, sildenafil in 30%.

The primary efficacy endpoint of the trial was the change in 6MWD relative to baseline at 12 weeks. 6MWD was measured at peak exposure (between 10 and 60 minutes after dosing), and 3 to 5 hours after bosentan or 0.5 to 2 hours after sildenafil. Patients receiving Tyvaso Inhalation Solution had a placebo-corrected median change from baseline in peak 6MWD of 20 meters at Week 12 (p<0.001). The distribution of these 6MWD changes from baseline at Week 12 were plotted across the range of observed values (Figure 1). 6MWD measured at trough exposure (defined as measurement of 6MWD at least 4 hours after dosing) improved by 14 meters. There were no placebo-controlled 6MWD assessments made after 12 weeks.

Figure 1: Distributions of 6MWD Changes from Baseline at Week 12 During Peak Plasma Concentration of Tyvaso Inhalation Solution

The placebo-corrected median treatment effect on 6MWD was estimated (using the Hodges-Lehmann estimator) within various subpopulations defined by age quartile, gender, geographic region of the study site, disease etiology, baseline 6MWD quartile, and type of background therapy (Figure 2).

Figure 2: Placebo-Corrected Median Treatment Effect (Hodges-Lehmann Estimate with 95% CI) on 6MWD Change from Baseline at Week 12 During Peak Plasma Concentration of Tyvaso Inhalation Solution for Various Subgroups

14.2 Long-term Treatment of PAH

In long-term follow-up of patients who were treated with Tyvaso Inhalation Solution in the pivotal study and the open-label extension (N=206) (NCT00147199), Kaplan-Meier estimates of survival at 1, 2, and 3 years were 97%, 91%, and 82%, respectively. These uncontrolled observations do not allow comparison with a control group not given Tyvaso Inhalation Solution and cannot be used to determine the long-term effect of Tyvaso Inhalation Solution on mortality.

14.3 Pulmonary Hypertension Associated with ILD (WHO Group 3)

INCREASE was a 16-week, randomized, double-blind, placebo-controlled, multicenter study that enrolled 326 patients with PH-ILD (NCT02630316). Enrolled study patients predominately had etiologies of idiopathic interstitial pneumonia (45%) inclusive of idiopathic pulmonary fibrosis, combined pulmonary fibrosis and emphysema (25%), and WHO Group 3 connective tissue disease (22%). The mean baseline 6MWD was 260 meters.

Patients in the INCREASE study were randomized (1:1) to either placebo or Tyvaso Inhalation Solution in 4 daily treatment sessions with a target dose of 9 breaths (54 mcg) per session and a maximum dose of 12 breaths (72 mcg) per session over the course of the 16-week study. Approximately 75% of patients randomized to Tyvaso Inhalation Solution titrated up to a dose of 9 breaths, 4 times daily or greater, with 48% of patients randomized to Tyvaso Inhalation Solution reaching a dose of 12 breaths, 4 times daily during the study.

The primary efficacy endpoint was the change in 6MWD measured at peak exposure (between 10 and 60 minutes after dosing) from baseline to Week 16. Patients receiving Tyvaso Inhalation Solution had a placebo-corrected median change from baseline in peak 6MWD of 21 meters at Week 16 (p=0.004) using Hodges-Lehmann estimate (Figure 3).

Figure 3: Hodges-Lehmann Estimate of Treatment Effect by Visit for 6MWD at Peak Exposure of Tyvaso Inhalation Solution (PH-ILD)

The treatment effect on 6MWD at Week 16 was consistent for various subgroups, including etiology of PH-ILD, disease severity, age, sex, baseline hemodynamics, and dose (Figure 4).

Figure 4: Forest Plot on Subgroup Analyses of Peak 6MWD (Meter) at Week 16 (PH-ILD)

Time to clinical worsening in the INCREASE study was defined as the time of randomization until 1 of the following criteria were met: hospitalization due to a cardiopulmonary indication, decrease in 6MWD >15% from baseline directly related to PH-ILD at 2 consecutive visits and at least 24 hours apart, death (all causes), or lung transplantation. Treatment with Tyvaso Inhalation Solution in patients with PH-ILD resulted in numerically fewer hospitalizations. The numbers of reported deaths were the same for both treatment groups (Table 3). Overall, treatment with Tyvaso Inhalation Solution demonstrated a statistically significant increase in the time to first clinical worsening event (log-rank test p=0.041; Figure 5), and a 39% overall reduction in the risk of a clinical worsening event (HR=0.61 [95% CI; 0.40, 0.92]; Figure 5).

Table 3: Clinical Worsening Events (PH-ILD)

		Tyvaso Inhalation Solution n=163 n (%)	Placebo n=163 n (%)	HR (95% CI)
Clinical worsening		37 (22.7%)	54 (33.1%)	0.61 (0.40, 0.92)
First contributing event	Hospitalization due to a cardiopulmonary indication	18 (11.0%)	24 (14.7%)
	Decrease in 6MWD >15% from baseline directly related to PH-ILD	13 (8.0%)	26 (16.0%)
	Death (all causes)	4 (2.5%)	4 (2.5%)
	Lung transplantation	2 (1.2%)	0
First of each event	Hospitalization due to a cardiopulmonary indication	21 (12.9%)	30 (18.4%)
	Decrease in 6MWD >15% from baseline directly related to PH-ILD	16 (9.8%)	31 (19.0%)
	Death (all causes)	8 (4.9%)	10 (6.1%)
	Lung transplantation	2 (1.2%)	1 (0.6%)

Figure 5: Kaplan-Meier Plot of Time to Clinical Worsening Events (PH-ILD)

16 HOW SUPPLIED/STORAGE AND HANDLING

Tyvaso DPI (treprostinil) inhalation powder is available as 16 mcg, 32 mcg, 48 mcg, 64 mcg, or 80 mcg of treprostinil in single-dose plastic cartridges with approximate fill weights of 1.6 mg, 3.2 mg, 4.8 mg, 6.4 mg, or 8.0 mg of Tyvaso DPI, respectively. Four cartridges are contained in a single cavity of a blister strip. A card contains 7 blister strips separated by perforations for a total of 28 cartridges of each labeled strength in Titration and Maintenance Kits. For convenience, the perforation allows users to remove a single blister strip containing 4 cartridges. The Institutional Kits contain 4 blister strips for a total of 16 cartridges of each labeled strength.

The cartridges are color-coded, purple for 16 mcg, dark blue for 32 mcg, light blue for 48 mcg, light green for 64 mcg, and orange for 80 mcg. Each cartridge is marked with "Tyvaso DPI" and the corresponding dosage strength of "16 mcg", "32 mcg", "48 mcg", "64 mcg", or "80 mcg".

The Tyvaso DPI Inhaler is individually packaged in a clear overwrap. The inhaler is fully assembled with a removable mouthpiece cover. The Tyvaso DPI Inhaler can be used for up to 7 days from the date of first use. After 7 days of use, the inhaler must be discarded and replaced with a new inhaler.

Tyvaso DPI is available in the following configurations:

		Kit Contents
Description	NDC	Number of Cartridges and Strength	Number of Inhalers
Tyvaso DPI (treprostinil) Inhalation Powder Titration Kit	66302-600-02	112 cartridges, each containing 16 mcg per cartridge	5
		84 cartridges, each containing 32 mcg per cartridge
	66302-610-02	112 cartridges, each containing 16 mcg per cartridge	5
		112 cartridges, each containing 32 mcg per cartridge
		28 cartridges, each containing 48 mcg per cartridge
Tyvaso DPI (treprostinil) Inhalation Powder Maintenance Kit	66302-616-03	112 cartridges, each containing 16 mcg per cartridge	5
	66302-632-03	112 cartridges, each containing 32 mcg per cartridge	5
	66302-648-03	112 cartridges, each containing 48 mcg per cartridge	5
	66302-664-03	112 cartridges, each containing 64 mcg per cartridge	5
	66302-680-03	112 cartridges, each containing 80 mcg per cartridge	5
	66302-620-03	112 cartridges, each containing 32 mcg per cartridge	5
		112 cartridges, each containing 48 mcg per cartridge
	66302-630-03	112 cartridges, each containing 32 mcg per cartridge	5
		112 cartridges, each containing 64 mcg per cartridge
	66302-640-03	112 cartridges, each containing 48 mcg per cartridge	5
		112 cartridges, each containing 64 mcg per cartridge
	66302-650-03	112 cartridges, each containing 16 mcg per cartridge	5
		112 cartridges, each containing 48 mcg per cartridge
		112 cartridges, each containing 64 mcg per cartridge
Tyvaso DPI (treprostinil) Inhalation Powder Institutional Kit	66302-716-04	16 cartridges, each containing 16 mcg per cartridge	2
	66302-732-04	16 cartridges, each containing 32 mcg per cartridge	2
	66302-748-04	16 cartridges, each containing 48 mcg per cartridge	2
	66302-764-04	16 cartridges, each containing 64 mcg per cartridge	2
	66302-780-04	16 cartridges, each containing 80 mcg per cartridge	2
	66302-720-04	16 cartridges, each containing 32 mcg per cartridge	2
		16 cartridges, each containing 48 mcg per cartridge

Blister Storage:

Storage
Tyvaso DPI Presentation	Refrigerated storage 2°C to 8°C (36°F to 46°F)	Room temperature storage 20°C to 25°C (68°F to 77°F), excursions permitted 15°C to 30°C (59°F to 86°F)
Sealed (Unopened) Blister Cards or Strips	May be stored until the expiration date printed on the blisters.	Must be used within 8 weeks.
Opened Blister Strips	Do not put a blister card or strip back into the refrigerator after being opened or stored at room temperature.	Must be used within 3 days.

Inhaler Storage:

Store at 2°C to 25°C (36°F to 77°F); excursions permitted. The Tyvaso DPI Inhaler may be stored refrigerated but should be at room temperature for 10 minutes before use. The inhaler can be used for up to 7 days from the date of first use. After 7 days of use, the inhaler must be discarded and replaced with a new inhaler.

Handling:

If refrigerated, cartridges and inhaler should be at room temperature for 10 minutes before use.

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Instructions for Use).

Train patients in the administration process for Tyvaso DPI, including dosing, Tyvaso DPI Inhaler setup, operation, cleaning, and maintenance, according to the instructions for use [see Dosage and Administration (2.1, 2.2)].

Advise patients that after 7 days of use, the inhaler must be discarded and replaced with a new inhaler [see Dosage and Administration (2.1)].

Instruct patients to use Tyvaso DPI only with the Tyvaso DPI Inhaler [see Dosage and Administration (2.1)].

If a scheduled treatment session is missed, resume therapy as soon as possible [see Dosage and Administration (2.2)].

SPL UNCLASSIFIED SECTION

©Copyright 2024 United Therapeutics Corp. All rights reserved.
Tyvaso DPI® and Tyvaso® are registered trademarks of United Therapeutics Corporation.

Tyvaso DPI manufactured by:

MannKind Corporation
Danbury, CT 06810

Tyvaso DPI manufactured for and distributed by:

United Therapeutics Corp.
Research Triangle Park, NC 27709

INSTRUCTIONS FOR USE

Instructions
for Use

TYVASO [ tī-vā'-sō ] DPI®
(treprostinil) Inhalation Powder
For oral inhalation only

Table of Contents
	page(s)
Read Before Starting	1
Important Information	2
Storing TYVASO DPI Inhalers and Cartridges	3
Preparing to Inhale TYVASO DPI	4-7
Inhaling TYVASO DPI	8-9
Removing the Used Cartridge	10
Disposing of TYVASO DPI Cartridge	11
Inhaling Multiple Cartridges of TYVASO DPI	12
Caring for Your TYVASO DPI Inhaler	13
Disposing of Your TYVASO DPI Inhaler	13

Read Before Starting

	Parts of the TYVASO DPI Inhaler; (see Figure A)	Your Starter Kit includes a Carrying Case; (see Figure B)	TYVASO DPI Blister Cards; (see Figure C)
This Instructions for Use contains information on how to inhale TYVASO DPI (treprostinil) Inhalation Powder. Read this Instructions for Use carefully before you start using your inhaler and each time you get a new inhaler. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.; Your healthcare provider should show you how to use your inhaler the right way before you use it for the first time.	Figure A	The TYVASO DPI inhaler and blister strips can be stored in the carrying case when using outside of your home or traveling.	Figure C
		Figure B

Important Information

Important information you need to know before inhaling TYVASO DPI Inhalation Powder using the TYVASO DPI Inhaler	Take TYVASO DPI exactly as prescribed by your healthcare provider. Take TYVASO DPI 4 times per day while you are awake, about 4 hours apart. If you miss a dose, take it as soon as possible at your usual dose. If your prescribed dose is higher than 80 mcg per treatment session, you will need to use more than 1 cartridge. If using more than 1 cartridge, the cartridges can be used in any order, regardless of cartridge strength. If you need to use more than 1 cartridge for your dose, remove the used cartridge from the inhaler before getting a new one. You can tell a cartridge has been used when the cartridge cup has moved from the front to the middle position in the cartridge base. Only TYVASO DPI cartridges should be used with the TYVASO DPI Inhaler. Each cartridge is for 1 time (single use) only. Use a new cartridge for each treatment session. After each treatment session, throw away the used cartridge right away. Do not open the cartridges. The inhaler opens the cartridge automatically during use. Warning: If any powder from the cartridge spills on your hands, throw away the cartridge right away into regular household trash and wash your hands.; Then start with a new cartridge. Do not breathe in the TYVASO DPI treprostinil powder in any other way. Do not put cartridges in your mouth. Do not swallow cartridges. Use only 1 inhaler at a time. The same inhaler should be used even when needing to use more than 1 cartridge for your dose. Inhale 1 cartridge at a time. The inhaler lasts for 7 days. After 7 days of use, throw away your used inhaler and get a new one. Store the inhaler in a clean, dry place with the mouthpiece cover on until your next dose.
TYVASO DPI cartridges come in 5 strengths (see Figure D).; Important: Always make sure you have the right number of TYVASO DPI cartridges for your dose before you start. Only use TYVASO DPI cartridges with the TYVASO DPI Inhaler.
Figure D
If you are having problems with your TYVASO DPI Inhaler, have any side effects, or if your TYVASO DPI Inhaler breaks and you need a new one, please call 1-844-UNITHER (1-844-864-8437).

Storing TYVASO DPI Inhalers and Cartridges

Storing TYVASO DPI Inhalers	Storing Unopened Blister Cards and Strips				Storing Opened Blister Strips
Store TYVASO DPI Inhalers, with the mouthpiece on, in a clean, dry place at room temperature between 68°F to 77°F (20°C to 25°C), such as a drawer or medicine cabinet (see Figure E).; Inhalers may be stored in the refrigerator between 36°F to 46°F (2°C to 8°C), but should be left out at room temperature for 10 minutes before use.	Store unopened blister cards and strips in a clean, dry place at room temperature, such as a drawer or medicine cabinet. You can store in the carrying case when using outside your home or traveling (see Figure F).   Do not use after 8 weeks if stored at room temperature. Unopened blister cards and strips may also be stored in the refrigerator (see Figure G).			Figure F	Store opened blister strips in a clean, dry place at room temperature (see Figure H), such as a drawer or medicine cabinet.; Opened blister strips must be used within 3 days.   Do not put a blister strip back into the refrigerator after being opened or stored at room temperature.
Do not leave or store cartridges in the inhaler.; Keep out of the reach of children.	Do not use after the Expiration Date has passed.				Figure H
Figure E		Important: If refrigerated, cartridges and inhaler should be left out at room temperature for 10 minutes before use.		Figure G
		ROOM TEMPERATURE	10 mins.

Preparing to Inhale TYVASO DPI

Step 1 : Select the TYVASO DPI cartridges for your dose (see Figure I)					Step 2 : Tear off 1 strip		Step 3 : Check the expiration date on the strip
Select the TYVASO DPI cartridges for your dose (see Figure I).; Note: If using more than 1 cartridge, the cartridges can be used in any order, regardless of cartridge strength.					Tear along the perforation to remove 1 strip from the blister card (see Figure J).	Figure J	Check the expiration date on the foil strip label (see Figure K).   Do not use the cartridges if the Expiration Date on the strip has passed.
If your prescribed TYVASO DPI dose is 16 mcg, use...	If your prescribed TYVASO DPI dose is 32 mcg, use...	If your prescribed TYVASO DPI dose is 48 mcg, use...	If your prescribed TYVASO DPI dose is 64 mcg, use...	If your prescribed TYVASO DPI dose is 80 mcg, use...			Figure K
If your prescribed TYVASO DPI dose is more than 80 mcg per treatment session, you will need to use more than 1 cartridge to get the right dose.; Example: If your prescribed TYVASO DPI dose is 96 mcg per treatment session, you can use...
Figure I

Step 4 : Remove cartridge(s) from strip					Step 5 : Check supplies before continuing
Remove cartridge(s) from the strip by pushing on the white plastic to push the cartridge out (see Figure L).; Note: Pushing on the cup will not damage the cartridge. Make sure to remove the right number of cartridges for your dose. After you have removed a cartridge (or cartridges) from the strip, if any unused cartridges remain in the strip, store the strip at room temperature.; Do not put a blister strip back into the refrigerator after being opened.						Check that you have the right cartridge(s) for your dose.
						Only use one inhaler for multiple cartridges. Your inhaler lasts for 7 days.
Figure L
	Important: If refrigerated, cartridges and inhaler should be left out at room temperature for 10 minutes before use.	ROOM TEMPERATURE	10 mins.

Step 6: Load a cartridge
Place Inhaler on Flat Surface; Place the inhaler on a flat surface (see Figure M).	Open Inhaler; Open the inhaler by lifting the mouthpiece to an upright (vertical) position (see Figure N).; Important: If the cartridge came from a strip stored in the refrigerator (or if you stored the inhaler in the refrigerator), leave the cartridge and inhaler at room temperature for 10 minutes to remove condensation.	Place Cartridge in Inhaler Hold the cartridge with the cup facing down (see Figure O). Line up the cartridge with the opening in the inhaler.; The pointed end of the cartridge should line up with the pointed end in the inhaler (see Figure P). Place the cartridge into the inhaler so that it lies flat.
Figure M
	Figure N	Figure O	Figure P

Close Inhaler; Close the inhaler (this will open the cartridge). You should feel a snap when the inhaler is closed (see Figure Q).; Important: Now that the cartridge is loaded, keep the inhaler level to avoid loss of the TYVASO DPI powder, until it is in your mouth (see Figure R).		Not keeping the inhaler level could cause a loss of TYVASO DPI powder (see Figure S)
		If any powder from the cartridge spills: Wash your hands right away if the powder comes into contact with your hands, Throw away the cartridge into household trash, and Repeat Steps 4, 5, and 6 to load a new cartridge
Figure Q	Figure R	DO NOT turn inhaler upside down.	DO NOT point the mouthpiece down.	DO NOT shake or drop the inhaler.
		This can cause a loss of TYVASO DPI powder.
		Figure S

Inhaling TYVASO DPI

Before inhaling TYVASO DPI, fully review all parts of Step 7 before you take your dose.

Step 7: Inhale Your Dose
Remove the Mouthpiece Cover (see Figure T).; Important: Keep the inhaler level during and after removal of the blue mouthpiece cover to prevent loss of TYVASO DPI powder.	Hold Inhaler Near Cheek; While keeping the inhaler level, carefully pick up the inhaler and bring it near your cheek, but not in front of your mouth (see Figure U).	Exhale; Holding the inhaler away from your mouth, fully blow out (exhale) (see Figure V).
Figure T	Figure U	Figure V

Position Inhaler in Mouth Keeping your head level, place the mouthpiece in your mouth and close your lips around the mouthpiece to form a seal. Tilt the inhaler slightly downward while keeping your head level (see Figure W).   Note: This helps prevent the powder from being blocked by your tongue.	Inhale Deeply, Hold Breath, then Exhale With your mouth closed around the mouthpiece, inhale deeply through the inhaler (see Figure X). Then remove the inhaler from your mouth and hold your breath for as long as you comfortably can (see Figure Y). Then blow out (exhale) and continue to breathe normally (see Figure Z).
Figure W	Figure X	Figure Y	Figure Z

Removing the Used Cartridge

Step 8 : Remove the used cartridge
Replace Mouthpiece Cover; Place the mouthpiece cover back onto the inhaler (see Figure AA).   Note: This keeps your fingers off the exposed mouthpiece.	Open Inhaler; Open the inhaler by lifting up the mouthpiece to an upright (vertical) position (see Figure AB).	Remove Cartridge Remove the used cartridge from the blue base (see Figure AC). The cup should now be in the middle of the used cartridge (see Figure AD).   Warning: If any powder from the cartridge spills on your hands, wash your hands right away.
Figure AA	Figure AB	Figure AC
			The cup moves to the middle of the cartridge when it has been used.
			Figure AD

Disposing of TYVASO DPI Cartridges

Step 9 : Throw away used cartridge
Throw away the used cartridge in your regular household trash (see Figure AE).
Figure AE

Inhaling Multiple Cartridges of TYVASO DPI

Step 10 : Inhaling multiple cartridges (skip if not needed)
If your dose requires you to inhale multiple cartridges, repeat steps 6 through 9 for each cartridge.		Warning: Be careful not to mix NEW cartridges with used cartridges (see Figure AG).
Example: If your prescribed TYVASO DPI dose is 96 mcg per treatment session, you can use one 32 mcg cartridge and one 64 mcg cartridge (see Figure AF):
			The cup moves to the middle of the cartridge when it has been used.
Figure AF			Figure AG

Caring for Your TYVASO DPI Inhaler		Disposing of Your TYVASO DPI Inhaler
Inhaler Care Instructions		Throw away used inhaler after 7 days of use
Cleaning; After taking your dose, powder residue in the mouthpiece is normal; this will not affect your dose.	Use Time; Only use 1 inhaler at a time.; The same inhaler can be used to take 16 mcg, 32 mcg, 48 mcg, 64 mcg, or 80 mcg cartridges.	After 7 days of use, throw away the used inhaler in your regular household trash (see Figure AH and Figure AI).
The outside of the inhaler can be wiped with a clean, dry cloth only, if needed.; Never wash the inhaler.; Always keep the inhaler dry.	Replace the inhaler after 7 days (see Figure AH and Figure AI). Keep track of 7 days from when you start using the inhaler with a calendar.	Figure AI
	Figure AH

For further questions and information, or to report a problem with your device or any side effects with your TYVASO DPI, please call 1-844-UNITHER (1-844-864-8437).

This Instructions for Use has been approved by the U.S. Food and Drug Administration.
Revised: October 2024

TYVASO DPI® is a registered trademark of United Therapeutics Corporation.

Patents: www.tyvasodpi.com/patent

Distributed by:
United Therapeutics Corporation
Research Triangle Park, NC 27709
USA

Manufactured by:
MannKind Corporation
Danbury, CT 06810
USA

10/2024
30-1311-006-03

PRINCIPAL DISPLAY PANEL - 16 mcg Maintenance Kit

NDC: 66302-616-03
Rx ONLY

Maintenance Kit

FOR ORAL INHALATION ONLY
KIT CONTAINS:

112 cartridges, each containing
16 mcg per cartridge
+ 5
Inhalers

This MAINTENANCE KIT is NOT intended
for initial titration.

TYVASO DPI®
(treprostinil)
INHALATION
POWDER

16
mcg per
cartridge

BLISTER STORAGE
Unopened Blister Cards/Strips:
Store refrigerated at 2°C to 8°C (36°F to 46°F). Discard
unopened blister strips stored at room temperature after 8 weeks.

Opened Blister Strips:
Store at 20°C to 25°C (68°F to 77°F) with excursions permitted
to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room
Temperature]. Discard opened blister strips holding unused
cartridges 3 days after opening.

INHALER STORAGE
Store at 2°C to 25°C (36°F to 77°F) excursions permitted.
May be stored refrigerated, but must be at room temperature
before use.

The inhaler can be used for up to 7 days from the date of
first use. After 7 days of use, discard the used inhaler and
replace with a new inhaler.

PRINCIPAL DISPLAY PANEL - 16 mcg Institutional Kit

NDC: 66302-716-04
Rx ONLY

Institutional Kit

FOR ORAL INHALATION ONLY
KIT CONTAINS:

16 cartridges, each containing
16 mcg per cartridge
+ 2
Inhalers

This INSTITUTIONAL KIT is NOT intended
for initial titration.

TYVASO DPI®
(treprostinil)
INHALATION
POWDER

16
mcg per
cartridge

BLISTER STORAGE
Unopened Blister Cards/Strips:
Store refrigerated at 2°C to 8°C (36°F to 46°F). Discard
unopened blister strips stored at room temperature after 8 weeks.

Opened Blister Strips:
Store at 20°C to 25°C (68°F to 77°F) with excursions permitted
to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room
Temperature]. Discard opened blister strips holding unused
cartridges 3 days after opening.

INHALER STORAGE
Store at 2°C to 25°C (36°F to 77°F) excursions permitted.
May be stored refrigerated, but must be at room temperature
before use.

The inhaler can be used for up to 7 days from the date of
first use. After 7 days of use, discard the used inhaler and
replace with a new inhaler.

PRINCIPAL DISPLAY PANEL - 32 mcg Maintenance Kit

NDC: 66302-632-03
Rx ONLY

Maintenance Kit

FOR ORAL INHALATION ONLY
KIT CONTAINS:

112 cartridges, each containing
32 mcg per cartridge
+ 5
Inhalers

This MAINTENANCE KIT is NOT intended
for initial titration.

TYVASO DPI®
(treprostinil)
INHALATION
POWDER

32
mcg per
cartridge

BLISTER STORAGE
Unopened Blister Cards/Strips:
Store refrigerated at 2°C to 8°C (36°F to 46°F). Discard
unopened blister strips stored at room temperature after 8 weeks.

Opened Blister Strips:
Store at 20°C to 25°C (68°F to 77°F) with excursions permitted
to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room
Temperature]. Discard opened blister strips holding unused
cartridges 3 days after opening.

INHALER STORAGE
Store at 2°C to 25°C (36°F to 77°F) excursions permitted.
May be stored refrigerated, but must be at room temperature
before use.

The inhaler can be used for up to 7 days from the date of
first use. After 7 days of use, discard the used inhaler and
replace with a new inhaler.

PRINCIPAL DISPLAY PANEL - 32 mcg Institutional Kit

NDC: 66302-732-04
Rx ONLY

Institutional Kit

FOR ORAL INHALATION ONLY
KIT CONTAINS:

16 cartridges, each containing
32 mcg per cartridge
+ 2
Inhalers

This INSTITUTIONAL KIT is NOT intended
for initial titration.

TYVASO DPI®
(treprostinil)
INHALATION
POWDER

32
mcg per
cartridge

BLISTER STORAGE
Unopened Blister Cards/Strips:
Store refrigerated at 2°C to 8°C (36°F to 46°F). Discard
unopened blister strips stored at room temperature after 8 weeks.

Opened Blister Strips:
Store at 20°C to 25°C (68°F to 77°F) with excursions permitted
to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room
Temperature]. Discard opened blister strips holding unused
cartridges 3 days after opening.

INHALER STORAGE
Store at 2°C to 25°C (36°F to 77°F) excursions permitted.
May be stored refrigerated, but must be at room temperature
before use.

The inhaler can be used for up to 7 days from the date of
first use. After 7 days of use, discard the used inhaler and
replace with a new inhaler.

PRINCIPAL DISPLAY PANEL - 48 mcg Maintenance Kit

NDC: 66302-648-03
Rx ONLY

Maintenance Kit

FOR ORAL INHALATION ONLY
KIT CONTAINS:

112 cartridges, each containing
48 mcg per cartridge
+ 5
Inhalers

This MAINTENANCE KIT is NOT intended
for initial titration.

TYVASO DPI®
(treprostinil)
INHALATION
POWDER

48
mcg per
cartridge

BLISTER STORAGE
Unopened Blister Cards/Strips:
Store refrigerated at 2°C to 8°C (36°F to 46°F). Discard
unopened blister strips stored at room temperature after 8 weeks.

Opened Blister Strips:
Store at 20°C to 25°C (68°F to 77°F) with excursions permitted
to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room
Temperature]. Discard opened blister strips holding unused
cartridges 3 days after opening.

INHALER STORAGE
Store at 2°C to 25°C (36°F to 77°F) excursions permitted.
May be stored refrigerated, but must be at room temperature
before use.

The inhaler can be used for up to 7 days from the date of
first use. After 7 days of use, discard the used inhaler and
replace with a new inhaler.

PRINCIPAL DISPLAY PANEL - 48 mcg Institutional Kit

NDC: 66302-748-04
Rx ONLY

Institutional Kit

FOR ORAL INHALATION ONLY
KIT CONTAINS:

16 cartridges, each containing
48 mcg per cartridge
+ 2
Inhalers

This INSTITUTIONAL KIT is NOT intended
for initial titration.

TYVASO DPI®
(treprostinil)
INHALATION
POWDER

48
mcg per
cartridge

BLISTER STORAGE
Unopened Blister Cards/Strips:
Store refrigerated at 2°C to 8°C (36°F to 46°F). Discard
unopened blister strips stored at room temperature after 8 weeks.

Opened Blister Strips:
Store at 20°C to 25°C (68°F to 77°F) with excursions permitted
to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room
Temperature]. Discard opened blister strips holding unused
cartridges 3 days after opening.

INHALER STORAGE
Store at 2°C to 25°C (36°F to 77°F) excursions permitted.
May be stored refrigerated, but must be at room temperature
before use.

The inhaler can be used for up to 7 days from the date of
first use. After 7 days of use, discard the used inhaler and
replace with a new inhaler.

PRINCIPAL DISPLAY PANEL - 64 mcg Maintenance Kit

NDC: 66302-664-03
Rx ONLY

Maintenance Kit

FOR ORAL INHALATION ONLY
KIT CONTAINS:

112 cartridges, each containing
64 mcg per cartridge
+ 5
Inhalers

This MAINTENANCE KIT is NOT intended
for initial titration.

TYVASO DPI®
(treprostinil)
INHALATION
POWDER

64
mcg per
cartridge

BLISTER STORAGE
Unopened Blister Cards/Strips:
Store refrigerated at 2°C to 8°C (36°F to 46°F). Discard
unopened blister strips stored at room temperature after 8 weeks.

Opened Blister Strips:
Store at 20°C to 25°C (68°F to 77°F) with excursions permitted
to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room
Temperature]. Discard opened blister strips holding unused
cartridges 3 days after opening.

INHALER STORAGE
Store at 2°C to 25°C (36°F to 77°F) excursions permitted.
May be stored refrigerated, but must be at room temperature
before use.

The inhaler can be used for up to 7 days from the date of
first use. After 7 days of use, discard the used inhaler and
replace with a new inhaler.

PRINCIPAL DISPLAY PANEL - 64 mcg Institutional Kit

NDC: 66302-764-04
Rx ONLY

Institutional Kit

FOR ORAL INHALATION ONLY
KIT CONTAINS:

16 cartridges, each containing
64 mcg per cartridge
+ 2
Inhalers

This INSTITUTIONAL KIT is NOT intended
for initial titration.

TYVASO DPI®
(treprostinil)
INHALATION
POWDER

64
mcg per
cartridge

BLISTER STORAGE
Unopened Blister Cards/Strips:
Store refrigerated at 2°C to 8°C (36°F to 46°F). Discard
unopened blister strips stored at room temperature after 8 weeks.

Opened Blister Strips:
Store at 20°C to 25°C (68°F to 77°F) with excursions permitted
to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room
Temperature]. Discard opened blister strips holding unused
cartridges 3 days after opening.

INHALER STORAGE
Store at 2°C to 25°C (36°F to 77°F) excursions permitted.
May be stored refrigerated, but must be at room temperature
before use.

The inhaler can be used for up to 7 days from the date of
first use. After 7 days of use, discard the used inhaler and
replace with a new inhaler.

PRINCIPAL DISPLAY PANEL - 80 mcg Maintenance Kit

NDC: 66302-680-03
Rx ONLY

Maintenance Kit

FOR ORAL INHALATION ONLY
KIT CONTAINS:

112 cartridges, each containing
80 mcg per cartridge
+ 5
Inhalers

This MAINTENANCE KIT is NOT intended
for initial titration.

TYVASO DPI®
(treprostinil)
INHALATION
POWDER

80
mcg per
cartridge

BLISTER STORAGE
Unopened Blister Cards/Strips:
Store refrigerated at 2°C to 8°C (36°F to 46°F). Discard
unopened blister strips stored at room temperature after 8 weeks.

Opened Blister Strips:
Store at 20°C to 25°C (68°F to 77°F) with excursions permitted
to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room
Temperature]. Discard opened blister strips holding unused
cartridges 3 days after opening.

INHALER STORAGE
Store at 2°C to 25°C (36°F to 77°F) excursions permitted.
May be stored refrigerated, but must be at room temperature
before use.

The inhaler can be used for up to 7 days from the date of
first use. After 7 days of use, discard the used inhaler and
replace with a new inhaler.

PRINCIPAL DISPLAY PANEL - 80 mcg Institutional Kit

NDC: 66302-780-04
Rx ONLY

Institutional Kit

FOR ORAL INHALATION ONLY
KIT CONTAINS:

16 cartridges, each containing
80 mcg per cartridge
+ 2
Inhalers

This INSTITUTIONAL KIT is NOT intended
for initial titration.

TYVASO DPI®
(treprostinil)
INHALATION
POWDER

80
mcg per
cartridge

BLISTER STORAGE
Unopened Blister Cards/Strips:
Store refrigerated at 2°C to 8°C (36°F to 46°F). Discard
unopened blister strips stored at room temperature after 8 weeks.

Opened Blister Strips:
Store at 20°C to 25°C (68°F to 77°F) with excursions permitted
to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room
Temperature]. Discard opened blister strips holding unused
cartridges 3 days after opening.

INHALER STORAGE
Store at 2°C to 25°C (36°F to 77°F) excursions permitted.
May be stored refrigerated, but must be at room temperature
before use.

The inhaler can be used for up to 7 days from the date of
first use. After 7 days of use, discard the used inhaler and
replace with a new inhaler.

PRINCIPAL DISPLAY PANEL - 16 mcg 32 mcg Titration Kit

NDC: 66302-600-02
Rx ONLY

Titration Kit

FOR ORAL INHALATION ONLY
KIT CONTAINS:

112 cartridges, each containing
16 mcg per cartridge
84 cartridges, each containing
32 mcg per cartridge
+ 5
Inhalers

TYVASO DPI™
(treprostinil)
INHALATION
POWDER

16
mcg per
cartridge
32
mcg per
cartridge

BLISTER STORAGE
Unopened Blister Cards/Strips:
Store refrigerated at 2°C to 8°C (36°F to 46°F). Discard
unopened blister strips stored at room temperature after 5 weeks.

Opened Blister Strips:
Store at 20°C to 25°C (68°F to 77°F) with excursions permitted
to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room
Temperature]. Discard opened blister strips holding unused
cartridges 3 days after opening.

INHALER STORAGE
Store at 2°C to 25°C (36°F to 77°F) excursions permitted.
May be stored refrigerated, but must be at room temperature
before use.

The inhaler can be used for up to 7 days from the date of
first use. After 7 days of use, discard the used inhaler and
replace with a new inhaler.

PRINCIPAL DISPLAY PANEL - 32 mcg 48 mcg Maintenance Kit

NDC: 66302-620-03
Rx ONLY

Maintenance Kit

FOR ORAL INHALATION ONLY
KIT CONTAINS:

112 cartridges, each containing
32 mcg per cartridge
112 cartridges, each containing
48 mcg per cartridge
+ 5
Inhalers

This MAINTENANCE KIT is NOT intended
for initial titration.

TYVASO DPI®
(treprostinil)
INHALATION
POWDER

32
mcg per
cartridge
48
mcg per
cartridge

BLISTER STORAGE
Unopened Blister Cards/Strips:
Store refrigerated at 2°C to 8°C (36°F to 46°F). Discard
unopened blister strips stored at room temperature after 8 weeks.

Opened Blister Strips:
Store at 20°C to 25°C (68°F to 77°F) with excursions permitted
to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room
Temperature]. Discard opened blister strips holding unused
cartridges 3 days after opening.

INHALER STORAGE
Store at 2°C to 25°C (36°F to 77°F) excursions permitted.
May be stored refrigerated, but must be at room temperature
before use.

The inhaler can be used for up to 7 days from the date of
first use. After 7 days of use, discard the used inhaler and
replace with a new inhaler.

PRINCIPAL DISPLAY PANEL - 32 mcg 64 mcg Maintenance Kit

NDC: 66302-630-03
Rx ONLY

Maintenance Kit

FOR ORAL INHALATION ONLY
KIT CONTAINS:

112 cartridges, each containing
32 mcg per cartridge
112 cartridges, each containing
64 mcg per cartridge
+ 5
Inhalers

This MAINTENANCE KIT is NOT intended
for initial titration.

TYVASO DPI®
(treprostinil)
INHALATION
POWDER

32
mcg per
cartridge
64
mcg per
cartridge

BLISTER STORAGE
Unopened Blister Cards/Strips:
Store refrigerated at 2°C to 8°C (36°F to 46°F). Discard
unopened blister strips stored at room temperature after 8 weeks.

Opened Blister Strips:
Store at 20°C to 25°C (68°F to 77°F) with excursions permitted
to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room
Temperature]. Discard opened blister strips holding unused
cartridges 3 days after opening.

INHALER STORAGE
Store at 2°C to 25°C (36°F to 77°F) excursions permitted.
May be stored refrigerated, but must be at room temperature
before use.

The inhaler can be used for up to 7 days from the date of
first use. After 7 days of use, discard the used inhaler and
replace with a new inhaler.

PRINCIPAL DISPLAY PANEL - 48 mcg 64 mcg Maintenance Kit

NDC: 66302-640-03
Rx ONLY

Maintenance Kit

FOR ORAL INHALATION ONLY
KIT CONTAINS:

112 cartridges, each containing
48 mcg per cartridge
112 cartridges, each containing
64 mcg per cartridge
+ 5
Inhalers

This MAINTENANCE KIT is NOT intended
for initial titration.

TYVASO DPI®
(treprostinil)
INHALATION
POWDER

48
mcg per
cartridge
64
mcg per
cartridge

BLISTER STORAGE
Unopened Blister Cards/Strips:
Store refrigerated at 2°C to 8°C (36°F to 46°F). Discard
unopened blister strips stored at room temperature after 8 weeks.

Opened Blister Strips:
Store at 20°C to 25°C (68°F to 77°F) with excursions permitted
to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room
Temperature]. Discard opened blister strips holding unused
cartridges 3 days after opening.

INHALER STORAGE
Store at 2°C to 25°C (36°F to 77°F) excursions permitted.
May be stored refrigerated, but must be at room temperature
before use.

The inhaler can be used for up to 7 days from the date of
first use. After 7 days of use, discard the used inhaler and
replace with a new inhaler.

PRINCIPAL DISPLAY PANEL - 32 mcg 48 mcg Institutional Kit

NDC: 66302-720-04
Rx ONLY

Institutional Kit

FOR ORAL INHALATION ONLY
KIT CONTAINS:

16 cartridges, each containing
32 mcg per cartridge
16 cartridges, each containing
48 mcg per cartridge
+ 2
Inhalers

This INSTITUTIONAL KIT is NOT intended
for initial titration.

TYVASO DPI®
(treprostinil)
INHALATION
POWDER

32
mcg per
cartridge
48
mcg per
cartridge

BLISTER STORAGE
Unopened Blister Cards/Strips:
Store refrigerated at 2°C to 8°C (36°F to 46°F). Discard
unopened blister strips stored at room temperature after 8 weeks.

Opened Blister Strips:
Store at 20°C to 25°C (68°F to 77°F) with excursions permitted
to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room
Temperature]. Discard opened blister strips holding unused
cartridges 3 days after opening.

INHALER STORAGE
Store at 2°C to 25°C (36°F to 77°F) excursions permitted.
May be stored refrigerated, but must be at room temperature
before use.

The inhaler can be used for up to 7 days from the date of
first use. After 7 days of use, discard the used inhaler and
replace with a new inhaler.

PRINCIPAL DISPLAY PANEL - 16 mcg 32 mcg 48 mcg Titration Kit

NDC: 66302-610-02
Rx ONLY

Titration Kit

FOR ORAL INHALATION ONLY
KIT CONTAINS:

112 cartridges, each containing
16 mcg per cartridge
112 cartridges, each containing
32 mcg per cartridge
28 cartridges, each containing
48 mcg per cartridge
+ 5
Inhalers

TYVASO DPI®
(treprostinil)
INHALATION
POWDER

16
mcg per
cartridge
32
mcg per
cartridge
48
mcg per
cartridge

BLISTER STORAGE
Unopened Blister Cards/Strips:
Store refrigerated at 2°C to 8°C (36°F to 46°F). Discard
unopened blister strips stored at room temperature after 8 weeks.

Opened Blister Strips:
Store at 20°C to 25°C (68°F to 77°F) with excursions permitted
to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room
Temperature]. Discard opened blister strips holding unused
cartridges 3 days after opening.

INHALER STORAGE
Store at 2°C to 25°C (36°F to 77°F) excursions permitted.
May be stored refrigerated, but must be at room temperature
before use.

The inhaler can be used for up to 7 days from the date of
first use. After 7 days of use, discard the used inhaler and
replace with a new inhaler.

PRINCIPAL DISPLAY PANEL - 16 mcg 48 mcg 64 mcg Maintenance Kit

NDC: 66302-650-03
Rx ONLY

Maintenance Kit

FOR ORAL INHALATION ONLY
KIT CONTAINS:

112 cartridges, each containing
16 mcg per cartridge
112 cartridges, each containing
48 mcg per cartridge
112 cartridges, each containing
64 mcg per cartridge
+ 5
Inhalers

This MAINTENANCE KIT is NOT intended
for initial titration.

TYVASO DPI®
(treprostinil)
INHALATION
POWDER

16
mcg per
cartridge
48
mcg per
cartridge
64
mcg per
cartridge

BLISTER STORAGE
Unopened Blister Cards/Strips:
Store refrigerated at 2°C to 8°C (36°F to 46°F). Discard
unopened blister strips stored at room temperature after 8 weeks.

Opened Blister Strips:
Store at 20°C to 25°C (68°F to 77°F) with excursions permitted
to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room
Temperature]. Discard opened blister strips holding unused
cartridges 3 days after opening.

INHALER STORAGE
Store at 2°C to 25°C (36°F to 77°F) excursions permitted.
May be stored refrigerated, but must be at room temperature
before use.

The inhaler can be used for up to 7 days from the date of
first use. After 7 days of use, discard the used inhaler and
replace with a new inhaler.

INGREDIENTS AND APPEARANCE

TYVASO DPI 
treprostinil inhalant

Product Information
Product Type	HUMAN PRESCRIPTION DRUG	Item Code (Source)	NDC: 66302-616
Route of Administration	ORAL

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
treprostinil (UNII: RUM6K67ESG) (treprostinil - UNII:RUM6K67ESG)	treprostinil	16 ug

Inactive Ingredients
Ingredient Name	Strength
fumaryl diketopiperazine (UNII: XB09609XSL)

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1	NDC: 66302-616-03	4 in 1 KIT	05/23/2022
1		7 in 1 BLISTER PACK
1		4 in 1 BLISTER PACK; Type 9: Other Type of Part 3 Combination Product (e.g., Drug/Device/Biological Product)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA214324	05/23/2022

TYVASO DPI 
treprostinil inhalant

Product Information
Product Type	HUMAN PRESCRIPTION DRUG	Item Code (Source)	NDC: 66302-716
Route of Administration	ORAL

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
treprostinil (UNII: RUM6K67ESG) (treprostinil - UNII:RUM6K67ESG)	treprostinil	16 ug

Inactive Ingredients
Ingredient Name	Strength
fumaryl diketopiperazine (UNII: XB09609XSL)

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1	NDC: 66302-716-04	1 in 1 KIT	05/23/2022
1		4 in 1 BLISTER PACK
1		4 in 1 BLISTER PACK; Type 9: Other Type of Part 3 Combination Product (e.g., Drug/Device/Biological Product)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA214324	05/23/2022

TYVASO DPI 
treprostinil inhalant

Product Information
Product Type	HUMAN PRESCRIPTION DRUG	Item Code (Source)	NDC: 66302-632
Route of Administration	ORAL

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
treprostinil (UNII: RUM6K67ESG) (treprostinil - UNII:RUM6K67ESG)	treprostinil	32 ug

Inactive Ingredients
Ingredient Name	Strength
fumaryl diketopiperazine (UNII: XB09609XSL)

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1	NDC: 66302-632-03	4 in 1 KIT	05/23/2022
1		7 in 1 BLISTER PACK
1		4 in 1 BLISTER PACK; Type 9: Other Type of Part 3 Combination Product (e.g., Drug/Device/Biological Product)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA214324	05/23/2022

TYVASO DPI 
treprostinil inhalant

Product Information
Product Type	HUMAN PRESCRIPTION DRUG	Item Code (Source)	NDC: 66302-732
Route of Administration	ORAL

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
treprostinil (UNII: RUM6K67ESG) (treprostinil - UNII:RUM6K67ESG)	treprostinil	32 ug

Inactive Ingredients
Ingredient Name	Strength
fumaryl diketopiperazine (UNII: XB09609XSL)

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1	NDC: 66302-732-04	1 in 1 KIT	05/23/2022
1		4 in 1 BLISTER PACK
1		4 in 1 BLISTER PACK; Type 9: Other Type of Part 3 Combination Product (e.g., Drug/Device/Biological Product)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA214324	05/23/2022

TYVASO DPI 
treprostinil inhalant

Product Information
Product Type	HUMAN PRESCRIPTION DRUG	Item Code (Source)	NDC: 66302-648
Route of Administration	ORAL

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
treprostinil (UNII: RUM6K67ESG) (treprostinil - UNII:RUM6K67ESG)	treprostinil	48 ug

Inactive Ingredients
Ingredient Name	Strength
fumaryl diketopiperazine (UNII: XB09609XSL)

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1	NDC: 66302-648-03	4 in 1 KIT	05/23/2022
1		7 in 1 BLISTER PACK
1		4 in 1 BLISTER PACK; Type 9: Other Type of Part 3 Combination Product (e.g., Drug/Device/Biological Product)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA214324	05/23/2022

TYVASO DPI 
treprostinil inhalant

Product Information
Product Type	HUMAN PRESCRIPTION DRUG	Item Code (Source)	NDC: 66302-748
Route of Administration	ORAL

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
treprostinil (UNII: RUM6K67ESG) (treprostinil - UNII:RUM6K67ESG)	treprostinil	48 ug

Inactive Ingredients
Ingredient Name	Strength
fumaryl diketopiperazine (UNII: XB09609XSL)

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1	NDC: 66302-748-04	1 in 1 KIT	05/23/2022
1		4 in 1 BLISTER PACK
1		4 in 1 BLISTER PACK; Type 9: Other Type of Part 3 Combination Product (e.g., Drug/Device/Biological Product)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA214324	05/23/2022

TYVASO DPI 
treprostinil inhalant

Product Information
Product Type	HUMAN PRESCRIPTION DRUG	Item Code (Source)	NDC: 66302-664
Route of Administration	ORAL

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
treprostinil (UNII: RUM6K67ESG) (treprostinil - UNII:RUM6K67ESG)	treprostinil	64 ug

Inactive Ingredients
Ingredient Name	Strength
fumaryl diketopiperazine (UNII: XB09609XSL)

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1	NDC: 66302-664-03	4 in 1 KIT	05/23/2022
1		7 in 1 BLISTER PACK
1		4 in 1 BLISTER PACK; Type 9: Other Type of Part 3 Combination Product (e.g., Drug/Device/Biological Product)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA214324	05/23/2022

TYVASO DPI 
treprostinil inhalant

Product Information
Product Type	HUMAN PRESCRIPTION DRUG	Item Code (Source)	NDC: 66302-764
Route of Administration	ORAL

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
treprostinil (UNII: RUM6K67ESG) (treprostinil - UNII:RUM6K67ESG)	treprostinil	64 ug

Inactive Ingredients
Ingredient Name	Strength
fumaryl diketopiperazine (UNII: XB09609XSL)

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1	NDC: 66302-764-04	1 in 1 KIT	05/23/2022
1		4 in 1 BLISTER PACK
1		4 in 1 BLISTER PACK; Type 9: Other Type of Part 3 Combination Product (e.g., Drug/Device/Biological Product)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA214324	05/23/2022

TYVASO DPI 
treprostinil inhalant

Product Information
Product Type	HUMAN PRESCRIPTION DRUG	Item Code (Source)	NDC: 66302-680
Route of Administration	ORAL

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
treprostinil (UNII: RUM6K67ESG) (treprostinil - UNII:RUM6K67ESG)	treprostinil	80 ug

Inactive Ingredients
Ingredient Name	Strength
fumaryl diketopiperazine (UNII: XB09609XSL)

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1	NDC: 66302-680-03	4 in 1 KIT	10/24/2024
1		7 in 1 BLISTER PACK
1		4 in 1 BLISTER PACK; Type 9: Other Type of Part 3 Combination Product (e.g., Drug/Device/Biological Product)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA214324	10/24/2024

TYVASO DPI 
treprostinil inhalant

Product Information
Product Type	HUMAN PRESCRIPTION DRUG	Item Code (Source)	NDC: 66302-780
Route of Administration	ORAL

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
treprostinil (UNII: RUM6K67ESG) (treprostinil - UNII:RUM6K67ESG)	treprostinil	80 ug

Inactive Ingredients
Ingredient Name	Strength
fumaryl diketopiperazine (UNII: XB09609XSL)

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1	NDC: 66302-780-04	1 in 1 KIT	10/24/2024
1		4 in 1 BLISTER PACK
1		4 in 1 BLISTER PACK; Type 9: Other Type of Part 3 Combination Product (e.g., Drug/Device/Biological Product)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA214324	10/24/2024

TYVASO DPI 
treprostinil kit

Product Information
Product Type	HUMAN PRESCRIPTION DRUG	Item Code (Source)	NDC: 66302-600

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1	NDC: 66302-600-02	1 in 1 PACKAGE	05/23/2022	03/31/2024

Quantity of Parts
Part #	Package Quantity	Total Product Quantity
Part 1	28 BLISTER PACK	112
Part 2	21 BLISTER PACK	84

Part 1 of 2

TYVASO DPI 
treprostinil inhalant

Product Information
Item Code (Source)	NDC: 66302-616
Route of Administration	ORAL

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
treprostinil (UNII: RUM6K67ESG) (treprostinil - UNII:RUM6K67ESG)	treprostinil	16 ug

Inactive Ingredients
Ingredient Name	Strength
fumaryl diketopiperazine (UNII: XB09609XSL)

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1		4 in 1 BLISTER PACK; Type 9: Other Type of Part 3 Combination Product (e.g., Drug/Device/Biological Product)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA214324	05/23/2022

Part 2 of 2

TYVASO DPI 
treprostinil inhalant

Product Information
Item Code (Source)	NDC: 66302-632
Route of Administration	ORAL

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
treprostinil (UNII: RUM6K67ESG) (treprostinil - UNII:RUM6K67ESG)	treprostinil	32 ug

Inactive Ingredients
Ingredient Name	Strength
fumaryl diketopiperazine (UNII: XB09609XSL)

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1		4 in 1 BLISTER PACK; Type 9: Other Type of Part 3 Combination Product (e.g., Drug/Device/Biological Product)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA214324	05/23/2022

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA214324	05/23/2022	03/31/2024

TYVASO DPI 
treprostinil kit

Product Information
Product Type	HUMAN PRESCRIPTION DRUG	Item Code (Source)	NDC: 66302-620

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1	NDC: 66302-620-03	1 in 1 PACKAGE	05/23/2022

Quantity of Parts
Part #	Package Quantity	Total Product Quantity
Part 1	28 BLISTER PACK	112
Part 2	28 BLISTER PACK	112

Part 1 of 2

TYVASO DPI 
treprostinil inhalant

Product Information
Item Code (Source)	NDC: 66302-632
Route of Administration	ORAL

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
treprostinil (UNII: RUM6K67ESG) (treprostinil - UNII:RUM6K67ESG)	treprostinil	32 ug

Inactive Ingredients
Ingredient Name	Strength
fumaryl diketopiperazine (UNII: XB09609XSL)

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1		4 in 1 BLISTER PACK; Type 9: Other Type of Part 3 Combination Product (e.g., Drug/Device/Biological Product)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA214324	05/23/2022

Part 2 of 2

TYVASO DPI 
treprostinil inhalant

Product Information
Item Code (Source)	NDC: 66302-648
Route of Administration	ORAL

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
treprostinil (UNII: RUM6K67ESG) (treprostinil - UNII:RUM6K67ESG)	treprostinil	48 ug

Inactive Ingredients
Ingredient Name	Strength
fumaryl diketopiperazine (UNII: XB09609XSL)

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1		4 in 1 BLISTER PACK; Type 9: Other Type of Part 3 Combination Product (e.g., Drug/Device/Biological Product)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA214324	05/23/2022

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA214324	05/23/2022

TYVASO DPI 
treprostinil kit

Product Information
Product Type	HUMAN PRESCRIPTION DRUG	Item Code (Source)	NDC: 66302-630

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1	NDC: 66302-630-03	1 in 1 PACKAGE	06/27/2023

Quantity of Parts
Part #	Package Quantity	Total Product Quantity
Part 1	28 BLISTER PACK	112
Part 2	28 BLISTER PACK	112

Part 1 of 2

TYVASO DPI 
treprostinil inhalant

Product Information
Item Code (Source)	NDC: 66302-632
Route of Administration	ORAL

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
treprostinil (UNII: RUM6K67ESG) (treprostinil - UNII:RUM6K67ESG)	treprostinil	32 ug

Inactive Ingredients
Ingredient Name	Strength
fumaryl diketopiperazine (UNII: XB09609XSL)

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1		4 in 1 BLISTER PACK; Type 9: Other Type of Part 3 Combination Product (e.g., Drug/Device/Biological Product)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA214324	06/27/2023

Part 2 of 2

TYVASO DPI 
treprostinil inhalant

Product Information
Item Code (Source)	NDC: 66302-664
Route of Administration	ORAL

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
treprostinil (UNII: RUM6K67ESG) (treprostinil - UNII:RUM6K67ESG)	treprostinil	64 ug

Inactive Ingredients
Ingredient Name	Strength
fumaryl diketopiperazine (UNII: XB09609XSL)

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1		4 in 1 BLISTER PACK; Type 9: Other Type of Part 3 Combination Product (e.g., Drug/Device/Biological Product)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA214324	06/27/2023

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA214324	06/27/2023

TYVASO DPI 
treprostinil kit

Product Information
Product Type	HUMAN PRESCRIPTION DRUG	Item Code (Source)	NDC: 66302-640

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1	NDC: 66302-640-03	1 in 1 PACKAGE	06/27/2023

Quantity of Parts
Part #	Package Quantity	Total Product Quantity
Part 1	28 BLISTER PACK	112
Part 2	28 BLISTER PACK	112

Part 1 of 2

TYVASO DPI 
treprostinil inhalant

Product Information
Item Code (Source)	NDC: 66302-648
Route of Administration	ORAL

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
treprostinil (UNII: RUM6K67ESG) (treprostinil - UNII:RUM6K67ESG)	treprostinil	48 ug

Inactive Ingredients
Ingredient Name	Strength
fumaryl diketopiperazine (UNII: XB09609XSL)

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1		4 in 1 BLISTER PACK; Type 9: Other Type of Part 3 Combination Product (e.g., Drug/Device/Biological Product)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA214324	06/27/2023

Part 2 of 2

TYVASO DPI 
treprostinil inhalant

Product Information
Item Code (Source)	NDC: 66302-664
Route of Administration	ORAL

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
treprostinil (UNII: RUM6K67ESG) (treprostinil - UNII:RUM6K67ESG)	treprostinil	64 ug

Inactive Ingredients
Ingredient Name	Strength
fumaryl diketopiperazine (UNII: XB09609XSL)

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1		4 in 1 BLISTER PACK; Type 9: Other Type of Part 3 Combination Product (e.g., Drug/Device/Biological Product)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA214324	06/27/2023

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA214324	06/27/2023

TYVASO DPI 
treprostinil kit

Product Information
Product Type	HUMAN PRESCRIPTION DRUG	Item Code (Source)	NDC: 66302-720

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1	NDC: 66302-720-04	1 in 1 PACKAGE	05/23/2022

Quantity of Parts
Part #	Package Quantity	Total Product Quantity
Part 1	4 BLISTER PACK	16
Part 2	4 BLISTER PACK	16

Part 1 of 2

TYVASO DPI 
treprostinil inhalant

Product Information
Item Code (Source)	NDC: 66302-632
Route of Administration	ORAL

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
treprostinil (UNII: RUM6K67ESG) (treprostinil - UNII:RUM6K67ESG)	treprostinil	32 ug

Inactive Ingredients
Ingredient Name	Strength
fumaryl diketopiperazine (UNII: XB09609XSL)

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1		4 in 1 BLISTER PACK; Type 9: Other Type of Part 3 Combination Product (e.g., Drug/Device/Biological Product)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA214324	05/23/2022

Part 2 of 2

TYVASO DPI 
treprostinil inhalant

Product Information
Item Code (Source)	NDC: 66302-648
Route of Administration	ORAL

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
treprostinil (UNII: RUM6K67ESG) (treprostinil - UNII:RUM6K67ESG)	treprostinil	48 ug

Inactive Ingredients
Ingredient Name	Strength
fumaryl diketopiperazine (UNII: XB09609XSL)

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1		4 in 1 BLISTER PACK; Type 9: Other Type of Part 3 Combination Product (e.g., Drug/Device/Biological Product)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA214324	05/23/2022

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA214324	05/23/2022

TYVASO DPI 
treprostinil kit

Product Information
Product Type	HUMAN PRESCRIPTION DRUG	Item Code (Source)	NDC: 66302-610

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1	NDC: 66302-610-02	1 in 1 PACKAGE	05/23/2022

Quantity of Parts
Part #	Package Quantity	Total Product Quantity
Part 1	28 BLISTER PACK	112
Part 2	28 BLISTER PACK	112
Part 3	7 BLISTER PACK	28

Part 1 of 3

TYVASO DPI 
treprostinil inhalant

Product Information
Item Code (Source)	NDC: 66302-616
Route of Administration	ORAL

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
treprostinil (UNII: RUM6K67ESG) (treprostinil - UNII:RUM6K67ESG)	treprostinil	16 ug

Inactive Ingredients
Ingredient Name	Strength
fumaryl diketopiperazine (UNII: XB09609XSL)

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1		4 in 1 BLISTER PACK; Type 9: Other Type of Part 3 Combination Product (e.g., Drug/Device/Biological Product)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA214324	05/23/2022

Part 2 of 3

TYVASO DPI 
treprostinil inhalant

Product Information
Item Code (Source)	NDC: 66302-632
Route of Administration	ORAL

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
treprostinil (UNII: RUM6K67ESG) (treprostinil - UNII:RUM6K67ESG)	treprostinil	32 ug

Inactive Ingredients
Ingredient Name	Strength
fumaryl diketopiperazine (UNII: XB09609XSL)

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1		4 in 1 BLISTER PACK; Type 9: Other Type of Part 3 Combination Product (e.g., Drug/Device/Biological Product)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA214324	05/23/2022

Part 3 of 3

TYVASO DPI 
treprostinil inhalant

Product Information
Item Code (Source)	NDC: 66302-648
Route of Administration	ORAL

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
treprostinil (UNII: RUM6K67ESG) (treprostinil - UNII:RUM6K67ESG)	treprostinil	48 ug

Inactive Ingredients
Ingredient Name	Strength
fumaryl diketopiperazine (UNII: XB09609XSL)

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1		4 in 1 BLISTER PACK; Type 9: Other Type of Part 3 Combination Product (e.g., Drug/Device/Biological Product)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA214324	05/23/2022

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA214324	05/23/2022

TYVASO DPI 
treprostinil kit

Product Information
Product Type	HUMAN PRESCRIPTION DRUG	Item Code (Source)	NDC: 66302-650

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1	NDC: 66302-650-03	1 in 1 PACKAGE	06/27/2023

Quantity of Parts
Part #	Package Quantity	Total Product Quantity
Part 1	28 BLISTER PACK	112
Part 2	28 BLISTER PACK	112
Part 3	28 BLISTER PACK	112

Part 1 of 3

TYVASO DPI 
treprostinil inhalant

Product Information
Item Code (Source)	NDC: 66302-616
Route of Administration	ORAL

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
treprostinil (UNII: RUM6K67ESG) (treprostinil - UNII:RUM6K67ESG)	treprostinil	16 ug

Inactive Ingredients
Ingredient Name	Strength
fumaryl diketopiperazine (UNII: XB09609XSL)

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1		4 in 1 BLISTER PACK; Type 9: Other Type of Part 3 Combination Product (e.g., Drug/Device/Biological Product)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA214324	06/27/2023

Part 2 of 3

TYVASO DPI 
treprostinil inhalant

Product Information
Item Code (Source)	NDC: 66302-648
Route of Administration	ORAL

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
treprostinil (UNII: RUM6K67ESG) (treprostinil - UNII:RUM6K67ESG)	treprostinil	48 ug

Inactive Ingredients
Ingredient Name	Strength
fumaryl diketopiperazine (UNII: XB09609XSL)

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1		4 in 1 BLISTER PACK; Type 9: Other Type of Part 3 Combination Product (e.g., Drug/Device/Biological Product)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA214324	06/27/2023

Part 3 of 3

TYVASO DPI 
treprostinil inhalant

Product Information
Item Code (Source)	NDC: 66302-664
Route of Administration	ORAL

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
treprostinil (UNII: RUM6K67ESG) (treprostinil - UNII:RUM6K67ESG)	treprostinil	64 ug

Inactive Ingredients
Ingredient Name	Strength
fumaryl diketopiperazine (UNII: XB09609XSL)

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1		4 in 1 BLISTER PACK; Type 9: Other Type of Part 3 Combination Product (e.g., Drug/Device/Biological Product)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA214324	06/27/2023

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA214324	06/27/2023

Labeler - United Therapeutics Corporation (965460025)

Establishment
Name	Address	ID/FEI	Business Operations
United Therapeutics Corporation		965460025	API MANUFACTURE(66302-616, 66302-632, 66302-648, 66302-664, 66302-680, 66302-600, 66302-610, 66302-620, 66302-630, 66302-640, 66302-650, 66302-716, 66302-732, 66302-748, 66302-764, 66302-780, 66302-720) , ANALYSIS(66302-616, 66302-632, 66302-648, 66302-664, 66302-680, 66302-600, 66302-610, 66302-620, 66302-630, 66302-640, 66302-650, 66302-716, 66302-732, 66302-748, 66302-764, 66302-780, 66302-720)

Establishment
Name	Address	ID/FEI	Business Operations
United Therapeutics Corporation		015718364	LABEL(66302-616, 66302-632, 66302-648, 66302-664, 66302-680, 66302-610, 66302-620) , PACK(66302-616, 66302-632, 66302-648, 66302-664, 66302-680, 66302-610, 66302-620)