SELECT IMPORTANT SAFETY INFORMATION
-
Orenitram is
Contraindicated in patients with severe hepatic impairment (Child Pugh
Class C).
-
TYVASO and
TYVASO DPI have a
Warning and Precaution for patients with low systemic arterial
pressure, as either product may produce symptomatic hypotension.
-
Remodulin has a
Warning and Precaution for chronic intravenous (IV) infusions of
Remodulin delivered using an external infusion pump with an indwelling central venous catheter,
as they are associated with the risk of blood stream infections (BSI) and sepsis, which may be
fatal. Therefore, continuous subcutaneous (SC) infusion is the preferred mode of administration.
Please see below for Indication, Important Safety Information, and links to the Full Prescribing
Information for Orenitram, TYVASO, TYVASO DPI, and Remodulin.
Orenitram® (treprostinil) Extended-Release Tablets
INDICATION
Orenitram is a prostacyclin mimetic indicated for treatment of pulmonary arterial hypertension (PAH)
(WHO Group 1) to delay disease progression and to improve exercise capacity. The studies that
established effectiveness included predominately patients with WHO functional class II-III symptoms
and etiologies of idiopathic or heritable PAH (66%) or PAH associated with connective tissue disease
(26%).
IMPORTANT SAFETY INFORMATION FOR ORENITRAM
CONTRAINDICATIONS
-
Avoid use of Orenitram in patients with severe hepatic impairment (Child Pugh Class C) due to
increases in systemic exposure.
WARNINGS AND PRECAUTIONS
-
Abrupt discontinuation or sudden large reductions in dosage of Orenitram may result in worsening
of PAH symptoms.
-
The Orenitram tablet shell does not dissolve. In patients with diverticulosis, Orenitram tablets
can lodge in a diverticulum.
ADVERSE REACTIONS
-
In the 12-week, placebo-controlled, monotherapy study, and an event-driven placebo-controlled,
combination therapy study, adverse reactions that occurred at rates at least 5% higher on
Orenitram than on placebo included headache, diarrhea, nausea, vomiting, flushing, pain in jaw,
pain in extremity, hypokalemia, abdominal discomfort, and upper abdominal pain.
DRUG INTERACTIONS
-
Co-administration of Orenitram and the CYP2C8 enzyme inhibitor gemfibrozil increases exposure to
treprostinil; therefore, Orenitram dosage reduction may be necessary in these patients.
SPECIFIC POPULATIONS
-
Animal reproductive studies with Orenitram have shown an adverse effect on the fetus. There are
no adequate and well-controlled studies with Orenitram in pregnant women.
-
It is not known whether treprostinil is excreted in human milk or if it affects the breastfed
infant or milk production.
- Safety and effectiveness of Orenitram in pediatric patients have not been established.
-
Use of Orenitram in patients aged 65 years and over demonstrated slightly higher absolute and
relative adverse event rates compared to younger patients. Caution should be used when selecting
a dose for geriatric patients.
-
There is a marked increase in the systemic exposure to treprostinil in hepatically impaired
patients.
Please see
Full Prescribing Information
and
Patient Information
at www.orenitram.com or
call 1-877-UNITHER
(1-877-864-8437).
OREISIhcpOCT19
TYVASO® (treprostinil) Inhalation Solution and TYVASO DPI™ (treprostinil)
Inhalation Powder
INDICATION
TYVASO (treprostinil) Inhalation Solution and TYVASO DPI (treprostinil) Inhalation Powder are
prostacyclin mimetics 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.
-
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%).
IMPORTANT SAFETY INFORMATION FOR TYVASO AND TYVASO DPI
WARNINGS AND PRECAUTIONS
-
TYVASO and TYVASO DPI are pulmonary and systemic vasodilators. In patients with low systemic
arterial pressure, either product may produce symptomatic hypotension.
- Both products inhibit platelet aggregation and increase the risk of bleeding.
-
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.
-
Like other inhaled prostaglandins, TYVASO and 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 and TYVASO DPI.
DRUG INTERACTIONS/SPECIFIC POPULATIONS
-
The concomitant use of either product with diuretics, antihypertensives, or other vasodilators
may increase the risk of symptomatic hypotension.
-
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.
-
Limited case reports of treprostinil use in pregnant women are insufficient to inform a
drug-associated risk of adverse developmental outcomes. However, pulmonary arterial hypertension
is associated with an increased risk of maternal and fetal mortality. There are no data on the
presence of treprostinil in human milk, the effects on the breastfed infant, or the effects on
milk production.
- Safety and effectiveness in pediatric patients have not been established.
-
Across clinical studies used to establish the effectiveness of TYVASO 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.
ADVERSE REACTIONS
-
Pulmonary Arterial Hypertension (WHO Group 1)
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 common adverse reactions seen with TYVASO in
≥4% of PAH patients and more than 3% greater than placebo were cough (54% vs 29%), headache
(41% vs 23%), throat irritation/pharyngolaryngeal pain (25% vs 14%), nausea (19% vs 11%),
flushing (15% vs <1%), and syncope (6% vs <1%). In addition, adverse reactions occurring
in ≥4% of patients were dizziness and diarrhea.
In a 3-week, open-label, single-sequence, safety and tolerability study (BREEZE) conducted in 51
patients on stable doses of TYVASO who switched to a corresponding dose of TYVASO DPI, the most
commonly reported adverse events seen with TYVASO DPI in ≥4% of PAH patients during the
3-week treatment phase included cough (35.3%), headache (15.7%), dyspnea (7.8%), and nausea
(5.9%).
-
Pulmonary Hypertension Associated with ILD (WHO Group 3)
In a 16-week, placebo-controlled study (INCREASE) of 326 patients with PH-ILD (WHO Group 3),
adverse reactions with TYVASO were similar to the experience in studies of PAH.
Please see Full Prescribing Information for
TYVASO
or
TYVASO DPI, Instructions for Use manuals for
TD-100
and
TD-300
TYVASO® Inhalation System and
TYVASO DPI™ Inhalation Powder, and additional information at
www.TYVASOhcp.com or call
1-877-UNITHER
(1-877-864-8437).
TYVISIhcpMAY2022
Remodulin® (treprostinil) Injection
INDICATION
Remodulin is a prostacyclin vasodilator indicated for the treatment of pulmonary arterial
hypertension (PAH; WHO Group 1) to diminish symptoms associated with exercise. Studies establishing
effectiveness included patients with NYHA Functional Class II-IV symptoms and etiologies of
idiopathic or heritable PAH (58%), PAH associated with congenital systemic-to-pulmonary shunts
(23%), or PAH associated with connective tissue diseases (19%).
In patients with PAH requiring transition from epoprostenol, Remodulin is indicated to diminish the
rate of clinical deterioration. Consider the risks and benefits of each drug prior to transition.
IMPORTANT SAFETY INFORMATION FOR REMODULIN
WARNINGS AND PRECAUTIONS
-
Chronic intravenous (IV) infusions of Remodulin delivered using an external infusion pump with
an indwelling central venous catheter are associated with the risk of blood stream infections
(BSIs) and sepsis, which may be fatal. Therefore, continuous subcutaneous (SC) infusion is the
preferred mode of administration.
-
Avoid abrupt withdrawal or sudden large reductions in dosage of Remodulin, which may result in
worsening of PAH symptoms.
-
Titrate slowly in patients with hepatic or renal insufficiency, because such patients will
likely be exposed to greater systemic concentrations relative to patients with normal hepatic or
renal function.
-
Remodulin is a pulmonary and systemic vasodilator. In patients with low systemic arterial
pressure, treatment with Remodulin may produce symptomatic hypotension.
- Remodulin inhibits platelet aggregation and increases the risk of bleeding.
ADVERSE REACTIONS
-
In clinical studies of SC Remodulin infusion, the most common adverse events reported were
infusion site pain and infusion site reaction (redness, swelling, and rash). These symptoms were
sometimes severe and sometimes required treatment with narcotics or discontinuation of
Remodulin. The IV infusion of Remodulin with an external infusion pump has been associated with
a risk of blood stream infections, arm swelling, paresthesias, hematoma, and pain. Other common
adverse events (≥3% more than placebo) seen with either SC or IV Remodulin were headache (27%
vs. 23%), diarrhea (25% vs. 16%), nausea (22% vs. 18%), rash (14% vs. 11%), jaw pain (13% vs.
5%), vasodilatation (11% vs. 5%), edema (9% vs. 3%), and hypotension (4% vs. 2%).
DRUG INTERACTIONS
-
Remodulin dosage adjustment may be necessary if inhibitors or inducers of CYP2C8 are added or
withdrawn.
SPECIFIC POPULATIONS
-
In patients with mild or moderate hepatic insufficiency, decrease the initial dose of Remodulin
to 0.625 ng/kg/min of ideal body weight, and monitor closely. Remodulin has not been studied in
patients with severe hepatic insufficiency.
- Safety and effectiveness of Remodulin in pediatric patients have not been established.
-
It is unknown if geriatric patients respond differently than younger patients. Caution should be
used when selecting a dose for geriatric patients.
-
There are no adequate and well-controlled studies with Remodulin in pregnant women. It is not
known whether treprostinil is excreted in human milk or if it affects the breastfed infant or
milk production.
Please see accompanying
Full Prescribing Information
for Remodulin.
For additional information, visit
www.RemodulinPro.com
or call Customer Service at 1-877-UNITHER
(1-877-864-8437).
REMISIhcpMAY2021