Janssen CarePath for Healthcare Professionals

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Select a medication below:

OPSUMIT® (macitentan)
TRACLEER® (bosentan)
UPTRAVI® (selexipag)
VELETRI® (epoprostenol)
VENTAVIS® (iloprost)
Important Safety Information For:
INDICATION

OPSUMIT® is an endothelin receptor antagonist (ERA) indicated for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) to reduce the risks of disease progression and hospitalization for PAH.

Effectiveness was established in a long-term study in PAH patients with predominantly WHO Functional Class II-III symptoms treated for an average of 2 years. Patients had idiopathic and heritable PAH (57%), PAH caused by connective tissue disorders (31%), and PAH caused by congenital heart disease with repaired shunts (8%).

IMPORTANT SAFETY INFORMATION

BOXED WARNING: EMBRYO-FETAL TOXICITY

  • Do not administer OPSUMIT® to a pregnant female because it may cause fetal harm.
  • Females of reproductive potential: Exclude pregnancy before the start of treatment, monthly during treatment, and 1 month after stopping treatment. Prevent pregnancy during treatment and for one month after stopping treatment by using acceptable methods of contraception.
  • For all female patients, OPSUMIT® is available only through a restricted program called the OPSUMIT® Risk Evaluation and Mitigation Strategy (REMS).

CONTRAINDICATIONS

Pregnancy: OPSUMIT® may cause fetal harm when administered to a pregnant woman. OPSUMIT® is contraindicated in females who are pregnant. If OPSUMIT® is used during pregnancy, advise the patient of the potential risk to a fetus.

Hypersensitivity: OPSUMIT® is contraindicated in patients with a history of a hypersensitivity reaction to macitentan or any component of the product.

WARNINGS AND PRECAUTIONS
Embryo-fetal Toxicity and OPSUMIT® REMS Program

Due to the risk of embryo-fetal toxicity, OPSUMIT® is available for females only through a restricted program called the OPSUMIT® REMS Program. For females of reproductive potential, exclude pregnancy prior to initiation of therapy, ensure use of acceptable contraceptive methods, and obtain monthly pregnancy tests.

Notable requirements of the OPSUMIT® REMS Program include:

  • Prescribers must be certified with the program by enrolling and completing training.
  • All females, regardless of reproductive potential, must enroll in the OPSUMIT® REMS Program prior to initiating OPSUMIT®. Male patients are not enrolled in the REMS.
  • Females of reproductive potential must comply with the pregnancy testing and contraception requirements.
  • Pharmacies must be certified with the program and must only dispense to patients who are authorized to receive OPSUMIT®.

Hepatotoxicity

  • ERAs have caused elevations of aminotransferases, hepatotoxicity, and liver failure. The incidence of elevated aminotransferases in the SERAPHIN study >3 x ULN was 3.4% for OPSUMIT® vs 4.5% for placebo, and >8 x ULN was 2.1% vs 0.4%, respectively. Discontinuations for hepatic adverse events were 3.3% for OPSUMIT® vs 1.6% for placebo.
  • Obtain liver enzyme tests prior to initiation of OPSUMIT® and repeat during treatment as clinically indicated.
  • Advise patients to report symptoms suggesting hepatic injury (nausea, vomiting, right upper quadrant pain, fatigue, anorexia, jaundice, dark urine, fever, or itching).
  • If clinically relevant aminotransferase elevations occur, or if elevations are accompanied by an increase in bilirubin >2 x ULN, or by clinical symptoms of hepatotoxicity, discontinue OPSUMIT®. Consider re-initiation of OPSUMIT® when hepatic enzyme levels normalize in patients who have not experienced clinical symptoms of hepatotoxicity.

Fluid Retention

  • Peripheral edema and fluid retention are known consequences of PAH and ERAs. In the pivotal PAH study SERAPHIN, edema was reported in 21.9% of the OPSUMIT® group vs 20.5% for placebo.
  • Patients with underlying left ventricular dysfunction may be at particular risk for developing significant fluid retention after initiation of ERA treatment. In a small study of pulmonary hypertension due to left ventricular dysfunction, more patients in the OPSUMIT® group developed significant fluid retention and had more hospitalizations due to worsening heart failure compared to placebo. Postmarketing cases of edema and fluid retention occurring within weeks of starting OPSUMIT®, some requiring intervention with a diuretic or hospitalization for decompensated heart failure, have been reported.
  • Monitor for signs of fluid retention after OPSUMIT® initiation. If clinically significant fluid retention develops, evaluate the patient to determine the cause and the possible need to discontinue OPSUMIT®.

Hemoglobin Decrease

  • Decreases in hemoglobin concentration and hematocrit have occurred following administration of other ERAs and in clinical studies with OPSUMIT®. These decreases occurred early and stabilized thereafter.
  • In the SERAPHIN study, OPSUMIT® caused a mean decrease in hemoglobin (from baseline to 18 months) of about 1.0 g/dL vs no change in the placebo group. A decrease in hemoglobin to below 10.0 g/dL was reported in 8.7% of the OPSUMIT® group vs 3.4% for placebo. Decreases in hemoglobin seldom require transfusion.
  • Initiation of OPSUMIT® is not recommended in patients with severe anemia. Measure hemoglobin prior to initiation of treatment and repeat during treatment as clinically indicated.

Pulmonary Edema with Pulmonary Veno-occlusive Disease (PVOD)

Should signs of pulmonary edema occur, consider the possibility of associated PVOD. If confirmed, discontinue OPSUMIT®.

Decreased Sperm Counts

OPSUMIT®, like other ERAs, may have an adverse effect on spermatogenesis. Counsel men about potential effects on fertility.

ADVERSE REACTIONS

Most common adverse reactions (more frequent than placebo by ≥3%) were anemia (13% vs 3%), nasopharyngitis/pharyngitis (20% vs 13%), bronchitis (12% vs 6%), headache (14% vs 9%), influenza (6% vs 2%), and urinary tract infection (9% vs 6%).

DRUG INTERACTIONS

  • Strong inducers of CYP3A4 such as rifampin significantly reduce macitentan exposure. Concomitant use of OPSUMIT® with strong CYP3A4 inducers should be avoided.
  • Strong inhibitors of CYP3A4 like ketoconazole approximately double macitentan exposure. Many HIV drugs like ritonavir are strong inhibitors of CYP3A4. Avoid concomitant use of OPSUMIT® with strong CYP3A4 inhibitors. Use other PAH treatment options when strong CYP3A4 inhibitors are needed as part of HIV treatment.
  • Moderate dual inhibitors of CYP3A4 and CYP2C9 such as fluconazole and amiodarone are predicted to increase macitentan exposure. Avoid concomitant use of OPSUMIT® with moderate dual inhibitors of CYP3A4 and CYP2C9.
  • Concomitant treatment of both a moderate CYP3A4 inhibitor and moderate CYP2C9 inhibitor with OPSUMIT® should also be avoided.

Please see accompanying full Prescribing Information, including BOXED WARNING.

cp-113979v5

INDICATION

TRACLEER® is an endothelin receptor antagonist indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1):

  • in adults to improve exercise ability and to decrease clinical worsening. Studies establishing effectiveness included predominantly patients with WHO Functional Class II-IV symptoms and etiologies of idiopathic or heritable PAH (60%), PAH associated with connective tissue diseases (21%), and PAH associated with congenital heart disease with left-to-right shunts (18%).
  • in pediatric patients aged 3 years and older with idiopathic or congenital PAH to improve pulmonary vascular resistance (PVR), which is expected to result in an improvement in exercise ability.
IMPORTANT SAFETY INFORMATION

BOXED WARNING: RISKS OF HEPATOTOXICITY and EMBRYO-FETAL TOXICITY

Because of the risks of hepatotoxicity and birth defects, TRACLEER® is available only through a restricted program called the Bosentan REMS Program, which is a component of the Bosentan Risk Evaluation and Mitigation Strategy (REMS). Under the Bosentan REMS, prescribers, patients, and pharmacies must enroll in the program

Hepatotoxicity

Elevations of liver aminotransferases (ALT, AST) and liver failure have been reported with TRACLEER®. In a setting of close monitoring, rare cases of liver failure and unexplained hepatic cirrhosis were observed after prolonged (>12 months) treatment. In general, avoid using TRACLEER® in patients with elevated aminotransferases (>3 × ULN) at baseline. Measure liver aminotransferases prior to initiation of treatment and then monthly. Discontinue TRACLEER® if aminotransferase elevations are accompanied by signs or symptoms of liver dysfunction or injury or increases in bilirubin ≥2 × ULN.

Embryo-fetal Toxicity

TRACLEER® is likely to cause major birth defects if used by pregnant females. Therefore, pregnancy must be excluded before the start of treatment with TRACLEER®. Throughout treatment and for one month after stopping TRACLEER®, females of reproductive potential must use two reliable methods of contraception unless the patient has an intrauterine device (IUD) or tubal sterilization, in which case no other contraception is needed. Hormonal contraceptives, including oral, injectable, transdermal, and implantable contraceptives should not be used as the sole means of contraception because these may not be effective in patients receiving TRACLEER®. Obtain monthly pregnancy tests.

CONTRAINDICATIONS

Pregnancy: Use of TRACLEER® is contraindicated in females who are or may become pregnant. To prevent pregnancy, females of reproductive potential must use two reliable forms of contraception during treatment and for one month after stopping TRACLEER®

Use with Cyclosporine A: Co-administration of cyclosporine A and bosentan resulted in markedly increased plasma concentrations of bosentan. Therefore, concomitant use of TRACLEER® and cyclosporine A is contraindicated

Use with Glyburide: An increased risk of liver enzyme elevations was observed in patients receiving glyburide concomitantly with bosentan. Therefore co-administration of glyburide and TRACLEER® is contraindicated

Hypersensitivity: TRACLEER® is contraindicated in patients who are hypersensitive to bosentan or any component of the product.

WARNINGS AND PRECAUTIONS

Hepatotoxicity

  • In clinical trials, ALT/AST elevation (>3 × ULN) were observed in 11% of patients treated with TRACLEER®, accompanied by elevated bilirubin in a few cases. In a pooled analysis of pediatric studies conducted in PAH, elevations in liver aminotransferases ≥3 × ULN were observed in 2% of patients.
  • The combination of hepatocellular injury (increases in aminotransferases of >3 × ULN) and increases in total bilirubin (≥2 × ULN) is a marker for potential serious hepatotoxicity.
  • Liver aminotransferase levels must be measured prior to initiation of treatment and then monthly and therapy adjusted accordingly. Discontinue TRACLEER® if liver aminotransferase elevations are accompanied by clinical symptoms of hepatotoxicity or increases in bilirubin ≥2 × ULN.
  • Avoid initiation of TRACLEER® in patients with elevated aminotransferases (>3 × ULN).

Embryo-fetal Toxicity

  • TRACLEER® may cause fetal harm when administered to a pregnant female and is contraindicated in females who are pregnant. Advise females of reproductive potential of the potential risk to a fetus.
  • Obtain a pregnancy test prior to TRACLEER® treatment, monthly during treatment and for one month after stopping treatment. Advise females of reproductive potential to use two reliable forms of contraception during treatment with TRACLEER® and for at least one month after the last dose.
  • TRACLEER® is only available for females through a restricted program under REMS.

Prescribing and Distribution Program for Bosentan

Because of the risks of hepatotoxicity and birth defects, TRACLEER® is available only through a restricted program called the Bosentan REMS Program.

Required components of the Bosentan REMS are:

  • Healthcare professionals who prescribe TRACLEER® must review the prescriber educational materials, enroll in the Bosentan REMS Program and comply with its requirements.
  • Healthcare professionals must (1) review serum aminotransferases (ALT/AST) and bilirubin, and agree to order and monitor these tests monthly; and (2) for females of reproductive potential, confirm that the patient is not pregnant, and agree to order and monitor pregnancy tests monthly.
  • To receive TRACLEER®, all patients must understand the risks and benefits, and complete a patient enrollment form.
  • Pharmacies that dispense TRACLEER® must enroll in the program and agree to comply with the Bosentan REMS Program requirements.

Fluid Retention

  • Peripheral edema is a known clinical consequence of PAH and worsening PAH and is also a known effect of TRACLEER® and other endothelin receptor antagonists.
  • If clinically significant fluid retention develops, with or without associated weight gain, further evaluation should be undertaken to determine the cause, such as TRACLEER® or underlying heart failure, and the possible need for treatment or discontinuation of TRACLEER®.

Pulmonary Veno-Occlusive Disease

  • If signs of pulmonary edema occur, consider the possibility of associated pulmonary veno-occlusive disease and consider whether TRACLEER® should be discontinued.

Decreased Sperm Counts

  • Decreased sperm counts have been observed in patients receiving TRACLEER®.
  • Preclinical data also suggest that TRACLEER®, similar to other endothelin receptor antagonists, may have an adverse effect on spermatogenesis.

Decreases in Hemoglobin and Hematocrit

  • Treatment with TRACLEER® can cause a dose-related decrease in hemoglobin and hematocrit.
  • It is recommended that hemoglobin concentrations be checked after 1 and 3 months, and every 3 months thereafter. If a marked decrease in hemoglobin concentration occurs, further evaluation should be undertaken to determine the cause and need for specific treatment.

ADVERSE REACTIONS

In TRACLEER® pivotal trials, the most common adverse events occurring more often in TRACLEER®-treated patients than in patients taking placebo were respiratory tract infection (22% vs 17%), headache (15% vs 14%), edema (11% vs 9%), chest pain (5% vs 5%), syncope (5% vs 4%), flushing (4% vs 3%), hypotension (4% vs 2%), sinusitis (4% vs 2%), arthralgia (4% vs 2%), abnormal serum aminotransferases (4% vs 2%), palpitations (4% vs 2%), and anemia (3% vs 0%). TRACLEER® was evaluated for safety in pediatric patients in uncontrolled studies. The safety profile was similar to that observed in adult patients with PAH.

DRUG INTERACTIONS

  • TRACLEER® is contraindicated for use with cyclosporine A and with glyburide.
  • TRACLEER® is metabolized by CYP2C9 and CYP3A and an inducer of CYP3A and CYP2C9.
    • Co-administration with agents that are metabolized by these pathways may affect plasma concentrations of one or both agents.
    • When initiating lopinavir/ritonavir and other ritonavir-containing HIV regimens, dosage adjustment of TRACLEER® is necessary.
    • When co-administered with simvastatin, or other statins that are CYP3A substrates, dosage adjustment of such statins may need to be considered.
    • When co-administered with rifampin, a CYP3A inducer, liver function should be monitored weekly.
    • When co-administered with ketoconazole, a potent CYP3A inhibitor, no dose adjustment of TRACLEER® is necessary, but increased effects of TRACLEER® may need to be considered.
  • Hormonal contraceptives, including oral, injectable, transdermal, and implantable forms, may not be reliable when TRACLEER® is co-administered.
  • There are no clinically relevant interactions between TRACLEER® and warfarin, digoxin, nimodipine, losartan, sildenafil, or tadalafil.
    • Dose adjustments are not necessary when TRACLEER® and sildenafil or tadalafil are co-administered.

LIVER ENZYME ELEVATIONS

  • Measure liver aminotransferases prior to initiation of treatment and then monthly.
  • Use of TRACLEER® should generally be avoided in patients with elevated aminotransferases (>3 x ULN) at baseline because monitoring for hepatotoxicity may be more difficult.
  • It is important to adhere strictly to the monthly monitoring schedule for the duration of treatment.
    • Changes in aminotransferases may occur early or late in treatment.
    • There have been rare postmarketing reports of liver failure and unexplained hepatic cirrhosis in a setting of close monitoring; the contribution of TRACLEER® could not be excluded.
  • For patients whose monthly LFTs are ≤3 x ULN, no change in monitoring schedule or dosage is required.
  • For patients whose monthly LFTs are >3 x ULN, close monitoring and either dose reduction or treatment cessation are necessary.

MONITORING

It is important to adhere strictly to the monthly monitoring schedule for LFTs and, if applicable, pregnancy for the duration of treatment.

Please see full Prescribing Information, including BOXED WARNING.

cp-113987v3

INDICATION

UPTRAVI® (selexipag) is indicated for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) to delay disease progression and reduce the risk of hospitalization for PAH.

Effectiveness of UPTRAVI® Tablets was established in a long-term study in PAH patients with WHO Functional Class II-III symptoms.

Patients had idiopathic and heritable PAH (58%), PAH associated with connective tissue disease (29%), and PAH associated with congenital heart disease with repaired shunts (10%).

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

Concomitant use of strong inhibitors of CYP2C8 (eg, gemfibrozil) with UPTRAVI® is contraindicated.

Hypersensitivity to the active substance or to any of the excipients is contraindicated.

WARNINGS AND PRECAUTIONS

Pulmonary Edema with Pulmonary Veno-Occlusive Disease (PVOD)

Should signs of pulmonary edema occur, consider the possibility of associated PVOD. If confirmed, discontinue UPTRAVI®.

ADVERSE REACTIONS

Adverse reactions more frequent compared to placebo (≥3%) seen with UPTRAVI® Tablets are headache (65% vs 32%), diarrhea (42% vs 18%), jaw pain (26% vs 6%), nausea (33% vs 18%), myalgia (16% vs 6%), vomiting (18% vs 9%), pain in extremity (17% vs 8%), flushing (12% vs 5%), arthralgia (11% vs 8%), anemia (8% vs 5%), decreased appetite (6% vs 3%), and rash (11% vs 8%).

These adverse reactions are more frequent during the dose titration phase.

Hyperthyroidism was observed in 1% (n=8) of patients on UPTRAVI® Tablets and in none of the patients on placebo.

DRUG INTERACTIONS

CYP2C8 Inhibitors

Concomitant administration with gemfibrozil, a strong inhibitor of CYP2C8, doubled exposure to selexipag and increased exposure to the active metabolite by approximately 11-fold. Concomitant use of UPTRAVI® with strong inhibitors of CYP2C8 is contraindicated.

Concomitant administration of UPTRAVI® with clopidogrel, a moderate inhibitor of CYP2C8, had no relevant effect on the exposure to selexipag and increased the exposure to the active metabolite by approximately 2.7-fold. Reduce the dosing of UPTRAVI® to once daily in patients on a moderate CYP2C8 inhibitor.

CYP2C8 Inducers

Concomitant administration with an inducer of CYP2C8 and UGT 1A3 and 2B7 enzymes (rifampin) halved exposure to the active metabolite. Increase UPTRAVI® dose, up to twice, when co-administered with rifampin. Reduce UPTRAVI® when rifampin is stopped.

DOSAGE AND ADMINISTRATION

Recommended Dosage

Recommended starting dose is 200 mcg twice daily for UPTRAVI® Tablets. Tolerability may be improved when taken with food. Increase by 200 mcg twice daily, usually at weekly intervals, to the highest tolerated dose up to 1600 mcg twice daily. If dose is not tolerated, reduce to the previous tolerated dose.

Patients With Hepatic Impairment

For patients with moderate hepatic impairment (Child-Pugh class B), the starting dose of UPTRAVI® Tablets is 200 mcg once daily. Increase by 200 mcg once daily at weekly intervals, as tolerated. Avoid use of UPTRAVI® in patients with severe hepatic impairment (Child-Pugh class C).

Co-administration With Moderate CYP2C8 Inhibitors

When co-administered with moderate CYP2C8 inhibitors (eg, clopidogrel, deferasirox and teriflunomide), reduce the dosing of UPTRAVI® to once daily.

Dosage Strengths

UPTRAVI® tablet strengths:
200, 400, 600, 800, 1000, 1200, 1400, and 1600 mcg.

Additional Important Safety Information for UPTRAVI® IV

Use UPTRAVI® for injection in patients who are temporarily unable to take oral therapy.

Administer UPTRAVI® for injection twice daily by intravenous infusion at a dose that corresponds to the patient’s current dose of UPTRAVI® Tablets (see Table 1 in full Prescribing Information). Administer UPTRAVI® for injection as an 80-minute intravenous infusion.

Adverse Reactions: Infusion-site reactions (infusion-site erythema/redness, pain and swelling) were reported with UPTRAVI® for injection.

Please see full Prescribing Information.

cp-126160v5

INDICATION

VELETRI® is a prostacyclin vasodilator indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to improve exercise capacity. Studies establishing effectiveness included predominantly patients with NYHA Functional Class III-IV symptoms and etiologies of idiopathic or heritable PAH or PAH associated with connective tissue diseases.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

VELETRI® is contraindicated in patients with congestive heart failure due to severe left ventricular systolic dysfunction.

VELETRI® should not be used chronically in patients who during dose initiation develop pulmonary edema, which may be associated with pulmonary veno-occlusive disease.

VELETRI® is also contraindicated in patients with known hypersensitivity to the drug or to structurally related compounds.

WARNINGS AND PRECAUTIONS

General

Reconstitute VELETRI® only as directed using Sterile Water for Injection, USP, or Sodium Chloride 0.9% Injection, USP. Do not mix VELETRI® with any other parenteral medications or solutions prior to or during administration. Each vial is for single use only; discard any unused solution. Use after reconstitution and immediate dilution to final concentration. Use at room temperature (77°F/25°C). Do not expose VELETRI® to direct sunlight.

VELETRI® should be used only by clinicians experienced in the diagnosis and treatment of pulmonary hypertension.

Dose Initiation

VELETRI® is a potent pulmonary and systemic vasodilator. Initiate VELETRI® in a setting with adequate personnel and equipment for physiologic monitoring and emergency care. During dose initiation, asymptomatic increases in pulmonary artery pressure coincident with increases in cardiac output occurred rarely. In such cases, consider dose reduction, but such an increase does not imply that chronic treatment is contraindicated.

Chronic Use and Dose Adjustment

During chronic use, deliver VELETRI® continuously on an ambulatory basis through a permanent indwelling central venous catheter. Unless contraindicated, administer anticoagulant therapy to patients receiving VELETRI® to reduce the risk of pulmonary thromboembolism or systemic embolism through a patent foramen ovale. To reduce the risk of infection, use aseptic technique in the reconstitution and administration of VELETRI® and in routine catheter care.

Because epoprostenol is metabolized rapidly, even brief interruptions in the delivery of VELETRI® may result in symptoms associated with rebound pulmonary hypertension including dyspnea, dizziness, and asthenia. Intravenous therapy with VELETRI® will likely be needed for prolonged periods, possibly years, so consider the patient’s capacity to accept and care for a permanent intravenous catheter and infusion pump.

Dosage of VELETRI® during chronic use should be adjusted at the first sign of recurrence or worsening of symptoms attributable to pulmonary hypertension or the occurrence of adverse events associated with epoprostenol. Following dosage adjustments, monitor standing and supine blood pressure and heart rate closely for several hours.

Withdrawal Effects

Abrupt withdrawal (including interruptions in drug delivery) or sudden large reductions in dosage of VELETRI® may result in symptoms associated with rebound pulmonary hypertension, including dyspnea, dizziness, and asthenia. Abrupt withdrawal should be avoided.

ADVERSE REACTIONS

The most common and dose-limiting adverse events during dose initiation and escalation (≥1%) were flushing (58%), headache (49%), nausea/vomiting (32%), hypotension (16%), anxiety/nervousness/agitation (11%), chest pain (11%), dizziness (8%), bradycardia (5%), abdominal pain (5%), musculoskeletal pain (3%), dyspnea (2%), back pain (2%), sweating (1%), dyspepsia (1%), hypesthesia/paresthesia (1%), and tachycardia (1%).

Adverse events occurring in patients with idiopathic or heritable PAH with ≥10% difference between epoprostenol and conventional therapy alone were chills/fever/sepsis/flu-like symptoms (25% vs 11%), tachycardia (35% vs 24%), flushing (42% vs 2%), diarrhea (37% vs 6%), nausea/vomiting (67% vs 48%), jaw pain (54% vs 0%), myalgia (44% vs 31%), nonspecific musculoskeletal pain (35% vs 15%), anxiety/nervousness/tremor (21% vs 9%), dizziness (83% vs 70%), headache (83% vs 33%), and hypesthesia/hyperesthesia/paresthesia (12% vs 2%).

Adverse events occurring in patients with PAH/CTD with ≥10% difference between epoprostenol and conventional therapy alone were flushing (23% vs 0%), hypotension (13% vs 0%), anorexia (66% vs 47%), nausea/vomiting (41% vs 16%), diarrhea (50% vs 5%), jaw pain (75% vs 0%), pain/neck pain/arthralgia (84% vs 65%), headache (46% vs 5%), skin ulcer (39% vs 24%), and eczema/rash/urticaria (25% vs 4%).

Thrombocytopenia has been reported during uncontrolled clinical trials in patients receiving epoprostenol.

Although the relationship to epoprostenol administration has not been established, pulmonary embolism has been reported in several patients taking epoprostenol and there have been reports of hepatic failure.

DRUG INTERACTIONS

Additional reductions in blood pressure may occur when VELETRI® is administered with diuretics, antihypertensive agents, or other vasodilators. When other antiplatelet agents or anticoagulants are used concomitantly, there is the potential for VELETRI® to increase the risk of bleeding. However, patients receiving infusions of epoprostenol in clinical trials were maintained on anticoagulants without evidence of increased bleeding. In clinical trials, epoprostenol was used with digoxin, diuretics, anticoagulants, oral vasodilators, and supplemental oxygen. However, patients on digoxin may show elevations of digoxin concentrations after initiation of therapy with epoprostenol, which may be clinically significant in patients prone to digoxin toxicity.

Please read full Prescribing Information.

cp-115420v3

INDICATION

VENTAVIS® is a prostacyclin mimetic indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to improve a composite endpoint consisting of exercise tolerance, symptoms (NYHA Class), and lack of deterioration. Studies establishing effectiveness included predominately patients with NYHA Functional Class III-IV symptoms and etiologies of idiopathic or heritable PAH (65%) or PAH associated with connective tissue diseases (23%).

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

RISK OF SYNCOPE

  • Monitor vital signs while initiating VENTAVIS®. Do not initiate VENTAVIS® in patients with systolic blood pressure below 85 mmHg.
  • Syncope can also occur in association with pulmonary arterial hypertension, particularly in association with physical exertion. The occurrence of exertional syncope may reflect a therapeutic gap or insufficient efficacy, and the need to adjust dose or change therapy should be considered.

PULMONARY VENOUS HYPERTENSION

  • Stop VENTAVIS® immediately if signs of pulmonary edema occur; this may be a sign of pulmonary venous hypertension.

BRONCHOSPASM

  • VENTAVIS® inhalation can induce bronchospasm. Bronchospasm may be more severe or frequent in patients with a history of hyperreactive airways.
  • VENTAVIS® has not been evaluated in patients with chronic obstructive pulmonary disease (COPD), severe asthma, or with acute pulmonary infections.

ADVERSE REACTIONS

SERIOUS ADVERSE EVENTS

  • Serious adverse events reported include congestive heart failure, chest pain, supraventricular tachycardia, dyspnea, peripheral edema, and kidney failure.

Adverse Events

  • Adverse events reported in a Phase 3 clinical trial occurring with a ≥3% difference between VENTAVIS® patients and placebo patients were vasodilation (flushing) (27% vs 9%), increased cough (39% vs 26%), headache (30% vs 20%), trismus (12% vs 3%), insomnia (8% vs 2%), nausea (13% vs 8%), hypotension (11% vs 6%), vomiting (7% vs 2%), alkaline phosphatase increased (6% vs 1%), flu syndrome (14% vs 10%), back pain (7% vs 3%), tongue pain (4% vs 0%), palpitations (7% vs 4%), syncope (8% vs 5%), GGT increased (6% vs 3%), muscle cramps (6% vs 3%), hemoptysis (5% vs 2%), and pneumonia (4% vs 1%).

DRUG INTERACTIONS

ANTIHYPERTENSIVES AND VASODILATORS

  • VENTAVIS® has the potential to increase the hypotensive effect of vasodilators and antihypertensive agents.

ANTICOAGULANTS AND PLATELET INHIBITORS

  • VENTAVIS® has the potential to increase the hypotensive effect of vasodilators and antihypertensive agents.

USE IN SPECIFIC POPULATIONS

LACTATION

  • Advise not to breastfeed during treatment with VENTAVIS®.

Please read full Prescribing Information.

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