Unither | United Therapeutics Corporation

Products

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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%). It may be administered as a continuous subcutaneous infusion or continuous intravenous infusion; however, because of the risks associated with chronic indwelling central venous catheters, including serious blood stream infections, continuous intravenous infusion should be reserved for patients who are intolerant of the subcutaneous route, or in whom these risks are considered warranted.

In patients with PAH requiring transition from Flolan® (epoprostenol sodium), Remodulin is indicated to diminish the rate of clinical deterioration. The risks and benefits of each drug should be carefully considered prior to transition.

Important Safety Information:

  • Chronic intravenous infusions of Remodulin are delivered using an indwelling central venous catheter. This route is associated with the risk of blood stream infections (BSI) and sepsis, which may be fatal. Therefore, continuous subcutaneous infusion is the preferred mode of administration.
  • Remodulin should be used only by clinicians experienced in the diagnosis and treatment of PAH.
  • Remodulin is a potent pulmonary and systemic vasodilator. It lowers blood pressure, which may be further lowered by other drugs that also reduce blood pressure.
  • Remodulin inhibits platelet aggregation and therefore, may increase the risk of bleeding, particularly in patients on anticoagulants.
  • Remodulin dosage adjustment may be necessary if inhibitors or inducers of CYP2C8 are added or withdrawn.
  • Initiation of Remodulin must be performed in a setting with adequate personnel and equipment for physiological monitoring and emergency care.
  • Therapy with Remodulin may be used for prolonged periods, and the patient’s ability to administer Remodulin and care for an infusion system should be carefully considered.
  • Remodulin dosage should be increased for lack of improvement in, or worsening of, symptoms and it should be decreased for excessive pharmacologic effects or for unacceptable infusion site symptoms.
  • Abrupt withdrawal or sudden large reductions in dosage of Remodulin may result in worsening of PAH symptoms and should be avoided.
  • Caution should be used in patients with hepatic or renal insufficiency.
  • Adverse Events: In clinical studies of SC Remodulin infusion, the most common adverse events reported were infusion site pain and infusion site reaction (redness and swelling). These symptoms were often severe and sometimes required treatment with narcotics or discontinuation of Remodulin. The IV infusion of Remodulin 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, diarrhea, nausea, jaw pain, vasodilatation, and edema.

For more information about REMODULIN, please see the Full Prescribing Information.

TYVASO® (treprostinil) Inhalation Solution

Indication

Tyvaso is a prostacyclin vasodilator indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to improve exercise ability. Studies establishing effectiveness included predominately patients with NYHA Functional Class III symptoms and etiologies of idiopathic or heritable PAH (56%) or PAH associated with connective tissue diseases (33%).

The effects diminish over the minimum recommended dosing interval of 4 hours; treatment timing can be adjusted for planned activities.

While there are long-term data on use of treprostinil by other routes of administration, nearly all controlled clinical experience with inhaled treprostinil has been on a background of bosentan (an endothelin receptor antagonist) or sildenafil (a phosphodiesterase type 5 inhibitor). The controlled clinical experience was limited to 12 weeks in duration.

Important Safety Information:

  • Tyvaso is intended for oral inhalation only. Tyvaso is approved for use only with the Tyvaso Inhalation System.
  • The safety and efficacy of Tyvaso have not been established in patients with significant underlying lung disease (such as asthma or chronic obstructive pulmonary disease) and in patients under 18 years of age. Patients with acute pulmonary infections should be carefully monitored to detect any worsening of lung disease and loss of drug effect.
  • Tyvaso may increase the risk of bleeding, particularly in patients receiving anticoagulants.
  • In patients with low systemic arterial pressure, Tyvaso may cause symptomatic hypotension. The concomitant use of Tyvaso with diuretics, antihypertensives, or other vasodilators may increase the risk of symptomatic hypotension.
  • Hepatic or renal insufficiency may increase exposure to Tyvaso and decrease tolerability. Tyvaso dosage adjustments may be necessary if inhibitors of CYP2C8 such as gemfibrozil or inducers such as rifampin are added or withdrawn.
  • There are no adequate and well-controlled studies with Tyvaso in pregnant women. It is not known whether treprostinil is excreted in human milk.
  • The most common adverse events seen with Tyvaso in ≥4% of PAH patients and more than 3% greater than placebo in the placebo-controlled clinical study 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%).

For more information about TYVASO, please see the Full Prescribing Information, Patient Package Insert and the TYVASO Inhalation System Instructions for Use manual.

ADCIRCA® (tadalafil) Tablets

Indication

ADCIRCA is a phosphodiesterase 5(PDE-5) inhibitor indicated for the treatment of pulmonary arterial hypertension(PAH)(WHO Group 1) to improve exercise ability. Studies establishing effectiveness included predominately patients with NYHA Functional Class II–III symptoms and etiologies of idiopathic or heritable PAH (61%) or PAH associated with connective tissue diseases (23%).

Important Safety Information:

CONTRAINDICATIONS
  • Nitrates: ADCIRCA should not be used in patients taking medicines that contain nitrates, as the combination could cause a sudden, unsafe drop in blood pressure
  • Hypersensitivity Reactions: Patients with a known serious hypersensitivity to tadalafil should not take ADCIRCA
WARNINGS AND PRECAUTIONS
  • Cardiovascular: Patients who experience anginal chest pain after taking ADCIRCA should seek immediate medical attention
  • Cardiovascular: Phosphodiesterase 5 inhibitors (PDE-5is), including tadalafil, have mild systemic vasodilatory properties that may result in transient decreases in blood pressure. Before prescribing ADCIRCA, physicians should carefully consider whether their patients with underlying cardiovascular disease could be adversely affected by such actions. Pulmonary vasodilators may significantly worsen the cardiovascular status of patients with pulmonary veno-occlusive disease (PVOD) and administration of ADCIRCA to these patients is not recommended
  • Cardiovascular: The use of ADCIRCA with alpha blockers, blood pressure medications, or alcohol may lower blood pressure significantly and may lead to symptomatic hypotension (light-headedness or fainting)
  • Potential Drug Interactions: Tadalafil is metabolized predominately by CYP3A in the liver. Use of ADCIRCA with potent CYP3A inhibitors, such as ketoconazole and itraconazole, should be avoided. For patients on ADCIRCA therapy that require treatment with ritonavir, ADCIRCA should be discontinued at least 24 hours prior to starting ritonavir. For patients on ritonavir therapy that require treatment with ADCIRCA, start ADCIRCA at 20 mg once a day. Use of ADCIRCA with potent inducers of CYP3A, such as rifampin, should be avoided
  • Special Populations: The use of ADCIRCA is not recommended for patients with severe renal or hepatic impairment. Please see Full Prescribing Information for dosing recommendations for patients with mild to moderate renal or hepatic impairment
  • Potential Drug Interactions: ADCIRCA contains the same ingredient (tadalafil) as Cialis®, which is used to treat erectile dysfunction (ED) and the signs and symptoms of benign prostatic hyperplasia (BPH). The safety and efficacy of combinations of ADCIRCA with Cialis or other PDE-5is have not been studied. Therefore, the use of such combinations is not recommended
  • Vision/Hearing: Patients who experience a sudden loss of vision in one or both eyes, which could be a sign of non-arteritic anterior ischemic optic neuropathy (NAION), or sudden decrease or loss of hearing after taking ADCIRCA should seek immediate medical attention
  • Prolonged Erection: In rare instances, men taking PDE-5is (including tadalafil) for ED reported an erection lasting more than four hours. Male patients who experience a prolonged erection should seek immediate medical attention
ADVERSE REACTIONS
  • Adverse Reactions: The most common adverse event with ADCIRCA is headache (42% ADCIRCA vs 15% placebo). Other common adverse events (reported by ≥9% of patients on ADCIRCA and more frequent than placebo by 2%) include myalgia (14% vs 4%), nasopharyngitis (13% vs 7%), flushing (13% vs 2%), respiratory tract infection (13% vs 6%), extremity pain (11% vs 2%), nausea (11% vs 6%), back pain (10% vs 6%), dyspepsia (10% vs 2%), and nasal congestion (9% vs 1%)

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For more information about Adcirca, please see the Full Prescribing Information and Patient Information or call 1-800-545-5979.

ORENITRAM® (treprostinil) Extended-Release Tablets

Indication

Orenitram is a prostacyclin vasodilator indicated for treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to improve exercise capacity. The study that established effectiveness included predominately patients with WHO functional class II-III symptoms and etiologies of idiopathic or heritable PAH (75%) or PAH associated with connective tissue disease (19%). When used as the sole vasodilator, the effect of Orenitram on exercise is about 10% of the deficit, and the effect, if any, on a background of another vasodilator is probably less than this. Orenitram is probably most useful to replace subcutaneous, intravenous, or inhaled treprostinil, but this use has not been studied.

Important Safety Information:

CONTRAINDICATIONS
  • Orenitram is contraindicated for patients with severe hepatic impairment (Child Pugh Class C).
WARNINGS AND PRECAUTIONS
  • Abrupt discontinuation or sudden large reductions in dosage of Orenitram may result in worsening of PAH symptoms.
  • Orenitram inhibits platelet aggregation and increases the risk of bleeding.
  • Orenitram should not be taken with alcohol as release of treprostinil from the tablet may occur at a faster rate than intended.
  • The Orenitram tablet shell does not dissolve. In patients with diverticulosis (blind-end pouches), Orenitram tablets can lodge in a diverticulum.
DRUG INTERACTIONS/SPECIFIC POPULATIONS
  • Concomitant administration of Orenitram with diuretics, antihypertensive agents, or other vasodilators increases the risk of symptomatic hypotension
  • Orenitram inhibits platelet aggregation; there is an increased risk of bleeding, particularly among patients receiving anticoagulants
  • Co-administration of Orenitram and the CYP2C8 enzyme inhibitor gemfibrozil increases exposure to treprostinil; therefore, Orenitram dosage reduction may be necessary in these patients
  • Pregnancy Category C. Animal reproductive studies with Orenitram have shown an adverse effect on the fetus. There are no adequate and well-controlled studies in humans
  • Safety and effectiveness in patients under 18 years of age have not been established
  • There is a marked increase in the systemic exposure to treprostinil in hepatically impaired patients
ADVERSE REACTIONS
  • In the 12-week placebo-controlled monotherapy study, adverse reactions with rates at least 5% higher on Orenitram than on placebo included headache, diarrhea, nausea, flushing, pain in jaw, pain in extremity, hypokalemia, and abdominal discomfort.

For more information about Orenitram, please see the Full Prescribing Information and Patient Information.