Dosing Guidelines
General
Remodulin is supplied in 20 mL vials containing 20, 50, 100 or 200 mg of treprostinil (1 mg/mL, 2.5 mg/mL, 5 mg/mL or 10 mg/mL). Remodulin can be administered as supplied or diluted for intravenous infusion with Sterile Water for Injection, 0.9% Sodium Chloride Injection, or Flolan® Sterile Diluent for Injection prior to administration.
Initial Dose for Patients New to Prostacyclin Infusion Therapy
Remodulin is indicated for subcutaneous (SC) or intravenous (IV) use only as a continuous infusion. Remodulin is preferably infused subcutaneously, but it can be administered by a central intravenous line if the subcutaneous route is not tolerated because of severe site pain or reaction.
The infusion rate is initiated at 1.25 ng/kg/min. If this initial dose cannot be tolerated because of systemic effects, the infusion rate should be reduced to 0.625 ng/kg/min.
Dosage Adjustments
The goal of chronic dosage adjustments is to establish a dose at which PAH symptoms are improved, while minimizing excessive pharmacological effects of Remodulin (headache, nausea, emesis, restlessness, anxiety and infusion site pain or reaction).
Infusion rate should be increased in increments of 1.25 ng/kg/min per week for 4 weeks, then 2.5 ng/kg/min per week thereafter. Dosing should be increased if symptoms of PAH either don't improve or worsen and should be decreased for excessive pharmacological effects. Dosage may be increased more frequently, if tolerated. However, there is little experience with doses >40 ng/kg/min.
- Abrupt cessation of infusion should be avoided.
- Restarting a Remodulin infusion within a few hours after an interruption can be done using the same dose rate.
- Interruptions for longer periods may require the dose of Remodulin to be retitrated.
In patients with mild or moderate hepatic insufficiency, the initial dose of Remodulin should be decreased to 0.625 ng/kg/min using ideal body weight and increased cautiously.
Remodulin has not been studied in patients with severe hepatic insufficiency. See Warnings and Precautions in the Full Prescribing Information.
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 for Remodulin
- 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.
- The most common side effects of Remodulin included those related to the method of infusion. For subcutaneous infusion, infusion site pain and
infusion site reaction (redness and swelling) occurred in the majority of patients. These symptoms were often severe and could lead to treatment
with narcotics or discontinuation of Remodulin. For intravenous infusion, line infections, sepsis, arm swelling, tingling sensations, bruising,
and pain were most common. General side effects (>5% more than placebo) were diarrhea, jaw pain, vasodilatation, and edema.
For more information about REMODULIN, please see the Full Prescribing Information.
Questions? Call the Customer Service Line at 1-877-UNITHER (1-877-864-8437).