Remodulin

Remodulin - General Information

Remodulin is a synthetic analogue of prostacyclin, used to treat pulmonary hypertension. Remodulin is marketed as Remodulin®. [Wikipedia]

Pharmacology of Remodulin

Pulmonary arterial hypertension (PAH) is a disease in which blood pressure is abnormally high in the arteries between the heart and lungs. PAH is characterized by symptoms of shortness of breath during physical exertion. The condition can ultimately lead to heart failure. Remodulin is a potent oral antiplatelet agent. The major pharmacologic actions of treprostinil are direct vasodilation of pulmonary and systemic arterial vascular beds and inhibition of platelet aggregation. In animals, the vasodilatory effects reduce right and left ventricular afterload and increase cardiac output and stroke volume. Other studies have shown that treprostinil causes a dose-related negative inotropic and lusitropic effect. No major effects on cardiac conduction have been observed.

Remodulin for patients

Patients receiving Remodulin should be given the following information: Remodulin is infused continuously through a subcutaneous or surgically placed indwelling central venous catheter, via an infusion pump. Therapy with Remodulin will be needed for prolonged periods, possibly years, and the patient's ability to accept and care for a catheter and to use an infusion pump should be carefully considered. In order to reduce the risk of infection, aseptic technique must be used in the preparation and administration of Remodulin. Additionally, patients should be aware that subsequent disease management may require the initiation of an alternative intravenous prostacyclin therapy, Flolan (epoprostenol sodium).

Remodulin Interactions

Reduction in blood pressure caused by Remodulin may be exacerbated by drugs that by themselves alter blood pressure, such as diuretics, antihypertensive agents, or vasodilators. Since Remodulin inhibits platelet aggregation, there is also a potential for increased risk of bleeding, particularly among patients maintained on anticoagulants. During clinical trials, Remodulin was used concurrently with anticoagulants, diuretics, cardiac glycosides, calcium channel blockers, analgesics, antipyretics, nonsteroidal anti-inflammatories, opioids, corticosteroids, and other medications.

Remodulin has not been studied in conjunction with Flolan or Tracleer® (bosentan).

Effect of Other Drugs on Remodulin

In vivo studies: Acetaminophen - Analgesic doses of acetaminophen, 1000 mg every 6 hours for seven doses, did not affect the pharmacokinetics of Remodulin, at a subcutaneous infusion rate of 15 ng/kg/min.

Effect of Remodulin on Other Drugs

In vitro studies: Remodulin did not significantly affect the plasma protein binding of normally observed concentrations of digoxin or warfarin.

In vivo studies: Warfarin - Remodulin does not affect the pharmacokinetics or pharmacodymamics of warfarin. The pharmacokinetics of R- and S- warfarin and the INR in healthy subjects given a single 25 mg dose of warfarin were unaffected by continuous subcutaneous Remodulin at an infusion rate of 10 ng/kg/min.

Hepatic and Renal Impairment

Caution should be used in patients with hepatic or renal impairment (see Special Populations).

Remodulin Contraindications

Treprostinil is contraindicated in patients with known hypersensitivity to the drug or to structurally related compounds.

Additional information about Remodulin

Remodulin Indication: For use as a continuous subcutaneous infusion or intravenous infusion (for those not able to tolerate a subcutaneous infusion) for the treatment of pulmonary arterial hypertension in patients with NYHA Class II-IV symptoms to diminish symptoms associated with exercise.
Mechanism Of Action: The major pharmacological actions of treprostinil are direct vasodilation of pulmonary and systemic arterial vascular beds and inhibition of platelet aggregation. In addition to treprostinil's direct vasodilatory effects, it also inhibits inflammatory cytokine.
Drug Interactions: Not Available
Food Interactions: Not Available
Generic Name: Treprostinil
Synonyms: Not Available
Drug Category: Antithrombotic Agents; Vitamin K antagonists
Drug Type: Small Molecule; Approved; Investigational

Other Brand Names containing Treprostinil: Remodulin;
Absorption: Relatively rapid and complete after subcutaneous infusion, with an absolute bioavailability approximately 100%. In patients with mild (n=4) or moderate (n=5) hepatic insufficiency and portopulmonary hypertension following a subcutaneous dose of 10 ng per kg of body weight per min for 150 mins the AUC 0-∞ was increased 3-fold and 5-fold respectively.
Toxicity (Overdose): Symptoms of overdose are extensions of its dose-limiting pharmacologic effects and include flushing, headache, hypotension, nausea, vomiting, and diarrhea. Most events were self-limiting and resolved with reduction or withholding of treprostinil.
Protein Binding: Human plasma protein binding is approximately 91% in in vitro concentrations ranging from 330 to 10,000 µ/L.
Biotransformation: Substantially metabolized by the liver, but the precise enzymes responsible are unknown. Five metabolites have been described (HU1 through HU5) however, the biological activity and metabolic fate of these are unknown. The chemical structure of HU1 is unknown. The metabolite HU5 is the glucuronide conjugate of treprostinil. The other metabolites are formed by oxidation of the 3-hydroxyoctyl side chain (HU2) and subsequent additional oxidation (HU3) or dehydration (HU4). Study results of in vitro human hepatic cytochrome P450 demonstrates that treprostinil does not inhibit CYP-1A2, 2C9, 2C19, 2D6, 2E1, or 3A. Whether treprostinil induces these enzymes has not been studied.
Half Life: Terminal elimination half-life is approximately 2 to 4 hours. Plasma half-life is 34 and 85 minutes for intravenous and subcutaneous infusion of the drug, respectively.
Dosage Forms of Remodulin: Solution Intravenous
Chemical IUPAC Name: 2-[[(2S,3S,3aR,9aR)-2-hydroxy-3-[(3R)-3-hydroxyoctyl]-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[g]naphthalen-8-yl]oxy]acetic acid
Chemical Formula: C23H34O5
Treprostinil on Wikipedia: https://en.wikipedia.org/wiki/Treprostinil
Organisms Affected: Humans and other mammals