Label Changes for:

Remodulin (treprostinil) 20 mg, 50 mg, 100 mg, and 200 mg for Injection

September 2013

Changes have been made to the WARNINGS, PRECAUTIONS and ADVERSE REACTIONS sections of the safety label.

Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)  

 

September 2013

5 WARNINGS AND PRECAUTIONS

5.1 Risks Attributable to the Drug Delivery System
  • In an open-label study of IV treprostinil (n=47), there were seven catheter-related line infections during approximately 35 patient years, or about 1 BSI event per 5 years of use. A CDC survey of seven sites that used IV treprostinil for the treatment of PAH found approximately 1 BSI (defined as any positive blood culture) event per 3 years of use. Administration of IV Remodulin with a high pH glycine diluent such as Sterile Diluent for Flolan or Sterile Diluent for Epoprostenol Sodium has been associated with a lower incidence of BSIs compared to neutral diluents (sterile water, 0.9% sodium chloride) when used along with catheter care guidelines.

6 ADVERSE REACTIONS

6.1 Clinical Trial Experience

Adverse Events during Chronic Dosing

  • The safety of Remodulin was also studied in a long-term, open-label extension study in which 860 patients were dosed for a mean duration of 1.6 years, with a maximum exposure of 4.6 years. Twenty-nine (29%) percent achieved a dose of at least 40 ng/kg/min (max: 290 ng/kg/min). The safety profile during this chronic dosing study was similar to that observed in the 12-week placebo controlled study except for the following suspected adverse drug reactions (occurring in at least 3%): anorexia, vomiting, infusion site infection, asthenia, and abdominal pain.

17 PATIENT COUNSELING INFORMATION

  • 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. Patients should use an infusion set with an in-line filter. .......

 

 

January 2010

 

WARNINGS AND PRECAUTIONS

Risks Attributable to the Drug Delivery System
  • Therefore, continuous subcutaneous infusion (undiluted) is the preferred mode of administration.
Patients with Hepatic or Renal Insufficiency
  • 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.
Effect of Other Drugs on Treprostinil
  • Co-administration of a cytochrome P450 (CYP) 2C8 enzyme inhibitor (e.g., gemfibrozil) may increase exposure (both Cmax and AUC) to treprostinil. Coadministration 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.

DRUG INTERACTIONS

Effect of Other Drugs on treprostinil
  • 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 treprostinil on Other Drugs
  • Pharmacokinetic/pharmacodynamic interaction studies have been conducted with treprostinil administered subcutaneously (Remodulin) and orally (treprostinil diethanolamine).
Effect of Other Drugs on Remodulin
  • Drug interaction studies have been carried out with treprostinil (oral or subcutaneous) co-administered with acetaminophen (4 g/day), warfarin (25 mg/day), and fluconazole (200 mg/day), respectively in healthy volunteers. These studies did not show a clinically significant effect on the pharmacokinetics of treprostinil. Treprostinil does not affect the pharmacokinetics or pharmacodynamics 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 infusion of treprostinil at an infusion rate of 10 ng/kg/min.

USE IN SPECIFIC POPULATIONS

Patients with Hepatic Insufficiency
  • In patients with mild or moderate hepatic insufficiency, decrease the initial dose of Remodulin to 0.625 ng/kg/min ideal body weight, and monitor closely.

 

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