DEFITELIO Solution for injection Ref.[9989] Active ingredients: Defibrotide

2.1 Recommended Dosage

The recommended dosage of DEFITELIO for adult and pediatric patients is 6.25 mg/kg every 6 hours given as a 2‑hour intravenous infusion. The dose should be based on patient’s baseline body weight, defined as the patient’s weight prior to the preparative regimen for HSCT.

Administer DEFITELIO for a minimum of 21 days. If after 21 days signs and symptoms of hepatic VOD have not resolved, continue DEFITELIO until resolution of VOD or up to a maximum of 60 days.

2.2 Administration Instructions

• DEFITELIO must be diluted prior to infusion [see Dosage and Administration (2.4)].
• Prior to administration of DEFITELIO, confirm that the patient is not experiencing clinically significant bleeding and is hemodynamically stable on no more than one vasopressor [see Warnings and Precautions (5.1)].
• Administer DEFITELIO by constant intravenous infusion over a 2-hour period.
• Administer the diluted DEFITELIO solution using an infusion set equipped with a 0.2 micron in-line filter. Flush the intravenous administration line (peripheral or central) with 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP immediately before and after administration.
• Do not co‑administer DEFITELIO and other intravenous drugs concurrently within the same intravenous line.

2.3 Treatment Modification

Treatment modification, including temporary or permanent discontinuation of DEFITELIO, should follow the recommendations in Table 1.

Table 1. Treatment Modifications for Toxicity or Invasive Procedures:

2.4 Preparation Instructions

Dilute DEFITELIO in 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP to a concentration of 4 mg/mL to 20 mg/mL. Administer the diluted solution over 2 hours.

Vials contain no antimicrobial preservatives and are intended for a single-patient-use only. Partially used vials should be discarded. Use the diluted DEFITELIO solution within 4 hours if stored at room temperature or within 24 hours if stored under refrigeration. Up to four doses of DEFITELIO solution may be prepared at one time, if refrigerated.

Preparation Instructions:

• Determine the dose (mg) and number of vials of DEFITELIO based on the individual patient’s baseline weight (weight prior to the preparative regimen for HSCT).
• Calculate the volume of DEFITELIO needed, withdraw this amount from the vial(s) and add it to the infusion bag containing 0.9% Sodium Chloride Injection or 5% Dextrose Injection for each dose to make a final concentration of 4 mg/mL to 20 mg/mL.
• Gently mix the solution for infusion.
• Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Only clear solutions without visible particles should be used. Depending on the type and amount of diluent, the color of the diluted solution may vary from colorless to light yellow.

There are no known cases of overdose with DEFITELIO. There is no known antidote for DEFITELIO, and DEFITELIO is not dialyzable. If an overdose occurs, institute general supportive measures.

Store DEFITELIO (defibrotide sodium) injection at 20°C-25°C (68°F-77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) (see USP controlled room temperature).