Defitelio

Vascular Occlusion Management Fibrinolytics

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Depending on the type and amount of diluent used, the color of the diluted solution may vary from colorless to light yellow.

Dilution
Determine the dose and number of defibrotide vials based on patient's baseline weight, defined as the weight prior to the preparative regimen for hematopoietic stem-cell transplantation.
Calculate the volume of defibrotide needed; withdraw the amount from the vial(s) and add 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.
Storage: Partially used vials should be discarded. Use diluted solution within 4 hours if stored at room temperature or within 24 hours if stored under refrigeration. Up to 4 doses of defibrotide may be prepared at one time, if refrigerated.
 
IV Infusion
Confirm that the patient is not experiencing clinically significant bleeding and is hemodynamically stable on no more than 1 vasopressor.
Use a 0.2 micron in-line filter.
Do not administer with other intravenous medications in the same line.
Administer diluted solution over 2 hours.
Flush the intravenous administration line (central or peripheral) with 5% Dextrose Injection or 0.9% Sodium Chloride Injection immediately before and after administration.

hypotension / Rapid / 7.0-7.0
angioedema / Rapid / 0-2.0
infection / Delayed / 2.0-2.0
hyperuricemia / Delayed / 2.0-2.0
anaphylactoid reactions / Rapid / Incidence not known
graft-versus-host disease (GVHD) / Delayed / Incidence not known

diarrhea / Early / 24.0-24.0
vomiting / Early / 18.0-18.0
nausea / Early / 16.0-16.0
epistaxis / Delayed / 14.0-14.0
urticaria / Rapid / 0-2.0
rash / Early / 0-2.0

Defitelio

Rx

Parenteral oligonucleotide mixture with profibrinolytic properties
Used for hepatic veno-occlusive disease (VOD) with renal or pulmonary dysfunction after hematopoietic stem-cell transplantation (HSCT) in adult and pediatric patients
Survival benefit at day +100 after HSCT

6.25 mg/kg/dose IV every 6 hours for a minimum of 21 days. Dose based on patient's baseline weight, defined as the weight prior to the preparative regimen for hematopoietic stem-cell transplantation (HSCT). If after 21 days, signs and symptoms of hepatic veno-occlusive disease (VOD) have not resolved, continue treatment until resolution of VOD or up to a maximum of 60 days. Defibrotide (n = 102) was evaluated in a historically controlled (n = 32), multicenter, open-label phase 3 trial in patients with established hepatic VOD and advanced multi-organ failure. Survival at day +100 post-HSCT was 38.2% in those receiving defibrotide compared to 25% in the historical control group. The estimated between group difference was 23% (95% CI 5.2 to 40.8, p = 0.0109), using propensity-adjusted analysis. Complete response at +100 day post-HSCT was observed in 25.5% of the defibrotide patients compared to 12.5% in the control group, with a 19% estimated difference between groups (95% CI 3.5 to 34.6, p = 0.016). Defibrotide was dosed as 25 mg/kg/day, and the median duration of treatment was 21.5 days (range, 1 to 58). Although defibrotide was generally well tolerated with adverse reactions similar to the historical control group, 10.7% of patients discontinued treatment prematurely for possible drug-related toxicity.

6.25 mg/kg/dose IV every 6 hours for a minimum of 21 days. Dose based on patient's baseline weight, defined as the weight prior to the preparative regimen for hematopoietic stem-cell transplantation (HSCT). If after 21 days, signs and symptoms of hepatic veno-occlusive disease (VOD) have not resolved, continue treatment until resolution of VOD or up to a maximum of 60 days. Defibrotide (n = 102) was evaluated in a historically controlled (n = 32), multicenter, open-label phase 3 trial in patients with established hepatic VOD and advanced multi-organ failure. Survival at day +100 post-HSCT was 38.2% in those receiving defibrotide compared to 25% in the historical control group. The estimated between group difference was 23% (95% CI 5.2 to 40.8, p = 0.0109), using propensity-adjusted analysis. Complete response at +100 day post-HSCT was observed in 25.5% of the defibrotide patients compared to 12.5% in the control group, with a 19% estimated difference between groups (95% CI 3.5 to 34.6, p = 0.016). Defibrotide was dosed as 25 mg/kg/day, and the median duration of treatment was 21.5 days (range, 1 to 58). Although defibrotide was generally well tolerated with adverse reactions similar to the historical control group, 10.7% of patients discontinued treatment prematurely for possible drug-related toxicity.

Efficacy has not been established. Due to a lack of clinical data, the National Institutes of Health (NIH) COVID-19 treatment guidelines do not recommend for or against the use of thrombolytics, such as defibrotide.[65314] 6.25 mg/kg/dose IV every 6 hours for 7 days or 25 mg/kg/day continuous IV infusion for 15 days is being evaluated in conjunction with best available therapy.

†Indicates off-label use

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Abciximab: (Contraindicated) Coadministration of defibrotide with antithrombotic agents like platelet inhibitors is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue antithrombotic agents prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated.
Acetaminophen; Aspirin, ASA; Caffeine: (Contraindicated) Coadministration of defibrotide with antithrombotic agents like aspirin is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue antithrombotic agents prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated.
Acetaminophen; Aspirin: (Contraindicated) Coadministration of defibrotide with antithrombotic agents like aspirin is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue antithrombotic agents prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated.
Acetaminophen; Aspirin; Diphenhydramine: (Contraindicated) Coadministration of defibrotide with antithrombotic agents like aspirin is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue antithrombotic agents prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated.
Alteplase: (Contraindicated) Coadministration of defibrotide with fibrinolytics (thrombolytic agents) is contraindicated. The pharmacodynamic activity and risk of hemorrhage with fibrinolytics are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue systemic fibrinolytic therapy (not including use for routine maintenance or reopening of central venous catheters) prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the fibrinolytic have abated.
Anagrelide: (Contraindicated) Coadministration of defibrotide with antithrombotic agents like platelet inhibitors is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue antithrombotic agents prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated.
Anticoagulants: (Contraindicated) Coadministration of defibrotide with antithrombotic agents like anticoagulants is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue systemic antithrombotic agents (not including use for routine maintenance or reopening of central venous catheters) prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated.
Antithrombin III: (Contraindicated) Coadministration of defibrotide with antithrombotic agents like anticoagulants is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue systemic antithrombotic agents (not including use for routine maintenance or reopening of central venous catheters) prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated.
Apixaban: (Contraindicated) Coadministration of defibrotide with antithrombotic agents like anticoagulants is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue systemic antithrombotic agents (not including use for routine maintenance or reopening of central venous catheters) prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated.
Argatroban: (Contraindicated) Coadministration of defibrotide with antithrombotic agents like anticoagulants is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue systemic antithrombotic agents (not including use for routine maintenance or reopening of central venous catheters) prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated.
Aspirin, ASA: (Contraindicated) Coadministration of defibrotide with antithrombotic agents like aspirin is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue antithrombotic agents prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated.
Aspirin, ASA; Butalbital; Caffeine: (Contraindicated) Coadministration of defibrotide with antithrombotic agents like aspirin is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue antithrombotic agents prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated.
Aspirin, ASA; Caffeine: (Contraindicated) Coadministration of defibrotide with antithrombotic agents like aspirin is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue antithrombotic agents prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated.
Aspirin, ASA; Caffeine; Orphenadrine: (Contraindicated) Coadministration of defibrotide with antithrombotic agents like aspirin is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue antithrombotic agents prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated.
Aspirin, ASA; Carisoprodol: (Contraindicated) Coadministration of defibrotide with antithrombotic agents like aspirin is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue antithrombotic agents prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated.
Aspirin, ASA; Carisoprodol; Codeine: (Contraindicated) Coadministration of defibrotide with antithrombotic agents like aspirin is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue antithrombotic agents prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Contraindicated) Coadministration of defibrotide with antithrombotic agents like aspirin is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue antithrombotic agents prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated.
Aspirin, ASA; Dipyridamole: (Contraindicated) Coadministration of defibrotide with antithrombotic agents like aspirin is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue antithrombotic agents prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated. (Contraindicated) Coadministration of defibrotide with antithrombotic agents like platelet inhibitors is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue antithrombotic agents prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated.
Aspirin, ASA; Omeprazole: (Contraindicated) Coadministration of defibrotide with antithrombotic agents like aspirin is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue antithrombotic agents prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated.
Aspirin, ASA; Oxycodone: (Contraindicated) Coadministration of defibrotide with antithrombotic agents like aspirin is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue antithrombotic agents prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated.
Betrixaban: (Contraindicated) Coadministration of defibrotide with antithrombotic agents like anticoagulants is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue systemic antithrombotic agents (not including use for routine maintenance or reopening of central venous catheters) prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated.
Bivalirudin: (Contraindicated) Coadministration of defibrotide with antithrombotic agents like anticoagulants is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue systemic antithrombotic agents (not including use for routine maintenance or reopening of central venous catheters) prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated.
Butalbital; Aspirin; Caffeine; Codeine: (Contraindicated) Coadministration of defibrotide with antithrombotic agents like aspirin is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue antithrombotic agents prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated.
Cangrelor: (Contraindicated) Coadministration of defibrotide with antithrombotic agents like cangrelor is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue antithrombotic agents prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated.
Cilostazol: (Contraindicated) Coadministration of defibrotide with antithrombotic agents like platelet inhibitors is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue antithrombotic agents prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated.
Clopidogrel: (Contraindicated) Coadministration of defibrotide with antithrombotic agents like platelet inhibitors is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue antithrombotic agents prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated.
Dabigatran: (Contraindicated) Coadministration of defibrotide with antithrombotic agents like anticoagulants is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue systemic antithrombotic agents (not including use for routine maintenance or reopening of central venous catheters) prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated.
Dalteparin: (Contraindicated) Coadministration of defibrotide with antithrombotic agents like anticoagulants is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue systemic antithrombotic agents (not including use for routine maintenance or reopening of central venous catheters) prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated.
Desirudin: (Contraindicated) Coadministration of defibrotide with antithrombotic agents like anticoagulants is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue systemic antithrombotic agents (not including use for routine maintenance or reopening of central venous catheters) prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated.
Dipyridamole: (Contraindicated) Coadministration of defibrotide with antithrombotic agents like platelet inhibitors is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue antithrombotic agents prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated.
Edoxaban: (Contraindicated) Coadministration of defibrotide with antithrombotic agents like anticoagulants is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue systemic antithrombotic agents (not including use for routine maintenance or reopening of central venous catheters) prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated.
Enoxaparin: (Contraindicated) Coadministration of defibrotide with antithrombotic agents like anticoagulants is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue systemic antithrombotic agents (not including use for routine maintenance or reopening of central venous catheters) prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated.
Eptifibatide: (Contraindicated) Coadministration of defibrotide with antithrombotic agents like platelet inhibitors is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue antithrombotic agents prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated.
Fondaparinux: (Contraindicated) Coadministration of defibrotide with antithrombotic agents like anticoagulants is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue systemic antithrombotic agents (not including use for routine maintenance or reopening of central venous catheters) prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated.
Heparin: (Contraindicated) Coadministration of defibrotide with antithrombotic agents like anticoagulants is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue systemic antithrombotic agents (not including use for routine maintenance or reopening of central venous catheters) prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated.
Pentosan: (Contraindicated) Coadministration of defibrotide with antithrombotic agents like anticoagulants is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue systemic antithrombotic agents (not including use for routine maintenance or reopening of central venous catheters) prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated.
Platelet Inhibitors: (Contraindicated) Coadministration of defibrotide with antithrombotic agents like platelet inhibitors is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue antithrombotic agents prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated.
Prasugrel: (Contraindicated) Coadministration of defibrotide with antithrombotic agents like platelet inhibitors is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue antithrombotic agents prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated.
Reteplase, r-PA: (Contraindicated) Coadministration of defibrotide with fibrinolytics (thrombolytic agents) is contraindicated. The pharmacodynamic activity and risk of hemorrhage with fibrinolytics are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue systemic fibrinolytic therapy (not including use for routine maintenance or reopening of central venous catheters) prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the fibrinolytic have abated.
Rivaroxaban: (Contraindicated) Coadministration of defibrotide with antithrombotic agents like anticoagulants is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue systemic antithrombotic agents (not including use for routine maintenance or reopening of central venous catheters) prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated.
Tenecteplase: (Contraindicated) Coadministration of defibrotide with fibrinolytics (thrombolytic agents) is contraindicated. The pharmacodynamic activity and risk of hemorrhage with fibrinolytics are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue systemic fibrinolytic therapy (not including use for routine maintenance or reopening of central venous catheters) prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the fibrinolytic have abated.
Thrombolytic Agents: (Contraindicated) Coadministration of defibrotide with fibrinolytics (thrombolytic agents) is contraindicated. The pharmacodynamic activity and risk of hemorrhage with fibrinolytics are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue systemic fibrinolytic therapy (not including use for routine maintenance or reopening of central venous catheters) prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the fibrinolytic have abated.
Ticagrelor: (Contraindicated) Coadministration of defibrotide with antithrombotic agents like platelet inhibitors is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue antithrombotic agents prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated.
Ticlopidine: (Contraindicated) Coadministration of defibrotide with antithrombotic agents like platelet inhibitors is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue antithrombotic agents prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated.
Tirofiban: (Contraindicated) Coadministration of defibrotide with antithrombotic agents like platelet inhibitors is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue antithrombotic agents prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated.
Vorapaxar: (Contraindicated) Coadministration of defibrotide with antithrombotic agents like platelet inhibitors is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue antithrombotic agents prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated.
Warfarin: (Contraindicated) Coadministration of defibrotide with antithrombotic agents like anticoagulants is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue systemic antithrombotic agents (not including use for routine maintenance or reopening of central venous catheters) prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated.

Defitelio Intravenous Inj Sol: 1mL, 80mg

25 mg/kg/day IV.

25 mg/kg/day IV.

25 mg/kg/day IV.

25 mg/kg/day IV.

25 mg/kg/day IV.

Safety and efficacy have not been established.

The exact mechanism of action of defibrotide is not fully understood. In vitro data indicate defibrotide enhances the enzymatic activity of plasmin to hydrolyze fibrin clots. Defibrotide also increases tissue plasminogen activator and thrombomodulin expression while decreasing von Willebrand factor and plasminogen activator inhibitor-1 expression, which reduces endothelial cell activation and increases endothelial cell-mediated fibrinolysis. In addition, defibrotide protects endothelial cells from damage caused by chemotherapy, tumor necrosis factor alpha, serum starvation, and perfusion.

Defibrotide is administered intravenously. Defibrotide is approximately 93% bound to plasma proteins and has a volume of distribution of 8.1 to 9.1 L. After intravenous administration, peak plasma concentrations occur approximately at the end of each infusion. The precise metabolism of defibrotide has not fully been elucidated. It has been suggested that nucleases, nucleotidases, deaminases, and phosphorylases metabolize polynucleotides progressively to oligonucleotides, nucleotides, nucleosides, and then to free 2'-deoxyribose sugar, purine, and pyrimidine bases. Defibrotide does not undergo appreciable metabolism by human hepatocyte cells. The main route of elimination of defibrotide is metabolism followed by urinary excretion. The estimated total clearance is 3.4 to 6.1 L/hour. After administration of 6.25 to 15 mg/kg as 2-hour infusions, approximately 5% to 15% of the total dose is excreted in urine as defibrotide, with the majority of the dose excreted during the first 4 hours. The elimination half life is less than 2 hours. No accumulation is expected following multiple-dose administration.
 
Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: none.

There are no data on the use of defibrotide in pregnant women. When administered to animals during organogenesis at doses comparable to the recommended human dose, defibrotide resulted in decreased number of implantations and viable fetuses. Patients should be advised of the risk of miscarriage during pregnancy.

There are no data on the presence of defibrotide in human milk, the effects on the breast-fed infant, or the effects on milk production. Breast-feeding is not recommended during treatment with defibrotide due to the potential for serious adverse reactions, including bleeding, in the breast-fed infant.