defibrotide (Rx)

Brand and Other Names:Defitelio
  • Print

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

IV solution

  • 200mg/2.5mL (80mg/mL) vial

Hepatic Veno-Occlusive Disease

Indicated for adults and children with hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), with renal or pulmonary dysfunction following hematopoietic stem cell transplantation (HSCT)

6.25 mg/kg IV q6hr infused over 2 hr

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

Dosage Modifications

Severe or life-threatening anaphylaxis: Discontinue permanently; do not resume treatment

Bleeding

  • Persistent, severe, or potentially life-threatening
    • Withhold defibrotide
    • Treat the cause of bleeding and give supportive care as clinically indicated
    • Consider resuming treatment (at the same dose and infusion volume) when bleeding has stopped and the patient is hemodynamically stable
  • Recurrent significant bleeding
    • Discontinue permanently; do not resume treatment

Invasive procedures

  • There is no known reversal agent for the profibrinolytic effects of defibrotide
  • Discontinue infusion at least 2 hr prior to an invasive procedure
  • Resume treatment after the procedure, as soon as any procedure-related risk of bleeding is resolved

Dosing Considerations

Dose is based on weight prior to preparative regimen for HSCT

Dosage Forms & Strengths

IV solution

  • 200mg/2.5mL (80mg/mL) vial

Hepatic Veno-Occlusive Disease

Indicated for adults and children with hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), with renal or pulmonary dysfunction following hematopoietic stem cell transplantation (HSCT)

6.25 mg/kg IV q6hr infused over 2 hr

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

Dosage Modifications

Severe or life-threatening anaphylaxis: Discontinue permanently; do not resume treatment

Bleeding

  • Persistent, severe, or potentially life-threatening
    • Withhold defibrotide
    • Treat the cause of bleeding and give supportive care as clinically indicated
    • Consider resuming treatment (at the same dose and infusion volume) when bleeding has stopped and the patient is hemodynamically stable
  • Recurrent significant bleeding
    • Discontinue permanently; do not resume treatment

Invasive procedures

  • There is no known reversal agent for the profibrinolytic effects of defibrotide
  • Discontinue infusion at least 2 hr prior to an invasive procedure
  • Resume treatment after the procedure, as soon as any procedure-related risk of bleeding is resolved

Dosing Considerations

Dose is based on weight prior to preparative regimen for HSCT

Next:

Interactions

Interaction Checker

and defibrotide

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

            All Interactions Sort By:
             activity indicator 

            Contraindicated (16)

            • alteplase

              defibrotide increases effects of alteplase by pharmacodynamic synergism. Contraindicated. Coadministration of defibrotide is contraindicated with antithrombotic/fibrinolytic drugs. This does not include use for routine maintenance or reopening of central venous lines.

            • apixaban

              defibrotide increases effects of apixaban by pharmacodynamic synergism. Contraindicated. Coadministration of defibrotide is contraindicated with antithrombotic/fibrinolytic drugs. This does not include use for routine maintenance or reopening of central venous lines.

            • argatroban

              defibrotide increases effects of argatroban by pharmacodynamic synergism. Contraindicated. Coadministration of defibrotide is contraindicated with antithrombotic/fibrinolytic drugs. This does not include use for routine maintenance or reopening of central venous lines.

            • bivalirudin

              defibrotide increases effects of bivalirudin by pharmacodynamic synergism. Contraindicated. Coadministration of defibrotide is contraindicated with antithrombotic/fibrinolytic drugs. This does not include use for routine maintenance or reopening of central venous lines.

            • dabigatran

              defibrotide increases effects of dabigatran by pharmacodynamic synergism. Contraindicated. Coadministration of defibrotide is contraindicated with antithrombotic/fibrinolytic drugs. This does not include use for routine maintenance or reopening of central venous lines.

            • dalteparin

              defibrotide increases effects of dalteparin by pharmacodynamic synergism. Contraindicated. Coadministration of defibrotide is contraindicated with antithrombotic/fibrinolytic drugs. This does not include use for routine maintenance or reopening of central venous lines.

            • desirudin

              desirudin increases effects of defibrotide by pharmacodynamic synergism. Contraindicated. Coadministration of defibrotide is contraindicated with antithrombotic/fibrinolytic drugs. This does not include use for routine maintenance or reopening of central venous lines.

            • edoxaban

              edoxaban increases effects of defibrotide by pharmacodynamic synergism. Contraindicated. Coadministration of defibrotide is contraindicated with antithrombotic/fibrinolytic drugs. This does not include use for routine maintenance or reopening of central venous lines.

            • enoxaparin

              defibrotide increases effects of enoxaparin by pharmacodynamic synergism. Contraindicated. Coadministration of defibrotide is contraindicated with antithrombotic/fibrinolytic drugs. This does not include use for routine maintenance or reopening of central venous lines.

            • fondaparinux

              defibrotide increases effects of fondaparinux by pharmacodynamic synergism. Contraindicated. Coadministration of defibrotide is contraindicated with antithrombotic/fibrinolytic drugs. This does not include use for routine maintenance or reopening of central venous lines.

            • heparin

              defibrotide increases effects of heparin by pharmacodynamic synergism. Contraindicated. Coadministration of defibrotide is contraindicated with antithrombotic/fibrinolytic drugs. This does not include use for routine maintenance or reopening of central venous lines.

            • reteplase

              defibrotide increases effects of reteplase by pharmacodynamic synergism. Contraindicated. Coadministration of defibrotide is contraindicated with antithrombotic/fibrinolytic drugs. This does not include use for routine maintenance or reopening of central venous lines.

            • rivaroxaban

              defibrotide increases effects of rivaroxaban by pharmacodynamic synergism. Contraindicated. Coadministration of defibrotide is contraindicated with antithrombotic/fibrinolytic drugs. This does not include use for routine maintenance or reopening of central venous lines.

            • tenecteplase

              defibrotide increases effects of tenecteplase by pharmacodynamic synergism. Contraindicated. Coadministration of defibrotide is contraindicated with antithrombotic/fibrinolytic drugs. This does not include use for routine maintenance or reopening of central venous lines.

            • vorapaxar

              defibrotide increases effects of vorapaxar by pharmacodynamic synergism. Contraindicated. Coadministration of defibrotide is contraindicated with antithrombotic/fibrinolytic drugs. This does not include use for routine maintenance or reopening of central venous lines.

            • warfarin

              defibrotide increases effects of warfarin by pharmacodynamic synergism. Contraindicated. Coadministration of defibrotide is contraindicated with antithrombotic/fibrinolytic drugs. This does not include use for routine maintenance or reopening of central venous lines.

            Serious - Use Alternative (0)

              Monitor Closely (42)

              • aminocaproic acid

                aminocaproic acid decreases effects of defibrotide by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Defibrotide may diminish effects of thrombolytic agents. Consider therapy modification.

              • aprotinin

                aprotinin decreases effects of defibrotide by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Defibrotide may diminish effects of thrombolytic agents. Consider therapy modification.

              • aspirin

                defibrotide increases effects of aspirin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Defibrotide may enhance effects of platelet inhibitors.

              • aspirin rectal

                defibrotide increases effects of aspirin rectal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Defibrotide may enhance effects of platelet inhibitors.

              • celecoxib

                defibrotide increases effects of celecoxib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Defibrotide may enhance effects of platelet inhibitors.

              • choline magnesium trisalicylate

                defibrotide increases effects of choline magnesium trisalicylate by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Defibrotide may enhance effects of platelet inhibitors.

              • citalopram

                defibrotide increases effects of citalopram by Other (see comment). Use Caution/Monitor. Comment: Defibrotide may enhance effects of platelet inhibitors.

              • clopidogrel

                defibrotide increases effects of clopidogrel by Other (see comment). Use Caution/Monitor. Comment: Defibrotide may enhance effects of platelet inhibitors.

              • diclofenac

                defibrotide increases effects of diclofenac by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Defibrotide may enhance effects of platelet inhibitors.

              • diflunisal

                defibrotide increases effects of diflunisal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Defibrotide may enhance effects of platelet inhibitors.

              • escitalopram

                defibrotide increases effects of escitalopram by Other (see comment). Use Caution/Monitor. Comment: Defibrotide may enhance effects of platelet inhibitors.

              • etodolac

                defibrotide increases effects of etodolac by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Defibrotide may enhance effects of platelet inhibitors.

              • fenoprofen

                defibrotide increases effects of fenoprofen by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Defibrotide may enhance effects of platelet inhibitors.

              • fish oil triglycerides

                fish oil triglycerides will increase the level or effect of defibrotide by anticoagulation. Use Caution/Monitor. Prolonged bleeding reported in patients taking antiplatelet agents or anticoagulants and oral omega-3 fatty acids. Periodically monitor bleeding time in patients receiving fish oil triglycerides and concomitant antiplatelet agents or anticoagulants.

              • fluoxetine

                defibrotide increases effects of fluoxetine by Other (see comment). Use Caution/Monitor. Comment: Defibrotide may enhance effects of platelet inhibitors.

              • flurbiprofen

                defibrotide increases effects of flurbiprofen by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Defibrotide may enhance effects of platelet inhibitors.

              • fluvoxamine

                defibrotide increases effects of fluvoxamine by Other (see comment). Use Caution/Monitor. Comment: Defibrotide may enhance effects of platelet inhibitors.

              • ibrutinib

                ibrutinib will increase the level or effect of defibrotide by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

              • ibuprofen

                defibrotide increases effects of ibuprofen by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Defibrotide may enhance effects of platelet inhibitors.

              • ibuprofen IV

                defibrotide increases effects of ibuprofen IV by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Defibrotide may enhance effects of platelet inhibitors.

              • indomethacin

                defibrotide increases effects of indomethacin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Defibrotide may enhance effects of platelet inhibitors.

              • ketoprofen

                defibrotide increases effects of ketoprofen by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Defibrotide may enhance effects of platelet inhibitors.

              • ketorolac

                defibrotide increases effects of ketorolac by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Defibrotide may enhance effects of platelet inhibitors.

              • ketorolac intranasal

                defibrotide increases effects of ketorolac intranasal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Defibrotide may enhance effects of platelet inhibitors.

              • meclofenamate

                defibrotide increases effects of meclofenamate by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Defibrotide may enhance effects of platelet inhibitors.

              • mefenamic acid

                defibrotide increases effects of mefenamic acid by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Defibrotide may enhance effects of platelet inhibitors.

              • meloxicam

                defibrotide increases effects of meloxicam by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Defibrotide may enhance effects of platelet inhibitors.

              • nabumetone

                defibrotide increases effects of nabumetone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Defibrotide may enhance effects of platelet inhibitors.

              • naproxen

                defibrotide increases effects of naproxen by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Defibrotide may enhance effects of platelet inhibitors.

              • oxaprozin

                defibrotide increases effects of oxaprozin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Defibrotide may enhance effects of platelet inhibitors.

              • paroxetine

                defibrotide increases effects of paroxetine by Other (see comment). Use Caution/Monitor. Comment: Defibrotide may enhance effects of platelet inhibitors.

              • piroxicam

                defibrotide increases effects of piroxicam by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Defibrotide may enhance effects of platelet inhibitors.

              • prasugrel

                defibrotide increases effects of prasugrel by Other (see comment). Use Caution/Monitor. Comment: Defibrotide may enhance effects of platelet inhibitors.

              • salsalate

                defibrotide increases effects of salsalate by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Defibrotide may enhance effects of platelet inhibitors.

              • sertraline

                defibrotide increases effects of sertraline by Other (see comment). Use Caution/Monitor. Comment: Defibrotide may enhance effects of platelet inhibitors.

              • sulindac

                defibrotide increases effects of sulindac by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Defibrotide may enhance effects of platelet inhibitors.

              • ticagrelor

                defibrotide increases effects of ticagrelor by Other (see comment). Use Caution/Monitor. Comment: Defibrotide may enhance effects of platelet inhibitors.

              • ticlopidine

                defibrotide increases effects of ticlopidine by Other (see comment). Use Caution/Monitor. Comment: Defibrotide may enhance effects of platelet inhibitors.

              • tirofiban

                defibrotide increases effects of tirofiban by Other (see comment). Use Caution/Monitor. Comment: Defibrotide may enhance effects of platelet inhibitors.

              • tolmetin

                defibrotide increases effects of tolmetin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Defibrotide may enhance effects of platelet inhibitors.

              • tranexamic acid injection

                tranexamic acid injection decreases effects of defibrotide by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Defibrotide may diminish effects of thrombolytic agents. Consider therapy modification.

              • tranexamic acid oral

                tranexamic acid oral decreases effects of defibrotide by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Defibrotide may diminish effects of thrombolytic agents. Consider therapy modification.

              Minor (0)

                Previous
                Next:

                Adverse Effects

                >10%

                Hypotension, any grade (37%)

                Diarrhea, any grade (24%)

                Vomiting, any grade (18%)

                Nausea, any grade (16%)

                Epistaxis, any grade (14%)

                1-10%

                Pulmonary alveolar hemorrhage (7-9%)

                GI hemorrhage (3-9%)

                Sepsis (5-7%)

                GVHD (4-6%)

                Lung infiltration (3-6%)

                Pneumonia (3-5%)

                Pulmonary hemorrhage (2-4%)

                Infection (2-3%)

                Hemorrhage intracranial (2-3%)

                Hyperuricemia (2%)

                Cerebral hemorrhage (2%)

                Hypersensitivity reactions (<2%)

                Previous
                Next:

                Warnings

                Contraindications

                Coadministration with systemic anticoagulant or fibrinolytic therapy

                Known hypersensitivity to defibrotide or any of its excipients

                Cautions

                Defibrotide increases activity of fibrinolytic enzymes in vitro, and it may increase risk of bleeding in patients with VOD; monitor for bleeding

                Do not initiate drug in patients with active bleeding

                If bleeding occurs, discontinue drug and treat the underlying cause (also see Dosage Modifications)

                Do not use with systemic anticoagulants or fibrinolytic agents (except for routine maintenance or reopening of central venous lines)

                Hypersensitivity reactions reported and may include rash, urticaria, and angioedema

                Previous
                Next:

                Pregnancy

                Pregnancy

                There are no available data on use in pregnant women Advise pregnant women of the potential risk of miscarriage (based on animal data)

                Animal data

                • When administered to pregnant rabbits during the period of organogenesis at doses that were comparable to the recommended human dose based on body surface area, defibrotide sodium decreased the number of implantations and viable fetuses

                Lactation

                Unknown if distributed in human breast milk

                Because of the potential for serious adverse reactions, including bleeding in a breastfed infant, advise patients that breastfeeding is not recommended during treatment

                Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition

                Pregnancy Categories

                A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

                B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

                C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

                D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

                X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

                NA: Information not available.

                Previous
                Next:

                Pharmacology

                Mechanism of Action

                The mechanism of action has not been fully elucidated

                Enhances the enzymatic activity of plasmin to hydrolyze fibrin clots

                Studies evaluating the pharmacological effects of defibrotide on endothelial cells (ECs) were conducted primarily in the human microvascular endothelial cell line

                In vitro, defibrotide increased tissue plasminogen activator (t-PA) and thrombomodulin expression and decreased von Willebrand factor (vWF) and plasminogen activator inhibitor-1 (PAI-1) expression, thereby reducing EC activation and increasing EC-mediated fibrinolysis

                Protected ECs from damage caused by chemotherapy, TNF-alpha, serum starvation, and perfusion

                Absorption

                Peak plasma time: At end of IV infusion

                Distribution

                Protein bound: 93%

                Vd: 8.1-9.1 L

                Metabolism

                Though the precise pathway of defibrotide degradation in plasma in vivo is largely unknown, it has been suggested that nucleases, nucleotidases, nucleosidases, deaminases, and phosphorylases metabolize polynucleotides progressively to oligonucleotides, nucleotides, nucleosides, and then to the free 2'-deoxyribose sugar, purine, and pyrimidine bases

                Elimination

                Half-life: <2 hr

                Total clearance: 3.4-5.1 L/hr

                Excretion: 5-15% urine

                Previous
                Next:

                Administration

                IV Preparation

                Dilute with D5W or 0.9% NaCl to a concentration of 4 mg/mL to 20 mg/mL

                Determine the dose (mg) and number of vials based on the individual patient’s baseline weight (weight prior to the preparative regimen for HSCT)

                Calculate the volume of defibrotide needed, withdraw this amount from the vial(s), and add it to the infusion bag to result in dilution 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

                IV Administration

                Must be diluted prior to infusion

                Prior to administration, confirm that the patient is not experiencing clinically significant bleeding and is hemodynamically stable on no more than 1 vasopressor

                Administer diluted solution by constant IV infusion over 2 hr

                Administer the diluted solution using an infusion set equipped with a 0.2-micron in-line filter

                Flush IV line (peripheral or central) with D5W or 0.9% NaCl immediately before and after administration

                Do not coadminister with other IV drugs concurrently within the same IV line

                Storage

                Unopened vials: 20-25°C (68-77°F); excursions permitted between 15-30°C (59-86°F)

                Vials contain no antimicrobial preservatives and are intended for a single-patient-use only

                Partially used vials should be discarded

                Use the diluted solution within 4 hr if stored at room temperature or within 24 hr if refrigerated

                Up to 4 doses may be prepared at one time, if refrigerated

                Previous
                Next:

                Images

                No images available for this drug.
                Previous
                Next:

                Patient Handout

                A Patient Handout is not currently available for this monograph.
                Previous
                Next:

                Formulary

                FormularyPatient Discounts

                Adding plans allows you to compare formulary status to other drugs in the same class.

                To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

                Adding plans allows you to:

                • View the formulary and any restrictions for each plan.
                • Manage and view all your plans together – even plans in different states.
                • Compare formulary status to other drugs in the same class.
                • Access your plan list on any device – mobile or desktop.

                The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

                Tier Description
                1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
                2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
                3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
                4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                NC NOT COVERED – Drugs that are not covered by the plan.
                Code Definition
                PA Prior Authorization
                Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
                QL Quantity Limits
                Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
                ST Step Therapy
                Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
                OR Other Restrictions
                Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
                Additional Offers
                Email to Patient

                From:

                To:

                The recipient will receive more details and instructions to access this offer.

                By clicking send, you acknowledge that you have permission to email the recipient with this information.

                Email Forms to Patient

                From:

                To:

                The recipient will receive more details and instructions to access this offer.

                By clicking send, you acknowledge that you have permission to email the recipient with this information.

                Previous
                Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.