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How to order Defitelio® (defibrotide sodium)

McKesson Plasma and Biologics

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Thank you!

A Jazz representative will contact you shortly.

Jazz Pharmaceuticals respects your interest in keeping your personal information private. The personal information you provide will be used by Jazz Pharmaceuticals to respond to your request. For more information about how Jazz Pharmaceuticals protects your personal information, please click here to view our Privacy Statement.

To contact Jazz Pharmaceuticals Customer Service, please call 1-800-833-3533.

To report suspected adverse reactions, please call Jazz Pharmaceuticals at 1-800-520-5568 or contact the FDA at 1-800-FDA-1088.

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DIAGNOSTIC CRITERIA FOR VOD

VOD diagnostic criteria and considerations

Historically, the Baltimore and modified Seattle criteria have been used for diagnosis of VOD1-3

However, there are limitations to these criteria1,4-7

  • Criteria do not consider that signs and symptoms of VOD can occur after the first 21 days post HSCT
  • Criteria do not consider VOD that presents in the absence of specified signs and symptoms; eg, VOD without hyperbilirubinemia is not considered in the Baltimore criteria
  • Criteria do not capture recent clinical descriptions of disease
  • Criteria do not include newer imaging capabilities, which may be more sensitive to specific indicators of VOD/SOS

Recently published criteria have been proposed to address limitations of these historical criteria

EBMT diagnostic criteria for VOD in adults

VOD that occurs ≤21 days post HSCT5

Baltimore criteriaa:

Presentation of bilirubin ≥2 mg/dL and at least 2 of the following:

  • Painful hepatomegaly
  • Weight gain (>5%)
  • Ascites

Late-onset VOD >21 days post HSCT5

Baltimore criteriaa beyond Day 21

OR histologically proven VOD
OR 2 or more of the following criteria must be present:

  • Bilirubin ≥2 mg/dL (or 34 µmol/L)
  • Painful hepatomegaly
  • Weight gain (>5%)
  • Ascites

AND hemodynamic or/and ultrasound evidence of VOD (hepatomegaly, ascites, and decrease in velocity or reversal of portal flow)

These proposed criteria have not been prospectively validated in clinical trials

aDefined as classical VOD in EBMT criteria.

EBMT diagnostic criteria for VOD in children, with implemention guidance

THE EMBT CRITERIA FOR CHILDREN DO NOT INCLUDE A LIMITATION FOR TIME OF VOD ONSET
The presence of 2 or more of the following is required6,b:
Implementation guidance from Mahadeo et al:
  • Unexplained consumptive and transfusion-refractory thrombocytopeniac
  • Defined as a CCI of <5000-7500 following ≥2 sequential ABO-compatible fresh platelet transfusions7
  • Otherwise unexplained weight gain on 3 consecutive days, despite the use of diuretics, or weight gain >5% above baseline value
  • Hepatomegaly above baseline value (best if confirmed by imaging)d
  • Defined as an absolute increase of ≥1 cm in liver length at the midclavicular line; if a baseline measurement is not available, can be defined as >2 SDs above normal for age7
  • Ascites above baseline value (best if confirmed by imaging)d
  • Mild (minimal fluid by liver, spleen, or pelvis), moderate (<1 cm fluid), or severe (fluid in all 3 regions with >1 cm fluid in at least 2 regions). When feasible, baseline ultrasound should be used to identify increased ascites7
  • Rising bilirubin from a baseline value on 3 consecutive days or bilirubin ≥2 mg/dL within 72 hours
  • Liver biopsy, portal venous wedge pressure, and reversal of portal venous flow on Doppler ultrasonography should not be used for the routine diagnosis of VOD in children, adolescents, and young adults7
  • Use of a structured radiologic reporting template is recommended when there is clinical concern for VOD7
THE EMBT CRITERIA FOR CHILDREN DO NOT INCLUDE A LIMITATION FOR TIME OF VOD ONSET

The presence of 2 or more of the following is required6,b:

  • Unexplained consumptive and transfusion-refractory thrombocytopeniac
Implementation guidance from Mahadeo et al:
  • Defined as a CCI of <5000-7500 following ≥2 sequential ABO-compatible fresh platelet transfusions7
  • Otherwise unexplained weight gain on 3 consecutive days, despite the use of diuretics, or weight gain >5% above baseline value
  • Hepatomegaly above baseline value (best if confirmed by imaging)d
Implementation guidance from Mahadeo et al:
  • Defined as an absolute increase of ≥1 cm in liver length at the midclavicular line; if a baseline measurement is not available, can be defined as >2 SDs above normal for age7
  • Ascites above baseline value (best if confirmed by imaging)d
Implementation guidance from Mahadeo et al:
  • Mild (minimal fluid by liver, spleen, or pelvis), moderate (<1 cm fluid), or severe (fluid in all 3 regions with >1 cm fluid in at least 2 regions). When feasible, baseline ultrasound should be used to identify increased ascites7
  • Rising bilirubin from a baseline value on 3 consecutive days or bilirubin ≥2 mg/dL within 72 hours
Additional implementation guidance from Mahadeo et al:
  • Liver biopsy, portal venous wedge pressure, and reversal of portal venous flow on Doppler ultrasonography should not be used for the routine diagnosis of VOD in children, adolescents, and young adults7
  • Use of a structured radiologic reporting template is recommended when there is clinical concern for VOD7

These proposed criteria have not been prospectively validated in clinical trials

bWith the exclusion of other potential differential diagnoses.

c≥1 weight-adjusted platelet substitution/day to maintain institutional transfusion guidelines.

dSuggested: imaging (US, CT, or MRI) immediately before HSCT to determine baseline value for both hepatomegaly and ascites.

Recent advances in making early and accurate diagnosis of VOD

EBMT5
ADULT

EBMT6,7
CORBACIOGLU/
MAHADEO
PEDIATRIC & AYA

CAIRO/
COOKE4 AGE AGNOSTIC

≤21 days post HSCT

>21 days post HSCT

No time constraint to diagnose VOD

Allows for cases of anicteric VOD

Includes refractoriness to excessive platelet transfusions

Includes abdominal ultrasound (hepatomegaly and/or ascites)

Includes Doppler ultrasound imaging (reversal of portal venous flow)

Hemodynamic stability/hepatic wedge pressure

g

Biopsy

g
g

These proposed criteria have not been prospectively validated in clinical trials

gWhile not recommended, if conducted and diagnostic, this allows for a VOD diagnosis independent of any other findings.

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IMPORTANT SAFETY INFORMATION AND INDICATION

Contraindications

Defitelio is contraindicated in the following conditions:

Indication

Defitelio® (defibrotide sodium) is indicated for the treatment of adult and pediatric patients with hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), with renal or pulmonary dysfunction following hematopoietic stem-cell transplantation (HSCT).

IMPORTANT SAFETY INFORMATION

Contraindications

Defitelio is contraindicated in the following conditions:

  • Concomitant administration with systemic anticoagulant or fibrinolytic therapy
  • Known hypersensitivity to Defitelio or to any of its excipients

Indication

Defitelio® (defibrotide sodium) is indicated for the treatment of adult and pediatric patients with hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), with renal or pulmonary dysfunction following hematopoietic stem-cell transplantation (HSCT).

IMPORTANT SAFETY INFORMATION

Contraindications

Defitelio is contraindicated in the following conditions:

  • Concomitant administration with systemic anticoagulant or fibrinolytic therapy
  • Known hypersensitivity to Defitelio or to any of its excipients

Warnings and Precautions

Hemorrhage

Defitelio may increase the risk of bleeding in patients with VOD after HSCT. Do not initiate Defitelio in patients with active bleeding. Monitor patients on Defitelio for signs of bleeding. If bleeding occurs, withhold or discontinue Defitelio.

Concomitant systemic anticoagulant or fibrinolytic therapy may increase the risk of bleeding and should be discontinued prior to Defitelio treatment. Consider delaying Defitelio administration until the effects of the anticoagulant have abated.

Hypersensitivity Reactions

Hypersensitivity reactions including rash, urticaria, and angioedema have occurred in less than 2% of patients treated with Defitelio. One case of an anaphylactic reaction was reported in a patient who had previously received Defitelio. Monitor patients for hypersensitivity reactions, especially if there is a history of previous exposure. If a severe hypersensitivity reaction occurs, discontinue Defitelio, treat according to the standard of care, and monitor until symptoms resolve.

Most Common Adverse Reactions

The most common adverse reactions (incidence ≥10% and independent of causality) with Defitelio treatment were hypotension, diarrhea, vomiting, nausea, and epistaxis.

Please see full Prescribing Information.

Indication

Defitelio® (defibrotide sodium) is indicated for the treatment of adult and pediatric patients with hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), with renal or pulmonary dysfunction following hematopoietic stem-cell transplantation (HSCT).

IMPORTANT SAFETY INFORMATION

Contraindications

Defitelio is contraindicated in the following conditions:

  • Concomitant administration with systemic anticoagulant or fibrinolytic therapy
  • Known hypersensitivity to Defitelio or to any of its excipients

Warnings and Precautions

Hemorrhage

Defitelio may increase the risk of bleeding in patients with VOD after HSCT. Do not initiate Defitelio in patients with active bleeding. Monitor patients on Defitelio for signs of bleeding. If bleeding occurs, withhold or discontinue Defitelio.

Concomitant systemic anticoagulant or fibrinolytic therapy may increase the risk of bleeding and should be discontinued prior to Defitelio treatment. Consider delaying Defitelio administration until the effects of the anticoagulant have abated.

Hypersensitivity Reactions

Hypersensitivity reactions including rash, urticaria, and angioedema have occurred in less than 2% of patients treated with Defitelio. One case of an anaphylactic reaction was reported in a patient who had previously received Defitelio. Monitor patients for hypersensitivity reactions, especially if there is a history of previous exposure. If a severe hypersensitivity reaction occurs, discontinue Defitelio, treat according to the standard of care, and monitor until symptoms resolve.

Most Common Adverse Reactions

The most common adverse reactions (incidence ≥10% and independent of causality) with Defitelio treatment were hypotension, diarrhea, vomiting, nausea, and epistaxis.

Please see full Prescribing Information.

AYA=adolescent and young adult; CCI=corrected count increment; CT=computed tomography; EBMT=European Society for Blood and Marrow Transplantation; HSCT=hematopoietic stem-cell transplantation; MRI=magnetic resonance imaging; SD=standard deviation; SOS=sinusoidal obstruction syndrome; US=ultrasonography; VOD=veno-occlusive disease.

References: 1. Carreras E. Early complications after HSCT. In: Apperley J, Carreras E, Gluckman E, et al, eds. The EBMT Handbook. 6th ed. Paris, France: European School of Haematology; 2012:176-195. 2. Jones RJ, Lee KS, Beschorner WE, et al. Venoocclusive disease of the liver following bone marrow transplantation. Transplantation. 1987;44(6):778-783. 3. McDonald GB, Sharma P, Matthews DE, et al. Venocclusive disease of the liver after bone marrow transplantation: diagnosis, incidence, and predisposing factors. Hepatology. 1984;4(1):116-122. 4. Cairo MS, Cooke KR, Lazarus HM, et al. Modified diagnostic criteria, grading classification and newly elucidated pathophysiology of hepatic SOS/VOD after haematopoietic cell transplantation. Br J Haematol. 2020;190(6):822-836. 5. Mohty M, Malard F, Abecassis M, et al. Revised diagnosis and severity criteria for sinusoidal obstruction syndrome/veno-occlusive disease in adult patients: a new classification from the European Society for Blood and Marrow Transplantation. Bone Marrow Transplant. 2016;51(7):906-912. 6. Corbacioglu S, Carreras E, Ansari M, et al. Diagnosis and severity criteria for sinusoidal obstruction syndrome/veno-occlusive disease in pediatric patients: a new classification from the European Society for Blood and Marrow Transplantation. Bone Marrow Transplant. 2018;53(2):138-145. 7. Mahadeo KM, Bajwa R, Abdel-Azim H, et al; Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network; Pediatric Diseases Working Party of the European Society for Blood and Marrow Transplantation. Diagnosis, grading, and treatment recommendations for children, adolescents, and young adults with sinusoidal obstructive syndrome: an international expert position statement. Lancet Haematol. 2020;7(1):e61-e72.