Defibrotide – Uses, Dosage, Side Effects, Interaction

Defibrotide is a deoxyribonucleic acid derivative extracted from mammalian organs, which has been developed for the treatment of a number of vascular disorders. It appears to increase fibrinolysis and may possess antithrombotic, antiatherosclerotic, and anti-ischaemic actions, probably due to its ability to selectively increase prostaglandin I2 and E2 levels and to increase tissue plasminogen activator and decrease plasminogen activator inhibitor function. Defibrotide is available as an intravenous and intramuscular preparation, and also as an oral formulation for long-term use.

Use in Cancer

Defibrotide sodium is approved to treat:

• Hepatic veno-occlusive disease (also known as sinusoidal obstruction syndrome) in adults and children who also have kidney or lung problems after receiving a stem cell transplant.

Contraindications

• an increased risk of bleeding
• bleeding
• The use of defibrotide for people who are already taking anticoagulants is dangerous and the use of other drugs that affect platelet aggregation, like NSAIDs, should be done with care.
• Defibrotide should not be given to people who have a difficult time maintaining steady blood pressure.^[rx]

Dosage?

Strengths: 80 mg/mL

Hepatic Veno-Occlusive Disease

• 6.25 mg/kg IV every 6 hours given as a constant 2-hour infusion
• Duration of therapy: Minimum of 21 days; if signs and symptoms of hepatic venous-occlusive disease (VOD) remain after 21 days, continue this drug until resolution of VOD or up to a maximum of 60 days. Baseline? body weight prior to the preparative regimen for hematopoietic stem-cell transplantation (HSCT) should be used to calculate the dose.

Pediatric Dose for Hepatic Veno-Occlusive Disease

1 Month or Older:

• 6.25 mg/kg IV every 6 hours given as a constant 2-hour infusion
• Duration of therapy: Minimum of 21 days; if signs and symptoms of hepatic venous-occlusive disease (VOD) remain after 21 days, continue this drug until resolution of VOD or up to a maximum of 60 days.
• Baseline body weight prior to the preparative regimen for hematopoietic stem-cell transplantation (HSCT) should be used to calculate the dose.

Dose Adjustments

TREATMENT MODIFICATIONS FOR TOXICITY OR INVASIVE? PROCEDURES:

• Severe or Life-Threatening Hypersensitivity Reaction (Anaphylaxis?): Discontinue this drug permanently; do not resume treatment.
• Persistent, Severe, or Potentially Life-Threatening Bleeding: Withhold this drug; treat the underlying cause and provide supportive care as indicated; consider resuming treatment at the same dose and infusion volume when bleeding stops and the patient is hemodynamically stable.
• Recurrent? Significant Bleeding: Discontinue this drug permanently; do not resume treatment.
• Invasive Procedures: Discontinue this drug at least 2 hours prior to an invasive procedure; resume treatment after the procedure as soon as any procedure-related risk of bleeding is resolved.

Administration advice:

• Use an infusion set equipped with a 0.2-micron in-line filter.
• Flush the IV line (peripheral or central) with a 5% dextrose injection or 0.9% sodium chloride injection immediately before and after administration.

Side Effects

The Most Common

• dizziness?
• diarrhea?
• vomiting?
• nausea?
• nose bleeding
• rash?
• hives?
• itching?
• swelling? of the face, lips, tongue or throat?
• unusual bleeding or bruising?
• blood in urine? or stool
• headache?
• confusion?
• slurred speech
• vision changes
• fever, cough, or other signs of infection

More common

• Black, tarry stools
• bloody nose
• bloody stools
• blurred vision
• chills
• confusion
• dizziness
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• fainting
• fast heartbeat
• fever
• lightheadedness
• rapid, shallow breathing
• sweating
• unusual tiredness or weakness
• vomiting of blood or material that looks like coffee grounds
• Chest pain
• cough or hoarseness
• lower back or side pain
• painful or difficult urination
• sneezing
• sore throat
• tightness in the chest
• troubled breathing

Rare

• abdominal pain
• dizziness
• headache
• increased menstrual bleeding
• Difficulty with swallowing
• hives, itching, or skin rash
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• itchy skin
• rash
• stiff, sore, hot, or painful joints
• sudden pain or swelling in muscles
• signs of anemia (low red blood cells; e.g., dizziness, pale skin, unusual tiredness or weakness, shortness of breath)
• signs of clotting problems (e.g., unusual nosebleeds, bruising, blood in urine, coughing blood, bleeding gums, cuts that don’t stop bleeding)
• signs of bleeding in the stomach (e.g., bloody, black, or tarry stools; spitting up of blood; vomiting blood or material that looks like coffee grounds)
• signs of stroke (e.g., sudden or severe headache; sudden loss of coordination; vision changes; sudden slurring of speech; or unexplained weakness, numbness, or pain in arm or leg)
• signs of a serious allergic reaction (e.g., abdominal cramps, difficulty breathing, nausea and vomiting, or swelling of the face and throat)
• signs of severe skin reactions (e.g., blistering, peeling, a rash covering a large area of the body, a rash that spreads quickly, or a rash combined with fever or discomfort)

Drug Interaction

Pregnancy and Lactation

US FDA pregnancy category: Not assigned

Pregnancy

There are no controlled data on human pregnancy. Use is not recommended unless clearly needed. The manufacturer makes no recommendation regarding use during pregnancy. No data exist regarding the use of this drug in pregnant women. Advise pregnant women of the potential risk of miscarriage.

Lactation

There are no adequate studies on women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

References