European Commission Grants Marketing Authorisation for Unituxin™ (dinutuximab) for the Treatment of Paediatric High-Risk Neuroblastoma - Seite 3

Important EU Safety Information for Unituxin

• This medicinal product is subject to additional monitoring.  This will allow quick identification of new safety information.  Healthcare professionals are asked to report any suspected adverse reactions.

Contraindications
Hypersensitivity (Grade 4) to the active substance or to any of the excipients in Unituxin.

SPECIAL WARNINGS AND PRECAUTIONS FOR USE

• Allergic Reactions
  • Antihistamine premedication (e.g. hydroxyzine or diphenhydramine) should be administered by intravenous injection approximately 20 minutes before starting each Unituxin infusion. 
  • It is recommended that antihistamine medicinal product be repeated every 4–6 hours as required during infusion of Unituxin.  Patients should be monitored for signs and symptoms of infusion reactions for 4 hours after the completion of the Unituxin infusion.
  • Epinephrine (adrenaline) and hydrocortisone for intravenous administration should be immediately available at the bedside during administration of dinutuximab to manage life-threatening allergic reactions. 
  • It is recommended that treatment for such reactions include hydrocortisone administered by intravenous bolus, and epinephrine administered by intravenous bolus once every 3–5 minutes as necessary according to clinical response.
  • Depending on the severity of the allergic reaction, the rate of infusion should be reduced or treatment discontinued.

• Capillary Leak Syndrome
  • Capillary leak syndrome is more likely when dinutuximab is co-administered with IL-2.  It is recommended to administer oral metolazone or intravenous furosemide every 6–12 hours as required.  Supplemental oxygen, respiratory support, and albumin replacement therapy should be used as necessary according to clinical response.
  • Characteristic symptoms and signs include hypotension, generalized oedema, ascites, dyspnoea, pulmonary oedema and acute renal failure associated with hypoalbuminaemia and haemoconcentration.

• Pain
  • Severe pain (Grade 3 or 4) occurs most frequently during the first 4-day course of Unituxin, often subsiding over time with subsequent courses.
  • For severe pain, the Unituxin infusion rate should be decreased to 0.875 mg/m2/hour.  Unituxin should be discontinued if pain is not adequately controlled despite infusion rate reduction and institution of maximum supportive measures.
  • Paracetamol should be administered orally 20 minutes prior to starting each dinutuximab infusion, and repeated every 4-6 hours as needed.  Regular dosing every 4–6 hours is recommended when IL-2 is coadministered.  If required for persistent pain, ibuprofen should be administered orally every 6 hours between doses of paracetamol.  Ibuprofen should not be administered if there is evidence of thrombocytopenia, bleeding, or renal dysfunction.
  • An opioid, such as morphine sulphate, is recommended to be administered by intravenous infusion prior to each dinutuximab infusion and continued as an intravenous infusion during and until 2 hours after completion of the treatment.  It is recommended that additional intravenous bolus doses of an opioid are administered as needed for treatment of pain up to once every 2 hours during the dinutuximab infusion.  If morphine is not tolerated, then fentanyl or hydromorphone may be utilised.
  • Lidocaine may be administered as an intravenous infusion (2 mg/kg in 50 mL of 0.9% sodium chloride) over 30 minutes prior to the start of each dinutuximab infusion and continued via intravenous infusion at 1 mg/kg/h up to 2 hours after completion of the treatment.  Lidocaine infusion should be discontinued if the patient develops dizziness, perioral numbness, or tinnitus.
  • Gabapentin may be administered at the time of starting morphine premedication, at an oral dose of 10 mg/kg/day.  The dose may be subsequently increased (up to a maximum of 60 mg/kg/day or 3600 mg/day) as needed for pain management.

• Hypotension
  • Intravenous sodium chloride 9 mg/mL (0.9%) solution for injection (10 mL/kg) should be administered over one hour just prior to the dinutuximab infusion.  If hypotension occurs, this can be repeated, or intravenous albumin or packed red blood cells can be administered as clinically indicated.