Prescribing information

 

Adverse reactions reported in ADAKVEO® patients:

 

Very common (≥10% of patients) 

  • Nausea
  • Abdominal pain*
  • Arthralgia
  • Back pain
  • Pyrexia    

These adverse drug reactions, along with myalgia, musculoskeletal chest pain and diarrhoea, may be signs and symptoms of an infusion related reaction when observed during infusion or within 24 hours of an infusion

Common (1 to 10% of patients)

  • Oropharyngeal pain
  • Diarrhoea
  • Vomiting
  • Pruritus*
  • Myalgia
  • Musculoskeletal chest pain
  • Infusion site reaction*
  • Infusion related reaction

 

Severe events were less common1

  • Arthralgia and pyrexia (each 0.9%)

 

Two patients on ADAKVEO® discontinued treatment due to adverse reactions vs. three patients on placebo in the SUSTAIN study

 

Adverse drug reactions reported in ≥5% of ADAKVEO® patients in a pooled safety analysis3,4

A table of results showing the Adverse drug reactions reported in ≥5% of ADAKVEO® patients in a pooled safety analysis.

 

Monitoring of patients1

Infusion-related reactions

ADAKVEO® patients should be monitored for and advised of signs and symptoms of infusion-related reactions.

These may include the following:

  • Fever
  • Pain in various locations
  • Headache
  • Chills
  • Nausea
  • Vomiting
  • Fatigue
  • Diarrhoea
  • Dizziness
  • Pruritus
  • Urticaria
  • Sweating
  • Shortness of breath or wheezing

In the event of a severe infusion-related reaction, ADAKVEO® should be discontinued and appropriate therapy should be instituted

Caution should be exercised with corticosteroids in patients with sickle cell disease unless clinically indicated (e.g. treatment of anaphylaxis)

Recommendations for managing infusion-related reactions: Mild (Grade 1) to moderate (Grade 2) infusion‑related reactions - temporarily interrupt or reduce the infusion rate, initiate symptomatic treatment, for subsequent infusions, consider premedication. Severe (≥ Grade 3) infusion‑related reactions - Discontinue treatment with Adakveo and initiate symptomatic treatment.

In the post-marketing setting, cases of infusion-related reactions were reported, including severe pain events, differing in location, severity, and/or nature from patient’s baseline and requiring hospitalisation in several cases. The majority of these infusion-related reactions occurred during infusion or within a few hours of the completion of the first or second infusion. However, later onset of severe pain events has also been reported, following previous well-tolerated infusions. Some patients have also experienced subsequent complications such as acute chest syndrome and fat embolism, particularly those treated with steroids.

 

Fertility, pregnancy and lactation1

Fertility and pregnancy

  • There are no data on the effect of ADAKVEO® on human fertility. Available non-clinical data do not suggest an effect on fertility under ADAKVEO® treatment
  • ADAKVEO® has the potential to cause foetal losses when administered to a pregnant woman so should be avoided during pregnancy and in women hoping to conceive
  • All pregnancy cases and complications should be reported to Novartis
  • Patients will be monitored through the PRegnancy outcomes Intension Monitoring programme (PRIM)

Lactation

  • It is unknown if ADAKVEO® is excreted in human milk. There are no data on the effects of the treatment on breast-fed newborns/infants or milk production
  • A decision may be needed to discontinue breast-feeding or ADAKVEO® therapy

Effects on ability to drive and use machines

ADAKVEO® may have a minor influence on the ability to drive and use machines. Dizziness, fatigue and somnolence may occur following administration

Reporting suspected adverse reactions after authorisation of ADAKVEO® is important to understand the safety profile of the treatment for sickle cell disease (SCD) patients

 

Banner: ADAKVEO is subject to additional monitoring. Healthcare professionals are asked to report any suspected adverse reactions via Yellow Card scheme (website given) or directly to Novartis.

 

ADAKVEO® is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. Reporting suspected adverse reactions after authorisation of ADAKVEO® is important to understand the safety profile of the treatment for SCD patients.

Indication: ADAKVEO® (crizanlizumab) is indicated for the prevention of recurrent VOCs in patients with SCD who are aged 16 years and over. It can be given as an add-on therapy to hydroxyurea/hydroxycarbamide (HU/HC) or as monotherapy in patients for whom HU/HC is inappropriate or inadequate.1

ADAKVEO® has a conditional marketing authorisation and further evidence is awaited.

*The following groupings contain the following MedDRA preferred terms:1 
- Abdominal pain: abdominal pain, abdominal pain upper, abdominal pain lower, abdominal discomfort, and abdominal tenderness 
- Pruritus: pruritus and vulvovaginal pruritus 
- Infusion site reaction: infusion site extravasation, infusion site pain and infusion site swelling

Abbreviations: HC, hydroxycarbamide; HU, hydroxyurea; PRIM, PRegnancy outcomes Intension Monitoring programme; SCD, sickle cell disease; VOC, vaso-occlusive crisis.

Reference

  1. ADAKVEO® Summary of Product Characteristics.
  2. Kutlar A, et al. Am J Hematol. 2019;94(1):55–61.
  3. Ataga KI, et al. N Engl J Med. 2017;376(5):429–439.
  4. ADAKVEO® EPAR CHMP assessment report. 2020.

 

 

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UK | April 2022 | 203802
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Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse events should also be reported to Novartis via [email protected] or online through the pharmacovigilance intake (PVI) tool at www.report.novartis.com
If you have a question about the product, please contact Medical Information on 01276 698370 or by email at [email protected]