Safety

IRRs may happen during/within 24 hours of infusion¹

With monoclonal antibodies such as ADAKVEO, there is the potential for IRRs.

• In the SUSTAIN study, IRRs were observed in 2 (3%) patients treated with ADAKVEO^® (crizanlizumab-tmca) 5 mg/kg (N=66) during/within 24 hours of infusion¹
• Postmarketing cases of IRRs, including severe pain events requiring hospitalizations, have been reported. The majority of these IRRs occurred during the first and second infusions. Some patients have also experienced subsequent complications, such as acute chest syndrome and fat embolism, particularly those treated with steroids¹
• Monitor for and advise patients of signs and symptoms such as¹:

• Pain in various locations
• Headache
• Fever
• Chills
• Nausea

• Vomiting
• Diarrhea
• Fatigue
• Dizziness
• Pruritus

• Urticaria
• Sweating
• Shortness of breath or wheezing

• These are not all the potential signs and symptoms of IRRs
• Advise your patients to contact their health care provider immediately if they experience any possible signs and symptoms of IRRs during and within 24 hours of the infusion¹

Recommended management for IRRs¹

Exercise caution with the use of corticosteroids in patients with sickle cell disease unless clinically indicated (eg, treatment of anaphylaxis).¹

*Slow rate of infusion at the clinical discretion of the treating physician or according to your institutional protocols.

For patients with SCD, use of corticosteroids may cause complications^1,2

 

 

 

Majority of ARs with ADAKVEO were mild to moderate (grade 1 or 2)¹

*Abdominal pain: abdominal pain, upper abdominal pain, lower abdominal pain, and abdominal tenderness.

Counsel patients about the possibility of an AR
If an AR occurs, manage according to your institutional protocols and consider the following tips:
Nausea (18%)		Arthralgia (18%) or Back Pain (15%)		Abdominal Pain (12%) or Pyrexia (11%)
Consider recommending routine management with supportive care Consider prescribing antiemetics, if needed		Consider prescribing analgesics, per standard of care, if needed		Evaluate individual cases, considering the patient's status and SCD medical history
Follow up with your patients who have experienced an AR to assess whether symptoms resolved

Counsel patients about the possibility of an AR

If an AR occurs, manage according to your institutional protocols and consider the following tips:

Nausea (18%)

Consider recommending routine management with supportive care Consider prescribing antiemetics, if needed

Arthralgia (18%) or Back Pain (15%)

Consider prescribing analgesics, per standard of care, if needed

Abdominal Pain (12%) or Pyrexia (11%)

Evaluate individual cases, considering the patient's status and SCD medical history

Follow up with your patients who have experienced an AR to assess whether symptoms resolved

Putting Patients First:

While some patients taking ADAKVEO may experience IRRs or ARs, depending on the severity of the reaction, steps may be taken to manage without disruption to the patient's treatment journey.

Putting Patients First:

While some patients taking ADAKVEO may experience IRRs or ARs, depending on the severity of the reaction, steps may be taken to manage without disruption to the patient's treatment journey.

 

Rates of infection, blood count results, and blood chemistry findings were similar to those with placebo⁹

Infection rates

• Similar infection rates were observed with ADAKVEO and placebo (overall, 51.5% vs 53.2%; serious, 12.1% vs 16.1%)
• Infections were observed with ADAKVEO and placebo, and included urinary tract infection (13.6% vs 11.3%), upper respiratory tract infection (10.6% vs 9.7%), pneumonia (6.1% vs 4.8%), and influenza (1.5% vs 0%)

Blood count results

• The incidence of neutropenia was 3.0% for ADAKVEO vs 6.5% for placebo
• No significant clinical differences between ADAKVEO vs placebo in hemoglobin (LSM: 1.5; 0.8 vs -0.7); reticulocyte count (LSM: -9.79; -7.12 vs 2.68); or haptoglobin (LSM: 0.03; 0.04 vs 0.01)

Blood chemistry findings

• No significant clinical differences between ADAKVEO vs placebo in LDH (LSM: 8.2; -25.4 vs -33.5) or indirect bilirubin (LSM: -3.0; -2.3 vs 0.7)

Laboratory Test Interference (Platelet Counts)

Lab interference with automated platelet counts (platelet clumping) has been observed following administration of ADAKVEO when blood samples were collected in tubes containing ethylenediaminetetraacetic acid (EDTA).

Run test as soon as possible or use citrate tubes.

AR, adverse reaction; IRR, infusion-related reaction; LSM, least squares mean; LDH, lactate dehydrogenase; NSAID, nonsteroidal anti-inflammatory drug; SCD, sickle cell disease.

References: 1. Adakveo [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2021. 2. Brandow AM, Carroll CP, Creary S, et al. American Society of Hematology 2020 guidelines for sickle cell disease: management of acute and chronic pain. Blood Adv. 2020;4(12):2656-2701. 3. Nausea & vomiting. Cleveland Clinic. https://my.clevelandclinic.org/health/symptoms/8106-nausea-vomiting. Accessed September 1, 2020. 4. Flake ZA, Linn BS, Hornecker JR. Practical selection of antiemetics in the ambulatory setting. Am Fam Physician. 2015;91(5):293-296. 5. Joint pain. Mayo Clinic. https://www.mayoclinic.org/symptoms/joint-pain/basics/definition/sym-20050668. Accessed September 1, 2020. 6. Back pain. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/back-pain/symptomscauses/syc-20369906. Accessed September 1, 2020. 7. Yawn BP, John-Sowah J. Management of sickle cell disease: recommendations from the 2014 expert panel report. Am Fam Physician. 2015;92(12):1069-1076A. 8. Ahmed S, Shahid RK, Russo LA. Unusual causes of abdominal pain: sickle cell anemia. Best Pract Res Clin Gastroenterol. 2005;19(2):297-310. 9. Data on file. Study NCT01895361. Novartis Pharmaceuticals Corp; 2016.

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