Infusion-Related Reactions (IRRs)
In the SUSTAIN clinical trial, IRRs (occurring during/within 24 hours of infusion) were observed in 2 (3%) patients treated with ADAKVEO
We’re moving on!
Join us at www.hcp.novartis.com—our new location for health care professionals to find product, access, and medical information. Now you can find the tools you need to help manage your patients, all in one place!
You’ll have access to the site in a moment, or click continue to close this message and advance directly to the site.
Safety
Infusion-Related Reactions (IRRs)
IRRs may happen during/within 24 hours of infusion with ADAKVEO1
- In the SUSTAIN study, IRRs were observed in 2 (3%) patients treated with ADAKVEO 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. The management of pain events included acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, antihistamines, intravenous fluids, and/or oxygen therapy. 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
- Counsel patients about the possibility of an IRR
- No dose reductions are recommended
| No IRR | Complete infusion | |
| Mild to Moderate IRR |
|
|
| Severe IRR |
|
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 complications1,2
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
Adverse Reactions (ARs)
Majority of ARs with ADAKVEO were mild to moderate (grade 1 or 2)1
Adverse Drug Reactions Reported ≥10% of ADAKVEO® (crizanlizumab-tmca) Patients With a Difference Between Arms of >3% Compared With Placebo in SUSTAIN
|
|
|
|||
|
ADAKVEO (5 mg/kg) |
Placebo |
|||
|
Adverse |
All Grades |
Grades ≥3 |
All Grades |
Grades ≥3 |
|
Gastrointestinal disorders |
||||
|
Nausea |
12 (18) |
0 |
7 (11) |
1 (2) |
|
Musculoskeletal disorders and connective tissue disorders |
|
|
|
|
|
Arthralgia |
12 (18) |
1 (2) |
5 (8) |
1 (2) |
|
General disorders and administration site conditions |
|
|
|
|
|
Pyrexia |
7 (11) |
1 (2) |
4 (7) |
0 |
*Abdominal pain: abdominal pain, upper abdominal pain, lower abdominal pain, and abdominal tenderness.
- Patients should be monitored for all possible ARs
- Advise your patients to discuss any ARs with their health care provider
- Serious ARs were reported in 2 patients (3%) treated with ADAKVEO 5 mg/kg; both reactions were pyrexia
- Two deaths (3%) occurred in the ADAKVEO 5 mg/kg treatment group. None of the deaths were considered to be related to ADAKVEO
- Clinically relevant ARs (all grades) that were reported in <10% of patients treated with ADAKVEO® (crizanlizumab-tmca) included: oropharyngeal pain, diarrhea, vomiting, pruritus (pruritus and vulvovaginal pruritus), musculoskeletal chest pain, myalgia, infusion-site reaction (infusion-site extravasation, infusion-site pain, and infusion-site swelling), and infusion-related reaction
Management considerations for the most common ARs1,3-8
Other Safety Measures
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.
LSM, least squares mean; LDH, lactate dehydrogenase; SCD, sickle cell disease.
References: 1. Adakveo [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp. 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.
Indication
ADAKVEO® (crizanlizumab-tmca) is indicated to reduce the frequency of vaso-occlusive crises (VOCs) in adults and pediatric patients, aged 16 years and older, with sickle cell disease.
Important Safety Information
Infusion-Related Reactions (IRRs)
In the SUSTAIN clinical trial, IRRs (occurring during/within 24 hours of infusion) were observed in 2 (3%) patients treated with ADAKVEO 5 mg/kg. 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. The management of pain events included acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, antihistamines, intravenous fluids, and/or oxygen therapy. Some patients have also experienced subsequent complications such as acute chest syndrome and fat embolism, particularly those treated with steroids.
Monitor patients for signs and symptoms of IRRs, which may include pain in various locations, headache, fever, chills, nausea, vomiting, diarrhea, fatigue, dizziness, pruritus, urticaria, sweating, or shortness of breath or wheezing.
For severe IRRs, discontinue infusion, institute appropriate medical care, and consider permanent discontinuation of ADAKVEO. For mild or moderate IRRs, temporarily interrupt or slow the rate of infusion and initiate symptomatic treatment. For subsequent infusions, consider premedication and/or reduce the infusion rate.
Exercise caution with corticosteroids in patients with sickle cell disease unless clinically indicated (eg, treatment of anaphylaxis).
Laboratory Test Interference (Platelet Counts)
Interference with automated platelet counts (platelet clumping) has been observed following administration of ADAKVEO, in particular, when blood samples were collected in tubes containing EDTA.
Run blood samples within 4 hours of blood collection or collect blood samples in tubes containing citrate. When needed, estimate platelet count via peripheral blood smear.
Pregnancy
Based on animal data, ADAKVEO has the potential to cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. ADAKVEO should only be used during pregnancy if the expected benefit to the patient justifies the potential risk to the fetus.
Most Common Adverse Reactions
The most frequently reported adverse reactions (≥10%) in patients treated with ADAKVEO were nausea (18%), arthralgia (18%), back pain (15%), abdominal pain (12%), and pyrexia (11%).
Other Clinically Important Adverse Reactions
Clinically relevant adverse reactions (all grades) that were reported in <10% of patients treated with ADAKVEO included: oropharyngeal pain, diarrhea, vomiting, pruritus (pruritus and vulvovaginal pruritus), musculoskeletal chest pain, myalgia, infusion-site reaction (infusion-site extravasation, infusion-site pain, and infusion-site swelling), and infusion-related reaction.
Please see accompanying full Prescribing Information.
