Adakveo

What Is Adakveo?

Adakveo (crizanlizumab-tmca) is a selectin blocker used to reduce the frequency of vasoocclusive crises in adults and pediatric patients aged 16 years and older with sickle cell disease.

What Are Side Effects of Adakveo?

Common side effects of Adakveo include:

• nausea,
• joint pain,
• back pain, and
• fever

Dosage for Adakveo

The dose of Adakveo is 5 mg/kg administered by intravenous infusion over a period of 30 minutes on Week 0, Week 2, and every 4 weeks thereafter.

Adakveo In Children

The safety and effectiveness of Adakveo for sickle cell disease have been established in pediatric patients aged 16 years and older. The safety and efficacy of Adakveo in pediatric patients below the age of 16 years have not been established.

What Drugs, Substances, or Supplements Interact with Adakveo?

Adakveo may interact with other medicines.

Tell your doctor all medications and supplements you use.

Adakveo During Pregnancy and Breastfeeding

Tell your doctor if you are pregnant or plan to become pregnant before using Adakveo; it may harm a fetus. Women with sickle cell disease have an increased risk of adverse pregnancy outcomes for the mother and the fetus. It is unknown if Adakveo passes into breast milk. Consult your doctor before breastfeeding.

Additional Information

Our Adakveo (crizanlizumab-tmca) Injection, for Intravenous Use Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

 

Adakveo Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Some side effects may occur within 24 hours after you receive this medicine. Call your doctor if you feel dizzy, nauseated, tired, itchy, chilled, sweaty, or have a fever, wheezing, or shortness of breath.

Common side effects may include:

• nausea;
• fever;
• joint pain; or
• back pain.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Adakveo (Crizanlizumab-tmca Injection)

 

Adakveo Professional Information

SIDE EFFECTS

The following clinically significant adverse reactions are described elsewhere in the labeling:

• Infusion-related reactions [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Sickle Cell Disease

The safety of ADAKVEO was evaluated in the SUSTAIN trial [see Clinical Studies]. Eligible patients were diagnosed with sickle cell disease (any genotype, including HbSS, HbSC, HbS beta⁰-thalassemia, HbSbeta⁺-thalassemia, and others). Patients received ADAKVEO 5 mg/kg (N = 66) or 2.5 mg/kg (N = 64) or placebo (N = 62) administered by intravenous infusion on Week 0, Week 2, and every 4 weeks thereafter. The safety evaluation below is limited to the patients who received the recommended dose of 5 mg/kg.

Among the 66 patients that received the recommended dose (5 mg/kg), 83% were exposed for 6 months or longer and 61% were exposed for approximately one year; forty-two (64%) patients were treated with ADAKVEO in combination with hydroxyurea.

Serious adverse reactions 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.

The most common adverse reactions (≥ 10%) were nausea, arthralgia, back pain, abdominal pain, and pyrexia. These adverse reactions, along with myalgia, musculoskeletal chest pain, and diarrhea may be signs and symptoms of an infusion-related reaction when observed during/within 24 hours of an infusion [see WARNINGS AND PRECAUTIONS].

Table 2 summarizes the adverse reactions in the SUSTAIN trial.

Table 2: Adverse Reactions (≥ 10%) in Patients Receiving ADAKVEO With a Difference Between Arms of > 3% Compared to Placebo in SUSTAIN

Adverse Reactions	ADAKVEO 5 mg/kg N = 66 n (%)		Placebo N = 62 n (%)
	All Grades (%)	Grade ≥ 3 (%)	All Grades (%)	Grade ≥ 3 (%)
Gastrointestinal Disorders
Nausea	12 (18)	0	7 (11)	1 (2)
Abdominal paina	8 (12)	0	3 (5)	0
Musculoskeletal and Connective Tissue Disorders
Arthralgia	12 (18)	1 (2)	5 (8)	1 (2)
Back pain	10 (15)	0	7 (11)	0
General Disorders and Administration Site Conditions
Pyrexia	7 (11)	1 (2)	4 (7)	0
aAbdominal pain: abdominal pain, upper abdominal pain, lower abdominal pain, and abdominal tenderness.

Clinically relevant adverse reactions (all Grades) that were reported in less than 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.

Immunogenicity

As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies in the studies described below with the incidence of antibodies in other studies or to other crizanlizumab products may be misleading.

The immunogenicity of ADAKVEO was evaluated using a validated bridging immunoassay for the detection of binding anti-crizanlizumab-tmca antibodies. In a single arm, open label multiple dose study, 0 of the 45 patients with sickle cell disease treated with ADAKVEO 5 mg/kg tested positive for treatment-induced anti-crizanlizumab-tmca antibodies. In a single-dose study of healthy subjects, 1 of the 61 (1.6%) evaluable subjects tested positive for a treatment-induced anticrizanlizumab-tmca antibodies.

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of ADAKVEO. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

General Disorders and Administration-site Conditions: Pain (in various locations) occurring during/within 24 hours of the infusion (e.g., potential infusion-related reaction) [see WARNINGS AND PRECAUTIONS].

DRUG INTERACTIONS

Laboratory Test Interference

Platelet Tests

ADAKVEO interferes with automated platelet counts (platelet clumping) in particular when blood samples are collected in tubes containing EDTA, which may lead to unevaluable or falsely decreased platelet counts. 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.

Read the entire FDA prescribing information for Adakveo (Crizanlizumab-tmca Injection)