Crizanlizumab
FDA Drug Information • Also known as: Adakveo
- Brand Names
- Adakveo
- Drug Class
- Selectin Blocker [EPC]
- Route
- INTRAVENOUS
- Dosage Form
- INJECTION
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
11 DESCRIPTION Crizanlizumab-tmca is a P-selectin blocker humanized IgG2 kappa monoclonal antibody that binds to P-selectin. Crizanlizumab-tmca is produced using recombinant DNA technology in Chinese hamster ovary (CHO) cells. It is composed of 2 heavy chains, each containing 448 amino acids, and 2 light chains each containing 218 amino acids, with a theoretical molecular weight of approximately 146 kDa. ADAKVEO (crizanlizumab-tmca) injection is supplied as a sterile, preservative-free, clear to opalescent, colorless to slightly brownish-yellow solution for dilution and subsequent administration by intravenous infusion. Each 10 mL vial contains 100 mg crizanlizumab-tmca, citric acid (5.4 mg), polysorbate 80 (2 mg), sodium citrate (50.5 mg), sucrose (753.3 mg), and water for injection with a pH of 6.
What Is Crizanlizumab Used For?
1 INDICATIONS AND USAGE ADAKVEO ® 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. ADAKVEO is a selectin blocker indicated to reduce the frequency of vasoocclusive crises in adults and pediatric patients aged 16 years and older with sickle cell disease.
Dosage and Administration
2 DOSAGE AND ADMINISTRATION Administer 5 mg/kg by intravenous infusion over a period of 30 minutes on Week 0, Week 2, and every 4 weeks thereafter. ( 2.1 ) See Full Prescribing Information for instructions on preparation and administration. ( 2.2 ) 2.1 Recommended Dosage Administer ADAKVEO 5 mg/kg by intravenous infusion over a period of 30 minutes at Week 0, Week 2, and every 4 weeks thereafter. If a dose is missed, administer ADAKVEO as soon as possible. If ADAKVEO is administered within 2 weeks after the missed dose, continue dosing according to the patient's original schedule. If ADAKVEO is administered more than 2 weeks after the missed dose, continue dosing every 4 weeks thereafter. Physicians should reevaluate the treatment at least yearly, to assess individual patient’s response to treatment and consider discontinuing therapy with ADAKVEO if no perceived benefit is achieved. ADAKVEO may be given with or without hydroxyurea. 2.2 Preparation and Administration ADAKVEO should be prepared and administered by a healthcare professional. Preparation Use aseptic technique to prepare the solution for infusion. Calculate the dose (mg) and the total volume (mL) of ADAKVEO solution required, and the number of ADAKVEO vials needed based on the patient’s actual body weight. Prepare 5 mg of ADAKVEO per kg of actual body weight. Calculate the volume of ADAKVEO to be used according to the following equation: Dilution Dilute ADAKVEO in 0.9% Sodium Chloride Injection or 5% Dextrose Injection to a total volume of 100 mL for intravenous infusion as follows: Obtain the number of vials required. One vial is needed for every 10 mL of ADAKVEO. Bring vials to room temperature for a maximum of 4 hours prior to the start of preparation (piercing the first vial). Visually inspect the vials. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. ADAKVEO is clear to opalescent, colorless or may have a slightly brownish-yellow tint. Do not use if particles are present in the solution. Obtain a 100 mL 0.9% Sodium Chloride Injection or 5% Dextrose Injection infusion bag/container. Infusion bags/containers must be made of either polyvinyl chloride (PVC), polyethylene (PE), or polypropylene (PP). Remove a volume of 0.9% Sodium Chloride Injection or 5% Dextrose Injection from the infusion bag/container that is equal to the required volume of ADAKVEO solution. Withdraw the necessary amount of ADAKVEO solution and dilute by adding to the infusion bag/container containing 0.9% Sodium Chloride Injection or 5% Dextrose Injection. The volume of ADAKVEO added to the infusion bag/container should not exceed 96 mL. Gently invert the infusion bag to mix the diluted solution. DO NOT SHAKE. Single-dose vials. Discard unused portion. Storage Conditions of the Diluted Solution Administer ADAKVEO diluted solution as soon as possible. If not administered immediately, store the prepared...
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Infusion-related reactions [see Warnings and Precautions (5.1)] The most common adverse reactions (incidence ≥ 10%) were headache, arthralgia, nausea, back pain, fatigue, abdominal pain, pyrexia, diarrhea, vomiting, and oropharyngeal pain. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Novartis Pharmaceuticals Corporation at 1-888-669-6682 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 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 SUSTAIN Trial The safety of ADAKVEO was evaluated in the SUSTAIN trial [see Clinical Studies (14.1)] . Eligible patients were diagnosed with sickle cell disease (any genotype, including HbSS, HbSC, HbS beta 0 -thalassemia, HbS beta + -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 arthralgia, nausea, back pain, abdominal pain, pyrexia, and diarrhea. Table 1 summarizes the adverse reactions in the SUSTAIN trial. Table 1: Adverse Reactions (≥ 10%) in Patients Receiving ADAKVEO With a Difference Between Arms of > 3% Compared to Placebo in SUSTAIN a Abdominal pain: abdominal pain, upper abdominal pain, lower abdominal pain, and abdominal tenderness. ADAKVEO 5 mg/kg N = 66 % Placebo N = 62 % Adverse Reactions All Grades % Grade ≥ 3 % All Grades % Grade ≥ 3 % Arthralgia 18 2 8 2 Nausea 18 0 11 2 Back pain 15 0 11 0 Abdominal pain a 12 0 5 0 Pyrexia 11 12 7 0 Diarrhea 11 0 3 2 Clinically relevant adverse reactions (all Grades) that were reported in less than 10% of patients treated with ADAKVEO included: oropharyngeal pain, 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. STAND Trial The safety of ADAKVEO was also evaluated in the STAND trial [see Clinical Studies (14.1)] . Eligible patients were diagnosed with sickle cell disease (any genotype, including HbSS, HbSC, HbS beta 0 -thalassemia, HbS beta + -thalassemia, and others). Patients received ADAKVEO 5 mg/kg (N = 84) or 7.5 mg/kg (N = 83) or placebo (N = 85) 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 84 patients that received the recommended dose (5 mg/kg), 93% were exposed for approximately 6 months or longer and 88% were exposed for approximately one year; sixty-two (74%) patients were treated with ADAKVEO in combination with hydroxyurea. Serious adverse reactions were reported in 2 patients (2%) treated with ADAKVEO 5 mg/kg and this reaction was pain. The most common adverse reactions (≥ 10%) were headache, nausea, fatigue, vomiting, and oropharyngeal pain. Table 2: Adverse Reactions (≥ 10%) in Patients Receiving ADAKVEO With a Difference Between Arms of > 3%...
Drug Interactions
7 DRUG INTERACTIONS 7.1 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.
Contraindications
4 CONTRAINDICATIONS None. None.
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary Based on data from animal studies, ADAKVEO has the potential to cause fetal harm when administered to a pregnant woman. In an animal reproduction study, intravenous administration of crizanlizumab-tmca to pregnant cynomolgus monkeys from the onset of organogenesis through delivery resulted in a non-dose related increased fetal loss (abortions/stillbirths) at doses approximately 2.8 times the exposure at the recommended clinical dose at 5 mg/kg/dose once every 4 weeks (see Data) . There are insufficient human data on ADAKVEO use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. 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. The estimated background risk of major birth defects and miscarriage for the indicated population is approximately 14% and up to 43%, respectively. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Women with sickle cell disease have an increased risk of adverse pregnancy outcomes for the mother and the fetus. Pregnant women are at greater risk for VOCs, pre-eclampsia, eclampsia, and maternal mortality. For the fetus, there is an increased risk for intrauterine growth restriction, preterm delivery, low birth weight, and perinatal mortality. Data Animal Data In an enhanced pre- and postnatal development study in cynomolgus monkeys, pregnant animals received intravenous doses of crizanlizumab-tmca at 10 and 50 mg/kg once every 2 weeks during the period of onset of organogenesis through delivery. No maternal toxicity was observed. Maternal exposures at doses of 10 and 50 mg/kg were between 2.8 and 16 times, respectively, the human clinical exposure based on area under the curve (AUC) in...
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied ADAKVEO (crizanlizumab-tmca) injection is a sterile, clear to opalescent, colorless to slightly brownish-yellow solution for intravenous infusion supplied as: Carton containing one 100 mg/10 mL (10 mg/mL) single-dose vial NDC 0078-0883-61 The single-dose vial has a rubber stopper and an aluminum cap with a plastic flip-off disk. Each 10 mL vial is made of Type 1 glass. Storage and Handling Store and transport refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Do not shake. Do not freeze.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.