Version May 2024
Sickle cell disease (to reduce frequency of vaso-occlusive crises):
IV: Initial: 5 mg/kg once every 2 weeks for 2 doses (at week 0 and week 2), followed by 5 mg/kg once every 4 weeks thereafter; crizanlizumab may be administered with or without hydroxyurea (Ref).
Missed dose: If a dose is missed, administer crizanlizumab as soon as possible; if administered within 2 weeks after the missed dose, continue dosing according to the original schedule. If administered >2 weeks after the missed dose, continue dosing every 4 weeks thereafter.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Infusion-related reactions:
Mild to moderate: Temporarily interrupt or slow rate of crizanlizumab infusion and manage as clinically necessary. Consider premedication(s) and/or reduced infusion rate with subsequent infusions.
Severe: Discontinue crizanlizumab and manage as clinically necessary. Consider permanent discontinuation of crizanlizumab.
Refer to adult dosing.
(For additional information see "Crizanlizumab: Pediatric drug information")
Sickle cell disease, to reduce frequency of vaso-occlusive crises: Note: May be given with or without hydroxyurea.
Adolescents ≥16 years: IV: 5 mg/kg on week 0, week 2, then every 4 weeks.
Missed dose: Administer missed dose as soon possible.
If dose administered within 2 weeks of missed dose, continue original schedule.
If dose administered more than 2 weeks after missed dose, administer dose every 4 weeks thereafter.
Dosage adjustment for toxicity:
Adolescents ≥16 years:
Infusion-related reactions:
Mild to moderate: Temporarily interrupt or slow rate of crizanlizumab infusion and manage as clinically necessary. Consider premedication(s) and/or reduced infusion rate with subsequent infusions.
Severe: Discontinue crizanlizumab infusion and manage as clinically necessary. Consider permanent discontinuation of crizanlizumab.
There are no dosage adjustments provided in the manufacturer's labeling; has not been studied.
There are no dosage adjustments provided in the manufacturer's labeling; has not been studied.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Gastrointestinal: Abdominal pain (12%), nausea (18%)
Neuromuscular & skeletal: Arthralgia (18%), back pain (15%)
Miscellaneous: Fever (11%)
1% to 10%:
Dermatologic: Pruritus (<10%)
Gastrointestinal: Diarrhea (<10%), vomiting (<10%)
Genitourinary: Vulvovaginal pruritus (<10%)
Immunologic: Antibody development (2%)
Local: Infusion site reaction (infusion site pain and swelling at the injection site: <10%)
Neuromuscular & skeletal: Musculoskeletal chest pain (<10%), myalgia (<10%)
Respiratory: Oropharyngeal pain (<10%)
Miscellaneous: Infusion related reaction (including pain [occurring within 24 hours of infusion]: 3%)
There are no contraindications listed in the manufacturer's labeling.
Concerns related to adverse effects:
• Infusion-related reactions: Infusion-related reactions (occurring during/within 24 hours of infusion), sometimes requiring hospitalization, have been reported. Most reactions occurred with first and second infusions. Symptoms may include pain in various areas, headache, fever, chills, nausea, vomiting, diarrhea, fatigue, dizziness, pruritus, urticaria, sweating, dyspnea, or wheezing. Interrupt or slow the infusion rate for mild or moderate infusion reactions (consider premedications with subsequent infusions). Discontinue crizanlizumab for severe reactions and manage as clinically necessary. Use caution when using corticosteroids if necessary for management of patients with sickle cell disease.
Dosage form specific issues:
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.
Other warnings/precautions:
• Laboratory test interference: Crizanlizumab may interfere with automated platelet counts (platelet clumping), particularly when blood samples are collected in tubes containing ethylenediaminetetraacetic acid (EDTA); platelet count may be unevaluable or falsely decreased. Collect blood samples in citrate-containing tubes, and run samples within 4 hours of sample collection.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous [preservative free]:
Adakveo: crizanlizumab-tmca 100 mg/10 mL (10 mL) [contains polysorbate 80]
No
Solution (Adakveo Intravenous)
100 mg/10 mL (per mL): $294.35
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
IV: Infuse over 30 minutes through a sterile, nonpyrogenic 0.2-micron inline filter. After infusion is complete, flush the line with ≥25 mL of NS or D5W. Do not mix or administer with other medications. Infusion must be completed within 4.5 hours of preparation (if stored at room temperature) or 24 hours (if refrigerated). For mild to moderate infusion-related reactions, temporarily interrupt or slow infusion rate (and manage symptomatically). Discontinue crizanlizumab for severe infusion-related reactions and manage as clinically necessary.
Incompatibilities have not been observed between crizanlizumab and infusion sets made of polyvinyl chloride, polyethylene, or polyurethane, or with inline membrane filters composed of polyethersulfone (neutral and positively charged), positively charged polyamide, and polysulphone.
IV: Administer by IV infusion over 30 minutes using a sterile, nonpyrogenic 0.2-micron inline filter; after infusion is complete, flush line with at least 25 mL of D5W or NS. Discontinue crizanlizumab for severe infusion-related reactions and manage as clinically necessary.
Sickle cell disease: To reduce the frequency of vaso-occlusive crises in adults and pediatric patients ≥16 years of age with sickle cell disease.
Crizanlizumab may be confused with benralizumab, caplacizumab, crizotinib, eculizumab, emicizumab, ravulizumab.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
Exagamglogene Autotemcel: Crizanlizumab may diminish the therapeutic effect of Exagamglogene Autotemcel. Risk X: Avoid combination
Lovotibeglogene Autotemcel: Crizanlizumab may diminish the therapeutic effect of Lovotibeglogene Autotemcel. Risk X: Avoid combination
Rozanolixizumab: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
Based on data from animal reproduction studies, in utero exposure to crizanlizumab may cause fetal harm.
Crizanlizumab is a humanized monoclonal antibody (IgG2). Placental transfer of human IgG is dependent upon the IgG subclass, maternal serum concentrations, birth weight, and gestational age, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis (Palmeira 2012; Pentsuk 2009).
Sickle cell disease increases the risk of adverse maternal and fetal outcomes, including an increased risk for vaso-occlusive crises, preeclampsia, eclampsia, intrauterine growth restriction, preterm delivery, low birth weight, and maternal and perinatal mortality.
It is not known if crizanlizumab is present in breast milk.
Crizanlizumab is a humanized monoclonal antibody (IgG2); maternal IgG is present in breast milk. According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.
Monitor for signs/symptoms of infusion-related reactions.
Crizanlizumab is a humanized IgG2 kappa monoclonal antibody which binds to P-selectin and blocks interaction with ligands, including P-selectin glycoprotein ligand 1. Translocation of P-selectin to the activated endothelial cell surface results in adhesion of sickle erythrocytes to vessels and the development of vascular occlusion (Ataga 2017). By binding to P-selectin, crizanlizumab inhibits interactions between endothelial cells, platelets, red blood cells, and leukocytes, which may result in decreased platelet aggregation, maintenance of blood flow, and minimized sickle cell-related pain crises.
Distribution: Vd: 4.26 L.
Metabolism: Expected to be metabolized into small peptides by catabolic pathways.
Half-life elimination: 11.2 days in patients with sickle cell disease; 10.6 days in healthy volunteers.
Excretion: Clearance: 11.7 mL/hour in healthy volunteers.
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
