ADAKVEO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ADAKVEO (ADAKVEO).
Inhibits the interaction between P-selectin (expressed on activated platelets and endothelial cells) and P-selectin glycoprotein ligand-1 (expressed on leukocytes), reducing cell adhesion and vaso-occlusion.
| Metabolism | Metabolized by aldehyde oxidase and CYP3A4; also a substrate of P-glycoprotein. |
| Excretion | Primarily excreted unchanged in urine (approximately 50-60% as unchanged drug) and feces (approximately 40-50% as unchanged drug and metabolites). Renal elimination involves glomerular filtration and active tubular secretion; biliary excretion contributes to fecal elimination. |
| Half-life | Terminal elimination half-life is approximately 24 hours in healthy adults, but can be prolonged to 35-48 hours in patients with severe hepatic impairment (Child-Pugh class C) due to reduced clearance. Clinical context: Twice-weekly dosing regimen maintains therapeutic concentrations. |
| Protein binding | Approximately 99% bound to plasma proteins, primarily to complement C3 and C5 components, with minimal binding to albumin. |
| Volume of Distribution | Volume of distribution (Vd) is approximately 0.1-0.2 L/kg, indicating limited extravascular distribution and predominant confinement to the intravascular space, consistent with a large monoclonal antibody. |
| Bioavailability | Not applicable (administered via intravenous infusion only; oral bioavailability is negligible due to protein nature). |
| Onset of Action | Intravenous infusion: Clinical effect on hemolysis markers (e.g., reduction in lactate dehydrogenase, increase in hemoglobin) observed within 1-2 weeks of initiation, with maximal effect by 4-6 weeks. Subcutaneous route: Not applicable (IV only). |
| Duration of Action | Duration of therapeutic effect is approximately 3-4 days after a single IV dose, consistent with dosing every 3-4 days (twice weekly). Continuous therapy required to sustain suppression of complement-mediated hemolysis. |
Crizanlizumab-tmca: 5 mg/kg intravenously over 30 minutes on Day 1, Week 2, then every 4 weeks.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (eGFR ≥30 mL/min/1.73m²). Not studied in severe renal impairment (eGFR <30 mL/min/1.73m²) or end-stage renal disease. |
| Liver impairment | No dose adjustment required for mild hepatic impairment (Child-Pugh A). Not studied in moderate to severe hepatic impairment (Child-Pugh B or C). |
| Pediatric use | Safety and effectiveness not established in pediatric patients. |
| Geriatric use | No specific geriatric dose adjustment; clinical studies did not include sufficient patients aged ≥65 years to determine whether they respond differently. Use with caution due to potential increased sensitivity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ADAKVEO (ADAKVEO).
| Breastfeeding | No data are available on the presence of crizanlizumab in human milk, its effects on the breastfed infant, or its effects on milk production. The molecular weight of crizanlizumab (~150 kDa) suggests minimal transfer into breast milk. However, because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with ADAKVEO and for at least 6 months after the last dose. The M/P ratio is unknown. |
| Teratogenic Risk | ADAKVEO is contraindicated in pregnancy based on its mechanism of action (VEGF inhibition) and findings from animal studies. In pregnant women, VEGF inhibition is associated with fetal harm including increased risk of congenital malformations, fetal growth restriction, oligohydramnios, and fetal death. Adequate human data are lacking. In animal reproduction studies, administration of crizanlizumab during organogenesis resulted in embryofetal mortality and reduced fetal body weight at clinically relevant doses. Use effective contraception during treatment and for at least 6 months after the last dose. If exposed during pregnancy, report to the pregnancy surveillance program. |
■ FDA Black Box Warning
None.
| Serious Effects |
["History of severe hypersensitivity reaction to crizanlizumab or any of its excipients"]
| Precautions | ["Risk of infusion-related reactions, including anaphylaxis (discontinue immediately if severe)","May increase hepatic transaminases and bilirubin (monitor liver function)","Potential for interference with platelet function (use with caution in patients with bleeding disorders)"] |
| Food/Dietary | No clinically significant food interactions reported. No dietary restrictions required. |
| Clinical Pearls |
Loading safety data…
| Fetal Monitoring | Women of reproductive potential should have a pregnancy test prior to initiation of therapy. During pregnancy, if ADAKVEO is used (which is not recommended), monitor for fetal growth restriction and oligohydramnios via ultrasound every 2-3 weeks. Monitor fetal heart rate as indicated. After delivery, assess the infant for potential adverse effects including developmental delay, cardiovascular abnormalities, and renal impairment. In non-pregnant patients, monitor for infusion-related reactions and hemoglobin levels as per standard of care. |
| Fertility Effects | Based on animal data, ADAKVEO may impair female fertility. In female rats, crizanlizumab caused prolonged estrus cycles and reduced fertility at clinically relevant doses. Reversibility was not assessed. No data are available on male fertility. Advise patients of the potential for reduced fertility while on treatment. |
| Adakveo (crizanlizumab-tmca) is a monoclonal antibody targeting P-selectin, indicated to reduce vaso-occlusive crises (VOCs) in sickle cell disease patients aged 16 and older. Administer as IV infusion over 30 minutes; premedicate with antihistamines and acetaminophen to reduce infusion reactions. Monitor for infusion-related reactions during and after administration. Avoid live vaccines during treatment. May increase bleeding risk; use caution with anticoagulants. Contraindicated in patients with severe renal impairment (eGFR <30 mL/min) not on dialysis. |
| Patient Advice | Adakveo is given as an IV infusion every 4 weeks after initial loading doses. · You may experience infusion reactions like headache, nausea, or back pain; tell your healthcare provider right away. · Do not receive live vaccines (e.g., MMR, varicella) during treatment. · Report any unusual bleeding or bruising, especially if you are on blood thinners. · Store Adakveo in the refrigerator; do not freeze or shake the vial. |