CABLIVI
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CABLIVI (CABLIVI).
CABLIVI (caplacizumab-yhdp) is a humanized, bivalent, variable-domain immunoglobulin fragment (Nanobody) that binds to the A1 domain of von Willebrand factor (vWF), inhibiting the interaction between vWF and platelets. This prevents platelet adhesion and aggregation, reducing microthrombi formation in acquired thrombotic thrombocytopenic purpura (aTTP).
| Metabolism | Caplacizumab is a monoclonal antibody fragment; it is expected to be degraded into small peptides and amino acids via catabolic pathways. No specific metabolic enzymes are involved. |
| Excretion | Primarily metabolized by proteolytic cleavage into endogenous amino acids; renal excretion of capiacimab (parent drug) is negligible (<1%) as it is a recombinant fusion protein; no biliary or fecal elimination data in humans. |
| Half-life | Terminal elimination half-life is approximately 3.5 days (84 hours) based on clinical studies in patients with acquired thrombotic thrombocytopenic purpura (aTTP), supporting weekly dosing. |
| Protein binding | Approximately 96% bound to plasma proteins, primarily to VWF and albumin. |
| Volume of Distribution | Central volume of distribution (Vc) is approximately 3.7 L, which does not scale to body weight; peripheral Vd not reported; clinical meaning: predominantly confined to intravascular space due to high protein binding. |
| Bioavailability | Subcutaneous: Approximately 89% (absolute bioavailability) based on a pharmacokinetic study in healthy subjects. |
| Onset of Action | Subcutaneous administration: Median time to normalization of platelet count (≥150 × 10^9/L) is 3 days (range 2–5 days). |
| Duration of Action | Duration of effect on von Willebrand factor (VWF) activity suppression lasts approximately 1 week, consistent with dosing interval; platelet count improvement is maintained with weekly administration. |
11 mg subcutaneously once daily for 30 days, then 11 mg subcutaneously once every 2 weeks starting on day 31.
| 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 dialysis. |
| 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 in pediatric patients have not been established. |
| Geriatric use | No specific dose adjustment required; clinical studies included patients aged 65 years and older, but no overall differences in safety or efficacy were observed. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for CABLIVI (CABLIVI).
| Breastfeeding | No data on presence in human milk, effects on breastfed infant, or milk production. M/P ratio unknown. Caution recommended; consider developmental and health benefits of breastfeeding along with maternal need for drug and potential infant adverse effects. |
| Teratogenic Risk | No adequate human data; based on animal studies, cablivi (caplacizumab) is not expected to increase the risk of major birth defects or miscarriages. However, maternal aTTP itself carries risks. Insufficient data for first, second, and third trimester-specific effects. |
■ FDA Black Box Warning
No FDA boxed warning.
| Serious Effects |
["History of severe hypersensitivity to caplacizumab or any component of the formulation"]
| Precautions | ["Bleeding risk: May cause serious or fatal bleeding; monitor for signs of bleeding","Coagulation abnormalities: Discontinue prior to surgery or invasive procedures if possible","Thrombotic events: Risk of recurrence of aTTP after treatment discontinuation","Immunogenicity: Hypersensitivity reactions including anaphylaxis"] |
| Food/Dietary | No clinically significant food interactions identified. No dietary restrictions required. |
| Clinical Pearls |
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| Fetal Monitoring |
| Monitor for bleeding complications (e.g., epistaxis, gingival bleeding) due to anti-von Willebrand factor effect. Monitor platelet count and aTTP disease activity (ADAMTS13 activity, schistocytes, LDH). Fetal monitoring per standard obstetric care for aTTP. |
| Fertility Effects | No human data on fertility impairment. In animal studies, no adverse effects on male or female fertility observed at exposures up to 5 times the human clinical exposure. |
| Monitor for bleeding; avoid use in patients with known severe hypersensitivity to caplacizumab or excipients. Administer as a starting intravenous bolus prior to plasma exchange, followed by subcutaneous injections. Discontinue if severe bleeding occurs. Can cause thrombocytopenia in addition to aPTT prolongation. |
| Patient Advice | Report any unusual bleeding or bruising immediately. · You may need to stop taking blood thinners or other medications that increase bleeding risk. · Injections are to be given subcutaneously after initial IV dose; rotate injection sites. · Do not drive if you feel dizzy or faint after injection. · Keep regular appointments for plasma exchange and lab monitoring. · Inform all healthcare providers that you are taking CABLIVI. |