TAKHZYRO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TAKHZYRO (TAKHZYRO).
Lanadelumab is a fully human monoclonal antibody that binds to and inhibits the activity of plasma kallikrein, thereby preventing the cleavage of high-molecular-weight kininogen (HMWK) to bradykinin. This reduces bradykinin-mediated angioedema formation in hereditary angioedema (HAE).
| Metabolism | Lanadelumab is degraded into small peptides and amino acids via general protein catabolic pathways; no specific metabolic enzymes are involved. |
| Excretion | Primarily eliminated via proteolytic degradation; renal excretion of intact drug is negligible. <1% excreted unchanged in urine. |
| Half-life | Terminal half-life is approximately 11-19 days (mean ~14 days) in patients with hereditary angioedema, supporting every-4-week dosing. |
| Protein binding | High, approximately 97-99% bound to plasma proteins, primarily to albumin. |
| Volume of Distribution | Approximately 6-10 L (0.08-0.14 L/kg based on 70 kg), indicating limited extravascular distribution consistent with a monoclonal antibody. |
| Bioavailability | Subcutaneous: Approximately 62% (range 50-80%) after SC injection into the abdomen, thigh, or arm. |
| Onset of Action | Subcutaneous: Median time to first attack reduction is approximately 2 weeks (range 1-3 weeks) after initial dose. |
| Duration of Action | Duration of effect lasts for the dosing interval (4 weeks) with sustained attack rate reduction over long-term treatment. Attack reduction persists for at least 70 days after last dose due to long half-life. |
300 mg subcutaneously every 2 weeks
| Dosage form | SOLUTION |
| Renal impairment | No dose adjustment required for renal impairment. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Not studied in severe hepatic impairment (Child-Pugh C). |
| Pediatric use | Not approved for pediatric use; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment; clinical studies included limited patients aged 65 and older, but no overall differences in safety or efficacy observed. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TAKHZYRO (TAKHZYRO).
| Breastfeeding | No data on presence in human milk, effects on breastfed infant, or milk production. Lanadelumab is a large protein molecule; expected to be present in very low levels in breast milk. M/P ratio unknown. |
| Teratogenic Risk | TAKHZYRO (lanadelumab) is a monoclonal antibody. Immunoglobulin G (IgG) is known to cross the placental barrier. No adequate human data exist; animal studies showed no adverse developmental effects. Theoretical risk of fetal monoclonal antibody exposure during second and third trimesters cannot be excluded. |
■ FDA Black Box Warning
None
| Serious Effects |
["Known hypersensitivity to lanadelumab or any of its excipients"]
| Precautions | ["Hypersensitivity reactions including anaphylaxis have been reported; discontinue if severe hypersensitivity occurs.","Monitor for signs and symptoms of hypersensitivity reactions and initiate appropriate treatment.","Increased risk of thrombotic events (based on animal studies) - use with caution in patients with known cardiovascular risk factors.","May cause fetal harm based on animal reproduction studies; advise females of reproductive potential to use effective contraception."] |
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| Fetal Monitoring |
| Standard prenatal monitoring; no specific additional monitoring required. Monitor for maternal adverse effects per standard prescribing information. |
| Fertility Effects | No human data on fertility. Animal studies (monkeys) showed no impairment of male or female fertility at doses up to 30 mg/kg. |