Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Subcutaneous [preservative free]:
Takhzyro: lanadelumab-flyo 300 mg/2 mL (2 mL) [contains polysorbate 80]
Pharmacology
Mechanism of Action
Human monoclonal antibody (IgG1/κ-light chain) that binds plasma kallikrein and inhibits its proteolytic activity, controlling excess bradykinin generation in patients with hereditary angioedema.
Pharmacokinetics/Pharmacodynamics
Distribution
Vd: 14.1 to 16.6 L
Time to Peak
4.11 to 5.17 days
Half-Life Elimination
14.2 to 15 days
Use: Labeled Indications
Hereditary angioedema, prophylaxis: Prevention of attacks of hereditary angioedema (HAE) in patients ≥12 years of age.
Contraindications
There are no contraindications listed in the manufacturer's labeling.
Dosage and Administration
Dosing: Adult
Hereditary angioedema, prophylaxis: SubQ: Initial: 300 mg every 2 weeks; dosing every 4 weeks may be considered in patients well-controlled (eg, attack free) for >6 months
Dosing: Geriatric
Refer to adult dosing.
Dosing: Pediatric
Hereditary angioedema (HAE), prophylaxis: Children ≥12 years and Adolescents: SubQ: Initial: 300 mg every 2 weeks; may consider administering every 4 weeks in patients who are well controlled (eg, attack free) for >6 months
Administration
SubQ: For SubQ injection into the abdomen, thigh, or upper arm. Allow vial to reach room temperature before injection (15 minutes). Before preparing dose, gently invert vial 3 to 5 times to mix; do not shake. Use an 18-gauge transfer needle to withdraw dose and a 27-gauge, ½-inch needle or other needle suitable for SubQ injection to administer dose. Rotate injection sites; injection site should be ≥2 inches (5 cm) away from any scars or navel. Do not inject in an area that is bruised, swollen, or painful.
Storage
Store at 36°F to 46°F (2°C to 8°C). Do not freeze. Do not shake. Keep the vial in the original carton to protect from light. Administer within 2 hours of preparing the dose; may also store prepared dose at 36ºF to 46ºF (2°C to 8°C) and must use within 8 hours. Discard any unused portion.
Drug Interactions
There are no known significant interactions.
Test Interactions
May increase activated partial thromboplastin time (aPTT) due to an interaction with the aPTT assay.
Adverse Reactions
>10%:
Central nervous system: Headache (33%)
Immunologic: Antibody development (12%)
Local: Injection site reaction (45% to 56%)
Neuromuscular & skeletal: Myalgia (11%)
Respiratory: Upper respiratory tract infection (44%)
1% to 10%:
Central nervous system: Dizziness (4% to 10%)
Dermatologic: Skin rash (10%)
Gastrointestinal: Diarrhea (4%)
Hepatic: Increased serum transaminases (4%), increased serum alanine aminotransferase (2%), increased serum aspartate aminotransferase (2%)
Hypersensitivity: Hypersensitivity (1%)
Warnings/Precautions
Concerns related to adverse effects:
- Hypersensitivity reactions: Have occurred. In case of a severe hypersensitivity reaction, discontinue therapy and institute appropriate treatment.
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.
Pregnancy
Pregnancy Considerations
Adverse events were not observed in animal reproduction studies. Lanadelumab is a humanized monoclonal antibody (IgG1). Potential placental transfer of human IgG is dependent upon the IgG subclass and gestational age, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis (Palmeira 2012; Pentsuk 2009).
Other agents are currently recommended for prophylaxis of hereditary angioedema (HAE) during pregnancy. Women with HAE should be monitored closely during pregnancy and for at least 72 hours after delivery (WAO/EEACI [Maurer 2018]).
Patient Education
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience common cold symptoms, headache, muscle pain, or diarrhea. Have patient report immediately to prescriber severe injection site irritation, fast heartbeat, severe dizziness, or passing out (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
