mab
System organ class
Adverse drug reaction
Frequency
Immune system disorders
Hypersensitivity*
Common
Nervous system disorders
Dizziness
Common
Skin and subcutaneous tissue disorders
Rash maculo-papular
Common
Musculoskeletal and connective tissue disorders
Myalgia
Common
General disorders and administration site conditions
Injection site reactions**
Very common
Investigations
Alanine aminotransferase increased
Common
Aspartate aminotransferase increased
Common
*Hypersensitivity includes: pruritus, discomfort and tingling of tongue.
**Injection site reactions include: pain, erythema, bruising, discomfort, haematoma, haemorrhage, pruritus, swelling, induration, paraesthesia, reaction, warmth, oedema and rash.
Paediatric population
The safety of TAKHZYRO was eva luated in a subgroup of 23 subjects aged 12 to <18 years old. Results of the subgroup analysis were consistent with overall study results for all subjects.
Immunogenicity
Treatment with lanadelumab has been associated with development of treatment emergent anti-drug antibodies (ADA) in 11.9% (10/84) of subjects. All antibody titres were low. The ADA response was transient in 20% (2/10) of ADA positive subjects. 2.4% (2/84) of lanadelumab-treated subjects tested positive for neutralizing antibodies.
The development of ADA including neutralising antibodies against TAKHZYRO did not appear to adversely affect the pharmacokinetic (PK) and pharmacodynamics (PD) profiles or clinical response.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via
United Kingdom
Yellow Card Scheme
Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store
Ireland
HPRA Pharmacovigilance
Earlsfort Terrace
IRL - Dublin 2
Tel: +353 1 6764971
Fax: +353 1 6762517
Website: www.hpra.ie
e-mail: medsafety@hpra.ie
Malta
ADR Reporting
Website: www.medicinesauthority.gov.mt/adrportal
4.9 Overdose
No case of overdose has been reported. There is no available information to identify potential signs and symptoms of overdose. If symptoms should occur, symptomatic treatment is recommended. There is no antidote available.
5. Pharmacological properties
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Other haematological agents, drugs used in hereditary angioedema, ATC code: B06AC05
Mechanism of action
Lanadelumab is a fully human, monoclonal antibody (IgG1/ κ-light chain). Lanadelumab inhibits active plasma kallikrein proteolytic activity. Increased plasma kallikrein activity leads to angioedema attacks in patients with HAE through the proteolysis of high-molecular-weight-kininogen (HMWK) to generate cleaved HMWK (cHMWK) and bradykinin. Lanadelumab provides sustained control of plasma kallikrein activity and thereby limits bradykinin generation in patients with HAE.
Pharmacodynamic effects
Concentration-dependent inhibition of plasma kallikrein, measured as reduction of cHMWK levels, was demonstrated after SC administration of TAKHZYRO 150 mg every 4 weeks, 300 mg every 4 weeks or 300 mg every 2 weeks in subjects with HAE.
The PK-PD relati |
