PLGB 54937/0017/OD1

Hereditary angioedema

TAKHZYRO is indicated for routine prevention of recurrent attacks of hereditary angioedema (HAE) in patients aged 2 years and older.

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Traceability In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. Hypersensitivity reactions Hypersensitivity reactions have been observed. In case of a severe hypersensitivity reaction, administration of TAKHZYRO must be stopped immediately and appropriate treatment must be initiated. General TAKHZYRO is not intended for treatment of acute HAE attacks. In case of a breakthrough HAE attack, individualized treatment should be initiated with an approved rescue medication. There is limited clinical data on the use of lanadelumab in HAE patients with normal C1-INH (see section 5.1). Patients with HAE nC1-INH having mutations that are not associated with the kallikrein-kinin system (KKS) pathway are not expected to respond to TAKHZYRO. It is recommended to perform genetic testing, if available, according to the current HAE guidelines and to discontinue the treatment if clinical response is not observed (see section 4.2 and 5.1). Interference with coagulation test Lanadelumab can increase activated partial thromboplastin time (aPTT) due to an

No dedicated drug-drug

Pregnancy There are no or limited data from the use of lanadelumab in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive or developmental toxicity (see section 5.3). As a precautionary measure, it is preferable to avoid the use of lanadelumab during pregnancy. Breast-feeding It is unknown whether lanadelumab is excreted in human milk. Human IgGs are known to be excreted in breast milk during the first few days after birth, which is decreasing to low concentrations soon afterwards; consequently, a risk to the breast- fed child cannot be excluded during this short period. Afterwards, lanadelumab could be used during breast-feeding if clinically needed. Fertility Lanadelumab’s effect on fertility has not been evaluated in humans. Lanadelumab had no effect on male or female fertility in cynomolgus monkeys (see section 5.3).

TAKHZYRO has no or negligible influence on the ability to drive and use machines.

Summary of the safety profile The most commonly (52.4%) observed adverse reaction associated with TAKHZYRO was injection site reactions (ISR) including injection site pain, injection site erythema and injection site bruising. Of these ISRs, 97% were of mild intensity, 90% resolved within 1 day after onset with a median duration of 6 minutes. Hypersensitivity reaction (mild and moderate pruritus, discomfort and tingling of tongue) was observed (1.2%), see section 4.4. Tabulated list of adverse reactions Table 2 summarises adverse reactions observed in the HELP study that included 84 subjects with HAE, who received at least one dose of TAKHZYRO. The frequency of adverse reactions listed in Table 2 is defined using the following convention: Very common (= 1/10); common (= 1/100 to < 1/10); uncommon (= 1/1 000 to < 1/100); rare (= 1/10 000 to < 1/1 000); very rare (< 1/10 000). Table 2: Adverse reactions reported with lanadelumab 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 Alanine aminotransferase increased Common Investigations 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. Safety data available from the HELP study extension are consistent with the safety data from the HELP study (described in Table 2). Paediatric population The safety of TAKHZYRO 300 mg/2 ml was evaluated in a subgroup of 23 subjects 12 to less than 18 years of age in the HELP and HELP study extension. In the SPRING study, safety of TAKHZYRO was also evaluated at 150 mg/1 ml in 21 subjects 2 to less than 12 years of age (see section 5.1). No subject below the age of 3.5 years was receiving lanadelumab in the study. No new adverse reactions were identified. Safety and tolerability results for paediatric subjects were consistent with overall study results for all subjects. 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 Yellow Card Scheme, Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

No case of has been reported. There is no available information to identify potential signs and symptoms of . If symptoms should occur, symptomatic treatment is recommended. There is no antidote available.

2 years. The injection should be administered within 2 hours of preparing the dosing syringe. If not administered immediately after preparation, the syringe may be stored in the refrigerator (2°C - 8°C), protected from light and administered within 8 hours. Chemical and physical in-use stability has been demonstrated for 2 hours at 25°C and for 8 hours at 2°C to 8°C. From a microbiological point of view, unless the method of preparation precludes the risks of microbial contamination, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user.

Store in a refrigerator (2°C - 8°C). Do not freeze. Keep the solution (vial) in the outer carton in order to protect from light. The solution (vial) may be stored below 25°C for a single period of 14 days, but not beyond the expiry date. Do not return TAKHZYRO to refrigerated storage after storage at room temperature. For storage conditions after first opening of the product in vial, see section 6.3.

2 ml of solution in a vial (type I glass) with a coated butyl rubber stopper and an aluminium seal with violet flip-off cap. TAKHZYRO is available as a single pack containing one 2 ml vial and in multipacks comprising 2 or 6 cartons, each carton containing 1 vial. Each pack also contains the following items: • Empty 3 ml syringe • 18G vial access needle • 27G x 13 mm injection needle

Lanadelumab is provided in single use vials. Before use, TAKHZYRO solution should be visually inspected for appearance. The solution should be clear or slightly yellow. Solutions that are discoloured or contain particles should not be used. Avoid vigorous agitation. Administration steps Using aseptic technique, withdraw the prescribed dose of TAKHZYRO from the vial into the syringe using an 18 gauge needle. Change the needle on the syringe to a 27 gauge needle or other needle suitable for subcutaneous injection. Inject TAKHZYRO subcutaneously into the abdomen, thigh, or upper arm (see section 4.2). Discard the vial with any unused contents.

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