ed treatment should be initiated with an approved rescue medication.
There are no available clinical data on the use of lanadelumab in HAE patients with normal C1-INH activity.
Interference with coagulation test
Lanadelumab can increase activated partial thromboplastin time (aPTT) due to an interaction of lanadelumab with the aPTT assay. The reagents used in the aPTT laboratory test initiate intrinsic coagulation through the activation of plasma kallikrein in the contact system. Inhibition of plasma kallikrein by lanadelumab can increase aPTT in this assay. None of the increases in aPTT in patients treated with TAKHZYRO were associated with abnormal bleeding adverse events. There were no differences in international normalised ratio (INR) between treatment groups.
Sodium content
This medicinal product contains less than 1 mmol sodium (23 mg) per vial, that is to say essentially 'sodium-free'.
4.5 Interaction with other medicinal products and other forms of interaction
No dedicated drug-drug interaction studies have been conducted. Based on the characteristics of lanadelumab, no pharmacokinetic interactions with co-administered medicinal products is expected.
As expected, concomitant use of the rescue medication C1 esterase inhibitor results in an additive effect on lanadelumab-cHMWK response based on the mechanism of action (MOA) of lanadelumab and C1 esterase inhibitor (see section 5.1).
4.6 Fertility, pregnancy and lactation
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 eva luated in humans. Lanadelumab had no effect on male or female fertility in cynomolgus monkeys (see section 5.3).
4.7 Effects on ability to drive and use machines
TAKHZYRO has negligible influence on the ability to drive or use machines.
4.8 Undesirable effects
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 1 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 1 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 1: Adverse reactions reported with lanadelu |
