SUMMARY OF PRODUCT CHARACTERISTICS
1.

NAME OF THE MEDICINAL PRODUCTTAKHZYRO2.
QUALITATIVE AND QUANTITATIVE COMPOSITION
One unit (pre-filled syringe) contains 150 mg of lanadelumab* in 1 ml solution.
One unit (pre-filled syringe or vial) contains 300 mg of lanadelumab* in 2 ml solution.
*Lanadelumab is produced in Chinese Hamster Ovary (CHO) cells by recombinant DNA technology.
For the full list of excipients, see section 6.1.

3.

PHARMACEUTICAL FORM

Solution for injection.
The solution is colourless to slightly yellow, appearing either clear or slightly opalescent.
The solution has a pH of approximately 6.0 and an osmolality of approximately 300 mOsm/kg.

4.

CLINICAL PARTICULARS

4.1 Therapeutic indications
TAKHZYRO is indicated for routine prevention of recurrent attacks of hereditary angioedema (HAE)
in patients aged 2 years and older.
4.2

Posology and method of administration

This medicinal product should be initiated under the supervision of a physician experienced in the
management of patients with hereditary angioedema (HAE).
Posology
Adults
The recommended starting dose is 300 mg lanadelumab every 2 weeks. In patients who are stably
attack free on treatment, a dose reduction to 300 mg lanadelumab every 4 weeks may be considered,especially in patients with low weight.
Adolescents 12 to less than 18 years of age
The recommended starting dose is 300 mg lanadelumab every 2 weeks. In patients who are stably
attack free on treatment, a dose reduction to 300 mg lanadelumab every 4 weeks may be considered,especially in patients with low weight.
Children 6 to less than 12 years of age
The recommended starting dose is 150 mg lanadelumab every 2 weeks. In patients who are stably
attack free on treatment, a dose reduction to 150 mg lanadelumab every 4 weeks, may be considered.
Children 2 to less than 6 years of age
The recommended dose is 150 mg lanadelumab every 4 weeks.

1

TAKHZYRO is not intended for treatment of acute HAE attacks (see section 4.4)
Missed doses
If a dose of TAKHZYRO is missed, the patient or caregiver should be instructed to administer thedose as soon as possible. The subsequent dosing schedule may need adjustment according to theintended dosing frequency to ensure•
at least 10 days between doses for patients on every 2 weeks dosing regimen,•
at least 24 days between doses for patients on every 4 weeks dosing regimen.

Special populations
Elderly
Age is not expected to affect exposure to lanadelumab. No dose adjustment is required for patientsabove 65 years of age (see section 5.2).
Hepatic impairment
No studies have been conducted in patients with hepatic impairment. Hepatic impairment is notexpected to affect exposure to lanadelumab. No dose adjustment is required in patients with hepatic
impairment (see section 5.2).
Renal impairment
No studies have been conducted in patients with severe renal impairment. Renal impairment is notexpected to affect exposure to lanadelumab or the safety profile. No dose adjustment is required inpatients with renal impairment. (see section 5.2).
Paediatric population
The safety and efficacy of TAKHZYRO in children aged less than 2 years have not been established.
No data are available.
Method of administration
TAKHZYRO is intended for subcutaneous (SC) administration only.
Each TAKHZYRO unit (pre-filled syringe or vial) is intended for single use only (see section 6.6).
The injection should be restricted to the recommended injection sites: the abdomen, the thighs, and theupper outer arms (see section 5.2). Rotation of the injection site is recommended.
For adults and adolescents (12 to less than 18 years of age), TAKHZYRO may be self-administered oradministered by a caregiver only after training on subcutaneous injection technique by a healthcare
professional.
For children (2 to less than 12 years of age), TAKHZYRO should only be administered by a caregiverafter training on subcutaneous injection technique by a healthcare professional.

4.3

Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
4.4

Special warnings and precautions for use
2

Traceability
In order to improve the traceability of biological medicinal products, the name and the batch numberof 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 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 patientstreated with TAKHZYRO were associated with abnormal bleeding adverse events. There were nodifferences in international normalised ratio (INR) between treatment groups.
Sodium content
This medicinal product contains less than 1 mmol sodium (23 mg) per pre-filled syringe or 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 oflanadelumab, no pharmacokinetic interactions with co-administered medicinal products is expected.
As expected, concomitant use of the rescue medication C1 esterase inhibitor results in an additiveeffect 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 notindicate direct or indirect harmful effects with respect to reproductive or developmental toxicity (seesection 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 soonafterwards; 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.
3

Fertility
Lanadelumab’s effect on fertility has not been evaluated in humans. Lanadelumab had no effect onmale or female fertility in cynomolgus monkeys (see section 5.3).
4.7

Effects on ability to drive and use machines

TAKHZYRO has no or negligible influence on the ability to drive and 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 durationof 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 lanadelumab
System organ class

Adverse drug reaction

Frequency

Immune system disorders

Hypersensitivity*

CommonNervous system disorders

Dizziness

CommonSkin and subcutaneous tissue disorders

Rash maculo-papular

CommonMusculoskeletal and connective tissue
disorders

Myalgia

CommonGeneral disorders and administrationsite conditions

Injection site reactions**

Very common

Alanine aminotransferase increased

CommonAspartate aminotransferase increased

CommonInvestigations*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 1).
4

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, the safety of
TAKHZYRO was also evaluated at 150 mg/1 ml in 21 subjects 2 to less than 12 years of age (seesection 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. Any suspected
adverse events should be reported to the Ministry of Health according to the National Regulation byusing an online form:
https://sideeffects.health.gov.il/
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. Thereis no antidote available.

5.

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

Pharmacotherapeutic group: Other haematological agents, drugs used in hereditary angioedema, ATCcode: 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) togenerate cleaved HMWK (cHMWK) and bradykinin. Lanadelumab provides sustained control ofplasma kallikrein activity and thereby limits bradykinin generation in patients with HAE.
Pharmacodynamic effects
In adult and adolescent (12 to less than 18 years of age) patients, concentration-dependent inhibition ofplasma kallikrein, measured as reduction of cHMWK levels, was demonstrated after subcutaneousadministration 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 relationship between TAKHZYRO and cHMWK is described by an indirect exposureresponse pharmacological model. The cHMWK formation rate was maximally reduced by 53.7% withan IC50 of 5705 ng/ml.
For children aged 2 to less than 6 years (150 mg every 4 weeks) and 6 to less than 12 years (150 mg
every 2 weeks), the observed mean percent change from baseline in cHMWK levels was similar tothat observed in adult and adolescent (12 to less than 18 years of age) patients.
Clinical efficacy and safety
5

HELP study
The HELP study was a multicenter, randomised, double-blind, placebo-controlled parallel-group study
in 125 (115 adults and 10 adolescents) subjects with symptomatic type I or II HAE. Subjects wererandomised into 1 of 4 parallel treatment arms, stratified by baseline attack rate, in a 3:2:2:2 ratio(placebo, lanadelumab 150 mg every 4 weeks, lanadelumab 300 mg every 4 weeks or lanadelumab
300 mg every 2 weeks by subcutaneous injection) for the 26-week treatment period.
The median (range) age of the study population was 42 (12 to 73) years with 88 female subjects(70%). A history of laryngeal angioedema attacks was reported in 65% (81/125) of subjects and
56% (70/125) were on prior long term prophylaxis (LTP). During the study run-in period, the mean
attack rate was 3.7 attacks/month with 52% (65/125) of subjects experiencing ≥3 attacks/month.
All TAKHZYRO treatment arms produced statistically significant reductions in the mean HAE attack
rate compared to placebo across all primary and secondary endpoints in the Intent-to-Treat population(ITT) (Table 2).
Table 2. Results of primary and secondary efficacy measures-ITT population
Lanadelumab
Endpoint statisticsa

150mg
every
4 weeks(N=28)

Placebo(N=41)

300 mgevery
4 weeks(N=29)

300 mgevery
2 weeks(N=27)

0.48 (0.31,
0.73)

0.53 (0.36,
0.77)

0.26 (0.14,
0.46)

76 (61, 85)

73 (59, 82)

87 (76, 93)<0.001<0.001<0.001Primary endpoint - Number of HAE attacks from Day 0 to 182
LS Mean (95% CI) monthly attack
rateb

1.97 (1.64,
2.36)% Reduction relative to placebo(95% CI)c
Adjusted p-valuesd

Secondary endpoint - Number of HAE attacks requiring acute treatment from Day 0 to 182
LS Mean (95% CI) monthly attack
rateb

1.64 (1.34,
2.00)% Reduction relative to placebo(95% CI)c

0.31 (0.18,
0.53)

0.42 (0.28,
0.65)

0.21 (0.11,
0.40)

81 (66, 89)

74 (59, 84)

87 (75, 93)

Adjusted p-valuesd<0.001<0.001<0.001
Secondary endpoint - Number of moderate or severe HAE attacks from Day 0 to 182
LS Mean (95% CI) monthly attack
rateb

1.22 (0.97,
1.52)% Reduction relative to placebo(95% CI)c0.36 (0.22,
0.58)

0.32 (0.20,
0.53)

0.20 (0.11,
0.39)

70 (50, 83)

73 (54, 84)

83 (67, 92)

Adjusted p-valuesd<0.001<0.001<0.001
Note: CI=confidence interval; LS=least squares.
a
Results are from a Poisson regression model accounting for over dispersion with fixed effects fortreatment group (categorical) and normalized baseline attack rate (continuous), and the logarithm oftime in days each subject was observed during the treatment period as an offset variable in the model.
bModel-based treatment period HAE attack rate (attacks/4 weeks).
c% reduction relative to placebo corresponds to 100% * (1-rate ratio). The rate ratio is ratio of themodel-based treatment period HAE attack rates.
dAdjusted p-values for multiple testing.
6

The mean reduction in HAE attack rate was consistently higher across the TAKHZYRO treatment
arms compared to placebo regardless of the baseline history of LTP, laryngeal attacks, or attack rateduring the run-in period. The percentage of subjects who were attack free is provided in Table 3.
Table 3. Percentage of subjects who were attack free through treatment
Lanadelumab
Criteria

Placebo

150 mgevery
4 weeks

300 mgevery
4 weeks

300 mgevery
2 weeks

Treatment period (Day 0 to Day 182, 26 weeks)
N

41

28

29

27

Attack free

2%

39%

31%

44%

The percentage of patients who were attack free for the last 16-weeks (Day 70 to Day 182) of thestudy was 77% in the 300 mg every 2 weeks group, compared to 3% of patients in the placebo group.
100% of the subjects on 300 mg every 2 weeks or every 4 weeks and 89% on 150 mg every 4 weeks
achieved at least a 50% reduction in HAE attack rate compared to the run-in period.
Health related quality of life
All TAKHZYRO treatment groups observed an improvement in Angioedema Quality of Life
Questionnaire (AE-QoL) total and domain (functioning, fatigue/mood, fear/shame, and nutrition)
scores compared to the placebo group; the largest improvement was observed in the functioning score
as shown in Table 4. A reduction of 6 points is considered a clinically meaningful improvement. The
percentage of patients who achieved a clinically meaningful improvement in AE-QoL total score was
65% (Odds ratio vs placebo, [95% CI]= 3.2 [1.1, 9.2]), 63% (2.9 [1.1, 8.1]), and 81% (7.2 [2.2, 23.4]),
in TAKHZYRO 150 mg every 4 weeks, 300 mg every 4 weeks, and 300 mg every 2 weeks groups,
respectively, compared to 37% of patients in the placebo group.
Table 4. Change in AE-QoL scorea - placebo vs TAKHZYRO at week 26 in HELP study

LS mean change (SD) from baseline at week 26

Placebo

TAKHZYRO
total

AE-QoL Total score-4.7 (18.8)-19.5 (18.6)

Functioning score-5.4 (22.7)-29.3 (22.9)

Fatigue/Mood score-1.8 (23.3)-13.0 (23.1)

Fear/Shame score-9.0 (24.0)-18.8 (23.7)

Nutrition score

0.5 (22.5)-17.0 (22.3)

Note: AE-QoL= Angioedema Quality of Life; LS=least squares; SD=standard deviation.
Lower scores indicate lower impairment (or better health-related quality of life).

a

7

HELP study extension
Long-term safety and efficacy, pharmacokinetics (PK), and impact on health-related quality of life
(HRQoL) of TAKHZYRO for prophylaxis to prevent HAE attacks were evaluated in an open-label
uncontrolled HELP study extension.
A total of 212 adult and adolescent (≥ 12 years) subjects with symptomatic type I or II HAE received
at least one dose of lanadelumab 300 mg every 2 weeks in this study, including 109 subjects whoentered as rollover subjects from the HELP study. Rollover subjects, regardless of randomisationgroup in the HELP Study, received a single dose of lanadelumab 300 mg at study entry and did notreceive additional treatment until the occurrence of an HAE attack. After the first HAE attack, allsubjects received open-label treatment with lanadelumab 300 mg every 2 weeks. The study also
included 103 new or non-rollover subjects (including 19 subjects from Phase1b study) who had an
historical baseline attack rate of ≥1 attack per 12 weeks. The non-rollover subjects received
lanadelumab 300 mg every 2 weeks at study entry. Subjects were allowed to initiate
self-administration after receiving the first 2 doses from a health care professional in clinic andcompleting appropriate training.
The majority of subjects (173/212; 81.6%) who were treated in this study completed at least
30 months of treatment (either as a rollover or non-rollover subjects). The mean (SD) time in the
HELP study extension was 29.6 (8.20) months. The majority of subjects self-administered
lanadelumab (60.6% of 8,018 injections).
There was a sustained reduction in attack rates compared to baseline during the HELP study extension,
with a similar response to TAKHZYRO observed in both rollover (92.4%) and non-rollover groups(82.0%) and an overall reduction rate of 87.4%. Though the magnitude of the attack rate reduction in
the HELP study limited the potential for further reductions in the HELP extension study, mean attack
rates for the rollover subjects decreased further at the time of the final analysis and ranged from0.08 to 0.26 attacks per month. In addition, the mean (SD) percentage of attack-free days was
97.7 (6.0)% and the mean (SD) duration of the attack-free period was 415.0 (346.1) days. The
proportion of patients with a maximum attack-free period of 6 months or more or 12 months or more
was 81.8% and 68.9%, respectively.
Paediatric population
SPRING study
The safety and efficacy of TAKHZYRO for prophylaxis to prevent HAE attacks in children were
evaluated in an open-label, multicenter, Phase 3 SPRING study. Dosing regimens were based on thefollowing pre-defined age groups: children from 2 to less than 6 years of age were to receive
lanadelumab 150 mg every 4 weeks and children from 6 to less than 12 years of age were to receive
lanadelumab 150 mg every 2 weeks. The overall treatment period was 52 weeks, equally divided into
Treatment Period A and B. The study enrolled 21 paediatric subjects who had a baseline attack rate of≥ 1 attack per 3 months (12 weeks) and a confirmed diagnosis of type I or II HAE.
In Treatment Period A, subjects aged 2 to < 6 years (n=4) and 6 to < 12 years (n=17) received
lanadelumab 150 mg every 4 weeks and 150 mg every 2 weeks, respectively. The youngest patient
included in the study was 3.5 years old.
In Treatment Period B, subjects receiving lanadelumab 150 mg every 2 weeks (i.e., subjects 6 to lessthan 12 years of age) could reduce dosing to 150 mg every 4 weeks if they were well-controlled (e.g.,
attack free) for 26 weeks with lanadelumab treatment. Seven subjects in the 6 to less than 12 years age
group switched to 150 mg every 4 weeks during Treatment Period B, and one subject (enrolled in the
2 to less than 6 years age group) turned 6 years of age during Treatment Period A and switched to
150 mg every 2 weeks during Treatment Period B after experiencing recurrent attacks.

8

The total exposure was 5.5 patient-years in the “every 4 weeks”- dosing regimen group (age range 3.510.4 years) and 14.47 patient-years in the “every 2 weeks”-dosing regimen group (age range 610.9 years).
The TAKHZYRO dose regimen in both age groups produced reduction in mean HAE attack ratecompared to baseline and an increased percentage of attack-free subjects in Treatment Period A(Table 5). Similar results were observed for the overall, 52-week treatment period.
Table 5. Results of efficacy measures
TAKHZYRO
Criteria

150 mgevery 4 weeksa

150 mgevery 2 weeksa

Total

Treatment Period A (26 weeks)
N

4

17

21

1.9 (1.0)

1.8 (1.6)

1.8 (1.5)

Attack rate (attacks/month ),mean (SD)

0.2 (0.3)

0.1 (0.2)

0.1 (0.2)

Attack-free subjects N (%)

3 (75.0)

14 (82.4)

17 (81.0)

Baseline attack rate, mean (SD)babThe actual treatment received during the given study period.
Month is defined as 28 days. Calculated over the 26-week treatment period.

Immunogenicity
Anti-drug antibodies (ADA) were very commonly detected. No evidence of ADA impact onpharmacokinetics, efficacy or safety was observed.

5.2

Pharmacokinetic properties

The single and multiple dose pharmacokinetics of lanadelumab have been studied in patients with
HAE. Pharmacokinetics of lanadelumab showed linear dose-exposure response with doses up to
400 mg and reproducible exposure following subcutaneous administration up to 12 months. The
absolute bioavailability of lanadelumab after subcutaneous administration has not been determined. In
the HELP study, patients treated with 300 mg every2 weeks presented mean (SD) area under the curve
over the dosing interval at steady-state (AUCtau,ss), maximum concentration at steady-state (Cmax,ss)
and minimum concentration at steady-state (Cmin,ss) of 408 µg*day/ml (138), 34.4 µg/ml (11.2), and25.4 µg/ml (9.18), respectively. The anticipated time to reach steady state concentration wasapproximately 70 days.
Absorption
Following subcutaneous administration, the time to maximum concentration is approximately 5 days.
The site of subcutaneous injection (thigh, arm, or abdomen) and self-administration did not affect theabsorption of lanadelumab.
Distribution
The mean (SD) volume of distribution of lanadelumab in patients with HAE is 14.5 litres (4.53).
Lanadelumab is a therapeutic monoclonal antibody and is not expected to bind to plasma proteins.
Elimination9

Lanadelumab has a mean (SD) total body clearance of 0.0297 L/h (0.0124) and a terminal elimination
half-life of approximately 14 days.
Special populations
No dedicated studies have been conducted to evaluate the pharmacokinetics of lanadelumab in special
patient populations including gender, or pregnant women.
Population pharmacokinetic analyses, showed that age, gender and race did not meaningfully
influence the pharmacokinetics of lanadelumab. Body weight was identified as an important covariate
describing the variability of clearance and volume of distribution of lanadelumab.

Paediatric population
Following subcutaneous administration of 150 mg every 4 weeks (2 to less than 6 years of age) and
150 mg every 2 weeks (6 to less than 12 years of age), the overall exposure (i.e., Cavg,ss) tolanadelumab was similar compared with adult and adolescent (12 to less than 18 years of age) patients
who received TAKHZYRO 300 mg every 2 weeks (ratio to adults ranged from 0.8 to 1.11).
Renal and hepatic impairment
As IgG monoclonal antibodies are mainly eliminated via intracellular catabolism, renal impairment or
hepatic impairment is not expected to influence clearance of lanadelumab.
Accordingly, in a population pharmacokinetic analysis, renal impairment (estimated GFR:
60 to 89 ml/min/1.73 m2 [mild, N=98] and 30 to 59 ml/min/1.73m2 [moderate, N=9]) had no effect on
the clearance or volume of distribution of lanadelumab.
5.3

Preclinical safety data

In repeat-dose studies evaluating once weekly subcutaneous injection in both rats (up to 28 days) andcynomolgus monkeys (up to 6 months) lanadelumab was well-tolerated at doses of up to and including
50 mg/kg (highest dose tested) with no organs of toxicity identified. Exposures in cynomolgus
monkeys following 6 months of administration were approximately 23-fold greater than that noted at
300 mg every 2 weeks based on AUC.
Lanadelumab is not expected to interact directly with DNA or other chromosomal material, as it ismade up entirely of naturally occurring amino acids and contains no inorganic or synthetic linkers orother nonprotein portions; therefore no genotoxicity evaluation has been conducted.
Carcinogenicity has not been evaluated in animals as based on the weight of evidence approach,lanadelumab is considered to have a low risk for carcinogenicity.
The effects of lanadelumab on fertility were evaluated in sexually mature cynomolgus monkeys. In a
13-week study, once weekly subcutaneous administration of lanadelumab had no effects on male orfemale fertility at doses of 10 or 50 mg/kg (highest dose tested). Exposures in sexually maturecynomolgus monkeys in the fertility study were approximately 20-and 22-fold greater than that noted
at 300 mg every 2 weeks based on Cmax and AUC, respectively.
In the ePPND study in pregnant cynomolgus monkeys administered once weekly doses of 10 or 50 mg/kg(highest dose tested), there were no lanadelumab-related effects on pregnancy and parturition,embryo-foetal development, survival, growth, and/or postnatal development of offspring. Exposures inthe ePPND study were approximately 32-fold greater than that noted at 300 mg every 2 weeks basedon AUC.

10

6.

PHARMACEUTICAL PARTICULARS

6.1

List of excipients

Water for injections
L- Histidine
Sodium phosphate dibasic, dihydrate
Sodium chloride
Citric acid monohydrate
Polysorbate 80
6.2

Incompatibilities

Not applicable.
6.3

Shelf life

The expiry date of the product is indicated on the packaging materials.
Vial only:
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 therisks 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. TAKHZYRO 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 to 8°C), protected from light andadministered within 8 hours.
6.4

Special precautions for storage

Store in a refrigerator (2°C to 8°C).
Do not freeze.
Keep the solution (pre-filled syringe or vial) in the outer carton in order to protect from light.
The solution (pre-filled syringe or 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.
When one pre-filled syringe from a multi-pack is removed from refrigeration, return the remaining
pre-filled syringes to the refrigerator until future use when needed.
For storage conditions after first opening of the product in vial, see section 6.3.
6.5
Nature and contents of container
TAKHZYRO 150 mg solution for injection in pre-filled syringe
1 ml of solution in pre-filed syringe with a bromobutyl stopper, 27G x 13 mm staked needle and rigid
needle cap. TAKHZYRO is available as unit packs containing 1 or 2 pre-filled syringes and in
multipacks containing 6 (3 packs of 2) pre-filled syringes.
TAKHZYRO 300 mg solution for injection in pre-filled syringe
2 ml of solution in pre-filled syringe with a bromobutyl stopper, 27G x 13 mm staked needle and rigid
needle cap. TAKHZYRO is available as unit packs containing 1 or 2 pre-filled syringes and in
multipacks containing 6 (3 packs of 2) pre-filled syringes.
11

TAKHZYRO 300 mg solution for injection in vial
2 ml of solution in a vial (type I glass) with a coated butyl rubber stopper and an aluminium seal withviolet flip-off cap. TAKHZYRO is available as a single pack containing one 2 ml vial.
Each pack also contains the following items:•••

Empty 3 ml syringe
18G vial access needle
27G x ½ inch (0.4 x 13 mm) injection needle

Not all pack sizes may be marketed.
6.6

Special precautions for disposal and other handling

Lanadelumab is provided in single use pre-filled syringes and vials.
Before use, TAKHZYRO solution should be visually inspected for appearance. The solution should beclear or slightly yellow. Solutions that are discoloured or contain particles should not be used.
Avoid vigorous agitation.
Administration steps
TAKHZYRO 150 mg solution for injection in pre-filled syringe
After removing the single use pre-filled syringe from the refrigerator, wait 15 minutes before injecting
to allow the solution to reach room temperature. Caregiver should inject TAKHZYRO subcutaneously
into the abdomen, thigh, or upper arm (see section 4.2).
TAKHZYRO 300 mg solution for injection in pre-filled syringe
After removing the single use pre-filled syringe from the refrigerator, wait 15 minutes before injecting
to allow the solution to reach room temperature. Inject TAKHZYRO subcutaneously into theabdomen, thigh, or upper arm (see section 4.2).
Each pre-filled syringe is for single use only. Discard the pre-filled syringe after injection iscompleted.
Any unused medicinal product or waste material should be disposed of in accordance with local
requirements.
All needles and syringes should be disposed of in a sharps container.
TAKHZYRO 300 mg solution for injection in vial
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.

7.

LICENSE HOLDER AND IMPORTER

Takeda Israel Ltd.,
25 Efal St., Petach-Tikva, 4951125
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9. REGISTRATION NUMBER
163-47-35885-00
This leaflet format has been revised according to the Ministry of Health guidelines in March 2024.

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