TAKHZYRO^®

▼ This medicinal product is subject to additional monitoring in Australia. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse events at www.tga.gov.au/reporting-problems.

MIMS Revision Date: 01 September 2024

1 Name of Medicine

Lanadelumab.

2 Qualitative and Quantitative Composition

Ready-to-use solution, for subcutaneous injection only.
Takhzyro is a sterile, preservative-free solution supplied in a single-dose pre-filled syringe or a single-dose vial.
Each pre-filled syringe contains either 300 mg of lanadelumab in 2 mL solution or 150 mg of lanadelumab in 1 mL solution. Each vial contains 300 mg of lanadelumab in 2 mL solution.
Excipient with known effect. Each mL of solution contains 3.45 mg (0.150 mmol) of sodium.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Solution for injection.
The solution is colourless to slightly yellow, appearing either clear or slightly opalescent.

4 Clinical Particulars

4.1 Therapeutic Indications

Takhzyro is indicated for routine prevention of recurrent attacks of hereditary angioedema (C1-esterase-inhibitor deficiency or dysfunction) in patients aged 2 years and older.

4.2 Dose and Method of Administration

Takhzyro therapy should be initiated under supervision of a physician experienced in the care of patients with hereditary angioedema (HAE).
Dosage. Adult patients. The recommended starting dose is 300 mg lanadelumab every 2 weeks administered subcutaneously. In patients who are well-controlled (e.g. attack free) on treatment, a dose reduction of 300 mg lanadelumab every 4 weeks may be considered, especially in patients with low weight.
Elderly. Limited information is available on patients above 65 years of age. Available data indicates that no dose adjustment is required for patients above 65 years of age.
Hepatic impairment. No studies have been conducted in patients with hepatic impairment.
Renal impairment. No studies have been conducted in patients with renal impairment.
Paediatric patients. 12 to < 18 years. The recommended dose is 300 mg administered subcutaneously every 2 weeks. A dosing interval of 300 mg every 4 weeks may be considered if the patient is well-controlled (e.g. attack-free) for 26 weeks (see Section 5.1 Pharmacodynamic Properties).
6 to < 12 years. The recommended dose is 150 mg administered subcutaneously every 2 weeks. A dosing interval of 150 mg every 4 weeks may be considered if the patient is well-controlled (e.g. attack free) for 26 weeks (see Section 5.1 Pharmacodynamic Properties).
2 to < 6 years. The recommended dose is 150 mg administered subcutaneously every 4 weeks (see Section 5.1 Pharmacodynamic Properties).
The safety and efficacy of Takhzyro in children aged < 2 years has not been established and therefore treatment in children aged < 2 years is not recommended.
The product is for single use in one patient only. Discard any residue.
Method of administration. Takhzyro is administered subcutaneously only.
Takhzyro is provided as a ready-to-use solution that does not require additional reconstitution or dilution for administration. Each Takhzyro pre-filled syringe or vial is intended for single use only. Do not use the pre-filled syringe or vial if the solution appears discoloured or contains visible particles. Avoid vigorous agitation of the pre-filled syringe or vial.
Takhzyro may be administered by a healthcare professional or by the patient/caregiver. The decision on the use of home treatment for an individual patient should be made by the treating physician, who should ensure that appropriate training is provided. The patient or caregiver should receive clear instructions and adequate training on how to perform subcutaneous administration. A healthcare professional should review the self-administration method at intervals to ensure the continued appropriate administration.
Detailed instructions for administration are provided in the Consumer Medicine Information that is included as a package insert and may be used as a training guide.
If a dose of Takhzyro is missed, instruct the patient or caregiver to administer the dose as soon as possible ensuring at least 10 days between the doses.
For paediatric patients, if a dose of Takhzyro is missed, instruct the caregiver to administer the dose as soon as possible, ensuring at least 10 days (6 to < 12 years) and at least 24 days (2 to < 6 years) between the doses.
Administration steps. Adult and paediatric patients (12 to < 18 years). For single-dose 2 mL pre-filled syringe. Inject Takhzyro subcutaneously into the abdomen, thigh, or upper arm. Patients should inject the complete dose as prescribed by their physician.
For single-dose 2 mL vial. An aseptic technique must be used. The 18 gauge needle is used to withdraw the Takhzyro dose from the vial and the 27 gauge needle is used to administer the complete dose as prescribed subcutaneously. Takhzyro may be administered into the abdomen, thigh, or upper arm. Takhzyro should be administered within 2 hours of preparing the dosing syringe at room temperature. After the dosing syringe is prepared, it can be refrigerated at 2°C to 8°C and must be used within 8 hours.
Discard any unused portions of drug remaining in the vial and syringe.
Paediatric patients (2 to < 12 years). For single-dose 1 mL prefilled syringe. Inject Takhzyro subcutaneously into the abdomen, thigh or upper arm. The complete dose should be injected as prescribed.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients.

4.4 Special Warnings and Precautions for Use

General. Takhzyro should not be used to treat an acute attack. Patients and caregivers should continue to be prepared to treat attacks with acute HAE treatments when necessary.
There are no available clinical data on the use of Takhzyro in HAE patients with normal C1 esterase inhibitor activity.
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, discontinue Takhzyro administration and institute appropriate treatment.
Use in hepatic impairment. No dedicated study has been conducted in subjects with hepatic impairment.
Use in renal impairment. No dedicated study has been conducted in subjects with renal impairment (see Section 5.2 Pharmacokinetic Properties, Special populations).
Use in the elderly. The clinical studies included 11 subjects aged ≥ 65 years, with 5 included in the main efficacy study. Results of the subgroup analysis by age were consistent with overall study results (see Section 5.1 Pharmacodynamic Properties, Clinical trials).
Paediatric use. The safety of Takhzyro 300 mg/2 mL was evaluated in a subgroup of 23 subjects aged 12 to < 18 years (HELP studies), with 10 included in the main efficacy study. The safety of Takhzyro was also evaluated at 150 mg/1 mL in a study with 21 subjects aged 2 to < 12 years (SPRING study). Safety and tolerability results for paediatric subjects (2 to < 18) were consistent with overall study results for all subjects (see Section 5.1 Pharmacodynamic Properties; 5.2 Pharmacokinetic Properties).
Effects on laboratory tests. Coagulation tests. Takhzyro can increase activated partial thromboplastin time (aPTT) due to an interaction of Takhzyro 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 Takhzyro 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.

4.5 Interactions with Other Medicines and Other Forms of Interactions

No dedicated drug interaction studies have been conducted. Based on the characteristics of lanadelumab, no pharmacokinetic interactions with co-administered medicinal products are expected.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility. Takhzyro effect on fertility has not been evaluated in humans.
In a 13-week study, once weekly subcutaneous administration at doses of 10 or 50 mg/kg (highest dose tested) lanadelumab had no effects on semen sample weight, total sperm count, sperm density, motility and morphology, testicular measurements, spermatogenesis staging, menstrual cycle length, or reproductive organs (organ weights, macroscopic and microscopic findings). Exposures in sexually mature cynomolgus monkeys were approximately 18-fold greater than that noted at 300 mg every 2 weeks based on AUC.
Use in pregnancy. (Category B1)
Takhzyro has not been studied in pregnant women. There are no or limited amount of data from the use of lanadelumab in pregnant women. A risk to the pregnant woman or developing fetus cannot be excluded. A decision should be made whether to initiate or discontinue treatment with Takhzyro, taking into account the risk/benefit of therapy.
The effects of lanadelumab were evaluated in an enhanced pre- and postnatal developmental (ePPND) toxicity study. In the ePPND study in pregnant cynomolgus monkeys administered once weekly doses of 10 or 50 mg/kg (highest dose tested) from gestation day 20 to delivery, there were no lanadelumab-related effects on pregnancy and parturition, embryo-fetal development, as well as survival, growth, and/or postnatal development of offspring. Exposures in the ePPND study were approximately 28-fold greater than that noted at 300 mg every 2 weeks based on AUC.
Use in lactation. Takhzyro has not been studied in lactating women. It is not known whether lanadelumab is present in human milk therefore a risk to the newborns/infants cannot be excluded. The developmental and health benefits of breastfeeding should be taken into consideration along with the mother's medical need for Takhzyro as well as any potential adverse effects on both the infant and the mother.
Available pharmacokinetic data from the ePPND study in cynomolgus monkeys have shown low excretion of lanadelumab in milk at approximately 0.2% of the maternal plasma level.

4.7 Effects on Ability to Drive and Use Machines

Takhzyro has negligible influence on the ability to drive or use machines.

4.8 Adverse Effects (Undesirable Effects)

The safety of lanadelumab was evaluated in 4 clinical studies: a Phase 1a, randomised, double-blind, placebo-controlled study in healthy subjects; a Phase 1b, randomised, double-blind, placebo-controlled, multiple-ascending dose study in subjects with HAE; a pivotal Phase 3, randomised, double-blind, and placebo-controlled study (HELP study) in subjects with HAE; and an open-label extension study (HELP study extension), which includes both subjects from the HELP study (rollover) and additional non-rollover HAE subjects. Two hundred and fifty-seven (257) unique subjects (233 subjects with HAE and 24 healthy subjects) were exposed to at least one dose of lanadelumab.
The safety data described below reflect exposure to Takhzyro in the HELP study and in the HELP study extension; in total, 220 subjects received treatment with lanadelumab in one or both of the studies.
Treatment-emergent adverse events that occurred in ≥ 5% of lanadelumab-treated subjects (overall) in the HELP study are presented in Table 1.

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 reaction 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).
In the HELP study, the most commonly observed adverse reaction associated with Takhzyro in subjects with HAE 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 Special Warnings and Precautions for Use, Hypersensitivity reactions).
Safety data available from the HELP study extension are consistent with 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 aged 12 to < 18 years old (HELP studies). The safety of Takhzyro was also evaluated at 150 mg/1 mL in a study with 21 subjects aged 2 to < 12 years (SPRING study). No new adverse reactions were identified. Safety and tolerability results for paediatric subjects (2 to < 18 years) were consistent with the overall study results for all subjects (see Section 5.1 Pharmacodynamic Properties; Section 5.2 Pharmacokinetic Properties).
Immunogenicity. In the HELP study, 10 (12%) lanadelumab-treated and 2 (5%) placebo-treated subjects had at least 1 anti-drug antibody (ADA)-positive sample during treatment period (26 weeks); antibody titres were low (range: 20 to 1280). The ADA response observed was transient in 2 of 10 lanadelumab-treated and 1 of 2 placebo-treated subjects. Pre-existing low titre antibodies were observed in 3 lanadelumab-treated subjects and 1 placebo-treated subject with ADAs. Two subjects receiving 150 mg every 4 weeks had low titre antibodies classified as neutralising.
In the SPRING study, 3/20 (15%) of lanadelumab-treated patients developed anti-lanadelumab antibodies (at 52 weeks); all of which were in the 6 to < 12 years group. The ADA response observed was transient in all 3 patients. None of these patients had pre-existing antibodies. One patient had neutralising antibodies.
The development of ADA including neutralising antibodies against Takhzyro did not appear to adversely affect pharmacokinetics, pharmacodynamics, safety or clinical response.
Reporting suspected adverse effects. Reporting suspected adverse reactions after registration 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 at www.tga.gov.au/reporting-problems.

4.9 Overdose

There is no clinical experience with overdosage of Takhzyro.
For information on the management of overdose, contact the Poisons Information Centre on 131126 in Australia, or the National Poisons Centre on 0800 POISON (0800 764766) in New Zealand.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Drugs used in hereditary angioedema, monoclonal antibody, ATC code: B06AC05.
Mechanism of action. Lanadelumab is a fully human, monoclonal antibody (IgG1/κ-light chain) produced in Chinese Hamster Ovary (CHO) cells by recombinant DNA technology. Lanadelumab inhibits active plasma kallikrein proteolytic activity without binding prekallikrein, the inactive precursor found in the circulation. 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, a potent vasodilator that increases vascular permeability resulting in swelling and pain associated with HAE. It has been demonstrated that patients with HAE due to C1 esterase inhibitor deficiency or dysfunction have increased plasma kallikrein activity, as indirectly measured by amount of cHMWK, both during and in between HAE attacks. Lanadelumab provides sustained control of plasma kallikrein activity and thereby limits bradykinin generation in patients with HAE.
Pharmacodynamic effects. At pharmacokinetic steady-state in adult and paediatric (12 to < 18 years) patients, similar inhibition of plasma kallikrein, measured as reduction of cHMWK levels, was demonstrated after subcutaneous administration of Takhzyro 150 mg every 4 weeks, 300 mg every 4 weeks, or 300 mg every 2 weeks in subjects with HAE.
The pharmacokinetic-pharmacodynamic relationship between Takhzyro and cHMWK is described by an indirect exposure-response pharmacological model. The cHMWK formation rate was maximally reduced by 53.7% with an IC₅₀ of 5705 nanogram/mL.
Serial 12 lead ECG monitoring in the clinical studies found that Takhzyro did not prolong the QT/QTc interval.
For paediatric patients 2 to < 6 years (150 mg every 4 weeks) and 6 to < 12 years (150 mg every 2 weeks), the observed mean percent change from baseline in cHMWK levels was similar to that observed in adult and paediatric (12 to < 18 years) patients.
Clinical trials. HELP study. The HELP study investigated efficacy and safety of Takhzyro for routine prevention of attacks of HAE in subjects 12 years of age and older in a multicentre, randomised, double-blind, placebo-controlled parallel-group study.
The study included 125 adult and paediatric (12 to < 18 years) subjects with symptomatic type I or II HAE, including 10 subjects aged 12 to 17 years and 5 subjects aged more than 65 years. Subjects were randomised 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 (q4wks), lanadelumab 300 mg q4wks, or lanadelumab 300 mg every 2 weeks (q2wks) by subcutaneous injection) for the 26-week treatment period. The use of rescue medications for treatment of breakthrough HAE attacks was allowed for subjects receiving placebo or Takhzyro.
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, attack rates of ≥ 3 attacks/month were observed in 52% (65/125) of subjects overall.
All Takhzyro treatment arms produced clinically meaningful and 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 3).

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 rate during the run-in period.
During the anticipated pharmacokinetic steady-state period (Day 70 to Day 182), percentage reductions in the mean monthly HAE attack rate for Takhzyro-treated subjects compared to placebo was 78% in the 150 mg q4wks arm, 81% in the 300 mg q4wks arm, and 91% in the 300 mg q2wks arm.
The percentage of subjects who were attack free is provided in Table 4.
A responder was defined as achieving a 50% reduction in HAE attack rate compared to the run-in period. One hundred percent (100%) of subjects on 300 mg q2wks or q4wks and 89% on 150 mg q4wks responded to treatment. Table 5 shows the percentage of subjects achieving pre-defined threshold (≥ 50%, ≥ 70%, ≥ 90%) reductions in HAE attack rates compared to run-in during the 26 week treatment period.
Health-related quality of life. The health-related quality of life (QoL) was investigated using a generic QoL questionnaire, EQ-5D-5L; and an angioedema-specific questionnaire, Angioedema Quality of Life (AE-QoL). The ED-5D-5L scores showed no differences between placebo and treatment groups. A higher proportion of Takhzyro treated subjects compared to placebo achieved a clinically meaningful improvement in QoL, as measured by a Minimal Clinically Important Difference (MCID) ≥ 6 for the AE-QoL total score; applying same MCID, a similar response was observed for functioning but not for fear/shame, fatigue/mood, and nutrition domains.
HELP study extension. Long-term safety and efficacy, pharmacokinetics, and impact on health-related QoL of Takhzyro for prophylaxis to prevent HAE attacks were evaluated in an open-label uncontrolled HELP study extension.
A total of 212 adult and paediatric (12 to < 18 years) subjects received at least one dose of lanadelumab 300 mg q2wks in this study including 109 subjects who entered as rollover subjects from the HELP study. Rollover subjects, regardless of randomisation group in the HELP study, received a single dose of lanadelumab 300 mg at study entry and did not receive additional treatment until the occurrence of an HAE attack. After the first HAE attack, all subjects received open-label treatment with lanadelumab 300 mg q2wks. The study also included 103 new or non-rollover subjects (including 19 subjects from the Phase 1b study) who had a historical baseline attack rate of ≥ 1 attack per 12 weeks and a confirmed diagnosis of type I or II HAE. The non-rollover subjects received lanadelumab 300 mg q2wks at study entry. The median (range) age of the study population was 43 (12 to 76) years with 67% female subjects. The majority of subjects (173 of 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 over 10 to 60 seconds (60.6% of 8018 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%. In the final analysis, mean attack rates for the rollover subjects decreased further from the end of Takhzyro treatment and ranged from 0.08 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.
In the HELP study extension, all Takhzyro treatment groups (rollover and non-rollover groups) observed an improvement in AE-QoL total and domain (functioning, fatigue/mood, fear/shame, and nutrition) scores.
The safety and efficacy of Takhzyro were evaluated in a subgroup of subjects (N=23) aged 12 to < 18 years. Results of the subgroup analysis by age were consistent with overall study results (see Section 4.8 Adverse Effects (Undesirable Effects); Section 5.1 Pharmacodynamic Properties; Section 5.2 Pharmacokinetic Properties).
SPRING study. The safety and efficacy of Takhzyro for prophylaxis to prevent HAE attacks in subjects aged 2 to < 12 years were evaluated in an open-label, multicentre, Phase 3 SPRING study. The study enrolled 21 paediatric subjects who had a baseline attack rate of ≥ 1 attacks per 3 months (12 weeks) and a confirmed diagnosis of type I or II HAE. The overall treatment period was 52 weeks, equally divided into Treatment Period A and B. In Treatment Period A, subjects aged 2 to < 6 years (n = 4) and 6 to < 12 years (n = 17) received lanadelumab 150 mg q4wks and 150 mg q2wks, respectively. In Treatment Period B, subjects in the 2 to < 6 years age group would continue the dosing regimen, while subjects in the 6 to < 12 years age group were permitted to switch to 150 mg q4wks if they were well-controlled (e.g. attack free) for 26 weeks with lanadelumab treatment. Seven subjects aged 6 to < 12 years switched to 150 mg q4wks during Treatment Period B, and one subject aged 2 to < 6 years switched to 150 mg q2wks during Treatment B after experiencing recurrent attacks.
The median (range) age of the study population was 8.7 (3.5, 10.9) years with 12 female subjects (57.1%) and the median HAE onset age (range) was 2.0 (0, 9) years. The Takhzyro dose regimen in both age groups produced marked clinically meaningful reduction in mean HAE attack rate compared to baseline and substantial percentage of attack-free subjects (Table 6). Results of the analysis indicate that Takhzyro was safe and effective in paediatric patients (2 to < 12 years) as shown in the Table 6.

5.2 Pharmacokinetic Properties

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 pharmacokinetic (PK) properties and exposure (steady-state) of lanadelumab in adult and paediatric (12 to < 18 years) HAE patients, following subcutaneous administration of 150 mg q4wks, 300 mg q4wks and 300 mg q2wks, are provided in Table 7. The anticipated population time to reach steady-state concentration was approximately 70 days.

Special populations. No dedicated studies have been conducted to evaluate the pharmacokinetics of lanadelumab in special patient populations including gender, pregnant women, or the presence of renal or hepatic impairment.
Population PK analyses were performed, using data from rich sampling in two Phase 1 studies and sparse sampling in two Phase 3 (HELP and HELP extension) studies.
The population PK analyses found that patient body weight was an important covariate describing the variability of clearance and volume of distribution, resulting in higher exposure (AUC and C_max) in lighter patients. After correcting for body weight, no influence of gender was apparent on the clearance or volume of distribution of Takhzyro. No dose adjustment is required.
The population PK analyses for the effects of age, including 22 adolescents [aged 12 to 18], 226 adults [aged > 18 and < 65 years] and 9 elderly [aged > 65 years]. The mean lanadelumab exposure under the same dosing regimen was found to be approximately 37% higher in adolescent patients compared to adult patients, due to lower body weight in adolescent patients.
Although body weight was identified as an important covariate describing the variability of clearance, a 300 mg q2wks dose regimen provided sufficient exposure for the indication.
The population PK analysis of the effect of renal impairment that included estimated GFR: 60 to 89 mL/min/1.73 m² [mild, N=98], 30 to 59 mL/min/1.73 m² [moderate, N=9] and < 30 mL/min/1.73 m² [severe, N=0] found no effect on the clearance or volume of distribution. No dose adjustment is required for mild or moderate renal impairment. No dose recommendation can be made for severe renal impairment.
Paediatric patients. Following subcutaneous administration of 150 mg every 4 weeks (2 to < 6 years) and 150 mg every 2 weeks (6 to < 12 years), the overall exposure (i.e. C_avg,ss) to lanadelumab was similar compared with adult and paediatric (12 to < 18 years) patients who received Takhzyro 300 mg every 2 weeks (ratio to adults ranged from 0.8 to 1.11).
Concomitant medications. There have been no dedicated investigations of PK interactions (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Based on the population PK analysis of the Phase 3 data, the use of analgesic, antibacterial, antihistamine, anti-inflammatory and anti-rheumatic medications had no effect on clearance and volume of distribution of Takhzyro.
For breakthrough HAE attacks, use of rescue medications such as icatibant or plasma-derived C1 esterase inhibitor had no effects on clearance and volume of distribution of Takhzyro.

5.3 Preclinical Safety Data

Genotoxicity. Given that lanadelumab is a monoclonal antibody and therefore is not expected to interact directly with DNA or other chromosomal material, no genotoxicity evaluation has been conducted.
Carcinogenicity. Carcinogenicity has not been evaluated in animals.

6 Pharmaceutical Particulars

6.1 List of Excipients

Dibasic sodium phosphate dihydrate, citric acid monohydrate, histidine, sodium chloride, polysorbate 80, water for injections.

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the ARTG. The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store in a refrigerator at 2°C to 8°C. Do not freeze.
Takhzyro pre-filled syringe removed from refrigeration should be stored below 25°C and used within 14 days. Do not return pre-filled syringes to refrigerated storage after storage at room temperature.
Takhzyro vial removed from refrigeration should be stored unopened, below 25°C, and used within 14 days or returned to refrigeration unopened until use. Total period stored out of refrigeration, below 25°C, should not exceed 14 days.
Keep the pre-filled syringe or vial in the original carton in order to protect it from light.

6.5 Nature and Contents of Container

Single-dose pre-filled syringe. Takhzyro is a ready-to-use solution supplied in a glass pre-filled syringe with bromobutyl rubber stopper, 27 gauge ½ inches staked needle with rigid needle cap. Pack size of 1 syringe available as: 150 mg/1 mL solution, 300 mg/2 mL solution.
Single-dose vial. Takhzyro is a ready-to-use solution supplied in a glass vial with chlorobutyl rubber stopper, aluminium crimp seal and violet flip-off cap. Pack size of 1 vial of 300 mg/2 mL.
Each pack also contains the following administration ancillaries: one empty 3 mL syringe, one 18 gauge vial access needle, and one 27 gauge ½ inches needle (for subcutaneous injection).
Note. Not all presentations may be marketed.

6.6 Special Precautions for Disposal

All needles and syringes should be disposed of in a sharps container.
In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Takhzyro is a sterile, preservative-free, colourless to slightly yellow solution, appearing either clear or slightly opalescent with a pH of approximately 6.0 and an osmolality of approximately 300 mOsm/kg.
Chemical structure. Based on the amino acid sequence, the molecular weight of the non-glycosylated lanadelumab is 146 kDa. The calculated molecular mass of the fully reduced light chain is 23 kDa. The calculated molecular mass of the fully reduced and non-glycosylated heavy chain is 49 kDa.
CAS number. 1426055-14-2.

7 Medicine Schedule (Poisons Standard)

Prescription Only Medicine.

Date of Revision

25 July 2024

Summary Table of Changes