Lumicef

Lumicef

brodalumab

Manufacturer:

Kyowa Kirin

Distributor:

DCH Auriga - Healthcare
/
Four Star
Full Prescribing Info
Contents
Brodalumab.
Description
Content per syringe (1.5 mL): Active ingredient: Brodalumab (genetical recombination) 210 mg.
Brodalumab is a human IgG2 monoclonal antibody against human interleukin (IL)-17 receptor A expressed in a Chinese hamster ovary cell line. It is a glycoprotein composed of 2 H-chains (γ2 chains) consisting of 442 amino acid residues and 2 L-chains (κ chains) consisting of 214 amino acid residues.
pH: pH 4.5 to 5.1.
Osmotic pressure ratio: Approximately 1 (to physiological saline).
Molecular weight: Approximately 147,000.
Excipients/Inactive Ingredients: L-Glutamic acid 6.5 mg, L-Proline 36 mg, Polysorbate 20 0.15 mg.
Action
Pharmacology: Brodalumab is a monoclonal antibody against human IL-17 receptor A (IL-17RA) that selectively binds to the human IL-17RA and blocks the signaling of the proinflammatory cytokines IL-17A, IL-17F, IL-17A/F heterodimer, IL-25 (also known as IL-17E), and IL-17C with IL-17RA.
IL-17RA Inhibitory Effect: In in vitro studies, brodalumab showed a high binding affinity for human IL-17RA and bound to human IL-17RA competitively with human IL-17A.
In in vitro studies, brodalumab bound to the cell surface of human lymphocytes, monocytes, granulocytes, and various human fibroblasts and inhibited IL-17RA-mediated biological activities induced by human IL-17A, IL-17F, IL-17A/F heterodimer, IL-25, and IL-17C stimulations.
Effects on Psoriasis: In a mouse model of psoriasis, the intraperitoneal injection of an anti-mouse IL-17RA antibody inhibited the psoriasis-like skin symptoms (epidermal hyperplasia, intra-epidermal neutrophilic pustule formation, and parakeratotic scaling) and the mRNA expressions for various inflammatory chemokines and cytokines at the sites of skin lesion.
Brodalumab inhibited the mRNA expressions for IL-17A, IL-17F, IL-17C, IL-12B, and IL-23A, the proliferation of keratinocytes, acanthosis, and the accumulation of inflammatory T-cells (non-Japanese study data) at the site of skin lesion in psoriasis patients.
Clinical Studies: Japanese Double-blind Comparative Study (subjects with psoriasis vulgaris and subjects with psoriatic arthritis): A randomized, placebo-controlled, double-blind, parallel-group comparative study was conducted in subjects with psoriasis vulgaris and subjects with psoriatic arthritis (with plaque lesions covering ≥ 10% of body surface area [BSA] and a PASINote) score of ≥ 12). Subjects received either placebo or brodalumab at 70, 140, or 210 mg* by subcutaneous injection at Weeks 0, 1, and 2 and at 2-week intervals thereafter for 12 weeks. The Week-12 PASI score improvement rates and percentages of subjects achieving an improvement from baseline in PASI score of ≥75%, ≥90%, and 100% (hereafter, PASI 75/90/100 responses) are shown in the table as follows. The PASI score improvement rate was significantly higher in the brodalumab-treated groups than in the placebo group.
Note) Psoriasis Area and Severity Index
See Table 1.

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Non-Japanese Double-blind Comparative Studies (subjects with plaque psoriasis): A randomized, placebo- and ustekinumab-controlled, double-blind, parallel-group comparative study was conducted in subjects with moderate to severe plaque psoriasis (with plaque lesions covering ≥ 10% BSA and a PASI score of ≥ 12). Subjects received either placebo or brodalumab at 210 mg by subcutaneous injection at Weeks 0, 1, and 2 and at 2-week intervals thereafter for 12 weeks, with the brodalumab treatment continuing up to Week 52.
Moreover, ustekinumab (45 mg for those weighing ≤ 100 kg and 90 mg for those weighing > 100 kg) was subcutaneously administered at Weeks 0, 4, 16, 28, and 40. As shown in the table as follows, the percentages of those achieving a PASI 75/100 response after 12 weeks of treatment were significantly higher in the brodalumab-treated group than those in either the placebo or the ustekinumab group. (See Table 2.)

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Incidences of malignant tumors (Non-Japanese clinical studies): In the non-Japanese clinical studies conducted in subjects with plaque psoriasis, the incidence of malignant tumors (excluding nonmelanoma skin cancers, the same hereafter) among 4,461 subjects (5,574.01 subject-years) treated with brodalumab was 0.4 per 100 subject-years (23 of 4,461 subjects). The malignant tumors included prostate cancer and adenocarcinoma pancreas, among other tumors. The incidence of malignant tumors was similar to that expected in the general population (standardized incidence rate, 0.91 [95% CI: 0.58, 1.37]). The incidence of nonmelanoma skin cancers was 0.5 per 100 subject-years (28 of 4,461 subjects).
* The approved dose of LUMICEF is 210 mg per dose (see DOSAGE & ADMINISTRATION).
Pharmacokinetics: Serum Concentrations: Single dose: The time courses of serum concentration and pharmacokinetic parameters in healthy Japanese adults after a single subcutaneous dose of brodalumab at 70, 140, 210, or 420 mgNote) are as follows. Cmax and AUC0-t increased more than dose-proportionally, indicating that brodalumab has a nonlinear pharmacokinetic profile. (See figure and Table 3.)

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Click on icon to see table/diagram/image

Repeated doses: The Weeks 8 to 10 pharmacokinetic parameters in Japanese subjects with moderate to severe plaque psoriasis who received brodalumab subcutaneously at 70, 140, or 210 mgNote) as the initial dose, once every week up to Week 2, and once every 2 weeks thereafter are as follows. (See Table 4.)

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Note) The approved dose of LUMICEF is 210 mg per dose (see DOSAGE & ADMINISTRATION).
Distribution: Based on the results of a population pharmacokinetic analysis, the volume of distribution of brodalumab was estimated to be approximately 6.52 L, indicating that non-plasma distributions are limited.
Interactions (data from non-Japanese): In subjects with moderate to severe psoriasis, the Cmax and AUC0-∞ of midazolam (a single 2-mg dose), a CYP3A4 substrate, increased to 1.16-fold (90% confidence interval (CI), 1.00 to 1.36; the same hereafter) and 1.24-fold (1.12 to 1.38), respectively, after the concomitant use with brodalumab (a single 210-mg dose).
Indications/Uses
Psoriasis vulgaris that respond inadequately to existing therapies.
Precautions related to INDICATIONS: Administer to any of the following patients: Patients who responded inadequately to phototherapies or other existing systemic therapies (except biologics) and who have skin eruptions over 10% or more of the body surface area.
Patients who have intractable skin eruptions.
Dosage/Direction for Use
Usually, for adults, administer subcutaneously 210 mg as brodalumab (genetical recombination) in the first dose, followed by doses at 1 week later, 2 weeks later, and once every 2 weeks thereafter.
Precautions related to DOSAGE AND ADMINISTRATION: The administration of LUMICEF must be initiated by a physician or under the direct supervision of a physician in a medical institution. After initiating LUMICEF treatment, the physician may allow self-administration in patients who are deemed by the physician to be suitable for self-administration. (See Important Precautions under Precautions).
Use a different site for each injection. Moreover, do not inject areas of the skin that are sensitive or abnormal (scratch, redness, sclerosis, thickness, scaling, or other abnormalities), or sites of psoriasis. (See Precautions concerning Use under Cautions for Usage).
Patients generally achieve a response to treatment with LUMICEF within 12 weeks of treatment initiation. If no response to treatment is achieved within 12 weeks, carefully reconsider whether to continue the treatment protocol with LUMICEF.
Overdosage
No serious adverse events have been noted after a single intravenous dose of brodalumab up to 700 mg. In case of an overdosage, observe patients with close attention for signs or symptoms of adverse reactions. Should symptoms develop, promptly administer appropriate symptomatic treatments.
Contraindications
LUMICEF is contraindicated in the following patients.
Patients with a serious infection [may exacerbate symptoms].
Patients with active tuberculosis [may exacerbate symptoms].
Patients with a history of hypersensitivity to any of the ingredients of LUMICEF.
Warnings
Use LUMICEF only at a medical institution capable of providing adequate responses to emergencies including tuberculosis and other infections, under the supervision of a physician who has thorough knowledge of LUMICEF and is well versed and experienced in treating psoriasis, for patients for whom the benefits outweigh the risks of treatment with LUMICEF. LUMICEF is associated with increased risks of infections and may activate tuberculosis in patients with a history of tuberculosis. There have also been reports of malignant tumors, although it is unclear whether they are causally related to LUMICEF. Before commencing treatment, make sure patients are well informed and understand the efficacy and risks of LUMICEF, including the fact that it is not curative.
Serious infection: Given reports of serious viral, bacterial, and fungal infections, instruct patients to observe closely or otherwise pay attention to any onset of infection and to contact their attending physician immediately when any signs or symptoms of infection occur after the administration of LUMICEF.
Before commencing treatment with LUMICEF, fully consider the use of phototherapies or other existing systemic therapies (except biologics).
Special Precautions
Careful Administration: LUMICEF should be administered with care in the following patients.
Patients with infections or suspected infections [may exacerbate infections] (see Important Precautions as follows).
Patients with a history of tuberculosis [may activate tuberculosis; thus, pay careful attention to look for onset of tuberculosis by having patients undergo periodic chest X-ray examinations or other tests] (see Important Precautions as follows).
Patients with depression, in a state of depression, or with such a history or patients with a history of suicidal ideation or suicidal attempt [patients may experience suicidal ideation or attempt suicide (see Other Precautions as follows).
Patients with active Crohn's disease [may exacerbate symptoms] (see Important Precautions as follows).
Elderly patients (see Use in the Elderly as follows).
Important Precautions: LUMICEF is associated with increased risks of infections. Thus, patients undergoing treatment with LUMICEF should be observed carefully, with attention paid to any onset or worsening of infections. Instruct patients to contact their attending physician promptly should any signs or symptoms of infection develop. Moreover, in the event of a serious infection, take appropriate actions. (See Clinically significant adverse reactions under Adverse Reactions).
Before administering LUMICEF, confirm whether a patient has a tuberculous infection by detailed medical interview about tuberculosis and performing a chest X-ray exam, an interferon-γ release assay or a tuberculin test, and a chest CT scan, as appropriate, among other tests. Consult a physician who is experienced in treating tuberculosis if the patient has a history of tuberculosis or a suspected tuberculous infection. Any of the following patients, in principle, should be treated with an anti-tuberculosis drug before receiving LUMICEF.
Patients whose chest imaging results show shadows consistent with or presumed to be old tuberculosis.
Patients with a medical history of tuberculosis (including extrapulmonary tuberculosis).
Patients whose interferon-γ release assay, tuberculin test, or any other exam shows a strong suspicion of existing infection.
Patients with a history of close contact with a tuberculosis patient.
Furthermore, perform appropriate tests such as chest X-ray regularly to closely monitor potential onset of tuberculosis in patients even while they are undergoing treatment with LUMICEF, and instruct patients to contact their attending physician promptly should they develop symptoms indicating suspected tuberculosis (such as persistent coughs, weight decreased, or fever, among other symptoms).
For patients who have a confirmed diagnosis of active tuberculosis, the tuberculosis treatment should be given priority, with the LUMICEF treatment withheld. (See CONTRAINDICATIONS and Careful Administration as previously mentioned).
There have been reports of events related to worsening of Crohn's disease in non-Japanese clinical studies conducted in subjects with Crohn's disease. Observe patients with active Crohn's disease carefully before administering LUMICEF and be mindful of possible worsening of Crohn's disease. Instruct patients to contact their attending physician promptly should any worsening of symptoms is noted. Moreover, in the event of worsened Crohn's disease, take appropriate actions. (See Careful Administration as previously mentioned).
There have been reports of malignant skin and non-skin tumors in clinical studies. Although it is unclear whether they are causally related to LUMICEF, be mindful of possible onset of malignant tumors. (See Pharmacology: Clinical Studies under Actions).
A risk of developing infection associated with live vaccines cannot be ruled out. Thus, no live vaccines are to be given to patients undergoing treatment with LUMICEF.
The safety and efficacy of the concomitant use of LUMICEF and another biologic have not been established. Any such concomitant use, therefore, should be avoided. Moreover, patients switching from another biologic to LUMICEF should be observed closely for signs of infection.
Patients who are allowed to self-administer LUMICEF should be given instructions on the injection procedure and the safe disposal procedure.
1) Self-administration should only be allowed under the control and direction of a physician after a careful assessment of the appropriateness by the physician, extensive education and training for the patient, understanding by the patient of the risks associated with LUMICEF treatment and countermeasures, and the confirmation that the patient is able to properly self-administer the drug. Furthermore, after beginning self-administration, patients are to suspend self-administration immediately if LUMICEF is suspected of causing adverse reactions such as infection or if they have difficulty with continuing self-administration. Physicians are to take appropriate actions such as placing such patients under careful physician-managed observation.
2) Provide patients with strict training and guidance to alert them not to reuse any used injection devices (with built-in needle) and to educate them on how to dispose the injection devices safely. Instruct patients on how to dispose all injection devices safely.
Other Precautions: In Japanese clinical studies, suicide attempt was reported in 1 of 177 subjects (0.6%). In non-Japanese clinical studies, suicidal ideation, suicide attempt, etc. were reported in 16 of 4,625 subjects (0.3%) exposed to brodalumab, and suicide was reported in 3 (0.06%). Moreover, in an non-Japanese clinical study in subjects with rheumatoid arthritis,Note) suicide was reported in 1 of 211 subjects (0.5%).
[As of the time of Japanese approval]
In Japanese and non-Japanese clinical studies in subjects with psoriasis, anti-brodalumab binding antibodies were noted in 3 of 177 Japanese subjects (1.7%) and in 122 of 4,461 non-Japanese subjects (2.7%), but no anti-brodalumab neutralising antibodies production has been reported. In non-Japanese clinical study in subjects with rheumatoid arthritis,Note) production of anti-brodalumab neutralising antibodies was reported in 2 of 211 subjects (0.9%).
[As of the time of Japanese approval]
The safety and efficacy of concomitant use with an immunosuppressant or phototherapy have not been established.
Note) The indication for treating rheumatoid arthritis has not been approved in Hong Kong.
Use in the Elderly: The elderly generally have reduced physiological functions. Observe such patients carefully and be mindful of possible adverse reactions such as infections.
Use in Children: Safety has not been established in low birth weight babies, neonates, babies, infants, or children (no clinical experience).
Use in Pregnancy & Lactation: Do not administer to women who are pregnant or may possibly be pregnant unless the expected therapeutic benefits of treatment are judged to outweigh the possible risks. (Safety of the treatment in pregnancy has not been established.)
Avoid breast feeding while receiving LUMICEF treatment. (It is unknown whether brodalumab penetrates into breast milk in humans, but animal experiments [monkeys] have indicated penetration into breast milk.)
Use In Pregnancy & Lactation
Use during Pregnancy, Delivery, or Lactation: Do not administer to women who are pregnant or may possibly be pregnant unless the expected therapeutic benefits of treatment are judged to outweigh the possible risks. (Safety of the treatment in pregnancy has not been established.)
Avoid breast feeding while receiving LUMICEF treatment. (It is unknown whether brodalumab penetrates into breast milk in humans, but animal experiments [monkeys] have indicated penetration into breast milk.)
Adverse Reactions
Of all subjects in the Japanese and non-Japanese safety evaluation studies combined (177 Japanese subjects with psoriasis vulgaris, psoriatic arthritis, pustular psoriasis, or psoriatic erythroderma; 4,625 non-Japanese subjects with psoriasis vulgaris or psoriatic arthritis; a total of 4,802 subjects), adverse reactions (including laboratory data abnormalities) occurred in 1,711 subjects (35.6%). Common adverse reactions (with an incidence of 1.5% or more) were upper respiratory tract infection (5.1%), nasopharyngitis (3.7%), headache (2.1%), arthralgia (2.1%), pruritus (1.9%), fatigue (1.7%), and oral candidiasis (1.6%).
[As of the time of Japanese approval]
Clinically significant adverse reactions: Serious infection (0.8%): Serious viral, bacterial, fungal, or other microbial infections may occur. Observe patients carefully and take appropriate actions when infections are suspected.
Neutrophil count decreased (0.7%): Neutrophil count decreased may occur. Observe patients carefully and take appropriate actions such as interrupting or discontinuing treatment when abnormalities are noted.
Serious hypersensitivity (0.02%): Serious hypersensitivity such as anaphylaxis may occur. Observe patients carefully; upon noting any abnormalities, immediately discontinue the injection and take appropriate actions.
Other adverse reactions: See Table 5.

Click on icon to see table/diagram/image
Caution For Usage
Precautions concerning Use: Route of administration: Use LUMICEF only by subcutaneous administration.
Administration: Before use, remove from the refrigerator and return to room temperature.
Do not inject areas of the skin that are sensitive or abnormal (scratch, redness, sclerosis, thickness, scaling, or other abnormalities), or sites of psoriasis.
It is recommended to administer the injection to the thigh, abdomen, or upper arm. Avoid repeated injections to the same site; use a different injection site for each injection.
LUMICEF is a single-use formulation; never reuse.
PRECAUTIONS FOR HANDLING: To avoid light exposure, store LUMICEF in its outer box. Moreover, continue to store protected from light even after the outer box has been opened.
Use immediately after opening the blister pack.
Storage
Store protected from light at 2°C to 8°C.
MIMS Class
ATC Classification
L04AC12 - brodalumab ; Belongs to the class of interleukin inhibitors. Used as immunosuppressants.
Presentation/Packing
Inj (pre-filled syringe) (colorless to pale yellow, transparent to slightly opaque liquid) 210 mg/1.5 mL x 1's.
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