Skyrizi喜開悅

Skyrizi

risankizumab

Manufacturer:

AbbVie

Distributor:

The Glory Medicina
/
DKSH
Full Prescribing Info
Contents
Risankizumab.
Description
Each pre-filled syringe contains 75 mg risankizumab in 0.83 ml solution.
Risankizumab is a humanised immunoglobulin G1 (IgG1) monoclonal antibody selective to the interleukin (IL)-23 protein produced in Chinese Hamster Ovary cells using recombinant DNA technology.
Excipients with known effect: This medicinal product contains 68.0 mg sorbitol per 150 mg dose.
This medicinal product contains less than 1 mmol sodium (23 mg) per 150 mg dose, that is to say essentially 'sodium free'.
Excipients/Inactive Ingredients: Disodium succinate hexahydrate, Succinic acid, Sorbitol, Polysorbate 20, Water for injections.
Action
Pharmacotherapeutic group: Immunosuppressants, interleukin inhibitors. ATC code: L04AC.
Pharmacology: Pharmacodynamics: Mechanism of action: Risankizumab is a humanised immunoglobulin G1 (IgG1) monoclonal antibody that selectively binds with high affinity to the p19 subunit of human interleukin 23 (IL-23) cytokine without binding to IL-12 and inhibits its interaction with the IL-23 receptor complex. IL-23 is a cytokine that is involved in inflammatory and immune responses. By blocking IL-23 from binding to its receptor, risankizumab inhibits IL-23-dependent cell signalling and release of proinflammatory cytokines.
Pharmacodynamic effects: In a study of subjects with psoriasis, expression of genes associated with the IL-23/IL-17 axis was decreased in the skin after single doses of risankizumab. Reductions in epidermal thickness, infiltration of inflammatory cells, and expression of psoriatic disease markers were also observed in psoriatic lesions.
Clinical efficacy and safety: The efficacy and safety of risankizumab was assessed in 2,109 subjects with moderate to severe plaque psoriasis in four multicentre, randomised, double-blind studies (ULTIMMA-1, ULTIMMA-2, IMMHANCE, and IMMVENT). Enrolled subjects were 18 years of age and older with plaque psoriasis who had a body surface area (BSA) involvement of ≥10%, a static Physician Global Assessment (sPGA) score of ≥3 in the overall assessment (plaque thickness/induration, erythema, and scaling) of psoriasis on a severity scale of 0 to 4, a Psoriasis Area and Severity Index (PASI) score ≥12, and who were candidates for systemic therapy or phototherapy.
Overall, subjects had a median baseline PASI score of 17.8, a median BSA of 20.0%, and a median baseline DLQI score of 13.0. Baseline sPGA score was severe in 19.3% of subjects and moderate in 80.7% of subjects. A total of 9.8% of study subjects had a history of diagnosed psoriatic arthritis.
Across all studies, 30.9% of subjects were naïve to any systemic therapy (including non-biologic and biologic), 38.1% had received prior phototherapy or photochemotherapy, 48.3% had received prior non-biologic systemic therapy, 42.1% had received prior biologic therapy, and 23.7% had received at least one anti-TNF alpha agent for the treatment of psoriasis.
ULTIMMA-1 and ULTIMMA-2: ULTIMMA-1 and ULTIMMA-2 enrolled 997 subjects (598 randomised to risankizumab 150 mg, 199 to ustekinumab 45 mg or 90 mg [according to baseline weight], and 200 to placebo). Subjects received treatment at week 0, week 4, and every 12 weeks thereafter. The two co-primary endpoints in ULTIMMA-1 and ULTIMMA-2 were the proportion of subjects who achieved 1) PASI 90 response and 2) sPGA score of clear or almost clear (sPGA 0 or 1) at week 16 versus placebo. The results for the co-primary and other endpoints are presented in Table 1 and Figure 1. (See Table 1 and Figure 1.)

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Click on icon to see table/diagram/image

Examination of age, gender, race, body weight ≤130 kg, baseline PASI score, concurrent psoriatic arthritis, previous non-biologic systemic treatment, previous biologic treatment, and previous failure of a biologic did not identify differences in response to risankizumab among these subgroups.
Improvements were observed in psoriasis involving the scalp, the nails, and the palms and soles at week 16 and week 52 in subjects treated with risankizumab. (See Table 2.)

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Anxiety and depression, as measured by the Hospital Anxiety and Depression Scale (HADS), improved in the risankizumab group at week 16 compared with the placebo group.
Maintenance of response: In an integrated analysis of subjects receiving risankizumab in ULTIMMA-1 and ULTIMMA-2 for PASI 100 responders at week 16, 79.8% (206/258) of the subjects who continued on risankizumab maintained the response at week 52. For PASI 90 responders at week 16, 88.4% (398/450) of subjects maintained the response at week 52.
The safety profile of risankizumab with up to 77 weeks of exposure was consistent with the profile observed up to 16 weeks.
IMMHANCE: IMMHANCE enrolled 507 subjects (407 randomised to risankizumab 150 mg and 100 to placebo). Subjects received treatment at week 0, week 4 and every 12 weeks thereafter. Subjects who were originally on risankizumab and had a sPGA response of clear or almost clear at week 28 were re-randomised to continue risankizumab every 12 weeks or have treatment withdrawn.
At week 16, risankizumab was superior to placebo on the co-primary endpoints of sPGA of clear or almost clear (83.5% risankizumab vs 7.0% placebo) and PASI 90 (73.2% risankizumab vs 2.0% placebo).
Of the 31 subjects from the IMMHANCE study with latent tuberculosis (TB) who did not receive prophylaxis during the study, none developed active TB during the mean follow-up of 55 weeks on risankizumab.
Among subjects with sPGA of clear or almost clear at week 28 in IMMHANCE, 81.1% (90/111) of subjects re-randomised to continued treatment with risankizumab maintained this response at week 104 compared to 7.1% (16/225) who were re-randomised to withdrawal from risankizumab. Of these subjects, 63.1% (70/111) of subjects re-randomised to continued treatment with risankizumab achieved a sPGA clear response at week 104 compared to 2.2% (5/225) who were re-randomised to withdrawal from risankizumab.
IMMVENT: IMMVENT enrolled 605 subjects (301 randomised to risankizumab and 304 to adalimumab). Subjects randomised to risankizumab received 150 mg of treatment at week 0, week 4 and every 12 weeks thereafter. Subjects randomised to adalimumab received 80 mg at week 0, 40 mg at week 1 and 40 mg every other week through week 15. Starting at week 16, subjects who were receiving adalimumab continued or switched treatment based on response: <PASI 50 were switched to risankizumab; PASI 50 to <PASI 90 were re-randomised to either continue adalimumab or switch to risankizumab; PASI 90 continued to receive adalimumab.
Results are presented in Table 3. (See Table 3.)

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For subjects who had PASI 50 to <PASI 90 with adalimumab at week 16 and were re-randomised, differences in PASI 90 response rates between switching to risankizumab and continuing adalimumab were noted 4 weeks after re-randomisation (49.1% vs 26.8%, respectively).
Results 28 weeks after re-randomisation are presented in Table 4 and Figure 2. (See Table 4 and Figure 2.)

Click on icon to see table/diagram/image


Click on icon to see table/diagram/image

In 270 patients who switched from adalimumab to risankizumab without a washout period, the safety profile of risankizumab was similar to that in patients who initiated risankizumab after wash out of any prior systemic therapies.
Pharmacokinetics: Absorption: Risankizumab exhibited linear pharmacokinetics with dose-proportional increase in exposure across dose ranges of 18 to 300 mg and 0.25 to 1 mg/kg administered subcutaneously, and 200 to 1,200 mg and 0.01 to 5 mg/kg administered intravenously.
Following subcutaneous dosing of risankizumab, peak plasma concentrations were achieved between 3-14 days after dosing with an estimated absolute bioavailability of 89%. With dosing of 150 mg at week 0, week 4 and every 12 weeks thereafter, estimated steady-state peak and trough plasma concentrations are 12 and 2 μg/mL, respectively.
Distribution: The mean (±standard deviation) steady-state volume of distribution (Vss) of risankizumab was 11.4 (±2.7) L in Phase 3 studies in subjects with psoriasis, indicating that the distribution of risankizumab is primarily confined to the vascular and interstitial spaces.
Biotransformation: Therapeutic IgG monoclonal antibodies are typically degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgGs. Risankizumab is not expected to be metabolised by cytochrome P450 enzymes.
Elimination: The mean (±standard deviation) systemic clearance (CL) of risankizumab was 0.3 (±0.1) L/day in Phase 3 studies in subjects with psoriasis. The mean terminal elimination half-life of risankizumab ranged from 28 to 29 days in Phase 3 studies in subjects with psoriasis.
As an IgG1 monoclonal antibody, risankizumab is not expected to be filtered by glomerular filtration in the kidneys or to be excreted as an intact molecule in the urine.
Linearity/non-linearity: Risankizumab exhibited linear pharmacokinetics with approximately dose-proportional increases in systemic exposure (Cmax and AUC) in the evaluated dose ranges of 18 to 300 mg or 0.25 to 1 mg/kg subcutaneous administration in healthy subjects or subjects with psoriasis.
Drug interactions: A drug interaction study was conducted in subjects with plaque psoriasis to assess the effect of repeated administration of risankizumab on the pharmacokinetics of cytochrome P450 (CYP) sensitive probe substrates. The exposure of caffeine (CYP1A2 substrate), warfarin (CYP2C9 substrate), omeprazole (CYP2C19 substrate), metoprolol (CYP2D6 substrate) and midazolam (CYP3A substrate) following risankizumab treatment were comparable to their exposures prior to risankizumab treatment, indicating no clinically meaningful drug interactions through these enzymes.
Population pharmacokinetic analyses indicated that risankizumab exposure was not impacted by concomitant medications (metformin, atorvastatin, lisinopril, amlodipine, ibuprofen, acetylsalicylate and levothyroxine) used by some subjects with plaque psoriasis during the clinical studies.
Special populations: Paediatric patients: The pharmacokinetics of risankizumab in paediatric subjects has not been established.
Elderly patients: Of the 2,234 subjects with plaque psoriasis exposed to risankizumab, 243 were 65 years or older and 24 subjects were 75 years or older. No overall differences in risankizumab exposure were observed between older and younger subjects who received risankizumab.
Patients with renal or hepatic impairment: No specific studies have been conducted to determine the effect of renal or hepatic impairment on the pharmacokinetics of risankizumab. Based on population pharmacokinetic analyses, serum creatinine levels, creatinine clearance, or hepatic function markers (ALT/AST/bilirubin) did not have a meaningful impact on risankizumab clearance in subjects with psoriasis.
As an IgG1 monoclonal antibody, risankizumab is mainly eliminated via intracellular catabolism and is not expected to undergo metabolism via hepatic cytochrome P450 enzymes or renal elimination.
Body weight: Risankizumab clearance and volume of distribution increase as body weight increases which may result in reduced efficacy in subjects with high body weight (>130 kg). However, this observation is based on a limited number of subjects. No dose adjustment based on body weight is currently recommended.
Gender or race: The clearance of risankizumab was not significantly influenced by gender or race in adult subjects with plaque psoriasis. No clinically meaningful differences in risankizumab exposure were observed in Chinese or Japanese subjects compared to Caucasian subjects in a clinical pharmacokinetic study.
Toxicology: Preclinical safety data: Nonclinical data revealed no special hazard for humans based on repeat-dose toxicity studies including safety pharmacology evaluations, and a reproductive and developmental toxicity study in cynomolgus monkeys at doses of up to 50 mg/kg/week (producing exposures of about 70 times the clinical exposure at maximum recommended human dose [MRHD]).
Mutagenicity and carcinogenicity studies have not been conducted with risankizumab. In a 26-week chronic toxicology study in cynomolgus monkeys at doses of up to 50 mg/kg/week (about 70 times the clinical exposure at the MRHD), there were no pre-neoplastic or neoplastic lesions observed and no adverse immunotoxicity or cardiovascular effects were noted.
Indications/Uses
Skyrizi is indicated for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy.
Dosage/Direction for Use
Skyrizi is intended for use under the guidance and supervision of a physician experienced in the diagnosis and treatment of psoriasis.
Posology: The recommended dose is 150 mg (two 75 mg injections) administered by subcutaneous injection at week 0, week 4, and every 12 weeks thereafter.
Consideration should be given to discontinuing treatment in patients who have shown no response after 16 weeks of treatment. Some patients with initial partial response may subsequently improve with continued treatment beyond 16 weeks.
Missed dose: If a dose is missed, the dose should be administered as soon as possible. Thereafter, dosing should be resumed at the regular scheduled time.
Special populations: Elderly (aged 65 years and over): No dose adjustment is required (see Pharmacology: Pharmacokinetics under Actions).
There is limited information in subjects aged ≥65 years.
Renal or hepatic impairment: No specific studies were conducted to assess the effect of hepatic or renal impairment on the pharmacokinetics of Skyrizi. These conditions are generally not expected to have any significant impact on the pharmacokinetics of monoclonal antibodies and no dose adjustments are considered necessary (see Pharmacology: Pharmacokinetics under Actions).
Paediatric population: The safety and efficacy of Skyrizi in children and adolescents aged 6 to 18 years have not yet been established. No data are available.
There is no relevant use of Skyrizi in children aged below 6 years for the indication of moderate to severe plaque psoriasis.
Overweight patients: No dose adjustment is required (see Pharmacology: Pharmacokinetics under Actions).
Method of administration: Skyrizi is administered by subcutaneous injection. For each dose, the injections should be administered at different anatomic locations (such as thighs or abdomen), and not into areas where the skin is tender, bruised, erythematous, indurated or affected by psoriasis. Administration of Skyrizi in the upper, outer arm may only be performed by a healthcare professional or caregiver.
Patients may self-inject Skyrizi after training in subcutaneous injection technique. Patients should be instructed to inject 2 pre-filled syringes for the full 150 mg dose and to read the Instructions for use under Patient Counselling Information.
Overdosage
In the event of overdose, it is recommended that the patient be monitored for any signs or symptoms of adverse reactions and appropriate symptomatic treatment be instituted immediately.
Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in Description.
Clinically important active infections (e.g. active tuberculosis, see Precautions).
Special Precautions
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.
Infections: Risankizumab may increase the risk of infection.
In patients with a chronic infection, a history of recurrent infection, or known risk factors for infection, risankizumab should be used with caution. Treatment with risankizumab should not be initiated in patients with any clinically important active infection until the infection resolves or is adequately treated.
Patients treated with risankizumab should be instructed to seek medical advice if signs or symptoms of clinically important chronic or acute infection occur. If a patient develops such an infection or is not responding to standard therapy for the infection, the patient should be closely monitored and risankizumab should not be administered until the infection resolves.
Tuberculosis: Prior to initiating treatment with risankizumab, patients should be evaluated for tuberculosis (TB) infection. Patients receiving risankizumab should be monitored for signs and symptoms of active TB. Anti-TB therapy should be considered prior to initiating risankizumab in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed.
Immunisations: Prior to initiating therapy with risankizumab, completion of all appropriate immunisations should be considered according to current immunisation guidelines. If a patient has received live vaccination (viral or bacterial), it is recommended to wait at least 4 weeks prior to starting treatment with risankizumab. Patients treated with risankizumab should not receive live vaccines during treatment and for at least 21 weeks after treatment (see Pharmacology: Pharmacokinetics under Actions).
Hypersensitivity: If a serious hypersensivity reaction occurs, administration of risankizumab should be discontinued immediately and appropriate therapy initiated.
Excipients with known effect: This medicinal product contains 68.0 mg sorbitol per 150 mg dose.
The additive effect of concomitantly administered products containing sorbitol (or fructose) and dietary intake of sorbitol (or fructose) should be taken into account.
This medicinal product contains less than 1 mmol sodium (23 mg) per 150 mg dose, that is to say essentially 'sodium free'.
Effects on ability to drive and use machines: Risankizumab has no or negligible influence on the ability to drive and use machines.
Use In Pregnancy & Lactation
Women of childbearing potential: Women of childbearing potential should use an effective method of contraception during treatment and for at least 21 weeks after treatment.
Pregnancy: There are no or limited amount of data (less than 300 pregnancy outcomes) from the use of risankizumab in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. As a precautionary measure, it is preferable to avoid the use of risankizumab during pregnancy.
Breast-feeding: It is unknown whether risankizumab is excreted in human milk. Human IgGs are known to be excreted in breast milk during the first few days after birth, which decreases to low concentrations soon afterwards; consequently, a risk to the breast-fed infant cannot be excluded during this short period. A decision should be made whether to discontinue/abstain from risankizumab therapy, taking into account the benefit of breast-feeding to the child and the benefit of risankizumab therapy to the woman.
Fertility: The effect of risankizumab on human fertility has not been evaluated. Animal studies do not indicate direct or indirect harmful effects with respect to fertility.
Adverse Reactions
Summary of the safety profile: The most frequently reported adverse reactions were upper respiratory infections, which occurred in 13% of patients.
Tabulated list of adverse reactions: Adverse reactions for risankizumab from clinical studies (Table 5) are listed by MedDRA system organ class and are based on 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); and very rare (< 1/10,000). (See Table 5.)

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Description of selected adverse reactions: Infections: Over the entire psoriasis programme including long-term exposure to risankizumab, the rate of infections was 75.5 events per 100 subject-years. The majority of cases were non-serious and mild to moderate in severity and did not lead to discontinuation of risankizumab. The rate of serious infections was 1.7 events per 100 subject-years (see Precautions).
Immunogenicity: As with all therapeutic proteins, there is the potential for immunogenicity with risankizumab. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay.
For subjects treated with risankizumab at the recommended clinical dose for up to 52 weeks in psoriasis clinical trials, treatment-emergent anti-drug antibodies and neutralising antibodies were detected in 24% (263/1,079) and 14% (150/1,079) of evaluated subjects, respectively.
For most subjects, antibodies to risankizumab including neutralising antibodies were not associated with changes in clinical response or safety. Among the few subjects (approximately 1%; 7/1,000 at week 16 and 6/598 at week 52) with high antibody titers (>128), clinical response appeared to be reduced. The incidence of injection site reactions is numerically higher in the anti-drug antibody-positive compared with anti-drug antibody-negative groups over short-term (16 weeks: 2.7% vs 1.3%) and longer term treatment (>52 weeks: 5.0% vs 3.3%). The injection site reactions were all mild to moderate in severity, none were serious, and none led to discontinuation of risankizumab.
Elderly: There is limited safety information in subjects aged ≥65 years.
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 according to the local requirements.
Drug Interactions
Risankizumab is not expected to undergo metabolism by hepatic enzymes or renal elimination. Drug interactions between risankizumab and inhibitors, inducers, or substrates of drug metabolising enzymes are not expected and no dose adjustment is needed (see Pharmacology: Pharmacokinetics under Actions).
Concomitant immunosuppressive therapy or phototherapy: The safety and efficacy of risankizumab in combination with immunosuppressants, including biologics, or phototherapy have not been evaluated.
Caution For Usage
Special precautions for disposal and other handling: Before injecting, patients may remove the carton from the refrigerator and allow to reach room temperature out of direct sunlight (15 to 30 minutes) without removing the pre-filled syringes from the carton.
Prior to use, a visual inspection of each pre-filled syringe is recommended. The solution should be colourless to slightly yellow and clear to slightly opalescent. It may contain a few translucent to white product-related particles. Skyrizi should not be used if the solution is cloudy or discoloured, or contains large particles.
Two pre-filled syringes should be injected for the full 150 mg dose. Comprehensive instructions for use are provided in the package leaflet.
Each pre-filled syringe is for single use only.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
Incompatibilities: In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
Storage
Store in a refrigerator (2°C - 8°C). Do not freeze.
Keep the pre-filled syringes in the outer carton in order to protect from light.
Patient Counseling Information
Instructions for use for patients before injecting Skyrizi yourself: Please read all as follows before using Skyrizi.
Important information to know before you inject Skyrizi: You should receive training on how to inject Skyrizi before giving an injection. Talk to your doctor, pharmacist or nurse if you need help.
Mark the dates on your calendar so you know when to inject Skyrizi.
Keep Skyrizi in the original carton to protect the medicine from light until it is time to use it.
Do not inject if the liquid is cloudy or contains flakes or large particles. The liquid should look clear to slightly yellow and may contain tiny white or clear particles.
Wait to remove the needle cover until just before the injection.
Return this medicine to the pharmacy: if the expiry date (EXP) has passed; if the liquid has ever been frozen (even if thawed); if the syringe has been dropped or damaged; if the syringe paper tray cover is broken or missing.
For a more comfortable injection: Take the carton out of the refrigerator and leave it at room temperature, out of direct sunlight, for 15 to 30 minutes before injecting.
Skyrizi should not be warmed in any other way (for example, in a microwave or in hot water).
Keep the syringes in the carton until ready to inject.
Follow the steps as follows each time you use Skyrizi: STEP 1: Place the following items on a clean, flat surface: 2 pre-filled syringes and 2 alcohol pads (included in the carton), 2 cotton balls or gauze pads (not included in the carton), Special disposal container (not included in the carton).
Wash and dry your hands.
Start with one syringe for the first injection.
For a full dose, 2 injections are required, one after the other.
STEP 2: Choose from these 3 areas to inject: front of left thigh, front of right thigh, your belly (abdomen) at least 5 cm from your belly button (navel).
For the second syringe, inject at least 3 cm away from the first injection. Do not inject into the same place.
Before each injection, wipe where you will inject in a circular motion with an alcohol pad.
Do not inject through clothes.
Do not inject into skin that is sore, bruised, red, hard, scarred, or has stretch marks.
Do not inject into areas affected by psoriasis.
STEP 3: Hold the syringe with the covered needle pointing down.
Check the liquid in the syringe.
It is normal to see bubbles in the window.
The liquid should look clear to slightly yellow and may contain tiny white or clear particles.
Do not use if the liquid is cloudy or contains flakes or large particles.
STEP 4: Removing the needle cover: Hold the syringe in one hand.
With the other hand, gently pull the needle cover straight off.
You may see a drop of liquid at the end of the needle. This is normal.
Throw away the needle cover.
Do not touch the needle with your fingers or let the needle touch anything.
STEP 5: Hold the body of the syringe in one hand between the thumb and index finger, like you would a pencil.
Gently pinch the area of cleaned skin with your other hand and hold it firmly.
Insert the needle all the way into the skin at about a 45-degree angle using a quick, short movement. Keep the syringe steady at the same angle.
STEP 6: Slowly push the plunger all the way in until all of the liquid is injected.
Pull the needle out of the skin while keeping the syringe at the same angle.
Slowly take your thumb off the plunger. The needle will then be covered by the needle guard.
The needle guard will not activate unless all the liquid is injected.
Speak to your doctor, pharmacist or nurse if you think you have not given a full dose.
Press a cotton ball or gauze pad where you have injected and hold for 10 seconds.
Do not rub the skin where you have injected. You may have slight bleeding from where you injected. This is normal.
STEP 7: For a full dose, two injections are needed, one after the other.
Repeat Steps 2 through 6 with the second syringe.
Inject the second syringe straight after the first injection but at least 3 cm away from the first injection.
STEP 8: Throw away used syringes in a special disposal container.
Do not throw away used syringes in the household waste.
Your doctor, pharmacist or nurse will tell you how to return the full special disposal container.
ATC Classification
L04AC18 - risankizumab ; Belongs to the class of interleukin inhibitors. Used as immunosuppressants.
Presentation/Packing
Soln for inj (pre-filled syringe) 75 mg/0.83 mL (colourless to slightly yellow and clear to slightly opalescent) x 2's.
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