KEVZARA Solution for Injection in Pre-filled Pen 200mg

Sarilumab

Source of information: Drugbank (External Link). Last updated on: 3rd July 18
*Trade Name used in the content below may not be the same as the HSA-registered product.

Active Ingredient / Synonyms

REGN88 | SAR153191 | Sarilumab |

Description

Sarilumab is a fully human anti-IL-6R monoclonal IgG1 antibody that binds to both membrane bound and soluble interleukin 6 (IL-6) receptor forms, thus blocking the cis- and trans-inflammatory signalling cascades of IL-6 [A27262]. Sarilumab was developped by Sanofi and Regeneron Pharmaceuticals, Inc; it was US FDA-approved in May 2017 and followed by EU approval in June 2017 for the treatment of moderate to severe Rheumatoid Arthritis (RA) in combination with methotrexate [A27265]. RA is a chronic inflammatory disease characterized by polyarthritis and its treatment has been challenged by the different response in every patient [A27264]. Subcutaneous administration of Sarilumab has been shown to decrease acute-phase reactant levels and improve in clinical RA symptoms [A27263].

Indication

Indicated for modere to severe reactive RA in adult patients who are irresponsive, respond inadequately or present intolerance to disease-modifying anti-rheumatic drugs (DMARDs) or tumor necrosis factor (TNF) antagonists. It is indicated to be used in combination with methotrexate (MTX) or as a monotherapy when there is intolerance to MTX or MTX administration is inappropriate.

Mechanism of Action

Sarilumab is a human recombinant IgG1 antibody that binds to both forms of interleukin 6 receptors (IL-6R), thus inhibiting the IL-6-mediated signaling. IL-6 is known to be a pleiotropic cytokine that activates immune cells (T and B cells), as well as hepatocytes for the release of acute phase proteins like CRP, serum amyloid A and fibrinogen which are biomarkers of RA activity. IL-6 is also found in synovial fluid and plays a major role in the pathological inflammation and joint destruction features of RA. Thus, it is used for the treatment of RA due to its ability to inhibit intra-articular and systemic IL-6 signaling [L1000, L1001, FDA file].

Pharmacodynamics

Single-dose subcutaneous administration of Sarilumab produced a rapid reduction of CRP levels, leading to normal levels after two weeks of treatment. Peak reduction in the absolute neutrophile count was observed after 3 to 4 days of treatment followed by a recovery to baseline levels. It is observed a decrease in fibrinogen and serum amyloid A as well as an increase in hemoglobin and serum albumin.

Pharmacokinetics

Absorption:

Sarilumab is shown to be well absorbed in RA patients after single SC administration with a maximum of serum concentration presented after 2 to 4 days. For the 150 mg every two weeks dose regimen, the AUC, Cmin and Cmax of sarilumab were 202 ± 120 mg.day/L, 6.35 ± 7.54 mg/L, and 20.0 ± 9.20 mg/L, respectively. For the 200 mg every two weeks dose regimen, the AUC, Cmin and Cmax of sarilumab were 395 ± 207 mg.day/L, 16.5 ± 14.1 mg/L, and 35.6 ± 15.2 mg/L, respectively [L1001, FDA file].

Distribution:

In patients with RA, the apparent volume of distribution at steady state was 7.3 L [L1001, FDA file].

Metabolism:

The metabolism of Sarilumab has not been characterized. As it is a monoclonal antibody, It is thought to be degraded into small peptides and amino acids [FDA file].

Elimination:

At high concentrations, Sarilumab is thought to be eliminated predominantly through a non-saturated proteolytic pathway, while at lower concentrations, the elimination will be done by saturable target-mediated elimination [A27262].

Half-life

The half life will depend on the administered concentration. At 200 mg every 2 weeks, half-life is up to 10 days in patients with RA at steady state. At 150 mg every 2 weeks, half-life is up to 8 days in patients with RA at steady state. After the last st

Clearance

Sarilumab is not eliminated via renal or hepatic pathways. RA patients have shown a trend toward higher clearance in presence of anti-sarilumab antibodies [FDA file].

Toxicity

Repeat dose exposure has been shown to produce a partially reversible decrease in neutophil count and a reversible decrease in fibrinogen [L1000].

References

  1. Health Science Authority of Singapore - Reclassified POM
  2. Drugbank

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Approval Information

KEVZARA Solution for Injection in Pre-filled Pen 200mg was registered with Health Science Authority of Singapore by SANOFI-AVENTIS SINGAPORE PTE LTD. It is marketed with the registration number of SIN15738P with effective from 2019-07-08.

This product contains 200mg of Sarilumab in the form of INJECTION, SOLUTION.

The medicine was manufactured by Sanofi Winthrop Industrie in FRANCE

It is a Presciption Only Medicine which can only be obtained from a doctor or a dentist, or from a pharmacist with a prescription from a Singapore-registered doctor or dentist.

Anatomical Therapeutic Chemical (ATC) Classification

ATC Code: L04AC14

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