Certolizumab Pegol

In this article, we will discuss about Certolizumab Pegol (Dosage). So, let’s get started.

Certolizumab Pegol (CIMZIA®)

CIMZIA (certolizumab pegol) is a TNF blocker. Certolizumab pegol (CIMZIA®) is a recombinant, humanized antibody Fab’ fragment, with specificity for human tumor necrosis factor alpha (TNFα), conjugated to an approximately 40kDa polyethylene glycol (PEG2MAL40K). The Fab’ fragment is manufactured in E.coli and is subsequently subjected to purification and conjugation to PEGAMAL40K, to generate certolizumab pegol. The Fab’ fragment is composed of a light chain with 214 amino acids and a heavy chain with 229 amino acids. The molecular weight of certolizumab pegol is approximately 91 kiloDaltons.

Certolizumab pegol (CIMZIA®) is supplied as either a sterile, white, lyophilized powder for solution or as a sterile, solution in a single-use prefilled I mL glass syringe for subcutaneous injection. After reconstitution of the lyophilized powder with 1 mL sterile Water for Injection, USP, the resulting pH is approximately 5.2. Each single-use vial provides approximately 200 mg certolizumab pegol, 0.9 ing lactic acid, 0.1 mg polysorbate, and 100 mg sucrose.

Each single-use prefilled syringe of Certolizumab pegol (CIMZIA®) delivers 200 mg in 1 mL of solution with a pH of approximately 4.7 for subcutaneous use. Each 1 mL syringe of CIMZIA contains certolizumab pegol (200 mg), sodium acetate (1.36 mg), sodium chloride (7.31 mg), and Water for Injection, USP.

Certolizumab pegol (CIMZIA®) is a clear to opalescent solution that is colorless to pale yellow and essentially free from particulates. No preservatives are present.

Mechanism of Action

Certolizumab pegol binds to human TNFα with a KD of 90pM. TNF is a key pro-inflammatory cytokine with a central role in inflammatory processes. Certolizumab pegol selectively neutralizes TNFα (IC90 of 4 ng/mL for inhibition of human TNFα in the in vitro L929 murine fibrosarcoma cytotoxicity assay) but does not neutralize lymphotoxin α (TNFβ). Certolizumab pegol cross-reacts poorly with TNF from rodents and rabbits, therefore in vivo efficacy was evaluated using animal models in which human
TNFα was the physiologically active molecule.

Certolizumab pegol was shown to neutralize membrane-associated and soluble human TNFα in a
dose-dependent manner. Incubation of monocytes with certolizumab pegol resulted in a dose-dependent
inhibition of LPS-induced TNFα and IL-1β production in human monocytes.

Certolizumab pegol does not contain a fragment crystallizable (Fc) region, which is normally present in a complete antibody, and therefore does not fix complement or cause antibody-dependent cell-mediated cytotoxicity in vitro. It does not induce apoptosis in vitro in human peripheral blood-derived monocytes or lymphocytes, nor does certolizumab pegol induce neutrophil degranulation.

A tissue reactivity study was carried out ex vivo to evaluate potential cross-reactivity of certolizumab pegol with cryosections of normal human tissues. Certolizumab pegol showed no reactivity with a designated standard panel of normal human tissues.

Dosage

Certolizumab Pegol (CIMZIA®) is administered by subcutaneous injection. Injection sites should be rotated and injections should not be given into areas where the skin is tender, bruised, red or hard. When a 400 mg dose is needed (given as two subcutaneous injections of 200 mg), injections should occur at separate sites in the thigh or abdomen.

The solution should be carefully inspected visually for particulate matter and discoloration prior to administration. The solution should be a clear colorless to yellow liquid, essentially free from particulates and should not be used if cloudy or if foreign particulate matter is present. Certolizumab Pegol (CIMZIA®) does not contain preservatives; therefore, unused portions of drug remaining in the syringe or vial should be discarded.

Crohn’s Disease

The recommended initial adult dose of CIMZIA is 400 mg (given as two subcutaneous injections of 200 mg) initially, and at Weeks 2 and 4. In patients who obtain a clinical response, the recommended maintenance regimen is 400 mg every four weeks.

Rheumatoid Arthritis

The recommended dose of Certolizumab Pegol (CIMZIA®) for adult patients with rheumatoid arthritis is 400 mg (given as two subcutaneous injections of 200 mg) initially and at Weeks 2 and 4, followed by 200 mg every other week. For maintenance dosing, Certolizumab Pegol (CIMZIA®) 400 mg every 4 weeks can be considered.

Psoriatic Arthritis

The recommended dose of Certolizumab Pegol (CIMZIA®) for adult patients with psoriatic arthritis is 400 mg (given as 2 subcutaneous injections of 200 mg each) initially and at week 2 and 4, followed by 200 mg every other week. For maintenance dosing, Certolizumab Pegol (CIMZIA®) 400 mg every 4 weeks can be considered.

Ankylosing Spondylitis

The recommended dose of Certolizumab Pegol (CIMZIA®) for adult patients with ankylosing spondylitis is 400 mg (given as 2 subcutaneous injections of 200 mg each) initially and at weeks 2 and 4, followed by 200 mg every 2 weeks or 400 mg every 4 weeks.

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