Drug information of Sarilumab

Mechanism of effect

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

Pharmacodynamic

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

Peak plasma time: 2-4 days

Peak plasma concentration: 20 mg/L (150 mg SC q2Weeks); 35.6 mg/L (200 mg SC q2Weeks)

Minimum plasma concentration: 6.35 mg/L (150 mg SC q2Weeks); 16.5 mg/L (200 mg SC q2Weeks)

AUC: 202 mg·day/L (150 mg SC q2Weeks); 395 mg·day/L (200 mg SC q2Weeks)

Steady state: Reached in 14-16 weeks

Distribution

Vd: 7.3 L

Metabolism

Expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG

Elimination

Half-life: 10 days (200 mg q2wk); 8 days (150 mg q2wk)

Excretion: Monoclonal antibodies are not eliminated via renal or hepatic pathways

Drug indications

artirit rhomatoid

Dosage

200 mg SC q2wk

May be used as monotherapy or in combination with methotrexate (MTX) or other conventional DMARDs

Drug contraindications

Hypersensitivity to this drug

Side effects

thrombocytopenia , Injection-site reaction , Leukopenia

Interactions

Levamisole , Primidone , Theophyline , Tacrolimus , Trastuzumab , Disopyramide , Sirolimus , Anthrax vaccine , Typhoid vaccine (live), oral , Yellow fever vaccine , Varicella-Zoster Vaccines , Quinine , Mechlorethamine , Fosphenytoin , Ofatumumab , Zoster Vaccines , Clonidine , Quinidine , Measles vaccine , Rubella Vaccines , Mumps vaccine , Valproic acid , Cyclosporine , Phenobarbital , Phenytoin , Lomustine , Warfarin , Carbamazepine , Adenovirus types 4 and 7 live, oral , Doravirine , cholera vaccine live , Clorazepate , Cabozantinib , Cariprazine , Cobimetinib , Temsirolimus , Remdesivir , Meningococcal conjugate vaccine , Venetoclax , Benralizumab , RESLIZUMAB , alirocumab

Alerts

• Use of sarilumab increases risk for developing serious infections that may lead to hospitalization or death
• Opportunistic infections reported
• Most patients who developed infections were taking concomitant immunosuppressants (eg, methotrexate, corticosteroids)
• Avoid use in patients with active infection
• Closely monitor for signs and symptoms of infection during treatment; if a serious infection develops, interrupt sarilumab therapy until the infection is controlled
• Consider the risks and benefits of using sarilumab before initiating in patients with chronic or recurrent infection; a history of opportunistic infections, underlying conditions, in addition to RA, that may predispose them to infection, have been exposed to tuberculosis, or lived in or traveled to areas of endemic tuberculosis or endemic mycoses

• Reported infections include

  • Active tuberculosis, which may present with pulmonary or extrapulmonary disease; test for latent TB before and during therapy; treatment for latent infection should be initiated before sarilumab is started; closely monitor patients for the development of signs and symptoms of TB including patients who tested negative for latent TB infection prior to initiating therapy
  • Invasive fungal infections (eg, candidiasis, pneumocystis); patients with invasive fungal infections may present with disseminated, rather than localized, disease
  • Bacterial, viral, and other infections due to opportunistic pathogens

  • Serious and sometimes fatal infections due to bacterial, mycobacterial, invasive fungal, viral, or other opportunistic pathogens have been reported (see Black Box Warnings)

    GI perforations reported in clinical studies, primarily as complications of diverticulitis; GI perforation risk may be increased with concurrent diverticulitis or concomitant use of NSAIDs or corticosteroids

    Immunosuppression may result in an increased risk of malignancies

    Hypersensitivity reactions reported

    Not recommended with active hepatic disease or hepatic impairment

Points of recommendation

SC Preparation

Remove from refrigerator and allow to sit at room temperature for 30 minutes (prefilled syringes) or 60 minutes (prefilled pen) y

Visually inspect syringe for particulate matter and discoloration prior to administration

Solution should be clear and colorless to pale yellow; do not use if the solution is cloudy, discolored, or contains particles, or if any part of the prefilled syringe appears to be damaged

SC Administration

Patient may self-inject or the patient's caregiver may administer after properly instructed

Instruct patients to inject the full amount in the syringe (1.14 mL), which provides 200 mg or 150 mg

Rotate injection sites with each injection; do not inject into skin that is tender, damaged, or has bruises or scars

Do not rub the injection site

Storage

Refrigerate at 36-46°F (2-8°C) in original carton to protect from light

Do not freeze

If needed, may store at room temperature up to 77°F (25°C) up to 14 days in the outer carton; do not store above 77°F (25°C)

Pregnancy level

HAVE NOT BEEN ESTABLISHED

Limited human data in pregnant women are not sufficient to inform drug-associated risk for major birth defects and miscarriage

Monoclonal antibodies are increasingly transported across the placenta as pregnancy progresses, with the largest amount transferred during the third trimester

Breast feeding warning

Unknown if distributed in human breast milk

Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition

Related drugs

Infliximab , Adalimumab , Golimumab , Tocilizumab , Canakinumab , Basiliximab , caplacizumab , Daclizumab , secukinumab , Alefacept , Ocrelizumab , Risankizumab , Guselkumab , Brodalumab , Ustekinumab , Tildrakizumab , sirukumab , RESLIZUMAB , mepolizumab

Tags