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Sarilumab

Generic name: sarilumab (sar IL ue mab)
Brand name: Kevzara, Kevzara Pre-filled Pen
Dosage forms: subcutaneous solution (150 mg/1.14 mL; 200 mg/1.14 mL)
Drug class: Antirheumatics, Interleukin inhibitors

What is sarilumab?

Sarilumab is used to treat moderate to severe rheumatoid arthritis in adults. Sarilumab is sometimes given together with other arthritis medicines.

Sarilumab is usually given after other treatments have failed.

Sarilumab (Kevzara) injection is used in the treatment of moderately to severely active rheumatoid arthritis that is poorly responsive to conventional treatment and DMARDs (disease-modifying antirheumatic drugs). It is a monoclonal antibody directed against IL-6 (interleukin-6) receptors.

Sarilumab may also be used for purposes not listed in this medication guide.

Sarilumab Uses:

• Rheumatoid arthritis:

  • Used for treating moderate to severely active rheumatoid arthritis in adults who show an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs.

Note: Do not initiate if ANC is <2,000/mm³, platelets are <150,000/mm³ or if ALT or AST are >1.5 times ULN.

Sarilumab (Kevzara) Dose in the treatment of Rheumatoid arthritis:

• Subcutaneous: 200 mg once 2 weekly.

Note: May be used as monotherapy or in combination with nonbiologic DMARDs. Not to be used in combination with biologic DMARDs.

 

Use in Children:

Not indicated.

 

Pregnancy Risk Category: C

• • • As pregnancy progresses, monoclonal antibodies are being increasingly transferred across the placenta. The largest amounts are transferred in the third trimester.
    • Based on animal data and the mechanism, maternal use may delay parturition.
    • Infants may experience a decreased immune response to sarilumab. Before administering live or live attenuated vaccines during pregnancy to infants exposed, it is important to consider the risks and benefits.
    • To monitor the pregnancy outcomes of women who have been exposed to sarilumab, a pregnancy registry was established. Registering with the registry should be encouraged by pregnant patients and health care professionals (877-3118972).

Use during breastfeeding:

• • It is unknown if breast milk contains sarilumab.
  • Breast milk however contains maternal immunoglobulins.
  • The manufacturer suggests that you consider the risks of infant exposure, the benefits to breastfeeding and the benefits to the mother when deciding whether to breastfeed during therapy.

 

Dose in Kidney Disease:

• CrCl 30 to 90 mL/minute:
  • Dosage adjustment not necessary.
• CrCl <30 mL/minute:
  • No dosage adjustments have been provided in the manufacturer’s labeling (has not been studied).

 

Dose in Liver disease:

• Hepatic impairment prior to treatment initiation:

  • No dosage adjustments have been provided in the manufacturer’s labeling (has not been studied). In patients with active hepatic disease or hepatic impairment, the use of sarilumab is not recommended.

• Hepatotoxicity during treatment:

  • ALT >1 to ≤3 x ULN:
    • Concomitant DMARDs should be adjusted as appropriate.
  • ALT >3 to ≤5 x ULN:
    • Interrupt therapy; resume at 150 mg once every 2 weeks once ALT is <3 x ULN,  (may increase to 200 mg once every 2 weeks as clinically appropriate).
  • ALT >5 x ULN: Discontinue the treatment.

 

Common Side Effects of Sarilumab (Kevzara):

• Hepatic:

  • Increased Serum ALT
  • Increased Serum AST

Less Common Side Effects of Sarilumab (Kevzara):

• Dermatologic:

  • Injection Site Pruritus

• Endocrine & Metabolic:

  • Hypertriglyceridemia

• Gastrointestinal:

  • Oral Herpes

• Genitourinary:

  • Urinary Tract Infection

• Hematologic & Oncologic:

  • Neutropenia
  • Leukopenia
  • Change in Platelet Count

• Immunologic:

  • Antibody Development

• Local:

  • Injection Site Reaction
  • Erythema at Injection Site

• Respiratory:

  • Upper Respiratory Tract Infection
  • Nasopharyngitis

Frequency of side effects not defined:

• Dermatologic:

  • Cellulitis

• Respiratory:

  • Pneumonia

 

Contraindications to Sarilumab (Kevzara):

• • • Hypersensitivity to sarilumab and any other component of the formulation

Warnings and precautions

• • Perforation of the GI:

    • There have been cases of GI perforation, most often secondary to diverticulitis and concomitant use NSAIDs or steroids therapy.
    • New abdominal symptoms should be monitored.

  • Hematologic effects

    • This condition can cause neutropenia or thrombocytopenia, which may require treatment interruption, dose modification or discontinuation.
    • It is important to monitor neutrophils and platelets.
    • Patients with ANC less than 2,000/mm3 and a platelet count less than 150,000/mm3 should not receive treatment. Treatment should be stopped if ANC falls below 500/mm3 and platelet count less than 50,000/mm3.

  • Hepatotoxicity:

    • Sarilumab can cause transaminase elevations. Before and during therapy, liver function should always be checked.
    • Patients with ALT or AST greater than 1.5 times the ULN should not receive treatment. If ALT exceeds 5x the ULN, it should be stopped.
    • Transaminase elevations are usually reversible, and do not cause clinically apparent hepatic injuries. Patients who receive concomitant hepatotoxic medications (eg methotrexate) are at increased risk for developing transaminase elevations.

  • Hyperlipidemia:

    • It is possible to experience an increase in LDL, triglycerides and/or HDL due to its use. Lipids should be checked approximately every 4-8 weeks, then every 6 months.

  • Hypersensitivity reactions

    • Reports of hypersensitivity reactions such as injection-site rash, skin rash and urticaria were made.
    • If symptoms of hypersensitivity reactions occur, it is important to seek medical attention.
    • Patients who have anaphylaxis or another hypersensitivity reaction to sarilumab should immediately stop taking the drug.

  • Infection: [US Boxed Warning]

    • Use of sarilumab has been associated with serious and possibly fatal infections (including active tuberculosis, invasive fungal and bacterial infections, as well as other opportunistic diseases).
    • Patients receiving concomitant immunosuppressive therapy are most likely to have the majority of serious infections.
    • Monitor patients closely for signs and symptoms of infection during treatment.
    • If you have a serious infection, stop taking sarilumab for a while to ensure that the infection is under control.
    • Before you start therapy, carefully consider the risks and benefits for patients with chronic or persistent infections, tuberculosis, tuberculosis-related conditions, history of or current infection, underlying conditions, patients who have traveled to areas with endemic mycosis or tuberculosis, or patients who are residing in such areas.
    • Cellulitis and pneumonia are the most prevalent serious infections. Other infections include tuberculosis and candidiasis.
    • It is possible to contract disseminated infections.
    • Sarilumab should never be given to patients with active infections, or localized infections.

  • Malignancy

    • Use of sarilumab could increase the likelihood of malignancy. However, the impact on the course and development of malignancies has not been fully determined. Clinical trials have shown that malignancies can be detected.

  • Tuberculosis: [US-Boxed Warning]

    • Tuberculosis (TB), whether pulmonary or extrapulmonary, has been reported using sarilumab. This includes both the reactivation and the induction of new infections.
    • Before starting treatment, TB risk factors should be evaluated and latent infection tests should be performed.
    • Before initiating sarilumab, latent TB should first be treated. Anti-TB treatment should also be considered in patients with a history or active TB if a suitable course of treatment is not possible.
    • Patients should monitor for signs and symptoms of TB during and after treatment. Some patients may contract an active infection if they test negative before starting therapy.

  • Viral activation:

    • Viral reactivation can be prevented by immunosuppressive biologic therapy.
    • Herpes zoster was reported in patients who received sarilumab.
    • Hepatitis B reactivation risks associated with sarilumab treatment are unknown. Signs/symptoms of viral activation should be closely monitored.

  • Hepatic impairment

    • Patients with active hepatic disease and hepatic impairment should not use this product.

 

Monitoring parameters:

• Screening for latent TB screening prior to therapy initiation
• CBC(Neutrophils, platelets), ALT/AST (prior to therapy, 4 to 8 weeks after the start of therapy, and every 3 months thereafter)
• Additional liver function tests as indicated clinically (eg, bilirubin)
• Lipid panel (4 to 8 weeks after initiation and approximately every 6 months during therapy)
• Signs/symptoms of infection (prior to, during, and after therapy)
• Hypersensitivity reaction
• GI perforation

 

How to administer Sarilumab (Kevzara)?

Subcutaneously:

• Administer subcutaneously and keep rotating injection sites; may be injected into the thigh, abdomen (2-inch area around the navel should be avoided), or outer area of the upper arm.
• The prefilled syringe and prefilled pen should be allowed to sit at room temperature for 30 or 60 minutes, respectively, prior to use; not to be warmed in any other way. The color of the solution should be clear and colorless to pale yellow; do not shake.
• The full amount should be administered in the prefilled syringe or prefilled pen; not to be administered if the window on the pen is solid yellow as it indicates that the pen has been already used). Not to be injected into the skin that is tender, damaged, or has bruises or scars.

 

Mechanism of action of Sarilumab (Kevzara):

It acts as an interleukin-6 antagonist (IL-6), binding to both membrane-bound and soluble IL-6 receptors. Inflammatory stimuli can induce endogenous IL-6, and mediate a variety immunological responses.

The synovial and endothelial cells produce IL-6, which is localized in the joints that are affected by inflammatory processes like rheumatoid. Sarilumab inhibits IL-6 receptors, which results in a decrease in CRP.

Half-life eliminationConcentration is a prerequisite

• 200mg every 2 weeks: Maximum of ten days
• 150 mg twice weekly for up to eight days

Time to reach peak2 – 4 Days

Excretion:

• Concentrations lower:
  • Primarily eliminated via the non-saturable, linear proteolytic pathway.
• High concentrations
  • Predominantly eliminated through a non-linear, saturable targetmediated pathway.

 

International Brand Names of Sarilumab:

• Kevzara

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