KEVZARA

KEVZARA- sarilumab injection, solution
sanofi-aventis U.S. LLC

1 INDICATIONS AND USAGE

1.1 Rheumatoid Arthritis (RA)

KEVZARA^® is indicated for treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs (DMARDs).

1.2 Polymyalgia Rheumatica (PMR)

​ KEVZARA is indicated for treatment of adult patients with polymyalgia rheumatica who have had an inadequate response to corticosteroids or who cannot tolerate corticosteroid taper.

2 DOSAGE AND ADMINISTRATION

2.1 General Considerations Prior to Administration

Not Recommended for Concomitant Use with Biological DMARDS

The concurrent use of KEVZARA with biological DMARDs such as TNF antagonists, IL-1R antagonists, anti-CD20 monoclonal antibodies and selective co-stimulation modulators has not been studied. Avoid using KEVZARA with biological DMARDs because of the possibility of increased immunosuppression and increased risk of infection.

Recommended Evaluations Prior to Treatment

• Complete blood count (CBC): Treatment initiation with KEVZARA is not recommended in patients with an absolute neutrophil count (ANC) below 2000 per mm³ , or platelet count below 150,000 per mm³. Monitor laboratory parameters [see Warnings and Precautions (5.2)].
• Liver function tests (LFT): Treatment initiation with KEVZARA is not recommended in patients with or who have alanine transaminase (ALT) or aspartate aminotransferase (AST) above 1.5 times the upper limit of normal (ULN). Monitor laboratory parameters [see Dosage and Administration (2.5) and Warnings and Precautions (5.2)].
• Lipid parameters (total cholesterol, LDL cholesterol, HDL cholesterol and/or triglycerides): Assess lipid parameters at baseline. Monitor laboratory parameters [see Warnings and Precautions (5.2)].
• Active and latent tuberculosis infection evaluation: Prior to initiating KEVZARA, test patients for active and latent tuberculosis (TB). KEVZARA should not be administered to patients with active TB. If positive for latent infection, consider treating for TB prior to KEVZARA use [see Warnings and Precautions (5.1)].
• Evaluate for infections: Avoid KEVZARA use in patients with active infections [see Warnings and Precautions (5.1)].

2.2 Recommended Dosage for Rheumatoid Arthritis

The recommended dosage of KEVZARA is 200 mg once every two weeks given as a subcutaneous injection (see Dosage and Administration 2.1).

KEVZARA may be used as monotherapy or in combination with methotrexate (MTX) or other conventional DMARDs.

Modify the dosage as recommended in Table 1 if the patient develops neutropenia, thrombocytopenia, or liver enzyme abnormalities [see Dosage and Administration (2.5), Warnings and Precautions (5.2) and Adverse Reactions (6.1)].

2.3 Recommended Dosage for Polymyalgia Rheumatica

​ The recommended dosage of KEVZARA is 200 mg once every two weeks given as a subcutaneous injection, in combination with a tapering course of systemic corticosteroids [see Dosage and Administration (2.1)]. KEVZARA can be used as monotherapy following discontinuation of corticosteroids.

​ Discontinue KEVZARA if the patient develops neutropenia (using ANC results obtained at the end of the dosing interval), thrombocytopenia, or liver enzyme abnormalities [see Dosage and Administration (2.5), Warnings and Precautions (5.2) and Adverse Reactions (6.1)].

2.4 Preparation and Administration Instructions

• KEVZARA is intended for use under the guidance of a healthcare professional. A patient may self-inject KEVZARA or the patient’s caregiver may administer KEVZARA. Provide proper training to patients and/or caregivers on the preparation and administration of KEVZARA prior to use according to the Instructions for Use (IFU).
• Allow the pre-filled syringe to sit at room temperature for 30 minutes prior to subcutaneous injection. Do not warm KEVZARA in any other way.
• If using a pre-filled pen, allow the pre-filled pen to sit at room temperature for 60 minutes prior to subcutaneous injection. Do not warm KEVZARA in any other way.
• Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. KEVZARA 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 pre-filled syringe or pre-filled pen appears to be damaged.
• Instruct patients to inject the full amount in the syringe or pen (1.14 mL), which provides 200 mg or 150 mg of KEVZARA, according to the directions provided in the IFU.
• Rotate injection sites with each injection. Do not inject into skin that is tender, damaged, or has bruises or scars.

2.5 Dosage Modifications for Cytopenias, Abnormal Liver Enzymes, or Infections

​ Dosage Modifications for Patients with Rheumatoid Arthritis

• ​ Laboratory Abnormalities: Modify dosage in case of neutropenia, thrombocytopenia, or liver enzyme elevations as shown in Table 1 [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.2)]. For treatment initiation criteria, refer to the dosage recommendations for RA [see Dosage and Administration (2.1, 2.2)].

Table 1: Dosage Modifications due to Neutropenia, Thrombocytopenia, or Elevated Liver Enzymes in Patients with Rheumatoid Arthritis

​ Low Absolute Neutrophil Count (ANC)
​ Lab Value (cells/mm3)	Recommendation
​ ANC greater than 1,000	Maintain current dosage of KEVZARA.
​ ANC 500 to 1,000	Hold treatment with KEVZARA until ANC greater than 1,000.KEVZARA can then be resumed at 150 mg every two weeks and increased to 200 mg every two weeks as clinically appropriate.
​ ANC less than 500	Discontinue KEVZARA.
​ Low Platelet Count
​ Lab Value (cells/mm3)	Recommendation
​ 50,000 to 100,000	Hold treatment with KEVZARA until platelets greater than 100,000.KEVZARA can then be resumed at 150 mg every two weeks and increased to 200 mg every two weeks as clinically appropriate.
​ Less than 50,000	If confirmed by repeat testing, discontinue KEVZARA.
​ Liver Enzyme Abnormalities
​ Lab Value	Recommendation
​ ALT or AST greater than ULN to 3 times ULN	Consider dosage modification of concomitant DMARDs as clinically appropriate.
​ ALT or AST greater than 3 times ULN to 5 times ULN	Hold treatment with KEVZARA until ALT or AST less than 3 times ULN.KEVZARA can then be resumed at 150 mg every two weeks and increased to 200 mg every two weeks as clinically appropriate.
​ ALT or AST greater than 5 times ULN	Discontinue KEVZARA.

• ​ Infections: If a patient with RA develops a serious infection or an opportunistic infection, hold treatment with KEVZARA until the infection is controlled [see Warnings and Precautions (5.1)].

​ Dosage Modifications for Patients with Polymyalgia Rheumatica

• ​ Laboratory Abnormalities: Discontinue KEVZARA in patients with PMR who develop the following laboratory abnormalities [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.2)]:
  • ​ neutropenia (ANC below 1,000 per mm³ at the end of the dosing interval)
  • ​ thrombocytopenia (platelet count below 100,000 per mm³)
  • ​ AST or ALT elevations 3 times above the ULN
  ​ Dosage modifications have not been studied in patients with PMR with these conditions. For treatment initiation criteria, refer to the dosage recommendations for PMR [see Dosage and Administration (2.1, 2.3)].
• ​ Infections: If a patient with PMR develops a serious infection or an opportunistic infection, hold treatment with KEVZARA until the infection is controlled [see Warnings and Precautions (5.1)].