sarilumab

Absorption: Well absorbed via SUBQ injection.

Distribution: Well distributed to tissues.

Metabolism/Excretion: Metabolic pathway has not been defined. Elimination is predominantly through the linear, nonsaturable proteolytic pathway at high concentrations; at lower concentrations, elimination is predominately through nonlinear saturable target-mediated pathway.

Half-Life: 200 mg every 2 wk dose: up to 10 days; 150 mg every 2 wk dose: up to 8 days.

Time/Action Profile ⬆ ⬇

( plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
SUBQ	unknown	2–4 days	28–43 days

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Active infection;
Hepatic impairment;
ANC <2000/mm³ (<500/mm³ while on therapy) or platelet count <150,000/mm³ (<50,000/mm³ while on therapy);
Concurrent use with biological DMARDs.

Use Cautiously in:

Chronic or recurrent infection;
History of serious or opportunistic infection;
Exposure to tuberculosis (TB);
Lived in or traveled to areas of endemic tuberculosis or endemic mycoses;
Diverticulitis or concurrent use of NSAIDs or corticosteroids (↑ risk for GI perforation);
Severe renal impairment;
OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
Pedi: Safety and effectiveness not established in children;
Geri: ↑risk of infections in older adults.

Adv. Reactions/Side Effects ⬆ ⬇

GI: ↑liver enzymes, GI PERFORATION

Hemat: NEUTROPENIA, THROMBOCYTOPENIA

Local: injection site reactions

Metab: dyslipidemia

Misc: infection (including TB, disseminated fungal infections, and infections with opportunistic pathogens), hypersensitivity reactions, MALIGNANCY

Interactions ⬆ ⬇

Drug-drug:

May alter the activity of CYP450 enzymes; the effects of the following drugs should be monitored: cyclosporine, theophylline, warfarin, hormonal contraceptives, atorvastatin, and lovastatin.
May ↓ antibody response to and ↑ risk of adverse reactions to live-virus vaccines; avoid concurrent use.

Route/Dosage ⬆ ⬇

Rheumatoid Arthritis

SUBQ (Adults ): 200 mg every 2 wk.

Polymyalgia Rheumatica

SUBQ (Adults ): 200 mg every 2 wk (in combination with a corticosteroid taper). May be used as monotherapy once corticosteroid taper is completed.

Polyarticular Juvenile Idiopathic Arthritis

SUBQ (Adults and Children ≥63 kg): 200 mg every 2 wk.

Availability ⬆ ⬇

Solution for SUBQ injection (prefilled syringes and pens): 150 mg/1.14 mL; 200 mg/1.14 mL

Assessment ⬆ ⬇

Assess for signs of infection (fever, dyspnea, flu-like symptoms, diverticulitis symptoms, dysuria, cellulitis, wound infection) prior to injection. The most common are upper respiratory tract infections, bronchitis, and urinary tract infections. Signs and symptoms of inflammation may be lessened due to suppression from sarilumab. Infections may be fatal, especially in patients taking immunosuppressive therapy. If patient develops a serious infection, discontinue sarilumab until infection is controlled.
Monitor patients for active and latent TB, and consider treating latent TB if positive prior to sarilumab initiation.
Monitor for signs and symptoms of viral reactivation (herpes zoster [rash, blisters], hepatitis B [jaundice, dark urine, light-colored stools, fatigue, weakness, loss of appetite, nausea, vomiting, stomach pain]) during therapy.

Lab Test Considerations:

Verify negative pregnancy test prior to initiation.
- Assess lipid parameters approximately 4–8 wk after starting therapy and then every 6 mo. May ↑ LDL-C, HDL-C, and/or triglycerides.
Rheumatoid Arthritis: Monitor neutrophil count prior to, at 4 and 8 wk after starting, and every 3 mo during therapy. Base dose modifications on measures from end of dosing interval. If ANC >1000 cells/mm³, maintain current dose of sarilumab. If ANC 500–1000 cells/mm³, withhold therapy until ANC >1000 cells/mm³. Resume at 150 mg every 2 wk and ↑ to 200 mg every 2 wk as appropriate. If ANC <500 cells/mm³, discontinue sarilumab.
- Monitor platelet count prior to, at 4 and 8 wk after starting, and every 3 mo during therapy. If platelet count 50,000–100,000 cells/mm³, suspend therapy until platelets >100,000 cells/mm³. Resume at 150 mg every 2 wk and ↑ to 200 mg every 2 wk as appropriate.
- Monitor AST and ALT prior to, at 4 and 8 wk after starting, and every 3 mo during therapy. If ALT > upper limit of normal (ULN) to ≤3 times ULN, consider modifying dose of concurrent DMARDs as clinically appropriate. If ALT >3 times ULN to ≤5 times ULN, hold therapy until ALT <3 times ULN. Resume at 150 mg every 2 wk and ↑ to 200 mg every 2 wk as appropriate. If ALT >5 times ULN, discontinue sarilumab.
Polymyalgia Rheumatica: If ANC <1000 cells/mm³ at the end of the dosing interval, platelet count <100,000 cells/mm³, or AST or ALT >3 times ULN, discontinue sarilumab.
Polyarticular Juvenile Idiopathic Arthritis: If platelet count >50,000–100,000 cells/mm³, ALT >3 times to ≤5 times ULN, or neutrophil count 500–<1000 cells/mm³, hold therapy. If platelet count ≤50,000 cells/mm³, ALT >5 times ULN, or neutrophil count <500 cells/mm³, discontinue sarilumab.

Implementation ⬆ ⬇

Update immunizations before starting therapy following current immunization guidelines for patients receiving immunosuppressive agents.
Administer a tuberculin skin test prior to administration of sarilumab. Patients with latent TB should be treated for TB prior to therapy.
- Other DMARDs should be continued during sarilumab therapy.
SUBQ: Refrigerate in original carton to protect from light; do not freeze. Only the prefilled syringe is approved for use in children. Allow dosage formulations to sit at room temperature for 30 min (prefilled syringe) or 60 min (prefilled pen) prior to administration; do not warm any other way. Do not shake. May be stored for up to 14 days in original carton at room temperature. Inject full amount in syringe. Rotate injection sites; avoid areas where skin is tender, damaged, or has bruises or scars. Solution is clear and colorless to pale yellow; do not administer solutions that are discolored or contain particulate matter.

Patient/Family Teaching ⬆ ⬇

Explain the purpose and side effects of sarilumab to patient. Do not stop receiving drug without consulting health care provider. If an appointment or dose is missed, contact health care provider as soon as possible to reschedule. Instruct patient and caregiver in correct technique for SUBQ injections and care and disposal of equipment. Rotate injection sites. Do not inject where skin is tender, damaged, bruised, or scarred. Advise patient to read the Medication Guide before starting and with each Rx refill in case of changes.
Caution patient to notify health care provider immediately if signs of infection (fever, sweating, chills, muscle aches, cough, shortness of breath, blood in phlegm, weight loss, warm, red or painful skin or sores, diarrhea or stomach pain that does not go away, burning on urination, urinary frequency, feeling tired) occur.
Advise patient to immediately report and seek treatment for allergic reaction. Signs and symptoms of anaphylaxis might include swelling of face, lips, or tongue; hives; severe rash; shortness of breath; or chest pain.
Advise patient to avoid receiving live vaccines during therapy.
Instruct patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care provider before taking any new medications.
Instruct patient to notify health care provider of medication regimen prior to treatment or surgery.
Rep: Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected or if breastfeeding. Encourage women who become pregnant while taking sarilumab to participate in the pregnancy registry by going to https://mothertobaby.org/ongoing-study/kevzara/ or calling 1-877-311-8972.

Evaluation/Desired Outcomes ⬆ ⬇

Slowed progression of rheumatoid arthritis and polyarticular juvenile idiopathic arthritis.
Sustained remission in polymyalgia rheumatica.

US Brand Names ⬆ ⬇

Code ⬆

NDC Code

0024- Sanofi-Aventis U.S. LLC
- 0024-5908- KEVZARA
  - 0024-5908-01- 2 SYRINGE in 1 PACKAGE (0024-5908-01) / 1.14 mL in 1 SYRINGE (0024-5908-00)

0024- Sanofi-Aventis U.S. LLC
- 0024-5908- KEVZARA
  - 0024-5908-02- 2 SYRINGE in 1 PACKAGE (0024-5908-02) / 1.14 mL in 1 SYRINGE

0024- Sanofi-Aventis U.S. LLC
- 0024-5910- KEVZARA
  - 0024-5910-01- 2 SYRINGE in 1 PACKAGE (0024-5910-01) / 1.14 mL in 1 SYRINGE (0024-5910-00)

0024- Sanofi-Aventis U.S. LLC
- 0024-5910- KEVZARA
  - 0024-5910-02- 2 SYRINGE in 1 PACKAGE (0024-5910-02) / 1.14 mL in 1 SYRINGE

0024- Sanofi-Aventis U.S. LLC
- 0024-5920- KEVZARA
  - 0024-5920-01- 2 SYRINGE in 1 PACKAGE (0024-5920-01) / 1.14 mL in 1 SYRINGE (0024-5920-00)

0024- Sanofi-Aventis U.S. LLC
- 0024-5920- KEVZARA
  - 0024-5920-02- 2 SYRINGE in 1 PACKAGE (0024-5920-02) / 1.14 mL in 1 SYRINGE

0024- Sanofi-Aventis U.S. LLC
- 0024-5922- KEVZARA
  - 0024-5922-01- 2 SYRINGE in 1 PACKAGE (0024-5922-01) / 1.14 mL in 1 SYRINGE (0024-5922-00)

0024- Sanofi-Aventis U.S. LLC
- 0024-5922- KEVZARA
  - 0024-5922-02- 2 SYRINGE in 1 PACKAGE (0024-5922-02) / 1.14 mL in 1 SYRINGE

51789- Sanofi Winthrop Industrie
- 51789-911-
  - 51789-911-00- 2 SYRINGE in 1 CARTON (51789-911-00) / 1.14 mL in 1 SYRINGE

51789- Sanofi Winthrop Industrie
- 51789-924-
  - 51789-924-00- 2 SYRINGE in 1 CARTON (51789-924-00) / 1.14 mL in 1 SYRINGE

61755- Regeneron Pharmaceuticals, Inc
- 61755-923-
  - 61755-923-00- 5000 mL in 1 BOTTLE (61755-923-00)

61755- Regeneron Pharmaceuticals, Inc
- 61755-924-
  61755-924-00- 5000 mL in 1 BOTTLE (61755-924-00)

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇