canakinumab (Rx)

>10%

Bronchitis (11%)

Diarrhea (20%)

Gastroenteritis (11%)

Headache (14%)

Influenza (17%)

Musculoskeletal pain (11%)

Nasopharyngitis (34%)

Nausea (14%)

Pharyngitis (11%)

Rhinitis (17%)

Weight increase (11%)

Vertigo (11%)

1-10%

Inj site pain (9%)

Decrease in calcium (4-8%)

Increase eosinophilis (3-7%)

Increase in ALT (3%)

Increase in bilirubin (3-7%)

Creatinine clearance (3-8%)

Proteinuria (4-8%)

< 1%

Hypersensitivity reactions

Contraindications

Active serious infection

Concomitant live vaccines

Hypersensitivity

Cautions

Concomitant use of TNF-alpha or IL-1 antagonists

Risk of infections, reactivation of latent hepatitis/TB; interrupt if serious infection develops

Increase risk of lymphoma

May impair defenses against malignancies

MWS: increase risk of vertigo

Macrophage activation syndrome (MAS) is a known, life-threatening disorder that may develop with rheumatic conditions, particularly SJIA; based on clinical trials, canakinumab did not increase incidence of MAS

Infections, predominantly of upper respiratory tract, in some instances serious, reported in isolated cases of unusual or opportunistic infections including aspergillosis, atypical mycobacterial infections, cytomegalovirus, herpes zoster; causal relationship of therapy to infections cannot be excluded

Pregnancy: The limited human data from postmarketing reports on use of therapy in pregnant women are not sufficient to inform a drug associated risk; monoclonal antibodies, such as canakinumab, are transported across the placenta in a linear fashion as pregnancy progresses; therefore, potential fetal exposure is likely to be greater during the second and third trimesters of pregnancy

Lactation: There is no information regarding the presence of canakinumab in human milk, the effects on the breastfed infant, or the effects on milk production. Human IgG is known to be present in human milk; the effects of canakinumab in breast milk and possible systemic exposure in the breastfed infant are unknown; the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy and any potential adverse effects on the breastfed infant from therapy or from underlying maternal condition

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Recombinant, human monoclonal antibody that reduces inflammation by inhibiting to interleukin-1-beta and preventing its interaction with cell surface receptors;

Pharmacokinetics

Bioavailability: 66%

Peak plasma time: 2-7 days (children); 7 days (adults)

Peak plasma concentration: 16 +/- 3.5 mcg/mL

Vd: 6 L

Half-life: 26 days

SC Preparation

Reconstitute lyophilized powder with 1 mL sterile water for injection to obtain 150 mg/mL solution

Swirl the vial slowly at an angle of about 45° for ~1 minute and allow to stand for 5 minutes

Do not shake; gently turn the vial upside down and back again 10 times; avoid touching the rubber stopper with your fingers

Allow stand for 15 minutes at room temperature

Do not shake

Do not use if particulate matter is present in the solution

Tap the side of the vial to remove any residual liquid from the stopper

The reconstituted solution should be clear to opalescent, colorless to a slightly brownish yellow tint, and essentially free from particulates

If the solution has a distinctly brown discoloration, do not use

Slight foaming of the product upon reconstitution is not unusual

Protect from light

Reconstituted solution can be kept at room temperature if used within 1 hr; otherwise, refrigerate at 2-8°C (36-46°F) and use within 4 hr

SC Administration

Using a sterile 1-mL syringe and needle, carefully withdraw the required volume depending on the dose to be administered and inject SC using a 27-gauge x 0.5-inch needle

Avoid injecting scar tissue as this may result in insufficient exposure

Discard any unused product or waste material in accordance with local requirements

Storage

Unopened vial

• Refrigerate at 2-8°C (36-46° F)
• Do not freeze
• Store in the original carton to protect from light

Reconstituted vial

• Room temperature if used within 1 hr; otherwise, refrigerate at 2-8°C (36-46°F) and use within 4 hr