emicizumab (Rx)

>10%

Injection site reaction (22%)

Headache (15%)

Arthralgia (15%)

Injection site erythema (11%)

1-10%

Pyrexia (6%)

Diarrhea (6%)

Injection site pruritus (4%)

Injection site pain (4%)

<1%

Rhabdomyolysis

Contraindications

None

Cautions

Cases of TMA reported from clinical trials; improvement was seen within 1 week following discontinuation of aPCC (see Black Box Warnings)

Thrombotic events reported from clinical trials when on average a cumulative amount of >100 U/kg/24 hr of aPCC was administered for ≥24 hr to patients receiving emicizumab-kxwh prophylaxis; no thrombotic event required anticoagulation therapy; evidence of improvement or resolution seen within one month following discontinuation of aPCC; consider benefits and risks of emicizumab-kxwh if aPCC must be used in patients receiving the drug or resuming prophylaxis following complete resolution of thrombotic event; monitor for development of thromboembolism when administering aPCC (see Black Box Warnings)

Drug interactions overview

• Clinical experience suggests that a drug interaction exists with emicizumab-kxwh and aPCC; due to long half-life of the drug, the potential for interaction with aPCC may persist for up to 6 months after last dose; possible for hypercoagulability with recombinant factor VIIa (rFVIIa) or Factor VIII (FVIII) with emicizumab-kxwh based on preclinical experiments

• Drug laboratory test interactions

  • Intrinsic pathway clotting-based laboratory tests were affected; therefore these laboratory tests should not be used in monitoring emicizumab-kxwh; due to the long half-life of the drug, effects on coagulation essays may persist for up to 6 months after last dose
  • Results affected by emicizumab: Activated aPTT; Bethesda assays (clotting-based) for FVIII inhibitor titers; one-stage, aPTT-based, single-factor assays; aPTT-based activated protein C resistance (APC-R); and activated clotting time
  • Results unaffected by emicizumab: Bethesda assays (bovine chromogenic) for FVIII inhibitor titers; thrombin time; one-stage, prothrombin time-based, single-factor assays; chromogenic-based single-factor assays other than FVIII; immuno-based assays (eg, ELISA, turbidimetric methods); and genetic tests of coagulation factors (eg, factor V Leiden, prothrombin 20210)

Pregnancy

No data are available regarding use in pregnant women to inform a drug-associated risk of major birth defects and miscarriage

Unknown whether treatment can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity

Should be used during pregnancy only if the potential benefit for the mother outweighs the risk to the fetus

Women of childbearing potential should use contraception during treatment

Lactation

No information is available regarding the presence of emicizumab-kxwh in human milk, the effects on the breastfed child, or the effects on milk production

Human IgG is known to be present in human milk

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

Bispecific factor IXa- and factor X-directed antibody that bridges activated factor IX and factor X in order to restore the function of missing activated factor VIII necessary for effective hemostasis

Absorption

Peak plasma concentration, steady-state: 55.1 mcg/mL (1.5 mg/kg-dose); 58.3 mcg/mL (3 mg/kg-dose); 67 mcg/mL (6 mg/kg-dose)

AUC, steady-state: 376 mcg/mL·day (1.5 mg/kg-dose); 752 mcg/mL·day (3 mg/kg-dose); 1503 mcg/mL·day (6 mg/kg-dose)

Bioavailability, 1 mg/kg dose: 80.4-93.1%

Observed similar pharmacokinetic profiles following SC administration in the abdomen, upper arm, and thigh

Distribution

Vd: 10.4L

Excretion

Clearance: 0.27 L/day

Half-life: 26.9 days

SC Preparation

Visually inspect vial for particulate matter and discoloration prior to administration; solution appears colorless to slightly yellow; do not use if particulate matter is visible or product is discolored

Do not use different vials of different concentrations when combining vials to administer prescribed dose

SC administration

SC use only

Administer doses of up to 1 mL with a 1-mL syringe (graduation 0.01 mL)

Administer doses >1 mL to ≤2 mL with a 2-mL or 3-mL syringe (graduation 0.1 mL)

Use a transparent polypropylene or polycarbonate syringe with Luer-Lok tip, sterile, for injection only, single-use, latex-free, nonpyrogenic, and commercially available in the United States

Rotate injection sites (upper outer arms, thighs, or any quadrant of abdomen) from previous injection

Do not inject into moles, scars, or areas where the skin is tender, bruised, red, hard, or not intact

Administration into the upper outer arm should only be performed by a caregiver or healthcare provider

Discard any unused drug remaining

Missed dose

• Administer as soon as possible prior to day of next scheduled dose, and then resume usual weekly dosing schedule
• Do not double doses to make up for a missed dose

Storage

Opened vials: Single-dose vials; discard any unused solution remaining after administering dose

Unopened vials

• Store in refrigerator at 2-8°C (36-46°F) in original carton to protect from light; do not freeze; do not shake
• If necessary, unopened vials may be stored at room temperature and then returned to refrigeration; temperature should not exceed 30°C (86°F) for up to 7 days