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Emicizumab: Drug information

Emicizumab: Drug information
(For additional information see "Emicizumab: Patient drug information" and see "Emicizumab: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US Boxed Warning
Thrombotic microangiopathy and thromboembolism:

Cases of thrombotic microangiopathy and thrombotic events were reported when on average a cumulative amount of >100 units/kg/24 hours of activated prothrombin complex concentrate (aPCC) was administered for 24 hours or more to patients receiving emicizumab prophylaxis. Monitor for the development of thrombotic microangiopathy and thrombotic events if aPCC is administered. Discontinue aPCC and suspend dosing of emicizumab if symptoms occur.

Brand Names: US
  • Hemlibra
Brand Names: Canada
  • Hemlibra
Pharmacologic Category
  • Antihemophilic Agent;
  • Monoclonal Antibody
Dosing: Adult
Hemophilia A, prophylaxis

Hemophilia A, prophylaxis: SUBQ:

Initial: 3 mg/kg once weekly for 4 weeks

Maintenance: 1.5 mg/kg once weekly or 3 mg/kg once every 2 weeks or 6 mg/kg once every 4 weeks

Note: Prophylactic use of bypassing agents should be discontinued the day before starting therapy. Prophylactic use of FVIII may be continued during the first week of therapy.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

CrCl ≥30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling.

CrCl <30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Dosing: Hepatic Impairment: Adult

Mild to moderate impairment: There are no dosage adjustments provided in the manufacturer's labeling.

Severe impairment: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Dosing: Pediatric

(For additional information see "Emicizumab: Pediatric drug information")

Hemophilia A, prophylaxis

Hemophilia A, prophylaxis: Note: Prophylactic use of bypassing agents should be discontinued the day before starting therapy. Prophylactic use of FVIII may be continued during the first week of therapy.

Infants, Children, and Adolescents:

Initial loading dose: SubQ: 3 mg/kg once weekly for first 4 weeks (4 doses)

Maintenance therapy: Note: Multiple regimens available, and selection should be based on health care provider preferences and increased patient adherence. SubQ: 1.5 mg/kg once weekly or 3 mg/kg once every 2 weeks or 6 mg/kg once every 4 weeks

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling; the pharmacokinetics of emicizumab were not shown to be altered in patients with mild (CrCl 60 to 89 mL/minute) and moderate (CrCl 30 to 59 mL/minute) renal impairment.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling; the pharmacokinetics of emicizumab were not shown to be altered in patients with mild (total bilirubin 1 to 1.5 times ULN) and moderate (total bilirubin 1.5 to 3 times ULN) hepatic impairment.

Dosing: Older Adult

Refer to adult dosing.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Subcutaneous [preservative free]:

Hemlibra: Emicizumab-kxwh 30 mg/1 mL (1 mL); Emicizumab-kxwh 150 mg/1 mL (1 mL); Emicizumab-kxwh 60 mg/0.4 mL (0.4 mL); Emicizumab-kxwh 105 mg/0.7 mL (0.7 mL)

Generic Equivalent Available: US

No

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Subcutaneous:

Hemlibra: 30 mg/mL (1 mL); 60 mg/0.4 mL (0.4 mL); 105 mg/0.7 mL (0.7 mL); 150 mg/mL (1 mL)

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:

Hemlibra: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761083s011lbl.pdf#page=21

Administration: Adult

SUBQ: For SUBQ administration. Do not shake. Use an 18-gauge transfer needle containing a 5-micron filter to withdraw dose and a 26-gauge injection needle (acceptable range: 25 to 27 gauge) with a 3/8- to ½-inch needle to administer dose. Administer immediately after removal from vial. Administer doses up to 1 mL with a 1 mL syringe and doses >1 mL and up to 2 mL with a 2 or 3 mL syringe. Rotate injection sites (upper outer arms, thighs, or any quadrant of abdomen). Do not inject into moles, scars, or areas where the skin is tender, bruised, red, hard, or not intact. Patient may self-inject, or the patient's caregiver may administer; however, only a health care provider should administer in the upper outer arm. Self-administration is not recommended for children <7 years of age.

Refer to product information for preparation and additional administration techniques. Do not use different vials of different concentrations when combining vials to administer prescribed dose.

Administration: Pediatric

SubQ: For SubQ administration. Do not shake. Administer immediately after removal of dose from vial. Use an 18-gauge transfer needle containing a 5-micron filter to withdraw dose and a 26-gauge injection needle (acceptable range: 25 to 27 gauge) with a 3/8- to 1/2-inch needle to administer dose. Administer doses up to 1 mL with a 1 mL syringe and doses >1 mL and up to 2 mL with a 2 or 3 mL syringe. Rotate injection sites (upper outer arms, thighs, or any quadrant of abdomen). Do not inject into moles, scars, or areas where the skin is tender, bruised, red, hard, or not intact.

Note: Patient may self-inject or the patient's caregiver may administer after training; however, only a health care provider or caregiver should administer in the upper outer arm. Self-administration is not recommended for patients <7 years of age.

Refer to product information for preparation and additional administration techniques. Do not use different vials of different concentrations when combining vials to administer prescribed dose.

Use: Labeled Indications

Hemophilia A, prophylaxis: Routine prophylaxis to prevent or reduce the frequency of bleeding episodes in patients with hemophilia A (congenital factor VIII deficiency) with or without factor VIII inhibitors

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in pediatric patients and adults.

>10%:

Local: Injection-site reaction (22%, including bruising at injection site, discomfort at injection site, erythema at injection site [11%], hematoma at injection site, induration at injection site, injection-site pruritus [4%], pain at injection site [4%], rash at injection site, swelling at injection site, urticaria at injection site, warm sensation at injection site)

Nervous system: Headache (15%)

Neuromuscular & skeletal: Arthralgia (15%)

1% to 10%:

Gastrointestinal: Diarrhea (6%)

Immunologic: Antibody development (5%; neutralizing: 3%)

Miscellaneous: Fever (6%)

<1%: Neuromuscular & skeletal: Rhabdomyolysis

Frequency not defined:

Cardiovascular: Superficial thrombophlebitis

Dermatologic: Skin necrosis

Hematologic & oncologic: Thrombotic microangiopathy

Postmarketing:

Dermatologic: Skin rash, urticaria

Hypersensitivity: Angioedema

Contraindications

There are no contraindications listed in the US manufacturer's labeling.

Canadian labeling: Hypersensitivity to emicizumab or any component of the formulation.

Warnings/Precautions

Concerns related to adverse effects:

• Antibody formation: Antibody formation may occur but is rarely associated with a decrease in emicizumab plasma concentrations or a decrease in efficacy. If clinical signs of loss of efficacy (eg, increase in breakthrough bleeding events) occur, consider a change in therapy if neutralizing anti-emicizumab antibodies are suspected.

• Thrombotic microangiopathy and thromboembolism: Patients presented with thrombocytopenia, microangiopathic hemolytic anemia, and acute kidney injury, without severe deficiencies in ADAMTS13 activity; improvement of thrombotic microangiopathy and thromboembolism was seen within 1 week and 1 month, respectively, following discontinuation of activated prothrombin complex concentrate (aPCC). The potential for an interaction with aPCC may persist for up to 6 months after the last dose of emicizumab due to the long half-life of emicizumab. If these complications occur, discontinue aPCC immediately and interrupt emicizumab; consider benefits vs risks of resuming emicizumab following complete resolution of thrombotic microangiopathy and thrombotic events.

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Anti-inhibitor Coagulant Complex (Human): Emicizumab may enhance the thrombogenic effect of Anti-inhibitor Coagulant Complex (Human). Risk C: Monitor therapy

Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy

Reproductive Considerations

Patients who could become pregnant should use effective contraception during therapy.

Pregnancy Considerations

Animal reproduction studies have not been conducted.

Emicizumab is a humanized monoclonal antibody (IgG4). Potential placental transfer of human IgG is dependent upon the IgG subclass and gestational age, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis (Palmeira 2012; Pentsuk 2009).

Therapies other than emicizumab are currently recommended for the management of hemophilia A in pregnant patients (WFH [Srivastava 2020]).

Breastfeeding Considerations

It is not known if emicizumab is present in breast milk. However, emicizumab is a humanized monoclonal immunoglobulin; endogenous IgG is present in breast milk.

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.

Monitoring Parameters

Monitor for thrombotic microangiopathy and thrombotic events if aPCC is administered with emicizumab.

Monitor factor activity using single factor assays utilizing chromogenic or immuno-based methods. Chromogenic FVIII activity tests may be manufactured with either human or bovine coagulation proteins; human coagulation factors assays may overestimate the clinical hemostatic potential of emicizumab; however, bovine coagulation factors assays are insensitive to emicizumab (no activity measured) and can be used to monitor endogenous or infused FVIII activity, or to measure anti-FVIII inhibitors. Emicizumab will produce a false negative result in clotting-based Bethesda assays for functional inhibition of FVIII; a chromogenic Bethesda assay utilizing a bovine-based FVIII chromogenic test that is insensitive to emicizumab may be used. Due to the long half-life of emicizumab, effects on coagulation assays may persist ≤6 months after the last dose.

For patients with suspected neutralizing antibody formation to emicizumab, measure emicizumab levels using a modified one-stage assay including an additional predilution step of test plasma and assay calibration with emicizumab calibrators (WFH 2020).

Reference Range

Classification of hemophilia; normal is defined as 100% factor VIII (WFH [Srivastava 2020])

Severe: Factor level <1% of normal

Moderate: Factor level 1% to 5% of normal

Mild: Factor level >5% to <40% of normal

Mechanism of Action

Emicizumab, a humanized monoclonal modified immunoglobulin G4 (IgG4) antibody with a bispecific factor IXa- and factor X-directed antibody, bridges activated factor IX and factor X to restore the function of missing activated factor VIII that is needed for effective hemostasis. Emicizumab has no structural relationship or sequence homology to FVIII and, therefore, does not induce or enhance the development of direct inhibitors to FVIII.

Pharmacokinetics

Note: Pharmacokinetic parameters were not influenced by age and similar in pediatric and adult patients (1 to 77 years of age).

Distribution: Vd: 10.4 L

Bioavailability: SubQ: 80.4% to 93.1%

Half-life elimination: 26.9 ± 9.1 days

Pharmacokinetics: Additional Considerations

Body weight: Clearance and volume of distribution increase with increasing body weight (9 kg to 156 kg). Dosing in mg/kg provides similar emicizumab exposure across body weight range.

Pricing: US

Solution (Hemlibra Subcutaneous)

30 mg/mL (per mL): $3,789.60

60 mg/0.4 mL (per 0.4 mL): $7,579.20

105 mg/0.7 mL (per 0.7 mL): $13,263.61

150 mg/mL (per mL): $18,948.01

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Hemlibra (AU, BE, CH, DE, DK, EE, FI, GB, HK, IE, LT, LV, MY, NL, NO, PL, PT, RO, SE, SK, TH, TW);
  • Hemlibra s.c. (JP)


For country code abbreviations (show table)
  1. Hemlibra (emicizumab-kxwh) [prescribing information]. South San Francisco, CA: Genentech Inc; December 2021.
  2. Hemlibra (emicizumab-kxwh) [prescribing information]. South San Francisco, CA: Genentech Inc; June 2022.
  3. Hemlibra (emicizumab) [product monograph]. Mississauga, Ontario, Canada: Hoffmann-La Roche Limited; November 2021.
  4. Mahlangu J, Oldenburg J, Paz-Priel I, et al. Emicizumab Prophylaxis in Patients Who Have Hemophilia A without Inhibitors. N Engl J Med. 2018;379(9):811-822. doi: 10.1056/NEJMoa1803550. [PubMed 30157389]
  5. Palmeira P, Quinello C, Silveira-Lessa AL, Zago CA, Carneiro-Sampaio M. IgG placental transfer in healthy and pathological pregnancies. Clin Dev Immunol. 2012;2012:985646. [PubMed 22235228]
  6. Pentsuk N, van der Laan JW. An interspecies comparison of placental antibody transfer: new insights into developmental toxicity testing of monoclonal antibodies. Birth Defects Res B Dev Reprod Toxicol. 2009;86(4):328-344. [PubMed 19626656]
  7. Srivastava A, Santagostino E, Dougall A, et al; WFH Guidelines for the Management of Hemophilia panelists and co-authors. WFH guidelines for the management of hemophilia, 3rd edition. Haemophilia. 2020;26(suppl 6):1-158. doi:10.1111/hae.14046 [PubMed 32744769]
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