Concizumab

Concizumab
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Nehal Eid

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Overview

Concizumab is a Monoclonal antibody that is FDA approved for the prophylaxis of It is a tissue factor pathway inhibitor (TFPI) antagonist indicated for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients 12 years of age and older with: - hemophilia A (congenital factor VIII deficiency) with FVIII inhibitors - hemophilia B (congenital factor IX deficiency) with FIX inhibitors. Common adverse reactions include The most frequently reported adverse reactions (incidence ≥5%) were injection site reactions and urticaria..

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Administer concizumab by subcutaneous injection to the abdomen or thigh with daily rotation of injection sites. Recommended dosing regimen: o Day 1: Loading dose of 1 mg/kg o Day 2: Once-daily dose of 0.2 mg/kg until individualization of maintenance dose (see below) - 4 weeks after initiation of treatment: For dose optimization, measure concizumab-mtci plasma concentration by Concizumab Enzyme-Linked Immunosorbent Assay (ELISA) prior to administration of next scheduled dose. An FDA-authorized test for the measurement of concizumab-mtci concentration in plasma is not currently available.

o Once the concizumab-mtci concentration result is available, individualize the maintenance dose of Alhemo no later than 8 weeks after initiation of treatment, based on the following concizumab-mtci plasma concentrations: - Less than 200 ng/mL: adjust to a once-daily dose of 0.25 mg/kg (2.1) - 200 to 4,000 ng/mL: continue once-daily dose of 0.2 mg/kg (2.1) - Greater than 4,000 ng/mL: adjust to a once-daily dose of 0.15 mg/kg

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Concizumab in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Concizumab in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

The safety and effectiveness of concizumab for hemophilia A and B with inhibitors have been established in pediatric patients aged 12 years and older. Use of concizumab for this indication is supported by evidence from adequate and well-controlled studies in adult and pediatric patients aged 12 years and older.

The safety and effectiveness of concizumab for hemophilia A and B with inhibitors have not been established in pediatric patients younger than 12 years of age.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Concizumab in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Concizumab in pediatric patients.

Contraindications

History of severe hypersensitivity reactions to concizumab or its components or the inactive ingredients.

Warnings

- Thromboembolic Events: Inform patients of the signs and symptoms of thromboembolic events. Monitor patients for thromboembolic events. Advise patients to report these signs and symptoms, and if they occur discontinue prophylaxis.

- Hypersensitivity Reactions: In the event of a severe hypersensitivity reaction, discontinue concizumab.

- Increased Laboratory Values of Fibrin D dimer and Prothrombin Fragment 1+2. concizumab increases values of fibrin D dimer and prothrombin fragment 1+2.

Adverse Reactions

Clinical Trials Experience

- Thromboembolic Events - Hypersensitivity Reactions - Increased Laboratory Values of Fibrin D-dimer and Prothrombin Fragment 1+2

Postmarketing Experience

There is limited information regarding Concizumab Postmarketing Experience in the drug label.

Drug Interactions

While treatment with all bypassing agents (e.g., rFVIIa or aPCC) can be used for breakthrough bleeds, high and/or frequent doses of bypassing agents with concizumab increases the risk of thromboembolism.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): There are no available data on its use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. Animal reproduction studies have not been conducted with concizumab.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Concizumab in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Concizumab during labor and delivery.

Nursing Mothers

There is no information regarding the presence of concizumab in either human or animal milk, the effect on the breastfed child, or the effects on milk production.

Pediatric Use

The safety and effectiveness of concizumab for hemophilia A and B with inhibitors have been established in pediatric patients aged 12 years and older.

Geriatic Use

Clinical studies of concizumab did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger adult patients.

Gender

There is no FDA guidance on the use of Concizumab with respect to specific gender populations.

Race

There is no FDA guidance on the use of Concizumab with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Concizumab in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Concizumab in patients with hepatic impairment.

Females of Reproductive Potential and Males

Pregnancy Testing: Pregnancy testing is recommended for females of reproductive potential. Contraception: Women of childbearing potential should use a highly effective form of contraception during treatment with concizumab and for 7 weeks after ending treatment. The benefits and thromboembolic risks of the type of contraceptives used should be evaluated by the treating physician.

Immunocompromised Patients

There is no FDA guidance one the use of Concizumab in patients who are immunocompromised.

Administration and Monitoring

Administration

It is administered through a subcutaneous injection.

Monitoring

There is limited information regarding Concizumab Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Concizumab and IV administrations.

Overdosage

There is limited information regarding Concizumab overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

Pharmacology

There is limited information regarding Concizumab Pharmacology in the drug label.

Mechanism of Action

Concizumab-mtci is a monoclonal antibody antagonist of endogenous Tissue Factor Pathway Inhibitor (TFPI). Through the inhibition of TFPI, concizumab-mtci acts to enhance FXa production during the initiation phase of coagulation which leads to improved thrombin generation and clot formation with the goal of achieving hemostasis in patients with Hemophilia A or B with inhibitors.The effect of concizumab-mtci is not influenced by the presence of inhibitory antibodies to FVIII or FIX. There is no structural relationship or sequence homology between concizumab-mtci and FVIII or FIX and, as such, treatment with concizumab-mtci does not induce or enhance the development of direct inhibitors to FVIII or FIX.

Structure

There is limited information regarding Concizumab Structure in the drug label.

Pharmacodynamics

Increasing concizumab-mtci dose levels resulted in decreased levels of free TFPI (plasma TFPI not bound to concizumab-mtci) and increased duration of free TFPI suppression. Free TFPI plasma levels pre-dose decreased from a geometric mean (CV%) of 88.3 (20%) ng/mL at baseline to 10.7 (105%) ng/mL at week 24 in patients on concizumab prophylaxis, while the geometric mean (CV%) was 76.0 (18%) ng/mL at week 24 for patients on no Alhemo prophylaxis. Mean thrombin peak within the range of normal plasma reflected that concizumab-mtci re‐established thrombin generation capacity.

Pharmacokinetics

Following a single concizumab loading dose of 1 mg/kg, the steady state concentrations were reached around Day 4 and remained within a stable exposure range with daily maintenance doses. Concizumab-mtci AUC and Cmax increased with increasing dose in a greater than dose proportional manner following subcutaneous administration.

Nonclinical Toxicology

There is limited information regarding Concizumab Nonclinical Toxicology in the drug label.

Clinical Studies

There is limited information regarding Concizumab Clinical Studies in the drug label.

How Supplied

There is limited information regarding Concizumab How Supplied in the drug label.

Storage

There is limited information regarding Concizumab Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Concizumab Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Concizumab interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Concizumab Brand Names in the drug label.

Look-Alike Drug Names

There is limited information regarding Concizumab Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

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