Concizumab-mtci (Monograph)

Brand name: Alhemo
Drug class: Hemostatics

Medically reviewed by Drugs.com on Sep 10, 2025. Written by ASHP.

Introduction

Humanized immune globulin G type 4 (IgG₄) monoclonal antibody, that binds to tissue factor pathway inhibitor (TFPI).

Uses for Concizumab-mtci

Hemophilia A and B

Routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and pediatric patients ≥12 years of age with hemophilia A (congenital factor VIII deficiency) with factor VIII inhibitors, or with hemophilia B (congenital factor IX deficiency) with factor IX inhibitors.

Designated an orphan drug by FDA for treatment of hemophilia A and hemophilia B.

The World Federation of Hemophilia (WFH) and the Medical and Scientific Advisory Council (MASAC) of the National Hemophilia Foundation publish evidence-based guidelines on hemophilia management.

Bypassing agents (activated prothrombin complex concentrate [aPCC] or recombinant factor VIIa) and emicizumab have been used for prophylaxis in patients with hemophilia A or B with inhibitors. Concizumab is not mentioned as guidelines were published prior to drug approval.

Concizumab-mtci Dosage and Administration

General

Pretreatment Screening

Confirm pregnancy status in female patients with reproductive potential.

Patient Monitoring

Measure plasma levels using a concizumab-specific ELISA. A concizumab-specific ELISA (ConcizuTrace™ ELISA) has been approved by FDA.
Monitor for signs and symptoms of thromboembolism.

Other General Considerations

Discontinue concizumab-mtci at least 4 days before major surgery. Resume maintenance dosing 10–14 days postoperatively based on the patient's clinical status. Consult a bleeding disorder specialist if needed. No dosage adjustment is required for minor surgeries.
The safety and efficacy of concizumab-mtci during immune tolerance induction (ITI) not established; weigh potential benefits and risks carefully before initiating or continuing concizumab-mtci in patients undergoing ITI.
Counsel patients and caregivers on appropriate use and timing of bypassing agents or factor VIII/factor IX during prophylactic treatment with concizumab-mtci.
Bypassing agents (factor VIIa or aPCC) may be used to manage breakthrough bleeding during concizumab-mtci therapy. Dose and duration should be based on severity and location of the bleed. Use lowest approved dosage for mild to moderate bleeds; limit aPCC to 100 units/kg in 24 hours. For severe bleeds, follow product labeling and apply clinical judgment.

Administration

Sub-Q Administration

Administer by sub-Q injection only.

Available as a 60 mg/1.5 mL, 150 mg/1.5 mL, and 300 mg/3 mL single-patient-use prefilled pen. Each pen contains multiple doses of concizumab-mtci.

Use concizumab-mtci under the guidance of a healthcare provider. May be self-administered or administered by a caregiver after appropriate training provided.

Can administer directly after removal from refrigerator or allow to reach room temperature prior to injection.

Administer sub-Q injections into abdomen (at least 2 inches away from navel) or thigh, rotating injection sites daily.

Avoid injecting into areas with tenderness, bruising, redness, hardness, scars, moles, or stretch marks.

Use techniques, such as pinching the skin, to reduce the risk of intramuscular injection in children and lean patients.

Use a new needle for each injection.

Use NovoFine or NovoFine Plus needles (32-gauge, 4 mm); if longer needles are used, apply techniques to minimize intramuscular injection.

Dosage

Concizumab-mtci is dosed by body weight (kg); recalculate the dose if the patient’s body weight changes.

Pediatric Patients

Hemophilia A or B with Inhibitors

Sub-Q

The recommended dosage of concizumab-mtci in pediatric patients ≥12 years of age:

Day 1: Administer loading dose of 1 mg/kg
Day 2: Begin once daily dose of 0.2 mg/kg until individualization of maintenance dosage.
4 weeks after initiation of treatment: Measure concizumab-mtci plasma concentration using a concizumab-mtci ELISA test prior to administration of the next scheduled dose to guide maintenance dosing.

Individualize maintenance dosage no later than 8 weeks after initiation of treatment based on the following concizumab plasma concentrations:

<200 ng/mL: Increase to 0.25 mg/kg once daily
200–4000 ng/mL: Continue 0.2 mg/kg once daily
>4000 ng/mL: Decrease to 0.15 mg/kg once daily

Round the calculated dose as follows based on vial strength: if using the 60 mg vial (40 mg/mL, brown label), round to nearest 0.4 mg; if using the 150 mg or 300 mg vial (100 mg/mL, gold or white label), round to nearest 1 mg.

After 8 weeks on a stable maintenance dosage, measure concizumab plasma levels during routine follow-ups to confirm steady-state. Maintaining concentrations >200 ng/mL is important to reduce bleeding risk. If levels remain <200 ng/mL on two consecutive tests, reassess benefit-risk of continuing concizumab-mtci and consider alternative therapies.

Adherence to the daily dosing schedule is important to maintain protection against bleeding, particularly during the first 4 weeks of treatment. If a dose is missed during the first 4 weeks, patients should contact their healthcare provider and resume dosing at the initial dosage of 0.2 mg/kg once daily. If any doses are missed once maintenance dosing established, the recommended course of action is dependent on how many doses are missed. If 1 dose is missed, resume once daily dosing at the maintenance dose level. If 2–6 doses are missed, resume treatment with a double dose followed by once daily treatment at the maintenance dose level. If ≥7 doses are missed, patients should contact their healthcare provider to determine whether a new loading dose is needed.

No dosage adjustment is required for breakthrough bleeds.

Adults

Hemophilia A or B

Sub-Q

The recommended dosage of concizumab-mtci:

Day 1: Administer a loading dosage of 1 mg/kg.
Day 2: Begin once daily dose of 0.2 mg/kg until individualization of maintenance dosage.
4 weeks after initiation of treatment: Measure concizumab-mtci plasma concentration using a concizumab-mtci ELISA test prior to administration of the next scheduled dose to guide maintenance dosing.

Once the concizumab-mtci plasma concentration result is available, individualize the maintenance dosage no later than 8 weeks after initiation of treatment based on the following plasma concentrations:

<200 ng/mL: Increase to 0.25 mg/kg once daily
200–4000 ng/mL: Continue 0.2 mg/kg once daily
>4000 ng/mL: Decrease to 0.15 mg/kg once daily

Round the calculated dose of concizumab-mtci as follows based on vial strength: if using the 60 mg vial (40 mg/mL, brown label), round to the nearest 0.4 mg; if using the 150 mg or 300 mg vial (100 mg/mL, gold or white label), round to the nearest 1 mg.

After 8 weeks on a stable maintenance dosage, measure concizumab-mtci plasma levels during routine follow-ups to confirm steady-state. Maintaining concentrations >200 ng/mL is important to reduce bleeding risk. If levels remain <200 ng/mL on two consecutive tests, reassess the benefit-risk of continuing concizumab-mtci and consider alternative therapies.

Adherence to the daily dosing schedule is important to maintain protection against bleeding, particularly during first 4 weeks of treatment to ensure that a correct maintenance dosage is established. If a dose is missed during the first 4 weeks, patients should contact their healthcare provider and resume dosing at the initial dosage of 0.2 mg/kg once daily. If any doses are missed once maintenance dosing established, the recommended course of action is dependent on how many doses are missed. If 1 dose is missed, resume once daily dosing at the maintenance dose level. If 2–6 doses are missed, resume treatment with a double dose followed by once daily treatment at the maintenance dose level. If ≥7 doses are missed, patients should contact their healthcare provider to determine whether a new loading dose is needed.

No dosage adjustment is required for breakthrough bleeds.

Switching to Concizumab from other Hemostatic Products

When switching patients from other hemostatic products to concizumab, the timing for discontinuation of the other hemostatic product is based on the specific agent as follows.

Recombinant factor VIIa: Discontinue treatment with recombinant factor VIIa at least 12 hours before initiating concizumab-mtci therapy.

Activated prothrombin complex concentrate (aPCC): Discontinue treatment with aPCC at least 48 hours before starting concizumab-mtci.

Factor VIII or factor IX: Discontinue prophylactic use of standard half-life factor VIII or factor IX at least 24 hours prior to starting concizumab-mtci.

When changing from other products to concizumab-mtci, consider the half-life of the hemostatic product.

Special Populations

Hepatic Impairment

No specific dosage recommendations.

Renal Impairment

No specific dosage recommendations.

Geriatric Patients

No specific dosage recommendations.

Cautions for Concizumab-mtci

Contraindications

Known history of serious hypersensitivity to the drug or any of its components.

Warnings/Precautions

Thromboembolic Events

Thromboembolic events reported, mainly in patients with multiple risk factors such as high or prolonged use of factor products or conditions linked to elevated tissue factor (e.g., atherosclerosis, cancer, disseminated intravascular coagulation, sepsis). Discontinue therapy and initiate appropriate evaluation and management if thromboembolism suspected.

Hypersensitivity Reactions

Contraindicated in patients with a history of serious hypersensitivity. Reactions reported include rash, pruritus, erythema, and abdominal pain. One case of anaphylaxis resolved with antihistamines and corticosteroids.

Laboratory Abnormalities

Increased D-dimer and prothrombin fragment 1+2 levels reported and found to correlate with drug levels and hemostatic effect. However, may not reliably predict thrombotic events and should be interpreted cautiously.

Immunogenicity

Anti-drug antibodies, including neutralizing antibodies, detected. In one case, neutralizing antibodies reduced drug effectiveness.

Specific Populations

Pregnancy

May cause fetal harm and crosses the placenta. Use during pregnancy should be limited to situations where potential benefit outweighs risk.

Lactation

No data on presence of concizumab-mtci in human or animal milk, or whether the drug has any effects on the breastfed child, or on milk production.

Females and Males of Reproductive Potential

Advise female patients of reproductive potential to use effective contraception during treatment and for 7 weeks after the last dose.

Pediatric Use

Safety and efficacy established in patients ≥12 years of age. Safety and efficacy in patients <12 years of age not established.

Geriatric Use

Clinical studies did not include sufficient numbers of patients ≥65 years of age to determine if they respond differently than younger patients.

Increased Body Weight

Concizumab-mtci exposure decreases as body weight increases.

Common Adverse Effects

Adverse reactions reported in ≥5% of concizumab-mtci-treated patients were injection site reactions and urticaria.

Drug Interactions

No formal drug interaction studies to date.

Bypassing Agents

Use caution when adding bypassing agents to concizumab-mtci for breakthrough bleeds; combined use increases risk of thrombin generation.

Interference with Laboratory Tests

Concizumab-mtci does not interfere with PT, aPTT, factor VIII/IX assays (clot-based or chromogenic), or the Bethesda assay for detecting factor VIII/IX inhibitors.

Concizumab-mtci Pharmacokinetics

Absorption

Plasma Concentrations

Steady-state concentrations reached by day 4.

Peak plasma concentrations achieved within 8–99 hours following single sub-Q dose of 0.05–3 mg/kg.

Exposure increases in a greater-than-dose-proportional manner following sub-Q administration.

Special Populations

Pharmacokinetics not significantly affected by age (12–79 years), race, or hemophilia type (A or B). No studies in renal or hepatic impairment; altered exposure not expected due to monoclonal antibody structure.

Distribution

Special Populations

Drug exposure increases with increasing body weight (range: 27–130.7 kg).

Elimination

Metabolism

Metabolized into small peptides by catabolic pathways

Elimination Route

Cleared through both linear and non-linear pathways due to target-mediated drug disposition (TMDD); shifts to linear catabolism after TFPI saturation.

Half-life

1 day

Stability

Storage

Parenteral

Prefilled Pen

Before first use, store in refrigerator (2–8°C) in original carton to protect from light.

After first use, store prefilled pen in refrigerator or at room temperature (<30°C) for up to 28 days and record first-use date on carton; discard any unused portion after 28 days.

Keep prefilled pen capped, protected from light, and away from direct heat, sunlight, or cooling elements. Do not use if frozen or stored >30°C.

Actions

Recombinant monoclonal antibody (IgG type 4) that inhibits endogenous TFPI, which enhances factor Xa production during the initiation phase of coagulation.
Promotes thrombin formation and clot development to achieve hemostasis in patients with hemophilia A or B with inhibitors.
Factor VIII or IX inhibitors do not affect concizumab, and concizumab does not induce or increase their development due to its lack of structural or sequence similarity.

Advice to Patients

Advise patients to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).
Inform patients of the signs and symptoms of thromboembolic events, including swelling, warmth, pain, or redness of the skin (and that these could be symptoms of a blood clot in the legs or arms); shortness of breath or severe chest pain (and that these could be symptoms of blood clots in the chest [heart and lungs]); headache, confusion, difficulty with speech or movement, numbness of the face, eye pain or swelling, or vision problems (and that these could be symptoms of a blood clot in the brain or eyes); or sudden pain in the stomach or lumbar area (and that these could be symptoms of blood clots in the gut or kidneys). Advise patients to contact their healthcare provider for mild reactions and to seek urgent medical attention for moderate to severe reactions.
Inform patients of the early signs of hypersensitivity reactions, including rash, redness, hives, and itching, facial swelling, tightness of the chest, and wheezing as well the signs of an anaphylactic reaction such as itching on large areas of skin; redness and/or swelling of lips, tongue, face, or hands; difficulty swallowing; shortness of breath; wheezing; tightness of the chest; pale and cold skin; fast heartbeat; or dizziness/low blood pressure. Advise patients to discontinue use of concizumab-mtci immediately and contact their healthcare provider if any signs or symptoms occur.
Advise patients on the importance of adherence to daily dosing and to speak with their healthcare provider before discontinuing treatment with concizumab-mtci as patients who are not adhering to daily dosing or stop treatment with concizumab-mtci may no longer be protected against bleeding.
Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.
Advise patients to inform their clinician if they are or plan to become pregnant or plan to breast-feed.
Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Concizumab-mtci is available through designated specialty pharmacies. Contact manufacturer or consult the concizumab-mtci website ([Web]) for specific information.

Concizumab-mtci
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	Injection, for subcutaneous use	60 mg/1.5 mL (40 mg/mL)	Alhemo (available in a single-patient-use prefilled pen)	Novo Nordisk
		150 mg/1.5 mL (100 mg/mL)	Alhemo (available in a single-patient-use prefilled pen)	Novo Nordisk
		300 mg/3 mL (100 mg/mL)	Alhemo (available in a single-patient-use prefilled pen)	Novo Nordisk