Version July 2025
Dosage guidance:
Dosing: Doses are weight based. Recalculate dose if body weight changes. The calculated dose is rounded to the nearest injectable dose.
Dosage form information: The 60 mg/1.5 mL pen can be administered in 0.4 mg increments. The 150 mg/1.5 mL and 300 mg/3 mL pens can be administered in 1 mg increments.
Clinical considerations: Initiate therapy during a nonbleeding state.
Breakthrough bleeding episodes: No dosage adjustment of concizumab is necessary. Treatment with bypassing agents (eg, rFVIIa or aPCC) can be used for breakthrough bleeds; the dose, duration, and need for repeat doses depend on location and severity of the bleed. Consultation with a hemophilia provider is recommended.
Management of perioperative patients: No dosage adjustment of concizumab is necessary for minor surgery. For major surgery, discontinue ≥4 days before surgery; resume treatment 10 to 14 days after surgery with the same maintenance dose (without a loading dose), while considering the overall clinical picture of the patient. Consultation with a hemophilia provider is recommended.
Hemophilia A, prophylaxis:
Note: Indicated for patients with hemophilia A with factor VIII inhibitors.
Initial dosage:
SUBQ: 1 mg/kg once on day 1 (loading dose) then 0.2 mg/kg once daily starting on day 2; continue for 4 to 8 weeks, then maintenance dosage is based on plasma concentrations.
Maintenance dosage:
Initial maintenance dosage adjustment: Measure concizumab trough plasma concentration prior to administration of the next dose using a concizumab enzyme-linked immunosorbent assay (ELISA); measure plasma concentration at least 4 weeks after initiation; adjust dose no later than 8 weeks after initiation based on the table below.
|
Concizumab plasma concentration |
Dosage adjustment (SUBQ)a |
|---|---|
|
a In patients who require a dosage reduction to 0.15 mg/kg once daily due to plasma concentration >4,000 ng/mL, consider obtaining a second concentration after 8 weeks of the reduced dose; if concentration remains >4,000 ng/mL, weigh risks and benefits of continuing therapy (eg, increased risk of thromboembolic events) (Alhemo Canadian product monograph). | |
|
<200 ng/mL |
Increase dose to 0.25 mg/kg once daily |
|
200 to 4,000 ng/mL |
Continue 0.2 mg/kg once daily |
|
>4,000 ng/mL |
Decrease dose to 0.15 mg/kg once dailya |
Further maintenance dosage adjustment: After initial dosage adjustment, monitor concizumab plasma concentration routinely (eg, once or twice yearly), ensuring that dose has been consistent for ≥8 weeks. Maintain concentration >200 ng/mL to decrease risk of bleeding episodes. If concentration remains <200 ng/mL or >4,000 ng/mL at two consecutive measurements (and dose has been consistent for ≥8 weeks), weigh risks and benefits and consider alternative therapies, if available (Ref).
Hemophilia B, prophylaxis:
Note: Indicated for patients with hemophilia B with factor IX inhibitors.
Initial dosage:
SUBQ: 1 mg/kg once on day 1 (loading dose) then 0.2 mg/kg once daily starting on day 2; continue for 4 to 8 weeks, then maintenance dosage is based on plasma concentrations.
Maintenance dosage:
Initial maintenance dosage adjustment: Measure concizumab trough plasma concentration prior to administration of the next dose using a concizumab enzyme-linked immunosorbent assay (ELISA); measure plasma concentration at least 4 weeks after initiation; adjust dose no later than 8 weeks after initiation based on the table below.
|
Concizumab plasma concentration |
Dosage adjustment (SUBQ)a |
|---|---|
|
a In patients who require a dosage reduction to 0.15 mg/kg once daily due to plasma concentration >4,000 ng/mL, consider obtaining a second concentration after 8 weeks of the reduced dose; if concentration remains >4,000 ng/mL, weigh risks and benefits of continuing therapy (eg, increased risk of thromboembolic events) (Alhemo Canadian product monograph). | |
|
<200 ng/mL |
Increase dose to 0.25 mg/kg once daily |
|
200 to 4,000 ng/mL |
Continue 0.2 mg/kg once daily |
|
>4,000 ng/mL |
Decrease dose to 0.15 mg/kg once dailya |
Further maintenance dosage adjustment: After initial dosage adjustment, monitor concizumab plasma concentration routinely (eg, once or twice yearly), ensuring that dose has been consistent for ≥8 weeks. Maintain concentration >200 ng/mL to decrease risk of bleeding episodes. If concentration remains <200 ng/mL or >4,000 ng/mL at two consecutive measurements (and dose has been consistent for ≥8 weeks), weigh risks and benefits and consider alternative therapies, if available (Ref).
Missed dose: Management depends on when dose is missed and number of missed doses:
During initial 4 weeks (before the first serum concentration is measured): Inform health care professional (may change timing of concizumab concentration measuring); resume once daily dosing.
During maintenance dosing, after dose adjustment based on concizumab concentration:
1 dose missed: Resume once daily treatment.
2 to 6 doses missed: Resume treatment with a double dose, followed by once daily treatment at prior dose.
≥7 doses missed: Contact physician; consider new loading dose.
Changing from other hemostatic products to concizumab:
Recombinant factor VIIa: Discontinue treatment with rFVIIa ≥12 hours before starting concizumab.
Activated prothrombin complex concentrate (aPCC): Discontinue treatment with aPCC ≥48 hours before starting concizumab.
Factor VIII or factor IX (standard half-life products): Discontinue prophylactic use of standard half-life factor VIII or factor IX products ≥24 hours before starting concizumab.
Other products: Consider the half-life of the previous product when changing from other products to concizumab.
Dose adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Refer to adult dosing.
(For additional information see "Concizumab: Pediatric drug information")
Dosage guidance:
Dosing: Round calculated doses to the nearest measurable dose. Routinely recalculate dose with body weight changes.
Dosage form information: Prefilled pens are available in multiple concentrations; use caution. Round to nearest measurable dose; the 60 mg/1.5 mL pen can be administered in 0.4 mg increments; the 150 mg/1.5 mL and 300 mg/3 mL pens can be administered in 1 mg increments.
Clinical considerations: Initiate treatment when patient is not bleeding. Plasma concentration monitoring is recommended; concentration >200 ng/mL is important to decrease the risk of bleeding episodes. No dosage adjustment is recommended for breakthrough bleeding; however, treatment with bypassing agents (eg, recombinant factor VIIa [rFVIIa] or activated prothrombin complex concentrate [aPCC]) may be used as necessary; refer to institutional protocol.
Hemophilia A, prophylaxis:
Initial dosage:
Children ≥12 years and Adolescents: SUBQ: 1 mg/kg/dose once on day 1 (loading dose), then 0.2 mg/kg/dose once daily starting on day 2; continue for 4 to 8 weeks, then maintenance dosage is based on plasma concentration.
Maintenance dosage:
Initial maintenance dosage adjustment: Children ≥12 years and Adolescents:
Measure predose concizumab plasma concentration 4 to 8 weeks after initiation, and adjust dose based on concentration as indicated in table.
|
Concizumab plasma concentration |
Dosage adjustment (SUBQ)a |
|---|---|
|
a Round calculated dose to nearest measurable dose based on dosage form used. | |
|
b In patients who require a dosage reduction to 0.15 mg/kg/dose due to plasma concentration >4,000 ng/mL, consider obtaining a second concentration after 8 weeks; if concentration remains >4,000 ng/mL, weigh risks and benefits of continuing therapy (Alhemo Canadian product monograph). | |
|
<200 ng/mL |
Increase dose to 0.25 mg/kg/dose once daily |
|
200 to 4,000 ng/mL |
Continue 0.2 mg/kg/dose once daily |
|
>4,000 ng/mL |
Decrease dose to 0.15 mg/kg/dose once dailyb |
Further maintenance dosing adjustment: Children ≥12 years and Adolescents:
After initial dosage adjustment, monitor routinely (eg, once or twice yearly), ensuring that dose has been consistent for ≥8 weeks. Maintain concentration >200 ng/mL to decrease risk of bleeding episodes. If concentration remains <200 ng/mL or >4,000 ng/mL at two consecutive measurements (and dose has been consistent for ≥8 weeks), weigh risks and benefits and consider alternative therapies, if available (Ref).
Hemophilia B, prophylaxis:
Initial dosage:
Children ≥12 years and Adolescents: SUBQ: 1 mg/kg/dose once on day 1 (loading dose), then 0.2 mg/kg/dose once daily starting on day 2; continue for 4 to 8 weeks, then maintenance dosage is based on plasma concentration.
Maintenance dosage:
Initial maintenance dosage adjustment: Children ≥12 years and Adolescents:
Measure predose concizumab plasma concentration 4 to 8 weeks after initiation, and adjust dose based on concentration as indicated in table.
|
Concizumab plasma concentration |
Dosage adjustment (SUBQ)a |
|---|---|
|
a Round calculated dose to nearest measurable dose based on dosage form used. | |
|
b In patients who require a dosage reduction to 0.15 mg/kg/dose due to plasma concentration >4,000 ng/mL, consider obtaining a second concentration after 8 weeks; if concentration remains >4,000 ng/mL, weigh risks and benefits of continuing therapy (Alhemo Canadian product monograph). | |
|
<200 ng/mL |
Increase dose to 0.25 mg/kg/dose once daily |
|
200 to 4,000 ng/mL |
Continue 0.2 mg/kg/dose once daily |
|
>4,000 ng/mL |
Decrease dose to 0.15 mg/kg/dose once dailyb |
Further maintenance dosing adjustment: Children ≥12 years and Adolescents:
After initial dosage adjustment, monitor routinely (eg, once or twice yearly), ensuring that dose has been consistent for ≥8 weeks. Maintain concentration >200 ng/mL to decrease risk of bleeding episodes. If concentration remains <200 ng/mL or >4,000 ng/mL at two consecutive measurements (and dose has been consistent for ≥8 weeks), weigh risks and benefits and consider alternative therapies, if available (Ref).
Changing from other hemostatic products to concizumab:
Children ≥12 years and Adolescents: SUBQ:
rFVIIa: Discontinue treatment with rFVIIa ≥12 hours before starting concizumab.
aPCC: Discontinue treatment with aPCC ≥48 hours before starting concizumab.
Factor VIII or factor IX (standard half-life products): Discontinue prophylactic use of standard half-life factor VIII or factor IX products ≥24 hours before starting concizumab.
Other products: Consider the half-life of the previous product when changing from other products to concizumab.
Management of perioperative patients:
Children ≥12 years and Adolescents: SUBQ:
Minor surgery: No dosage adjustment necessary.
Major surgery: Limited experience available. Discontinue ≥4 days before surgery. Resume 10 to 14 days after surgery on the same maintenance dose as before surgery, without a new loading dose, depending on the overall clinical status of the patient.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Immunologic: Antibody development (25%; neutralizing: 26%)
Local: Injection-site reaction
1% to 10%:
Dermatologic: Urticaria
Hematologic & oncologic: Blood coagulation test abnormality (increased levels of D-dimer [9%], increased levels of prothrombin fragment 1.2 [6%])
Frequency not defined:
Cardiovascular: Thromboembolism
Hypersensitivity: Hypersensitivity reaction (including anaphylaxis)
Renal: Renal infarction
Serious hypersensitivity to concizumab or any component of the formulation.
Concerns related to adverse effects:
• Increased laboratory values of fibrin D-dimer and prothrombin fragment 1.2: Increased levels of fibrin D-dimer and increased levels of prothrombin fragment 1.2 were seen in 29 (9.1%) and 18 (5.6%) of patients, respectively. The plasma concentration of concizumab is positively correlated with fibrin D-dimer and prothrombin fragments 1.2, indicating a hemostatic effect of concizumab. These coagulation biomarkers may not be reliable predictive markers for clinical decision-making with suspicion of thrombosis such as deep vein thrombosis and pulmonary embolism.
• Thromboembolic events: Venous and arterial thromboembolism occurred in patients with multiple risk factors for thromboembolism. Risk factors may include the use of high and/or frequent doses of breakthrough bleed treatments (factor products or bypassing agents) or conditions in which tissue factor is overexpressed (eg, atherosclerotic disease, crush injury, cancer, disseminated intravascular coagulation, thrombotic microangiopathy, septicemia).
Dosage form specific issues:
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Ref). Thrombocytopenia, ascites, pulmonary deterioration, and kidney and liver failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Ref). See manufacturer's labeling.
Other warnings/precautions:
• Immune tolerance induction: Safety and efficacy of concomitant use in patients receiving ongoing immune tolerance induction (ITI), a desensitization strategy for the eradication of inhibitors, have not been established. Careful assessment of the potential benefits and risks should be performed if continuing or initiating concizumab therapy in patients receiving ITI.
• Antibody formation: Clinical trials identified patients with antidrug and neutralizing antibodies; the clinical significance of these antibodies is unknown.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Pen-injector, Subcutaneous:
Alhemo: Concizumab-mtci 300 mg per 3 mL (3 mL); Concizumab-mtci 60 mg per 1.5 mL (1.5 mL); Concizumab-mtci 150 mg per 1.5 mL (1.5 mL) [contains phenol, polysorbate 80]
No
Solution Pen-injector (Alhemo Subcutaneous)
60 mg/1.5 mL (per mL): $8,256.00
150 mg/1.5 mL (per mL): $20,640.00
300 mg/3 mL (per mL): $20,640.00
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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Pen-injector, Subcutaneous:
Alhemo: Concizumab-mtci 150 mg per 1.5 mL (1.5 mL) [contains phenol, polysorbate 80]
SUBQ: May be self-administered or administered by a caregiver after appropriate training. Administer by SUBQ injection into the abdomen (at least 2 inches from navel) or thigh; rotate injection site every day. Do not inject in areas where skin is tender, bruised, red, or hard, or areas where there are moles, scars, or stretch marks. Injection is a clear to slightly opalescent and colorless to slightly yellow solution that may contain translucent to white particles. Do not use if the solution is discolored. Prior to each dose, attach a new needle to pen and prime the pen by dialing the 60 mg pen to 0.4 mg or dialing the 150 mg or 300 mg pen to 1 mg, and pressing the dose button; ensure that a stream of concizumab leaves the needle tip. Choose dose by selecting on the dial. Each 60 mg pen can deliver a maximum dose of 32 mg in one injection and each 150 mg or 300 mg pen can deliver a maximum dose of 80 mg in one injection; if a larger dose is needed than can be dialed, multiple injections may be needed. Inject needle at a 90-degree angle; press and hold dose button until dose counter returns to "0"; leave needle in injection site for a slow count of 6, then remove from skin. Remove and discard needle, then recap pen. Refer to manufacturer's labeling and/or instructions for use for additional information.
Note: Properly trained patients may self-inject, or caregivers may administer.
Parenteral: For SUBQ administration only. Administer by SUBQ injection into the abdomen (at least 2 inches away from naval) or thigh; rotate injection site every day. Do not inject in areas where the skin is tender, bruised, red, or hard, or areas where there are moles, scars, or stretch marks. Ensure injection technique results in SUBQ administration (eg, may need to inject into a pinched fold of skin to avoid injecting too deep, into muscle).
Prefilled pen: Injection is clear to slightly opalescent, and colorless to slightly yellow solution that may contain translucent to white particles. May inject immediately after removing from refrigerator, or may let pen reach room temperature prior to injection; pen may be warmed in palms of hands; do not use any other heating sources. Prior to each dose, attach a new needle to pen and prime pen by dialing pen to "1" and pressing the dose button; ensure that a stream of concizumab leaves the needle tip. Choose dose by selecting on the dial; if a larger dose is needed than can be dialed, multiple injections may be needed. Inject needle at a 90-degree angle; press and hold dose button until dose counter returns to "0"; leave needle in injection site for a slow count of 6, then remove from skin. Remove and discard needle, then recap pen. Refer to manufacturer's labeling for troubleshooting or additional information.
Missed dose: Depends on when dose is missed (eg, initial dosing or during maintenance dosing after individual dose has been established per concentration) and number of missed doses:
During initial 4 weeks: Inform health care professional (may change timing of concizumab concentration measuring); resume once-daily dosing.
During maintenance dosing, based on concizumab concentration:
1 dose missed: Resume once-daily treatment.
2 to 6 doses missed: Resume treatment with a double dose, followed by once-daily treatment at prior dose.
≥7 doses missed: Contact physician; consider new loading dose.
Hemophilia A, prophylaxis: 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.
Hemophilia B, prophylaxis: Routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and pediatric patients ≥12 years of age with hemophilia B (congenital factor IX deficiency) with factor IX inhibitors.
None known.
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 drug interactions program by clicking on the “Launch drug interactions program” link above.
Anti-inhibitor Coagulant Complex (Human): May increase thrombogenic effects of Concizumab. Management: Discontinue anti-inhibitor coagulant complex (aPCC) at least 48 hours before starting concizumab. If aPCC is required during concizumab prophylaxis, use the lowest possible effective aPCC dose. Risk D: Consider Therapy Modification
Efgartigimod Alfa: May decrease therapeutic effects of Fc Receptor-Binding Agents. Risk C: Monitor
Factor VIIa (Recombinant): May increase thrombogenic effects of Concizumab. Management: Discontinue treatment with recombinant factor VIIa (rFVIIa) at least 12 hours before starting concizumab. If rFVIIa is required as a bypassing agent in a patient receiving concizumab prophylaxis, use the lowest possible effective rFVIIa dose. Risk D: Consider Therapy Modification
Nipocalimab: May decrease therapeutic effects of Fc Receptor-Binding Agents. Risk C: Monitor
Rozanolixizumab: May decrease therapeutic effects of Fc Receptor-Binding Agents. Risk C: Monitor
Evaluate pregnancy status prior to use; pregnancy testing is recommended prior to use in patients who may become pregnant.
Patients who could become pregnant should use highly effective contraception during therapy and for 7 weeks after the last dose of concizumab. Consider benefits and thromboembolic risks of contraceptive type.
Animal reproduction studies have not been conducted. Based on the mechanism of action, in utero exposure to concizumab may cause fetal harm.
Concizumab is a humanized monoclonal antibody (IgG4). Human IgG crosses the placenta. Fetal exposure is dependent upon the IgG subclass, maternal serum concentrations, placental integrity, newborn birth weight, and GA, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis and the highest during the third trimester (Ref).
It is not known if concizumab is present in breast milk.
Concizumab is a humanized monoclonal antibody (IgG4). Human IgG is present in breast milk; concentrations are dependent upon IgG subclass and postpartum age (Ref). The highest breast milk concentrations are expected during the first few days after birth.
Concizumab plasma concentrations; thromboembolic or bleeding events; anti-concizumab antibodies (if clinically indicated); evaluate pregnancy status (prior to initiation of concizumab treatment in patients who can become pregnant).
Classification of hemophilia; normal is defined as 100% factor VIII (Ref):
Severe: Factor level <1% of normal.
Moderate: Factor level 1% to 5% of normal.
Mild: Factor level >5% to <40% of normal.
Concizumab is a humanized IgG4 monoclonal antibody antagonist of endogenous tissue factor pathway inhibitor (TFPI). Inhibition of TFPI enhances FXa production during the initiation phase of coagulation, which improves thrombin generation and clot formation.
Inhibitory antibodies to FVIII or FIX do not influence the effect of concizumab. Concizumab has no structural relationship or sequence homology to FVIII or FIX, therefore does not induce or enhance the development of direct inhibitors to FVIII or FIX.
Distribution: ~3 L for a 70 kg patient.
Metabolism: Catabolized into small peptides.
Half-life elimination: ~24 hours; steady state concentration is reached in ~4 days.
Time to peak: 8 to 99 hours.
Excretion: Elimination occurs via nonrenal mechanisms (ie, catabolism).
Clearance: Nonlinear due to target-mediated drug disposition, which occurs when concizumab/tissue factor pathway inhibitor (TFPI) complexes form; however, once the target becomes saturated, linear pathway (ie, catabolism) dominates.
