Alhemo
(Concizumab)Alhemo Prescribing Information
Alhemo is 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 or without FVIII inhibitors• hemophilia B (congenital factor IX deficiency) with or without FIX inhibitors
Administer Alhemo by subcutaneous injection to the abdomen or thigh with daily rotation of injection sites. (
• Discontinue treatment with rFVIIa at least 12 hours before starting Alhemo.• Discontinue treatment with activated prothrombin complex concentrate (aPCC) at least 48 hours before starting Alhemo.• Discontinue prophylactic use of standard half-life factor VIII (FVIII) or factor IX (FIX) at least 24 hours before starting Alhemo.• When changing from other products to Alhemo, the half-life of the previous product should be considered.
Healthcare providers should discuss with patients receiving Alhemo and/or their caregivers the dose and schedule of bypassing agents or FVIII or FIX, if required, while receiving Alhemo prophylaxis.
Recommended dosing regimen:
• Day 1: Loading dose of 1 mg/kg• Day 2: Once daily dose of 0.2 mg/kg until individualization of maintenance dose ()2.1 Recommended DosageFor subcutaneous use only.Alhemo should be administered once daily. Avoid missed doses.
Recommended dosing regimen:
• Day 1: Loading dose of 1 mg/kg• 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 using an FDA-authorized test. Information on the FDA-authorized test for the measurement of concizumab-mtci plasma concentration is available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/denovo.cfm. 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:o Less than 200 ng/mL: adjust to a once daily dose of 0.25 mg/kgo 200 to 4,000 ng/mL: continue once daily dose of 0.2 mg/kgo Greater than 4,000 ng/mL: adjust to a once daily dose of 0.15 mg/kg
The calculated dose is rounded off to the nearest injectable dose as follows:
• 60 mg/1.5 mL (40 mg/mL) in increments of 0.4 mg (brown label)• 150 mg/1.5 mL (100 mg/mL) in increments of 1 mg (gold label)• 300 mg/3 mL (100 mg/mL) in increments of 1 mg (white label)
Additional measurements of concizumab-mtci plasma concentration should be taken at routine clinical follow-ups provided the patient has been on the same maintenance dose for 8 weeks of treatment to ensure steady state plasma concentration. Maintenance of concizumab plasma concentration above 200 ng/mL is important to decrease the risk of bleeding episodes. If concizumab-mtci plasma concentration remains below 200 ng/mL at two consecutive measurements, evaluate the benefits of continued Alhemo treatment versus the potential risk of bleeding events, and consider alternative therapies if available.
As Alhemo is dosed by body weight (mg/kg), it is important to recalculate the dose when patients experience body weight changes.
Missed DoseAdherence to daily dosing of Alhemo is important to maintain protection against bleeding. This is especially important during the initial 4 weeks of treatment to ensure a correct maintenance dose is established. Patients who miss a dose during the initial 4-week period should inform their healthcare professional and resume once daily dosing at the initial 0.2 mg/kg dose level.
Missed Doses Once the Maintenance Dose Has Been EstablishedThe following dosing guidelines should apply
ONLYwhen a patient has forgotten to or neglected to take their once daily maintenance dose:• 1 missed dose: Resume once daily treatment at the maintenance dose level• 2 to 6 missed doses: Resume treatment with a double dose followed by once daily treatment at the maintenance dose level• 7 or more missed doses: Physician should be contacted, and a new loading dose should be considered[see Dosage and Administration ]
Management of Breakthrough BleedsNo dose adjustment of Alhemo is required in the case of breakthrough bleeds.
Management in the Perioperative SettingNo dose adjustment of Alhemo is required in the case of minor surgeries.
As there is limited experience in the perioperative setting, it is generally recommended to pause Alhemo at least 4 days prior to major surgery. Alhemo therapy can be resumed 10-14 days after surgery on the same maintenance dose without a new loading dose, considering the overall clinical picture of the patient. If necessary, consult a physician experienced in surgery of patients with bleeding disorders.
Immune Tolerance InductionThe safety and efficacy of concomitant use of Alhemo in patients receiving ongoing Immune Tolerance Induction (ITI), a desensitization strategy for the eradication of inhibitors, have not been established, and no data are available. Careful assessment of the potential benefits and risks should be performed if continuation or initiation of Alhemo during ITI is considered.
o 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 using an FDA-authorized test for the measurement of concizumab-mtci concentration in plasma.
See full Prescribing Information for important preparation and administration instructions and dosage adjustment. (
Alhemo should be administered once daily. Avoid missed doses.
Recommended dosing regimen:
• Day 1: Loading dose of 1 mg/kg• 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 using an FDA-authorized test. Information on the FDA-authorized test for the measurement of concizumab-mtci plasma concentration is available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/denovo.cfm. 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:o Less than 200 ng/mL: adjust to a once daily dose of 0.25 mg/kgo 200 to 4,000 ng/mL: continue once daily dose of 0.2 mg/kgo Greater than 4,000 ng/mL: adjust to a once daily dose of 0.15 mg/kg
The calculated dose is rounded off to the nearest injectable dose as follows:
• 60 mg/1.5 mL (40 mg/mL) in increments of 0.4 mg (brown label)• 150 mg/1.5 mL (100 mg/mL) in increments of 1 mg (gold label)• 300 mg/3 mL (100 mg/mL) in increments of 1 mg (white label)
Additional measurements of concizumab-mtci plasma concentration should be taken at routine clinical follow-ups provided the patient has been on the same maintenance dose for 8 weeks of treatment to ensure steady state plasma concentration. Maintenance of concizumab plasma concentration above 200 ng/mL is important to decrease the risk of bleeding episodes. If concizumab-mtci plasma concentration remains below 200 ng/mL at two consecutive measurements, evaluate the benefits of continued Alhemo treatment versus the potential risk of bleeding events, and consider alternative therapies if available.
As Alhemo is dosed by body weight (mg/kg), it is important to recalculate the dose when patients experience body weight changes.
Adherence to daily dosing of Alhemo is important to maintain protection against bleeding. This is especially important during the initial 4 weeks of treatment to ensure a correct maintenance dose is established. Patients who miss a dose during the initial 4-week period should inform their healthcare professional and resume once daily dosing at the initial 0.2 mg/kg dose level.
The following dosing guidelines should apply
• 1 missed dose: Resume once daily treatment at the maintenance dose level• 2 to 6 missed doses: Resume treatment with a double dose followed by once daily treatment at the maintenance dose level• 7 or more missed doses: Physician should be contacted, and a new loading dose should be considered[see Dosage and Administration ]
No dose adjustment of Alhemo is required in the case of breakthrough bleeds.
No dose adjustment of Alhemo is required in the case of minor surgeries.
As there is limited experience in the perioperative setting, it is generally recommended to pause Alhemo at least 4 days prior to major surgery. Alhemo therapy can be resumed 10-14 days after surgery on the same maintenance dose without a new loading dose, considering the overall clinical picture of the patient. If necessary, consult a physician experienced in surgery of patients with bleeding disorders.
The safety and efficacy of concomitant use of Alhemo in patients receiving ongoing Immune Tolerance Induction (ITI), a desensitization strategy for the eradication of inhibitors, have not been established, and no data are available. Careful assessment of the potential benefits and risks should be performed if continuation or initiation of Alhemo during ITI is considered.
Treatment with FVIII or FIX or all bypassing agents (e.g., rFVIIa or aPCC) can be used for breakthrough bleeds, and the dose and duration will depend on the location and severity of the bleed.
For mild and moderate bleeds that require additional treatment with FVIII or FIX or bypassing agents (e.g., rFVIIa or aPCC), the lowest-approved dose and the dose interval in the approved product labeling is recommended. For aPCC, a maximum dose of 100 units/kg body weight within 24 hours is recommended.
For severe bleeds, follow the dosing instructions provided in the approved labeling for the specific product based on clinical judgement.
Treatment is intended for use under the guidance of a healthcare provider. Treatment should be initiated in a nonbleeding state.
Alhemo may be self-administered or administered by a caregiver after appropriate training and reading the Instructions for Use, if a healthcare provider determines that is appropriate.
Administer Alhemo by subcutaneous injection to the abdomen or thigh with rotation of injection site every day. Subcutaneous injections should not be given in areas where the skin is tender, bruised, red or hard, or areas where there are moles, scars, or stretch marks. Children and lean patients should be instructed to use injection techniques that minimize risk of intramuscular injection, e.g. injecting into a pinched fold of skin.
Always use a new needle for each injection.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Alhemo 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.
Each Alhemo prefilled pen is for use by a single patient. An Alhemo pen must not be shared between patients, even if the needle is changed.
Alhemo is recommended to be used with NovoFine®or NovoFine®Plus needles with a gauge of 32 and a length of 4 mm. If needles longer than 4 mm are used, injection techniques that minimize the risk of intramuscular injection should be used.
Instructions for delivering the dosage are provided in the Instructions for Use leaflet enclosed with each Alhemo single-patient-use prefilled pen.
Alhemo injection is a clear to slightly opalescent and colorless to slightly yellow solution that may contain translucent to white particles, available in the following presentations:
• 60 mg/1.5 mL (40 mg/mL) in a single-patient-use prefilled pen• 150 mg/1.5 mL (100 mg/mL) in a single-patient-use prefilled pen• 300 mg/3 mL (100 mg/mL) in a single-patient-use prefilled pen
Based on its mechanism of action, Alhemo may cause fetal harm when administered to a pregnant woman
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 regardless of their inhibitor status.
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.
The estimated background risk of birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defect and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Alhemo is contraindicated in patients with a history of known serious hypersensitivity to Alhemo or its components or the inactive ingredients
Concizumab-mtci, is a humanized IgG4 monoclonal antibody produced by recombinant DNA technology in Chinese Hamster Ovary (CHO) cells with an approximate molecular weight of 149 kDa.
Alhemo (concizumab-mtci) injection is a clear to slightly opalescent, and colorless to slightly yellow solution that may contain translucent to white particles. Alhemo is supplied as a single-patient-use prefilled pen for subcutaneous injection.
Each 1 mL of Alhemo single-patient-use prefilled pen (60 mg/1.5 mL) contains 40 mg active ingredient concizumab-mtci. Each 1 mL of Alhemo single-patient-use prefilled pen (150 mg/1.5 mL) contains 100 mg active ingredient concizumab-mtci. Each 1 mL of Alhemo single-patient-use prefilled pen (300 mg/3 mL) contains 100 mg active ingredient concizumab-mtci.
Each 1 mL of Alhemo single-patient-use prefilled pen contains the following excipients: arginine hydrochloride (5.27 mg), histidine (5.12 mg), phenol (3.5 mg), polysorbate 80 (0.25 mg), sodium chloride (1.46 mg), sucrose (51.3 mg), and water for injection. Hydrochloric acid and sodium hydroxide may be added to adjust the pH to 6.0.
• Thromboembolic Events: Monitor patients for thromboembolic events. Advise patients to report signs and symptoms, and if they occur discontinue prophylaxis.• Hypersensitivity Reactions: In the event of a severe hypersensitivity reaction, discontinue Alhemo.• Increased Laboratory Values of Fibrin D dimer and Prothrombin Fragment 1.2: Alhemo increases values of fibrin D dimer and prothrombin fragment 1.2.