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ALHEMO is a brand name for Concizumab, supplied as a solution. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: TBD TABLE OF CONTENTS TABLE OF CONTENTS ........................................................................................................... 2 PART I: HEALTH PROFESSIONAL INFORMATION ............................................................... 4 1 INDICATIONS…
Verbatim from this product's HC label. Tap a section to expand.
1 Dosing Considerations • Treatment should be initiated under the supervision of a health professional experienced in treatment of hemophilia and/or bleeding disorders. • Prior to initiation of Alhemo, patients should discontinue prophylactic treatment with bypassing agents.
Treatment with recombinant activated Factor VII (rFVIIa) should be discontinued at least 12 hours before starting Alhemo and treatment with activated prothrombin complex concentrates (aPCC) should be discontinued at least 48 hours before starting Alhemo.
• Hemophilia A patients with FVIII inhibitors should discontinue emicizumab 6 months before starting treatment with Alhemo. • Treatment should be initiated in a non-bleeding state. g. parent) only after proper training by a health professional..
• Intramuscular injections should be avoided and these may occur inadvertently, particularly in lean and younger patients where it is recommended to inject into a loosely-held skin-fold. 2 mg/kg, which is followed by an individualized daily maintenance dose according to the following schedule: • Day 1: a loading dose of 1 mg/kg once.
20 mg/kg. • 4 weeks after initiation of treatment: measurement of concizumab pre-dose plasma concentration by a validated concizumab enzyme-linked immunosorbent assay (ELISA) as determined by an accredited laboratory. • Once the week 4 concizumab plasma concentration result is available the individual maintenance dose is set as indicated below in Table 1.
Table 1 Individual maintenance dose based on concizumab plasma concentration. 15 mg/kg While Alhemo can be administered at any time point of the day, it is recommended to advise patients to inject at the same time each day, in order to prevent doses occurring too close together.
The individual maintenance dose should be established at the earliest convenience (after concizumab plasma concentration week 4 result is available) and no later than 6-8 weeks after Alhemo™ (concizumab injection) Product Monograph Page 6 of 60 initiation of treatment.
The individual maintenance dose should only be determined in patients who adhere to their initial everyday dose. Patients who miss consecutive daily doses during this dose finding phase should inform their health professional so that a new 4 week uninterrupted daily dose period is established before plasma concizumab concentrations are measured.
1 Adverse Reaction Overview Hemophilia Patients with Inhibitors Treatment-emergent adverse events (TEAEs) are reported from the main NN7415-4311 (explorer7) clinical study. Patients included in the safety and efficacy analyses were randomized 1:2 to Arm 1 (n = 19) and received on-demand therapy with bypassing agents or to Arm 2 (n = 33) and received Alhemo prophylaxis (see efficacy results in Clinical Trials [14]).
Additional nonrandomized patients treated with Alhemo in Arms 3 and 4 of the study were included in the overall Alhemo safety population for a total of 114 hemophilia patients with inhibitors (78 adults and 36 adolescents). 25 mg/kg daily dose and events reported in patients treated with the recommended Alhemo dosing regimen after the clinical pause (see Dosage and Administration [4]).
2 Clinical Trial Adverse Reactions Clinical trials are conducted under very specific conditions. The adverse reaction rates observed in the clinical trials; therefore, may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.
Adverse reaction information from clinical trials may be useful in identifying and approximating rates of adverse drug reactions in real-world use. 9%); both led to permanent discontinuation of Alhemo. Common TEAEs (≥ 5%) are reported in Table 4.
3% *Injection site reactions: Include the preferred terms injection site rash, injection site erythema, injection site urticaria, injection site reaction, injection site bruising, injection site hematoma, injection site swelling, injection site pruritus, injection site hemorrhage, injection site hypoesthesia, injection site induration, and injection site pain.
8%) of the patients. 5%). One event of moderate injection site rash led to interruption of Alhemo therapy. 1%) patients. 2 indicating hemostatic effect of concizumab. 1 Clinical Trial Adverse Reactions – Pediatrics Hemophilia Patients with Inhibitors The safety profile of Alhemo was similar between adolescent and adult patients.
See Serious Warnings And Precautions [3]. General Route of Administration Dosage Form / Strength/Composition Non-medicinal Ingredients Subcutaneous Solution for injection in a pre-filled, multi-dose disposable pen 15 mg (10 mg/mL) 60 mg (40 mg/mL) 150 mg (100 mg/mL) 300 mg (100 mg/mL) L-Arginine HCl L-Histidine Sodium chloride Sucrose Polysorbate 80 Phenol Water for injection Hydrochloric acid Sodium hydroxide Alhemo™ (concizumab injection) Product Monograph Page 10 of 60 Health professionals should discuss with patients or caregivers at the start of treatment with Alhemo that one or more missed doses of Alhemo may significantly affect the efficacy of the product and the ability to establish a proper maintenance dose.
If a patient or caregiver can not follow the every day dosing regimen then alternative treatment options should be considered. Driving and Operating Machinery There is no evidence that Alhemo affects one’s ability to drive and use machines.
Hematologic Thromboembolic Events Serious thromboembolic events (TEEs) reported in association with Alhemo resulted in a pause in clinical development from March to August 2020, and a new dosing regimen based on plasma concizumab concentrations was implemented (see Dosage and Administration [4]).
Patients treated with Alhemo should be informed of and monitored for the occurrence of signs and symptoms of thromboembolic events. Patients who experienced thromboembolic events in clinical trials were exposed to additional hemostatic agents in close proximity with administration of Alhemo.
The half-life of bypassing agents and emicizumab should be considered when switching to Alhemo (see Dosage and Administration [4]). Patients should be advised on how to treat breakthrough bleeds. In the case where other hemostatic agents are required to treat mild or moderate breakthrough bleeds, it is recommended to treat with the lowest possible effective dose (see Dosage and Administration [4]).
Alhemo is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see Dosage Forms, Strengths, Composition and Packaging [6].
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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15 mg/kg. 15 mg/kg, a second concizumab concentration should be considered. Ideally, the second concizumab concentration should be taken 8 weeks after initiation of the lower dose to ensure patients reach steady-state. If the plasma concentration remains above 4000 ng/mL then the benefits of Alhemo should be evaluated versus the potential for an increased risk of thromboembolic events.
Additional concizumab plasma concentration measurements can also be taken after 8 weeks on the same maintenance dose according to the patient’s medical condition. For example, this should be considered if a patient experiences an increased bleeding frequency or acquires a comorbidity, which could affect their coagulation system or drug metabolism/excretion.
In some instances, a more frequent therapeutic type monitoring of plasma concizumab concentrations may be considered appropriate (semi- annual or annual) and this should be discussed in consultation with the patient. Geriatrics (> 65 years of age) No dose adjustments (besides individual maintenance dose setting) are recommended in patients ≥65 years of age.
Pediatrics (<12 years of age) The efficacy and safety of Alhemo in children less than 12 years of age has not yet been established. 3]). 5x ULN) were not included in the clinical trials. Guidance on the Use of Breakthrough Bleed Treatment No dose adjustment of Alhemo should be done in case of breakthrough bleeds.
Health professionals should discuss with all patients and/or caregivers about the dose and schedule of bypassing agents to use, if required, while receiving Alhemo prophylaxis, including using the lowest possible effective dose to minimize the risk of thromboembolic events for mild and moderate bleeds, which includes a maximum aPCC dose of 100 U/kg within 24 hours.
For severe bleeds, it may be necessary to follow the dosing scheme provided in the approved label for a bypassing agent but this should be based on clinical judgement taking into account the Alhemo™ (concizumab injection) Product Monograph Page 7 of 60 potential for life-threatening thromboembolic events.
Management in the perioperative setting No dose adjustment of Alhemo is needed in case of minor surgeries. For a major surgery, consult a health professional experienced in treatment of hemophilia and/or bleeding disorders. As there is no clinical experience in using Alhemo during major surgeries […]
There is limited clinical data in children below 12 years of age. 3 Less Common Clinical Trial Adverse Reactions Hemophilia Patients with Inhibitors The following less common but significant clinical trial adverse reactions have been reported in association with Alhemo.
9%)
Patients were to be excluded from clinical studies if they were at high risk for developing thromboembolic events and there should be careful consideration whether the potential benefit of Alhemo treatment outweighs the potential risk of thromboembolic complications in these patients.
Risk factors include a history or family history of TEEs, obesity, arrhythmias, hypertension, diabetes, hypercholesterolaemia, smoking, recent major surgeries, and old age taking into consideration the totality of risk factors for the individual patient.
g. advanced atherosclerotic disease, crush injury, cancer or septicaemia), may have further risks of thromboembolic events or disseminated intravascular coagulation (DIC) with Alhemo treatment. In clinical studies, there was a positive correlation with concizumab plasma concentrations and D-dimer and prothrombin fragment 1+2 plasma levels (see Adverse Reactions [8]).
In case of suspicion of thromboembolic events, Alhemo should be permanently discontinued and further investigations and appropriate medical treatment should be initiated. Immune Hypersensitivity Reactions Allergic-type hypersensitivity reactions have occurred with Alhemo, including hospitalization and permanent discontinuation of therapy.
Patients should be informed of the signs of acute hypersensitivity reactions while receiving Alhemo. Discontinue use of Alhemo if hypersensitivity Alhemo™ (concizumab injection) Product Monograph Page 11 of 60 symptoms occur and initiate appropriate treatment.
3]). Most patients found to have anti-concizumab antibodies did not experience a change in concizumab plasma concentrations, an increase in bleeding events or any additional safety concerns; however, there were two cases (one in a clinical trial and one in a compassionate use program) where reduction of effectiveness of Alhemo was reported.
g. increase in breakthrough bleeding events), prompt evaluation by a physician should be sought to assess the etiology and a possible change in treatment should be considered.
Reproductive Health:
Female and Male Potential Fertility Animal studies do not indicate direct or indirect harmful effects with respect to fertility (see Non- Clinical Toxicology [16]). No fertility data are available in humans. Thus, the effect of Alhemo on male and female fertility is unknown.
Contraception Women of childbearing potential receiving Alhemo should use highly effective contraception during treatment with Alhemo and until 7 weeks after end of treatment. The benefits and risks of the type of contraceptives used should be evaluated by the treating health professional.
1 Pregnant Women There are no clinical studies of Alhemo use in pregnant women. Animal reproduction studies have not been conducted with Alhemo as most patients treated with Alhemo are male. It is not known whether Alhemo can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity.
Alhemo should be used during pregnancy only if the potential benefit outweighs the potential risk to the fetus. 2 Breast-feeding There is no information regarding the presence of Alhemo in human milk, the effect on the breastfed infant, or the effects on milk production.
Human IgG is known to be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for and any potential adverse effects on the breastfed infant from Alhemo or from the underlying maternal condition.
3 Pediatrics Forty-two adolescent patients (aged 12 to less than 18 years) were included in the main NN7415-4311 (explorer7) clinical study to evaluate the safety and […]