Generic: CONCIZUMAB
Tissue Factor Pathway Inhibitor Antagonist [EPC]
1 INDICATIONS AND USAGE 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 Alhemo is a tissue factor pathway inhibitor (TFPI) antagonist indicated for routine prophylaxis to prevent or reduce the frequency of bleeding episo...
1 INDICATIONS AND USAGE 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 Alhemo 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 or without FVIII inhibitors • hemophilia B (congenital factor IX deficiency) with or without FIX inhibitors ( 1 )
5 WARNINGS AND PRECAUTIONS • Thromboembolic Events: Monitor patients for thromboembolic events. Advise patients to report signs and symptoms, and if they occur discontinue prophylaxis. ( 5.1 ) • Hypersensitivity Reactions: In the event of a severe hypersensitivity reaction, discontinue Alhemo. ( 5.2 ) • Increased Laboratory Values of Fibrin D dimer and Prothrombin Fragment 1.2: Alhemo increases values of fibrin D dimer and prothrombin fragment 1.2. ( 5.3 ) 5.1 Thromboembolic Events Alhemo may ca...
5 WARNINGS AND PRECAUTIONS • Thromboembolic Events: Monitor patients for thromboembolic events. Advise patients to report signs and symptoms, and if they occur discontinue prophylaxis. ( 5.1 ) • Hypersensitivity Reactions: In the event of a severe hypersensitivity reaction, discontinue Alhemo. ( 5.2 ) • Increased Laboratory Values of Fibrin D dimer and Prothrombin Fragment 1.2: Alhemo increases values of fibrin D dimer and prothrombin fragment 1.2. ( 5.3 ) 5.1 Thromboembolic Events Alhemo may cause thromboembolic events. Venous and arterial thromboembolic events were reported in 1.9% of patients (6/320) in Alhemo clinical trials. These cases occurred in patients with multiple risk factors for thromboembolism, including the use of high doses or prolonged treatment with factor product or bypassing agent (2 of 6 patients). Risk factors for thromboembolism 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 (e.g., atherosclerotic disease, crush injury, cancer, disseminated intravascular coagulation, thrombotic microangiopathy, or septicemia). Inform Alhemo treated patients of signs and symptoms of thromboembolic events. Monitor patients for thromboembolic events. In case of suspicion of thromboembolic events, discontinue Alhemo and initiate further investigations and management strategies. 5.2 Hypersensitivity Reactions Alhemo can cause hypersensitivity reaction, including serious cases. Alhemo is contraindicated in patients with a history of known serious hypersensitivity to Alhemo or its components or the inactive ingredients. Hypersensitivity reactions including erythema, rash, pruritus, and abdominal pain have occurred in Alhemo treated patients. One patient (less than 1% of patients treated in the clinical studies) experienced anaphylaxis which resolved after treatment with antihistamines and corticosteroids. Instruct patients of the signs of acute hypersensitivity reactions. Instruct patients to contact their healthcare provider for mild reactions and to seek urgent medical attention for moderate to severe reactions. Discontinue Alhemo if severe hypersensitivity symptoms occur and initiate medical management. 5.3 Increased Laboratory Values of Fibrin D-dimer and Prothrombin Fragment 1.2 Alhemo can cause increased levels 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 26 (8.1%) of patients, respectively. The plasma concentration of concizumab-mtci is positively correlated with fibrin D-dimer and prothrombin fragments 1.2 indicating a hemostatic effect of concizumab-mtci. For patients taking Alhemo, these coagulation biomarkers may not be reliable predictive markers for clinical decision-making with suspicion of thrombosis such as deep vein thrombosis (DVT) and pulmonary embolism (PE).
6 ADVERSE REACTIONS The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling: • Thromboembolic Events [see Warnings and Precautions ( 5.1 )] • Hypersensitivity Reactions [see Warnings and Precautions ( 5.2 )] • Increased Laboratory Values of Fibrin D-dimer and Prothrombin Fragment 1.2 [see Warnings and Precautions ( 5.3 )] The most frequently reported adverse reactions (incidence ≥5%) were injection site reactions, headache and urti...
6 ADVERSE REACTIONS The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling: • Thromboembolic Events [see Warnings and Precautions ( 5.1 )] • Hypersensitivity Reactions [see Warnings and Precautions ( 5.2 )] • Increased Laboratory Values of Fibrin D-dimer and Prothrombin Fragment 1.2 [see Warnings and Precautions ( 5.3 )] The most frequently reported adverse reactions (incidence ≥5%) were injection site reactions, headache and urticaria. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Novo Nordisk Inc. at 1-800-727-6500 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates observed in clinical practice. The data in the WARNINGS AND PRECAUTIONS reflect exposure to Alhemo based on pooled data from clinical trials explorer3 (phase 1b), explorer4 (phase 2), explorer5 (phase 2), explorer7 (phase 3) and explorer8 (phase 3), in which a total of 320 male patients with hemophilia A with and without inhibitors and hemophilia B with and without inhibitors received at least one dose of Alhemo as routine prophylaxis. The patients were exposed for a total of 475 exposure years. Patients with HAwI (hemophilia A with inhibitors) and HBwI (hemophilia B with inhibitors) The data described below reflect exposure of 52 patients with HAwI and HBwI who were previously treated on-demand therapy and who were randomized in explorer7 to arm 1 to receive on- demand treatment with bypassing agents (n = 19) or arm 2 to receive Alhemo prophylaxis (n = 33) at the recommended dosing regimen [see Clinical Studies ( 14.1 )] . The median duration of treatment was 31.1 weeks (range 3.9, 72.9 weeks) in arm 1 (on-demand arm) and 40.1 weeks (range 3.1, 56.3 weeks) in arm 2 (Alhemo prophylaxis). Serious adverse reactions were reported in 6.1% of patients who received Alhemo. These serious adverse reactions were renal infarct and hypersensitivity reaction. Permanent discontinuation of Alhemo due to an adverse reaction occurred in 1 patient due to a renal infarct. Dosage interruptions of Alhemo due to an adverse reaction occurred in 1 patient (3%) and was a hypersensitivity reaction. The most common adverse reactions (≥5%) were injection site reactions and urticaria (see Table 1 ). Table 1. Adverse Reactions Reported in ≥5% HAwI and HBwI Patients Randomized to Alhemo in Explorer7 Adverse Reaction Alhemo Prophylaxis N=33 (%) On-demand Treatment N=19 (%) Injection site reactions 18% 0% Urticaria 6% 0% Injection site reactions included: Injection site bruising, Injection site erythema, Injection site hematoma, Injection site hemorrhage, Injection site reaction and Injection site urticaria. Urticaria included: Urticaria and Injection site urticaria. Patients with HA (hemophilia A without inhibitors) and HB (hemophilia B without inhibitors) The data described below reflect exposure of 63 patients with HA and HB who were previously treated on-demand therapy and who were randomized in explorer8 to arm 1 to receive on- demand treatment with factor product (n = 21) or arm 2 to receive Alhemo prophylaxis (n = 42) at the recommended dosing regimen [see Clinical Studies ( 14.2 )] . The median duration of treatment was 24.1 weeks (range 23.6, 56.1 weeks) in arm 1 (on- demand arm) and 32.1 weeks (range 3.9, 33.6 weeks) in arm 2 (Alhemo prophylaxis). The most common adverse reactions (≥5%) were injection site reactions and headache (see Table 2 ). Table 2. Adverse Reactions Reported in ≥5% HA and HB Patients Randomized to Alhemo in Explorer8 Adverse Reaction Alhemo Prophylaxis N=42 (%) On-demand Treatment N=21 (%) Injection site reactions 7% 0% Headache 7% 0% Injection site reactions included: injection site reaction, injection site rash, and injection site nodule
Medical Disclaimer: This information is for educational purposes only and does not constitute medical advice. Always consult a licensed healthcare provider before making any decisions about your medications. Data sourced from openFDA.