Concizumab

Concizumab is a prescription medication indicated for routine prophylaxis to prevent or reduce frequency of bleeding episodes in adult and pediatric patients aged 12 years and older with:

• hemophilia A (congenital factor VIII deficiency) with factor VIII inhibitors
• hemophilia B (congenital factor IX deficiency) with factor IX inhibitors

Concizumab is available under the following different brand names: Alhemo, concizumab-mtci.

Common side effects of Concizumab include:

• bruising, redness, bleeding, or itching at the site of injection 
• hives

Serious side effects of Concizumab include:

• blood clots (thromboembolic events) symptoms include swelling, warmth, pain, or redness of the skin, headache, trouble speaking or moving, eye pain or swelling, sudden pain in the stomach or lower back area, feeling shortness of breath or severe chest pain, confusion, numbness in the face, problems with the vision
• allergic reaction symptoms include Itching on large areas of skin, trouble swallowing, wheezing, pale and cold skin, dizziness due to low blood pressure, redness or swelling of lips, tongue, face, or hands, shortness of breath, tightness of the chest, fast heartbeat 

Rare side effects of Concizumab include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult and pediatric dosage

Solution for SC injection

• Single-use prefilled pen
  • 60 mg/1.5 mL (40 mg/mL)
  • 150 mg/1.5 mL (100 mg/mL)
  • 300 mg/3 mL (100 mg/mL)

Hemophilia A

Adult and pediatric dosage

See Dosage Modifications for dose rounding guidance

• Day 1
  • Loading dose: 1 mg/kg SC
• Day 2
  • 0.2 mg/kg SC once daily for 4 weeks
  • Measure concizumab plasma concentration by enzyme-linked immunosorbent assay (ELISA) before the next scheduled dose
• Maintenance dose
  • Start maintenance after the concizumab plasma concentration result is available and no later than 8 weeks from the start of therapy
  • Individualize dose based on concizumab plasma concentration
  • Less than 200 nanograms (ng)/mL: Increase to 0.25 mg/kg SC once daily
  • Between 200 to 4000 ng/mL: Continue 0.2 mg/kg SC once daily
  • More than 4000 ng/mL: Decrease to 0.15 mg/kg SC once daily

Hemophilia B

Adult and pediatric dosage

See Dosage Modifications for dose rounding guidance

• Day 1
  • Loading dose: 1 mg/kg SC
• Day 2
  • 0.2 mg/kg SC once daily for 4 weeks
  • Measure concizumab plasma concentration by ELISA before the next scheduled dose
• Maintenance dose
  • Start maintenance after the concizumab plasma concentration result is available and no later than 8 weeks from the start of therapy
  • Individualize dose based on concizumab plasma concentration
  • Less than 200 nanograms (ng)/mL: Increase to 0.25 mg/kg SC once daily
  • Between 200 to 4000 ng/mL: Continue 0.2 mg/kg SC once daily
  • More than 4000 ng/mL: Decrease to 0.15 mg/kg SC once daily

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Concizumab has no noted severe interactions with any other drugs
• Concizumab has no noted serious interactions with any other drugs
• Concizumab has no noted moderate interactions with any other drugs
• Concizumab has no noted minor interactions with any other drugs

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• Serious hypersensitivity to concizumab or any product components (eg, inactive ingredients)

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Concizumab?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Concizumab?”

Cautions

• Thromboembolic events
  • Venous and arterial thromboembolic events reported in clinical trials
  • Half of the events occurred in patients with multiple risk factors for thromboembolism (e.g., use of high doses of or prolonged treatment with factor product or bypassing agent)
  • Risk factors for thromboembolism may include
    • High and/or frequent doses of breakthrough bleed treatments (e.g., factor products or bypassing agents)
    • Conditions that overexpress tissue factors (eg, atherosclerotic disease, crush injury, cancer, disseminated intravascular coagulation, thrombotic microangiopathy, septicemia)
    • Monitor for thromboembolic events
    • Educate patients on the signs and symptoms of thromboembolic events
    • Discontinue if a thromboembolic event is suspected and evaluate further
• Hypersensitivity reactions
  • Hypersensitivity reactions (e.g., erythema, rash, pruritus, abdominal pain) reported
  • Reaction may resolve following treatment with antihistamines and corticosteroids
  • Educate patients of signs of acute hypersensitivity reactions
  • Advise patients to:
    • Contact their healthcare provider for mild reactions
    • Seek urgent medical attention for moderate to severe reactions
    • Discontinue therapy for severe hypersensitivity symptoms occur and manage medically
• Increased coagulation biomarkers
  • Concizumab plasma concentration positively correlates 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 (DVT) and pulmonary embolism (PE)
• Drug interaction overview
  • Immune tolerance induction (ITI)
    • Safety and efficacy of concomitant use with ITI, desensitization strategy for eradication of inhibitors, not established
    • Carefully weigh potential benefits with risks if ITI is continued or concizumab is started during ITI
  • Bypassing agents
    • Bypassing agents may be used with concizumab for break-through bleeding events
    • Take appropriate precautions when these agents are used together; dosage adjustments of bypassing agents may be necessary
    • Additive and sometimes synergistic increase in thrombin peak, as quantified in thrombin generation assay, has been observed in plasma from hemophilia patients receiving concizumab prophylaxis and rFVIII, rFIX or bypassing agents (eg, rFVIIa, aPCC)

Pregnancy and Lactation

• May cause fetal harm if used during pregnancy, based on the mechanism of action
• Monoclonal antibodies, such as concizumab, can be actively transported across the placenta
• No available data on use in pregnant women to evaluate for drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes
• Animal reproduction studies have not been conducted
• It is not known if concizumab affects reproductive capacity
• Use during pregnancy only if the potential benefit for the mother outweighs the potential fetal risk
• Perform pregnancy testing in females of reproductive potential
• Contraception
  • Highly effective contraception recommended in females of reproductive potential during and for 7 weeks after therapy
  • Evaluate the benefits and thromboembolic risks of contraceptive types to determine the best option
• Lactation
  • No available data on the presence of concizumab  in human or animal milk, its effect on breastfed children, or milk production
  • Human IgGs are excreted in breast milk during the first few days after birth, decreasing to low concentrations soon afterward
  • Risk to breast-fed infants cannot be excluded during this period