Concizumab Dosage

Usual Adult Dose for Hemophilia A with Inhibitors

Loading dose (Day 1): 1 mg/kg subcutaneously once

Initial dose (Day 2 and until maintenance dose established): 0.2 mg/kg subcutaneously once a day

• Assess plasma drug concentration 4 weeks after treatment initiation.

Maintenance dose (individualized based on Week 4 plasma drug concentration):

• Less than 200 ng/mL: Adjust to 0.25 mg/kg subcutaneously once a day
• Between 200 to 4000 ng/mL: Continue 0.2 mg/kg subcutaneously once a day
• Greater than 4000 ng/mL: Adjust to 0.15 mg/kg subcutaneously once a day

Comments:

• To measure pre-dose plasma drug concentrations, utilize a concizumab enzyme-linked immunosorbent assay (ELISA); a US FDA-authorized test is not currently available.
• The maintenance dose should be established no later than 8 weeks after starting treatment.
• Plasma drug concentrations should be measured at routine follow-ups (as long as the patient has received the same dose for 8 weeks) and maintained above 200 ng/mL to decrease the risk of bleeding episodes.
• If plasma drug concentrations remain below 200 ng/mL after 2 consecutive measurements, reevaluate risk vs benefit of continued treatment; alternative therapies should be considered, if available.
• Recalculate the dose if the patient experiences body weight changes.

Use: For routine prophylaxis to prevent or reduce the frequency of bleeding episodes in patients with hemophilia A (congenital factor VIII [FVIII] deficiency) with FVIII inhibitors, and hemophilia B (congenital factor IX [FIX] deficiency) with FIX inhibitors

Usual Adult Dose for Hemophilia B with Inhibitors

Loading dose (Day 1): 1 mg/kg subcutaneously once

Initial dose (Day 2 and until maintenance dose established): 0.2 mg/kg subcutaneously once a day

• Assess plasma drug concentration 4 weeks after treatment initiation.

Maintenance dose (individualized based on Week 4 plasma drug concentration):

• Less than 200 ng/mL: Adjust to 0.25 mg/kg subcutaneously once a day
• Between 200 to 4000 ng/mL: Continue 0.2 mg/kg subcutaneously once a day
• Greater than 4000 ng/mL: Adjust to 0.15 mg/kg subcutaneously once a day

Comments:

• To measure pre-dose plasma drug concentrations, utilize a concizumab enzyme-linked immunosorbent assay (ELISA); a US FDA-authorized test is not currently available.
• The maintenance dose should be established no later than 8 weeks after starting treatment.
• Plasma drug concentrations should be measured at routine follow-ups (as long as the patient has received the same dose for 8 weeks) and maintained above 200 ng/mL to decrease the risk of bleeding episodes.
• If plasma drug concentrations remain below 200 ng/mL after 2 consecutive measurements, reevaluate risk vs benefit of continued treatment; alternative therapies should be considered, if available.
• Recalculate the dose if the patient experiences body weight changes.

Use: For routine prophylaxis to prevent or reduce the frequency of bleeding episodes in patients with hemophilia A (congenital factor VIII [FVIII] deficiency) with FVIII inhibitors, and hemophilia B (congenital factor IX [FIX] deficiency) with FIX inhibitors

Usual Pediatric Dose for Hemophilia A with Inhibitors

12 YEARS AND OLDER:
Loading dose (Day 1): 1 mg/kg subcutaneously once

Initial dose (Day 2 and until maintenance dose established): 0.2 mg/kg subcutaneously once a day

• Assess plasma drug concentration 4 weeks after treatment initiation.

Maintenance dose (individualized based on Week 4 plasma drug concentration):

• Less than 200 ng/mL: Adjust to 0.25 mg/kg subcutaneously once a day
• Between 200 to 4000 ng/mL: Continue 0.2 mg/kg subcutaneously once a day
• Greater than 4000 ng/mL: Adjust to 0.15 mg/kg subcutaneously once a day

Comments:

• To measure the pre-dose plasma drug concentrations, utilize a concizumab ELISA; a US FDA-authorized test is not currently available.
• The maintenance dose should be established no later than 8 weeks after starting treatment.
• Plasma drug concentrations should be measured at routine follow-ups (as long as the patient has received the same dose for 8 weeks) and maintained above 200 ng/mL to decrease the risk of bleeding episodes.
• If plasma drug concentrations remain below 200 ng/mL after 2 consecutive measurements, reevaluate risk vs benefit of continued treatment; alternative therapies should be considered, if available.
• Recalculate the dose if the patient experiences body weight changes.

Use: For routine prophylaxis to prevent or reduce the frequency of bleeding episodes in patients with hemophilia A (congenital FVIII deficiency) with FVIII inhibitors, and hemophilia B (congenital FIX deficiency) with FIX inhibitors

Usual Pediatric Dose for Hemophilia B with Inhibitors

12 YEARS AND OLDER:
Loading dose (Day 1): 1 mg/kg subcutaneously once

Initial dose (Day 2 and until maintenance dose established): 0.2 mg/kg subcutaneously once a day

• Assess plasma drug concentration 4 weeks after treatment initiation.

Maintenance dose (individualized based on Week 4 plasma drug concentration):

• Less than 200 ng/mL: Adjust to 0.25 mg/kg subcutaneously once a day
• Between 200 to 4000 ng/mL: Continue 0.2 mg/kg subcutaneously once a day
• Greater than 4000 ng/mL: Adjust to 0.15 mg/kg subcutaneously once a day

Comments:

• To measure the pre-dose plasma drug concentrations, utilize a concizumab ELISA; a US FDA-authorized test is not currently available.
• The maintenance dose should be established no later than 8 weeks after starting treatment.
• Plasma drug concentrations should be measured at routine follow-ups (as long as the patient has received the same dose for 8 weeks) and maintained above 200 ng/mL to decrease the risk of bleeding episodes.
• If plasma drug concentrations remain below 200 ng/mL after 2 consecutive measurements, reevaluate risk vs benefit of continued treatment; alternative therapies should be considered, if available.
• Recalculate the dose if the patient experiences body weight changes.

Use: For routine prophylaxis to prevent or reduce the frequency of bleeding episodes in patients with hemophilia A (congenital FVIII deficiency) with FVIII inhibitors, and hemophilia B (congenital FIX deficiency) with FIX inhibitors

Renal Dose Adjustments

Renal dysfunction: Data not available

Liver Dose Adjustments

Liver dysfunction: Data not available

Dose Adjustments

DOSE MODIFICATIONS FOR BREAKTHROUGH BLEEDING:

• No dose adjustment is required for this drug in the case of breakthrough bleeding.
• For mild and moderate bleeds that require additional treatment with bypassing agents (e.g., recombinant activated factor VIIa [rFVIIa] or activated prothrombin complex concentrate [aPCC]): It is recommended to use the lowest-approved dose and interval.
• For aPCC: A maximum dose of 100 units/kg body weight within 24 hours is recommended.
• For severe bleeds: Follow the dosing recommendations in the manufacturer product information of the hemostatic agent, as guided by clinical judgement.

DOSE MODIFICATIONS IN THE PERIOPERATIVE SETTING

• For minor surgeries: No dose adjustment is required for this drug.
• For major surgeries: It is recommended to pause therapy at least 4 days prior, and then resume 10 to 14 days after surgery at the same maintenance dose, in consideration of the overall clinical picture.
• If necessary, consider consulting a specialist experienced in surgery of patients with bleeding disorders.

Precautions

CONTRAINDICATIONS:

• Known serious hypersensitivity to the active component or any of the ingredients

Safety and efficacy have not been established in patients younger than 12 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• For subcutaneous use only; each pen is for single patient use
• Prior to therapy, the manufacturer product information and Instructions for Use should be consulted for guidance on administration, dose calculation, monitoring, and other important considerations.
• Before treatment, ensure patients have discontinued use of other hemostatic products:
• For rFVIIa: Discontinue at least 12 hours prior
• For standard half-life FVIII or FIX: Discontinue at least 24 hours prior
• For aPCC: Discontinue at least 48 hours prior
• Therapy should be administered by a health care provider, or a patient/caregiver after proper training.
• Administer as a subcutaneous injection into the abdomen or thigh; rotate injection site every day.
• Do not deliver into areas that are tender, bruised, red, or hard; avoid moles, scars, or stretch marks.
• In children and lean patients, utilize injection techniques that minimize risk of IM injection.
• After 4 weeks of initial treatment, ensure plasma drug concentration is assessed in order to individualize the maintenance dose within 8 weeks of starting therapy. Subsequent monitoring is recommended, provided that the patient has adhered to the same dose for 8 weeks.

Missed doses:

• Dose missed during the initial 4-week dosing period: Resume once a day dosing at the initial 0.2 mg/kg dose level; health care provider should be contacted.
• Dose missed during the maintenance dosing period:
• For 1 missed dose: Resume once a day dosing at the maintenance dose level.
• For 2 to 6 missed doses: Resume therapy with a double dose, followed by maintenance dose once a day.
• For 7 or more missed doses: A new loading dose should be considered; health care provider should be contacted.

Storage requirements:

• Before first use: Store refrigerated (2C to 8C [36F to 46F])
• After first use: Store refrigerated or at room temperature (below 30C [86F]) for up to 28 days; discard any unused portion.
• It is recommended to store this drug with the cap on and in the original carton to protect from light/sunlight.
• Do not freeze or store close to the cooling element of a refrigerator, and keep away from direct heat.
• Do not use this product if previously frozen or stored above room temperature.

Reconstitution/preparation techniques:

• Consult the manufacturer product information for illustrated instructions.
• Inspect prefilled pen visually for particulate matter and discoloration; do not use if discolored.
• Calculated doses should be rounded to the nearest injectable dose.
• Always attach a new pen needle before injection.

General:

• Treatment should be initiated in a non-bleeding state.
• Adherence is essential to maintain protection against bleeding, especially during the initial dosing period.
• If bypassing agents, FVIII, or FIX are required during therapy, the dose and duration will depend on the location and severity of the bleed; ensure patients/caregivers understand the proper dosing.
• Consult the manufacturer product information of any bypassing agents used in combination with this drug.

Monitoring:

• General: For body weight changes that may require dose change (during therapy); plasma drug concentrations (4 weeks after initiation, then routinely after 8 weeks on maintenance dose)
• Hematologic: For signs/symptoms of thromboembolic or bleeding events (during therapy)

Patient advice:

• Read the US FDA-approved patient labeling (Medication Guide and Instructions for Use).
• Recognize the signs and symptoms of thromboembolic events; notify your health care provider for mild reactions and seek urgent medical attention for moderate to severe reactions.
• Immediately discontinue therapy if signs of hypersensitivity occur and contact your health care provider.
• Understand the importance of daily adherence to the dosing regimen; before stopping treatment, discuss with your health care provider as you may no longer be protected against bleeding.
• Speak to your health care provider if you are pregnant, intend to become pregnant, or are breastfeeding.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Medical Disclaimer