For U.S. Healthcare Professionals Only

How to start and administer CABLIVI1

Initiate CABLIVI in combination with PEX and continue for at least 30 days after last daily PEX

Day 1 Calendar

INITIATE CABLIVI

ON DAY 1, USE IV AND SC

11-mg bolus IV injection at least 15 minutes prior to PEX

Followed by an 11-mg SC injection after completed PEX

Plasma Bag

ADMINISTER DURING PEX

DAILY DURING PEX

Daily 11-mg SC injection following completion of daily PEX MISSED DOSE DURING PEX

  • If a dose of CABLIVI is missed during the PEX period, it should be given as soon as possible

30-Day Calendar

ADMINISTER POST-PEX

DAILY FOR 30 DAYS

Daily 11-mg SC injection for 30 days after stopping daily PEX treatment TREATMENT EXTENSION (UP TO 28 DAYS IF NEEDED) Daily 11-mg SC injection after initial treatment if signs of underlying disease persist (such as suppressed ADAMTS13) MISSED DOSE AFTER PEX

  • If a dose of CABLIVI is missed after the PEX period, it can be administered within 12 hours of the scheduled time of administration
  • Beyond 12 hours, the missed dose should be skipped and the next daily dose administered according to the usual dosing schedule

Discontinue CABLIVI if the patient experiences >2 recurrences of aTTP while on CABLIVI.

Withhold CABLIVI treatment 7 days prior to elective surgery, dental procedures, or other invasive interventions.

Reconstituting and administering CABLIVI1,2

For full reconstitution and administration instructions, please refer to the Instructions for Use.

The first dose of CABLIVI should be administered by a healthcare provider as a bolus intravenous injection. Administer subsequent doses subcutaneously in the abdomen. Avoid injections around the navel. Do not administer consecutive injections in the same abdominal quadrant.

Patients or caregivers may inject CABLIVI subcutaneously after proper training on the preparation and administration of CABLIVI, including aseptic technique.

Administration training video

You may use this video with your patients to help them better understand CABLIVI administration.

Keep watching for CABLIVI Important Safety Information at the end of this video. Talk to your doctor about any questions you have about CABLIVI. Be sure that you read, understand, and follow the Instructions for Use before you inject CABLIVI and each time you get a refill. There may be new information. Your healthcare provider should show you how to prepare and inject CABLIVI properly before your first injection. Talk to your healthcare provider if you have any questions.

When it’s time for your injection, take CABLIVI out of the refrigerator. Never freeze your vials. If needed, CABLIVI may be stored at room temperature for up to 2 months. It may be helpful to write the date it was removed from the refrigerator in the space provided on the carton. Keep CABLIVI in the carton that it came in to protect it from light. For each injection, one carton of CABLIVI is needed.

Wash your hands with soap and water and place all components of the kit on a clean, flat surface. Check to make sure the carton contains all the items needed to prepare a dose of CABLIVI. Only use the supplies that are provided in the carton to prepare your prescribed dose. Do not reuse any of the supplies. Check the expiration date on the package and vial.

If the carton was stored in the refrigerator, allow the vial and the syringe to reach room temperature by holding in your hands for 10 seconds.

Remove the green plastic flip-off cap from the vial, and clean the rubber stopper using one of the alcohol pads. Allow to dry for a few seconds.

Take the packed vial adapter and remove the paper cover leaving the vial adapter in its packaging for now.

Place the adapter over the vial, while keeping the adapter in its plastic packaging.

Press down firmly until the adapter snaps into place, with the adapter spike pushing through the vial stopper.

Leave the adapter attached to the vial, still in its outer packaging.

Holding the syringe in one hand, break off the white cap by snapping at the perforation of the cap with your other hand. Then lay the syringe on a clean flat surface.

Remove the plastic packaging from the adapter by pressing the sides of the adapter packaging, and then lifting the packaging upwards. Be sure that the adapter does not detach from the vial. Hold the adapter with the attached vial. Place the tip of the syringe on the connector part of the vial adapter. Gently lock the syringe onto the vial by turning it clockwise until it cannot twist any further.

Place the vial upright on a flat surface. Slowly push the syringe plunger down until the syringe is empty.

Gently swirl the vial with connected syringe until the powder is dissolved. Allow the vial with connected syringe to stand on the flat surface for 2 minutes to allow the solution to completely dissolve.

Use the mixed CABLIVI solution immediately. The mixed CABLIVI solution can be stored for up to 4 hours in the refrigerator. Check the solution for particles, cloudiness, or clumps. All powder must be fully dissolved, and the solution must be clear. Use a new carton or call your healthcare provider if solution is not clear. Slowly press the syringe’s plunger fully down. Turn the whole - vial, adapter and syringe - upside down. While keeping it vertical, slowly pull the plunger to transfer all the solution into the syringe.

Turn the whole - vial, adapter and syringe - right-side up and place on the flat surface. Detach the filled syringe from the adapter by gently turning the syringe counter-clockwise. Put the vial and the attached adapter into a sharps disposal container. Place the syringe on the clean flat surface.

Remove the needle from the package, and attach it to the syringe without removing the needle cap by turning clockwise until it cannot twist any further. Pull back the needle safety shield.

Use the second alcohol pad to clean the injection site on your abdomen. Avoid the 2-inch area around your belly button. Let your skin dry.

Carefully remove the needle protection cap from the needle. Hold the syringe at eye level with the needle pointing upwards to see if there are any air bubbles. Remove any air bubbles by tapping the side of the syringe with your finger until they rise towards the tip. Then, slowly push the plunger until a small amount of liquid drips out of the needle. Gently pinch the cleaned skin between your thumb and forefinger to make a fold. Hold the pinch during the entire injection. Insert the full length of the needle into the skin fold at a 45- to 90-degree angle and press the plunger down until all of the solution is gone. Pull out the needle at the same angle you inserted it.

Right after your injection, move the needle safety shield over the needle until it clicks into place. In case you are bleeding at the injection site, place a cotton ball over the skin right away. Press gently on the cotton ball until the bleeding has stopped.

Put the syringe, needle, and vial with adapter in a sharps disposal container right away after use. If you do not have an FDA-cleared sharps disposal container, you may use a household container that meets specific requirements according to your community guidelines.

Important Safety Information

Who should not take CABLIVI?

Do not take CABLIVI if you’ve had an allergic reaction to caplacizumab-yhdp or to any of the ingredients in CABLIVI.

What should I tell my healthcare team before starting CABLIVI?

Tell your doctor if you have a medical condition including if you have a bleeding disorder. Tell your doctor about any medicines you take.

Talk to your doctor before scheduling any surgery, medical or dental procedure.

What are the possible side effects of CABLIVI?

CABLIVI can cause severe bleeding. In clinical studies, severe bleeding adverse reactions of nosebleed, bleeding from the gums, bleeding in the stomach or intestines, and bleeding from the uterus were each reported in 1% of subjects. Contact your doctor immediately if excessive bleeding or bruising occur.

You may have a higher risk of bleeding if you have a bleeding disorder (i.e. hemophilia) or if you take other medicines that increase your risk of bleeding such as anti-coagulants.

CABLIVI should be stopped for 7 days before surgery or any medical or dental procedure. Talk to your doctor before you stop taking CABLIVI.

The most common side effects include nosebleed, headache and bleeding gums.

Tell your doctor if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of CABLIVI. Call your doctor for medical advice about side effects.

Please see accompanying full Prescribing Information.

CABLIVI Dosing Guide

CABLIVI Dosing Guide

Important information for you and your patients regarding the CABLIVI dosing schedule.

CABLIVI Administration Training Guide

CABLIVI Administration Training Guide

Information to share with your patients regarding the administration of CABLIVI.

Patients

Support for you and your patients

CABLIVI dots

Educational and financial assistance for patients

aTTP=acquired thrombotic thrombocytopenic purpura; IV=intravenous; PEX=plasma exchange; SC=subcutaneous.

IMPORTANT SAFETY INFORMATION AND INDICATIONS

CONTRAINDICATIONS:

CABLIVI is contraindicated in patients with a previous severe hypersensitivity reaction to caplacizumab-yhdp or to any of its excipients. Hypersensitivity reactions have included urticaria.

WARNINGS AND PRECAUTIONS:

Bleeding Risk:

  • CABLIVI increases the risk of bleeding. In clinical studies, severe bleeding adverse reactions of epistaxis, gingival bleeding, upper gastrointestinal hemorrhage, and metrorrhagia were each reported in 1% of subjects. Overall, bleeding events occurred in approximately 58% of patients on CABLIVI versus 43% of patients on placebo. The risk of bleeding is increased, in patients with underlying coagulopathies and concomitant use of CABLIVI with drugs affecting hemostasis.
  • If clinically significant bleeding occurs, interrupt use of CABLIVI. Von Willebrand factor concentrate may be administered to rapidly correct hemostasis. If CABLIVI is restarted, monitor closely for signs of bleeding.
  • Withhold CABLIVI for 7 days prior to elective surgery, dental procedures or other invasive interventions. If emergency surgery is needed, the use of von Willebrand factor concentrate may be considered to correct hemostasis. After the risk of surgical bleeding has resolved, and CABLIVI is resumed, monitor closely for signs of bleeding.

ADVERSE REACTIONS:

The most common adverse reactions (>15% of patients) were epistaxis (29%), headache (21%) and gingival bleeding (16%).

CONCOMITANT USE OF ANTICOAGULANTS:

Concomitant use of CABLIVI with any anticoagulant may increase the risk of bleeding. Assess and monitor closely for bleeding with concomitant use.

PREGNANCY:

There are no available data on CABLIVI use in pregnant women to inform a drug associated risk of major birth defects and miscarriage.

  • Fetal/neonatal adverse reactions: CABLIVI may increase the risk of bleeding in the fetus and neonate. Monitor neonates for bleeding.
  • Maternal adverse reactions: All patients receiving CABLIVI, including pregnant women, are at risk for bleeding. Pregnant women receiving CABLIVI should be carefully monitored for evidence of excessive bleeding.

INDICATIONS:

CABLIVI (caplacizumab-yhdp) is indicated for the treatment of adult patients with acquired thrombotic thrombocytopenic purpura (aTTP), in combination with plasma exchange and immunosuppressive therapy.

References:
  1. 1. CABLIVI [package insert]. Cambridge, MA: Genzyme Corporation; 2019.
  2. 2. Scully M, Cataland SR, Peyvandi F, et al; for the HERCULES Investigators. Caplacizumab treatment for acquired thrombotic thrombocytopenic purpura. N Engl J Med. 2019;380(4):335-346.
References:
  1. 1. Grall M, Azoulay E, Galicier L, et al. Thrombotic thrombocytopenic purpura misdiagnosed as autoimmune cytopenia: causes of diagnostic errors and consequence on outcome. Experience of the French thrombotic microangiopathies reference centre. Am J Hematol. 2017;92(4):381-387.
  2. 2. Scully M, Hunt BJ, Benjamin S, et al; on behalf of British Committee for Standards in Haematology. Guidelines on the diagnosis and management of thrombotic thrombocytopenic purpura and other thrombotic microangiopathies. Br J Haematol. 2012;158(3):323-335.
  3. 3. Goel R, King KE, Takemoto CM, Ness PM, Tobian AAR. Prognostic risk-stratified score for predicting mortality in hospitalized patients with thrombotic thrombocytopenic purpura: national representative data from 2007 to 2012. Transfusion. 2016;56(6):1451-1458.
  4. 4. Peyvandi F, Scully M, Kremer Hovinga JA, et al. Caplacizumab reduces the frequency of major thromboembolic events, exacerbations and death in patients with acquired thrombotic thrombocytopenic purpura. J Thromb Haemost. 2017;15(7):1448-1452.
  5. 5. Joly BS, Coppo P, Veyradier A. Thrombotic thrombocytopenic purpura. Blood. 2017;129(21):2836-2846.
References:
  1. 1. CABLIVI [package insert]. Cambridge, MA: Genzyme Corporation; 2019.
  2. 2. Scully M, Cataland SR, Peyvandi F, et al; for the HERCULES Investigators. Caplacizumab treatment for acquired thrombotic thrombocytopenic purpura. N Engl J Med. 2019;380(4):335-346.
  3. 3. Kremer Hovinga JA, Coppo P, Lämmle B, Moake JL, Miyata T, Vanhoorelbeke K. Thrombotic thrombocytopenic purpura. Nat Rev Dis Primers. 2017;3:17020. doi:10.1038/nrdp.2017.20
  4. 4. Holz J-B. The TITAN trial—assessing the efficacy and safety of an anti-von Willebrand factor Nanobody in patients with acquired thrombotic thrombocytopenic purpura. Transfus Apher Sci. 2012;46(3):343-346.
References:
  1. 1. CABLIVI [package insert]. Cambridge, MA: Genzyme Corporation; 2019.
  2. 2. Scully M, Cataland SR, Peyvandi F, et al; for the HERCULES Investigators. Caplacizumab treatment for acquired thrombotic thrombocytopenic purpura. N Engl J Med. 2019;380(4):335-346.
  3. 3. Supplement to: Scully M, Cataland SR, Peyvandi F, et al; for the HERCULES Investigators. Caplacizumab treatment for acquired thrombotic thrombocytopenic purpura. N Engl J Med. 2019;380(4):335-346.
  4. 4. Protocol for: Scully M, Cataland SR, Peyvandi F, et al; for the HERCULES Investigators. Caplacizumab treatment for acquired thrombotic thrombocytopenic purpura. N Engl J Med. 2019;380(4):335-346.
References:
  1. 1. CABLIVI [package insert]. Cambridge, MA: Genzyme Corporation; 2019.
  2. 2. Scully M, Cataland SR, Peyvandi F, et al; for the HERCULES Investigators. Caplacizumab treatment for acquired thrombotic thrombocytopenic purpura. N Engl J Med. 2019;380(4):335-346.
Reference:
  1. 1. Scully M, Cataland SR, Peyvandi F, et al; for the HERCULES Investigators. Caplacizumab treatment for acquired thrombotic thrombocytopenic purpura. N Engl J Med. 2019;380(4):335-346.
Reference:
  1. 1. CABLIVI [package insert]. Cambridge, MA: Genzyme Corporation; 2019.
References:
  1. 1. CABLIVI [package insert]. Cambridge, MA: Genzyme Corporation; 2019.
  2. 2. CABLIVI [instructions for use]. Cambridge, MA: Genzyme Corporation; 2019.
References:
  1. 1. Centers for Medicare & Medicaid Services. Draft ICD-10-CM/PCS MS-DRGv28 Definitions Manual: MDC 8 Diseases & Disorders of the Musculoskeletal System & Connective Tissue Disorders. https://www.cms.gov/icd10manual/fullcode_cms/P0209.html. Accessed July 25, 2019.
  2. 2. Centers for Medicare & Medicaid Services. Department of Health and Human Services. 42 CFR §412, 413, 495. Medicare Program; Hospital Inpatient Prospective Payment Systems for Acute Care Hospitals and the Long-Term Care Hospital Prospective Payment System and Proposed Policy Changes and Fiscal Year 2020 Rates; Proposed Quality Reporting Requirements for Specific Providers; Medicare and Medicaid Promoting Interoperability Programs Proposed Requirements for Eligible Hospitals and Critical Access Hospitals. Fed Regist. 2019;84:19158-19677.
  3. 3. Data on file. Conshohocken, PA: Sanofi; 2018.
  4. 4. Centers for Medicare & Medicaid Services. 2019 ICD-10-CM. https://www.cms.gov/Medicare/Coding/ICD10/2019-ICD-10-CM.html. Updated June 20, 2019. Accessed July 23, 2019.
  5. 5. Centers for Medicare & Medicaid Services. 2020 ICD-10-PCS. https://www.cms.gov/Medicare/Coding/ICD10/2020-ICD-10-PCS.html. Accessed July 25, 2019.