Caplacizumab-yhdp (Monograph)

Brand name: Cablivi
Drug class:

Medically reviewed by Drugs.com on Apr 10, 2024. Written by ASHP.

Introduction

Caplacizumab-yhdp is an antithrombotic agent.

Uses for Caplacizumab-yhdp

Caplacizumab-yhdp has the following uses:

Caplacizumab-yhdp is a von Willebrand factor-directed antibody fragment indicated for the treatment of adult patients with acquired thrombotic thrombocytopenic purpura (aTTP), in combination with plasma exchange and immunosuppressive therapy.

Caplacizumab-yhdp Dosage and Administration

General

Caplacizumab-yhdp is available in the following dosage form(s) and strength(s):

For injection: 11 mg as a lyophilized powder in a single-dose vial.

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

Dosage and Administration

• The first dose should be administered by a healthcare provider as a bolus intravenous injection. Administer subsequent doses subcutaneously in the abdomen.

• Caplacizumab-yhdp should be administered upon the initiation of plasma exchange therapy. The recommended dose of caplacizumab-yhdp is as follows:

• First day of treatment: 11 mg bolus intravenous injection at least 15 minutes prior to plasma exchange followed by an 11 mg subcutaneous injection after completion of plasma exchange on day 1.

• Subsequent treatment during daily plasma exchange: 11 mg subcutaneous injection once daily following plasma exchange.

• Treatment after the plasma exchange period: 11 mg subcutaneous injection once daily for 30 days beyond the last plasma exchange.

• If after initial treatment course, sign(s) of persistent underlying disease such as suppressed ADAMTS13 activity levels remain present, treatment may be extended for a maximum of 28 days.

• Discontinue caplacizumab-yhdp if the patient experiences more than 2 recurrences of aTTP while on caplacizumab-yhdp.

Cautions for Caplacizumab-yhdp

Contraindications

Previous severe hypersensitivity reaction to caplacizumab-yhdp or any of the excipients.

Warnings/Precautions

Bleeding

Caplacizumab-yhdp 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 caplacizumab-yhdp versus 43% of patients on placebo.

The risk of bleeding is increased in patients with underlying coagulopathies (e.g. hemophilia, other coagulation factor deficiencies). It is also increased with concomitant use of caplacizumab-yhdp with drugs affecting hemostasis and coagulation.

Interrupt use of caplacizumab-yhdp if clinically significant bleeding occurs. If needed, von Willebrand factor concentrate may be administered to rapidly correct hemostasis. If caplacizumab-yhdp is restarted, monitor closely for signs of bleeding.

Withhold caplacizumab-yhdp 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 caplacizumab-yhdp is resumed, monitor closely for signs of bleeding.

Specific Populations

Pregnancy

Risk Summary: There are no available data on caplacizumab-yhdp use in pregnant women to inform a drug-associated risk of major birth defects and miscarriage. However, there are potential risks of hemorrhage in the mother and fetus associated with use of caplacizumab-yhdp. In animal reproduction studies, there was no evidence of adverse developmental outcomes with intramuscular administration of caplacizumab-yhdp during organogenesis in guinea pigs at exposures approximately 30 times the AUC in humans at the recommended subcutaneous injection dose of 11 mg.

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The background rate of major birth defects and miscarriage in the indicated population is unknown. In the U.S. general population, the estimated background rate of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Clinical Considerations: Caplacizumab-yhdp may increase the risk of bleeding in the fetus and neonate. Monitor neonates for bleeding.

All patients receiving caplacizumab-yhdp, including pregnant women, are at risk for bleeding. Pregnant women receiving caplacizumab-yhdp should be carefully monitored for evidence of excessive bleeding.

Animal Data: Two separate reproduction studies were conducted in pregnant guinea pigs with administration of caplacizumab-yhdp during the organogenesis period.

In an embryo-fetal development study, caplacizumab-yhdp was administered intramuscularly at doses up to 20 mg/kg/day from gestational day (GD) 6 to GD 41 in guinea pigs. No maternal toxicity or adverse developmental outcomes were observed.

In a toxicokinetic study assessing the exposure of caplacizumab-yhdp in the dams and fetuses, caplacizumab-yhdp was administered once daily to female guinea pigs at doses up to 40 mg/kg/day (corresponding to a drug exposure of approximately 30 times the AUC in humans at the recommended dose of 11 mg) by intramuscular injection from GD 6 to GD 41 or GD 61. Exposure to caplacizumab-yhdp was observed in the dams and fetuses, with no effects on embryo-fetal development.

Lactation

There is no information regarding the presence of caplacizumab-yhdp in human milk, the effects on the breastfed child, or the effects on milk production.

The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for caplacizumab-yhdp and any potential adverse effects on the breastfed child from caplacizumab-yhdp, or from the underlying maternal condition.

Pediatric Use

The safety and effectiveness of caplacizumab-yhdp in pediatric patients have not been established.

Geriatric Use

Clinical studies of caplacizumab-yhdp did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

Hepatic Impairment

No formal studies with caplacizumab-yhdp have been conducted in patients with severe acute or chronic hepatic impairment and no data regarding the use of caplacizumab-yhdp in these populations are available. Due to a potential increased risk of bleeding, use of caplacizumab-yhdp in patients with severe hepatic impairment requires close monitoring for bleeding.

Common Adverse Effects

Most common adverse reactions (incidence >15%) are epistaxis, headache, and gingival bleeding.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Concomitant use of anticoagulants with caplacizumab-yhdp may increase the risk of bleeding. Monitor closely for bleeding with concomitant use.

Actions

Mechanism of Action

Caplacizumab-yhdp targets the A1-domain of von Willebrand factor, and inhibits the interaction between von Willebrand factor and platelets, thereby reducing both von Willebrand factor-mediated platelet adhesion and platelet consumption.

Advice to Patients

Advise the patient to read the FDA-approved patient labeling (Instructions for Use).

Bleeding

Advise patients that bruising and bleeding may occur more easily, that nose bleeds and bleeding of gums may occur, and that it may take them longer than usual to stop bleeding. Advise patients to contact their healthcare provider immediately if excessive bleeding or bruising occur.

Advise patients to inform their healthcare provider before scheduling any elective surgery, dental procedure or other invasive interventions.

Additional Information

AHFSfirstRelease^™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Reload page with references included

Medical Disclaimer