Dosing and Administration

SARCLISA^® Dosing Schedule¹

• Administer premedications
• Each treatment cycle consists of a 28-day period

Recommended dose: 10 mg/kg actual body weight administered as an IV infusion in combination with pomalidomide and dexamethasone or in combination with carfilzomib and dexamethasone*

• No dose reduction of SARCLISA^® is recommended for infusion-related reactions or neutropenia; temporary interruption or definitive discontinuation of SARCLISA^® treatment may be required

• If a planned dose is missed, administer the dose as soon as possible and adjust the treatment schedule accordingly, maintaining the treatment interval 
• Treatment is continued until disease progression or unacceptable toxicity

Preparation for Administration of SARCLISA^®1

Preparation of the Infusion Solution Must Be Done under Aseptic Conditions

• Vials of SARCLISA^® concentrate should be visually inspected before dilution to ensure they do not contain any particles and are not discoloured
• The dose (mg) of required SARCLISA^® concentrate should be calculated based on patient weight (measured prior to each cycle to have the administered dose adjusted accordingly); more than one vial may be necessary to obtain the required dose for the patient

Sample dose calculations of SARCLISA^® based on actual patient weight

Dilute SARCLISA^® in an infusion bag to a final volume of 250 mL of 0.9% sodium chloride or dextrose 5% solution. Gently mix the diluted solution by inverting the bag; do not shake.

The infusion bag must be made of polyolefins (PO), polyethylene (PE), polypropylene (PP), polyvinyl chloride (PVC) with di (2-ethylhexyl) phthalate (DEHP) or ethyl vinyl acetate (EVA).

Administer by IV infusion using an IV tubing infusion set.

The IV tubing infusion set must be made of polyethylene (PE), polyvinyl chloride (PVC) with or without di (2-ethylhexyl) phthalate (DEHP), polybudadiene (PBD) or polyurethane (PU) with an in-line filter (polyethersulfone [PES], polysulfone or nylon).

The infusion solution should be administered for a period of time that will depend on the infusion rate.

Prepared solution should be used within 48 hours when stored at 2°C to 8°C (36°F to 46°F), followed by 8 hours (including the infusion time) at room temperature.

Do not infuse SARCLISA^® solution concomitantly with other agents in the same IV line.

On the days when both SARCLISA^® and carfilzomib are administered, administer dexamethasone first, followed by SARCLISA^® infusion, then followed by carfilzomib infusion.

Premedications¹

The following medications should be given or administered 15 to 60 minutes prior to the SARCLISA^® infusion to reduce the risk and severity of IRRs: 

Dexamethasone

SARCLISA^® + Kd:

• 20 mg: IV on the days of SARCLISA^® and/or carfilzomib infusions and PO on day 22 in cycle 2 and beyond, and PO on day 23 in all cycles

SARCLISA^® + Pd: 

• 40 mg PO or IV in patients <75 years old
• 20 mg PO or IV in patients ≥75 years old

The above recommended dose of dexamethasone (PO or IV) corresponds to the total dose to be administered before infusion, as part of the premedication and of the backbone treatment; do not administer another dose. Administer dexamethasone before SARCLISA^® and pomalidomide and before SARCLISA^® and carfilzomib administration.

Acetaminophen

650 mg to 1000 mg PO (or equivalent)

H2 Antagonists

Diphenhydramine

25 mg to 50 mg IV or PO or equivalent (e.g., cetirizine, promethazine, dexchlorpheniramine)

• IV route is preferred for at least the first 4 infusions

Example of SARCLISA^® Infusion Rates¹

Follow the table below and increase the infusion rate only if there are no IRRs:

Total timing shown above represents the minimum infusion times in patients who do not experience IRRs.* 

SARCLISA^® should be administered by a healthcare professional who has immediate access to emergency equipment and appropriate medical support to manage IRRs if they occur.

Infusion Management Following IRRs¹

Warnings and Precautions

It is important to monitor patients for IRRs.

SARCLISA^® may cause serious infusion reactions including anaphylactic reactions.

• Signs and symptoms of anaphylactic reactions included bronchospasm, dyspnea, angioedema and swelling

Most commonly reported symptoms of an IRR in clinical studies:

• Dyspnea
• Cough
• Nasal congestion 
• Chills 
• Vomiting
• Nausea

Other reported symptoms included:

• Hypertension
• Hypoxia
• Pulmonary edema
• Hypotension
• Tachycardia
• Syncope
• Bronchospasm
• Cytokine release syndrome
• Anaphylactic reaction
• Face edema
• Hyperglycemia

 NCI-CTCAE version 4.03 criteria definitions.

*Infusion interruption or intervention not indicated.
†Infusion interruption indicated, but responsive promptly to symptomatic treatment (e.g., antihistamines, NSAIDs, narcotics, IV fluids); prophylactic medications indicated for ≤24 hours.
‡Grade 3: prolonged symptoms (e.g., not rapidly responsive to symptomatic treatments and/or brief interruption of infusion); recurrence of symptoms following initial improvement; hospitalization indicated for clinical sequelae. Grade 4: life-threatening consequences; urgent intervention indicated.

Restarting Infusions after Grade 2 IRRs

• If symptoms improve to Grade ≤1, restart SARCLISA^® infusion at half the initial infusion rate, with supportive care as needed, and closely monitor patients. If symptoms do not recur after 30 minutes, the infusion rate may be increased to the initial rate and then increased incrementally per the Infusion Rates of SARCLISA^® Administration, consistent with the Product Monograph.
• If symptoms do not resolve rapidly or do not improve to Grade ≤1 after interruption of SARCLISA^® infusion, persist or worsen despite appropriate medications, or require hospitalization or are life-threatening, treatment with SARCLISA^® should be permanently discontinued and additional supportive therapy should be administered, as needed.

Presentation, Storage and Handling¹

SARCLISA^® Is Supplied as Follows: 

• 100 mg/5 mL (6 mL single-use vial); pack size of one or three single-use vials 
• 500 mg/25 mL (30 mL single-use vial); pack size of one single-use vial

Storage Requirements

• Store SARCLISA^® vials in a refrigerator at 2°C to 8°C (36°F to 46°F) and protect from light 
• Do not freeze 
• Do not shake 

Disposal

• Discard any unused portion of solution. All materials that have been utilized for dilution and administration should be disposed of according to standard procedures.