Usual Adult Dose for Chronic Lymphocytic Leukemia

ARZERRA:
PREVIOUSLY UNTREATED CLL:
300 mg IV on Day 1 followed by 1000 mg IV on Day 8 (Cycle 1) followed by 1000 mg IV on Day 1 of subsequent 28-day cycles for a minimum of 3 cycles until best response or a maximum of 12 cycles

RELAPSED CLL:
In combination with fludarabine and cyclophosphamide:

300 mg IV on Day 1 followed by 1000 mg IV on Day 8 (Cycle 1), followed by
1000 mg IV on Day 1 of subsequent 28-day cycles for a maximum of 6 cycles

EXTENDED TREATMENT IN CLL:
As a single agent:
300 mg IV on Day 1 followed by 1000 mg IV on Day 8 followed by 1000 mg IV 7 weeks later and every 8 weeks thereafter for up to a maximum of 2 years

REFRACTORY CLL:
300 mg IV on Day 1 followed by 2000 mg IV weekly for 7 doses (infusions 2 through 8), followed 4 weeks later by 2000 mg IV every 4 weeks for 4 doses (infusions 9 through 12)

PREMEDICATION:
Patients should receive premedication 30 minutes to 2 hours prior to each infusion:
Previously Untreated CLL, Relapsed CLL or Extended Treatment in CLL:

• Infusions 1 and 2: IV corticosteroid (prednisolone or equivalent) 50 mg AND oral acetaminophen 1000 mg AND oral or IV antihistamine (diphenhydramine 50 mg or cetirizine 10 mg [or equivalent])
• Infusions 3 and beyond (up to 13 infusions in previously untreated CLL; up to 14 infusions in extended treatment in CLL): IV corticosteroid (prednisolone or equivalent) 0 to 50 mg (the corticosteroid may be reduced or omitted for subsequent infusions if a Grade 3 or greater infusion related adverse event did not occur with the preceding infusion) AND oral acetaminophen 1000 mg AND oral or IV antihistamine (diphenhydramine 50 mg or cetirizine 10 mg [or equivalent])

Refractory CLL:

• Infusions 1, 2, and 9: IV corticosteroid (prednisolone or equivalent) 100 mg AND oral acetaminophen 1000 mg AND oral or IV antihistamine (diphenhydramine 50 mg or cetirizine 10 mg [or equivalent])
• Infusions 3 to 8: IV corticosteroid (prednisolone or equivalent) 0 to 100 mg (the corticosteroid may be reduced or omitted for subsequent infusions if a Grade 3 or greater infusion related adverse event did not occur with the preceding infusion) AND oral acetaminophen 1000 mg AND oral or IV antihistamine (diphenhydramine 50 mg or cetirizine 10 mg [or equivalent])
• Infusions 10 to 12: IV corticosteroid (prednisolone or equivalent) 50 to 100 mg (the corticosteroid may be given at a reduced dose of 50 mg to 100 mg if a Grade 3 or greater infusion related adverse event did not occur with Infusion 9) AND oral acetaminophen 1000 mg AND oral or IV antihistamine (diphenhydramine 50 mg or cetirizine 10 mg [or equivalent])

ADMINISTRATION:
PREVIOUSLY UNTREATED CLL AND EXTENDED TREATMENT IN CLL:

• Initiate the first 300 mg dose IV at 3.6 mg/hr (12 mL/hr) for 30 minutes
• For subsequent infusions of 1000 mg, initiate at 25 mg/hr (25 mL/hr); initiate infusion at 12 mg/hour if a Grade 3 or greater infusion-related reaction was experienced during the previous infusion
• In the absence of an infusion-related reaction, the rate of infusion may be increased every 30 minutes:

Infusion rates for this drug in previously untreated CLL, relapsed CLL, and extended treatment in CLL:
300 mg IV at 12 mL/hr for the first 30 minutes; if tolerated, increase to 25 mL/hr for 30 minutes; if tolerated increase to 50 mL/hr for 30 minutes; if tolerated increase to 100 mL/hr for 30 minutes; if tolerated increase to 200 mL/hr for 30 minutes; if tolerated increase to 300 mL/hr for 30 minutes; if tolerated increase to 400 mL/hr for remainder of the infusion. The median duration of infusion is 4.2 to 4.4 hours.
REFRACTORY CLL:

• Infusion 1 (300 mg dose): Initiate infusion at 3.6 mg/hr (12 mL/hour)
• Infusion 2 (2000 mg dose): Initiate infusion at 24 mg/hr (12 mL/hour)
• Infusions 3 through 12 (2000 mg doses): Initiate infusion at 50 mg/hr (25 mL/hour)

In the absence of an infusion-related adverse event, the rate of infusion may be increased every 30 minutes:
300 mg IV at 12 mL/hr for the first 30 minutes; if tolerated, increase to 25 mL/hr for 30 minutes; if tolerated increase to 50 mL/hr for 30 minutes; if tolerated increase to 100 mL/hr for 30 minutes; if tolerated increase to 200 mL/hr for 30 minutes; if tolerated increase to 300 mL/hr for 30 minutes; if tolerated increase to 400 mL/hr for remainder of the infusion. The median duration of infusion is 4.2 to 4.4 hours.

Uses:
Chronic Lymphocytic Leukemia (CLL):

• In combination with chlorambucil, for the treatment of previously untreated patients with CLL for whom fludarabine-based therapy is considered inappropriate
• In combination with fludarabine and cyclophosphamide for the treatment of patients with relapsed CLL
• For extended treatment of patients who are in complete or partial response after at least 2 lines of therapy for recurrent or progressive CLL
• For the treatment of patients with CLL refractory to fludarabine and alemtuzumab

Usual Adult Dose for Multiple Sclerosis

KESIMPTA:
20 mg subcutaneously at Weeks 0, 1, and 2, followed by 20 mg subcutaneously once a month starting at Week 4
NOTE: If a dose is missed, administer it as soon as possible without waiting until the next scheduled dose. Subsequent doses should be administered at the recommended intervals.

Comments:

• Not all products are approved for the same indications. Refer to the manufacturer product information for indications.
• Administer by subcutaneous injection only.
• This drug is intended for patient self-administration by subcutaneous injection.
• Administer in the abdomen, thigh, or outer upper arm subcutaneously. Do not give injection into moles, scars, stretch marks or areas where the skin is tender, bruised, red, scaly, or hard.
• The first injection of should be performed under the guidance of a healthcare professional.
• The pens and syringes are for one-time use only and should be discarded after use.

Use: For the treatment of relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease

Renal Dose Adjustments

No formal studies of this drug in patients with renal impairment have been performed. No dose adjustment is recommended for mild to moderate renal impairment (creatinine clearance greater than 30 mL/min).

Liver Dose Adjustments

No formal studies of this drug in patients with renal impairment have been performed.

Dose Adjustments

INFUSION RATE DOSE MODIFICATION FOR INFUSION REACTIONS:

• Interrupt infusion for infusion reactions of any severity.
• Therapy may be resumed at the discretion of the physician.
• The following infusion rate modifications can be used as a guide: if the infusion reaction resolves or remains less than or equal to Grade 2, resume infusion with the following modifications according to the initial Grade of the infusion reaction:
• Grade 1 or 2: Infuse at one-half of the previous infusion rate.
• Grade 3 or 4: Infuse at a rate of 12 mL/hour.
• After resuming the infusion, the infusion rate may be increased according to the standard schedule, based on patient tolerance.
• Consider permanent discontinuation of therapy if the severity of the infusion reaction does not resolve to less than or equal to Grade 2 despite adequate clinical intervention.
• Permanently discontinue therapy for patients who develop an anaphylactic reaction.

Precautions

US BOXED WARNINGS:
ARZERRA:

• HEPATITIS B VIRUS REACTIVATION: Hepatitis B Virus (HBV) reactivation can occur in patients receiving CD20-directed cytolytic antibodies, including this drug, in some cases resulting in fulminant hepatitis, hepatic failure, and death.
• PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY: Progressive Multifocal Leukoencephalopathy (PML) resulting in death can occur in patients receiving CD20-directed cytolytic antibodies, including this drug.

CONTRAINDICATIONS:

• Arzerra: None
• Kesimptz: Active Hepatitis B Virus (HPV) infection

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• Do not administer as an IV push or bolus.
• The infusion should be carried out in an environment equipped to monitor for and manage infusion reactions.
• Administer with infusion pump and administration set.
• Recommended infusion rates should not be exceeded.
• The IV formulation should be administered under the supervision of a physician experienced in cancer therapy and in an environment where full resuscitation facilities are immediately available.
• Patients should be premedicated before each IV infusion.
• Patients should be closely monitored during the IV infusion for the onset of infusion reactions, including cytokine release syndrome, particularly during the first infusion.

Storage requirements:

• ARZERRA: Store refrigerated between 2C to 8C (36F to 46F). Do not freeze. Vials should be protected from light.
• KESIMPTA Sensoready pens and prefilled syringes should be refrigerated at 2C to 8C (36F to 46F). Keep the product in the original carton to protect from light until the time of use. Do not freeze. To avoid foaming, do not shake.

Frequently asked questions

• How is Arzerra administered and how long to work?