Arzerra (ofatumumab)

Generic drug: ofatumumab

Brand name: Arzerra

Arzerra (ofatumumab) Injection is amonoclonal antibodyused to treatchronic lymphocytic leukemia. Arzerra is usually given after other medications have been tried without successful treatment of symptoms.

Common side effects of Arzerra include:

• nausea,
• vomiting,
• diarrhea,
• tiredness,
• swelling of hands/ankles/feet,
• trouble sleeping,
• skinrash, or
• coldsymptoms such asstuffy nose,sneezing, andsore throat.

Arzerra decreasesbone marrowfunction, an effect that may lead to a low number of blood cells such asred cells, white cells, and platelets. This side effect of Arzerra can causeanemia, decrease your body's ability to fight an infection, or causeeasy bruisingor bleeding. Tell your doctor if you have the following symptoms:

• easy bruising/bleeding,
• pale skin,
• unusual tiredness, or
• signs of infection (such asfever,chills,cough, persistentsore throat).

Recommended Dosage Regimen

• Dilute and administer as an intravenous infusion according to the following schedules.
• Do not administer as an intravenous push or bolus or as a subcutaneous injection.
• Pre-medicate before each infusion.

Previously Untreated CLL:

The recommended dosage and schedule in combination withchlorambucilis:

• 300 mg on Day 1, followed 1 week later by 1,000 mg on Day 8 (Cycle 1), followed by
• 1,000 mg 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:

The recommended dosage and schedule in combination with fludarabine andcyclophosphamideis:

• 300 mg on Day 1, followed 1 week later by 1,000 mg on Day 8 (Cycle 1), followed by
• 1,000 mg on Day 1 of subsequent 28-day cycles for a maximum of 6 cycles.

Extended Treatment In CLL:

The recommended dosage and schedule as single-agent extended treatment in CLL is:

• 300 mg on Day 1, followed by
• 1,000 mg 1 week later on Day 8, followed by
• 1,000 mg 7 weeks later and every 8 weeks thereafter for up to a maximum of 2 years.

Refractory CLL:

The recommended dosage and schedule is 12 doses administered as follows:

• 300 mg initial dose on Day 1, followed 1 week later by
• 2,000 mg weekly for 7 doses (Infusions 2 through 8), followed 4 weeks later by
• 2,000 mg every 4 weeks for 4 doses (Infusions 9 through 12).

Administration

Administer Arzerra in anenvironmentwhere facilities to adequately monitor and treat infusion reactions are available.

Prepare all doses in 1,000 mL of 0.9% Sodium Chloride Injection, USP.

Previously Untreated CLL, Relapsed CLL, And Extended Treatment In CLL:

• For initial 300-mg dose: Initiate infusion at a rate of 3.6 mg/hour (12 mL/hour).
• For subsequent infusions of 1,000 mg: Initiate infusion at a rate of 25 mg/hour (25 mL/hour). Initiate infusion at a rate of 12 mg/hour if a Grade 3 or greater infusion-related adverse event was experienced during the previous infusion.

In the absence of an infusion-related adverse event, the rate of infusion may be increased every 30 minutes (Table 1). Do not exceed the infusion rates in Table 1.

Table 1. Infusion Rates for Arzerra in Previously Untreated CLL, Relapsed CLL, and Extended Treatment in CLL

Interval After Start of Infusion (min)	Initial 300 mg Dosea (mL/hour)	Subsequent Infusionsb (mL/hour)
0-30	12	25
31-60	25	50
61-90	50	100
91-120	100	200
121-150	200	400
151-180	300	400
>180	400	400
aInitial 300 mg: median durations of infusions = 4.8 to 5.2 hours. bSubsequent infusions of 1,000 mg: median durations of infusions = 4.2 to 4.4 hours.

Refractory CLL:

• Infusion 1 (300-mg dose): Initiate infusion at a rate of 3.6 mg/hour (12 mL/hour).
• Infusion 2 (2,000-mg dose): Initiate infusion at a rate of 24 mg/hour (12 mL/hour).
• Infusions 3 through 12 (2,000-mg doses): Initiate infusion at a rate of 50 mg/hour (25 mL/hour).

In the absence of an infusion-related adverse event, the rate of infusion may be increased every 30 minutes (Table 2). Do not exceed the infusion rates in Table 2.

Table 2. Infusion Rates for Arzerra in Refractory CLL

Interval after Start of Infusion (min)	Infusions 1 and 2a (mL/hour)	Subsequent Infusionsb (mL/hour)
0-30	12	25
31-60	25	50
61-90	50	100
91-120	100	200
>120	200	400
aInfusions 1 and 2 (300 mg and 2,000 mg): median duration of infusions = 6.8 hours. bSubsequent infusions of 2,000 mg: median durations of infusions = 4.2 to 4.4 hours.

Infusion Rate Dose Modification For Infusion Reactions

• Interrupt infusion for infusion reactions of any severity. Treatment can be resumed at the discretion of the treating 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:Infuseat 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 Tables 1 and 2 above, based on patient tolerance.
• Consider permanent discontinuation of Arzerra 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 to Arzerra.

Premedication

Patients should receive all of the following premedication agents 30 minutes to 2 hours prior to each infusion of Arzerra. See Table 3 for pre-medication schedule prior to each infusion.

Table 3. Premedication Schedule for Arzerra

	Previously Untreated CLL, Relapsed CLL or Extended Treatment in CLL		Refractory CLL
Infusion Number	1 and 2	3 and beyonda	1, 2, and 9	3 to 8	10 to 12
Intravenous corticosteroid (prednisolone or equivalent)	50 mg	0-50 mgb	100 mg	0-100 mgb	50-100 mgc
Oral acetaminophen	1,000 mg
Oral or intravenous antihistamine	Diphenhydramine 50 mg or cetirizine 10 mg (or quivalent)
aUp to 13 infusions in previously untreated CLL; up to 7 infusions in relapsed CLL, up to 14 infusions in extended treatment in CLL. bCorticosteroid 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(s). c强的松可以at reduced dose of 50 mg to 100 mg (or equivalent) if a Grade 3 or greater infusion-related adverse event did not occur with Infusion 9.

Preparation And Administration

• 不动摇的产品。
• Inspectparenteraldrug products visually for particulate matter and discoloration prior to administration. Arzerra should be a clear to opalescent, colorless solution. The solution should not be used if discolored or cloudy, or if foreign particulate matter is present.

Preparation Of Solution:

• 300-mg dose: Withdraw and discard 15 mL from a 1,000-mL bag of 0.9% Sodium Chloride Injection, USP. Withdraw 5 mL from each of 3 single-use 100-mg vials of Arzerra and add to the bag. Mix diluted solution by gentle inversion.
• 1,000-mg dose: Withdraw and discard 50 mL from a 1,000-mL bag of 0.9% Sodium Chloride Injection, USP. Withdraw 50 mL from 1 single-use 1,000-mg vial of Arzerra and add to the bag. Mix diluted solution by gentle inversion.
• 2,000-mg dose: Withdraw and discard 100 mL from a 1,000-mL bag of 0.9% Sodium Chloride Injection, USP. Withdraw 50 mL from each of 2 single-use 1,000-mg vials of Arzerra and add to the bag. Mix diluted solution by gentle inversion.
• Store diluted solution between 2° to 8°C (36° to 46°F).
• No incompatibilities between Arzerra and polyvinylchloride or polyolefinbagsand administration sets have been observed.

Administration Instructions:

• Do not mix Arzerra with, or administer as an infusion with other medicinal products.
• Administer using an infusion pump and an administration set.
• Flushthe intravenous line with 0.9% Sodium Chloride Injection, USP before and after each dose.
• Start infusion within 12 hours of preparation.
• Discard prepared solution after 24 hours.

No Information Provided

• Arzerra may cause fetal B-cell depletion based on findings from animal studies and the drug's mechanism of action.
• There are no data on Arzerra use inpregnantwomen to inform a drug-associated risk. However, there are clinical considerations.
• There is no information regarding the presence of Arzerra in母乳, the effects on thebreastfedinfant, or the effects on milk production.
• Human IgG is known to be present in human milk. Published data suggest that antibodies inbreast milkdo not enter theneonataland infant circulations in substantial amounts.