Usual Adult Dose for Multiple Sclerosis

First Infusion:
150 mg IV over at least 4 hours

• Initiate infusion at a rate of 10 mL per hour for the initial 30 minutes.
• Increase the flow to 20 mL per hour for the next 30 minutes.
• Increase the flow to 35 mL per hour for the next hour.
• Increase the flow to 100 mL per hour for the remaining 2 hours.

Second Infusion (2 weeks after the first infusion):
450 mg IV over at least 1 hour

• Initiate infusion at a rate of 100 mL per hour for the first 30 minutes.
• Increase the flow to 400 mL per hour for the remaining 30 minutes.

Subsequent Infusions (24 weeks after the first infusion):
450 mg IV every 24 weeks over at least 1 hour

• Initiate infusion at a rate of 100 mL per hour for the first 30 minutes.
• Increase the flow to 400 mL per hour for the remaining 30 minutes.

Comments:

• Premedicate with an appropriate corticosteroid approximately 30 minutes prior to each infusion of this drug, an antihistamine 30-60 minutes prior to each infusion of this drug, and an additional antipyretic if required to reduce the frequency and severity of infusion reactions.
• Monitor for infusion reactions during and for at least one hour after the first two infusions; based on the physician's discretion, continue monitoring after subsequent infusions unless an infusion reaction and/or hypersensitivity have been observed during the current or any prior infusion.
• Verify pregnancy status in females of childbearing potential prior to each infusion.

Use: For the treatment of relapsing forms of multiple sclerosis in adults

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Dose adjustment may be required; however, no specific guidelines have been suggested.

Dose Adjustments

Refer to manufacturer product information for full details on dose modification and management of adverse reactions.

Life-Threatening Infusion Reactions:

• If signs of a life threatening or disabling infusion reaction are observed, withhold, and permanently discontinue the treatment with this drug and institute appropriate therapy.

Severe Infusion Reactions:

• Withhold the treatment with this drug immediately and institute appropriate therapy.
• Resume treatment with this drug after the infusion reaction symptoms are resolved.
• When restarting, begin at half the infusion rate at the time of the onset of the infusion reaction.
• Based on the tolerance, increase the rate of the infusion as instructed by the manufacturer.
• This change in rate will increase the total duration of the infusion but not the total dose.

Mild to Moderate Infusion Reactions:

• Reduce the infusion rate to half the rate at the onset of the infusion reaction and maintain the reduced rate for at least 30 minutes.
• If the reduced rate is tolerated, increase the rate as instructed in the prescribing information.
• This change in rate will increase the total duration of the infusion but not the total dose.

Precautions

CONTRAINDICATIONS:
Active HBV infection; life-threatening infusion reaction

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:

• Visually inspect the parenteral drug product for particulate matter and discoloration prior to administration. Do not use if discoloration occurs or foreign particulate matter is detected.
• Ensure that the contents of the infusion bag are at room temperature prior to administration.
• Administer under the supervision of an experienced healthcare professional who is well equipped to manage severe reactions, such as serious infusion reactions.
• Infusion duration may take longer if the infusion is interrupted or slowed.

Storage requirements:

• To protect from light, keep refrigerated at 2C to 8C (36F to 46F) in the outer carton.
• Do not freeze or shake.

Diluted solution:

• Store in a refrigerator at 2C to 8C (36F to 46F) for up to 24 hours.
• The diluted solution can be stored for an additional 8 hours at room temperature up to 25C (77F) which includes the equilibration time and infusion time.
• Do not freeze.

Preparation techniques:
Use 0.9% Sodium Chloride Injection, USP to dilute this drug.

Preparation of Solution for First Infusion:

• Withdraw 6 mL of 0.9% Sodium Chloride Injection, USP, from the 250 mL infusion bag and discard.
• Withdraw 6 mL (150 mg) of the solution of this drug from the vial (6 mL per vial) and add it to the infusion bag containing 0.9% sodium chloride injection, USP.
• By inversion, gently mix the ingredients. Do not shake.

Preparation of Solution for Second Infusion and Subsequent Infusions:

• Withdraw 18 mL of 0.9% Sodium Chloride Injection, USP, from the 250 mL infusion bag and discard.
• Withdraw 18 mL (450 mg) solution of this drug from the vials (6 mL per vial) and add it to the infusion bag containing 0.9% sodium chloride injection, USP.
• By inversion, gently mix the ingredients. Do not shake.

IV compatibility: No incompatibilities were observed between this drug and polyvinyl chloride (PVC) or polyolefin (PO) bags or intravenous (IV) administration sets.

General:

• Administer all immunizations according to immunization guidelines at least 4 weeks (for live, live-attenuated vaccines) and 2 weeks (for non-live vaccines) before starting this drug.
• Immunizations with live-attenuated or live vaccines are not recommended during treatment and after discontinuation until B-cell repletion.
• Perform HBV Screening before initiating the treatment with this drug.
• If the results are negative for HBsAg and positive for Hepatitis B core antibody [HBcAb+] or if the patient is a carrier of HBV [HBsAg+], consult liver disease experts prior to starting and during treatment with this drug.
• Determine serum immunoglobulin levels prior to initiating treatment with this drug.
• In cases of low serum immunoglobulin levels, seek the advice of immunology experts prior to initiating treatment with this drug.
• Verify for the presence of an active infection prior to each infusion of this drug; in the case of an active infection, delay the infusion of this drug until the infection resolves.
• Infusions of this drug must be separated by at least 5 months.

Monitoring:

• Immunologic: Serum immunoglobulin levels
• Hepatic: Hepatitis B infection (reactivation)

Patient advice:

• Read the US FDA-approved patient labeling (Medication Guide).
• Complete any required immunizations prior to initiating treatment with this drug, do not administer live-attenuated or live vaccines during treatment with this drug and until B-cell recovery.
• Use effective contraception during treatment and for 6 months after the last dose.
• Inform your doctor if you become pregnant while taking this drug, as it has the potential to harm the fetus.
• Monitor for the signs and symptoms of infusion reactions, which can occur up to 24 hours after the infusion.
• Monitor for signs and symptoms of hepatitis B infection as this drug may cause reactivation of the hepatitis B infection.

­Contact your health care provider immediately if you have signs or symptoms of infusion reactions during treatment or after the last infusion. Signs may include fever, chills, a constant cough, or dysuria.

• Other drugs that are similar to this drug caused progressive multifocal leukoencephalopathy (PML), which usually resulted in death or severe disability.
• Contact your health care provider if you develop any symptoms suggestive of PML.
• Typical symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes.