Drug information of Ocrelizumab

Ocrelizumab is a recombinant humanized IgG monoclonal antibody directed against B-cells which express the cell surface antigen CD20; CD20 is present on pre-B and mature B lymphocytes. B-cells are thought to influence the course of multiple sclerosis through antigen presentation, autoantibody production, cytokine regulation, and formation of ectopic lymphoid aggregates in the meninges . Ocrelizumab selectively targets and binds with high affinity to the cell surface to deplete CD20 expressing B-cells through antibody-dependent cell-mediated phagocytosis and cytotoxicity, as well as complement-mediated cytolysis .

Distribution

Central V_d: 2.78 L; Peripheral: 2.68 L

Metabolism

Antibodies are primarily cleared by catabolism

Excretion

Constant clearance (estimated): 0.17 L/day; Initial time-dependent clearance: 0.05 L/day.

Onset of Action

Serum CD-19+ B-cell counts (used as a marker for B-cell counts) are reduced within 14 days after infusion.

Duration of Action

Median time for B-cell recovery (to baseline or the lower limit of normal): 72 weeks (range: 27 to 175 weeks).

Half-Life Elimination

26 days

Labeled Indications

Multiple sclerosis, relapsing or primary progressive: Treatment of primary progressive multiple sclerosis (MS) and relapsing forms of MS, including clinically isolated syndrome, relapsing remitting disease, and active secondary progressive disease.

Usual Adult Dose for Multiple Sclerosis

Initial dose: 300 mg IV followed 2 weeks later by a second 300 mg IV infusion
Maintenance dose: 600 mg IV every 6 months

Manufacturer recommended infusion rates (consult manufacturer product information):
-Infusions 1 and 2 (300 mg of this drug in 250 mL 0.9% sodium chloride injection): Start at 30 mL/hr and increase by 30 mL/hr every 30 minutes to a maximum of 180 mL/hr; duration of 2.5 hours or longer
-Subsequent infusions (600 mg of this drug in 500 mL 0.9% sodium chloride injection): Start at 40 mL/hr and increase by 40 mL/hr every 30 minutes to a maximum of 200 mL/hr; duration of 3.5 hours or longer

Comments:
-Observe the patient for at least 1 hour after the completion of the infusion.

Uses:
-For relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease
-Primary progressive MS

History of life-threatening infusion reaction to ocrelizumab; active hepatitis B virus (HBV) infection.

Canadian labeling: Additional contraindications (not in US labeling): Known hypersensitivity to ocrelizumab or any component of the formulation; severe, active infections; current or history of confirmed progressive multifocal leukoencephalopathy (PML); active malignancies; severely immunocompromised states

Side effects requiring immediate medical attention

Along with its needed effects, ocrelizumab may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur while taking ocrelizumab:

More common

• Back pain
• bloatingor swelling of the face, arms, hands, lower legs, or feet
• blurred vision
• body aches or pain
• chest tightness
• chills
• confusion
• cough
• difficulty with breathing
• dizziness
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• ear congestion
• fast, pounding, or irregular heartbeator pulse
• feeling of warmth
• fever
• headache
• hives, itching, or skin rash
• itching, pain, redness, swelling, tenderness, or warmth on the skin
• loss of voice
• nausea
• redness of the face, neck, arms, and occasionally, upper chest
• runny or stuffy nose
• sneezing
• sore throat
• sweating
• unusual tiredness or weakness
• vomiting

Less common

• Burning or stinging of the skin
• painful blisters on the trunk of the body
• painful cold soresor blisters on the lips, nose, eyes, or genitals

Side effects not requiring immediate medical attention

Some side effects of ocrelizumab may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

• Diarrhea
• discouragement
• feeling sad or empty
• irritability
• lack of appetite
• loss of interest or pleasure
• rapid weight gain
• tingling of the hands or feet
• trouble concentrating
• trouble sleeping
• unusual weight gain or loss

Some side effects may occur during the injection or up to 24 hours later. Tell your caregiver if you feel dizzy, nauseated, itchy, or have chest tightness, trouble breathing, or swelling in your throat.

Ocrelizumab affects your immune system. You may get infections more easily, even serious or fatal infections. Call your doctor if you have a fever, chills, cough, mouth sores, skin sores or blisters, itching, tingling, burning pain, or problems with speech, thought, vision, or muscle movement.

If you've ever had hepatitis B, it may become active or get worse while you are using or after you stop using ocrelizumab. You may need frequent liver function tests for several months.

You should not be treated with ocrelizumab if you are allergic to it, or if you have:

• active infection with hepatitis B.

Your doctor may perform tests to make sure you do not have hepatitis B or other infections.

You should not receive any "live" or "live-attenuated" vaccine within the 4 weeks before you start treatment with ocrelizumab. If you need a "non-live" vaccine, you should receive it at least 2 weeks before you start treatment with ocrelizumab.

Also tell your doctor if:

• you have any type of active infection;
• you are a carrier of hepatitis B; or
• you have ever used medicine that can weaken your immune system.

Using ocrelizumab may increase your risk of developing certain types of cancer, such as breast cancer. Ask your doctor about your specific risk.

It is not known whether ocrelizumab will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant. Use effective birth control to prevent pregnancy while you are using this medicine and for at least 6 months after your last dose.

If you are pregnant, you will need to tell your baby's doctor if you used ocrelizumab during pregnancy, especially before the baby receives any childhood vaccines.

It may not be safe to breastfeed while using this medicine. Ask your doctor about any risk.

Ocrelizumab is not approved for use by anyone younger than 18 years old.

Ocrelizumab is given as an infusion into a vein. A healthcare provider will give you this injection.

Your first dose of ocrelizumab will be split into 2 separate infusions given 2 weeks apart. The following doses will be given once every 6 months.

This medicine must be given slowly, and the infusion can take from 2.5 to 3.5 hours to complete.

You may be given other medications to help prevent serious side effects of ocrelizumab.

You will be watched closely for at least 1 hour after receiving ocrelizumab, to make sure you do not have an allergic reaction to the medication.

Ocrelizumab affects your immune system. You may get infections more easily, even serious or fatal infections. Your doctor will need to examine you on a regular basis.

If you've ever had hepatitis B, this virus may become active or get worse during treatment with ocrelizumab or in the months after you stop using this medicine. You may need frequent liver function tests while using this medicine and for several months after your last dose.

Storage

Store intact vials at 2°C to 8°C (36°F to 46°F) in the outer carton to protect from light. Do not freeze. Do not shake. Solutions diluted for infusion should be used immediately, however may be stored for up to 24 hours refrigerated and 8 hours at room temperature (including infusion time); discard if infusion cannot be completed on the same day.