Ocrelizumab is indicated for the treatment of patients with

• relapsing forms of multiple sclerosis (RMS) to reduce relapse rates and slow both clinical and subclinical disease progression.
• It is also indicated for primary progressive multiple sclerosis (PPMS) to delay disease progression and reduce decline in walking ability.

Ocrelizumab is a recombinant humanized monoclonal antibody that selectively binds to CD20-positive B cells. CD20 is a surface antigen expressed on pre-B cells, mature B cells, and memory B cells, while it is absent on lymphoid stem cells and plasma cells. The exact mechanism of action in multiple sclerosis is not fully understood, but it is believed to work through immunomodulation by reducing the number and functional activity of CD20-expressing B cells. After binding to the cell surface, ocrelizumab induces selective depletion of CD20-positive B cells through antibody-dependent cellular phagocytosis (ADCP), antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and apoptosis. B-cell reconstitution and pre-existing humoral immunity are preserved, while innate immunity and total T-cell counts remain unaffected.

Substitution by any other biological medicinal product approved in the indication requires the consent of the prescribing physician. Premedication for infusion-related reactions. Premedicate with 100 mg IV methylprednisolone (or an equivalent) approximately 30 minutes prior to each Ocrelizumab infusion (see section 2.4 Warnings and Precautions) and with an antihistaminic drug (e.g. diphenhydramine) approximately 30-60 minutes before each infusion of Ocrelizumab to reduce the frequency and severity of infusion-related reactions. The addition of an antipyretic (e.g. acetaminophen/paracetamol) may also be considered approximately 30-60 minutes before each infusion of Ocrelizumab.

Administration of Ocrelizumab: Ocrelizumab is administered as an IV infusion through a dedicated line under the close supervision of an experienced healthcare professional with access to appropriate medical support to manage severe reactions such as serious IRRs. Ocrelizumab infusions should not be administered as an intravenous push or bolus. Use isotonic 0.9% sodium chloride solution as the infusion vehicle. In the event an IV infusion cannot be completed the same day, the remaining liquid in the infusion bag must be discarded. Observe the patient for at least one hour after the completion of the infusion.

Initial Dose: Ocrelizumab is administered by IV infusion as a 600 mg dose every 6 months. The initial 600 mg dose is administered as two separate IV infusions; first as a 300 mg infusion, followed 2 weeks later by a second 300 mg infusion.

Subsequent Doses: Subsequent doses of Ocrelizumab thereafter are administered as a single 600 mg IV infusion every 6 months. If patients did not experience a serious infusion-related reaction (IRR) with any previous Ocrelizumab infusion, a shorter (2-hour) infusion can be administered for subsequent doses. A minimum interval of 5 months should be maintained between each dose of Ocrelizumab.

No dedicated drug interaction studies have been conducted, as interactions via CYP enzymes, other metabolizing enzymes, or transporters are not expected.

Ocrelizumab should not be used in patients with known hypersensitivity to ocrelizumab or any of its components.

Pregnancy: Ocrelizumab is a humanized monoclonal antibody of the immunoglobulin G1 subclass, and immunoglobulins are known to cross the placental barrier.
Lactation: It is not known whether Ocrelizumab is excreted in human breast milk or affects the breastfed infant or milk production. Animal studies have shown excretion of ocrelizumab in milk. Since human IgG is excreted in breast milk and the potential for absorption leading to B-cell depletion is unknown, women should be advised to discontinue breastfeeding during OCREVUS therapy.

Pediatric Use: The safety and efficacy of Ocrelizumab in patients under 18 years of age have not been established.
Geriatric Use: The safety and efficacy of Ocrelizumab in patients aged 65 years and above have not been established.
Renal Impairment: The safety and efficacy of Ocrelizumab in patients with renal impairment have not been formally evaluated. Dose adjustment is not expected to be necessary.

Store vials at 2–8°C. Keep in the original outer carton to protect from light. Do not freeze. Do not shake.