Ocrelizumab is indicated for the treatment of patients with-

• Relapsing forms of multiple sclerosis (RMS) to suppress relapses and disease progression (clinical and subclinical disease activity).
• Primary progressive multiple sclerosis (PPMS) to delay disease progression and reduce deterioration in walking speed.

Ocrelizumab is a recombinant humanized monoclonal antibody that selectively targets CD20-expressing B-cells. CD20 is a cell surface antigen found on pre-B-cells, mature and memory B-cells but not expressed on lymphoid stem cells and plasma cells. The precise mechanisms through which ocrelizumab exerts its therapeutic clinical effects in MS are not fully elucidated but is presumed to involve immunomodulation through the reduction in the number and function of CD20-expressing B-cells. Following cell surface binding, ocrelizumab selectively depletes CD20-expressing B-cells through antibody-dependent cellular phagocytosis (ADCP), antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and apoptosis. The capacity of B-cell reconstitution and preexisting humoral immunity are preserved. In addition, innate immunity and total T-cell numbers are not affected.

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 formal drug interaction studies have been performed, as no drug interactions are expected via the CYP and other metabolizing enzymes or transporters.

Ocrelizumab is contraindicated in patients with a known hypersensitivity to ocrelizumab or to any of the excipients.

Pregnancy: Ocrelizumab is a humanized monoclonal antibody of an immunoglobulin G1 subtype and immunoglobulins are known to cross the placental barrier.

Lactation: It is unknown whether Ocrelizumab is excreted in human breast milk or has any effect on the breastfed child and on milk production. Animal studies have shown excretion of ocrelizumab in breast milk. Because human IgG is excreted in human milk, and the potential for ocrelizumab 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 children and adolescents (<18 years) has not been
studied.

Geriatric Use: The safety and efficacy of Ocrelizumab in patients ≥65 years of age has not been studied.

Renal Impairment: The safety and efficacy of Ocrelizumab in patients with renal impairment has not been formally studied. A change in dose is not expected to be required for patients with renal impairment.

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