Ocrevus

• Approved Indications:
• Treatment of relapsing forms of multiple sclerosis (RMS), including clinically isolated syndrome, relapsing-remitting MS, and active secondary progressive MS.
• Treatment of primary progressive multiple sclerosis (PPMS) in adults.
• Off-label and Investigational Uses:
• Investigated in other autoimmune neurological disorders.
• Not currently approved for other indications.

• Adults:
• Initial Dose: 300 mg intravenous (IV) infusion on Day 1, followed by 300 mg IV infusion on Day 15.
• Maintenance Dose: 600 mg IV infusion every 6 months thereafter.
• Pediatrics: Safety and efficacy not established; use not recommended.
• Elderly: No specific dose adjustments; monitor tolerability.
• Special Populations:
• Renal or Hepatic Impairment: No dose adjustments necessary.
• Administration Notes:
• Administered by intravenous infusion.
• Pre-medicate with corticosteroids and antihistamines to reduce infusion-related reactions.
• Infusion duration approximately 3.5 hours for initial doses, possibly shorter for maintenance.
• Monitor patients during and after infusion for signs of hypersensitivity.

Ocrelizumab is a humanized monoclonal antibody targeting CD20, a surface antigen expressed on B lymphocytes. By binding to CD20, ocrelizumab mediates selective depletion of CD20-positive B cells through antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). This B-cell depletion reduces inflammatory activity in the central nervous system that contributes to demyelination and neurodegeneration in multiple sclerosis, thereby slowing disease progression and reducing relapse frequency.

• Absorption: Not applicable (intravenous administration).
• Distribution: Plasma volume distribution with limited extravascular penetration.
• Metabolism: Proteolytic degradation into small peptides and amino acids.
• Elimination: Half-life approximately 26 days; clearance decreases with repeated dosing due to B-cell depletion.
• Onset: B-cell depletion occurs within days after infusion.
• Steady State: Achieved after approximately 3 doses (about 1 year).

• Pregnancy:
• No adequate controlled studies in pregnant women.
• Animal studies show fetal harm; risk cannot be ruled out.
• Use only if potential benefit justifies potential fetal risk.
• Lactation:
• Unknown if ocrelizumab is excreted in human milk.
• Breastfeeding not recommended during treatment and for at least 6 months after last dose.
• Caution: Limited human data; exercise caution during pregnancy and lactation.

• Primary Class: Monoclonal antibody
• Subclass: Anti-CD20 B-cell depleting agent

• Known hypersensitivity to ocrelizumab or any excipients.
• Active hepatitis B infection.
• Severe active infections.
• History of life-threatening infusion reactions to ocrelizumab.

• Infusion-Related Reactions: Common and can be severe; pre-medication and monitoring required.
• Infections: Increased risk of upper respiratory and herpesvirus infections; screen for hepatitis B before treatment.
• Malignancies: Cases of malignancies, including breast cancer, reported; monitor accordingly.
• Immunizations: Live vaccines should be avoided during treatment and for 6 months post-treatment.
• Progressive Multifocal Leukoencephalopathy (PML): Rare but serious risk; monitor neurological symptoms.
• Monitoring: Regular blood counts and liver function tests recommended.

• Common:
• Infusion-related reactions (fever, rash, headache, throat irritation)
• Upper respiratory tract infections
• Nasopharyngitis
• Fatigue
• Skin infections
• Serious:
• Severe infusion reactions (anaphylaxis)
• Infections (including herpesvirus)
• Malignancies (breast cancer reported)
• PML (rare)
• Rare:
• Autoimmune disorders
• Cytopenias

• No significant CYP450 metabolism; low potential for drug-drug interactions.
• Immunosuppressive agents may increase risk of infections and immunosuppression.
• Live vaccines contraindicated during and post-treatment.

• FDA approved ocrelizumab in 2017 as the first therapy for primary progressive MS.
• Recent guidelines endorse ocrelizumab for early treatment of relapsing MS forms.
• Post-marketing surveillance emphasizes vigilance for infusion reactions and malignancies.
• EMA and NICE guidelines align with FDA indications and safety monitoring recommendations.

• Store refrigerated at 2°C to 8°C (36°F to 46°F).
• Protect from light; keep in original packaging until use.
• Do not freeze.
• Avoid shaking or agitation.
• Use reconstituted or diluted solutions promptly according to prescribing information.