Usage
- Ocrelizumab is prescribed for the treatment of relapsing forms of multiple sclerosis (RMS), including relapsing-remitting disease and active secondary progressive disease, in adults. It is also indicated for primary progressive multiple sclerosis (PPMS) in adults.
- Pharmacological Classification: Disease-modifying therapy (DMT), monoclonal antibody, anti-CD20
- Mechanism of Action: Ocrelizumab selectively targets and depletes CD20-positive B cells, which are thought to play a central role in the pathogenesis of multiple sclerosis. It binds to the CD20 surface antigen on pre-B and mature B lymphocytes, leading to antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity, ultimately reducing the inflammatory processes that contribute to MS.
Alternate Names
- International Nonproprietary Name (INN): Ocrelizumab
- Brand Name: Ocrevus, Ocrevus ZunOvo (subcutaneous formulation containing hyaluronidase)
How It Works
- Pharmacodynamics: Ocrelizumab targets and removes CD20-positive B cells, reducing inflammation and the frequency and severity of MS relapses. This specific targeting leads to reduced impact on other immune cells compared to broader immunosuppressants.
- Pharmacokinetics:
- Absorption: Administered intravenously (IV infusion) or subcutaneously. IV administration results in near-complete bioavailability. Subcutaneous formulation reaches maximum concentration rapidly.
- Distribution: Distributes throughout the body with an average half-life of 26 days, requiring approximately 5 half-lives for full elimination, or approximately 18.5 weeks.
- Metabolism: Being a large molecule, it is primarily eliminated through catabolism into small peptides and amino acids.
- Elimination: Not significantly renally or hepatically excreted; the majority of elimination occurs through intracellular catabolism.
- Mode of Action: Binds to the CD20 antigen on B cells, initiating cell lysis via antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC).
- Receptor Binding: Specific to CD20 surface antigen on B lymphocytes.
- Enzyme Inhibition: Does not act through enzyme inhibition.
- Neurotransmitter Modulation: Does not directly modulate neurotransmitters.
- Elimination Pathways: Intracellular catabolism is the primary mechanism, not renal or hepatic excretion.
Dosage
Standard Dosage
Adults:
- Initial Dose: 300 mg IV infusion, followed by a second 300 mg IV infusion two weeks later.
- Maintenance Dose: 600 mg IV infusion every six months.
- Subcutaneous Formulation: 120mg every 2 weeks, started 2 weeks after first and second IV loading doses.
Children:
- Ocrelizumab is not approved for use in children.
Special Cases:
- Elderly Patients: No dose adjustments are typically necessary based on age alone.
- Patients with Renal Impairment: No dose adjustments are necessary.
- Patients with Hepatic Dysfunction: No dose adjustments are necessary.
- Patients with Comorbid Conditions: Evaluate for possible drug interactions based on existing medication.
Clinical Use Cases
- Ocrelizumab is specifically indicated for the treatment of RMS and PPMS. It is not intended for other clinical use cases like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.
Dosage Adjustments
- No standard dose adjustments are required based on renal/hepatic function, metabolic disorders, or genetic polymorphisms.
Side Effects
Common Side Effects
- Infusion-related reactions (itching, rash, hives, throat irritation, shortness of breath, flushing, fever, chills, fatigue, headache, dizziness, nausea)
- Upper respiratory tract infections
- Skin infections
- Lower respiratory tract infections
Rare but Serious Side Effects
- Progressive multifocal leukoencephalopathy (PML)
- Hepatitis B reactivation
- Severe allergic reactions
- Certain cancers (e.g., breast cancer)
Long-Term Effects
- Increased risk of infections, especially with prolonged use.
- Potential for secondary autoimmunity or immune-related adverse events.
Adverse Drug Reactions (ADR)
- Severe infusion-related reactions (anaphylaxis, bronchospasm) require immediate medical attention.
Contraindications
- Active hepatitis B infection
- History of life-threatening infusion reaction to ocrelizumab
Drug Interactions
- Live vaccines (avoid during treatment and until B-cell repletion)
- Immunosuppressants (increased risk of infection)
- Other B-cell depleting agents
- Medications affecting the immune system
Pregnancy and Breastfeeding
- Pregnancy: According to updated labeling (February 13, 2025) breastfeeding is now permitted while receiving Ocrelizumab treatment. Earlier recommendations were to avoid treatment during pregnancy unless the benefits outweigh the potential risks. Consult with a physician for personalized advice.
- Breastfeeding: According to updated labeling (February 13, 2025) breastfeeding is now permitted while receiving Ocrelizumab treatment. Minimal amounts are present in breast milk. Earlier recommendations suggested exercising caution.
Drug Profile Summary
- Mechanism of Action: Depletes CD20-positive B cells.
- Side Effects: Infusion reactions, infections (upper respiratory, skin), rare PML.
- Contraindications: Active hepatitis B, prior severe reaction.
- Drug Interactions: Live vaccines, immunosuppressants.
- Pregnancy & Breastfeeding: Breastfeeding now allowed while taking ocrelizumab. Consult with a physician for any concerns.
- Dosage: 300 mg x 2 initial doses, then 600 mg every 6 months.
- Monitoring Parameters: B-cell counts, liver function tests, signs of infection.
Popular Combinations
Ocrelizumab is generally used as monotherapy for MS. Concomitant use with other DMTs is generally avoided due to increased infection risk.
Precautions
- General Precautions: Screen for HBV infection before initiation. Monitor for infusion reactions.
- Specific Populations: Discuss risks and benefits with pregnant/breastfeeding women (breastfeeding now allowed while taking ocrelizumab) No dosage adjustments needed for children (not applicable) or elderly.
- Lifestyle Considerations: Vaccination should be addressed with a physician (generally live attenuated vaccines are avoided during treatment and until B-cell recovery.)
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Ocrelizumab?
A: Initial dose is 300 mg IV infusion x 2, two weeks apart. Maintenance is 600 mg IV every 6 months.
Q2: What are the common side effects?
A: Infusion reactions, upper respiratory and skin infections are common.
Q3: What are the contraindications?
A: Active hepatitis B infection and prior severe reaction.
Q4: How does Ocrelizumab work?
A: Depletes CD20+ B cells, thought to drive MS inflammation.
Q5: Can Ocrelizumab be used during pregnancy or breastfeeding?
A: As of February 13, 2025, breastfeeding is permitted while taking ocrelizumab. Earlier recommendations were to exercise caution. Discuss individual cases with physician.
Q6: What are the serious side effects?
A: PML, Hepatitis B reactivation, severe allergic reactions.
Q7: What should be monitored during treatment?
A: B-cell counts, liver function, signs of infection.
Q8: How is Ocrelizumab administered?
A: Intravenous infusion or subcutaneous injection.
Q9: Does it interact with other medications?
A: Yes, notably live vaccines and other immunosuppressants. Consult a doctor for details.
