OCREVUS
Clinical safety rating
cautionComprehensive clinical and safety monograph for OCREVUS (OCREVUS).
Comprehensive clinical and safety monograph for OCREVUS (OCREVUS).
Relapsing forms of multiple sclerosis (RMS), including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive diseasePrimary progressive multiple sclerosis (PPMS)
Ocrelizumab is a recombinant humanized monoclonal antibody that selectively targets CD20-positive B cells. It binds to the CD20 antigen expressed on pre-B cells, mature B cells, and memory B cells, but not on plasma cells or hematopoietic stem cells. Binding induces antibody-dependent cellular cytotoxicity and complement-mediated lysis, resulting in B-cell depletion.
| Metabolism | Ocrelizumab is a monoclonal antibody; it is catabolized into small peptides and amino acids via general protein degradation pathways. No specific metabolic enzymes are involved, and it does not rely on hepatic or renal pathways for clearance. |
| Excretion | Ocrelizumab is a humanized monoclonal antibody that is catabolized by general protein degradation pathways; it is not excreted renally or hepatically. Less than 1% is eliminated unchanged in urine. Biliary/fecal excretion is negligible as intact IgG. |
| Half-life | Terminal elimination half-life is approximately 26 days (range: 18–39 days) for the 600 mg intravenous dose. This supports every-6-month dosing for sustained B-cell depletion. |
| Protein binding | Ocrelizumab is an IgG1 monoclonal antibody; it does not bind to plasma proteins. Estimated protein binding is negligible (< 1%). |
| Volume of Distribution | Volume of distribution is approximately 2.78 L (range: 1.89–4.23 L), which corresponds to about 0.04 L/kg for a 70 kg adult. This low Vd indicates distribution primarily in the vascular and interstitial spaces. |
| Bioavailability | Ocrelizumab is only administered intravenously; bioavailability is 100% by the IV route. Subcutaneous or oral routes are not approved; bioavailability via these routes is unknown. |
| Onset of Action | For intravenous administration, B-cell depletion in peripheral blood occurs within 2 weeks of the first dose. Clinical onset of effect in relapsing multiple sclerosis may be seen as early as 4 weeks. |
| Duration of Action | Duration of B-cell suppression is sustained for at least 6 months. After treatment cessation, B-cell counts generally recover over 6–12 months but may remain low beyond 18 months in some patients. |
| Molecular Weight | 145 |
300 mg intravenous infusion followed 2 weeks later by a second 300 mg intravenous infusion; then 600 mg intravenous infusion every 6 months.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment; not studied in severe renal impairment (CrCl <15 mL/min). |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B); not studied in severe hepatic impairment (Child-Pugh C). |
| Pediatric use | Safety and efficacy in pediatric patients (<18 years) have not been established; no dosage recommendation. |
| Geriatric use | No specific dose adjustment required based on age; consider comorbidities and concomitant medications. Clinical studies included patients up to age 65, limited data in >65 years. |
| 1st trimester | Ocrelizumab is a humanized monoclonal antibody that crosses the placenta. Use during the first trimester is associated with potential fetal harm based on the drug's mechanism of action (B-cell depletion). Limited human data; animal studies have shown embryotoxicity and fetotoxicity. Avoid use unless clearly needed. |
| 2nd trimester | During the second trimester, placental transfer increases. There is a risk of fetal B-cell depletion and potential immunomodulatory effects. Use only if potential benefit justifies potential risk to the fetus. |
| 3rd trimester | Significant placental transfer occurs in the third trimester, leading to detectable levels in neonates. Use is associated with increased risk of neonatal B-cell depletion and infection. Avoid use, especially near delivery. |
Clinical note
Comprehensive clinical and safety monograph for OCREVUS (OCREVUS).
| Placental transfer | Ocrelizumab is an IgG1 monoclonal antibody that actively crosses the placenta via FcRn receptors. Transfer is minimal in the first trimester but increases significantly in the second and third trimesters. Fetal levels may exceed maternal levels near term. |
| Breastfeeding | Ocrelizumab is a large molecule and is expected to be present in human milk in low amounts. However, due to the potential for adverse effects in the breastfed infant (e.g., B-cell depletion, increased risk of infections), breastfeeding is not recommended during treatment and for at least 6 months after the last dose. |
| Lactation Rating | L5 (Contraindicated) |
| Teratogenic Risk | Ocrevus (ocrelizumab) is a humanized monoclonal antibody that depletes CD20-positive B cells. IgG antibodies cross the placenta, especially in the third trimester. There are no adequate and well-controlled studies in pregnant women. In animal studies, ocrelizumab was not teratogenic but caused B-cell depletion in offspring. Use is not recommended unless the benefit outweighs the risk. Based on limited human data, there is no known structural teratogenicity; however, the potential for B-cell depletion and immunosuppression in the fetus, particularly if administered during the second and third trimesters, exists. |
| Fetal Monitoring | For infants exposed in utero, monitor for B-cell count and immune function; assess for infections and evaluate response to vaccinations, particularly live vaccines. In the mother, monitor for infections and infusion-related reactions. No specific fetal monitoring beyond routine prenatal care is recommended. |
| Fertility Effects | No formal fertility studies in humans. Animal studies at doses up to 100 mg/kg showed no adverse effects on male or female fertility. Based on its mechanism (B-cell depletion), fertility is unlikely to be affected, but data are insufficient to rule out potential impact. |
■ FDA Black Box Warning
None
| Serious Effects |
Active hepatitis B infectionHistory of life-threatening infusion reaction to ocrelizumabSevere immunodeficiency (e.g., current opportunistic infection, CD4+ count < 50 cells/μL)
| Precautions | Infusion reactions: May require premedication; monitor during infusion, Infections: Increased risk, including herpes zoster and respiratory tract infections; screen for hepatitis B virus before initiation, Progressive multifocal leukoencephalopathy (PML): Rare but serious; discontinue if suspected, Immunoglobulin levels: Monitor; low IgG associated with increased infection risk, Malignancies: Possible increased risk, particularly breast cancer, Fetal harm: Avoid in pregnancy; women of childbearing potential should use contraception |
| Food/Dietary | No food interactions have been reported with ocrelizumab. The medication is administered intravenously, and there are no dietary restrictions required. |
| Clinical Pearls | Ocrevus (ocrelizumab) is a recombinant humanized monoclonal antibody that selectively targets CD20-positive B cells. It is administered as an intravenous infusion. Premedication with methylprednisolone, an antihistamine, and an antipyretic is required to reduce infusion-related reactions. Screen for hepatitis B virus (HBV) infection before initiating therapy; do not use in patients with active HBV. Monitor for infections, especially upper respiratory tract infections, herpes, and urinary tract infections. Live and live-attenuated vaccines are contraindicated during treatment and until B-cell repletion. Administer all required vaccines at least 4-6 weeks before starting therapy. No dose adjustment needed for renal or hepatic impairment. |
| Patient Advice | Ocrevus is given as an intravenous infusion every 6 months. · You will receive premedication before each infusion to reduce the risk of infusion reactions. · Report any symptoms of infection promptly, including fever, cough, or painful urination. · Avoid receiving live vaccines while on Ocrevus and for a period after treatment. · Tell your doctor if you have a history of hepatitis B infection. · You may be at increased risk for certain cancers, including breast cancer; follow recommended screening. · Inform all healthcare providers that you are taking Ocrevus. |
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