Ocrelizumab

FDA Drug Information • Also known as: Ocrevus

Brand Names: Ocrevus
Drug Class: CD20-directed Cytolytic Antibody [EPC]
Route: INTRAVENOUS
Dosage Form: INJECTION
Product Type: HUMAN PRESCRIPTION DRUG

Description

11 DESCRIPTION Ocrelizumab is a recombinant humanized monoclonal antibody directed against CD20-expressing B-cells. Ocrelizumab is a glycosylated immunoglobulin G1 (IgG1) with a molecular mass of approximately 145 kDa. OCREVUS (ocrelizumab) injection for intravenous infusion is a preservative-free, sterile, clear or slightly opalescent, and colorless to pale brown solution supplied in single-dose vials. Each mL of solution contains 30 mg ocrelizumab, glacial acetic acid (0.25 mg), polysorbate 20 (0.2 mg), sodium acetate trihydrate (2.14 mg), and trehalose dihydrate (40 mg) at pH 5.3.

What Is Ocrelizumab Used For?

1 INDICATIONS AND USAGE OCREVUS is indicated for the treatment of: Relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults Primary progressive MS, in adults OCREVUS is a CD20-directed cytolytic antibody indicated for the treatment of: Relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults ( 1 ) Primary progressive MS, in adults ( 1 )

Dosage and Administration

2 DOSAGE AND ADMINISTRATION Before initiating OCREVUS, screen for Hepatitis B virus and obtain serum quantitative immunoglobulins, aminotransferases, alkaline phosphatase, and bilirubin ( 2.1 ) Pre-medicate with methylprednisolone (or an equivalent corticosteroid) and an antihistamine (e.g., diphenhydramine) prior to each infusion ( 2.2 ) Administer OCREVUS by intravenous infusion Start dose: 300 mg intravenous infusion, followed two weeks later by a second 300 mg intravenous infusion ( 2.3 ) Subsequent doses: 600 mg intravenous infusion every 6 months ( 2.3 ) Must be diluted prior to administration ( 2.3 , 2.6 ) Monitor patients closely during and for at least one hour after infusion ( 2.3 , 2.5 ) 2.1 Assessments Prior to First Dose of OCREVUS Hepatitis B Virus Screening Prior to initiating OCREVUS, perform Hepatitis B virus (HBV) screening. OCREVUS is contraindicated in patients with active HBV confirmed by positive results for HBsAg and anti-HBV tests. For patients who are negative for surface antigen [HBsAg] and positive for HB core antibody [HBcAb+] or are carriers of HBV [HBsAg+], consult liver disease experts before starting and during treatment [see Warnings and Precautions (5.2) ] . Serum Immunoglobulins Prior to initiating OCREVUS, perform testing for quantitative serum immunoglobulins [see Warnings and Precautions (5.4) ] . For patients with low serum immunoglobulins, consult immunology experts before initiating treatment with OCREVUS. Vaccinations Because vaccination with live-attenuated or live vaccines is not recommended during treatment and after discontinuation until B-cell repletion, administer all immunizations according to immunization guidelines at least 4 weeks prior to initiation of OCREVUS for live or live-attenuated vaccines and, whenever possible, at least 2 weeks prior to initiation of OCREVUS for non-live vaccines [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.2) ] . Liver Function Tests Prior to initiating OCREVUS, obtain serum aminotransferases (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]), alkaline phosphatase, and bilirubin levels [see Warnings and Precautions (5.7) ] . 2.2 Preparation Before Every Infusion Infection Assessment Prior to every infusion of OCREVUS, determine whether there is an active infection. In case of active infection, delay infusion of OCREVUS until the infection resolves [see Warnings and Precautions (5.2) ]. Recommended Premedication Pre-medicate with 100 mg of methylprednisolone (or an equivalent corticosteroid) administered intravenously approximately 30 minutes prior to each OCREVUS infusion to reduce the frequency and severity of infusion reactions [see Warnings and Precautions (5.1) ] . Pre-medicate with an antihistamine (e.g., diphenhydramine) approximately 30-60 minutes prior to each OCREVUS infusion to further reduce the frequency and severity of infusion reactions. The addition of an antipyretic (e.g., acetaminophen) may also be considered....

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following serious adverse reactions are discussed in greater detail in other sections of the labeling: Infusion Reactions [see Warnings and Precautions (5.1) ] Infections [see Warnings and Precautions (5.2) ] Progressive Multifocal Leukoencephalopathy [see Warnings and Precautions (5.3) ] Reduction in Immunoglobulins [see Warnings and Precautions (5.4) ] Malignancies [see Warnings and Precautions (5.5) ] Immune-Mediated Colitis [see Warnings and Precautions (5.6) ] Liver Injury [see Warnings and Precautions (5.7) ] The most common adverse reactions were: RMS (incidence ≥10% and > REBIF ® ): upper respiratory tract infections and infusion reactions ( 6.1 ) PPMS (incidence ≥10% and > placebo): upper respiratory tract infections, infusion reactions, skin infections, and lower respiratory tract infections ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Genentech at 1-888-835-2555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reactions rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The safety of OCREVUS has been evaluated in 1311 patients across MS clinical studies, which included 825 patients in active-controlled clinical trials in patients with relapsing forms of MS (RMS) and 486 patients in a placebo-controlled study in patients with primary progressive MS (PPMS). Adverse Reactions in Patients with Relapsing Forms of MS In active-controlled clinical trials (Study 1 and Study 2), 825 patients with RMS received OCREVUS 600 mg intravenously every 24 weeks (initial treatment was given as two separate 300 mg infusions at Weeks 0 and 2) [see Clinical Studies (14.1) ]. The overall exposure in the 96-week controlled treatment periods was 1448 patient-years. The most common adverse reactions in RMS trials (incidence ≥ 10%) were upper respiratory tract infections and infusion reactions. Table 2 summarizes the adverse reactions that occurred in RMS trials (Study 1 and Study 2). Table 2 Adverse Reactions in Adult Patients with RMS with an Incidence of at least 5% for OCREVUS and Higher than REBIF Adverse Reactions Studies 1 and 2 OCREVUS 600 mg IV Every 24 Weeks The first dose was given as two separate 300 mg infusions at Weeks 0 and 2. (n=825) % REBIF 44 mcg SQ 3 Times per Week (n=826) % Upper respiratory tract infections 40 33 Infusion reactions 34 10 Depression 8 7 Lower respiratory tract infections 8 5 Back pain 6 5 Herpes virus- associated infections 6 4 Pain in extremity 5 4 Adverse Reactions in Patients with Primary Progressive MS In a placebo-controlled clinical trial (Study 3), a total of 486 patients with PPMS received one course of OCREVUS (600 mg of OCREVUS administered as two 300 mg infusions two weeks apart) given intravenously every 24 weeks and 239 patients received placebo intravenously [see Clinical Studies (14.2) ]. The overall exposure in the controlled treatment period was 1416 patient-years, with median treatment duration of 3 years. The most common adverse reactions in the PPMS trial (incidence ≥ 10%) were upper respiratory tract infections, infusion reactions, skin infections, and lower respiratory tract infections. Table 3 summarizes the adverse reactions that occurred in the PPMS trial (Study 3). Table 3 Adverse Reactions in Adult Patients with PPMS with an Incidence of at least 5% for OCREVUS and Higher than Placebo Adverse Reactions Study 3 OCREVUS 600 mg IV Every 24 Weeks One dose of OCREVUS (600 mg administered as two 300 mg infusions two weeks apart) Placebo (n=486) % (n=239) % Upper respiratory tract infections 49 43 Infusion reactions 40 26 Skin infections 14 11 Lower respiratory tract infections 10 9 Cough 7 3 Diarrhea 6 5 Edema peripheral 6 5 Herpes virus associated infections 5 4 Adverse Reactions in Patients who Received...

Drug Interactions

7 DRUG INTERACTIONS 7.1 Immunosuppressive or Immune-Modulating Therapies The concomitant use of OCREVUS and other immune-modulating or immunosuppressive therapies, including immunosuppressant doses of corticosteroids, is expected to increase the risk of immunosuppression. Consider the risk of additive immune system effects when coadministering immunosuppressive therapies with OCREVUS. When switching from drugs with prolonged immune effects, such as daclizumab, fingolimod, natalizumab, teriflunomide, or mitoxantrone, consider the duration and mode of action of these drugs because of additive immunosuppressive effects when initiating OCREVUS [see Warnings and Precautions (5.2) ]. 7.2 Vaccinations A Phase 3b randomized, open-label study examined the concomitant use of OCREVUS and several non-live vaccines in adults 18-55 years of age with relapsing forms of MS (68 subjects undergoing treatment with OCREVUS at the time of vaccination and 34 subjects not undergoing treatment with OCREVUS at the time of vaccination). Concomitant exposure to OCREVUS attenuated antibody responses to tetanus toxoid-containing vaccine, pneumococcal polysaccharide, pneumococcal conjugate vaccines, and seasonal inactivated influenza vaccines. The impact of the observed attenuation on vaccine effectiveness in this patient population is unknown. The safety and effectiveness of live or live-attenuated vaccines administered concomitantly with OCREVUS have not been assessed [see Warnings and Precautions (5.2) ] .

Contraindications

4 CONTRAINDICATIONS OCREVUS is contraindicated in patients with: Active HBV infection [see Dosage and Administration (2.1) and Warnings and Precautions (5.2) ] A history of life-threatening infusion reaction to OCREVUS [see Warnings and Precautions (5.1) ] Active hepatitis B virus infection ( 4 ) History of life-threatening infusion reaction to OCREVUS ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary OCREVUS is a humanized monoclonal antibody of an immunoglobulin G1 subtype and immunoglobulins are known to cross the placental barrier. There are no adequate data on the developmental risk associated with use of OCREVUS in pregnant women. However, transient peripheral B-cell depletion and lymphocytopenia have been reported in infants born to mothers exposed to other anti-CD20 antibodies during pregnancy. B-cell levels in infants following maternal exposure to OCREVUS have not been studied in clinical trials. The potential duration of B-cell depletion in such infants, and the impact of B-cell depletion on vaccine safety and effectiveness, is unknown [see Warnings and Precautions (5.2) ] . Following administration of ocrelizumab to pregnant monkeys at doses similar to or greater than those used clinically, increased perinatal mortality, depletion of B-cell populations, renal, bone marrow, and testicular toxicity were observed in the offspring in the absence of maternal toxicity [see Data ] . In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Data Animal Data Following intravenous administration of OCREVUS to monkeys during organogenesis (loading doses of 15 or 75 mg/kg on gestation days 20, 21, and 22, followed by weekly doses of 20 or 100 mg/kg), depletion of B-lymphocytes in lymphoid tissue (spleen and lymph nodes) was observed in fetuses at both doses. Intravenous administration of OCREVUS (three daily loading doses of 15 or 75 mg/kg, followed by weekly doses of 20 or 100 mg/kg) to pregnant monkeys throughout the period of organogenesis and continuing through the neonatal period resulted in perinatal deaths (some associated with bacterial infections), renal toxicity (glomerulopathy and inflammation), lymphoid...

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING OCREVUS (ocrelizumab) injection is a preservative-free, sterile, clear or slightly opalescent, and colorless to pale brown solution supplied as a carton containing one 300 mg/10 mL (30 mg/mL) single-dose vial (NDC 50242-150-01). Store OCREVUS vials at 2°C to 8°C (36°F to 46°F) in the outer carton to protect from light. Do not freeze or shake.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.