Ocrelizumab
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CD20-directed Cytolytic Antibody
Dosing in kidney impairment
This label has no separate kidney-impairment dosing section. Check warnings and clinical pharmacology in the full label.
Preparation and administration
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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 ]. Recommended Premedication To reduce the frequency and severity of infusion reactions, administer the following premedications [see Warnings and Precautions ] : Methylprednisolone (or an equivalent corticosteroid) by intravenous infusion to be completed approximately 30 minutes prior to each OCREVUS infusion, as follows: Adults and pediatric patients who weigh 40 kg or more: 100 mg Pediatric patients who weigh less than 40 kg: 2 mg/kg An antihistamine (e.g., diphenhydramine) 30 to 60 minutes prior to each OCREVUS infusion.
An antipyretic (e.g., acetaminophen) may also be considered. Administer the antipyretic 30 minutes to 60 minutes prior to OCREVUS infusion.
Recommended Dosage and Dose Administration Administer OCREVUS under the close supervision of an experienced healthcare professional with access to appropriate medical support to manage severe reactions such as serious infusion reactions. Observe the patient for at least one hour after the completion of the infusion [see Warnings and Precautions ] .
OCREVUS is administered as an intravenous infusion. The initial dose is split into two equal infusions administered two weeks apart. Subsequent doses are administered every 6 months thereafter (see Table 1 ). Dosing for pediatric patients (10 years of age and older) is according to body weight (see Table 2 ). [See table below.] [See table below.]
Delayed or Missed Doses If a planned infusion of OCREVUS is missed, administer OCREVUS as soon as possible; do not wait until the next scheduled dose. Reset the dose schedule to administer the next sequential dose 6 months after the missed dose is administered. Doses of OCREVUS must be separated by at least 5 months [see Dosage and Administration ] .
Dose Modifications Because of Infusion Reactions Dose modifications in response to infusion reactions depends on the severity. Life-threatening Infusion Reactions Immediately stop and permanently discontinue OCREVUS if there are signs of a life-threatening or disabling infusion reaction [see Warnings and Precautions ] .
Provide appropriate supportive treatment. Severe Infusion Reactions Immediately interrupt the infusion and administer appropriate supportive treatment, as necessary [see Warnings and Precautions ] . Restart the infusion only after all symptoms have resolved. When restarting, begin at half of the infusion rate at the time of onset of the infusion reaction.
If this rate is tolerated, increase the rate as described in Table 1 and Table 2 [see Dosage and Administration ] . This change in rate will increase the total duration of the infusion but not the total dose. Mild to Moderate Infusion Reactions Reduce the infusion rate to half the rate at the onset of the infusion reaction and maintain the reduced rate for at least 30 minutes [see Warnings and Precautions ] .
If this rate is tolerated, increase the rate as described in Table 1 and Table 2 [see Dosage and Administration ] . This change in rate will increase the total duration of the infusion but not the total dose.
Preparation and Storage of the Dilute Solution for Infusion Preparation OCREVUS must be prepared by a healthcare professional using aseptic technique. A sterile needle and syringe should be used to prepare the diluted infusion solution. Visually inspect for particulate matter and discoloration prior to administration. Do not use the solution if discolored or if the solution contains discrete foreign particulate matter.
Do not shake. Withdraw the required dose of OCREVUS and further dilute into an infusion bag containing 0.9% Sodium Chloride Injection, as described in Table 3. [See table below.] 600 mg 20 mL 500 mL 1.2 mg/mL Do not use other diluents to dilute OCREVUS because their use has not been tested. The product contains no preservative and is intended for single use only.
Discard any unused portion left in the vial. Storage of Infusion Solution Prior to the start of the intravenous infusion, the content of the infusion bag should be at room temperature. Use the prepared infusion solution immediately. If not used immediately, store up to 24 hours in the refrigerator at 2°C to 8°C (36°F to 46°F) and 8 hours at room temperature up to 25°C (77°F), which includes infusion time.
In the event an intravenous infusion cannot be completed the same day, discard the remaining solution. No incompatibilities between OCREVUS and polyvinyl chloride (PVC) or polyolefin (PO) bags and intravenous (IV) administration sets have been observed. Administration Administer the diluted infusion solution through a dedicated line using an infusion set with a 0.2 or 0.22 micron in-line filter.
| Amount and Volume Solutions of OCREVUS for intravenous infusion are prepared by dilution of the drug product into an infusion bag containing 0.9% Sodium Chloride Injection, to a final drug concentration of approximately 1.2 mg/mL. | Infusion Rate and Duration Infusion time may take longer if the infusion is interrupted or slowed [see Dosage and Administration (2.5)]. | ||
|---|---|---|---|
| Initial Dose (two infusions) | Infusion 1 | 300 mg in 250 mL | Start at 30 mL per hourIncrease by 30 mL per hour every 30 minutesMaximum: 180 mL per hourDuration: 2.5 hours or longer |
| Infusion 2 (2 weeks later) | 300 mg in 250 mL | ||
| Subsequent Doses (one infusion) every 6 months) Administer the first Subsequent Dose 6 months after Infusion 1 of the Initial Dose. | Option 1 Infusion of approximately 3.5 hours duration | 600 mg in 500 mL | Start at 40 mL per hourIncrease by 40 mL per hour every 30 minutesMaximum: 200 mL per hourDuration: 3.5 hours or longer |
| OR | |||
| Option 2 (If no prior serious infusion reaction with any previous OCREVUS infusion)[see Adverse Reactions (6.1) and Clinical Studies (14.3)]. Infusion of approximately 2 hours duration | 600 mg in 500 mL | Start at 100 mL per hour for the first 15 minutesIncrease to 200 mL per hour for the next 15 minutesIncrease to 250 mL per hour for the next 30 minutesIncrease to 300 mL per hour for the remaining 60 minutesDuration: 2 hours or longer | |
| Infusion | Amount and VolumeSolutions of OCREVUS for intravenous infusion are prepared by dilution of the drug product into an infusion bag containing 0.9% Sodium Chloride for Injection [see Dosage and Administration (2.6)]. | Infusion Rate and DurationInfusion time may take longer if the infusion is interrupted or slowed [see Dosage and Administration (2.5)]. | |
|---|---|---|---|
| Body Weight 25 kg to Less Than 35 kg | |||
| Initial Dose (two infusions) | Infusion 1 | 150 mg in 250 mL | Start at 30 mL per hourIncrease by 30 mL per hour every 30 minutesMaximum: 180 mL per hourDuration: 2.5 hours or longer |
| Infusion 2 (2 weeks later) | 150 mg in 250 mL | ||
| Subsequent Doses (one infusion every 6 months) | Single infusion once every 6 months | 300 mg in 250 mL | |
| Body Weight 35 kg or More | |||
| Initial Dose (two infusions) | Infusion 1 | 300 mg in 250 mL | Start at 30 mL per hourIncrease by 30 mL per hour every 30 minutesMaximum: 180 mL per hourDuration: 2.5 hours or longer |
| Infusion 2 (2 weeks later) | 300 mg in 250 mL | ||
| Subsequent Doses (one infusion every 6 months) | Single infusion once every 6 months | 600 mg in 500 mL | Start at 40 mL per hourIncrease by 40 mL per hour every 30 minutesMaximum: 200 mL per hourDuration: 3.5 hours or longer |
| Dose of OCREVUS (mg) | Volume of OCREVUS (mL) | Volume of 0.9% Sodium Chloride Injection (mL) | Final Drug Concentration (mg/mL) |
|---|---|---|---|
| 150 mg | 5 mL | 250 mL | 0.6 mg/mL |
| 300 mg | 10 mL | 250 mL | 1.2 mg/mL |
| 600 mg | 20 mL | 500 mL | 1.2 mg/mL |
Drug interactions
Check ocrelizumab against a medication listLabel text (4 paragraphs)
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 )
Safety data
Reported adverse events (FAERS)
Liver injury (LiverTox)
CLikelihood score C: Rare cause of clinically apparent liver injury, sometimes due to reactivation of hepatitis B.
Ocrelizumab is a humanized monoclonal antibody to CD20 which is used as therapy of multiple sclerosis. Ocrelizumab is associated with a low rate serum enzyme elevations during therapy and to rare instances of clinically apparent liver injury and to reactivation of hepatitis B in susceptible patients which is usually mild but can be severe.
ABCDEA: well known cause; E: unlikely cause. [HD]: high doses only.
Pregnancy and lactation
Pregnancy
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 follicle formation in the bone marrow, and severe decreases in circulating B-lymphocytes in neonates. The cause of the neonatal deaths is uncertain; however, both affected neonates were found to have bacterial infections. Reduced testicular weight was observed in neonates at the high dose.
A no-effect dose for adverse developmental effects was not identified; the doses tested in monkey are 2 and 10 times the recommended human dose of 600 mg, on a mg/kg basis.
Breastfeeding (LactMed)
Amounts of ocrelizumab in milk are low and undetectable in the serum of breastfed infants. Many infants have been exposed to ocrelizumab during breastfeeding. No excess of infections or reductions of B-cells have been reported. Infant growth has been normal, and no evidence of severe or persistent harm has been reported. Most expert guidelines consider breastfeeding with ocrelizumab to be acceptable and ocrelizumab is approved for use during breastfeeding in the UK and Europe. Waiting for at least 2 weeks postpartum to resume therapy may minimize transfer to the infant.
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Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
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