Ocrevus

/ Roche

Assessments Prior to First Dose
Hepatitis B Virus Screening: Prior to initiating Ocrelizumab, perform Hepatitis B virus (HBV) screening. Ocrelizumab 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.
Vaccinations: Because vaccination with live-attenuated or live vaccines is not recommended during treatment and after discontinuation until B-cell repletion, administer all necessary immunizations according to immunization guidelines at least 6 weeks prior to initiation of Ocrelizumab.
Preparation Before Every Infusion
Infection Assessment: Prior to every infusion of Ocrelizumab, determine whether there is an active infection. In case of active infection, delay infusion of Ocrelizumab until the infection resolves.
Recommended Premedication: Pre-medicate with 100 mg of methylprednisolone (or an equivalent corticosteroid) administered intravenously approximately 30 minutes prior to each Ocrelizumab infusion to reduce the frequency and severity of infusion reactions.
Pre-medicate with an antihistamine (e.g., diphenhydramine) approximately 30-60 minutes prior to each Ocrelizumab infusion to further reduce the frequency and severity of infusion reactions. The addition of an antipyretic (e.g., acetaminophen) may also be considered.
Recommended Dosage and Dose Administration: Administer Ocrelizumab under the close supervision of an experienced healthcare professional with access to appropriate medical support to manage severe reactions such as serious infusion reactions.
– Initial dose: 300 mg intravenous infusion, followed two weeks later by a second 300 mg intravenous infusion.
– Subsequent doses: single 600 mg intravenous infusion every 6 months.
– Observe the patient for at least one hour after the completion of the infusion.
For Recommended Dose, Infusion Rate, and Infusion Duration for RMS and PPMS: See prescribing information for full details.
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.
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. Provide appropriate supportive treatment.
Severe Infusion Reactions: Immediately interrupt the infusion and administer appropriate supportive treatment, as necessary. 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. 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. If this rate is tolerated, increase the rate as described in Table 1. This change in rate will increase the total duration of the infusion but not the total dose.

Treatment of adult patients with relapsing or primary progressive forms of multiple sclerosis.

Hypersensitivity to the active substance or to any of the excipients. Active HBV infection. A history of life-threatening infusion reaction to Ocrelizumab.

Infusion Reactions: Ocrelizumab can cause infusion reactions, which can include pruritus, rash, urticaria, erythema, bronchospasm, throat irritation, oropharyngeal pain, dyspnea, pharyngeal or laryngeal edema, flushing, hypotension, pyrexia, fatigue, headache, dizziness, nausea, and tachycardia.
Infections: A higher proportion of Ocrelizumab-treated patients experienced infections compared to patients taking Rebif or placebo.
Respiratory Tract Infections: A higher proportion of Ocrelizumab-treated patients experienced respiratory tract infections compared to patients taking Rebif or placebo.
Herpes: In active-controlled (RMS) clinical trials, herpes infections were reported more frequently in Ocrelizumab-treated patients than in Rebif-treated patients, including herpes zoster (2.1% vs. 1.0%), herpes simplex (0.7% vs. 0.1%), oral herpes (3.0% vs. 2.2%), genital herpes (0.1% vs. 0%), and herpes virus infection (0.1% vs. 0%). Infections were predominantly mild to moderate in severity. There were no reports of disseminated herpes.
Progressive Multifocal Leukoencephalopathy (PML): PML is an opportunistic viral infection of the brain caused by the John Cunningham (JC) virus that typically only occurs in patients who are immune-compromised, and that usually leads to death or severe disability. Although no cases of PML were identified in Ocrelizumab clinical trials, JC virus infection resulting in PML has been observed in patients treated with other anti-CD20 antibodies and other MS therapies and has been associated with some risk factors (e.g., immune-compromised patients, polytherapy with immunosuppressants).
Hepatitis B Virus (HBV) Reactivation: There were no reports of hepatitis B reactivation in MS patients treated with Ocrelizumab. Fulminant hepatitis, hepatic failure, and death caused by HBV reactivation have occurred in patients treated with other anti-CD20 antibodies. Perform HBV screening in all patients before initiation of treatment with Ocrelizumab. Do not administer Ocrelizumab to patients with active HBV confirmed by positive results for HBsAg and anti-HB 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.
Possible Increased Risk of Immunosuppressant Effects with Other Immunosuppressants: When initiating Ocrevus after an immunosuppressive therapy or initiating an immunosuppressive therapy after Ocrevus, consider the potential for increased immunosuppressive effects. Ocrevus has not been studied in combination with other MS therapies.
Vaccinations: Administer all immunizations according to immunization guidelines at least 6 weeks prior to initiation of Ocrelizumab. The safety of immunization with live or live-attenuated vaccines following Ocrelizumab therapy has not been studied, and vaccination with live-attenuated or live vaccines is not recommended during treatment and until Bcell repletion. No data are available on the effects of live or non-live vaccination in patients receiving Ocrelizumab.
Malignancies: An increased risk of malignancy with Ocrelizumab may exist. In controlled trials, malignancies, including breastcancer, occurred more frequently in Ocrelizumab-treated patients.
See prescribing information for full details.

Most common: Upper respiratory tract infections and infusion reactions.
See prescribing information for full details.

Immunosuppressive or Immune-Modulating Therapies: The concomitant use of Ocrelizumab 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 Ocrelizumab. 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 Ocrelizumab.

Pregnancy: There are no adequate data on the developmental risk associated with use of Ocrelizumab in pregnant women. There are no data on B-cell levels in human neonates following maternal exposure to Ocrelizumab. However, transient peripheral B-cell depletion and lymphocytopenia have been reported in infants born to mothers exposed to other anti-CD20 antibodies during pregnancy.
Lactation: There are no data on the presence of ocrelizumab in human milk, the effects on the breastfed infant, or the effects of the drug on milk production.
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Ocrevus and any potential adverse effects on the breastfed infant from Ocrevus or from the underlying maternal condition. 
See prescribing information for full details.    

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, chemical and physical in use stability has been demonstrated for 24 hours (in the refrigerator) at 2°C–8°C and 8 hours at room temperature (up to 25°C), which includes infusion time. In the event an intravenous infusion cannot be completed the same day, discard the remaining solution. From microbiological point of view, the prepared infusion should be used immediately. If not used immediately, in use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2°C–8°C and 8 hours at room temperature, unless dilution is undertaken in controlled and validated aseptic conditions. No incompatibilities between Ocrelizumab and polyvinyl chloride (PVC) or polyolefin (PO) bags and intravenous (IV) administration sets have been observed.