Ocrelizumab-Hyaluronidase

Ocrelizumab/hyaluronidase is a combination medication indicated in adults for the treatment of: 

• Relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease
• Primary progressive MS

Ocrelizumab/hyaluronidase is available under the following different brand names: Ocrevus Zunovo.

Common side effects of Ocrelizumab/hyaluronidase include:

• upper respiratory tract infections
• infusion reactions (itching, rash, hives, redness, bronchospasm, swollen and sore throat, mouth pain, shortness of breath, flushing, hypotension, fever, fatigue, headache, dizziness, nausea, and fast heart rate)
• skin infections
• lower respiratory tract infections
• depression
• back pain
• pain in the extremities

Serious side effects of Ocrelizumab/hyaluronidase include:

• infusion reactions symptoms include itchy skin, trouble breathing, nausea, shortness of breath,
• rash, throat irritation or pain, headache, fatigue, hives, feeling faint, swelling of the throat, fast
• heartbeat, tiredness, fever, dizziness, coughing or wheezing, redness on the face (flushing),
• injection site pain swelling or redness
• Infection symptoms include cold sores, genital sores, pain, shingles, skin rash, itching
  • Hepatitis B virus (HBV) reactivation
  • Weakened immune system
•  Progressive multifocal leukoencephalopathy symptoms include problems with:
  • thinking, 
  • balance, 
  • eyesight, 
  • weakness on one side of the body, 
  • strength, 
  • using arms or legs
  • decreased immunoglobulins
  • risk of cancers (malignancies) including breast cancer
  • inflammation of the colon, or colitis symptoms such as diarrhea (loose stools) or more frequent
  • bowel movements than usual; stools that are black, tarry, sticky, or have blood or mucus, severe stomach area (abdomen) pain or tenderness
• Rare side effects of Ocrelizumab/hyaluronidase include:
  • none 
• Seek medical care or call 911 at once if you have the following serious side effects:
  • Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
  • Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
  • Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Solution for SC infusion

• 920 mg/23,000 units/23 mL (40 mg/1,000 units/mL single-dose vial)

Multiple Sclerosis

Adult dosage

• 920 mg/23,000 units (23 mL) SC every 6 months; infuse SC over approximately 10 minutes in the abdomen

Premedication

• Administer the following at least 30 minutes before each dose to reduce the risk of local and systemic injection reactions
• Dexamethasone 20 mg orally (or equivalent corticosteroid), plus
• An antihistamine (e.g., desloratadine)
• Addition of an antipyretic (e.g., acetaminophen) may also be considered

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Ocrelizumab/hyaluronidase has severe interactions with no other drugs
• Ocrelizumab/hyaluronidase has serious interactions with at least 38 other drugs
• Ocrelizumab/hyaluronidase has moderate interactions with at least 46 other drugs
• Ocrelizumab/hyaluronidase has minor interactions with no other drugs

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• Active HBV infection
• History of life-threatening infusion reaction to ocrelizumab
• History of hypersensitivity to ocrelizumab, hyaluronidase, or any component

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Ocrelizumab/hyaluronidase?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Ocrelizumab/hyaluronidase?”

Cautions

• Injection reactions
  • Can cause injection reactions, which can be local or systemic
  • Common symptoms of local injection reactions reported included erythema, pain, swelling, and pruritus
  • Common symptoms of systemic injection reactions reported included headache and nausea
  • Monitor during and after injections; inform patients that injection reactions can occur during or within 24 hours after injection
• Administer premedication (dexamethasone plus an antihistamine) before each dose; consider adding acetaminophen for premedication
• Management recommendations
  • Management depends on the type and severity of the reaction
• For life-threatening injection reactions, immediately and permanently stop infusion and administer appropriate supportive treatment
• For less severe injection reactions, immediately interrupt the injection
• Initiate symptomatic treatment
  • Complete injection at the healthcare provider’s discretion and only after all symptoms have resolved
• Infections
  • Serious, including life-threatening or fatal, bacterial, viral, parasitic, and fungal infections reported in patients receiving ocrelizumab
  • An increased risk of infections (including serious and fatal bacterial, fungal, and new or reactivated viral infections) has been observed in patients during and following completion of treatment with anti-CD20 B-cell depleting therapies
  • Delay dose in patients with active infection until resolved
• Herpes infections
  • Serious herpes virus infections may occur at any time during treatment
  • If serious herpes infections occur, discontinue or withhold treatment until the infection is resolved
  • Administer appropriate herpes treatment
• Progressive multifocal leukoencephalopathy
  • Postmarketing reports of progressive multifocal leukoencephalopathy (PML)
  • PML is an opportunistic viral infection of the brain caused by the JC virus (JCV) may lead to death or severe disability
    • Immunocompromised patients may be at increased risk of developing PML
    • JCV infection resulting in PML observed in patients treated with other anti-CD20 antibodies and other MS therapies
    • At the first sign or symptom suggestive of PML, withhold therapy and perform an appropriate diagnostic evaluation (e.g., MRI, JCV DNA in cerebrospinal fluid); discontinue if PML confirmed
    • Typical symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes
    • Monitoring with MRI for signs that may be consistent with PML may be useful, and any suspicious findings should lead to further investigation to allow for an early diagnosis of PML, if present
    • Following discontinuation of another MS medication associated with PML, lower PML-related mortality and morbidity were reported in patients who were initially asymptomatic at diagnosis compared to patients who had characteristic clinical signs and symptoms at diagnosis
    • Unknown whether these differences are due to early detection and discontinuation of MS treatment or differences in disease in these patients
• Reduction in immunoglobulins
  • With any B-cell depleting therapy, decreased immunoglobulin levels are observed
  • The pooled data of IV ocrelizumab clinical studies (RMS and PPMS) and their open-label extensions (up to approximately7 years of exposure) have shown an association between decreased levels of immunoglobulin G (IgG less than the lower limit of normal value [LLN]) 
  • Consider discontinuing for serious opportunistic or recurrent serious infections or prolonged hypogammaglobulinemia requiring treatment with IV immunoglobulins
• Malignancies
  • Risk of malignancy with therapy
  • In controlled trials, malignancies, including breast cancer, occurred more frequently in patients treated with IV ocrelizumab
  • Ensure patients follow standard breast cancer screening guidelines
• Immune-mediated colitis
  • Postmarketing reports of immune-mediated colitis can present as a severe and acute-onset form of colitis
  • Some cases required hospitalization or surgical intervention; systemic corticosteroids were required in many cases
  • Time to onset of symptoms ranged from a few weeks to years
  • Monitor during treatment; evaluate promptly if signs and symptoms of immune-mediated colitis (e.g., new or persistent diarrhea or other gastrointestinal (GI) signs and symptoms) occur
• Drug interaction overview
  • Immunosuppressive or immune-modulating therapies
    • Coadministration with immunosuppressants (including immunosuppressant corticosteroid doses) may increase risk for immunosuppressive effects
    • When switching from drugs with prolonged immune effects (e.g., daclizumab, fingolimod, natalizumab, teriflunomide, or mitoxantrone), consider the duration and mode of action of these drugs
  • Vaccinations
  • May interfere with the efficacy of vaccines
  • Concomitant exposure to IV ocrelizumab attenuated antibody responses to tetanus toxoid-containing vaccine, pneumococcal polysaccharide, pneumococcal conjugate vaccines, and seasonal inactivated influenza vaccines
  • Administer all immunizations according to immunization guidelines at least 4 weeks before initiation for live or live-attenuated vaccines and, whenever possible, at least 2 weeks before initiation for non-live vaccines
  • Vaccination of infants of mothers exposed to ocrelizumab during pregnancy
  • Do not administer live or live-attenuated vaccines before confirming recovery of B-cell counts (measured by CD19+ B-cells)
  • Depletion of B-cells in these infants may increase risks from live or live-attenuated vaccines
  • Nonlive vaccines may be administered as indicated, before recovery from B-cell depletion; consider assessing vaccine immune responses, including consultation with a qualified specialist, to assess whether a protective immune response was mounted

Pregnancy and Lactation

• Immunoglobulins are known to cross the placental barrier
• There are no adequate data regarding the developmental risk associated with use in pregnant women
• However, transient peripheral B-cell depletion and lymphocytopenia were reported in infants born to mothers exposed to other anti-CD20 antibodies during pregnancy
• B-cell levels in infants following maternal exposure to ocrelizumab-containing products have not been studied in clinical trials
• The potential duration of B-cell depletion in infants, and the impact of B-cell depletion on vaccine safety and effectiveness, is unknown
• Contraception
  • Females of reproductive potential should use effective contraception during treatment and for 6 months after the last dose
• Lactation
  • Data are unknown regarding the presence of ocrelizumab or hyaluronidase in human milk, their effects on breastfed infants, or milk production
  • Excreted in the milk of ocrelizumab-treated monkeys
  • Human IgG is excreted in human milk, and the potential for absorption of ocrelizumab to lead to B-cell depletion in infants is unknown