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Hyaluronidase / rituximab Side Effects

Medically reviewed by Philip Thornton, DipPharm. Last updated on Mar 17, 2023.

Applies to hyaluronidase / rituximab: subcutaneous solution.


Subcutaneous route (Solution)

Severe, including fatal, mucocutaneous reactions can occur in patients receiving rituximab-containing products, including rituximab and hyaluronidase human, recombinant. Hepatitis B Virus (HBV) reactivation can occur in patients treated with rituximab-containing products, including rituximab and hyaluronidase human, recombinant, in some cases resulting in fulminant hepatitis, hepatic failure, and death. Screen all patients for HBV infection before treatment initiation, and monitor patients during and after treatment with rituximab and hyaluronidase human, recombinant. Discontinue rituximab and hyaluronidase human, recombinant and concomitant medications in the event of HBV reactivation. Progressive Multifocal Leukoencephalopathy (PML), including fatal PML, can occur in patients receiving rituximab-containing products, including rituximab and hyaluronidase human, recombinant.

Serious side effects

Along with its needed effects, hyaluronidase / rituximab may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking hyaluronidase / rituximab:

More common

  • Back pain
  • black, tarry stools
  • bladder pain
  • bloating or swelling of the face, arms, hands, lower legs, or feet
  • bloody or cloudy urine
  • blurred vision
  • body aches or pain
  • bone pain
  • chest pain
  • chills
  • cough
  • cough producing mucus
  • difficult or labored breathing
  • difficult, burning, or painful urination
  • difficulty in moving
  • dizziness
  • ear congestion
  • fever or chills
  • frequent urge to urinate
  • headache
  • joint pain
  • loss of voice
  • lower back or side pain
  • muscle aches or cramps
  • muscle pain or stiffness
  • muscle spasm
  • nasal congestion
  • nervousness
  • pale skin
  • pounding in the ears
  • rapid weight gain
  • severe pain
  • slow or fast heartbeat
  • sneezing
  • sore throat
  • sores, ulcers, or white spots on the lips or in the mouth
  • stomach pain
  • stuffy or runny nose
  • swelling or inflammation of the mouth
  • swollen glands
  • swollen joints
  • tightness in the chest
  • tingling of the hands or feet
  • unusual bleeding or bruising
  • unusual tiredness or weakness
  • unusual weight gain or loss

Less common

  • Cracked lips
  • difficulty in swallowing
  • dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
  • general feeling of discomfort or illness
  • hoarseness
  • loss of appetite
  • nausea
  • shivering
  • sweating
  • trouble sleeping
  • upper stomach pain
  • vomiting

Incidence not known

  • Bloody, black, or tarry stools
  • blurred vision or other change in vision
  • dilated neck veins
  • extreme fatigue
  • eye pain
  • feeling of discomfort
  • high fever
  • inflammation of the joints
  • irregular breathing
  • irregular heartbeat
  • itching
  • rash
  • redness of the eye
  • sensitivity of the eye to light
  • severe stomach pain
  • severe vomiting, sometimes with blood
  • tearing
  • unexplained bleeding or bruising

Other side effects

Some side effects of hyaluronidase / rituximab may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

  • Belching
  • bleeding, blistering, burning, coldness, discoloration of the skin, feeling of pressure, hives, infection, inflammation, itching, lumps, numbness, pain, rash, redness, scarring, soreness, stinging, swelling, tenderness, tingling, ulceration, or warmth at the injection site
  • burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
  • constipation
  • hair loss
  • heartburn
  • indigestion
  • lack or loss of strength
  • pain in the mouth and throat
  • pain or tenderness around the eyes and cheekbones
  • stomach discomfort, upset, or pain
  • unsteadiness or awkwardness
  • weakness in the arms, hands, legs, or feet

Less common

  • Burning, dry, or itching of the eyes
  • discharge, excessive tearing
  • redness, pain, swelling of the eye, eyelid, or inner lining of the eyelid

For Healthcare Professionals

Applies to hyaluronidase / rituximab: subcutaneous solution.


Very common (10% or more): Neutropenia (32%), thrombocytopenia (20% or greater), anemia (15%)

Common (1% to 10%): Febrile neutropenia, leukopenia, lymphopenia

Postmarketing reports: Prolonged pancytopenia, marrow hypoplasia, Grade 3 to 4 prolonged or late onset neutropenia, hyperviscosity syndrome in Waldenstrom's macroglobulinemia, prolonged hypogammaglobulinemia


Frequency not reported: Hypersensitivity[Ref]


Very common (10% or more): Infections (20% or greater)

Common (1% to 10%): Influenza, immunogenicity

Postmarketing reports: Lupus-like syndrome, serum sickness, viral infections (including progressive multifocal leukoencephalopathy [PML], increase in fatal infections in HIV-associated lymphoma, and an increased incidence of Grade 3 and 4 infections)[Ref]


Very common (10% or more): Injection site erythema (13%)

Common (1% to 10%): Injection site pain, injection site edema[Ref]


Very common (10% or more): Arthralgia (13%), bone pain (10%), pain in extremity (10%)

Common (1% to 10%): Back pain, muscle spasms, myalgia

Postmarketing reports: Polyarticular arthritis[Ref]


Common (1% to 10%): Conjunctivitis

Postmarketing reports: Uveitis, optic neuritis[Ref]


Very common (10% or more): Arthralgia (13%)

Common (1% to 10%): Myalgia, anorexia, weight loss

Frequency not reported: Tumor lysis syndrome[Ref]


Common (1% to 10%): Insomnia[Ref]


Common (1% to 10%): Urinary tract infection[Ref]


Frequency not reported: Hepatitis B reactivation including fulminant hepatitis[Ref]


Postmarketing reports: Disease progression of Kaposi's sarcoma[Ref]


Very common (10% or more): Cough (23%), upper respiratory tract infection (15%), pneumonia (11%), dyspnea (11%), nasopharyngitis (10%)

Common (1% to 10%): Bronchitis, sinusitis, oropharyngeal pain, respiratory tract infection

Postmarketing reports: Pleuritis, fatal bronchiolitis obliterans, fatal interstitial lung disease[Ref]


Very common (10% or more): Fatigue (20%), asthenia (17%), pyrexia (15%)[Ref]

Nervous system

Very common (10% or more): Paresthesia (16%), headache (13%), peripheral neuropathy (12%)

Common (1% to 10%): Chills, dizziness

Frequency not reported: Progressive multifocal leukoencephalopathy[Ref]


Frequency not reported: Renal toxicity


Common (1% to 10%): Flushing, chest pain, peripheral edema, hypertension

Frequency not reported: Cardiac arrhythmias

Postmarketing reports: Fatal cardiac failure, systemic vasculitis[Ref]


Very common (10% or more): Alopecia (16%), pruritus (10%), rash (10%)

Common (1% to 10%): Erythema

Frequency not reported: Mucocutaneous reactions

Postmarketing reports: Vasculitis with rash[Ref]


Very common (10% or more): Nausea (31%), constipation (25%), diarrhea (18%), abdominal pain (14%), vomiting (14%)

Common (1% to 10%): Dyspepsia, stomatitis, upper abdominal pain, throat irritation, mucosal inflammation

Frequency not reported: Bowel obstruction and perforation[Ref]


1. Product Information. Rituxan Hycela (hyaluronidase-rituximab). Genentech. 2017.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Some side effects may not be reported. You may report them to the FDA.