Applies to hyaluronidase / rituximab: subcutaneous solution.

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.

Hematologic

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

Hypersensitivity

Frequency not reported: Hypersensitivity^[Ref]

Immunologic

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]

Local

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

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

Musculoskeletal

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]

Ocular

Common (1% to 10%): Conjunctivitis

Postmarketing reports: Uveitis, optic neuritis^[Ref]

Metabolic

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

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

Frequency not reported: Tumor lysis syndrome^[Ref]

Psychiatric

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

Genitourinary

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

Hepatic

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

Oncologic

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

Respiratory

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]

Other

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]

Renal

Frequency not reported: Renal toxicity

Cardiovascular

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

Frequency not reported: Cardiac arrhythmias

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

Dermatologic

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]

Gastrointestinal

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]