Orthoclone OKT3 Side Effects

Generic name: muromonab-cd3

Note: This document contains side effect information about muromonab-cd3. Some of the dosage forms listed on this page may not apply to the brand name Orthoclone OKT3.

Some side effects of Orthoclone OKT3 may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

For the Consumer

Applies to muromonab-cd3: intravenous solution

Some people receiving a muromonab-CD3 injection have had a reaction to the infusion (within 30 to 60 minutes after the medicine is injected into the vein). Tell your caregiver right away if you feel chilled or feverish, nauseated, weak, shaky, or light-headed, or if you have a headache, or joint and muscle aches. These side effects may also occur up to several hours after your injection.

Tell your caregivers right away if you have any of these serious side effects:

• wheezing, gasping, shortness of breath;

• fast or uneven heart rate, chest pain or heavy feeling, pain spreading to the arm or shoulder, sweating, general ill feeling;

• confusion, hallucinations, unusual thoughts or behavior;

• fever, headache, neck stiffness, chills, increased sensitivity to light;

• loss of vision or muscle control;

• seizure (black-out or convulsions);

• pain or burning when you urinate;

• easy bruising or bleeding, unusual weakness; or

• high fever, chills, stomach pain, vomiting, diarrhea, tremors, body aches, flu symptoms.

Less serious side effects of muromonab-cd3 (the active ingredient contained in Orthoclone OKT3) may include:

• mild headache;

• nausea, constipation, upset stomach;

• sleep problems (insomnia); or

• swelling in your hands, ankles, or feet.

This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect.

For Healthcare Professionals

Applies to muromonab-cd3: intravenous solution

General

General side effects of muromonab CD3 include an acute clinical syndrome known as the Cytokine Release Syndrome or CRS. CRS, attributed to the release of cytokines by activated T cells, is most commonly characterized by a "flu-like" illness, including fever (spiking as high as 107 degrees Fahrenheit), chills, rigors, headache, nausea, vomiting, diarrhea, malaise, arthralgias, myalgias, and weakness. More serious, and sometimes fatal, manifestations, include pulmonary edema, hemodynamic instability, shock, respiratory arrest, and cardiac arrest.

The CRS is associated with the first few doses of muromonab CD3. Onset of symptoms is typically within 30 to 60 minutes after the first dose. Symptoms are thought to be due to the release of cytokines, including tumor necrosis factor, gamma interferon, interleukin-2, interleukin-3, interleukin-4, interleukin-6, and granulocyte colony stimulating factor, from T cells following binding of muromonab CD3.

Pretreatment with 8 mg/kg methylprednisolone sodium succinate intravenously one to four hours before and 100 mg hydrocortisone sodium succinate 30 minutes after administration of the first dose of muromonab CD3 may reduce the severity of symptoms associated with the CRS. While data are conflicting, other agents which may be of benefit include indomethacin, heparin, pentoxifylline, and experimental anti-TNF monoclonal antibodies.

Patients at increased risk for serious complications associated with the CRS include those with unstable angina, recent myocardial infarction, symptomatic ischemic heart disease, heart failure, pulmonary edema, intravascular volume overload or depletion, cerebrovascular disease, septic shock, or a history of seizures.

Cardiovascular

Cardiovascular side effects may be more common in patients receiving muromonab CD3 for prophylaxis of allograft rejection than in patients receiving muromonab CD3 for reversal of rejection. Tumor necrosis factor is thought to be involved in the pathogenesis of the cardiovascular side effects.

In one study involving 18 patients treated with muromonab CD3 5 mg per day for ten days for renal allograft rejection, mean systolic and diastolic blood pressures increased 20.9 and 10.8 mmHg, respectively, on day one, in nine patients. On day 2, mean systolic and diastolic pressures increased 41.7 and 19.1 mmHg, respectively, in 10 patients. Heart rate increased 23.7 beats per minute on day one but no change was noted on day two. No significant changes in blood pressure or heart rate were noted on day three. The increase in blood pressure lasted approximately two hours on day one and 11 to 13 hours on day two.

Thrombosis of allografts and other vascular beds has been reported during therapy with muromonab CD3. In one study of 93 renal allograft recipients receiving muromonab CD3 prophylactically, nine patients had intragraft thromboses within two weeks of transplantation. Elevated prothrombin fragments 1 and 2 were noted as compared to a control group. Tumor necrosis factor as well as endothelial cell activation are suspected of playing a role in the thrombotic events.

Cardiovascular side effects have included hypertension (24% to 64%), hypotension (12% to 18%), chest pain or angina (14%), tachycardia (3% to 45%), bradycardia, and hemodynamic instability. Cardiac arrest, severe hypotension or shock, heart failure, cardiovascular collapse, left ventricular dysfunction, and arrhythmias have also been reported. In addition, thrombotic events within main graft vessels have been reported.

Respiratory

Pulmonary edema, sometimes fatal, has been reported in up to 13% of patients in early studies. However, affected patients were determined to be fluid overloaded in the pretreatment period. Restrictions against use in patients who are volume overloaded as evidenced by a 3% or greater increase in body weight during the week prior to muromonab CD3 treatment has drastically reduced the occurrence of pulmonary edema; although, cases of pulmonary edema in euvolemic patients have been reported. Increased pulmonary vascular permeability and/or reduced left ventricular compliance or contractility are additional risk factors.

The mechanism may involve tumor necrosis factor-alpha as well as complement activation and pulmonary sequestration of activated granulocytes.

The use of muromonab CD3 is considered contraindicated in patients with volume overload and/or uncompensated heart failure.

Respiratory side effects have included dyspnea, shortness of breath, bronchospasm, apnea, and tachypnea. More serious effects, including pulmonary edema (cardiogenic and noncardiogenic), respiratory distress syndrome, and respiratory failure have also been attributed to muromonab CD3 therapy and may be fatal.

Nervous system

Nervous system side effects have included headache and mental status changes as well as more serious sequelae including seizures, cerebritis, aseptic meningitis, and encephalopathy.

Aseptic meningitis usually presents within 72 hours following the first dose of muromonab CD3, accompanied by symptoms of fever, headache, nuchal rigidity, and photophobia. Cerebral spinal fluid findings include pleocytosis, elevated protein, and negative cultures. Symptoms typically resolve in two or three days regardless of whether or not muromonab CD3 therapy is continued.

Encephalopathy, also known as cytokine encephalopathy, may occur in up to 7% of patients and is typically characterized by confusion, hallucinations, seizures, obtundation, coma, and occasionally, blindness. Cytokine encephalopathy usually regresses without significant intervention. However, severe cases necessitate discontinuation of the drug. Permanent neurologic deficits have been reported. One study identified delayed graft function as a significant risk factor for the development of cytokine encephalopathy in patients treated prophylactically with muromonab CD3.

Hematologic

Hematologic side effects have included pancytopenia, aplastic anemia, neutropenia, leukopenia, thrombocytopenia, lymphopenia, leukocytosis, and disturbances in coagulation. Graft vessel thromboses have also been reported.

Elevations in prothrombin fragments 1 and 2 and von Willebrand's factor have been found following the first dose of muromonab CD3. Tumor necrosis factor-alpha appears to be the mediator of muromonab CD3-induced coagulopathy.

Oncologic

The majority of lymphomas have been diagnosed within the first four months following transplantation, and are often rapidly progressive and disseminated at the time of diagnosis.

Reduction in doses of other immunosuppressants during muromonab CD3 therapy for reversal of rejection is recommended to reduce the risk of neoplastic disease.

Oncologic side effects, or the development of new malignancies, are of particular concern in post-transplant patients. Lymphoproliferative disorders are of the most concern. Lymphadenopathy and benign polyclonal B cell hyperplasia as well as malignant, often fatal, B cell lymphomas have been reported.

Hypersensitivity

Hypersensitivity side effects from muromonab CD3 have included rash, pruritus, angioedema, and anaphylaxis. In addition, serum sickness; immune complex deposition causing glomerulonephritis, vasculitis, and temporal arteritis; and eosinophilia have been reported.

Muromonab CD3 is considered contraindicated in patients with a history of hypersensitivity to murine-derived products or with an anti-mouse antibody titer greater than 1:1000. Retreatment with muromonab CD3 may be associated with an increased incidence of hypersensitivity reactions and should be done with caution.

Renal

Reversible renal dysfunction, known as cytokine nephropathy, is characterized by transient increases in serum creatinine and blood urea nitrogen. In one study, serum creatinine increased by an average of 2.9 mg/dl and fell to prerejection levels by the end of muromonab CD3 therapy.

Renal side effects have included a slight decline in renal function, as evidenced by a transient increase in serum creatinine and blood urea nitrogen. In addition, anuria, oliguria, delayed renal graft function, interstitial nephritis, and abnormal urinalysis have been reported.

Gastrointestinal

Gastrointestinal side effects, such as nausea/vomiting (18% to 51%) and diarrhea (21%), may be severe requiring fluid management. In addition, cases of bowel infarction and pancreatitis have been reported.

Other

Other side effects associated with muromonab CD3 have included blindness, anterior scleritis, blurred vision, double vision, conjunctivitis, hearing loss, vertigo, tinnitus, and VI cranial nerve palsy.

Immunologic

Cytomegalovirus, Herpes simplex, and fungal infections are the most commonly encountered infections during muromonab CD3 immunosuppressive therapy. Other infections, including bacterial, viral, and protozoal, have been reported as well.

Several studies have identified an increased risk of invasive cytomegalovirus infection in recipients of CMV-positive grafts which is associated with a significant increase in morbidity and mortality.

Immunologic side effects including infections have been associated with muromonab CD3 therapy and are a result of immunosuppression.

Disclaimer: Every effort has been made to ensure that the information provided is accurate, up-to-date, and complete, but no guarantee is made to that effect. In addition, the drug information contained herein may be time sensitive and should not be utilized as a reference resource beyond the date hereof. This information does not endorse drugs, diagnose patients, or recommend therapy. This drug information is a reference resource designed as supplement to, and not a substitute for, the expertise, skill , knowledge, and judgement of healthcare practitioners in patient care. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug of drug combination is safe, effective, or appropriate for any given patient. Drugs.com does not assume any responsibility for any aspect of healthcare administered with the aid of information provided. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse, or pharmacist.