Orthoclone OKT 3

Name: Orthoclone OKT 3

Orthoclone OKT 3 side effects
Orthoclone OKT 3 dosage
Orthoclone OKT 3 average dose
Orthoclone OKT 3 injection
Orthoclone OKT 3 orthoclone okt 3 side effects
Orthoclone OKT 3 8 mg
Orthoclone OKT 3 drug
Orthoclone OKT 3 effects of

Before Using Orthoclone OKT 3

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

There is no specific information comparing use of muromonab-CD3 in children with use in other age groups. However, children are more likely to get dehydrated from the diarrhea and vomiting that may be caused by this medicine.

Geriatric

Many medicines have not been studied specifically in older people. Therefore, it may not be known whether they work exactly the same way they do in younger adults or if they cause different side effects or problems in older people. There is no specific information comparing use of muromonab-CD3 in the elderly with use in other age groups.

Pregnancy

	Pregnancy Category	Explanation
All Trimesters	C	Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.

Breast Feeding

Studies in women breastfeeding have demonstrated harmful infant effects. An alternative to this medication should be prescribed or you should stop breastfeeding while using this medicine.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Proper Use of Orthoclone OKT 3

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

For injection dosage form:
- To prevent organ transplant rejection:
  - Adults—5 milligrams (mg) injected into a vein once a day.
  - Children less than 12 years of age—Dose is based on body weight and must be determined by your doctor.

Precautions While Using Orthoclone OKT 3

It is very important that your doctor check your progress at regular visits to make sure that this medicine is working properly and to check for unwanted effects.

While you are being treated with muromonab-CD3 and after you stop treatment with it, do not have any immunizations (vaccinations) without your doctor's approval. Muromonab-CD3 may lower your body's resistance. For some immunizations, there is a chance you might get the infection the immunization is meant to prevent. For other immunizations, it may be especially important to receive the immunization to prevent a disease. In addition, other persons living in your house should not take oral polio vaccine since there is a chance they could pass the polio virus on to you. Also, avoid persons who have recently taken oral polio vaccine. Do not get close to them and do not stay in the same room with them for very long. If you cannot take these precautions, you should consider wearing a protective face mask that covers the nose and mouth.

Treatment with muromonab-CD3 may also increase the chance of getting other infections. If you can, avoid people with colds or other infections. If you think you are getting a cold or other infection, check with your doctor.

This medicine commonly causes chest pain, dizziness, fever and chills, shortness of breath, stomach upset, and trembling within a few hours after the first dose. These effects should be less after the second dose. However, check with your doctor or nurse immediately if you have chest pain, rapid or irregular heartbeat, shortness of breath or wheezing, or swelling of the face or throat after any dose.

Orthoclone OKT 3 Side Effects

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

Because of the way that muromonab-CD3 acts on the body, there is a chance that it may cause effects that may not occur until years after the medicine is used. These delayed effects may include certain types of cancer, such as lymphomas and skin cancers. Discuss these possible effects with your doctor.

Although not all of the following 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:

Less common

Chest pain
rapid or irregular heartbeat
shortness of breath or wheezing
swelling of face or throat

Check with your doctor as soon as possible if any of the following side effects occur:

More common

Diarrhea
dizziness or faintness
fever and chills
general feeling of discomfort or illness
headache
muscle or joint pain
nausea and vomiting

Less common or rare

Confusion
black, tarry stools
blood in urine or stools
convulsions (seizures)
cough or hoarseness
hallucinations (seeing, hearing, or feeling things that are not there)
itching or tingling
loss of hearing or vision
lower back or side pain
painful or difficult urination
pinpoint red spots on skin
skin rash
sores, ulcers, or white spots on the lips or in the mouth
stiff neck
swollen or painful glands
tightness in the chest
trembling and shaking of hands
troubled breathing
unusual sensitivity of eyes to light
unusual bleeding or bruising
unusual tiredness
weakness

After you stop using this medicine, it may still produce some side effects that need attention. During this period of time, check with your doctor immediately if you notice the following side effects:

Fever and chills

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

For the Consumer

Applies to muromonab-cd3: intravenous solution

Along with its needed effects, muromonab-cd3 (the active ingredient contained in Orthoclone OKT3) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Although not all of the following 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 muromonab-cd3:

Less common

Chest pain
rapid or irregular heartbeat
shortness of breath or wheezing
swelling of face or throat

Check with your doctor as soon as possible if any of the following side effects occur while taking muromonab-cd3:

More common

Diarrhea
dizziness or faintness
fever and chills
general feeling of discomfort or illness
headache
muscle or joint pain
nausea and vomiting

Less common or rare

Confusion
black, tarry stools
blood in urine or stools
convulsions (seizures)
cough or hoarseness
hallucinations (seeing, hearing, or feeling things that are not there)
itching or tingling
loss of hearing or vision
lower back or side pain
painful or difficult urination
pinpoint red spots on skin
skin rash
sores, ulcers, or white spots on the lips or in the mouth
stiff neck
swollen or painful glands
tightness in the chest
trembling and shaking of hands
troubled breathing
unusual sensitivity of eyes to light
unusual bleeding or bruising
unusual tiredness
weakness

Fever and chills

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.[Ref]

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.[Ref]

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.[Ref]

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.[Ref]

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.[Ref]

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.[Ref]

Nervous system

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.[Ref]

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

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.[Ref]

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.[Ref]

Oncologic

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.[Ref]

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.[Ref]

Hypersensitivity

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.[Ref]

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.[Ref]

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.[Ref]

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.[Ref]

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.[Ref]

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.[Ref]

Immunologic

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

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.[Ref]

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.