Rituximab is a genetically engineered chimeric murine/human monoclonal antibody directed against the CD20 antigen found on the surface of normal and malignant B lymphocytes. The antibody is an IgG1 kappa immunoglobulin containing murine light- and heavy-chain variable region sequences and human constant region sequences. Rituximab is composed of two heavy chains of 451 amino acids and two light chains of 213 amino acids. It is used for non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, idiopathic thrombocytopenic purpura, pemphigus vulgaris and myasthenia gravis. It is given by slow injection into a vein.
Mechanisms of Action of Rituximab
Rituximab tends to stick to one side of B cells, where CD20 is, forming a cap and drawing proteins over to that side. The presence of the cap changed the effectiveness of natural killer (NK) cells in destroying these B cells. When an NK cell latched onto the cap, it had an 80% success rate at killing the cell. In contrast, when the B cell lacked this asymmetric protein cluster, it was killed only 40% of the time.
The following effects have been found:
- The Fc portion of rituximab mediates antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC).
- Rituximab has a general regulatory effect on the cell cycle.
- It increases MHC II and adhesion molecules LFA-1 and LFA-3 (lymphocyte function-associated antigen).
- It elicits shedding of CD23.
- It downregulates the B cell receptor.
- It induces apoptosis of CD20+ cells.
The combined effect results in the elimination of B cells (including the cancerous ones) from the body, allowing a new population of healthy B cells to develop from lymphoid stem cells.
Rituximab binds to amino acids 170-173 and 182-185 on CD20, which are physically close to each other as a result of a disulfide bond between amino acids 167 and 183.
Indications of Rituximab
- Chronic lymphocytic leukemia
- Evan’s syndrome
- Non-Hodgkin’s lymphoma
- Bullous pemphigoid
- Diffuse Large B-Cell Lymphoma
- Focal segmental glomerulosclerosis
- Follicular lymphoma
- Idiopathic thrombocytopenic purpura
- Mantle cell lymphoma
- Microscopic polyangiitis
- Pemphigoid
- Pemphigus
- Rheumatoid arthritis
- Wegener’s granulomatosis
- Granulomatosis with polyangiitis
- Microscopic polyangiitis
Contra-Indications of Rituximab
- Herpes simplex infection
- Disease caused by cytomegalovirus infection
- Infection caused by a fungus
- Pneumonia caused by Pneumocystis Jirovecii Organism
- Severe infection
- The high amount of phosphate in the blood
- Low amount of calcium in the blood
- The high amount of potassium in the blood
- Anemia
- Decreased Blood Platelets
- Decreased Neutrophils a Type of White Blood Cell
- Angina
- Abnormal heart rhythm
- Stomach or Intestine Blockage
- Acute Renal Failure
- Kidney disease with a reduction in kidney function
- A mother who is producing milk and breastfeeding
- Infection caused by the Varicella Zoster Virus
- A Rupture in the Wall of the Stomach or Intestine
- Resolved hepatitis B
- Relapse of Hepatitis B Infection Symptoms
- Hypogammaglobulinemia
- Hepatitis C
- Progressive Disease in the White Matter of the Brain
- Disease due to West Nile Virus
Side Effects of Rituximab
The most common
- nausea, vomiting, stomach pain, indigestion, constipation, diarrhea;
- fever, flu symptoms, cough, sore throat, sneezing, runny nose;
- nervousness, depression, sleep problems (insomnia);
- a headache, dizziness, drowsiness, memory problems, unusual thoughts;
- rash, hair loss, bruising;
- weakness, tremors, problems with balance or walking;
- swelling in your hands or feet;
- vision problems, ringing in your ears; or
- changes in appetite, weight gain.
More common
- Abdominal or stomach pain
- black, tarry stools
- bleeding gums
- bloating or swelling of the face, arms, hands, lower legs, or feet
- blood in the urine or stools
- blurred vision
- body aches or pain
- chest pain
- confusion
- convulsions
- cough or hoarseness
- difficulty with breathing
- dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
Less Common
- burning, tingling, numbness or pain in the hands, arms, feet, or legs
- decreased frequency and amount of urination
- diarrhea
- difficulty with moving
- discouragement
- feeling sad or empty
- irregular heartbeat
- irritability
- joint or muscle pain
- loss of appetite
- loss of interest or pleasure
- muscle cramps
- muscle pain or stiffness
- numbness or tingling in the hands, feet, or lips
Drug Interactions of Rituximab
- abatacept
- alpha blockers (e.g., alfuzosin, doxazosin, tamsulosin)
- alpha agonists (e.g., clonidine, methyldopa)
- angiotensin-converting enzyme inhibitors (ACEIs; captopril, ramipril)
- angiotensin receptor blockers (ARBs; e.g., candesartan, irbesartan, losartan)
- belimumab
- beta-adrenergic blockers (e.g., atenolol, propranolol, sotalol)
- calcium channel blockers (e.g., amlodipine, diltiazem, nifedipine, verapamil)
- certolizumab pegol
- clozapine
- diuretics (water pills; e.g., furosemide, hydrochlorothiazide, triamterene)
- natalizumab
- pimecrolimus
- roflumilast
- tofacititinb
- trastuzumab
- vaccines
Pregnancy & Lactation
FDA Pregnancy Category C
Pregnancy
This medication is not recommended for use during pregnancy. If you may become pregnant, use an effective method of birth control while you are using this medication, and for at least 12 months after the last treatment. Tell your doctor immediately if you become pregnant.
Lactation
It is not known if rituximab passes into breast milk. If you are breast feeding mother and are taking this medication, it may affect your baby. Talk to your doctor about whether you should continue breast-feeding
References
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