Acellbia

Clear or slightly opalescent, colorless to light yellow liquid.
Acellbia 100 mg (10 mg/mL) Concentrate for Solution for Infusion (IV): Each vial contains: Rituximab 100 mg.
Acellbia 500 mg (10 mg/mL) Concentrate for Solution for Infusion (IV): Each vial contains: Rituximab 500 mg.
Excipients/Inactive Ingredients: The other ingredients are sodium citrate, polysorbate 80, sodium chloride, hydrochloric acid and water for injections.

Monoclonal Antibodies.
Pharmacology: Pharmacodynamics: Mechanism of Action: Rituximab is a chimeric mouse/human monoclonal antibody that binds specifically to the transmembrane antigen CD20. This antigen is located on pre-B- and mature B-lymphocytes, but not on hemopoietic stem cells, pro-B-cells, normal plasma cells, or other normal tissue. Rituximab binds to the CD20 antigen on B-lymphocytes and initiates immunologic reactions that mediate B-cell lysis.
Pharmacokinetics: Elimination: Mean terminal elimination half-life - approximately 20 days.
Pharmacokinetics in Special Populations: No pharmacokinetics data are available in patients with hepatic or renal impairment.

Non-Hodgkin's Lymphoma: Rituximab is indicated for the treatment of: patients with relapsed or chemoresistant low-grade of follicular, CD20-positive, B-cell non-Hodgkin's lymphoma; previously untreated patients with stage III-IV follicular lymphoma in combination with chemotherapy; patients with follicular lymphoma a maintenance treatment, after response to induction therapy; patients with CD20-positive diffuse large B-cell non-Hodgkin's lymphoma in combination with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy.
Chronic Lymphocytic Leukemia: Rituximab in combination with chemotherapy is indicated for the treatment of patients with previously untreated and relapsed/refractory chronic lymphocytic leukemia (CLL).
Rheumatoid Arthritis: Rituximab in combination with Methotrexate is indicated in adult patients for: the treatment of moderate to severe, active rheumatoid arthritis when the response to disease-modifying anti-rheumatic drugs including methotrexate has been inadequate; treatment of moderate to severe, active rheumatoid arthritis in patients with an inadequate response or intolerance to one or more tumor necrosis factor (TNF) inhibitor therapies.
Granulomatosis with Polyangiitis (Wegener's) (GPA) and Microscopic Polyangiitis (MPA): Rituximab in combination with glucocorticoids is indicated for the treatment of patients with severe active granulomatosis with polyangiitis (GPA, also known as Wegener's granulomatosis) and microscopic polyangiitis (MPA).

The dose of Rituximab needed depends on the body weight and the type of cancer to be treated. The recommended dose is 5 mg, 7.5 mg, 10 mg, or 15 mg per kilogram of a patient's body weight. Treatment with Rituximab will be once every 2 or 3 weeks.
Non-Hodgkin's Lymphoma: If Rituximab is used alone, it will be given once a week for 4 weeks. Repeated treatment courses with Rituximab are possible. If Rituximab with chemotherapy, it will be given on the same day as the chemotherapy. This is usually given 3 weeks up to 8 times.
If responds well to the treatment, Rituximab as maintenance treatment may be given every 2 or 3 months for two years.
Chronic Lymphocytic Leukemia: If treated with Rituximab in combination with chemotherapy, Rituximab infusions on Day 0 cycle 1 then Day 1 of each cycle for 6 cycles in total. Each cycle has a duration of 28 days. The chemotherapy should be given after the Rituximab infusion. Physician has to decide whether patients should receive concomitant supportive therapy.
Granulomatosis with Polyangiitis (Wegener's) (GPA) and Microscopic Polyangiitis (MPA): Treatment with Rituximab uses four separate infusions given at weekly intervals.
Corticosteroids will usually be given by injection before the start of Rituximab treatment. Corticosteroids given by mouth may be started at any time by the physician to treat.

Limited experience with doses higher than the approved intravenous doses of Rituximab are available from clinical trials in humans. The highest IV dose tested in humans to date is 5000 mg (2250 mg/m²), tested in a dose escalation study in patients with chronic lymphocytic leukemia. No additional safety signals were identified. Patients who experience overdose should have immediate interruption of their infusion and be closely monitored.
Three patients in the Rituximab study were inadvertently administered the SC formulation through the IV route up to a maximum rituximab dose of 2780 mg, with no untoward effect. Patients who experience an overdose or medication error with Rituximab should be closely monitored.
Consideration should be given to the need for regular monitoring of blood cell count and for increased risk of infections while patients are B-cell depleted.

Rituximab is contraindicated in patients who are allergic to Rituximab, other proteins which are like Rituximab, or any of the other ingredients of this medicine, in patients who have a severe infection at the moment, in patients who have weak immune systems, and in patients who have severe heart failure or severe uncontrolled heart disease.

Infusion/administration-related reactions: Rituximab is associated with infusion/administration-related reactions, which may be related to release of cytokines and/or other chemical mediators. Cytokine release syndrome may be clinically indistinguishable from acute hypersensitivity reactions.
Hypersensitivity reactions/Anaphylaxis: Anaphylactic and other hypersensitivity reactions have been reported following the intravenous administration of proteins to patients. Epinephrine, antihistamines, and glucocorticoids should be available for immediate use in the event of a hypersensitivity reaction to Rituximab.
Cardiovascular: Since hypotension may occur during Rituximab administration consideration should be given to withholding antihypertensive medications 12 hours prior to and throughout Rituximab administration.
Monitoring of blood counts: Although Rituximab is not myelosuppressive in monotherapy, caution should be exercised when considering treatment of patients with neutrophil counts of <1.5 x 10⁹/L and/or platelet counts <75 x 10⁹/L, as clinical experience with such patients is limited. Rituximab IV has been used in patients who underwent autologous bone marrow transplantation and in other risk groups with a presumable reduced bone marrow function without inducing myelotoxicity.
Infections: Rituximab treatment should not be initiated in patients with severe active infections.
Hepatitis B infections: Cases of hepatitis B reactivation, including reports of fulminant hepatitis, some of which were fatal, have been reported in subjects receiving Rituximab, although the majority of these subjects were also exposed to cytotoxic chemotherapy.
Progressive multifocal leukoencephalopathy: Cases of progressive multifocal leukoencephalopathy (PML) have been reported during use of Rituximab in NHL and CLL.
Skin reactions: Severe skin reactions such as toxic epidermal necrolysis and Stevens-Johnson syndrome, some with fatal outcomes, have been reported.
Immunization: The safety of immunization with live viral vaccines following Rituximab therapy has not been studied and vaccination with live virus vaccines is not recommended.
Driving and Using other machines: It is not known whether Rituximab has an effect on the ability to drive or use any tools or machines.
This medicine contains 2.3 mmol (or 52.6 mg) sodium per 10 mL vial. Take this into account if the patient is on low-sodium diet.

Pregnancy: Rituximab can cross the placenta and may affect the baby; therefore, physician should be informed if pregnant, might be pregnant or planning to become pregnant.
Breastfeeding: Patient should not breastfeed while being treated with Rituximab. Also, patient must not breastfeed for 12 months after the last treatment with Rituximab. This may pass into the breast milk.

Most side effects are mild to moderate but some may be serious and require treatment.
Rarely, some of these reactions have been fatal.
Infusion reactions: During or within the first 2 hours of the first infusion, patient may develop fever, chills, and shivering. Less frequently, some patients may experience pain at the infusion site, blisters, itching, sickness, tiredness, headache, breathing difficulties, tongue or throat swelling, itchy or runny nose, vomiting, flushing or palpitations, heart attack, or low number of platelets. If the patient has heart disease or angina, these reactions might get worse. Inform the person giving the infusion immediately if the patient develops any of these symptoms, as the infusion may need to be slowed down or stopped. Patient may require additional treatment such as an antihistamine or paracetamol. When these symptoms go away or improve, the infusion can be continued. These reactions are less likely to happen after the second infusion. The doctor may decide to stop Rituximab treatment if these reactions are serious.
Infections: Inform the doctor immediately if the patient gets signs of an infection including: Fever, cough, sore throat, burning pain when passing urine or feeling weak or generally unwell; memory loss, trouble thinking, difficulty walking, or sight loss may be due to a very rare, serious brain infection, which has been fatal (Progressive Multifocal Leukoencephalopathy or PML). The patient might get infections more easily during treatment with Rituximab.
Skin Reactions: Very rarely, severe blistering skin conditions that can be life-threatening may occur. Redness, often associated with blisters, may appear on the skin or on mucous membranes, such as inside the mouth, the genital areas, or the eyelids, and fever may be present.
Other side effects include: If the patient is being treated for non-Hodgkin's Lymphoma or chronic lymphocytic leukemia: Very common side effects (may affect more than 1 in 10 people): Bacterial or viral infections, bronchitis; low number of white blood cells, with or without fever or low blood platelet count; feeling sick (nausea); bald spots on the scalp, chills, headache; lower immunity: because of lower levels of antibodies called "immunoglobulins" (IgG) in the blood which help protect against infection.
Common side effects (may affect up to 1 in 10 people): Infections of the blood (sepsis), pneumonia, shingles, cold, bronchial tube infections, fungal infections, infections of unknown origin, sinus inflammation, hepatitis B; low number of red blood cells (anemia), low number of white blood cells, allergic reactions (hypersensitivity); high blood sugar level, weight loss, swelling in the face and body, high levels of the enzyme "LDH" in the blood, low calcium levels in the blood; unusual feelings of the skin: such as numbness, tingling, pricking, burning, a creeping skin feeling, reduced sense of touch; feeling restless, problems falling asleep; becoming very red in the face and other areas of the skin as a consequence of dilation of the blood vessels; feeling dizzy or anxious; producing more tears, tear duct problems, inflamed eye (conjunctivitis); ringing sound in the ears, ear pain; heart problems: such as heart attack, uneven or fast heart rate; high or low blood pressure (low blood pressure especially when standing upright); tightening of the muscles in the airways which causes wheezing (bronchospasm), inflammation, irritation in the lungs, throat, or sinuses, shortness of breath, runny nose; being sick (vomiting), diarrhea, pain in the stomach, irritation or ulcers in the throat and mouth, problems swallowing, constipation, indigestion; eating disorders, not eating enough, leading to weight loss; hives, increased sweating, night sweats; muscle problems: such as tight muscles, joint or muscle pain, back and neck pain; general discomfort or feeling uneasy or tired, shaking, signs of flu; multiple-organ failure.
Uncommon side effects (may affect up to 1 in 100 people): Blood clotting problems, decrease of red blood cell production and increase of red blood cell destruction (aplastic hemolytic anemia), swollen or enlarged lymph nodes; low mood and loss of interest or enjoyment in doing things, feeling nervous; taste problems: such as changes in the way things taste; swelling of the stomach.
Very rare side effects (may affect up to 1 in 10, 000 people): Short-term increase in the amount of some types of antibodies in the blood (called immunoglobulins - IgM), chemical disturbances in the blood caused by break-down of dying cancer cells; nerve damage in arms and legs, paralyzed face; heart failure; inflammation of blood vessels including those leading to skin symptoms; respiratory failure; damage to the intestinal wall (perforation); severe skin problems causing blisters that can be life-threatening. Redness, often associated with blisters, may appear on the skin or on mucous membranes, such as inside the mouth, the genital areas, or the eyelids, and fever may be present.
Not known (it is not known how often these side effects happen): A reduction in white blood cells which does not happen straight away; reduced platelets number just after the infusion - this can be reversed, but can be fatal in rare cases; hearing loss, loss of other senses.
If the patient is being treated for rheumatoid arthritis: Very common side effects (may affect more than 1 in 10 people): Infections such as pneumonia (bacterial); pain on passing water (urinary tract infection); allergic reactions that are most likely to occur during an infusion, but can occur up-to 24-hours after infusion; changes in blood pressure, nausea, rash, fever, feeling itchy, runny or blocked nose and sneezing, shaking, rapid heartbeat, and tiredness; headache; changes in laboratory tests carried out by the doctor. These include a decrease in the amount of some specific proteins in the blood (immunoglobulins) which help protect against infection.
Common side effects (may affect up to 1 in 10 people): Infections such as bronchial tube inflammation (bronchitis); a feeling of fullness or a throbbing pain behind the nose, cheeks and eyes (sinusitis), pain in the abdomen, vomiting and diarrhoea, breathing problems; fungal foot infection (athlete's foot); high cholesterol levels in the blood; abnormal sensations of the skin, such as numbness, tingling, pricking or burning, sciatica, migraine, dizziness; loss of hair; anxiety, depression; indigestion, diarrhoea, acid reflux, irritation and/or ulceration of the throat and the mouth; pain in the tummy, back, muscles and/or joints.
Uncommon side effects (may affect up to 1 in 100 people): Excess fluid retention in the face and body; inflammation, irritation and/or tightness of the lungs, and throat, coughing; skin reactions including hives, itching and rash; allergic reactions including wheezing or shortness of breath, swelling of the face and tongue, collapse.
Very rare side effects (may affect up to 1 in 10, 000 people): A complex of symptoms occurring within a few weeks of an infusion of Rituximab including allergic like reactions such as rash, itching, joint pain, swollen lymph glands and fever; severe blistering skin conditions that can be life-threatening. Redness, often associated with blisters, may appear on the skin or on mucous membranes, such as inside the mouth, the genital areas or the eyelids, and fever may be present.
Other rarely reported side-effects due to Rituximab include a decreased number of white cells in the blood (neutrophils) that help to fight against infection. Some infections may be severe.
If the patient is being treated for granulomatosis with polyangiitis or microscopic polyangiitis: Very common side effects (may affect more than 1 in 10 people): Infections, such as chest infections, urinary tract infections (pain on passing water), colds and herpes infections allergic reactions that are most likely to occur during an infusion, but can occur up-to 24-hours after infusion; diarrhea; coughing or shortness of breath; nose bleeds; raised blood pressure; painful joints or back; muscle twitches or shakiness; feeling dizzy; tremors (shakiness, often in the hands); difficulty sleeping (insomnia); swelling of the hands or ankles.
Common side effects (may affect up to 1 in 10 people): Indigestion; constipation; skin rashes, including acne or spots; flushing or redness of the skin; blocked nose; tight or painful muscles; pain in the muscles or in the hands or feet; low number of red blood cells (anemia); low numbers of platelets in the blood; an increase in the amount of potassium in the blood; changes in the rhythm of the heart, or the heart beating faster than normal.
Very rare side effects (may affect up to 1 in 10, 000 people): Severe blistering skin conditions that can be life-threatening. Redness, often associated with blisters, may appear on the skin or on mucous membranes, such as inside the mouth, the genital areas or the eyelids, and fever may be present; recurrence of a previous Hepatitis B infection.
Rituximab may also cause changes in laboratory tests carried out.
If the patient is having Rituximab with other medicines, some of the side effects that they may get may be due to the other medicines.

At present, there аrе limited data оn possible drug interactions with Rituximab. ln CLL patients, co-administration with Rituximab did not appear to have аn effect оn the pharmacokinetics of Fludarabine or Cyclophosphamide, in addition, there was nо apparent effect of Fludarabine and Cyclophosphamide оn the pharmacokinetics of Rituximab. Co-administration with Methotrexate had nо effect оn the pharmacokinetics of Rituximab in RA patients. Patients with human anti-mouse antibody (НАМА) or human anti-chimeric antibody (НАСА) titers may develop allergic or hypersensitivity reactions when treated with other diagnostic оr therapeutic monoclonal antibodies.

Special precautions for disposal and other handling: Rituximab is provided in sterile, preservative-free, non-pyrogenic, single use vials.
Aseptically withdraw the necessary amount of Rituximab, and dilute to a calculated concentration of 1 to 4 mg/mL rituximab into an infusion bag containing sterile, pyrogen-free sodium chloride 9 mg/mL (0.9%) solution for injection or 5% D-Glucose in water. For mixing the solution, gently invert the bag in order to avoid foaming. Care must be taken to ensure the sterility of prepared solutions. Since the medicinal product does not contain any antimicrobial preservative or bacteriostatic agents, aseptic technique must be observed. Parenteral medicinal products should be inspected visually for particulate matter and discolouration prior to administration.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Store at temperatures between 2-8°C.
Keep the container in the outer carton in order to protect from light.
Do not throw away any medicines via wastewater or household waste.

Targeted Cancer Therapy

L01FA01 - rituximab ; Belongs to the class of CD20 (Clusters of Differentiation 20) inhibitors. Used in the treatment of cancer.

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