Zytux (Rituximab) – A biosimilar product

Zytux contains the active ingredient called Rituximab, which is a monoclonal antibody and an anti-neoplastic (anti-cancer) agent. agent. Zytux binds to the CD20 antigen located on pre-B and mature B lymphocytes (a type of white blood cell). CD20 is present in more than 90 %of B-cell non-Hodgkin’s lymphomas (NHL), cancer that starts in the lymphocytes. By doing so, it causes the malignant cells to die.

NHL is a disease of the lymph tissue (part of the immune system) that affects B-Lymphocytes.

Zytux is indicated for the treatment of CD20-positive Hodgkinnon lymphomas (NHL) including:

• Follicular lymphoma (stage III-IV), as initial treatment in combination with other chemotherapy agents in patients who were previously untreated.

• As maintenance therapy in patients with follicular lymphoma (stage III-IV )who have responded to initial therapy.

• As single-agent therapy in patients with follicular lymphoma (stage III-IV ) who experienced a recurrence of the disease or who did not respond to the initial treatment.

• Diffuse large B-cell NHL ,in combination with CHOP (cyclophosphamide ,doxorubicin ,vincristine ,and prednisolone) chemotherapy.

CLL is a type of cancer in which the bone marrow makes too many abnormal lymphocytes which accumulate mainly in the bone marrow and blood. CLL is one of the most common types of leukemia in adults. Zytux is indicated for the treatment of CD20-positive chronic lymphocytic leukemia (CLL) in combination with fludarabine and cyclophosphamide

Zytux is used for the treatment of moderately to severely active RA in adults. If you did not respond well to other medicines specific for the treatment of RA, such as disease-modifying anti-rheumatic drugs( DMARD) and TNF (factor necrosis tumor), you will be given Zytux in combination with Methotrexate.

GPA and MPA are two forms of inflammation of the blood vessels mainly affecting the lungs and kidneys, but other organs could also be affected. Zytux, combined with glucocorticoids, is indicated for remission induction in adult patients with severe, active GPA (Wegener’s) and MPA.

Do not use Zytux:

• If you have ever had an allergic reaction to Rituximab, murine proteins or any of the other ingredients of this medicine

• If you have a severe active infection

• If you have a weak immune system

• If you have severe heart failure or severe uncontrolled heart disease

• If you are under 18 years of age

Before using Zytux, tell your doctor about all your medical conditions including if you:

• Have a history of heart disease (such as angina, palpitations, or heart failure) or chemotherapy toxic to the heart.

• Notice low neutrophil and low platelet counts in your regular full blood counts consult with your doctor.

• Have an infection, are being treated for infection, or have symptoms of an infection.

• You have ever had a hepatitis B infection.

• Recently received or planning to receive a vaccine. You shouldn’t receive live vaccines during treatment with Zytux.

• Take medicines for high blood pressure. You may experience a drop in blood pressure during Zytux infusion. Your doctor may ask you not to use antihypertensive drugs 12 hours prior to Zytux administration.

• Are pregnant or planning to become pregnant. Make sure to use effective birth control during treatment with Zytux and for 12 months after treatment has concluded.

• Are breastfeeding or planning to breastfeed. Women using Zytux should not breastfeed during treatment and for 12 months after treatment has ended, since Rituximab may pass into your breast milk.

Zytux is available on prescription only and will be administered to you by an experienced healthcare doctor in the hospital

The recommended dose of Zytux is 375 mg/m2 body surface area once weekly for 4 weeks. Repeated treatment courses with Zytux are possible.

The recommended dose of Zytux is 375 mg/m2 body surface area per cycle on day 1 of each chemotherapy cycle, up to 8 cycles.

If you respond well to treatment the recommended dose is 375 mg/m2 of body surface area every 2 months (for untreated patients) or 3 months (for patients with disease recurrence) for a maximum period of two years (8 administrations in total).

The recommended dose of Zytux is 1000 mg on days 1 and 15 in combination with methotrexate. Repeated courses of Zytux depend on your treatment evaluation.

The recommended dose of Zytux is 375 mg/m2 of body surface area once weekly for 4 weeks.

The diluted solution of Zytux should be administered as an intravenous infusion. Due to possible side effects of Zytux premedication with antipyretic, antihistamine, and in some cases, corticosteroids will usually be given by injection before starting Zytux administration. respond to Zytux. In Rheumatoid arthritis available data suggest that clinical response is usually achieved within 16 – 24 weeks of an initial treatment course.

• Infusion-related reactions: Infusion reactions may occur during the first two hours of infusion. Tell your doctor right away if you have
  • headache
  • fever
  • chills
  • shivering
  • vomiting
  • flushing
  • palpitations
  • pain at the infusion site
  • blisters
  • itching
  • sickness
  • tiredness
  • breathing difficulties, tongue, throat swelling itchy, or runny nose.

If you have a low platelet count in your blood or a history of heart disease such as angina, Zytux may worsen these conditions. In this situation, your doctor may decide to slow down the infusion rate or stop the infusion and may give you medications such as antihistamines or Paracetamol. When these symptoms go away or improve, the infusion can be continued.

• Infections: the probability of developing a very serious and fatal brain infection PML (Progressive Multifocal Leukoencephalopathy) may increase by taking Zytux. Tell your doctor immediately if you experience:
  • memory loss
  • trouble in thinking
  • difficulty walking and inability to coordinate movements
  • vision loss, and
  • speech disturbances
  • Tell your doctor immediately

If you have a fever, cough, sore throat, chills, or painful urination, these may be signs of an infection. Zytux may increase the risk of colds, pneumonia, and urinary tract infections.

• Skin Reactions: serious skin reactions can occur during treatment with Zytux. Call your doctor right away if you have
  • blistering
  • peeling
  • red skin lesions
  • severe acne
  • skin rash
  • fever
  • chills
  • sores on the skin, or
  • on mucous membranes such as inside the mouth, genital areas, or eyelids

• Bacterial or viral infections, bronchitis

• Decrease in Neutrophils (with or without fever) and platelets counts

• Nausea

• hair loss, rash, Itching

• Fever, chills, headache, weakness, or lack of energy

• Decrease in immunoglobulin (IgG) and immunity

• Blood infection (sepsis), pneumonia, cold, herpes zoster, respiratory tract infection, fungal infections, infection of unknown origin, hepatitis B, sinus, and bronchial inflammation

• Decrease in red blood cells and all blood cells

• Allergic reactions

• Increase in blood sugar level, weight loss, swelling in the face low, high levels of enzyme LDH, and low calcium levels in the blood

• Sleeplessness, vasodilation, anxiety, dizziness, and agitation

• Abnormal sensation of the skin, typically tingling, pricking, and numbness

• Conjunctivitis

• Ringing sound in the ears and ear pain

• High or low blood pressure, orthostatic hypotension (drop in blood pressure while standing after sitting for a while)

• Cardiac disorder – such as heart attack, uneven, or fast heart rate

• Bronchospasm, respiratory disease, chest pain, shortness of breath, cough, and runny nose

• Vomiting, diarrhea, constipation, abdominal pain, difficulty or discomfort in swallowing, irritation or ulcers in the throat and mouth, indigestion, lack or loss of appetite

• Muscle problems such as tight muscles, joint or muscle pain, back and neck pain

• Shivering, weakness, fatigue, signs of flu, and multiple-organ failure

• Hives, increased sweating night sweats

• Depression, feeling nervous

• Blood clotting problems, a decrease in red blood cell production, an increase in red blood cell destruction (aplastic and haemolytic anemia), swollen or enlarged lymph nodes)

• Decrease in taste sensitivity

• Heart problems, angina, and uneven heart

• Asthma, airway obstruction and inflammation, lower than normal concentration of oxygen in the blood

• Swelling of the stomach

• Infusion site pain

• Serious viral infection

• Severe cardiac disorder

• Severe life-threatening allergic reaction

• Lung disease affecting the tissue and space around the air sacs of the lungs

• Brain infection (Progressive Multifocal Leukoencephalopathy)

• Chemical disturbances in the blood caused by the breakdown of dying cancer cells

• Nerve damage in arms and legs, paralysed face

• Short-term increase in the amount of some types of antibodies in the blood (IgM)

• Blindness

• Inflammation of blood vessels including those leading to skin symptoms

• Heart failure

• Respiratory failure

• Damage to the intestinal wall (perforation)

• Severe life-threatening skin problems causing fever, blisters, redness on the skin or on mucous membranes

• Kidney failure

• Nerve damage and loss of other senses

• Late-onset reduction in white blood cells

• Reduced platelets number that can be reversed, but can be fatal in rare cases

• Abnormal substance accumulation in the lungs (lung infiltration)

• Hearing loss

• Allergic reactions that occur during an infusion or up to 24 hours after the infusion with symptoms of changes in blood pressure, nausea, rash, hives, itching, fever, blocked nose, shaking, rapid heartbeat, and fatigue

• Urinary tract infections

• Upper respiratory tract infection

• Decrease in the amount of some types of antibodies in the blood (IgM)

• High cholesterol levels in the blood

• Decrease in Neutrophils

• Abnormal sensations of the skin such as numbness or tingling

• Inflammation of the stomach causing vomiting and diarrhea

• Fungal foot infection

• Decrease in the amount of some types of antibodies in the blood (IgG)

• Bronchitis, sinusitis

• Pain in muscles or abdominal joints pain

• Indigestion, diarrhea, acid reflux, ulceration of the mouth, abdominal pain

• Anxiety, depression

• Hair loss

• Dizziness

• Pain affecting the back and/or hip

• Infusion-related reactions, edema, and fluid retention in the face and body

• Inflammation of the lungs and throat

• Late-onset reduction in neutrophils

• Allergic reactions including wheezing or shortness of breath

• Heart failure, myocardial infarction

• Reactivation of Hepatitis B

• Brain infection (Progressive Multifocal Leukoencephalopathy)

• Severe life-threatening skin problems causing fever, blisters, redness on the skin or on mucous membranes

• Hypersensitivity reactions and Immune complex deposits that cause itching, arthritis, swollen lymph glands, fever, and other systemic symptoms

• Allergic reactions which usually occur during infusion but may happen 24 hours after the infusion

• Infections such as chest infections, urinary tract infections colds, and herpes

• Difficulty in sleeping

• Swelling and edema of the hands or ankles

• Dizziness

• Tremor

• Pain and inflammation of joint and muscle, back pain

• High blood pressure

• Nose bleeds

• Cough or shortness of breath

• Diarrhea

• Decrease in platelets

• Increase in the amount of potassium in the blood and changes in the normal rhythm of the heart

• Muscle weakness

• Pain in the muscles or in the hands or feet

• Blocked nose

• Flushing or redness of the skin

• Acne

• Constipation

• Indigestion

• Severe life-threatening skin problems causing fever, blisters, redness on the skin or on mucous membranes

• Recurrence of a previous Hepatitis B infection

• Keep this medicine out of the sight and reach of children.

• Store in a refrigerator (2-8°C).

• Do not freeze

• Keep the vial in the outer carton in order to protect it from light.

The active substance is Rituximab.

Other ingredients are Sodium chloride, Polysorbate 80, Sodium citrate dihydrate, and Water for Injections.