Holoxan 500 mg/1 g/2 g Injection

HOLOXAN contains the active substance Ifosfamide, HOLOXAN is a cytotoxic or anti-cancer medicine. It works by killing cancer cells. Treatment with HOLOXAN is sometimes called “chemotherapy”. It is used to treat lots of different cancers. HOLOXAN is often used together with other anti-cancer medicines or radiotherapy.

HOLOXAN should not be administered to you if:

• you are hypersensitive (allergic) to ifosfamide. An allergic reaction can include shortness of breath, wheezing, rash, itching or swelling of the face and lips.
• if your bone marrow is not working properly (especially if you have previously had chemotherapy or radiotherapy). You will have blood tests to check how well your bone marrow is working.
• If you have severe kidney problems. Your doctor will check how well your kidneys are working by doing regular tests.
• if you have a condition which decreases your ability to urinate (urinary outflow obstruction).
• if you have a urinary tract infection, which can be recognised as pain when passing urine (cystitis).
• if you currently have any infections.
• if you are pregnant or breastfeeding.
• if you have a nervous system condition called advanced cerebral sclerosis.
• if you have a blood platelet count below 50000 platelets per mm3 (this will be confirmed with a blood test).

Warnings and precautions

Tell your doctor or health care provider before being given the injection:

• If you are already having, or have recently had, radiotherapy, chemotherapy, any other medicines which suppress your immune system, medicines which affect your kidneys or medicines which affect your bladder.
• If you are receiving dialysis.
• If you have blood in your urine or experience pain whilst urinating.
• If you have heart problems.
• If you have or had cancer.
• If you have poor general health or are frail.
• If you are elderly.
• If you have diabetes.

Take special care with HOLOXAN

HOLOXAN can have effects on your bone marrow, blood and immune system. After taking HOLOXAN, your white blood cell blood count will drop and will stay low for a few days after you finish the course. You may be more likely to get infections when your white blood cell count drops. Try to avoid close contact with people who have coughs, colds and other infections. Your doctor will treat you with appropriate medicine if they think you have, or are at risk, of an infection. Your doctor will check that your white blood cell count and other blood component levels are high enough before and during your treatment with HOLOXAN. Depending on the test results, your dose may need to be reduced or your next dose may need to be delayed. HOLOXAN can affect wound healing. Ensure that all cuts or wounds are treated carefully and check regularly to ensure that they are healing normally. It is important to keep your gums healthy, as mouth ulcers and infections can occur. Ask your doctor about this if you are unsure. HOLOXAN can affect your nervous system and may cause confusion, sleepiness (somnolence), coma, hallucinations, blurred vision, psychotic behaviour, involuntary muscle movements (extrapyramidal symptoms), inability to control urinating (urinary incontinence), seizures, pain in the extremities (peripheral neuropathy).

You will not be expected to give yourself HOLOXAN. It will be given to you by a person qualified to do so. HOLOXAN should only be administered by doctors experienced with this medicine and the treatment of cancer. The dosage, duration of treatment and treatment frequency of HOLOXAN will be calculated specifically for you by your doctor and depends on:

• the type of illness you have.
• how big you are (combination of your height and weight).
• your general health and how well your organs are functioning.
• your laboratory test results.
• your age.
• whether you are being given other anti-cancer medicines or are having radiotherapy.

HOLOXAN will be administered via the intravenous (into a vein) route. The administration may be a slow injection or a slow infusion over a longer period of time. Whilst receiving treatment with HOLOXAN, you should ingest adequate amounts of fluid. HOLOXAN is usually given as a series of courses of treatment. After a course there is a break (a period when no injections are given) before the next course. Your doctor will determine how many courses you require and how long the breaks between courses will be.

If you receive more HOLOXAN than you should Since a healthcare professional will administer this medicine, he/she will control the dosage. However, in the event of overdosage, your doctor will manage the overdosage.

If you forget to take HOLOXAN Since a healthcare provider will administer HOLOXAN, it is unlikely that the dose will be missed.

HOLOXAN can have side effects. Not all side effects reported for HOLOXAN are included in this leaflet. Should your general health worsen or if you experience any untoward effects while taking HOLOXAN, please consult your health care provider for advice. If any of the following happens after you have received HOLOXAN, tell your doctor immediately or go to the casualty department at your nearest hospital:

• Swelling of the hands, feet, ankles, face, lips, mouth or throat, which may cause difficulty in swallowing or breathing,
• rash or itching,
• fainting,
• yellowing of the skin and eyes, also called jaundice.

These are all very serious side effects. If you have them, you may have had a serious allergic reaction to HOLOXAN. You may need urgent medical attention or hospitalisation.

Frequent side effects are:

• effects on the brain (encephalopathy), signs of this can range from mild, such as subtle personality changes, memory loss to severe, such as seizures, coma and death.
• central nervous system toxicity presenting with the following signs and symptoms: abnormal behaviour, irregular emotional response (affect lability), aggression, agitation, anxiety, inability to communicate (aphasia), abnormal lack of energy (asthenia), movement disorders and gait disturbances (ataxia, cerebellar syndrome), mental health disorders that affect cognitive abilities including learning, memory, perception, and problem solving, coma, confusion, convulsions (fits), ability to decrease in your ability to remain awake and aware, depression, disorientation, dizziness, abnormal brain function (EEG test), severe reduction in emotional expressiveness (flat affect), hallucinations, headache, abnormal thoughts, lifelessness, memory impairment, mood change, muscle and nerve dysfunction, muscle spasms or twitching (myoclonus), loss of reflexes, psychosis, restlessness, feeling drowsy (somnolence), tremor, urinary incontinence,
• infections.
• decrease in the activity of your bone marrow (myelosuppression).
• decrease or low levels of various white blood cells - which fight infection. This may be associated with fever (leukopenia, granulocytopenia, neutropenia, lymphopenia).
• decrease in red and white blood cells, as well as platelets (pancytopenia).
• decrease of platelets - which help your blood clot (thrombocytopenia).
• decrease of red blood cells - which carry oxygen around the body (anaemia).
• increase of acidity of body fluids (metabolic acidosis).
• anorexia (weight loss).
• drowsiness.
• feeling sick (nausea).
• being sick (vomiting).
• increases of liver enzymes in the blood (hepatotoxicity).
• hair loss (alopecia).
• blood in the urine (haematuria).
• inflammation of the bladder lining which causes pain, bleeding, blood in the urine, reduced urine flow (haemorrhagic cystitis).
• life threatening decrease in the abilities of your kidney to adequately remove toxins and waste products from the blood (renal dysfunction, renal failure).

Less frequent side effects are:

• pneumonia.
• severe infection spreading through the blood which may have a possible fatal outcome (sepsis).
• secondary tumours in various parts of the body, often in the area of the bladder.
• progression of underlying cancers (myelodysplastic syndrome, acute leukaemia).
• a condition causing abnormal break down of the red blood cells, decreased numbers of platelets in the blood and kidney failure (haemolytic uremic syndrome).
• formation of small blood clots in your blood vessels disrupting the normal blood flow around your body (disseminated intravascular coagulation).
• allergic and hypersensitivity reactions, which may include rash, fever, low blood pressure, hypotension, angioedema (swelling of the skin around the face, inside of the mouth and throat), immunosuppression (inhibition of the immune system), urticaria (skin rash or red itchy swellings). These reactions may develop to anaphylactic shock (a systemic reaction to an allergy) and death.
• irreversible ovulation disturbances.
• increase in the release of antidiuretic hormone from the pituitary gland (SIADH). This affects the kidneys, causing low levels of sodium in your blood (hyponatraemia), water retention and associated symptoms such as confusion and cramps.
• dehydration.
• electrolyte imbalance.
• low blood levels of potassium (hypokalaemia).
• depression accompanied by psychotic symptoms.
• disorientation.
• restlessness.
• confusion.
• feeling drowsy (somnolence).
• forgetfulness.
• dizziness.
• a disorder of the nerves which can cause weakness, tingling or numbness of the extremities (peripheral neuropathy, polyneuropathy).
• cerebellar syndrome (a condition where the blood flow in the brain is reduced).
• coma.
• seizures.
• blurring, reduction or loss of sight.
• changes in your heart rhythm (dysrhythmia).
• decrease in your hearts ability to pump enough blood around your body which may be life threatening (cardiac failure or cardiac arrest).
• increase in heartrate (tachycardia).
• heart attack (myocardial infarction).
• fluid in the lungs, which can cause breathing problems (pulmonary oedema).
• bleeding.
• low blood pressure (hypotension), that can lead to shock and death.
• thromboembolism (the formation of a blood clot in a blood vessel).
• ongoing lung diseases.

If you notice any side effects not mentioned in this leaflet, please inform your doctor or pharmacist.

Reporting of side effects

If you get side effects, talk to your doctor, pharmacist or nurse. You can also report side effects to SAHPRA via the “6.04 Adverse Drug Reaction Reporting Form”, found online under SAHPRA’s publications: https://www.sahpra.org.za/Publications/Index/8. By reporting side effects, you can help provide more information on the safety of HOLOXAN.

Store at or below 25 °C. The solution of HOLOXAN injection can be kept for up to 24 hours in the refrigerator at 5 °C. Store all medicines out of reach of children.