Holoxan

Leaflet accompanying the packaging: patient information

HOLOXAN, 1 g, powder for solution for injection

HOLOXAN, 2 g, powder for solution for injection

Ifosfamide

You should carefully read the contents of the leaflet before using the medicine, as it contains

important information for the patient.

• You should keep this leaflet so that you can read it again if you need to.
• In case of any doubts, you should consult a doctor or pharmacist.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor or pharmacist. See section 4.

Important information about HOLOXAN medicine

HOLOXAN medicine is prescribed to patients for the treatment of cancer.
HOLOXAN medicine destroys cancer cells, but it also affects healthy cells
in the body. Therefore, HOLOXAN medicine may cause many side effects. The doctor
will decide to prescribe this medicine if the cancer disease poses a greater threat to the patient than possible side effects of the medicine. The doctor will perform regular
check-ups on the patient and treat the effects of side effects as much as possible.
HOLOXAN medicine:

• reduces the number of blood cells, which can cause fatigue and increase the susceptibility to infections.
• may affect kidney and bladder function. The patient may be given another medicine, UROMITEXAN (containing mesna), to prevent damage. If blood is found in the urine, the doctor should be informed immediately.
• may cause mental disorders, such as confusion, excessive drowsiness, and more severe: seizures and loss of consciousness. If such symptoms occur, the doctor should be informed immediately.
• as with most anticancer medicines, the patient may lose hair (from thinning to baldness), but hair should grow back after the end of treatment. The medicine may also cause nausea or vomiting. The doctor will advise the patient or prescribe appropriate medicines to alleviate these ailments.
• both men and women should not try to conceive during treatment, and also for at least 6-12 months after the end of ifosfamide therapy. Therefore, patients should use effective contraception methods. You should read the rest of the leaflet.It contains other important information about the use of HOLOXAN medicine that may be particularly important for the patient.

Table of contents of the leaflet:

• 1. What is HOLOXAN medicine and what is it used for
• 2. Important information before using HOLOXAN medicine
• 3. How to use HOLOXAN medicine
• 4. Possible side effects
• 5. How to store HOLOXAN medicine
• 6. Contents of the packaging and other information

1. What is HOLOXAN medicine and what is it used for

HOLOXAN is a cytotoxic or anticancer medicine. Its action involves
destroying cancer cells, which is sometimes referred to as "chemotherapy".
HOLOXAN medicine is used to treat many different cancers. It is often used
in combination with other anticancer medicines or radiation therapy.

2. Important information before using HOLOXAN medicine

When not to use HOLOXAN medicine

• if the patient has ever had an allergic reaction to ifosfamide. An allergic reaction may include: shortness of breath, wheezing, rash, itching, or swelling of the face and lips;
• if the patient has bone marrow function disorders (especially in patients who have undergone chemotherapy or radiation therapy previously). The doctor will order blood tests to assess bone marrow function;
• if the patient has difficulty urinating or a urinary tract infection, which may be manifested by pain during urination (cystitis);
• if the patient has liver and kidney function disorders. The patient will have blood tests done in this regard;
• if the patient has an infection;
• if the patient has ever had kidney or bladder function disorders as a result of previous chemotherapy or radiation therapy;
• if the patient has a disease that reduces the ability to urinate (urinary outflow obstruction).

Warnings and precautions

Before starting HOLOXAN medicine, you should discuss it with your doctor if:

• the patient is or has recently undergone chemotherapy or radiation therapy;
• the patient has diabetes;
• the patient has liver or kidney disease. The doctor will check the liver and kidney function by doing a blood test;
• the patient has heart disease or has received radiation therapy in the heart area;
• the patient's health is poor or if the patient is weakened;
• the patient is elderly;
• the patient is or has been treated with cisplatin before or during ifosfamide treatment; because it may be necessary to perform additional blood or urine tests and this may affect the treatment change.

When to be particularly careful when using HOLOXAN medicine

• Ifosfamide may affect the blood and immune system.
• Blood cells are produced in the bone marrow. Three different types of blood cells are produced:
• red blood cells, which transport oxygen in the body,
• white blood cells, which fight infections, and
• platelets, which help in blood clotting.
• After using ifosfamide, the number of these three types of blood cells will decrease. This is an unavoidable effect of ifosfamide. The lowest number of blood cells is achieved after about 5-10 days from the start of ifosfamide administration and persists until a few days after the end of the treatment cycle. In most patients, the number of blood cells returns to normal within 21 to

28 days. If the patient has been previously subjected to multiple chemotherapies, this time may be slightly longer.

• The patient may be more susceptible to infections when the number of blood cells decreases. You should avoid direct contact with people who cough, have a cold, or have other infections.
• Before starting ifosfamide treatment and during its duration, the doctor will check if the number of red blood cells, white blood cells, and platelets is sufficient.
• Ifosfamide may affect wound healing. All cuts should be kept clean, dry, and observed to heal properly.
• It is essential to take care of gum health, as ulcers and mouth infections may occur. In case of doubts, you should ask the doctor.
• Ifosfamide may damage the bladder mucosa, causing bleeding into the urine. The doctor is aware that such cases may occur and, if necessary, will administer mesna, which will protect the bladder.
• UROMITEXAN (mesna) medicine may be administered either as a short injection or added to the ifosfamide drip or given in tablet form.
• More information about UROMITEXAN (mesna) medicine can be found in the patient leaflet accompanying UROMITEXAN (mesna) solution for injection.
• Most people using ifosfamide with UROMITEXAN (mesna) medicine do not experience any problems with the bladder, but the doctor may want to perform a urine test for blood using a dipstick or microscope.
• If blood is found in the urine, the doctor should be informed immediately.
• Ifosfamide may cause kidney damage and impaired function.
• This is more likely if the patient has only one kidney or if their kidneys are already damaged.
• This condition is usually temporary and resolves after the end of ifosfamide therapy. Sometimes the damage is permanent and severe.
• The doctor will check the test results for signs of kidney damage.
• Ifosfamide may have a toxic effect on the brain and spinal cord and cause encephalopathy (non-inflammatory brain disease). You should immediately inform the doctor if any of the following conditions occur, which may be symptoms of toxic effects on the brain and spinal cord: disorientation, drowsiness, loss of consciousness/coma, hallucinations/delusions, blurred vision, perception disorders, extrapyramidal symptoms (such as muscle stiffness, muscle spasms, restlessness, slowed movement, uncoordinated movements), uncontrolled urination, and seizures (seizures). The doctor or nurse may monitor the occurrence of symptoms and signs of toxic effects on the brain and spinal cord in patients.
• Cancer medicines and radiation therapy may increase the risk of developing other cancers, which may occur several years after the end of therapy.
• Ifosfamide may cause heart damage or affect heart rhythm. This is exacerbated by high doses of ifosfamide, if the patient is being treated with radiation therapy or other chemotherapeutic agents, or in elderly patients. During treatment, the doctor will closely monitor heart function.
• Ifosfamide may cause inflammation or scarring of the lungs. This may occur more than 6 months after the end of treatment. If difficulty breathing occurs, the doctor should be informed as soon as possible.
• Ifosfamide may have a life-threatening effect on the liver. If the patient observes a sudden weight gain, liver pain, and jaundice, they should inform the doctor as soon as possible.
• There may be hair loss or baldness. Hair should grow back, but its structure and color may be different.
• Ifosfamide may cause nausea or vomiting. This may last for about 24 hours after taking ifosfamide. The patient may require administration of anti-nausea and vomiting medicines. You should ask the doctor about this.

HOLOXAN medicine and other medicines

You should tell the doctor or nurse about all medicines being taken currently or
recently, including those available without a prescription.
In particular, you should inform the doctor or nurse about taking the following
medicines or undergoing the following treatments, which may interact with HOLOXAN medicine:

The following medicines may increase the toxicity of HOLOXAN medicine:

Medicines that may enhance the toxic effect on blood cells and the immune system:

• angiotensin-converting enzyme (ACE) inhibitors (used to treat high blood pressure)
• carboplatin (used to treat cancer)
• cisplatin (used to treat cancer)
• natalizumab (used to treat multiple sclerosis)

Medicines that may enhance the toxic effect on the heart:

• anthracycline antibiotics, such as bleomycin, doxorubicin, epirubicin, mitomycin (used to treat cancer)
• radiation therapy in the heart area

Medicines that may enhance the toxic effect on the lungs:

• amiodarone (used to treat heart rhythm disorders)
• G-CSF, GM-CSF hormones (used to increase the number of white blood cells after chemotherapy)

Medicines that may enhance the toxic effect on the kidneys:

• acyclovir (used to treat viral infections)
• aminoglycosides (used to treat bacterial infections)
• amphotericin B (used to treat fungal infections)
• carboplatin (used to treat cancer)
• cisplatin (used to treat cancer)

Medicines that may enhance the toxic effect on the bladder:

• busulfan (used to treat cancer)
• radiation therapy in the bladder area

Medicines that affect the brain, such as anti-nausea and vomiting medicines, sleeping pills, some painkillers (opioid medicines), or medicines used to treat allergies.

The following medicines may increase the toxicity of HOLOXAN medicine:

• carbamazepine, phenytoin, phenobarbital (used to treat epilepsy)
• corticosteroids (used to treat inflammatory conditions)
• rifampicin (used to treat bacterial infections)
• St. John's Wort (a herbal medicine used to treat mild depression)

The following medicines may reduce the effect of HOLOXAN medicine:

• ketokonazole, fluconazole, itraconazole (used to treat bacterial or parasitic infections)
• sorafenib (used to treat cancer)

Other medicines that may interact with HOLOXAN medicine or HOLOXAN medicine may interact with their effect:

• docetaxel (used to treat cancer)
• coumarins, such as warfarin (used to thin the blood)
• vaccines
• tamoxifen (used to treat breast cancer)
• cisplatin (used to treat cancer)
• irinotecan (used to treat cancer)

HOLOXAN medicine with food and drink

Consuming alcohol may enhance the nausea and vomiting caused by HOLOXAN medicine.

Contraception, pregnancy, breastfeeding, and fertility

During HOLOXAN medicine therapy, you should not become pregnant, as it may cause
miscarriages or fetal damage. If the patient is pregnant or suspects they are pregnant or plans to become pregnant, they should inform the doctor.

• Both men and women should not try to conceive during HOLOXAN medicine therapy, and also for at least 6-12 months after the end of therapy. Effective contraception methods should be used. You should ask the doctor for advice.
• HOLOXAN medicine may affect the ability to conceive in the future. You should consult the doctor about the possibility of freezing sperm or eggs before starting treatment.

You should not breastfeed during HOLOXAN medicine therapy. You should consult the doctor.

Driving and using machines

Some side effects related to HOLOXAN medicine therapy may affect the ability to drive or operate machines safely. The doctor will decide whether the patient can perform these activities safely.

Procedure when visiting another doctor or hospital

In case of visiting another doctor or hospital during treatment, regardless of the reason, you should inform the medical staff about the medicines being taken. You should not take any other medicines before informing the doctor about taking HOLOXAN medicine.

3. How to use HOLOXAN medicine

HOLOXAN medicine is administered to the patient by a doctor or nurse.

• HOLOXAN medicine is usually administered from a large bag of fluid, in a slow infusion (drip), directly into the patient's vein. The vein for injection may be on the arm, hand, or a large vein under the collarbone. Depending on the dose used, the administration of the medicine may take several hours, but it may also be administered over several days.
• HOLOXAN medicine is usually administered in combination with other anticancer medicines or radiation therapy.

Usual doses

• The doctor will decide how much medicine and when to administer it to the patient.
• The dose of HOLOXAN medicine to be administered to the patient depends on:
• the type of condition the patient has,
• the patient's height and weight,
• the patient's overall health,
• the use of other anticancer medicines or radiation therapy. HOLOXAN medicine is usually administered in several treatment cycles.

Administration of a higher dose of HOLOXAN medicine than recommended

It is unlikely that the patient will be administered a higher dose of HOLOXAN medicine than
recommended, as the medicine is administered by trained and qualified medical personnel.
The injection of the medicine will be stopped immediately if too much medicine is administered.

4. Possible side effects

Like all medicines, HOLOXAN medicine may cause side effects, although not everybody gets them. During treatment, the following side effects may occur.

You should immediately inform the doctor if you observe any of the following serious side effects:

• bruising without injury, slowed blood clotting, or bleeding from the nose or gums. This may be a sign that the number of platelets is decreasing.
• a decrease in the number of white blood cells, which the doctor will check during treatment. There may be no symptoms, but the patient will be more susceptible to infections. If the patient suspects they have an infection (fever, feeling cold and shivering, or feeling hot and sweating, or any sign of infection such as cough or burning during urination), an antibiotic may be necessary to combat the infection.
• pallor, lethargy, and fatigue. This may be a sign of a low number of red blood cells (anemia). The doctor will decide on the appropriate course of action.
• blood in the urine, pain, or difficulty urinating.
• mental disorders. In some patients, ifosfamide may affect brain function. Sometimes patients taking ifosfamide may not be aware of it, but friends and relatives may notice changes in them. If any of the following side effects occur, the doctor will decide to stop using ifosfamide in the patient:
• confusion
• drowsiness
• loss of consciousness/coma
• disorientation
• restlessness
• depression
• hallucinations
• delusions (false beliefs)
• blurred vision
• perception disorders
• extrapyramidal symptoms (such as muscle stiffness, muscle spasms, restlessness, slowed movement, uncoordinated movements)
• rapid speech
• repetition of words
• compulsive behavior
• aggression
• uncontrolled urination
• seizures

The above side effects may be accompanied by fever and rapid heart rate.

Other possible side effects:

Immune system and infections

• allergic reactions, whose symptoms are shortness of breath, wheezing, rash, itching, or swelling of the face and lips (hypersensitivity). Severe allergic reactions may cause difficulty

breathing or shock, which can lead to death (anaphylactic shock, anaphylactic/anaphylactoid reactions);

• reduced effectiveness of the immune system (immunosuppression);
• increased risk and severity of bacterial, fungal, viral, protozoal, or parasitic infections related to the effect of ifosfamide on the immune system;
• reactivation of previous infections (latent infections);
• severe blood-borne infections that can lead to a significant drop in blood pressure, leading to death (sepsis, shock).

Cancer

• secondary tumors in different parts of the body, often in the bladder area;
• bone marrow cancer (myelodysplastic syndrome);
• blood cancer (leukemia);
• lymphatic system cancer (non-Hodgkin's lymphoma).

Blood and lymphatic system

• decrease in bone marrow activity (myelosuppression). This may lead to a decrease in the number of blood cells:
• white blood cells, which fight infections (leukopenia, agranulocytosis, granulocytopenia, lymphopenia, neutropenia). This may lead to the occurrence of fever (neutropenia with fever);
• platelets, which help in blood clotting (thrombocytopenia);
• red blood cells, which transport oxygen (anemia). This may lead to a decrease in the ability to transport oxygen (decrease in hemoglobin concentration);
• red blood cells, white blood cells, and platelets at the same time (pancytopenia);
• formation of small blood clots in blood vessels that disrupt normal blood flow in the body (disseminated intravascular coagulation);
• a condition that causes abnormal breakdown of red blood cells, decreased platelet count, and kidney failure (hemolytic-uremic syndrome).

Endocrine system

• brain swelling due to excessive water in the blood (water intoxication). Its symptoms may include headaches, personality or behavior changes, confusion, drowsiness;
• increased secretion of antidiuretic hormone by the pituitary gland. This may affect the kidneys, causing low sodium levels in the blood (hyponatremia) and water retention in the body.

Metabolism and nutrition

• decreased or absent appetite (anorexia);
• changes in metabolism caused by the breakdown of cancer cells (tumor lysis syndrome);
• increased acidity of body fluids (metabolic acidosis);
• low potassium levels in the blood, which can cause heart rhythm disorders, constipation, fatigue, weakness, or muscle cramps, depression, psychosis, hallucinations, confusion;
• low calcium levels in the blood, which can cause muscle cramps and twitches, irregular heartbeat, increased reflexes, burning or tingling in hands and feet (hypocalcemia);
• low phosphate levels in the blood, which can cause bone pain, confusion, and muscle weakness (hypophosphatemia);
• high blood sugar levels, which can cause thirst, fatigue, and irritability (hyperglycemia);
• excessive thirst, which is accompanied by excessive fluid intake (polydipsia).

Gastrointestinal system

• nausea and vomiting;
• diarrhea;
• inflammation of the mucous membrane of the mouth, including ulcers (stomatitis);
• inflammation of the intestines, which can cause bleeding (enteritis, colitis, hemorrhagic enteritis);
• a condition that causes inflammation of the large intestine, which can cause abdominal pain or diarrhea (colitis);
• bleeding from the stomach or intestines (gastrointestinal bleeding);
• severe abdominal and back pain (pancreatitis);
• constipation.

Nervous system

• nerve disorders, which can cause weakness, numbness, or tingling (peripheral neuropathy). This condition may occur in more than one nerve bundle (polyneuropathy);
• difficulty controlling or coordinating muscles used during speech or weakness of these muscles (dysarthria);
• seizures;
• a condition that causes seizures (seizure disorder) defined as a single, continuous, uninterrupted seizure that lasts longer than 5 minutes or recurring seizures without regaining consciousness between seizures for more than 5 minutes;
• reversible posterior leukoencephalopathy, which can cause brain swelling, headache, confusion, seizures, and loss of vision;
• effect on the brain (encephalopathy), whose symptoms may include: thinking or concentration problems, decreased alertness, personality changes, fatigue, seizures, muscle spasms, and tremors;
• dizziness;
• movement and gait disorders;
• effect on the spinal cord (myelopathy), which can cause numbness, weakness, and tingling in the arms, loss of motor skills;
• nerve pain, which can also be felt as pain or a burning sensation (neuralgia);
• tingling or numbness, often in the hands or feet (paresthesia);
• changes in touch sensation (sensory disturbances) or loss of sensation (hypoesthesia);
• changes in taste sensation (taste disturbances) or loss of taste;
• inability to control bowel movements (fecal incontinence).

Eyes and ears

• vision disorders, deterioration, or loss of vision;
• eye inflammation (conjunctivitis);
• hearing loss or hearing disorders;
• ringing in the ears (tinnitus).

Heart and circulation

• life-threatening decrease in the ability of the lungs to transport oxygen to the blood (respiratory failure);
• conditions that cause lung inflammation, which can cause difficulty breathing, cough, and elevated temperature or scarring of the lungs (pneumonia, acute respiratory distress syndrome, allergic alveolitis);
• scarring of the lungs, which can cause difficulty breathing (pulmonary fibrosis);
• fluid in the lungs or around the lungs (pulmonary edema, pleural effusion);
• high blood pressure in the lungs, which can cause difficulty breathing, fatigue, cough, shortness of breath, fainting, peripheral edema (pulmonary hypertension);
• difficulty breathing or wheezing (bronchospasm);
• shortness of breath;
• decrease in oxygen levels in the body (hypoxia);
• cough.

Liver

• accumulation of toxins in the body due to liver failure (hepatotoxicity);
• liver failure;
• obstruction of small liver veins (veno-occlusive liver disease), which can cause weight gain, liver enlargement, pain, and jaundice;
• decreased blood flow or obstruction of the portal vein in the liver (portal vein thrombosis);
• conditions that cause liver inflammation, which can lead to jaundice, weight loss, and malaise (hepatitis);
• disorders of bile production by the liver, which can cause itching, jaundice, pale-colored stools, dark urine (cholestasis);
• increased levels of certain proteins produced by the liver, i.e., enzymes. The doctor will order blood tests to examine them.

Skin and subcutaneous tissue

• hair loss (baldness);
• skin rashes or the formation of small, round, raised nodules with clear boundaries (papular rash);
• skin inflammation, which can cause rash, blisters, itching, ulcers, discharge, and scarring (dermatitis);
• life-threatening conditions that can cause rash, ulcers, throat pain, fever, conjunctivitis, separation of skin layers (toxic epidermal necrolysis, Stevens-Johnson syndrome);
• swelling, numbness, red nodules, and peeling of the skin on the hands and feet (hand-foot syndrome);
• redness and blisters on the skin that appear several months or years after the end of treatment (radiation dermatitis);
• skin rashes, where the changes are flat, less than 1 cm in diameter (maculopapular rash);
• itching;
• itchy red rash, which can develop into ulcers (erythema);
• changes in nail and skin color;
• separation of the nail bed, which can cause the nail to fall off;
• facial swelling;
• excessive sweating.

Musculoskeletal and connective tissue

• abnormal breakdown of muscles, which can lead to kidney problems (rhabdomyolysis);
• softening of bones, which can cause severe bone pain, bone pain caused by small cracks in the bones, back pain, partial or complete bone fractures, muscle weakness (osteomalacia, rickets);
• delayed growth;
• muscle pain (myalgia) or joint pain (arthralgia);
• discomfort in the upper or lower limbs (limb pain);
• muscle spasms.

Kidney and urinary tract

• inflammation of the bladder mucosa, which can cause pain, bleeding, blood in the urine, decreased urine flow (hemorrhagic cystitis);
• blood in the urine (hematuria);
• life-threatening decrease in the ability of the kidney to properly remove toxins and waste products from the blood (renal failure);
• changes in kidney structure that prevent them from functioning properly (structural kidney damage);
• impaired kidney function, leading to excessive urine production and excessive thirst, causing water, calcium, potassium, magnesium, and other substance deficiencies in the body (Fanconi syndrome);
• glucose in the urine (tubular diabetes);
• impaired kidney function, manifested by cloudy urine (phosphaturia);
• impaired kidney function, causing an increase in the total concentration of amino acids in the urine (aminoaciduria). The doctor will order a urine test in this regard.
• a condition usually defined as excessive or abnormally high urine production or excretion (polyuria);
• repeated inability to control urination (urinary incontinence);
• feeling of urinary retention;
• kidney failure.

Pregnancy and fertility

• infertility. Sperm production in men and egg production in women may be reduced or stopped. In some cases, this may be an irreversible condition;
• loss of ovarian function before the age of 40 (ovarian failure, premature menopause);
• absence of menstruation or ovulation (ovulation disorders);
• absence of measurable sperm count in male semen (azoospermia) or a lower number of sperm in the ejaculate (oligospermia);
• decreased estrogen levels in the blood;
• increased gonadotropin hormone levels in the blood;
• use in young patients may result in future fertility disorders.

Congenital anomalies, familial and genetic disorders

• growth inhibition, malformations, or fetal death in the womb.

General disorders and administration site reactions

• inflammation of the veins, usually in the legs;
• fever, usually in combination with signs of infection (febrile neutropenia);
• fatigue;
• general feeling of discomfort or anxiety (malaise);
• life-threatening damage to multiple organs;
• overall deterioration of physical condition;
• skin changes and irritation at the injection or infusion site;
• chest pain;
• swelling;
• inflammation of the mucous membranes of the body cavities (mucositis);
• flu-like symptoms such as headache, fever, chills, joint and muscle pain, weakness, fatigue.

Reporting side effects

If you experience any side effects, including any side effects not listed in this leaflet, you should tell your doctor or nurse. Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
tel.: +48 22 49 21 301
Website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder.
By reporting side effects, you can help gather more information on the safety of the medicine.

5. How to store HOLOXAN medicine

Since HOLOXAN medicine is usually administered in a hospital, it will be stored safely and properly by medical personnel. If necessary, storage conditions are given below.

• The medicine should be stored out of sight and reach of children.
• Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the given month.

Store at a temperature below 25°C.
Store in the original packaging.

6. Contents of the packaging and other information

What HOLOXAN medicine contains

The active substance of HOLOXAN medicine is ifosfamide. Each vial contains 1 g or 2 g of ifosfamide.
HOLOXAN medicine does not contain any other ingredients.

What HOLOXAN medicine looks like and what the packaging contains

HOLOXAN medicine is a dry, white powder and is supplied in vials made of colorless glass. The packaging contains 1 vial or 10 vials.
The contents of each vial should be mixed with water for injection before use.

Marketing authorization holder and manufacturer

Marketing authorization holder

Baxter Polska Sp. z o.o.
ul. Kruczkowskiego 8
00-380 Warsaw

Manufacturer

Baxter Oncology GmbH
Kantstrasse 2
D-33790 Halle, Germany
Date of last update of the leaflet:03.03.2023
Baxter, Holoxan, and Uromitexan are trademarks of Baxter International Inc.
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Information intended only for healthcare professionals

Preparation of the solution for infusion:

When handling the HOLOXAN medicine solution, you should follow the general guidelines for the safe handling of cytostatics.
Any unused product or waste materials should be disposed of in accordance with local regulations.
For administration as an infusion, it is recommended to dilute the prepared solution of HOLOXAN medicine with 5% glucose solution, 0.9% sodium chloride solution, or Ringer's solution. The following guidelines can be used: HOLOXAN medicine for short intravenous infusions (about 30-60 minutes)
is prepared by diluting to a final volume of 250 ml, and for longer infusions (1 to 2 hours) to 500 ml. For the preparation of a solution for continuous 24-hour infusions of high doses of HOLOXAN medicine, e.g., 5 g/m², the prepared solution should be diluted to 3 liters of 5% glucose solution and/or sodium chloride solution.
It has been shown that the solution obtained after dissolving the powder, as well as after diluting the prepared solution, retains chemical and physical stability for 48 hours at 25°C.
From a microbiological point of view, it is recommended that the diluted solutions be used immediately after preparation. Otherwise, the person administering the medicine is responsible for the shelf life and storage conditions, but the solution should not be stored for more than 24 hours at 2°C to 8°C.

Dosage and administration

HOLOXAN medicine should only be administered by doctors with experience in its use.
Dosage must be determined individually for each patient. Doses, duration of treatment, and (or) breaks in treatment depend on the therapeutic indication, combined therapy scheme,
overall health of the patient, and kidney and liver function, as well as laboratory test results.
The concentration of ifosfamide in the ready-to-use solution should not exceed 4%.
Fractionated administration:
1.2 – 2.4 g/m² body surface area (30 to 60 mg/kg body weight) per day for 5 consecutive days.
The total dose administered in the entire cycle is 6 – 12 g/m² body surface area (150 to 300 mg/kg body weight). Administration as a short intravenous infusion over a period of about 30 to 120 minutes,
depending on the infusion volume.
Continuous infusion
5 g/m² body surface area (125 mg/kg body weight), administered as a continuous 24-hour infusion.
The maximum dose in one treatment cycle should not exceed 8 g/m² body surface area
(200 mg/kg body weight). Compared to fractionated doses, a single high dose may cause more severe hematological, urological, nephrological, and central neurotoxicity.
Guidelines for dose reduction in case of bone marrow suppression

Note:
The above dosage recommendations apply to ifosfamide monotherapy. In the case of combined therapy with other cytostatics, the relevant treatment scheme should be followed.