powder for solution for injection or infusion.
ifosfamide

Read all of this leaflet carefully before you start using this medicine. It contains information that is important to you.

  • Save this information, you may need to read it again.
  • If you have any further questions, ask your doctor, pharmacist or nurse.
  • This medicine has been prescribed for you only. Do not give it to others. It can harm them, even if they show signs of illness similar to yours.
  • If you get any side effects , talk to your doctor, pharmacist or nurse. This also applies to any side effects not mentioned in this information. See section 4.

In this leaflet you will find information about:
1. What Holoxan is and what it is used for
2. What you need to know before using Holoxan
3. How to use Holoxan
4. Possible side effects
5. How to store Holoxan
6. Contents of the packaging and other information

1. What Holoxan is and what it is used for

Holoxan is a cancer drug that damages the genetic material in the cancer cells so that the cells’ growth and division are hindered.

Holoxan is used in various types of cancer.

2. What you need to know before using Holoxan

Do not use Holoxan

  • If you have had an allergic reaction to ifosfamide. An allergic reaction may have symptoms such as difficulty breathing, wheezing, itching or swelling of the face and lips.
  • If your bone marrow is not working properly (especially if you have previously been treated with chemotherapy and / or radiation therapy). Your blood will be tested to check your bone marrow function.
  • If you have severe renal impairment and / or urinary tract obstruction or have a urinary tract infection ( cystitis ), which may manifest as pain / burning when urinating.
  • If you have an ongoing infection is.
  • If you have daughter tumors ( metastasize ) in the brain.
  • If you are breast-feeding, breast-feeding should be discontinued during treatment with Holoxan.

Warnings and cautions

Talk to your doctor, pharmacist, or nurse before using Holoxan:

  • If you see blood in your urine, contact a doctor immediately.
  • If you have diabetes .
  • If you are receiving or have recently received radiation therapy and chemotherapy .
  • If you have heart problems or have received radiation therapy to the heart area.
  • Holoxan can sometimes affect brain function. In case of signs of this, eg abnormal fatigue, severe headache, confusion and / or changed reality experience, a doctor should be contacted immediately.
  • As Holoxan weakens the immune system, caution should be exercised when vaccinating with live vaccine. Therefore, consult your doctor before any vaccination.
  • If you have impaired kidney or liver function, bone marrow damage or heart disease, it is important that you tell your doctor before starting treatment. Dose selection should therefore be made with caution to take these factors into account.
  • If you are planning to become pregnant (see section “Pregnancy, breast-feeding and fertility”).

Effects on the blood and immune system

Holoxan can affect the blood and the immune system.

  • The blood cells are produced in the bone marrow . There are three types: red blood cells, which carry oxygen around the body, white blood cells that fight infection and platelets , which cause the blood to clot.
  • After taking Holoxan, the number of all three types of blood cells will decrease. This is an inevitable side effect of Holoxan. The number of blood cells will reach its lowest level about 8-10 days after you start taking Holoxan, and will remain low until a few days after the end of the treatment. Most people achieve a normal number of blood cells within 21-28 days. If you have received a lot of chemotherapy before, it may take longer to reach a normal level.
  • You may be more likely to get an infection as your blood cell count decreases. Try to avoid close contact with people who cough, have a cold or have other infections .
  • Your doctor will check if your blood cell count is high enough before and during treatment with Holoxan.

Effects on the bladder

  • Holoxan can damage the inner walls of the bladder and cause bleeding. Your doctor knows that this can happen, and if necessary you will be given a medicine called Uromitexan (mesna) which protects the bladder.
  • Uromitexane (mesna) can be given as an injection , mixed with the intravenous solution or as tablets.
  • Most people who receive Holoxan together with Uromitexan (mesna) do not experience any problems with the bladder, but your doctor may want to test your urine for any blood content by using a urine stick or microscope.

Impact of wound healing

  • Holoxan can affect wound healing. Keep wounds clean and dry and check that they heal normally.

Impact on kidneys

  • Holoxan can damage your kidneys so that they do not work properly. This is more likely to happen if you have only one kidney or if your kidneys are already damaged. This is often temporary and the kidneys return to normal function as soon as Holoxan treatment is stopped. Sometimes the damage is more permanent and more serious. Your doctor will check your test results if there are signs of kidney damage.

Impact on the liver

  • Holoxan can have life-threatening effects on your liver. If you suddenly gain weight, experience liver pain or jaundice, tell your doctor immediately.

Impact on lungs

  • Holoxan can cause inflammation or scarring of your lungs. It may occur more than 6 months after your treatment. If you have difficulty breathing, tell your doctor immediately.

Impact on the heart

  • Holoxan can damage your heart or affect its rhythm. This risk increases with a higher dose of Holoxan, if you are being treated with radiation therapy or other anticancer medicines or if you are older.

Other cancer drugs or radiation therapy can increase the risk of you developing other cancers, this can happen several years after the end of treatment.

Other drugs and Holoxan

Tell your doctor or pharmacist if you have recently taken or might take any other medicines.

When Holoxan is used at the same time as other medicines, the effect can affect or be affected by the other medicine/medicines, which increases the risk of side effects and other unwanted effects. Examples of drugs that affect or are affected by Holoxan are:

  • Some medicines for diabetes (eg glibenclamide, glipizide, glimepiride). Holoxan may increase the blood sugar lowering effect.
  • Blood thinners ( warfarin ), Holoxan may increase the blood thinning effect and control of blood clotting ability must therefore be done frequently.
  • Some muscle relaxants (suxamethone) given during surgery may have a stronger effect than expected.
  • Some medicines for gout (allopurinol).
  • Tamoxifen, used in hormone therapy for breast cancer.
  • Some medicines for high blood pressure ( hydrochlorothiazide , ACE inhibitors ).
  • Some medicines for infection (clarithromycin, erythromycin).
  • Some medicines for HIV , also known as protease inhibitors (indinavir, ritonavir).
  • Some other cytostatics (cisplatin, carboplatin, docetaxel, busulfan, anthracyclines , irinotecan).
  • Some medicines for nausea in chemotherapy (aprepiant).
  • Certain antibiotics ( aminoglycosides and amphotericin B).
  • Some medicines for herpes infections (aciclovir).
  • Some medicines for epilepsy (phenobarbital, phenytoin , carbamazepine).
  • Some sedatives and hypnotics (so-called benzodiazepines ).
  • Some medicines for tuberculosis (rifampicin).
  • Some medicines for heart problems ( amiodarone ).
  • Drugs belonging to the group of corticosteroids (used to treat inflammation ).
  • Some medicines for multiple sclerosis (natalizumab).
  • Some medicines for fungal infections ( ketoconazole , fluconazole , itraconazole).
  • Some drugs that increase the number of white blood cells ( G-CSF , GM- CSF ).
  • Some medicines for alcohol abuse ( disulfiram ).
  • Some medicines for smoking cessation or for depression (bupropion).
  • Medicines for mild depression such as St. John’s wort also called hypericum  perforatum .
  • Radiation of the heart and bladder.

If you get a side effect that causes a disturbance of brain function ( encephalopathy ), the use of drugs that affect the central nervous system should be used with special caution or if possible discontinued. Examples of such drugs are:

  • antiemetic drugs (antiemetics)
  • medicines for allergic symptoms ( antihistamines )
  • sedatives
  • drug-classified drugs.

If you are going to be vaccinated, you must inform them that you are being treated with Holoxan because in some cases the vaccination may have a worsening effect and in some cases, the vaccination can cause an infection.

Holoxan with alcohol

The risk of nausea and vomiting may increase with alcohol consumption.

Pregnancy, breastfeeding and fertility

You should not get pregnant while receiving Holoxan. This is because it can cause miscarriage or harm the fetus. Tell your doctor if you are pregnant, suspect you may be pregnant, or are planning to have a baby. Neither men nor women should try to have children during or up to 6 months after the end of treatment. Use an effective contraceptive. Ask your doctor for advice.

  • Holoxan may affect your ability to have children. Talk to your doctor about the possibility of freezing semen or eggs before starting treatment.
  • Holoxan passes into breast milk. It is possible that a breastfed baby may be affected. Therefore, do not use Holoxan during breast-feeding. Breast-feeding should be discontinued during treatment with Holoxan.

Driving and using machines

Certain side effects (eg seizures, uncontrolled twitching, and movement disorders, dizziness, blurred vision, visual impairment, nausea, or vomiting) may affect your ability to react. You should therefore avoid driving or using machines until you know how you react to Holoxan.

You are responsible for assessing whether you are fit to drive a motor vehicle or perform work that requires increased vigilance. One of the factors that can affect your ability in these respects is the use of drugs due to their effects and/or side effects.

Descriptions of these effects and side effects can be found in other sections. Read all the information in this leaflet for guidance. If you are not sure, talk to your doctor or pharmacist.

3. How to use Holoxan

Holoxan solution for injection/info should only be given by hospital staff.

  • Holoxan is normally added to a large bag of fluid and injected slowly ( infusion ) directly into a vein. The vein can be in your arm, on the back of your hand or in a large vein under your collarbone. Depending on the dose one, the infusion takes several hours but can also be given for several days.
  • Holoxan is usually given together with other anticancer medicines or radiation therapy.

Dose one is determined by the doctor, who adjusts it individually for you. Factors that determine the size of the dose are:

  • what disease you are being treated for
  • your height and weight
  • your general condition
  • if you are taking any other medicines for cancer or radiation therapy.

Holoxan is usually given as a series of cures. After each course, a break (a period without the addition of Holoxan) is taken before the next course.

If you take more Holoxan than you should

If you have ingested too much medicine or if, for example, a child has ingested the medicine by mistake, always contact a doctor, hospital, or Poison Information for risk assessment and advice. Because Holoxan is given to you by healthcare professionals, you are unlikely to ingest too much. Injection one will be stopped immediately if too much has been given.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Stop taking Holoxan and contact a doctor immediately if you get any of the following symptoms ( angioedema ):

  • swelling of the face, tongue or throat
  • difficulty swallowing
  • hives and difficulty breathing.

The above side effects have been reported with unknown frequency. The frequency cannot be calculated from the available data.

  • unexplained muscle pain, muscle cramps or muscle weakness.

The above side effects have been reported with a frequency of “Very rare”.

Seek medical attention immediately at:

  • symptoms that may indicate an effect on brain function, such as abnormal fatigue, severe headache, confusion, altered reality and / or hallucinations.
  • hypersensitivity reaction which can manifest itself as extensive skin rash, itching , swelling of the face, hives, shortness of breath.
  • pneumonia which may manifest itself as difficulty breathing and / or pain when inhaled.

Very common (may affect more than 1 user in 10):

  • Impaired bone marrow function, which can lead to a lack of white blood cells (susceptibility to infection), platelets (risk of bleeding) and anemia
  • Nausea / vomiting
  • Hair loss ( alopecia )
  • Toxic effects on the central nervous system
  • Disorder of brain function ( encephalopathy ). 10–20% of all treated patients experience symptoms within a few hours up to a few days after starting treatment
  • Inflammation of the bladder with blood in the urine (may be so small that it is not visible to the naked eye)
  • Fever.

Common (may affect up to 1 in 10 people): 

  • Infection is
  • Decreased pH in the blood caused by acidic residues from ex. fatty acids (metabolic acidosis )
  • Decreased appetite
  • Inflammation of blood vessels ( phlebitis )
  • Toxic effects on the liver that may lead to hepatic impairment or acute inflammation of the liver
  • Absence / reduction of sperm in the semen
  • Fatigue, malaise, general physical deterioration.

Uncommon (may affect up to 1 in 100 people):

  • Blood poisoning (symptoms may be high fever, affected general condition and increased respiratory rate) and severe drop in blood pressure due to severe infection ( septic shock )
  • Tumor disease / cancer disease caused by the treatment (such as blood cancer ( acute leukemia ), cancer of the supporting tissue ( sarcoma ), kidney cell carcinoma, lymph node cancer and myelodysplastic syndrome (bone marrow disease with disturbed formation of one or more types of blood cells )
  • Altered mental state which includes mania, increased forgetfulness, paranoia , acute state of confusion with hallucinations ( delirium ), panic attacks, altered muscle tension and impaired motor skills (catatonia)
  • Dizziness
  • Toxic effects on the heart
  • Cardiac arrhythmias ( arrhythmia ), heart failure
  • Low blood pressure
  • Diarrhea, constipation
  • Inflammation of the mouth ( stomatitis )
  • Elevated liver enzyme levels
  • Disturbed bladder emptying frequency including incontinence
  • Bladder irritation
  • Disturbed ovulation
  • Loss of menstruation.

Rare (may affect up to 1 in 1,000 people): 

  • Muscle cramps
  • Inflammation of the skin and mucous membranes
  • Skin rash of various kinds
  • Hypersensitivity s
  • Kidney disease (renal impairment), acute or chronic renal failure
  • Deviating value in urine analysis ( proteinuria , phosphaturia, amino aciduria)
  • Swelling due to decreased fluid secretion (SIADH) with decreased sodium content in the blood, dehydration and fluid retention
  • Disorders of blood salt balance (electrolyte disturbances)
  • Shortness of breath ( dyspnoea )
  • Cough
  • Difficulty controlling bowel movements
  • Dimsyn
  • Local reactions at the injection / infusion site.

Very rare (may affect up to 1 in 10,000 people):

  • Severe disorders of blood coagulation
  • Hemolytic uremic syndrome (complex symptom picture with, among other things, anemia , spotty bleeding in the skin and sometimes acute renal failure )
  • Severe hypersensitivity reaction ( anaphylactic reaction )
  • Nerve disease / disorder of nerve function ( polyneuropathy )
  • Seizures including epilepsy
  • Cardiac arrest, myocardial infarction
  • Renal impairment (fanconis syndrome)
  • Visual impairment
  • Fluid in the lungs, pulmonary fibrosis , impaired respiratory function, pneumonia (so-called interstitial pneumonitis )
  • Acute pancreatitis
  • Severe skin reactions with skin detachment ( toxic epidermal necrolysis ).

Has been reported (occurs in an unknown number of users):

  • Progression of underlying malignancy is
  • Toxic effects on the blood that can lead to red blood cell breakdown ( haemolytic anemia ) and skin bluishness (methemoglobin anemia ) and decreased blood cell count (pancytopenia)
  • Immunocompromised
  • Hives ( urticaria )
  • Abnormally high blood sugar (hyperglycemia)
  • Increased thirst ( polydipsia )
  • Rapid decay of tumor cells (tumor lysis syndrome)
  • Difficulty controlling or coordinating muscles you use when you speak ( dysarthria ), uncontrolled twitching (extrapyramidal disorder), movement disorders, gait disorders, nerve and hand nerves ( peripheral neuropathy )
  • Inflammation of the conjunctiva of the eye ( conjunctivitis ), eye irritation
  • Earrings, deafness, hearing loss
  • Fluid formation in the pericardium (pericardial effusion), effects / disease on the heart muscle, angina (chest pain), inflammation of the tissues in and around the heart ( myocarditis , pericarditis), changes in ECG , cardiogenic shock (a condition in which the heart can not supply the body with blood in sufficient quantity)
  • Pain
  • Blood clots in vessels and lungs, leakage of fluid from blood vessels (capillary leakage syndrome), inflammation of blood vessels ( vasculitis ), high blood pressure
  • Hot flashes
  • Acute Respiratory Syndrome (ARDS)
  • Lung impact with eg difficulty breathing
  • Inflammation of the intestine, bleeding in the gastrointestinal tract, intestinal upset, abdominal pain, increased salivation
  • Stop the bile ducts (cholestasis)
  • Blood clots in the liver, blockage in the small veins in the liver (veno-occlusive liver disease), liver failure, severe hepatitis ( fulminant hepatitis )
  • Severe mucosa – and skin inflammation with high fever ( Stevens-Johnson syndrome )
  • Intensified reaction to radiation therapy with aggravated skin damage
  • Skin and nail changes including small punctate skin haemorrhages ( petechiae )
  • Increased sweating ( hyperhidrosis )
  • Itching
  • Muscle and joint pain, growth retardation, pain in arms and legs
  • Morbidly large amounts of urine due to dysfunction of the pituitary gland ( diabetes insipidus ), production of abnormally large amount of urine ( polyuria ), feeling of not being able to empty the bladder completely, kidney inflammation (tubulointerstitial nephritis)
  • Inability to have children ( infertility ), menstruation ends prematurely (early menopause ), impaired ovarian function (ovarian failure)
  • Fetal growth inhibition
  • The function of two or more organs in the body is disturbed (multi-organ failure)
  • Freezing breaks.

Skin damage caused by radiation therapy may be exacerbated by medication with Holoxan.

After treatment with Holoxan, ovulation usually returns (in women who have not entered menopause) or sperm production is normalized in men.

In some cases, however, ovulation and sperm production are not normalized, which can result in permanent infertility.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist, or nurse. This also applies to any side effects not mentioned in this information. You can also report side effects directly to the Medical Products Agency. By reporting side effects, you can help increase drug safety information.

5. How to store Holoxan

Keep out of sight and reach of children.

Store below 25  ° C.

Do not use this medicine after the expiry date which is stated on the carton and bottle after EXP. dat. or EXP. The expiration date is the last day of the specified month.

The reconstituted solution should be used within 12 hours.

6. Contents of the packaging and other information

Content declaration

  • The active substance is ifosfamide. One vial contains ifosfamide 500 mg, 1000 mg and 2000 mg respectively.
  • Contains no excipients.

What the medicine looks like and contents of the pack

Powder for solution for injection or infusion.

White or almost white crystalline powder in a glass vial sealed with a bromobutyl rubber stopper and aluminum / plastic cap.

The bottles are packed with or without a protective plastic cover. The protective secondary package consists of two parts: the lower part is a transparent cylindrical polypropylene container and the upper part is a blue-colored screw cap made of polyethylene. The protective plastic cover does not come into contact with the medicine and provides extra transport protection, which increases the safety of medical and pharmaceutical personnel when handling the product.

Marketing Authorization Holder and Manufacturer

Marketing Authorisation Holder

Baxter Medical AB

Box 63

164 94 Kista

Manufacturer

Baxter Oncology GmbH

Kantstrasse 2

33790 Halle

Germany

Muhammad Nadeem

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