Endoxan

Leaflet attached to the packaging: patient information

Endoxan, 1 g, powder for solution for injection

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

important for the patient.

• You should keep this leaflet, so that you can read it again if you need to.
• You should consult a doctor or pharmacist if you have any further doubts.
• 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 any of the side effects get worse or if you notice any side effects not listed in the leaflet, you should tell your doctor or pharmacist.

Important information about Endoxan

Endoxan is prescribed to patients for the treatment of cancer.
Endoxan is a very potent medicine that destroys cancer cells, but it also attacks healthy cells in the body. Therefore, Endoxan can cause many serious side effects.
Your doctor has decided to prescribe this medicine because the cancer poses a greater threat to you than the potential side effects of the medicine. Your doctor will perform regular check-ups and treat any side effects as much as possible.
Endoxan

• reduces the number of blood cells, which can cause fatigue and a tendency to infections.
• may affect kidney and bladder function. Your doctor may prescribe another medicine, Uromitexan (containing mesna), to prevent bladder damage. If blood is found in the urine, you should immediately inform your doctor.
• as with most anticancer medicines, you may lose your hair (from thinning to baldness), but your hair should grow back after treatment. The medicine can also cause nausea or vomiting. Your doctor will advise you and prescribe appropriate medicines to alleviate these symptoms. Men and women should not conceive children during treatment with cyclophosphamide or for at least 6 months after treatment. You should use effective contraception during this time. You should ask your doctor for advice.

You should read the rest of the leaflet.It contains important information about using Endoxan, which may be particularly important for you.

Table of contents of the leaflet:

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

1. What is Endoxan and what is it used for

Endoxan is a cytotoxic medicine or anticancer medicine. Its action consists in destroying cancer cells (which is called "chemotherapy").
Endoxan is used to treat many different types of cancer. It is often used in combination with other anticancer medicines or radiotherapy. Some doctors may sometimes prescribe this medicine to treat other diseases unrelated to cancer; in such cases, the doctor will inform you of the reason for prescribing this medicine.

2. Important information before using Endoxan

When not to use Endoxan

• if you are allergic to Endoxan (cyclophosphamide). An allergic reaction can be recognized by such symptoms as: shortness of breath, wheezing, rash, itching, or swelling of the face and lips;
• if you have bone marrow disorders (especially in patients who have undergone chemotherapy or radiotherapy previously). Your doctor will order blood tests to assess bone marrow function;
• if you have a urinary tract infection, manifested by pain while urinating (cystitis);
• if you have difficulty urinating (cystitis);
• if you have an infection;
• if you have ever had kidney or bladder problems due to previous chemotherapy or radiotherapy;
• if you have limited ability to urinate (urinary flow obstruction).

You should inform your doctor if:

• you are undergoing or have recently undergone radiotherapy or chemotherapy;
• you have diabetes;
• you have liver or kidney problems. Your doctor will check your liver and kidney function by performing a blood test;
• you have had your adrenal glands removed;
• you have heart problems or have undergone radiotherapy to the heart area;
• your general health is poor or you are weakened;
• you are elderly.

Warnings and precautions

• Cyclophosphamide may affect the blood and immune system.
• Blood cells are produced in the bone marrow. There are three types of blood cells:
• red blood cells, which carry oxygen throughout the body;
• white blood cells, which fight infections;
• platelets, which help blood to clot.
• After taking cyclophosphamide, the number of all three types of blood cells will decrease. This is an unavoidable effect of cyclophosphamide. The lowest number of blood cells is reached 5-10 days after starting cyclophosphamide and lasts until a few days after the end of the treatment cycle. In most people, the number of blood cells returns to normal within 21 to 28 days. If you have been treated with chemotherapy before, the period of normalization of blood cell count may take a little longer.
• When the number of blood cells decreases, you may be more susceptible to infections. You should avoid close contact with people who have a cough, are cold or have other infections. Your doctor will start appropriate treatment if they think you are sick or at risk of infection.
• Before starting cyclophosphamide and during treatment, your doctor will check if you have enough red blood cells, white blood cells, and platelets. It may be necessary to reduce the dose of the medicine or delay the next dose.
• Cyclophosphamide may affect wound healing. All cuts should be kept clean, dry, and observed to see if they are healing properly.
• It is essential to take care of your gums, as mouth ulcers and infections can occur. If in doubt, you should ask your doctor.
• Cyclophosphamide may damage the tissue lining the bladder, causing bleeding in the urine and pain while urinating. Your doctor knows this can happen and may give you a medicine called mesna, which protects the bladder. Mesna can be given as a short injection or added to the cyclophosphamide drip or given as tablets. More information about mesna can be found in the patient leaflet for the injection and tablets.
• In most people taking cyclophosphamide with mesna, no bladder problems occur, but your doctor may decide to perform a urine test for blood using a dipstick or microscope.
• If blood is found in the urine, you should immediately inform your doctor, as it may be necessary to stop cyclophosphamide treatment.
• Cancer medicines and radiotherapy can increase the risk of developing other cancers; this can happen even after a few years after treatment. Cyclophosphamide increases the risk of developing bladder cancer.
• Cyclophosphamide may damage the heart or affect heart rhythm. This is more likely to happen with high doses of cyclophosphamide, if you are being treated with radiotherapy or other chemotherapy medicines, or if you are elderly. During treatment, your doctor will closely monitor your heart.
• Cyclophosphamide may cause infection or scarring of the lungs. This can happen more than 6 months after treatment. If you experience breathing difficulties, you should immediately inform your doctor.
• Cyclophosphamide can have a life-threatening effect on the liver.
• If you suddenly gain weight, experience liver pain, and jaundice, you should immediately inform your doctor.
• Hair loss leading to thinning or baldness may occur. Your hair will start to grow back normally, although it may have a different texture or color.
• Cyclophosphamide can cause nausea and vomiting. This can last for about 24 hours after taking cyclophosphamide. You may need to be given medicines to prevent nausea and vomiting. You should ask your doctor about this.

Other medicines and Endoxan

You should tell your doctor or nurse about all medicines you are currently taking or have recently taken, including those available without a prescription. You should inform your doctor or nurse especially about taking the following medicines or treatments, as they may interfere with cyclophosphamide:

• medicines that reduce the effectiveness of cyclophosphamide:
• aprepitant (used to prevent vomiting)
• bupropion (an antidepressant)
• busulfan, tiotepa (used to treat cancer)
• ciprofloxacin, chloramphenicol (used to treat bacterial infections)
• fluconazole, itraconazole (used to treat fungal infections)
• prasugrel (used to thin the blood)
• sulfonamides, such as sulfadiazine, sulfasalazine, sulfamethoxazole (used to treat bacterial infections)
• medicines that increase the toxicity of cyclophosphamide:
• allopurinol (used to treat gout)
• azathioprine (used to reduce immune system activity)
• chloral hydrate (used to treat insomnia)
• cimetidine (used to treat stomach acid)
• disulfiram (used to treat alcoholism)
• aldehyde glyceryl (used to treat warts)
• protease inhibitors (used to treat viral infections)
• ondansetron (used to prevent vomiting)
• medicines that increase liver enzyme activity, such as:
• rifampicin (used to treat bacterial infections)
• carbamazepine, phenobarbital, phenytoin (used to treat epilepsy)
• St. John's Wort (a herbal preparation for mild depression)
• corticosteroids (used to treat inflammatory conditions)
• medicines that increase the toxic effect on blood cells and the immune system
• ACE inhibitors (used to treat high blood pressure)
• natalizumab (used to treat multiple sclerosis)
• paclitaxel (used to treat cancer)
• thiazide diuretics such as hydrochlorothiazide or chlorthalidone (used to treat high blood pressure or water retention)
• zidovudine (used to treat viral infections)
• clozapine (used to treat symptoms of certain mental disorders)
• medicines that increase the toxic effect on the heart
• anthracycline antibiotics, such as bleomycin, doxorubicin, epirubicin, mitomycin (used to treat cancer)
• cytarabine, pentostatin, trastuzumab (used to treat cancer)
• radiotherapy to the heart area
• medicines that increase 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 increase the toxic effect on the kidneys
• amphotericin B (used to treat bacterial infections)
• indomethacin (used to treat pain and inflammatory conditions)

Other medicines that interfere with cyclophosphamide or whose action is interfered with by cyclophosphamide

• etanercept (used to treat rheumatoid arthritis)
• metronidazole (used to treat bacterial and protozoal infections)
• tamoxifen (used to treat breast cancer)
• bupropion (used as an aid to stop smoking)
• coumarins such as warfarin (used to thin the blood)
• cyclosporin (used to reduce immune system activity)
• suxamethonium (used to relax muscles during medical procedures)
• digoxin, β-acetyldigoxin (used to treat heart conditions)
• vaccines
• verapamil (used to treat high blood pressure, angina, or heart rhythm disorders)

Endoxan with food and drink

Alcohol may increase the nausea and vomiting caused by cyclophosphamide.

Pregnancy, breastfeeding, and contraception

You should not become pregnant while taking cyclophosphamide. It may cause miscarriages or damage to the fetus. If you are pregnant or think you may be pregnant or plan to become pregnant, you should inform your doctor.

• Men and women should not try to conceive a child during treatment or for at least 6 to 12 months after treatment. You should use effective contraception during this time. You should ask your doctor for advice.
• Cyclophosphamide may affect your ability to conceive in the future. You should discuss with your doctor the possibility of freezing sperm or eggs before starting treatment. You should not breastfeed while taking cyclophosphamide. You should ask your doctor for advice.

Driving and using machines

Some side effects of cyclophosphamide may affect your ability to drive or use machines safely. Your doctor will decide whether you can perform these activities safely.

What to do if you need to see another doctor or go to hospital during treatment

If you need to see another doctor or go to hospital during treatment, regardless of the reason, you should inform the medical staff that you are taking cyclophosphamide. You should not take any other medicines before telling your doctor that you are taking cyclophosphamide.

3. How to use Endoxan

Cyclophosphamide is given by a doctor or nurse.

• Endoxan can be given as an infusion.
• Endoxan is given from a large bag, in a slow drip infusion directly into a vein. The infusion can be given through a small needle inserted into your arm or hand. In some patients, a central catheter is inserted into the jugular vein, and Endoxan can be given through this catheter. The infusion usually lasts from a few minutes to an hour, depending on the dose.
• Cyclophosphamide is often given with other anticancer medicines or in combination with radiotherapy.

Usual dose

• Your doctor will decide on the dose needed for you and the duration of treatment.
• The dose of cyclophosphamide depends on:
• the type of disease;
• body size (height and weight);
• your general health;
• the use of other anticancer medicines or radiotherapy.

Cyclophosphamide is usually given as a series of treatments. After each treatment cycle, there is a break (a period without cyclophosphamide) before the next cycle.
Your doctor may consider it necessary to change the dose of the medicine and closely monitor you if:

• you have liver or kidney problems
• you are elderly

Taking a higher dose of Endoxan than recommended

In case of overdose or accidental ingestion of any patient's tablets, you should immediately contact your doctor or the emergency department of your local hospital. Specialized treatment may be necessary.

4. Possible side effects

Endoxan is a very potent anticancer medicine. Like all medicines, Endoxan can cause side effects, although not everybody gets them.

If you experience any of the following serious side effects, you should immediately inform your doctor:

• allergic reactions, whose symptoms are shortness of breath, wheezing, rash, itching, or swelling of the face and lips;
• bruises that appear without being hit or bleeding from the gums. This may be a sign of too few platelets in the blood;
• reduced number of white blood cells, your doctor will monitor this during treatment. It will not cause any visible symptoms, but you will be more susceptible to infections. If you suspect an infection (high temperature, feeling cold and shivering or feeling hot and sweating or any sign of infection such as cough or burning pain while urinating), you may need to be given antibiotics to fight the infection, as your blood cell count is lower than usual;
• paleness, lethargy, fatigue. These may be signs of a low number of red blood cells (anemia). Usually, no treatment is needed, as your body will eventually produce red blood cells again. If the anemia is severe, you may need a blood transfusion;
• blood in the urine, pain, or decreased amount of urine.

Other possible side effects that may occur:

Immune system

• allergic reactions, whose symptoms are shortness of breath, wheezing, rash, itching, or swelling of the face and lips.

Digestive system

• nausea and vomiting. These can last for about 24 hours after taking cyclophosphamide. You may need to be given medicines to prevent nausea and vomiting. You should ask your doctor about this;
• mouth ulcers, including ulcers;
• severe abdominal and back pain (pancreatitis).

Skin and hair

• hair loss. You may notice a slight increase in hair loss when combing or washing, or you may lose most or all of your hair. The degree of hair loss depends on the dose of cyclophosphamide, hair density, and the use of other anticancer medicines. When cyclophosphamide is used in combination with other anticancer medicines, the likelihood of hair loss increases significantly compared to using cyclophosphamide alone;
• yellowing of the skin or whites of the eyes (jaundice), caused by liver problems;
• paleness (anemia), caused by a low number of red blood cells. Your doctor will monitor this during treatment;
• increased tendency to bruise, caused by slow blood clotting;
• changes in nail and skin color.

Urinary system

• burning or pain while urinating;
• scarring and shrinkage of the bladder (pain and frequent need to urinate);
• blood cancer (leukemia);
• kidney problems, including kidney failure.

Chest

• shortness of breath;
• pneumonia, causing shortness of breath, cough, and high temperature;
• scarring of the lungs, causing shortness of breath.

Heart and circulation

• rapid heartbeat, heart attack;
• changes in heart rhythm and function with high doses, which will be visible to your doctor on an EKG (electrocardiogram).

Reproductive system

• absence of sperm in the semen (in some cases irreversible);
• increased menstrual bleeding in women;
• absence of menstruation (in some cases irreversible).

General

• weakness;
• loss of appetite;
• secondary cancers (sometimes in the bladder);
• bloating and swelling (water retention);
• high blood sugar levels (thirst, easy fatigue, irritability);
• low blood sugar levels (confusion, increased sweating);
• enlarged red blood cells.

Changes in the results of some blood tests may also occur:

• increased levels of certain chemicals called enzymes;
• low sodium levels in the blood.

If you experience any side effects, including any not listed in the leaflet, you should consult your doctor or nurse.

Reporting side effects

If you experience any side effects, including any not listed in the leaflet, you should tell your doctor, pharmacist, 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
PL 02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
e-mail: ndl@urpl.gov.pl
Side effects can also be reported to the marketing authorization holder.
By reporting side effects, you can help provide more information on the safety of this medicine.

• 5.

How to store Endoxan

Since Endoxan is usually administered in a hospital, it is stored safely and properly by hospital staff. The storage conditions are as follows:

• Keep out of the reach and sight of children.
• Do not use Endoxan after the expiry date stated on the label after: EXP. The expiry date refers to the last day of the given month.
• Store below 25°C. Store in the original packaging.

6. Contents of the packaging and other information

What Endoxan contains

The active substance of Endoxan is cyclophosphamide, and each vial contains 1 g of this substance.
Endoxan does not contain any other ingredients.

What Endoxan looks like and what the pack contains

Endoxan is a dry, white powder and is supplied in clear, colorless glass vials. Each carton contains 1 vial.

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 revision of the leaflet: 28.03.2016