Endoxan

Leaflet accompanying the packaging: patient information

Endoxan, 200 mg, 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 powerful medicine that destroys cancer cells, but it also attacks healthy
cells in the body. Therefore, Endoxan can cause many serious side effects.
The doctor has decided to prescribe this medicine because the cancer poses a greater threat to the patient than the potential side effects of the medicine. The doctor will perform regular check-ups on the patient and treat the side effects as much as possible.
Endoxan

• will reduce the number of blood cells, which can cause fatigue and a tendency to infections.
• may affect kidney and bladder function. The doctor may prescribe another medicine, Uromitexan (containing mesna), to prevent bladder damage. If blood is found in the urine, 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 treatment. The medicine can also cause nausea or vomiting. The doctor will advise the patient and prescribe appropriate medicines to alleviate these symptoms. Men and women should not conceive children during cyclophosphamide treatment or for at least 6 months after treatment. Patients 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 the patient.

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
involves destroying cancer cells (also known as "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 for the treatment of other diseases unrelated to cancer; in such cases, the doctor will inform the patient of the reason for prescribing this medicine.

2. Important information before using Endoxan

When not to use Endoxan

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

You should inform your doctor if:

• you are currently or have recently been treated with radiotherapy or chemotherapy;
• you have diabetes;
• you have liver or kidney problems. The doctor will check the 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 21-28 days. If the patient has 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, the patient may be more prone to infections. They should avoid close contact with people who have a cough, are cold or have other infections. The doctor will initiate appropriate treatment if they think the patient is ill or at risk of infection.
• Before starting cyclophosphamide and during treatment, the doctor will check if the number of red blood cells, white blood cells, and platelets is sufficient. It may be necessary to reduce the dose of the medicine or delay the administration of 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 gum health, 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 when urinating. The doctor is aware that this may happen and will prescribe mesna, which protects the bladder, if necessary.
• Mesna can be given either as a short injection or added to the cyclophosphamide drip or given as tablets.
• More information about mesna can be found in the patient information leaflet for the injection and tablets.
• Most people taking cyclophosphamide with mesna do not have any problems with their bladder, but the doctor may decide to perform a urine test to check for blood using a dipstick or microscope.
• If blood is found in the urine, you should inform your doctor immediately, as it may be necessary to stop cyclophosphamide treatment.
• Anticancer medicines and radiotherapy can increase the risk of developing other cancers; this may happen even after several years after treatment. Cyclophosphamide increases the risk of tumors in the bladder.
• Cyclophosphamide may damage the heart or affect the heart rhythm. This is more likely to happen with high doses of cyclophosphamide, if the patient is being treated with radiotherapy or other chemotherapy medicines, or in elderly patients. During treatment, the doctor will closely monitor the heart.
• Cyclophosphamide may cause infection or scarring of the lungs. This may happen more than 6 months after treatment. If you experience difficulty breathing, you should inform your doctor immediately.
• Cyclophosphamide may have a life-threatening effect on the liver.
• If you experience sudden weight gain, liver pain, and jaundice, you should inform your doctor immediately.
• Hair loss leading to thinning or baldness may occur. Hair will start to grow back normally, although it may have a different texture or color.
• Cyclophosphamide may cause nausea and vomiting. This may last for about 24 hours after taking cyclophosphamide. You may need to take 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 the action of 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 inflammation)
• 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 inflammation)

Other medicines that interfere with the action of 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)
• succinylcholine (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 harm 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. You should ask your doctor for advice.
• Cyclophosphamide may affect the 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 the ability to drive and use machines safely.
The doctor will decide whether the patient can perform these activities safely.

Procedure after visiting another doctor or hospital during treatment

If you visit another doctor or hospital during treatment, regardless of the reason, you should inform the medical staff about the medicines you are taking. You should not take other medicines before informing your doctor about taking cyclophosphamide.

3. How to use Endoxan

Cyclophosphamide is administered by a doctor or nurse.

• Endoxan may be given as an infusion.
• Endoxan is administered from a large bag, in a slow drip infusion (drip) directly into a vein. The infusion can be given through a small needle inserted into the arm or hand. In some patients, a central catheter is inserted into the jugular vein, and Endoxan can be administered 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

• The doctor will decide on the dose needed for the individual patient and the duration of treatment.
• The dose of cyclophosphamide depends on:
• the type of disease;
• body size (height and weight);
• the patient's overall 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.
The doctor may decide to change the dose of the medicine and closely monitor the patient
if:

• the patient has liver or kidney problems
• the patient is 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 a doctor or the emergency department of your local hospital. Specialized treatment may be necessary.

4. Possible side effects

Endoxan is a very powerful anticancer medicine. Like all medicines, Endoxan can
cause side effects, although they may not occur in everyone.

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;
• the appearance of bruises that occur without impact or bleeding from the gums. This may be a sign of too low a blood count;
• a decrease in the number of white blood cells, which the doctor will monitor during treatment. This will not cause any visible symptoms, but the patient will be more prone to infections. If an infection is suspected (high temperature, feeling cold and shivering or feeling hot and sweating or any sign of infection such as cough or burning pain when urinating), the patient may need to take antibiotics to fight the infection, as the blood count is lower than usual;
• severe pallor, lethargy, fatigue. These may be signs of a low number of red blood cells (anemia). Usually, no treatment is needed, as the body will eventually produce red blood cells again. If the anemia is severe, a blood transfusion may be necessary;
• blood in the urine, pain, or decreased urine output.

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 may last for about 24 hours after taking cyclophosphamide. You may need to take medicines to prevent nausea and vomiting. You should ask your doctor about this;
• inflammation of the mucous membrane of the mouth, 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;
• pallor (anemia), caused by a low number of red blood cells. The doctor will monitor this during treatment;
• increased tendency to bruise, caused by slow blood clotting;
• changes in nail and skin color.

Urinary system

• a burning sensation or pain when urinating;
• scarring and contraction 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 elevated temperature;
• scarring of the lungs, causing shortness of breath.

Heart and circulation

• rapid heartbeat, heart attack;
• changes in heart rhythm and function at higher doses, which will be visible to the 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 tumors (sometimes in the bladder);
• bloating and swelling (water retention in the body);
• 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 those not listed in the leaflet, you should consult your doctor or nurse.

Reporting side effects

If you experience any side effects, including those not listed in the leaflet, you should tell your doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Monitoring of Adverse Reactions to Medicinal Products of the Office for Registration 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 the 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:

• Store in a place inaccessible and invisible to children.
• Do not use Endoxan after the expiry date stated on the label after: Expiry date. 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 Endoxan contains

The active substance of Endoxan is cyclophosphamide, and each vial contains 200 mg of this substance.
Endoxan does not contain any other substances.

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 or 10 vials.

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