Endoxan

Leaflet attached to the packaging: patient information

Endoxan, 50 mg, effervescent tablets

You should read the contents of the leaflet before taking 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 questions.
• 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 as yours.
• If any of the side effects get worse, or if you notice any side effects not listed in this 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 strong medicine that destroys cancer cells, but it also attacks healthy
body cells. 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 on you and treat the side effects as much as possible.
Endoxan

• may reduce 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.
• like 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
taking 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 taking Endoxan
• 3. How to take 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, in other words, an anticancer medicine. Its action
involves 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. Sometimes, doctors may 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 taking Endoxan

When not to take Endoxan

• if you are allergic to Endoxan (cyclophosphamide) or any of the other ingredients of this medicine. An allergic reaction can be recognized by symptoms such as: shortness of breath, wheezing, rash, itching, or swelling of the face and lips;
• if you have bone marrow disorders (especially if you have previously undergone chemotherapy or radiotherapy). 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 an infection;
• if you have ever had kidney or bladder problems due to previous chemotherapy or radiotherapy;
• if you have limited ability to urinate (difficulty urinating).

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. Your doctor will check the condition of your liver and kidneys 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 occurs 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 in the past, the period of normalization of blood cell count may take a little longer.
• When the number of blood cells decreases, you may be more prone 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 ill 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 gum health, as ulcers and mouth infections can occur. If you are unsure, you should ask your doctor.
• Cyclophosphamide may damage the tissue lining the bladder, causing bleeding in the urine and pain while urinating. Your doctor is aware that this may happen and will give you a medicine called mesna, which protects the bladder.
• 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 leaflet prepared for the injection and tablets.
• In most people taking cyclophosphamide with mesna, there are no problems with the bladder, 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 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 developing bladder cancer.
• Cyclophosphamide may damage the heart or affect the 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 function.
• 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 may occur, leading to thinning or baldness. Your 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 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 illnesses)
• 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 smoking cessation)
• 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 if you 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 have children 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 operating machinery

Some side effects of cyclophosphamide may affect your ability to drive or operate machinery. 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, for any reason, you should inform the medical staff that you are taking cyclophosphamide. You should not take any other medicines before informing your doctor that you are taking cyclophosphamide.

3. How to take Endoxan

Taking the medicine

• Cyclophosphamide effervescent tablets are taken orally. You should not suck on an effervescent tablet.
• If you are also taking mesna, your doctor will tell you how much fluid to drink. You should swallow the effervescent tablet with a sufficient amount of fluid to make it easy to swallow.
• 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 how long you should take it.
• 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.
• The dose of the medicine is usually between 100 mg (2 effervescent tablets) and 300 mg (6 effervescent tablets) per day. You can take all the effervescent tablets prescribed for the day at once, but you should try to take them at the same time every day, preferably in the morning. If you have any doubts about taking the medicine, you should consult your doctor or pharmacist.

Cyclophosphamide is usually taken for several days in a row as one course, followed by a break (a period without taking effervescent tablets) before starting the next course.
Sometimes it is necessary to take a different number of effervescent tablets every other day, for example, three effervescent tablets one day and four effervescent tablets the next day.
Your doctor may decide to change the dose of the medicine and closely monitor you if:

• you have liver or kidney problems
• you are elderly

Missing a dose of Endoxan

If you forget to take cyclophosphamide:

• You should do so as soon as possible, if you remember to take the effervescent tablets on the same day. If you miss a whole daily dose, you should contact your doctor.
• You should never take more effervescent tablets on a given day than prescribed- i.e., you should never take a double dose of effervescent tablets on one day to make up for a missed dose.

Taking more than the recommended dose of Endoxan

In case of overdose or accidental ingestion of any of your effervescent tablets by a child, you should immediately contact your doctor or the emergency department of your local hospital. Specialized treatment may be necessary.

4. Possible side effects

Like all medicines, Endoxan can cause side effects, although not everybody gets them.
The following side effects may occur when taking this medicine:

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 injury, or bleeding gums. This may be a sign of a low platelet count;
• a decrease in the number of white blood cells, which your doctor will monitor during treatment. This will not cause any visible symptoms, but you will be more prone 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 take antibiotics to fight the infection, because your blood cell count is lower than usual;
• obvious pallor, lethargy, fatigue. These may be signs of a low red blood cell count (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 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;
• mouth ulcers, including ulcers in the mouth;
• severe abdominal and back pain (pancreatitis).

Skin and hair

• hair loss. You may notice increased hair loss when combing or washing your hair, 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 red blood cell count. Your 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 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 elevated 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 of cyclophosphamide, which will be visible to your doctor on an ECG (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 in the body);
• high blood sugar levels (thirst, easy fatigue, irritability);
• low blood sugar levels (confusion, increased sweating);
• enlarged red blood cells.

There may also be changes in the results of some blood tests:

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

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

Reporting side effects

If you experience any side effects, including those not listed in this 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

• Keep out of the reach and sight of 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 that month.
• Store below 25°C. Store in the original packaging.

Medicines should not be disposed of via wastewater or household waste. You should ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the packaging and other information

What Endoxan contains

The active substance of the medicine is cyclophosphamide, and each effervescent tablet contains 50 mg of cyclophosphamide.
Other ingredients of the effervescent tablet core are: cornstarch, lactose monohydrate, calcium phosphate dihydrate, talc, magnesium stearate, gelatin, glycerol.
The coating contains: sucrose, talc, titanium dioxide, calcium carbonate, polyethylene glycol 35,000, silicon dioxide, povidone 25, sodium carboxymethylcellulose, polysorbate 20, wax (Montan glycol wax).

What Endoxan looks like and contents of the pack

Endoxan is a white, round effervescent tablet with a white core. Each blister pack contains 10 effervescent tablets, and each carton contains 5 blister packs.

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