Endoxan

Patient Information Leaflet

Endoxan, 50 mg, coated tablets
Read the entire leaflet before using this medicine, as it contains important information for the patient.

• Keep this leaflet for future reference.
• Consult your doctor or pharmacist if you have any further questions.
• This medicine has been prescribed for a specific individual. Do not share it with others.
• This medicine may harm another person, even if their symptoms are similar.
• If any of the side effects worsen or if any side effects occur, including those not listed in this leaflet, inform your doctor or pharmacist immediately.

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 may cause many serious side effects.
Your doctor has decided to prescribe this medicine because the risk posed by the cancer is greater than the potential risks of side effects. Your doctor will perform regular check-ups and, whenever possible, treat any side effects that may occur.
Endoxan

• may reduce the number of blood cells, which can lead to fatigue and increased susceptibility to infections.
• may affect kidney and bladder function. Your doctor may prescribe another medicine, Uromitexan (containing mesna), to prevent bladder damage. If blood is noticed in the urine, inform your doctor immediately.
• like most anticancer medicines, may cause hair loss (ranging from thinning hair to complete baldness), although hair should regrow after treatment ends. The medicine may also cause nausea or vomiting. Your doctor will provide advice and prescribe appropriate medicines to help relieve these symptoms. Men and women should not father or conceive children during treatment with cyclophosphamide, or for at least 6 months after treatment ends. Patients should use effective contraception during this time. Please consult your doctor for advice.

Please read the remainder of this leaflet. It contains important information about the use of Endoxan that may be particularly relevant to the patient.
Leaflet Contents:

1. What Endoxan is and what it is used for
2. What you need to know before taking Endoxan
3. How to take Endoxan
4. Possible side effects
5. How to store Endoxan
6. Contents of the pack and other information

1. What Endoxan is and what it is used for

Endoxan is a cytotoxic medicine, also known as an anticancer medicine. It works by destroying cancer cells (a process known as "chemotherapy").
Endoxan is used in the treatment of many different types of cancer. It is often used in combination with other anticancer medicines or radiotherapy. Occasionally, some doctors may prescribe this medicine for the treatment of non-cancerous conditions; in such cases, your doctor will inform you why this medicine has been prescribed.

2. Important information before using Endoxan

When not to use Endoxan

• if the patient is allergic to Endoxan (cyclophosphamide) or any of the other ingredients of this medicine. Allergic reactions may include symptoms such as: shortness of breath, wheezing, rash, itching or swelling of the face and lips;
• if the patient has impaired bone marrow function (especially in patients previously treated with chemotherapy or radiotherapy). The doctor will order blood tests to assess bone marrow function;
• if the patient has a urinary tract infection, presenting with pain during urination (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 pass urine (urinary retention).

Please inform your doctor if:

• the patient is currently undergoing or has recently received radiotherapy or chemotherapy;
• the patient has diabetes;
• the patient has liver or kidney problems. The doctor will check liver and kidney function by blood tests;
• the patient has had adrenal glands removed;
• the patient has heart problems or has undergone radiotherapy to the chest area;
• the patient’s general health is poor or the patient is weakened;
• the patient is elderly.

Warnings and precautions

• Cyclophosphamide may affect blood and the 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 decreases. This is an unavoidable effect of cyclophosphamide. The lowest blood cell counts usually occur 5 to 10 days after starting cyclophosphamide and may last for several days after the end of a treatment cycle. In most people, blood cell counts return to normal within 21 to 28 days. However, if the patient has previously undergone multiple chemotherapy treatments, it may take longer for blood counts to normalize.
• When blood cell counts are low, the patient may be more susceptible to infections. Close contact with people who have coughs, colds, or other infections should be avoided. The doctor will initiate appropriate treatment if infection is suspected or develops.
• Before and during treatment with cyclophosphamide, the doctor will monitor whether the levels of red blood cells, white blood cells, and platelets are sufficiently high. It may be necessary to reduce the dose or delay the next dose.
• Cyclophosphamide may affect wound healing. All cuts and wounds should be kept clean, dry, and monitored for proper healing.
• It is important to maintain good oral hygiene, as mouth ulcers and infections may occur. Consult your doctor if in doubt.
• Cyclophosphamide may damage the lining of the bladder, causing bleeding in the urine and pain during urination. The doctor is aware of this risk and may prescribe mesna, which protects the bladder.
• Mesna may be administered either as a short injection, added to the cyclophosphamide infusion, or taken orally as tablets.
• More information about mesna can be found in the patient leaflet provided with mesna injections and tablets.
• Most patients receiving cyclophosphamide together with mesna do not experience bladder problems, but the doctor may decide to perform urine tests (dipstick or microscopic examination) to check for blood in the urine.
• If blood is detected in the urine, the doctor should be informed immediately, as treatment with cyclophosphamide may need to be discontinued.
• Anticancer drugs and radiotherapy may increase the risk of developing other cancers, which may occur years after treatment. Cyclophosphamide increases the risk of bladder cancer.
• Cyclophosphamide may damage the heart or affect heart rhythm. This risk is greater with high doses of cyclophosphamide, in patients receiving radiotherapy or other chemotherapy drugs, or in elderly patients. The doctor will closely monitor heart function during treatment.
• Cyclophosphamide may cause lung infection or scarring (pulmonary fibrosis). This may occur more than 6 months after treatment ends. If breathing difficulties occur, inform the doctor immediately.
• Cyclophosphamide may have life-threatening effects on the liver.
• If sudden weight gain, liver pain, or jaundice occurs, inform the doctor immediately.
• Hair loss may occur, leading to thinning or complete hair loss. Hair will regrow normally after treatment, although it may have a different texture or color.
• Cyclophosphamide may cause nausea and vomiting. This may last for about 24 hours after administration. The patient may require anti-nausea medication. Please consult your doctor.

Other medicines and Endoxan
Tell your doctor or nurse about all medicines you are currently taking or have recently taken, including those available without a prescription. Inform your doctor or nurse especially if you are taking or have received any of 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, thiotepa (used in cancer treatment)
• 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 suppress the immune system)
• chloral hydrate (used to treat insomnia)
• cimetidine (used to treat stomach acidity)
• disulfiram (used to treat alcoholism)
• glyceryl aldehyde (used to treat tetanus)
• 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 remedy for mild depression)
  • corticosteroids (used to treat inflammatory conditions)
• medicines that increase toxic effects on blood cells and the immune system:
  • angiotensin-converting enzyme (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 fluid retention)
  • zidovudine (used to treat viral infections)
  • clozapine (used to treat symptoms of certain psychiatric disorders)
• medicines that increase toxic effects on the heart:
  • anthracycline antibiotics, such as bleomycin, doxorubicin, epirubicin, mitomycin (used in cancer treatment)
  • cytarabine, pentostatin, trastuzumab (used in cancer treatment)
  • radiotherapy to the chest area
• medicines that increase toxic effects on the lungs:
  • amiodarone (used to treat heart rhythm disorders)
  • G-CSF, GM-CSF hormones (used to increase white blood cell counts after chemotherapy)
• medicines that increase toxic effects on the kidneys:
  • amphotericin B (used to treat fungal infections)
  • indomethacin (used to treat pain and inflammation)

Other medicines that interfere with cyclophosphamide or whose effects are altered 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 quit smoking)
• coumarins such as warfarin (used to thin the blood)
• cyclosporine (used to suppress the immune system)
• 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 worsen nausea and vomiting caused by cyclophosphamide.

Pregnancy, breastfeeding and contraception
Do not become pregnant while receiving cyclophosphamide. It may cause miscarriage or harm the unborn baby. If the patient is pregnant, suspects pregnancy, or plans to become pregnant, she must inform her doctor.

• Men and women should not attempt to conceive a child during treatment or for at least 6 to 12 months after treatment ends. Effective contraception methods should be used. Consult your doctor for advice.
• Cyclophosphamide may affect future fertility. Discuss with your doctor the possibility of sperm or egg freezing before starting treatment.
• Do not breastfeed while receiving cyclophosphamide. Consult your doctor for advice.

Driving and operating machinery
Some side effects of cyclophosphamide may affect the ability to drive or operate machinery safely. Your doctor will decide whether it is safe for the patient to perform these activities.

What to do when visiting another doctor or hospital during treatment
If you visit another doctor or hospital during treatment, regardless of the reason, inform the medical staff about all medicines you are taking. Do not take any other medicines without informing your doctor that you are receiving cyclophosphamide.

3. How to use Endoxan

Using the medicine

• Cyclophosphamide coated tablets should be taken orally. Do not suck the coated tablets.
• If the patient is also taking mesna, the doctor will advise how much fluid should be consumed. The coated tablet should be taken with a sufficient amount of liquid to allow easy swallowing.
• Cyclophosphamide is often administered together with other antineoplastic drugs or in combination with radiotherapy.

Typical dosage

• The doctor will determine the appropriate dose required 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 general health;
  • the use of other antineoplastic drugs or radiotherapy.
• The usual dose ranges from 100 mg (2 coated tablets) to 300 mg (6 coated tablets) per day. All daily tablets may be taken at once, but they should be taken at approximately the same time each day, preferably in the morning. In case of any doubts regarding the use of the medicine, consult the doctor or pharmacist.

Cyclophosphamide is usually taken for several consecutive days as one course of treatment, followed by
a break (a period without taking the coated tablets) before starting the next course.
Sometimes it may be necessary to take a varying number of coated tablets every other day, for example,
three coated tablets one day and four coated tablets the next day.
The doctor may consider it necessary to adjust the dose of the medicine and to closely monitor the patient if:

• the patient has liver or kidney problems;
• the patient is elderly.

Missed dose of Endoxan
If the patient forgets to take cyclophosphamide:

• The dose should be taken as soon as possible, provided the patient remembers on the same day. If the entire daily dose has been missed, the patient should contact the doctor.
• Never take more coated tablets in one day than prescribed – i.e., never take a double dose on the same day to make up for a missed dose.

Overdose of Endoxan
In case of overdose or accidental ingestion of any tablet by a child,
contact the doctor or the emergency department of the local hospital immediately.
Specialized treatment may be required.

4. Possible adverse reactions

Like all medicines, Endoxan may cause adverse reactions, although not everyone will experience them.
The following adverse reactions may occur when using this medicine:
If any of the following serious adverse reactions occur, contact your doctor immediately:

• allergic reactions, with symptoms such as shortness of breath, wheezing, rash, itching, or swelling of the face and lips;
• appearance of bruises without injury, or bleeding gums. This may be a sign indicating too low a platelet count;
• decreased number of white blood cells, which your doctor will monitor during treatment. This may not cause any visible symptoms, but the patient will be more susceptible to infections. If infection is suspected (high temperature, feeling cold with chills or feeling hot with sweating, or any sign of infection such as cough or burning pain during urination), the patient may require antibiotics to treat the infection, as the number of blood cells is lower than usual;
• marked paleness, lethargy, fatigue. These may be signs of low red blood cell count (anemia). Usually no treatment is required, as the body will eventually produce red blood cells again. If anemia is severe, blood transfusion may be necessary;
• blood in the urine, pain or reduced amount of urine passed.

Other possible adverse reactions that may occur:
Immune system

• allergic reactions, with symptoms such as shortness of breath, wheezing, rash, itching, or swelling of the face and lips.

Gastrointestinal system

• nausea and vomiting. These may last for about 24 hours after taking cyclophosphamide. The patient may require anti-nausea and anti-vomiting medications. Please consult your doctor;
• inflammation of the mucous membrane of the mouth, including ulceration;
• severe abdominal and back pain (pancreatitis).

Skin and hair

• hair loss. The patient may notice slightly increased hair shedding during combing or washing, or may lose most or all of their hair. The degree of hair loss depends on the dose of cyclophosphamide, hair density, and concomitant use of other anticancer drugs. When cyclophosphamide is used in combination with other anticancer drugs, the likelihood of hair loss is significantly higher compared to using cyclophosphamide alone;
• yellowing of the skin or whites of the eyes (jaundice), caused by liver problems;
• paleness (anemia), caused by low red blood cell count. Your doctor will monitor this during treatment;
• increased tendency to bruising, caused by slow blood clotting;
• changes in nail and skin color.

Urinary system

• burning sensation or pain during urination;
• scarring and shrinkage of the urinary bladder (pain and frequent urge to urinate);
• blood cancer (leukemia);
• kidney problems, including kidney failure.

Chest

• shortness of breath;
• lung inflammation, causing shortness of breath, cough, and fever;
• lung fibrosis, causing shortness of breath.

Heart and circulatory system

• rapid heartbeat, heart attack;
• changes in heart rhythm and function at higher doses, which will be visible to the doctor on an ECG (electrocardiogram).

Reproductive system

• absence of sperm in 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 within the urinary bladder);
• bloating and swelling (fluid retention in the body);
• high blood sugar levels (thirst, easy fatigue, nervousness);
• low blood sugar levels (confusion, excessive sweating);
• increased red blood cells.

Changes in the results of certain blood laboratory tests may also occur:

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

If any adverse symptoms occur, including any adverse symptoms not listed in this leaflet, consult your doctor or nurse.
Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. Adverse reactions can be reported directly to the Department of Monitoring of Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
PL 02-222 Warsaw
Tel.: +48 22 49 21 301
Fax: +48 22 49 21 309
e-mail: [email protected]
Adverse reactions can also be reported to the responsible entity.
Reporting adverse reactions helps to provide more information on the safety of using this medicine.

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

Do not dispose of medicines via the sewage system or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures help protect the environment.

6. Contents of the package and other information

What Endoxan contains
The active substance is cyclophosphamide; each coated tablet contains 50 mg of cyclophosphamide.
Other components of the tablet core are: maize starch, monohydrate lactose, calcium hydrogen phosphate dihydrate, talc, magnesium stearate, gelatin, glycerol.
Coating composition: sucrose, talc, titanium dioxide, calcium carbonate, polyethylene glycol 35 000, silicon dioxide, polyvinylpyrrolidone 25, sodium carboxymethylcellulose, polysorbate 20, wax (Montan glycol wax).
What Endoxan looks like and contents of the pack
Endoxan is a white, round coated tablet with a white core. Each blister contains 10 coated tablets, and each carton contains 5 blisters.
Marketing Authorisation Holder and Manufacturer:
Marketing Authorisation Holder
Baxter Polska Sp. z o.o.
Kruczkowskiego 8
00-380 Warsaw
Poland
Manufacturer
Baxter Oncology GmbH
Kantstrasse 2
D-33790 Halle
Germany