Prospecto:information for the patient

GENOXAL 50 mg coated tablets

Ciclofosfamida

Read this prospectus carefully before starting to take the medicine,because it contains important information for you.

• Keep this prospectus, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed for you and should not be given to others, even if they have the same symptoms, as it may harm them.
• If you experience adverse effects, consult your doctor or pharmacist, even if they are not listed in this prospectus. See section 4.

1.What is GENOXAL and what it is used for.

2.What you need to know before starting to take GENOXAL.

3.How to take GENOXAL

4.Possible adverse effects

5.Storage of GENOXAL

6.Contents of the package and additional information

Genoxalcontains as active substance Cyclophosphamide.It belongs to the group of medications known as “cytotoxic or antineoplastic drugs”, which acts by stopping the growth of cancer cells.

Genoxalis usually used in monotherapy or in combination with other antineoplastic drugs or radiation therapy, in the treatment of various types of cancer. This includes:

-different forms of lymphomas that affect the immune system (Hodgkin's lymphoma, non-Hodgkin's lymphoma, and multiple myeloma),

-certain types of white blood cell cancer (acute lymphocytic leukemia, chronic lymphocytic leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia),

-ovarian cancer and breast cancer,

-Ewing's sarcoma (a type of bone cancer),

-microcytic lung carcinoma,

-in the treatment of metastatic or advanced central nervous system tumors (neuroblastoma)

Furthermore,Genoxalis used in bone marrow transplant preparation.

In some cases, some doctors may prescribeGenoxalfor other conditions unrelated to cancer:

- autoimmune diseases that compromise life: progressive severe forms of lupus nephritis (kidney inflammation caused by an autoimmune disease) and Wegener's granulomatosis (a rare form of vasculitis)

Do not take Genoxal:

• If you are allergic to cyclophosphamide, any of its metabolites, or any of the other components of this medication (listed in section 6).A hypersensitivity reaction may include difficulty breathing, wheezing, hives, itching, or inflammation of the face and lips.
• If you currently have an infection.
• If your bone marrow does not function properly (especially if you have previously undergone chemotherapy or radiation therapy). Blood tests will be performed to check the function of your bone marrow.
• If you have a urinary tract infection that can be recognized by pain while urinating (cystitis).
• If you have had kidney or bladder problems as a result of chemotherapy or radiation therapy.
• If you have a disease that reduces your ability to urinate (obstruction of urine flow).
• If you are pregnant or breastfeeding.
• In the treatment of non-malignant diseases, except for immunosuppression in life-threatening situations.

Warnings and precautions

Consult your doctor or pharmacist before starting to take Genoxal:

• If you have low blood cell counts.
• If you have severe infections.
• If you have liver or kidney problems. Your doctor will check through a blood test if your liver and kidneys are functioning correctly and if you have had your adrenal gland removed.
• If you are receiving or have recently received radiation therapy or chemotherapy; have heart problems or have received radiation therapy in the heart area.
• If you have diabetes.
• If you have a poor general health or are a fragile or elderly person.
• If you have undergone surgery less than 10 days ago.

Severe allergic reactions (anaphylactic reactions) may occur during treatment with Genoxal.

Genoxal may affect your blood and immune system.

Red blood cells, white blood cells, and platelets are produced in your bone marrow. These cells are of three types:

- Red blood cells, which transport oxygen in the body,

- White blood cells, which fight infections, and

- Platelets, which allow blood to clot.

After receiving cyclophosphamide, the count of blood cells for the three types of cells will decrease. This is an inevitable side effect of the medication. Your blood count will reach its lowest level approximately between 5 and 10 days after starting to receive Genoxal and will remain low for a few days after completing the treatment cycle. Most people recover normal blood cell counts within 21 to 28 days. If you have received a large amount of chemotherapy in the past, it may take a little longer to return to normal.

You are more likely to contract infections if your blood cell count is reduced. Try not to approach people who have a cold, flu, and other infections. Your doctor will treat you with the appropriate medication if they think you have an infection or are at risk of contracting one.

Your doctor will ensure that the count of erythrocytes, leukocytes, and platelets is high enough before and during treatment with cyclophosphamide. You may need to reduce the amount of medication you receive or delay the next dose.

Genoxal may affect the normal healing of wounds. Keep cuts clean and dry and check that they are healing normally. It is essential to maintain good oral health, as infections and mouth ulcers can occur. Consult your doctor if you are unsure.

Genoxal may damage the lining of the urinary bladder and cause bleeding in the urine or pain while urinating. Your doctor knows that this can occur and, if necessary, will give you a medication called Mesna (Uromitexan) to protect your bladder. Mesna can be administered as a short injection or mixed with cyclophosphamide in the infusion solution. You can find more information about Mesna in the leaflet included in the Uromitexan package.

Most people who receive Genoxal with Mesna do not develop bladder problems, but your doctor may want to analyze your urine to detect the presence of blood using a dipstick or microscope. If you observe blood in your urine, you must inform your doctor immediately.

Cancer treatments and radiation therapy may increase the risk of developing other types of cancer; this can occur several years after the completion of your treatment.Genoxalincreases the risk of developing cancer in the urinary bladder area.

Genoxal may cause cardiac damage or affect the rhythm at which your heart beats. This effect is greater at higher doses of Genoxal, if you are receiving or have received radiation therapy or other chemotherapy medications, or if you are an elderly person. Your doctor will closely monitor your heart during treatment.

Genoxal may cause lung problems such as inflammation or pulmonary fibrosis.

This can occur more than six months after the completion of treatment. If you start to experience difficulty breathing, inform your doctor immediately.

Genoxal may have potentially fatal effects on your liver.

If you experience a sudden weight gain, liver pain, and the skin or white part of your eyes turn yellow (jaundice), inform your doctor immediately.

Alopecia or hair loss may occur. Your hair should grow back normally, although its texture and color may be different.

Genoxal may cause nausea and vomiting. This can last approximately 24 hours after taking the medication. You may need to take medication to prevent nausea and vomiting. Consult your doctor about this.

Children and adolescents

Based on established treatment regimens, in children and adolescents, doses similar to those recommended for adults should be used.

Taking Genoxal with other medications:

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication.In particular, inform them of the following medications or treatments because they may be incompatible with the use of Genoxal.

The following medications may reduce the effectiveness of Genoxal:

• 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 as an anticoagulant),
• Sulfonamides, such as sulfadiazine, sulfasalazine, sulfamethoxazole (used to treat bacterial infections),

The following medications may increase the toxicity of Genoxal:

• Aloprim (used to treat gout),
• Chloral hydrate (used to treat insomnia),
• Cimetidine (used to reduce stomach acidity),
• Disulfiram (used to treat alcoholism),
• Glyceryl aldehyde (used to treat warts),
• Protease inhibitors (used to treat viruses),
• Medications that increase liver enzymes such as: rifampicin (used to treat bacterial infections), carbamazepine, phenobarbital, phenytoin (used to treat epilepsy), St. John's Wort (a medicinal plant for mild depression), corticosteroids (used to treat inflammation),
• Benzodiazepines (used as anxiolytics),
• Ondansetron (used to prevent vomiting).

Medications that may increase the toxic effects of Genoxal on blood cells and the immune system:

• ACE inhibitors (used to treat hypertension),
• Natalizumab (used to treat multiple sclerosis),
• Paclitaxel (used to treat cancer),
• Diuretics such as hydrochlorothiazide or clortalidone (used to treat hypertension or fluid retention),
• Zidovudine (used to treat viral infections),
• Clozapine (used to treat symptoms of some psychiatric disorders).

Medications that may increase the toxic effects of Genoxal on the heart:

• Anthracyclines such as bleomycin, doxorubicin, epirubicin,
• Cytarabine, pentostatin, trastuzumab (used to treat cancer),
• Radiation therapy in the heart area.

Medications that may increase the toxic effects of Genoxal on the lungs:

• Amiodarone (used to treat irregular heartbeat),
• G-CSF, GM-CSF (used to increase leukocyte counts after chemotherapy).

Medications that may increase the toxic effects of Genoxal on the kidneys:

• Amphotericin B (used to treat fungal infections),
• Indomethacin (used to treat pain and inflammation).

Other medications that may affect Genoxal or be affected by it include:

• Azathioprine (used to reduce immune system activity),
• Etanercept (used to treat rheumatoid arthritis),
• Metronidazole (used to treat bacterial or protozoal infections),
• Tamoxifen (used to treat breast cancer),
• Bupropion (used to quit smoking),
• Coumarins such as warfarin (used as an anticoagulant),
• Cyclosporine (used to reduce immune system activity),
• Suxamethonium (used as a muscle relaxant during medical procedures),
• Digoxin, acetildigoxina ß (used to treat cardiac conditions),
• Vaccines,
• Verapamil (used to treat hypertension, angina, or irregular heartbeat),
• Sulfonilurea derivatives (glucose levels may decrease if cyclophosphamide and sulfonilurea derivatives are used simultaneously).

Taking Genoxal with food, drinks, and alcohol

Alcohol consumption should be avoided, as it may increase nausea and vomiting caused by cyclophosphamide.

Pomelo (in the form of fruit or juice) should not be consumed while taking Genoxal.

It may interfere with the usual effect of your medication and alter its efficacy.

Pregnancy, lactation, and fertility

If you are pregnant or breastfeeding, or think you may be pregnant, consult your doctor or pharmacist before using this medication.

Pregnancy

Genoxal may cause miscarriage or fetal damage.

Do not become pregnant during treatment with cyclophosphamide or for 12 months after completing treatment. Both men and women who are sexually active should use effective contraceptive methods during treatment and for 6 months after completing treatment. If you become pregnant during treatment, you may receive genetic counseling (medical advice to assess the risk of congenital malformations in the fetus).

Lactation

Do not breastfeed while being treated with Genoxal. Consult your doctor.

Fertility

Genoxal may cause sterility in both sexes. Consult your doctor about cryopreservation (freezing) of sperm or eggs before treatment, as it may result in irreversible sterility due to cyclophosphamide treatment. If you are considering having children after treatment, you should discuss this with your doctor.

Driving and using machines

Some of the side effects of treatment with cyclophosphamide may affect your ability to drive and use machines safely. Your doctor will decide if you can do so safely.

Patients should exercise caution when performing tasks such as driving cars and operating machines until they have checked that the treatment with the medication does not affect their ability to perform these activities.

Genoxal contains lactose and saccharose

This medication contains lactose and saccharose. If your doctor has told you that you have an intolerance to certain sugars, consult them before taking this medication.

Follow exactly the administration instructions for this medication as indicated by your doctor. In case of doubt, consult your doctor or pharmacist.

The recommended dose is:

Your doctor will prescribe a treatment schedule and correct dose for you. The recommended dose, unless otherwise prescribed by a doctor, is 1 to 4 tablets (50 to 200 mg) per day for continuous treatment; if your doctor considers it necessary, more tablets can be taken.

Administration form:

Genoxal is administered orally. Take the tablets in the morning..The tablets must be swallowed whole, during administration or immediately after taking it, drink a sufficient amount of liquid..

Treatment duration:

The treatment cycles of the intermittent regimen can be repeated every 3 or 4 weeks.The duration of treatment and intervals will be decided by your doctor.

Use in children and adolescents

Genoxal is also indicated in children. The safety profile of Genoxal in children is similar to that in adults.

If you take more Genoxal than you should

You may require urgent medical attention.

The symptoms of a cyclophosphamide overdose include the side effects listed in the "Adverse Reactions" section, but are usually more severe.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone 915.620.420, indicating the medication and the amount ingested.

If you forgot to take Genoxal

If you accidentally forget to take a dose, simply take your normal dose when it is due next. Do not take a double dose to compensate for the missed doses. If you have any doubts about the use of this medication, consult your doctor.

If you interrupt the treatment with Genoxal

There are no side effects caused by the end of treatment with Genoxal.

If you have any other doubts about the use of this medication, ask your doctor or pharmacist.

Like all medications,this medicationcanproduce side effects, although not all people will experience them.

Inform your doctor immediately if you experience:

• Allergic reactions. Your symptoms would be difficulty breathing, wheezing, increased heart rate, decreased blood pressure, hives, itching, or inflammation of the face and lips. Severe allergic reactions could produce respiratory distress or shock, with a possible fatal outcome (anaphylactic shock, anaphylactic/anaphylactoid reaction).
• Appearance of bruises without being hit, or bleeding in the gums. This could be a sign that your blood platelet levels are too low.
• Severe infection or fever, cough, shortness of breath, signs of septicemia such as fever, rapid breathing, elevated heart rate, confusion, and edema. This could be a sign of a decrease in your white blood cell count and you may need antibiotics to fight infections.
• Pale skin, feeling tired and lethargic. This could be indicative of low red blood cell levels (anemia). Normally, no treatment is required, as your body will replenish red blood cells over time. In case of severe anemia, you may need a blood transfusion.
• Blood in the urine, pain while urinating, or reduced urine volume.
• Signs of septicemia such as fever, rapid breathing, elevated heart rate, confusion, and edema.
• Severe chest pain.
• Severe lung inflammation that causes shortness of breath, cough, and increased temperature.
• Symptoms such as weakness, loss of vision, difficulty speaking, loss of touch sensation.

The following side effects may also occur during treatment withGenoxal.

Very Common(may affect more than 1 in 10 patients)

• Reduction in the number of blood cells (myelosuppression),
• reduction in white blood cells, which are important in fighting infections (leucopenia, neutropenia),
• Nausea and vomiting,
• Burning sensation while urinating and frequent need to urinate (cystitis),
• Blood in the urine (microhematuria),
• Hair loss (alopecia),
• Fever,
• Suppression of the immune system.

Common(may affect up to 1 in 10 patients)

• Reduction in white blood cell count and fever (neutropenic fever).
• Blood in the urine and pain while urinating (hemorrhagic cystitis),
• Blood in the urine (macrohematuria),
• Male pattern baldness,
• Infections,
• Chills,
• Feeling weak,
• General feeling of discomfort,
• Inflammation of mucous membranes (mucositis),
• Azooospermia in males.

Rare(may affect up to 1 in 100 patients)

• Increased lactate dehydrogenase in the blood,
• Increased C-reactive protein,
• Changes in the electrocardiogram,
• Cardiac problems (myocarditis, cardiomyopathy, heart failure),
• Fast heart rate,
• Tendency to bruise due to thrombocytopenia (reduced platelet count),
• Anemia (low red blood cell count) that may cause fatigue and drowsiness,
• Damage to nerves that may cause numbness, pain, and weakness (neuropathy),
• Pain in the distribution of a nerve (neuralgia),
• Reduced levels of sex hormones,
• Anorexia,
• Lung inflammation (pneumonia),
• Sepsis,
• Disorders in ovulation,
• Allergic reactions.

Very Rare(may affect up to 1 in 10,000 patients)

• Weight gain,
• Angina,
• Myocardial infarction,
• Cardiac arrest,
• Fibrillation of the ventricles,
• Pericarditis (inflammation of the pericardium),
• Fibrillation of the auricles,
• Formation of blood clots in all small blood vessels of the body (disseminated intravascular coagulation),
• Syndrome of hemolytic uremic (a condition that affects the blood and kidneys),
• Dizziness,
• Alteration of the sense of taste (dysgeusia, hypogeusia),
• Sensation of tingling, pinching, itching, or burning (paresthesia),
• Hepatic encephalopathy,
• Conjunctivitis, edema of the eye,Visual impairment,
• Deafness,
• Pulmonary lesion (acute respiratory distress syndrome),
• Pulmonary fibrosis that causes difficulty breathing (chronic interstitial pulmonary fibrosis),
• Respiratory failure due to accumulation of fluid in the lungs (pulmonary edema),
• Difficulty breathing with wheezing or cough (bronchospasm),
• Shortness of breath,
• A condition in which the body or a region of the body lacks adequate oxygen supply (hypoxia),
• Cough,
• Unspecified pulmonary disorders,
• Intestinal inflammation,
• Pancreatitis,
• Accumulation of fluid in the abdominal cavity (ascites).
• Mucosal ulceration,
• Stomach or intestinal bleeding,
• Suburethral bleeding,
• Presence of fluid in the bladder wall,
• Renal problems, including renal insufficiency,
• Inflammation of the bladder wall,
• Inflammation, sclerosis, and contraction of the bladder,
• High levels of creatinine in the blood,
• Severe hypersensitivity reactions with fever (high), red skin rash, joint pain, and/or eye infection (Stevens-Johnson syndrome),
• Sudden severe reaction (hypersensitivity) with fever and blisters on the skin/skin peeling (toxic epidermal necrolysis),
• Itching,
• Severe skin reactions,
• Changes in the color of your nails and skin,
• Radiation dermatitis,
• Abnormal muscle degradation that may cause renal problems (rhabdomyolysis),
• Cramps,
• Increased release of antidiuretic hormone from the pituitary gland (SIADH). This affects the kidneys and causes low sodium levels in your body (hyponatremia) and fluid retention, leading to cerebral edema due to excessive water in your blood. Symptoms may include headache, changes in personality or behavior, confusion, and drowsiness,
• Low sodium levels in the blood (hyponatremia),
• Sepsis shock,
• Complications that may occur after cancer treatment caused by products of cell death (tumor lysis syndrome),
• Blockage of a blood vessel due to a clot in the circulatory system (thromboembolism),
• High blood pressure (hypertension),
• Low blood pressure (hypotension),
• Headache,
• Multi-organ failure,
• Clot in the liver (hepatic veno-occlusive disease),
• Activation of the hepatitis virus,
• Enlargement of the liver (hepatomegaly),
• Yellow eyes or skin,
• Confusion,
• Anaphylactic shock

Frequency not known(cannot be estimated from available data)

• Cerebral disorder (encephalopathy), neurotoxicity manifested as a syndrome characterized by headache, confusion, bone marrow disorders (myelopathy), seizures, and loss of vision (posterior reversible leukoencephalopathy syndrome), abnormal sensation (dysesthesia, hypoaesthesia),degenerative brain disease (encephalopathy),shaking, alteration of the sense of smell (parosmia), different types of cardiac disorders (ventricular tachycardia, cardiogenic shock, pericardial effusion,myocardial hemorrhage,left ventricular insufficiency, bradycardia, palpitations, prolongation of the QT interval on the electrocardiogram,decreased ejection fraction),
• Intrauterine death,
• Fetal malformation,
• Delayed fetal growth,
• Different types of blood disorders (low blood cell counts, agranulocytosis, lymphopenia, reduced hemoglobin),
• Increased tear production,
• Tinnitus and hearing defects
• Pleural effusion,
• Blockage of nasal passages (nasal congestion),
• Unpleasant nasal sensation,
• Orofacial pain,
• Rhinorrhea,
• Stifling,
• Pulmonary veno-occlusive disease,
• Obliterative bronchiolitis,
• Allergic alveolitis,
• Organizing pneumonia,
• Pneumonitis,
• Unpleasant abdominal sensation,
• Certain renal diseases (tubular necrosis, renal tubular disorder, toxic nephropathy, hemorrhagic ureteritis, ulcerative cystitis, vesical contracture, nephrogenic diabetes insipidus, atypical urinary epithelial cells, elevated urea nitrogen in the blood),
• Itching, hives, blisters on the lips, eyes, or mouth, skin peeling (erythema multiforme, urticaria, erythema),
• Hand-foot syndrome,
• Facial swelling,
• Increased sweating,
• Hardening of the skin (scleroderma),
• Muscle spasms and pain,
• Pain in the joints,
• Water intoxication,
• Changes in the results of some blood tests (glucose, hormone levels),
• Different types of cancer, such as blood cancer (non-Hodgkin's lymphoma), renal cancer, pelvic renal cancer, thyroid cancer, sarcoma,carcinogenic effectin offspring,
• Blockage of a blood vessel by a clot in the circulatory system (thromboembolic episodes), including the possibility of blockage of the pulmonary vessels (pulmonary embolism)
• Inflammation of the blood vessel wall (vasculitis).
• Peripheral ischemia,
• Redness,
• Swelling,
• Flu-like symptoms
• Premature birth,
• Bone marrow disorders (hepatitis, cholestasis,hepatotoxicity with liver failure, elevated bilirubin levels, abnormal liver function, elevated liver enzymes)
• Azooospermia in males and females,
• Changes in menstrual frequency,
• Loss of ovarian function,
• Testicular atrophy.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect that does not appear in this prospectus. You can also report them directly through theSpanish System for Pharmacovigilance of Medicinal Products for Human Use:www.notificaRAM.es.

By reporting adverse effects, you can contribute to providing more information on the safety of this medication.

Keep this medication out of the sight and reach of children.

Do not store at a temperature above 25°C. Store in the original packaging to protect it from light. Exposure to direct sunlight or heat sources should be avoided, as it may cause changes in the product's appearance, although this does not affect the active ingredient.

Do not usethis medicationafter the expiration date shown on the packagingafter CAD. The expiration date is the last day of the month indicated.

Medications should not be disposed of through drains or in the trash. Dispose of packaging and unused medications at the SIGREpoint at the pharmacy. If in doubt, ask your pharmacist how to dispose of packaging and unused medications. By doing so, you will help protect the environment.

Composition ofGenoxal

The active ingredient isCiclofosfamida. Each coated tablet contains 50 mg of Ciclofosfamida (equivalent to 53,500 mg of ciclofosfamida monohydrate).

The other components (excipients) are:

Tablet core:Glycerol 85%, gelatine,magnesium stearateTalc, calcium dihydrogen phosphate dihydrate, lactose monohydrate, cornstarch.

Tablet coating: Sucrose, calcium carbonate (E170), titanium dioxide (CI=77891, E-171), talc, polyethylene glycol 35000 (macrogol 35000), colloidal silicon dioxide, povidone K25 (polyvidone 25), sodium carmellose (sodium carboxymethyl cellulose), polysorbate 20, montan wax.

Appearance of the product and contents of the packaging

Genoxal are coated tabletsof white color and round shape.

It is presented in blister packaging and each package contains20 coated tablets.

Marketing authorization holder::

Baxter S.L.

Camilo Pouet 2, 46394 Ribarroja del Turia (Valencia)

Spain

Responsible for manufacturing:

Prasfarma S.L.
C/ San Joan 11-15
08560 Manlleu (Barcelona)

Spain

Date of the last review of this leaflet:March 2017

The detailed and updated information on this medication is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es/