CYCLOPHOSPHAMIDE SEACROSS 500 MG POWDER FOR INJECTABLE SOLUTION AND FOR INFUSION

Introduction

Package Leaflet: Information for the Patient

CyclophosphamideSeacross500 mg powder for solution for injection and infusionEFG

CyclophosphamideSeacross1,000 mg powder for solution for injection and infusionEFG

Read all of this leaflet carefully before you are given this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or nurse.
• If you experience any side effects, talk to your doctor or nurse, even if they are not listed in this leaflet. See section 4.

Important things you need to know aboutCyclophosphamideSeacross

Your doctor has prescribed cyclophosphamide because you have a cancer that can be treated.

Cyclophosphamide is a medicine that kills cancer cells, but as a result, it also attacks normal cells. Therefore, you may have a number of side effects. Your doctor will only give you cyclophosphamide if they consider that your cancer poses a greater risk to you than the possible side effects. Your doctor will regularly check you and treat any side effects as much as possible.

Cyclophosphamide Seacross:

• will reduce your blood cell count, which can make you feel tired and more prone to infections.
• may affect your kidneys and bladder. You may be given another medicine called Mesna to help prevent any damage. If you see blood in your urine, tell your doctor immediately.
• like most anticancer or chemotherapy medicines, you may lose your hair (from weakening to total loss), although it should start to grow back once treatment is finished. It can also make you feel sick or be sick. Your doctor may give you advice or medicines to help.
• men and women should not have children during treatment with cyclophosphamide or for at least 3 to 6 months after treatment. You must use an effective method of contraception. Ask your doctor for advice.

Now read the rest of this leaflet.It includes other important information about the use of cyclophosphamide that may be particularly important for you.

Contents of the package leaflet

1. What is Cyclophosphamide Seacross and what is it used for
2. What you need to know before you are given Cyclophosphamide Seacross
3. How to use Cyclophosphamide Seacross
4. Possible side effects
5. Storage of Cyclophosphamide Seacross
6. Contents of the pack and further information

1. What is Cyclophosphamide Seacross and what is it used for

Cyclophosphamide Seacross contains an active substance called cyclophosphamide. Cyclophosphamide is a cytotoxic or antineoplastic medicine. It works by killing cancer cells, which is sometimes called "chemotherapy".

Cyclophosphamide is usually used alone or in combination with other antineoplastic medicines or radiotherapy in the treatment of various types of cancer. This includes:

• certain types of white blood cell cancer (acute lymphoblastic leukemia, chronic lymphocytic leukemia),
• various forms of lymphomas that affect the immune system (Hodgkin's lymphoma, non-Hodgkin's lymphoma, and multiple myeloma),
• ovarian and breast cancer,
• Ewing's sarcoma (a type of bone cancer),
• small cell lung carcinoma,
• in the treatment of metastatic or advanced tumors of the central nervous system (neuroblastoma).

In addition, cyclophosphamide is used in the preparation of bone marrow transplants to treat certain types of white blood cell cancer (acute lymphoblastic leukemia, chronic myeloid leukemia, and acute myeloid leukemia).

Occasionally, some doctors may prescribe cyclophosphamide for conditions unrelated to cancer:

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

2. What you need to know before you are given Cyclophosphamide Seacross

You will not be given Cyclophosphamide Seacross:

• if you are allergic to cyclophosphamide or any of its metabolites. An allergic reaction can include difficulty breathing, wheezing, rash, itching, or swelling of the face and lips.
• if you currently have an infection.
• if your bone marrow is not working properly (especially if you have previously undergone chemotherapy or radiotherapy). You will have blood tests to check your bone marrow function.
• if you have a urinary tract infection that can be recognized by pain when urinating (cystitis).
• if you have had kidney or bladder problems as a result of chemotherapy or radiotherapy.
• if you have a disease that reduces your ability to urinate (obstruction of urine flow).
• if you are breastfeeding.

Warnings and precautions

Tell your doctor before starting treatment with cyclophosphamide if:

• you have low blood cell counts,
• you have severe infections,
• you are receiving or have recently received radiotherapy or chemotherapy;
• you have diabetes,
• you have liver or kidney problems. Your doctor will check your liver and kidney function with a blood test,
• you have had your adrenal gland removed,
• you have heart problems or have received radiotherapy in the heart area,
• you have poor general health or are a frail person,
• you are elderly,
• you have had surgery in the last 10 days.

Potentially life-threatening allergic reactions (anaphylactic reactions) may occur during treatment with cyclophosphamide.

Be careful with Cyclophosphamide Seacross

Cyclophosphamide can have effects on your blood and immune system.

• Blood cells are produced in your bone marrow. There are three types of blood cells:

• red blood cells, which carry 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 all three types of cells will decrease. This is an inevitable side effect of cyclophosphamide. Your blood count will reach its lowest level about 5 to 10 days after starting cyclophosphamide and will remain low for a few days after the treatment cycle ends. Most people recover normal blood cell counts over 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 get infections if your blood cell count is low. Try to avoid close contact with people who have coughs, colds, and other infections. Your doctor will treat you with the appropriate medicine if they think you have an infection or are at risk of getting one.

• Your doctor will make sure that your red blood cell, white blood cell, and platelet counts are high enough before treatment with cyclophosphamide and during treatment. You may need to reduce the amount you receive or delay the next dose.

• Cyclophosphamide can affect wound healing. Keep cuts clean and dry and check that they are healing normally.
• It is important to maintain good oral health, as infections and mouth ulcers can occur. Consult your doctor if you are unsure.

• Cyclophosphamide can damage the lining of the urinary bladder and cause bleeding in the urine or pain when urinating. Your doctor knows this can happen and, if necessary, will give you a medicine called Mesna to protect your bladder.

• Mesna can be given as a short injection or mixed with cyclophosphamide in the infusion solution, or as tablets.
• You can find more information about Mesna in the patient leaflet for Mesna injection and Mesna tablets.

• Most people given cyclophosphamide with Mesna do not develop bladder problems, but your doctor may want to check your urine for blood with a dipstick or microscope.

• If you see blood in your urine, you must tell your doctor immediately, as it may be necessary to stop cyclophosphamide.

• Your doctor will make sure you are well-hydrated and will check your fluid balance to keep a good flow of urine.

• Cancer medicines and radiotherapy can increase the risk of developing other types of cancer; this can happen several years after the end of your treatment. Cyclophosphamide carries a higher risk of causing cancer in the bladder area. Your doctor is aware of this and may give you therapies to reduce this risk.

• Cyclophosphamide can cause heart damage or affect the rhythm of your heartbeat. This effect is greater at higher doses of cyclophosphamide, if you are being treated with radiotherapy or other chemotherapy medicines, or if you are an elderly person. Your doctor will closely monitor your heart during treatment.

• Cyclophosphamide can cause inflammation or scarring of the lungs. This can happen more than six months after the end of treatment. If you start to have difficulty breathing, tell your doctor immediately.
• Cyclophosphamide can have potentially life-threatening effects on your liver. If you experience a sudden increase in weight, liver pain, and your skin or the white of your eyes turn yellow (jaundice), tell your doctor immediately.

• You may experience hair loss or baldness. Your hair should grow back normally, although its texture and color may be different.

• Cyclophosphamide can cause nausea and vomiting. This can last for about 24 hours after taking cyclophosphamide. You may need to take medicines to stop feeling sick or being sick. Consult your doctor about this.

Other medicines and Cyclophosphamide Seacross

Tell your doctor or nurse if you are using, have recently used, or might use any other medicines, including those you have bought yourself. In particular, tell them about the following medicines or treatments because they may be incompatible with the use of cyclophosphamide.

The following medicines may 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 as an anticoagulant),
• sulfonamides, such as sulfadiazine, sulfasalazine, sulfamethoxazole (used to treat bacterial infections),
• ondansetron (used to prevent vomiting).

The following medicines may increase the toxicity of cyclophosphamide:

• allopurinol (used to treat gout),
• azathioprine (used to reduce the activity of the immune system),
• chloral hydrate (used to treat insomnia),
• cimetidine (used to reduce stomach acidity),
• disulfiram (used to treat alcoholism),
• glyceraldehyde (used to treat warts),
• protease inhibitors (used to treat viruses),
• medicines that increase liver enzymes 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 inflammation),
• dabrafenib (an anticancer medicine).

• medicines that may increase the toxic effects of cyclophosphamide on blood cells and immunity:

• other anticancer medicines (used to treat cancer),
• clozapine (used to treat symptoms of some psychiatric disorders),
• zidovudine (used to treat viral infections),
• ACE inhibitors (used to treat high blood pressure),
• natalizumab (used to treat multiple sclerosis),
• thiazide diuretics such as hydrochlorothiazide or chlorthalidone (used to treat high blood pressure or fluid retention),

• medicines that may increase the toxic effects on the heart:

• anthracyclines such as bleomycin, doxorubicin, epirubicin, mitomycin (used to treat cancer),
• radiotherapy in the heart area,
• cytarabine, pentostatin, trastuzumab (used to treat cancer).

• medicines that may increase the toxic effects on the lungs:

• amiodarone (used to treat irregular heartbeat),
• G-CSF, GM-CSF hormones (used to increase white blood cell counts after chemotherapy).

• medicines that may increase the toxic effects on the kidneys:

• amphotericin B (used to treat fungal infections),
• indomethacin (used to treat pain and inflammation).

• other medicines that may affect cyclophosphamide or be affected by it include:

• etanercept (used to treat rheumatoid arthritis),
• metronidazole (used to treat bacterial or protozoal infections),
• tamoxifen (used to treat breast cancer),
• bupropion (used to help stop smoking),
• coumarins such as warfarin (used as an anticoagulant),
• cyclosporin (used to reduce the activity of the immune system),
• succinylcholine (used as a muscle relaxant during medical procedures),
• digoxin, acetyldigoxin ß (used to treat heart conditions),
• vaccines,
• verapamil (used to treat high blood pressure, angina, or irregular heartbeat),
• sulfonylurea derivatives (it may be necessary to reduce blood sugar if cyclophosphamide and sulfonylurea derivatives are used at the same time).

Using Cyclophosphamide Seacross with food, drinks, and alcohol

Drinking alcohol may increase the nausea and vomiting caused by cyclophosphamide.

You should not consume grapefruit (fruit or juice) while taking cyclophosphamide. It may interfere with the usual effect of your medicine and alter the effectiveness of cyclophosphamide.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before taking this medicine.

Pregnancy

Cyclophosphamide may cause miscarriage or harm to the fetus.

If you are a woman, you must not become pregnant during treatment with cyclophosphamide or for 6 months after the end of treatment.

If you are a man, you must take appropriate precautions, including the use of effective contraception, to ensure that you do not father a child during treatment with cyclophosphamide or for 3 months after treatment.

Breastfeeding

You must not breastfeed while being treated with cyclophosphamide. Ask your doctor for advice.

Fertility

Cyclophosphamide may affect your ability to have children in the future. Consult your doctor about the cryopreservation (freezing) of sperm or eggs before treatment, as there is a possibility of irreversible sterility due to treatment with cyclophosphamide. If you are considering becoming a parent 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 or use machines safely. Your doctor will decide if you can do so safely.

What to do if you change doctors or have to go to the hospital

If you go to another doctor or have to go to the hospital for any reason, tell them what medicines you are taking. Do not take any other medicine unless your doctor knows you are taking this medicine.

3. How to use Cyclophosphamide Seacross

Method of administration

By intravenous route.

Cyclophosphamide will be administered by a doctor or nurse with experience in the use of antineoplastic chemotherapy.

Cyclophosphamide will be administered by a doctor or nurse.

• It is administered in an injection
• Normally, it will be added to a large bag of liquid and injected slowly (perfused) directly into a vein. The vein can be in the arm, the back of the hand, or a large vein under your collarbone. Depending on the dose, administration usually takes between a few minutes and an hour.
• Cyclophosphamide is usually administered in combination with other antineoplastic medications or radiotherapy.

The recommended dose is:

• Your doctor will decide how much medication you need and when you should receive it.
• The amount of cyclophosphamide that you will be administered will depend on:

• the type of disease you have,
• your build (a combination of your height and weight),
• your overall health status,
• if you are being administered other antineoplastic medications or receiving radiotherapy.

It is advisable to administer cyclophosphamide in the morning. Before, during, and after administration, it is essential that you receive adequate amounts of fluid to avoid possible adverse effects on the urinary tract.

Cyclophosphamide is usually administered in a series of treatment cycles. After each course, there is a break (a period during which cyclophosphamide is not administered) before the next course.

It is possible that your doctor may need to change the amount of medication you take and monitor you more closely if:

• you have liver or kidney problems,
• you are an elderly person.

Use in children and adolescents

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

If you use more Cyclophosphamide Seacross than you should

Since cyclophosphamide is administered under the supervision of your doctor, it is very unlikely that you can receive too much. Nevertheless, if you experience adverse effects after receiving cyclophosphamide, inform your doctor immediately or go to the emergency department of the nearest hospital. You may need urgent medical attention.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone 91 562 04 20, indicating the medication and the amount ingested.

The symptoms of an overdose with cyclophosphamide include the side effects detailed in the "Possible adverse effects" section, but they are usually more severe.

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

4. Possible adverse effects

Like all medications, this medication can produce adverse effects, although not all people experience them.

Sometimes, side effects may appear after treatment has finished. The following side effects may occur with this medication.

Tell your doctor immediately if you experience any of the following serious adverse effects:

• Allergic reactions.The signs would be difficulty breathing, wheezing, increased heart rate, reduced blood pressure (extreme fatigue), rash, itching, or swelling of the face and lips.Severe allergic reactions could cause breathing difficulties 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 the levels of platelets in your blood are too low.
• decrease in white blood cell count; your doctor will check it during treatment. It will not cause any signs, but you will be more likely to contract infections. If you think you have an infection (high fever, feeling cold and chills, or heat and sweating, or any sign of infection such as cough or discomfort when urinating) you may need antibiotics to combat infections because your blood count is lower than usual.
• Pallor, feeling of lethargy, and fatigue. These signs could be indicative of a low level of red blood cells (anemia). Normally, no treatment is required, as your body will replace the red blood cells over time. In case of pronounced anemia, you may need a blood transfusion.
• Blood in the urine, pain when urinating, or reduced urine volume.
• Severe chest pain.
• Symptoms such as weakness, loss of vision, speech difficulties, loss of touch.

Other possible effects may be:

Very common(may affect more than 1 in 10 people):

• reduction in the number of blood cells (myelosuppression),
• reduction in white blood cells, which are important in fighting infections (leukopenia, neutropenia),
• hair loss (alopecia),
• burning sensation when urinating and frequent need to do so (cystitis),
• presence of blood in the urine (microhematuria),
• fever,
• suppression of the immune system.

Common(may affect up to 1 in 10 people):

• infections,
• inflammation of the mucous membranes (mucositis),
• blood in the urine and pain when urinating (hemorrhagic cystitis),
• presence of blood in the urine (macrohematuria),
• abnormalities in liver function,
• sterility in males,
• chills,
• feeling of weakness,
• general feeling of discomfort,
• reduction in white blood cell count and fever (febrile neutropenia).

Uncommon(may affect up to 1 in 100 people)

• anemia (low red blood cell count) that can cause fatigue and drowsiness,
• propensity to bruising due to low platelet count (thrombocytopenia),
• lung inflammation (pneumonia),
• septicemia,
• allergic reactions,
• sterility in women (rarely irreversible),
• chest pain,
• rapid heartbeat,
• heart problems,
• changes in the results of some blood tests,
• redness of the skin (rash),
• nerve damage that can cause numbness, pain, and weakness (neuropathy),
• nerve pain (neuralgia),
• loss of appetite,
• deafness,
• changes in ECG
• Decreased FEV1
• lower levels of female sex hormones

Rare(may affect up to 1 in 1,000 people)

• increased risk of white blood cell cancer (acute leukemia) and some other cancers (bladder cancer, ureter cancer),
• ineffective production of the myeloid class of blood cells (myelodysplastic syndrome),
• increased release of antidiuretic hormone from the pituitary gland (inappropriate antidiuretic hormone secretion syndrome). This affects the kidneys and causes low sodium levels in your body (hyponatremia) and fluid retention, leading to brain swelling due to excess water in the blood. The signs may include headache, changes in personality or behavior, confusion, and drowsiness,
• changes in heart rhythm,
• liver inflammation,
• skin rash,
• skin inflammation,
• absence of menstruation (periods),
• absence of sperm,
• dizziness,
• vision changes, blurred vision,
• changes in the color of your nails and skin,
• dehydration,
• seizures,
• bleeding,

• chest pain

Very rare(may affect up to 1 in 10,000 people)

• breakdown of red blood cells and kidney failure (hemolytic uremic syndrome),
• formation of blood clots in all small blood vessels of the body (disseminated intravascular coagulation),
• shock,
• complications that can occur after cancer treatment caused by breakdown products of dying cancer cells (tumor lysis syndrome),
• low sodium levels in the blood (hyponatremia),
• high blood pressure (hypertension),
• low blood pressure (hypotension),
• angina,
• heart attack,
• blockage of a blood vessel due to a blood clot in the circulatory system (thromboembolism),
• lung damage (acute respiratory distress syndrome),
• lung fibrosis that causes breathing difficulties (chronic interstitial pulmonary fibrosis),
• difficulty breathing with wheezing or cough (bronchospasm),
• shortness of breath (dyspnea),
• a condition in which the body or a region of the body lacks adequate oxygen supply (hypoxia),
• cough,
• discomfort or ulcers in the mouth (stomatitis),
• nausea (nausea) or vomiting or diarrhea
• constipation,
• inflammation of the intestine,
• inflammation of the pancreas,
• blood clot in the liver (hepatic veno-occlusive disease),
• liver enlargement (hepatomegaly),
• yellowing of the eyes or skin,
• severe hypersensitivity reactions with fever (high), red spots on the skin, joint pain, and/or eye infection (Stevens-Johnson syndrome),
• sudden severe reaction (hypersensitivity) with fever and blisters on the skin/desquamation of the skin (toxic epidermal necrolysis),
• radiation erythema,
• itching,
• alteration of taste (dysgeusia, hypogeusia),
• tingling, pinching, itching, or burning sensation (paresthesia),
• alteration of smell (parosmia),
• abnormal muscle breakdown that can cause kidney problems (rhabdomyolysis),
• cramps,
• bladder problems,
• kidney problems, including kidney failure,
• headache,
• multi-organ failure,
• reaction at the injection site and perfusion,
• weight gain,
• confusion,
• conjunctivitis, eye swelling,
• respiratory failure due to fluid accumulation in the lungs (pulmonary edema),
• fluid accumulation in the abdominal cavity (ascites),
• ventricular fibrillation
• pericarditis
• atrial fibrillation
• suburethral hemorrhage
• myocardial infarction
• increased creatinine levels in blood

Frequency not known(cannot be estimated from the available data)

• different types of cancer, such as blood cancer (non-Hodgkin's lymphoma), kidney cancer, thyroid cancer,
• sarcoma,
• different types of blood disorders (agranulocytosis, lymphopenia, reduction of hemoglobin),
• blockage of a blood vessel by a clot in the circulatory system (thromboembolic events), including the possibility of blockage of the pulmonary vessels (pulmonary embolism),
• blood clot, usually in a leg, that causes pain, swelling, or redness (venous thrombosis)
• inflammation of the blood vessels (vasculitis)
• reduced blood flow to hands and feet (peripheral ischemia). This can cause pain, weakness, numbness, ulcers, changes in skin color or temperature
• increased tear production (lacrimation)
• ringing in the ears (tinnitus)
• hearing impairment
• nasal congestion (nasal congestion),
• oropharyngeal pain,
• runny nose,
• sneezing,
• veno-occlusive pulmonary disease,
• obliterative bronchiolitis,
• allergic alveolitis,
• pneumonitis,
• pleural effusion,
• abdominal pain,
• stomach or intestinal bleeding,
• intestinal problems/hemorrhage,
• liver failure,
• rash, redness of the skin, 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,
• joint pain,
• inflammation, scarring, and contraction of the bladder,
• fetal damage or death,
• changes in the results of some blood tests (glucose, hormone levels),
• brain disorder (encephalopathy), neurotoxicity manifested as a syndrome characterized by headache, confusion, seizures, and loss of vision (posterior reversible encephalopathy syndrome), abnormal sensation (dysesthesia, hypesthesia), tremor, alteration of taste (dysgeusia, hypogeusia), alteration of smell (parosmia),
• different types of heart disorders (ventricular tachycardia, cardiogenic shock, pericardial effusion, bradycardia, palpitations, QT interval prolongation in the electrocardiogram),
• sterility in men and women,
• changes in menstrual frequency,
• intrauterine death,
• fetal malformation,
• fetal growth retardation,
• cardiogenic effect on offspring,
• inflammation of the salivary glands (usually in the cheek area; parotid gland inflammation),
• redness of the skin (flushing) that may be accompanied by a feeling of heat or sweating (hot flashes)
• increased blood pressure in the lungs that can cause difficulty breathing, fatigue, cough, chest pain, fainting, peripheral edema (pulmonary hypertension)
• alteration of bile formation by the liver, which can cause itching, jaundice, pale stools, dark urine (cholestasis)
• accumulation of toxins in the body due to liver failure (hepatotoxicity). It can affect the brain, causing confusion, decreased consciousness, or coma (hepatic encephalopathy)
• death of cells and tissues (necrosis), ulceration, or scarring (fibrosis) of the bladder
• ovarian disorder
• general physical deterioration
• localized swelling (edema)
• changes in kidney tissue that prevent proper function (tubular necrosis, tubular disorder)
• kidney damage due to toxins in the blood (toxic nephropathy)
• inflammation of the urethra that causes pain and bleeding (hemorrhagic urethritis)
• glucose in the urine (nephrogenic diabetes insipidus)
• increased urea nitrogen levels in blood. Your doctor will perform blood tests to check it.
• Premature birth
• Nail disorder
• Toxic skin rash
• Blisters
• Brain swelling due to excess water in the blood (water intoxication). Signs may include headache, changes in personality or behavior, confusion, and drowsiness.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor, even if it is a possible adverse effect that is not listed in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es.

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

5. Storage of Cyclophosphamide Seacross

Keep this medication out of sight and reach of children.

Do not use this medication after the expiration date that appears on the box and on the label of the vial after "EXP". The expiration date is the last day of the month indicated.

Do not store above 25°C.

After reconstitution for intravenous administration

After reconstitution/dilution:

Chemical and physical stability has been demonstrated for 24 hours at 2°C - 8°C, for both the reconstituted solution and the diluted solution.

From a microbiological point of view, the reconstituted and diluted solution should be used immediately, unless the reconstitution has been carried out under controlled and validated aseptic conditions. If not used immediately, the storage times and conditions before use are the responsibility of the user and normally should not exceed 24 hours at 2 - 8°C, unless the reconstitution/dilution has been carried out under controlled and validated aseptic conditions.

Medications should not be thrown away through wastewater or household waste. Ask your doctor how to dispose of the packaging and medications that you no longer need. This will help protect the environment.

6. Container Content and Additional Information

Composition of Cyclophosphamide Seacross

• The active ingredient is cyclophosphamide.

Each Cyclophosphamide Seacross 500 mg powder for solution for injection/infusion EFG contains 534.5 mg of cyclophosphamide monohydrate equivalent to 500 mg of cyclophosphamide.

Each Cyclophosphamide Seacross 1,000 mg powder for solution for injection/infusion EFG contains 1,069.0 mg of cyclophosphamide monohydrate equivalent to 1,000 mg of cyclophosphamide.

• It does not contain other components.

Appearance of the Product and Container Content

Cyclophosphamide Seacross is a white crystal or crystalline powder.

Cyclophosphamide Seacross 500 mg powder for solution for injection/infusion EFG is a white or crystalline crystal and is supplied in a 50 ml colorless glass vial sealed with a butyl rubber stopper and a flip-off aluminum cap with a red polypropylene plastic button, containing 500 mg of cyclophosphamide.

Cyclophosphamide Seacross 1,000 mg powder for solution for injection/infusion EFG is a white or crystalline crystal and is supplied in a 100 ml colorless glass vial sealed with a butyl rubber stopper and a flip-off aluminum cap with a green polypropylene plastic button, containing 1,000 mg of cyclophosphamide.

Each container contains one vial of this medication.

Marketing Authorization Holder and Manufacturer

Seacross Pharma (Europe) Limited

POD 13, The Old Station House

15A Main Street, Blackrock

Dublin, A94 T8P8

Ireland

Local Representative

Pharmavic Ibérica, S.L.

C/ Compositor Lehmberg Ruiz

6 Edificio Ibiza, Oficina 7

29007 Málaga, (Spain)

Phone: 676295501

This Medication is Authorized in the Member States of the European Economic Area with the Following Names:

Date of Last Revision of this Prospectus: October 2024

Detailed information about this medication is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/

--------------------------------------------------------------------------------------------------------------------

This information is intended only for healthcare professionals:

Cyclophosphamide should only be used by professionals experienced in the use of cancer chemotherapy.

Cyclophosphamide should only be administered when there are means for regular monitoring of clinical, biochemical, and hematological parameters before, during, and after administration, and under the direction of a specialized oncology service.

Dosage and Administration

The dosage should be individualized. The doses and duration of treatment and/or its intervals depend on the therapeutic indication, the scheme of a combined treatment, the patient's general health status, and organic function, and the results of analytical monitoring (in particular, blood cell monitoring).

In combination with other cytostatics of similar toxicity, a reduction in dose or extension of treatment-free intervals may be necessary.

The use of hematopoietic stimulants (colony-stimulating factors and erythropoiesis-stimulating medications) may be considered to reduce the risk of myelosuppressive complications and/or contribute to facilitating the administration of the planned dosage.

Before, during, and immediately after administration, adequate amounts of liquid should be ingested or infused to induce diuresis and reduce the risk of toxicity in the urinary tract. Therefore, this medication should be administered in the morning.

Cyclophosphamide is inert until activated by hepatic enzymes. Nevertheless, as with all cytotoxic medications, it is recommended that reconstitution be performed by trained personnel in a designated area.

Personnel responsible for preparation should wear protective gloves.Splashes of the material in the eyes should be avoided. The material should not be handled by pregnant or breastfeeding women.

Handling

The choice of solvent for reconstitution of this medication containing cyclophosphamide depends on the route of administration to be used.

Infusion

If the solution is to be used for intravenous infusion, this medication (containing cyclophosphamide) is reconstituted by adding sterile water for injection or sodium chloride 9 mg/ml (0.9%) injectable solution.

The reconstituted solution of this medication should be diluted subsequently in 5% glucose or sodium chloride 9 mg/ml (0.9%) solution for infusion before infusion; the solution should be diluted to a minimum concentration of 2 mg per ml.

Direct Injection

If the solution is to be used for direct injection, this medication (containing cyclophosphamide) is reconstituted by adding sodium chloride 9 mg/ml (0.9%) injectable solution.

Note that only this medication reconstituted in sodium chloride 9 mg/ml (0.9%) injectable solution is suitable for bolus injection.

Cyclophosphamide Seacross(containing cyclophosphamide) reconstituted in water is hypotonic and should not be injected directly.

The following amounts of water for injection or sodium chloride 9 mg/ml (0.9%) injectable solution are added to the vials containing Cyclophosphamide Seacross powder for solution for injection/infusion:

Vial of 500 mg: 25 ml

Vial of 1,000 mg: 50 ml

Injection of the solvent into the vial for injection creates abnormally high pressure, which disappears as soon as a second sterile needle is introduced into the rubber stopper of the vial for injection. The powder dissolves easily when the vial for injection is shaken vigorously to produce a clear solution. If the powder does not dissolve immediately, continue shaking the vial vigorously for several minutes until the powder is completely dissolved. The solution should be administered as soon as possible after its reconstitution.

After reconstitution, the solution is clear and colorless to light yellow. Please verify the vial before use. Only transparent solutions should be used.

Infusion:

This reconstituted medication should also be diluted in 5% glucose or sodium chloride 9 mg/ml (0.9%) solution for infusion before infusion; the solution should be diluted to a minimum concentration of 2 mg per ml.

General guidelines for the handling of cytostatics should be observed when reconstituting or handling this medication. Whenever possible, reconstitution should be performed in a laminar flow safety cabinet. The person handling the product should wear a protective mask and gloves. In case of spills, the area should be washed abundantly with water. If Cyclophosphamide Seacross powder for solution for injection/infusion is stored (e.g., during transport) at a temperature above the maximum allowed, cyclophosphamide may melt. Vials for injection containing melted cyclophosphamide can be identified by sight. Cyclophosphamide is a white powder. Melted cyclophosphamideis a clear or yellowish viscous liquid (normally in the form of drops in the corresponding vials). Vials for injection containing melted cyclophosphamide should not be used.

Guidelines for the Safe Handling of Antineoplastic Medications

When reconstituting or handling this medication, the rules and regulations for the handling of cytotoxics in general should be observed.

Reconstitution should be performed, whenever possible, in a laminar flow safety cabinet.

Pregnant women should not handle cytotoxic preparations. The medication should be diluted by properly trained personnel. This should be done in the designated area. The work surface should be covered with absorbent paper with a disposable plastic backing.

Protective gloves, masks, and clothing should be used. Precautions should be taken to avoid accidental contact of the medication with the skin or mucous membranes, and the affected area should be washed thoroughly with water and soap. If accidental contamination of the eyes occurs, they should be washed immediately and thoroughly with water.

Use Luer-Lock connectors on all syringes and equipment. The use of large-caliber needles is recommended to minimize pressure and possible aerosol formation. This can also be reduced with the use of a vacuum needle.

Unused quantities should be discarded. Special precautions should be taken in the disposal of items used to dilute cyclophosphamide. Any unused product or contaminated materials should be placed in a high-risk waste bag. Sharp objects (syringes, needles, vials, etc.) should be placed in a suitable rigid container. The personnel responsible for collecting and disposing of these residues should be aware of the risks involved.

Disposal

Disposal of unused medication and all materials that have come into contact with it will be carried out in accordance with local regulations for cytotoxic agents.