Cyclophosphamide Seacross 1.000 mg powder for injection and for infusion EFG: detailed information

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Cyclophosphamide Seacross 500 mg powder for solution for injection and infusion EFG

Cyclophosphamide Seacross 1,000 mg powder for solution for injection and infusion EFG

Read the entire leaflet carefully before this medicine is administered to you, because it contains important information for you.

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

Important things you should know about Cyclophosphamide Seacross

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

Cyclophosphamide is a medicine that destroys cancer cells, but as a consequence, it also attacks normal cells. Therefore, it may cause a number of side effects. Your doctor will not administer cyclophosphamide to you unless they consider that your cancer poses a greater risk to you than the possible side effects. Your doctor will monitor you regularly and treat any side effects as much as possible.

Cyclophosphamide Seacross:

will reduce your blood cell counts, which may 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 harm. If you notice blood in your urine, inform your doctor immediately.
like most anticancer or chemotherapy medicines, may cause hair loss (ranging from thinning to complete loss), although your hair should start growing back once treatment is completed. It may also make you feel unwell or nauseous. Your doctor can give you advice or medicines to help.
men or women must 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 especially important for you.

Leaflet contents

What Cyclophosphamide Seacross is and what it is used for
What you need to know before you are given Cyclophosphamide Seacross
How to use Cyclophosphamide Seacross
Possible side effects
How to store Cyclophosphamide Seacross
Contents of the pack and other information

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

Ciclofosfamida Seacross contains an active substance called ciclofosfamida. Ciclofosfamida is a cytotoxic or antineoplastic medicine. It works by killing cancer cells, which is sometimes referred to as "chemotherapy".

Ciclofosfamida is usually used as monotherapy or in combination with other antineoplastic medicines or radiotherapy for the treatment of various types of cancer. These include:

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

In addition, ciclofosfamida is used in the preparation for bone marrow transplantation to treat certain types of white blood cell cancers (acute lymphoblastic leukemia, chronic myeloid leukemia, and acute myeloid leukemia).

Occasionally, some doctors may prescribe ciclofosfamida 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 being given Ciclofosfamida Seacross

Ciclofosfamida Seacross will not be administered to you if:

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

Warnings and precautions

Talk to your doctor before starting cyclophosphamide if:

you have low blood cell counts,
you have serious 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 through blood tests,
you have had your adrenal gland removed,
you have heart problems or have received radiotherapy to the area of the heart,
you are in poor general health or are frail,
you are elderly,
you have undergone surgery less than 10 days ago.

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

Take special care with Ciclofosfamida Seacross

Cyclophosphamide may affect your blood and immune system.

Blood cells are produced in your bone marrow. Three types of blood cells are produced:
red blood cells, which carry oxygen throughout the body,
white blood cells, which fight infections,
platelets, which allow blood to clot.
After receiving cyclophosphamide, the count of all three types of blood cells will decrease. This is an inevitable side effect of cyclophosphamide. Your blood count will reach its lowest level approximately between 5 and 10 days after starting cyclophosphamide and will remain low for several days after treatment ends. Most people return to normal blood counts within 21 to 28 days. If you have previously received large amounts of chemotherapy, it may take longer to return to normal.
You are more likely to develop infections if your blood cell count is reduced. Try to avoid close contact with people who have coughs, colds, or other infections. Your doctor will treat you with appropriate medication if they suspect you have an infection or are at risk of developing one.
Your doctor will ensure that your red blood cell, white blood cell, and platelet counts are sufficiently high before and during treatment with cyclophosphamide. It may be necessary to reduce your dose or delay your next dose.
Cyclophosphamide may impair wound healing. Keep cuts clean and dry and monitor them for normal healing.
It is important to maintain good gum health, as oral infections and mouth ulcers may occur. Consult your doctor if you have any concerns.
Cyclophosphamide may damage the inner lining of the urinary bladder, causing bleeding in the urine or pain when urinating. Your doctor is aware of this risk and, if necessary, will give you a medication called Mesna to protect your bladder.
Mesna can be administered as a short injection, mixed with cyclophosphamide in the infusion solution, or taken as tablets.
More information about Mesna can be found in the patient information leaflet for Mesna injection and Mesna tablets.
Most people receiving cyclophosphamide with Mesna do not develop bladder problems, but your doctor may wish to test your urine for blood using a dipstick or microscope.
If you notice blood in your urine, inform your doctor immediately, as it may be necessary to discontinue cyclophosphamide treatment.
Your doctor will ensure you are well hydrated and will monitor your fluid balance to maintain adequate urine flow.
Cancer medications and radiotherapy may increase the risk of developing other types of cancer; this may occur several years after completion of treatment. Cyclophosphamide carries an increased risk of causing cancer in the urinary bladder area. Your doctor is aware of this and may provide therapies to reduce this risk.
Cyclophosphamide may cause heart damage or affect your heart rhythm. This risk is greater at higher doses of cyclophosphamide, if you are receiving radiotherapy or other chemotherapy drugs, or if you are elderly. Your doctor will closely monitor your heart during treatment.
Cyclophosphamide may cause lung inflammation or fibrosis. This may occur more than six months after treatment ends. If you develop breathing difficulties, inform your doctor immediately.
Cyclophosphamide may have potentially life-threatening effects on your liver. If you experience sudden weight gain, liver pain, or yellowing of the skin or whites of the eyes (jaundice), inform your doctor immediately.
Hair loss or baldness (alopecia) may occur. Your hair should regrow normally, although its texture and color may be different.
Cyclophosphamide may cause nausea and vomiting. This may last approximately 24 hours after receiving cyclophosphamide. You may need to take medication to prevent nausea and vomiting. Discuss this with your doctor.

Other medicines and Ciclofosfamida Seacross

Inform your doctor or nurse if you are taking, have recently taken, or might need to take any other medicines, including those obtained without a prescription. In particular, inform them about the following medicines or treatments, as they may interact with cyclophosphamide.

The following medicines may reduce the effectiveness of cyclophosphamide:

Aprepitant (used to prevent vomiting),
bupropion (an antidepressant),
busulfan, thiotepa (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 immune system activity),
chloral hydrate (used to treat insomnia),
cimetidine (used to reduce stomach acid),
disulfiram (used to treat alcoholism),
glycerol aldehyde (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 certain psychiatric disorders),
zidovudine (used to treat viral infections),
ACE inhibitors (used to treat hypertension),
natalizumab (used to treat multiple sclerosis),
thiazide diuretics such as hydrochlorothiazide or chlorothalidone (used to treat hypertension or fluid retention),
medicines that may increase toxic effects on the heart:
anthracyclines such as bleomycin, doxorubicin, epirubicin, mitomycin (used to treat cancer),
radiotherapy to the heart area,
cytarabine, pentostatin, trastuzumab (used to treat cancer).
medicines that may increase 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 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 quit smoking),
coumarins such as warfarin (used as an anticoagulant),
cyclosporine (used to reduce immune system activity),
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 (blood glucose may decrease if cyclophosphamide and sulfonylurea derivatives are used together).

Use of Ciclofosfamida Seacross with food, drinks, and alcohol

Alcohol consumption may increase nausea and vomiting caused by cyclophosphamide.

Grapefruit (fruit or juice) must not be consumed while taking cyclophosphamide. It may interfere with the normal effect of your medicine and alter the efficacy of cyclophosphamide.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor before using this medicine.

Pregnancy

Cyclophosphamide may cause miscarriage or harm to the unborn baby.

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

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

Breastfeeding

You must not breastfeed while being treated with cyclophosphamide. Seek advice from your doctor.

Fertility

Cyclophosphamide may affect your ability to have children in the future. Discuss sperm or egg cryopreservation (freezing) with your doctor before treatment, due to the possibility of irreversible sterility caused by cyclophosphamide. If you are considering becoming a parent after treatment, you should discuss this with your doctor.

Driving and using machines

Some of the adverse effects of cyclophosphamide treatment may affect your ability to drive or operate machinery safely. Your doctor will decide whether you can do so safely.

What to do if you change doctors or need to go to hospital

If you see another doctor or need to go to hospital for any reason, inform them about the 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 physician or nurse experienced in the use of antineoplastic chemotherapy.

Cyclophosphamide will be administered by a physician or nurse.

It is given as an injection.
It is usually added to a large bag of fluid and slowly infused (perfused) directly into a vein. The vein may be in your arm, the back of your hand, or a large vein beneath your clavicle. Depending on the dose, administration usually takes from a few minutes to one hour.
Cyclophosphamide is usually administered in combination with other antineoplastic medicines 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 you will receive depends on:
the type of disease you have,
your body size (a combination of your height and weight),
your general health,
whether you are receiving other antineoplastic medicines or radiotherapy.

It is advisable to administer cyclophosphamide in the morning. Adequate fluid intake before, during, and after administration is important to prevent possible adverse effects on the urinary tract.

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

Your doctor may need to adjust your dose and monitor you more closely if:

you have problems with your liver or kidneys,
you are elderly.

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 highly unlikely that you could receive too much. However, if you experience adverse effects after receiving cyclophosphamide, inform your doctor immediately or go to the nearest hospital emergency department. You may require urgent medical attention.

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

Symptoms of cyclophosphamide overdose include the side effects listed in section "Possible side effects", but are generally more severe in nature.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

Sometimes side effects may occur after treatment has ended. The following side effects may occur with this medicine.

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

Allergic reactions. Signs may include difficulty breathing, wheezing, increased heart rate, drop in blood pressure (extreme tiredness), rash, itching, or swelling of the face and lips. Severe allergic reactions could lead to breathing difficulties or shock, possibly resulting in death (anaphylactic shock, anaphylactic/anaphylactoid reaction).
Appearance of bruises without injury, or bleeding gums. This could be a sign that your blood platelet levels are too low.
Decrease in white blood cell count; your doctor will monitor this during treatment. It will not cause any symptoms, but you may be more prone to infections. If you suspect you have an infection (high fever, chills and shivering, or feeling hot and sweaty, or any signs of infection such as cough or burning when urinating), you may need antibiotics to treat infections due to lower-than-normal blood counts.
Paleness, feeling lethargic and tired. These signs could indicate low red blood cell levels (anemia). Treatment is usually not required, as your body will naturally restore red blood cells over time. In cases of severe anemia, a blood transfusion may be necessary.
Blood in the urine, pain when urinating, or reduced urine volume.
Severe chest pain.
Symptoms such as weakness, vision loss, speech difficulties, or loss of sense of touch.

Other possible side effects may include:

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

Reduction in 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 urinate (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 mucous membranes (mucositis),
Blood in the urine and pain when urinating (hemorrhagic cystitis),
Presence of blood in the urine (macrohematuria),
Abnormal liver function,
Male infertility,
Chills,
Feeling of weakness,
General feeling of discomfort,
Low white blood cell count and fever (febrile neutropenia).

Uncommon (may affect up to 1 in 100 people):

Anemia (low red blood cell count) which may cause fatigue and drowsiness,
Tendency to bruise due to thrombocytopenia (low platelet count),
Lung inflammation (pneumonitis),
Septicemia,
Allergic reactions,
Female infertility (rarely irreversible),
Chest pain,
Rapid heartbeat,
Heart problems,
Changes in results of certain blood tests,
Skin redness (rash),
Nerve damage which may cause numbness, pain, and weakness (neuropathy),
Pain along the distribution of a nerve (neuralgia),
Anorexia,
Deafness,
Changes in ECG,
Decrease in LVEF (Left Ventricular Ejection Fraction),
Lower levels of female sex hormones.

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

Increased risk of blood cancer (acute leukemia) and some other cancers (bladder cancer, ureter cancer),
Ineffective production of myeloid blood cells (myelodysplastic syndrome),
Increased release of antidiuretic hormone from the pituitary gland (syndrome of inappropriate antidiuretic hormone secretion). This affects the kidneys and causes low sodium levels in the body (hyponatremia) and fluid retention, leading to brain swelling due to excess water in the blood. Signs may include headache, personality or behavioral changes, confusion, and drowsiness,
Changes in heart rhythm,
Liver inflammation,
Skin rash,
Skin inflammation,
Absence of menstruation (periods),
Absence of sperm,
Dizziness,
Vision disturbances, blurred vision,
Changes in the color of 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),
Blood clots forming in small blood vessels throughout the body (disseminated intravascular coagulation),
Shock,
Complications that may occur after cancer treatment due to 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,
Myocardial infarction,
Blockage of a blood vessel due to a blood clot in the circulatory system (thromboembolism),
Lung injury (acute respiratory distress syndrome),
Pulmonary fibrosis causing 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,
Mouth pain or ulcers (stomatitis),
Nausea, vomiting, or diarrhea,
Constipation,
Intestinal inflammation,
Pancreatitis,
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 hypersensitivity reaction with fever and skin blisters/skin peeling (toxic epidermal necrolysis),
Radiation erythema,
Itching,
Altered sense of taste (dysgeusia, hypogeusia),
Tingling, pins and needles, stinging, or burning sensations (paresthesia),
Altered sense of smell (parosmia),
Abnormal muscle breakdown which may lead to kidney problems (rhabdomyolysis),
Cramps,
Bladder problems,
Kidney problems, including kidney failure,
Headache,
Multi-organ failure,
Reaction at injection or infusion site,
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 blood creatinine.

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

Various types of cancer, such as blood cancer (non-Hodgkin lymphoma), kidney cancer, thyroid cancer,
Sarcoma,
Various types of blood disorders (agranulocytosis, lymphopenia, reduced hemoglobin),
Blockage of a blood vessel by a clot in the circulatory system (thromboembolic episodes), including possible blockage of pulmonary vessels (pulmonary embolism),
Blood clot, usually in a leg, causing pain, swelling, or redness (venous thrombosis),
Inflammation of blood vessels (vasculitis),
Reduced blood flow to hands and feet (peripheral ischemia). This may cause pain, weakness, numbness, ulcers, changes in skin color or temperature,
Increased tear production (lacrimation),
Ringing in the ears (tinnitus),
Hearing impairment,
Nasal blockage (nasal congestion),
Oropharyngeal pain,
Rhinorrhea,
Sneezing,
Veno-occlusive lung disease,
Obliterative bronchiolitis,
Allergic alveolitis,
Pneumonitis,
Pleural effusion,
Abdominal pain,
Stomach or intestinal bleeding,
Intestinal problems/bleeding,
Liver failure,
Rash, skin redness, blisters on lips, eyes or mouth, skin peeling (erythema multiforme, urticaria, erythema),
Hand-foot syndrome,
Facial swelling,
Increased sweating,
Skin hardening (scleroderma),
Muscle spasms and pain,
Joint pain,
Inflammation, sclerosis, and contraction of the bladder,
Fetal damage or death,
Changes in results of certain blood tests (blood glucose, hormone levels),
Brain disorder (encephalopathy), neurotoxicity manifested as a syndrome characterized by headache, confusion, seizures, and vision loss (posterior reversible encephalopathy syndrome), abnormal sensation (dysesthesia, hypoesthesia), tremor, altered sense of taste (dysgeusia, hypogeusia), altered sense of smell (parosmia),
Various types of heart disorders (ventricular tachycardia, cardiogenic shock, pericardial effusion, bradycardia, palpitations, QT interval prolongation on electrocardiogram),
Infertility in men and women,
Changes in menstrual frequency,
Intrauterine death,
Fetal malformation,
Fetal growth retardation,
Cardiogenic effect on offspring,
Inflammation of salivary glands (usually in the cheek area; parotid gland inflammation),
Skin redness (flushing) which may be accompanied by feeling of warmth or sweating (hot flush),
Increased blood pressure in the lungs which may cause difficulty breathing, fatigue, cough, chest pain, fainting, peripheral edema (pulmonary hypertension),
Impaired bile formation by the liver, which may cause itching, jaundice, pale stools, dark urine (cholestasis),
Accumulation of toxins in the body due to liver failure (hepatotoxicity). This may affect the brain, causing confusion, reduced 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),
Kidney tissue changes impairing proper function (renal tubular necrosis, renal tubular disorder),
Kidney damage due to toxins in the blood (toxic nephropathy),
Urethral inflammation causing pain and bleeding (hemorrhagic ureteritis),
Glucose in urine (nephrogenic diabetes insipidus),
Increased blood urea nitrogen levels. Your doctor will perform blood tests to monitor this,
Premature birth,
Nail disorder,
Toxic skin rash,
Blister,
Brain swelling due to excess water in the blood (water intoxication). Signs may include headache, personality or behavioral changes, confusion, drowsiness.

Reporting of adverse effects

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

By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Cyclophosphamide Seacross

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

Do not use this medicine after the expiry date stated on the carton and on the label of the vial following “EXP”. The expiry date refers to 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 standpoint, the reconstituted and diluted solution should be used immediately, unless reconstitution was carried out under controlled and validated aseptic conditions. If not used immediately, the in-use storage times and conditions prior to use are the responsibility of the user and normally should not exceed 24 hours at 2 - 8°C, unless the reconstitution/dilution was performed under controlled and validated aseptic conditions.

Medicines should not be disposed of via wastewater or household waste. Ask your doctor how to dispose of medicines and containers you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Cyclophosphamide Seacross

The active substance is cyclophosphamide.

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

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

It does not contain any other components.

Appearance of the product and contents of the pack

Cyclophosphamide Seacross is a white crystal or crystalline powder.

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

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

Each pack contains one vial of this medicine.

Marketing Authorisation 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)

Tel: 676295501

This medicine is authorised in the Member States of the European Economic Area under the following names:

Ireland	Cyclophosphamide Seacross 200 mg powder for solution for injection/infusion Cyclophosphamide Seacross 500 mg powder for solution for injection/infusion Cyclophosphamide Seacross 1000 mg powder for solution for injection/infusion Cyclophosphamide Seacross 2000 mg powder for solution for injection/infusion
Germany	Cyclophosphamide Seacross 200 mg powder for solution for injection/infusion Cyclophosphamide Seacross 500 mg powder for solution for injection/infusion Cyclophosphamide Seacross 1000 mg powder for solution for injection/infusion Cyclophosphamide Seacross 2000 mg powder for solution for injection/infusion
Netherlands	Cyclophosphamide Seacross 500 mg powder for solution for injection/infusion Cyclophosphamide Seacross 1000 mg powder for solution for injection/infusion Cyclophosphamide Seacross 2000 mg powder for solution for injection/infusion
Portugal	Cyclophosphamide Seacross
Spain	Cyclophosphamide Seacross 500 mg powder for injectable solution and for infusion EFG Cyclophosphamide Seacross 1,000 mg powder for injectable solution and for infusion EFG
France	CYCLOPHOSPHAMIDE SEACROSS 500 mg, powder for injectable solution/for infusion CYCLOPHOSPHAMIDE SEACROSS 1000 mg, powder for injectable solution/for infusion
Italy	CYCLOPHOSPHAMIDE SEACROSS

Date of the most recent review of this leaflet: October 2024

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

This information is intended for healthcare professionals only:

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

Cyclophosphamide should only be administered when facilities are available for routine monitoring of clinical, biochemical, and hematological parameters before, during, and after administration, and under the supervision of a specialized oncology department.

Dosage and method of administration

Dosage must be individualized. Doses, duration of treatment, and/or treatment intervals depend on the therapeutic indication, the regimen of a combination therapy, the patient's general health status and organ function, and the results of laboratory monitoring (particularly blood cell counts).

When used in combination with other cytostatic agents with similar toxicity, dose reduction or extension of treatment-free intervals may be necessary.

The use of hematopoiesis-stimulating agents (colony-stimulating factors and erythropoiesis-stimulating agents) may be considered to reduce the risk of myelosuppressive complications and/or to facilitate administration of the intended dose.

Adequate amounts of fluid should be ingested or infused before, during, and immediately after administration to promote diuresis and reduce the risk of urinary tract toxicity. Therefore, this medicine should be administered in the morning.

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

Personnel preparing the medication must wear protective gloves. Splashing of material into the eyes must be avoided. The material must not be handled by pregnant or breastfeeding women.

Handling

The choice of solvent for reconstitution of this cyclophosphamide-containing medicine depends on the intended route of administration.

Infusion

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

The reconstituted solution of this medicine must then be further diluted in 5% glucose or sodium chloride 9 mg/ml (0.9%) solution for infusion before administration.

Direct injection

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

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

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

The following volumes of water for injection or sodium chloride 9 mg/ml (0.9%) solution for injection should be added to vials containing Cyclophosphamide Seacross powder for solution for injection and for infusion:

500 mg vial: 25 ml
1,000 mg vial: 50 ml

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

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

Infusion:

The reconstituted medicine must 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 standards and guidelines for handling cytotoxic agents must be observed when reconstituting or manipulating this medicine. Whenever possible, reconstitution should be performed in a laminar airflow safety cabinet. Personnel handling the product must wear a protective mask and gloves. In case of spills, the area should be thoroughly washed with water. If Cyclophosphamide Seacross powder for solution for injection and for infusion is stored (e.g., during transport) at temperatures above the maximum permitted, cyclophosphamide may melt. Vials containing melted cyclophosphamide can be identified visually. Cyclophosphamide is a white powder. Melted cyclophosphamide is a clear or yellowish viscous liquid (usually appearing as droplets in the corresponding vials). Vials containing melted cyclophosphamide must not be used.

Guidelines for safe handling of antineoplastic drugs

When reconstituting or handling this medicine, general rules and regulations for handling cytotoxic agents must be observed.

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

Pregnant women must not handle cytotoxic preparations. The medicine must be diluted by appropriately trained personnel, in a designated area. The work surface should be covered with absorbent paper with a plastic backing.

Protective gloves, masks, and appropriate clothing must be worn. Precautions must be taken to avoid accidental contact of the medicine with skin or mucous membranes. Any affected area should be thoroughly washed with water and soap. In case of accidental eye contamination, eyes should be immediately and thoroughly rinsed with water.

Use Luer-Lock connectors on all syringes and equipment. Use of large-bore needles is recommended to minimize pressure and the potential for aerosol formation. This can also be reduced by using a vacuum needle.

Any unused amount should be discarded. Special precautions must be taken in the disposal of materials used to dilute cyclophosphamide. Any unused product or contaminated materials should be placed in a high-risk waste bag. Sharps (syringes, needles, vials, etc.) should be placed in an appropriate rigid container. Personnel responsible for collecting and disposing of these wastes must be aware of the associated risks.

Disposal

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