Ciclophosphamide Sandoz

Leaflet accompanying the packaging: patient information

Cyclophosphamide Sandoz, 100 mg/mL,

concentrate for solution for injection/infusion
Cyclophosphamide

Read the leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• In case of any doubts, consult a doctor, pharmacist, or nurse.
• If the patient experiences any side effects, including those not listed in this leaflet, they should inform their doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet

• 1. What is Cyclophosphamide Sandoz and what is it used for
• 2. Important information before using Cyclophosphamide Sandoz
• 3. How to use Cyclophosphamide Sandoz
• 4. Possible side effects
• 5. How to store Cyclophosphamide Sandoz
• 6. Contents of the packaging and other information

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

Cyclophosphamide Sandoz contains the active substance cyclophosphamide.
Cyclophosphamide is a cytotoxic medicine, also known as an anticancer medicine. Its action
consists in destroying cancer cells, which is sometimes called "chemotherapy".
Cyclophosphamide is often used alone or in combination with other anticancer medicines or with radiation therapy to treat various types of cancer in adults and children over 5 years old. These include:
certain types of blood cancer (acute lymphoblastic leukemia, chronic lymphocytic leukemia);
various forms of lymphoma that affect the immune system (Hodgkin's disease, non-Hodgkin's lymphoma, and multiple myeloma);
ovarian cancer and breast cancer;
Ewing's sarcoma (a type of bone cancer);
small cell lung cancer
treatment of advanced or metastatic central nervous system tumors (neuroblastoma);
In addition, cyclophosphamide is used in preparation for bone marrow transplantation to treat various types of blood cancer (acute lymphoblastic leukemia, chronic myeloid leukemia, and acute myeloid leukemia) in adults and children over 5 years old.
Occasionally, some doctors may prescribe cyclophosphamide to treat other, non-cancerous diseases:
life-threatening autoimmune diseases: severe, progressive forms of kidney inflammation (kidney inflammation caused by an immune system disease)
and Wegener's granulomatosis (a rare form of blood vessel inflammation) in adults and children over 5 years old.

2. Important information before using Cyclophosphamide Sandoz

Cyclophosphamide Sandoz will not be given to children under 5 years of age, as it contains excipients harmful to patients in this age group [see "Cyclophosphamide Sandoz contains propylene glycol" and "Cyclophosphamide Sandoz contains ethanol (alcohol)"].

When not to use Cyclophosphamide Sandoz

If the patient is allergic to cyclophosphamide, any of its metabolites, or any of the other ingredients of this medicine. Symptoms of an allergic reaction may include:
shortness of breath, wheezing, rash, itching, or swelling of the face and lips.
If the patient currently has any infection.
If the patient has bone marrow disorders (especially if the patient has previously undergone chemotherapy or radiation therapy). The doctor will order blood tests to check the bone marrow function.
If the patient has a urinary tract infection, which may cause pain when urinating (cystitis).
If the patient has ever had kidney or bladder diseases due to previous chemotherapy or radiation therapy, if the patient has difficulty urinating (urinary retention).
If the patient is breastfeeding.
If the patient has a non-life-threatening autoimmune disease.

Warnings and precautions

Before starting treatment with Cyclophosphamide Sandoz, the patient should discuss with their doctor if they have:
a low blood cell count;
severe infections;
liver or kidney disease. The doctor will order blood tests to check liver and kidney function;
had their adrenal glands removed;
have recently undergone radiation therapy or chemotherapy;
heart disease or have undergone radiation therapy to the chest area;
diabetes;
poor overall health or are weakened;
are elderly;
have undergone surgery in the last 10 days.
During cyclophosphamide treatment, potentially life-threatening allergic reactions (anaphylactic reaction) may occur.
Cyclophosphamide may affect the blood and immune system.
Blood cells are produced in the bone marrow. There are three different types:

• red blood cells, which transport oxygen in the body,
• white blood cells, which fight infection, and
• platelets, which help blood clot.

After receiving cyclophosphamide, the number of all three types of blood cells decreases. This is an unavoidable side effect of cyclophosphamide. The lowest number of blood cells is reached after about 5-10 days from the start of treatment and remains low for several days after the end of the treatment cycle. In most people, the blood cell count returns to normal within 21 to 28 days. If the patient has undergone multiple chemotherapy treatments in the past, the period of normalization of the blood cell count may take a little longer.
During the time when the blood cell count decreases, the patient may be more susceptible to infections.
It is recommended to avoid close contact with people who cough, have a cold, or have other infections.
If the doctor considers that the patient has an infection or is at risk of developing an infection, they will prescribe appropriate treatment.
Before starting cyclophosphamide treatment and during treatment, the doctor will check if the patient has a sufficient number of red blood cells, white blood cells, and platelets. It may be necessary to reduce the dose of the medicine or delay the administration of the next dose.
Cyclophosphamide may affect the process of proper wound healing. It is essential to keep any wound clean and dry and check if it is healing properly. It is also crucial to take care of oral health, as mouth ulcers and oral infections may occur. In case of doubts, the patient should consult their doctor.
Cyclophosphamide may damage the tissue lining the bladder, causing blood in the urine and pain when urinating. This effect is known to the doctor, so they may prescribe a medicine called mesna, which protects the bladder. Mesna can be given as a short injection or added to the cyclophosphamide infusion or given in tablet form.
In most people receiving cyclophosphamide with mesna, there are no problems with the bladder, but the doctor may order a urine test to detect the presence of blood using a dipstick test or a microscope. If the patient notices blood in their urine, they should immediately inform their doctor.
Anticancer medicines and radiation therapy may increase the risk of developing other cancers, even years after the end of treatment. Cyclophosphamide increases the risk of bladder cancer.
Cyclophosphamide may damage the heart or affect its rhythm. This effect is increased when high doses of cyclophosphamide are used, when radiation therapy is given, or when other chemotherapeutic medicines are used, or in elderly people. During treatment, the doctor will closely monitor the patient's heart function.
Cyclophosphamide may cause lung diseases, such as inflammation or scarring of the lungs. This may occur more than 6 months after the end of treatment. If the patient experiences difficulty breathing, they should immediately inform their doctor.
Cyclophosphamide may have a life-threatening effect on the liver.
In case of sudden weight gain, liver pain, and yellowing of the skin or whites of the eyes (jaundice), the patient should immediately inform their doctor.
It is possible to experience hair loss or baldness. Hair should grow back normally, although it may have a different texture or color.
Cyclophosphamide may cause nausea or vomiting. This may last for about 24 hours after administration. It may be necessary to take anti-emetic medicines. The patient should consult their doctor about this.

Children and adolescents

Cyclophosphamide Sandoz will not be given to children under 5 years of age due to the risk associated with the excipients. (See section 2 "Important information before using Cyclophosphamide Sandoz", "Cyclophosphamide Sandoz contains propylene glycol" and "Cyclophosphamide Sandoz contains ethanol (alcohol)").
Cyclophosphamide has been given to children. The safety profile of the active substance - cyclophosphamide - in children and adolescents is similar to that in adults.

Cyclophosphamide Sandoz and other medicines

The patient should tell their doctor about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take. The patient should inform their doctor especially about the following medicines or treatments, as they may not work properly with cyclophosphamide:

The following medicines may reduce the effectiveness of cyclophosphamide:

• aprepitant (anti-emetic medicine)
• bupropion (antidepressant medicine)
• busulfan, tiotepa (anticancer medicines)
• ciprofloxacin, chloramphenicol, rifampicin (antibacterial medicines)
• fluconazole, itraconazole (antifungal medicines)
• prasugrel (antiplatelet medicine)
• sulfonamides, such as sulfadiazine, sulfasalazine, sulfamethoxazole (antibacterial medicines)
• ondansetron (anti-emetic medicine)
• St. John's Wort (herbal preparation used for mild depression)

The following medicines may increase the toxicity of cyclophosphamide:

• allopurinol (medicine used to treat gout)
• azathioprine (medicine used to suppress the immune system)
• chloral hydrate (medicine used to treat insomnia)
• cimetidine (medicine that reduces stomach acid production)
• disulfiram (medicine used to treat alcoholism)
• aldehyde glycerin (used to treat warts)
• protease inhibitors (medicines used to treat viral infections)
• medicines that increase liver enzyme activity, such as rifampicin (antibacterial medicine), carbamazepine, phenobarbital, phenytoin (antiepileptic medicines), St. John's Wort (herbal preparation used for mild depression), corticosteroids (medicines used to treat inflammatory conditions)
• dabrafenib (medicine used to treat cancer)

Medicines that may increase the toxic effect of cyclophosphamide on the hematopoietic system and immune system:

• angiotensin-converting enzyme inhibitors (medicines used to treat high blood pressure)
• natalizumab (medicine used to treat multiple sclerosis)
• paclitaxel (medicine used to treat cancer)
• thiazide diuretics, such as hydrochlorothiazide or chlorthalidone (used to treat high blood pressure or fluid retention)
• zidovudine (medicine used to treat viral infections)
• clozapine (medicine used to treat symptoms of certain mental disorders)

Medicines and treatments that may increase the toxic effect of cyclophosphamide on the heart:

• anthracyclines, such as bleomycin, doxorubicin, epirubicin,
• mitomycin (anticancer medicines)
• cytarabine, pentostatin, trastuzumab (anticancer medicines)
• radiation to the chest area

Medicines that may increase the toxic effect of cyclophosphamide on the lungs:

• amiodarone (medicine used to treat heart rhythm disorders)
• G-CSF, GM-CSF hormones (used to increase the number of white blood cells after chemotherapy)

Medicines that may increase the toxic effect of cyclophosphamide on the kidneys

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

Other medicines that may affect the action of cyclophosphamide or be affected by cyclophosphamide:

• etanercept (medicine used to treat rheumatoid arthritis)
• metronidazole (medicine used to treat bacterial or protozoal infections)
• tamoxifen (medicine used to treat breast cancer)
• bupropion (medicine used to help quit smoking)
• coumarins, such as warfarin (anticoagulant medicines)
• cyclosporine (medicine used to suppress the immune system)
• succinylcholine (medicine used to relax muscles during surgery)
• digoxin, beta-acetyldigoxin (medicines used to treat heart conditions)
• vaccines
• verapamil (medicine used to treat high blood pressure, angina, or heart rhythm disorders)
• sulfonylurea derivatives (oral antidiabetic medicines) (concomitant use with cyclophosphamide may cause a decrease in blood sugar levels)

Using Cyclophosphamide Sandoz with food, drink, and alcohol

Alcohol may increase nausea and vomiting caused by cyclophosphamide.
During cyclophosphamide treatment, the patient should not consume grapefruits (as fruit or juice).
They may interfere with the proper action of the medicine and change its effectiveness.

Pregnancy, breastfeeding, and fertility

If the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a child, they should consult their doctor before using this medicine.
Pregnancy
Cyclophosphamide may cause miscarriage or harm to the fetus.
Women should not become pregnant while using Cyclophosphamide Sandoz and for 12 months after the end of treatment.
Men should take appropriate precautions, including the use of effective contraception, to avoid conceiving a child while using Cyclophosphamide Sandoz and for 6 months after the end of treatment.
If a girl is treated with cyclophosphamide before puberty, sexual development is usually normal, and it is possible to become pregnant. However, if the ovaries function properly after cyclophosphamide treatment, there is a risk of premature menopause.
Breastfeeding
The patient should not breastfeed while using this medicine, as cyclophosphamide passes into human milk and may harm breastfed babies. The patient should consult their doctor before using this medicine.
Fertility
Cyclophosphamide may affect the ability to conceive in the future. The patient should consult their doctor about the possibility of cryopreservation (freezing) of sperm or eggs before starting treatment, due to the risk of irreversible infertility caused by cyclophosphamide treatment. Patients planning to have children after the end of treatment should discuss this with their doctor.

Driving and using machines

After receiving cyclophosphamide, side effects such as seizures and vision disturbances may occur, which may affect the ability to drive and use machines. The amount of alcohol in this medicine may affect the ability to drive and use machines (see "Cyclophosphamide Sandoz contains ethanol (alcohol)"). The decision to drive or use machines is made individually by the doctor.

Cyclophosphamide Sandoz contains ethanol (alcohol)

This medicine contains 585 mg of alcohol (ethanol) per milliliter. The amount of alcohol in 1 mL of this medicine is equivalent to 15 mL of beer or 6 mL of wine.
Alcohol in this medicine may affect children. Symptoms may include drowsiness and changes in behavior. It may also affect their concentration and physical activity.
This medicine should not be used in children under 5 years of age.
The amount of alcohol in this medicine may affect the ability to drive and use machines, as it may affect judgment and reaction time.
If the patient has epilepsy or liver disease, they should consult their doctor or pharmacist before using this medicine.
The amount of alcohol in this medicine may change the effect of other medicines.
If the patient is taking other medicines, they should consult their doctor or pharmacist.
If the patient is pregnant or breastfeeding, they should consult their doctor or pharmacist before using this medicine.
If the patient is addicted to alcohol, they should consult their doctor or pharmacist before using this medicine.

Cyclophosphamide Sandoz contains propylene glycol

This medicine contains 192 mg of propylene glycol per milliliter. For this reason, the medicine should not be used in children under 5 years of age.
Do not give this medicine to a child under 5 years of age without a doctor's recommendation.
Pregnant or breastfeeding women should not take this medicine without a doctor's recommendation.
The doctor may decide to perform additional tests on these patients.
Patients with liver or kidney disorders should not take this medicine without a doctor's recommendation. The doctor may decide to perform additional tests during treatment with this medicine.

3. How to use Cyclophosphamide Sandoz

Method of administration
Intravenous administration
Cyclophosphamide Sandoz will be administered to the patient by a doctor or nurse with experience in using anticancer chemotherapy. Cyclophosphamide Sandoz is given by intravenous injection and usually added to a large bag of fluid, and then administered as a slow infusion directly into a vein. This can be a vein in the arm, back of the hand, or a large vein under the collarbone.
Depending on the dose, the infusion usually lasts from 30 to 120 minutes.
Cyclophosphamide is often used with other anticancer medicines or with radiation therapy.
Recommended dose:
The doctor decides on the amount of medicine to be given to the patient and the time of administration.
The amount of cyclophosphamide administered depends on:

• the type of disease;
• the patient's body size (height and weight);
• the patient's overall health;
• the use of other anticancer medicines or radiation therapy.

It is recommended to administer cyclophosphamide in the morning. It is essential to ensure that the patient receives adequate amounts of fluids before, during, and after administration to prevent adverse effects on the urinary tract.
If the patient notices that Cyclophosphamide Sandoz is working too strongly or too weakly, they should contact their doctor or pharmacist.
The doctor may decide to change the dose of the medicine and closely monitor the patient's condition if:
the patient has liver or kidney disease
the patient is elderly

Using a higher dose of Cyclophosphamide Sandoz than recommended

Cyclophosphamide is administered under the supervision of a doctor, so it is very unlikely that too much of it will be given. However, if the patient experiences any side effects after administration, they should immediately inform their doctor or go to the emergency department of the nearest hospital. Emergency medical attention may be necessary.
Symptoms of cyclophosphamide overdose include side effects listed below in the "Side effects" section, but they are usually more severe.
In case of any further doubts about using this medicine, the patient should consult their doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

The patient should immediately consult their doctor if they experience:

an allergic reaction. Symptoms are shortness of breath, wheezing, rapid heartbeat, low blood pressure (severe exhaustion), rash, itching, or
swelling of the face and lips. Severe allergic reactions can cause difficulty breathing or shock, which can be life-threatening (anaphylactic shock, anaphylactic reaction, or pseudo-anaphylactic reaction).
unexplained bruising or bleeding from the gums. These may be signs of a low platelet count.
severe infection or fever, mouth ulcers, cough, shortness of breath, signs of sepsis, such as fever, rapid breathing, rapid heartbeat, confusion, and swelling. These may be signs of a low white blood cell count and may require the use of antibiotics to fight the infection.
significant pallor, lethargy, and fatigue. These may be signs of a low red blood cell count (anemia). Usually, no treatment is necessary - the body will compensate for the lack of red blood cells. Severe anemia may require blood transfusion.
blood in the urine, pain when urinating, or decreased urine output
severe chest pain
symptoms such as weakness, loss of vision, speech disturbances, loss of touch
severe hypersensitivity reactions with (high) fever, red spots on the skin, joint pain, and (or) eye infection (Stevens-Johnson syndrome)
severe, sudden (hypersensitive) reaction with fever and blisters on the skin/exfoliative dermatitis (toxic epidermal necrolysis)
rhabdomyolysis (a condition that causes muscle tissue to break down)
decreased white blood cell count, which plays an important role in fighting infection (agranulocytosis).
Cyclophosphamide may also cause the following side effects:

Very common: may occur in more than 1 in 10 people

decreased blood cell count (myelosuppression)
decreased white blood cell count, which is important for fighting infection (leukopenia, neutropenia)
hair loss (alopecia)
burning sensation when urinating or frequent urination (cystitis)
blood in the urine, which can only be detected by urine tests (microhematuria)
fever
suppression of the immune system

Common: may occur in up to 1 in 10 people

infections
inflammation of the mucous membranes
blood in the urine and painful urination (hemorrhagic cystitis)
visible blood in the urine (macrohematuria)
abnormal liver function
male infertility
chills
feeling of weakness
general malaise
decreased white blood cell count with fever (febrile neutropenia)

Uncommon: may occur in up to 1 in 100 people

anemia (low red blood cell count), which may cause fatigue and sleepiness
easy bruising due to low platelet count (thrombocytopenia)
pneumonia
sepsis
allergic reactions
female infertility (rarely permanent)
chest pain
rapid heartbeat
heart rhythm disturbances
changes in the results of some blood tests
sudden redness of the skin (mainly on the face)
nerve damage, causing numbness, tingling, and weakness (neuropathy)
nerve pain (neuralgia)
eating disorders (anorexia)
hearing loss

Rare: may occur in up to 1 in 1,000 people

increased risk of developing blood cancer (acute leukemia) and other cancers (bladder cancer, ureteral cancer)
ineffective production of myeloid blood cells (myelodysplastic syndrome)
increased release of antidiuretic hormone by the pituitary gland (syndrome of inappropriate antidiuretic hormone secretion). This affects the kidneys, causing low sodium levels in the blood (hyponatremia) and water retention, leading to brain swelling due to excessive water in the blood. Symptoms may include headache, personality or behavioral changes, confusion, and sleepiness.
changes in heart rhythm
hepatitis
rash
dermatitis
amenorrhea
oligomenorrhea
gynecomastia
dizziness
visual disturbances, blurred vision
changes in nail color and skin
dehydration
seizures
bleeding

Very rare: may occur in up to 1 in 10,000 people

breakdown of red blood cells and kidney failure (hemolytic-uremic syndrome)
formation of blood clots in small blood vessels of the body (disseminated intravascular coagulation)
shock
complications of anticancer treatment due to the breakdown of cancer cells (tumor lysis syndrome)
low sodium levels in the blood (hyponatremia)
high blood pressure (hypertension)
low blood pressure (hypotension)
angina pectoris
heart attack
blockage of a blood vessel due to a blood clot in the circulatory system (thromboembolic events), including the possibility of blockage of pulmonary vessels (pulmonary embolism)
lung damage (acute respiratory distress syndrome)
scarring of the lungs, causing shortness of breath (chronic interstitial pneumonitis)
difficulty breathing with wheezing or coughing (bronchospasm)
shortness of breath (dyspnea)
condition in which the body or a part of the body is deprived of adequate oxygen supply (hypoxia)
cough
mouth and throat pain
runny nose
sneezing
blockage of small veins in the lungs (pulmonary veno-occlusive disease)
blockage of the smallest airways in the lungs due to inflammation (bronchiolitis obliterans)
allergic inflammation of the lung air sacs (allergic pneumonitis)
pneumonia
fluid in the lungs (pleural effusion)
abdominal pain
bleeding in the stomach or intestines
gastrointestinal disorders/bleeding
abnormal liver function
rash, redness of the skin, blistering of the lips, eyes, or mouth, and skin peeling (erythema multiforme, urticaria, rash)
hand-foot syndrome
facial swelling
excessive sweating
scleroderma
muscle spasms and pain
joint pain
inflammation, scarring, and contraction of the bladder
fetal damage or death
stillbirth
birth defects
delayed fetal development
carcinogenic effect on offspring
changes in the results of some blood tests (glucose levels, hormone levels)
brain function disorders (encephalopathy), neurotoxicity manifested as a syndrome characterized by headache, disorientation, seizures, and vision loss (posterior reversible encephalopathy syndrome), sensory disturbances (dysesthesia, hypesthesia), tremors, taste disorders (dysgeusia, hypogeusia), smell disorders (parosmia)
various types of heart rhythm disorders (ventricular tachycardia, cardiogenic shock, pericardial effusion, bradycardia, palpitations, QT interval prolongation on the electrocardiogram)
infertility in women and men
changes in menstrual frequency
parotid gland inflammation (usually in the cheek area; parotid gland inflammation)
If any of the side effects get worse or if the patient experiences any side effects not listed in this leaflet, they should inform their doctor, pharmacist, or nurse.

Reporting side effects

If the patient experiences any side effects, including those not listed in this leaflet, they should inform their doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Monitoring of Adverse Reactions to Medicinal Products of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder.
Reporting side effects will help to gather more information on the safety of the medicine.

5. How to store Cyclophosphamide Sandoz

The medicine should be stored out of sight and reach of children.
Do not use this medicine after the expiry date stated on the label and carton after:
Expiry date (EXP). The expiry date refers to the last day of the month.
Store in a refrigerator (2°C - 8°C).
After first opening:
The partially used vial should be stored in a refrigerator at a temperature between 2°C and 8°C. The medicine should be used within 28 days of first opening. Any remaining medicine should be discarded.
After dilution:
The chemical and physical stability of the diluted solution has been demonstrated in accordance with the following table.

Table: Storage of diluted cyclophosphamide solutions

From a microbiological point of view, the diluted medicine should be used immediately. If the diluted medicine is not used immediately, the user is responsible for the storage time and conditions before use. Usually, this time should not exceed 24 hours at 2°C - 8°C, unless the dilution took place in controlled and validated aseptic conditions.
Medicines should not be disposed of via wastewater. The patient should ask their pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the packaging and other information

What Cyclophosphamide Sandoz contains

• The active substance of the medicine is cyclophosphamide. Each milliliter contains cyclophosphamide monohydrate equivalent to 100 mg of cyclophosphamide. Each vial containing 5 mL of concentrate contains cyclophosphamide monohydrate equivalent to 500 mg of cyclophosphamide. Each vial containing 10 mL of concentrate contains cyclophosphamide monohydrate equivalent to 1000 mg of cyclophosphamide. Each vial containing 20 mL of concentrate contains cyclophosphamide monohydrate equivalent to 2000 mg of cyclophosphamide.
• Other ingredients are ethanol and propylene glycol (see sections "Cyclophosphamide Sandoz contains ethanol (alcohol)" and "Cyclophosphamide Sandoz contains propylene glycol").

What Cyclophosphamide Sandoz looks like and contents of the pack

Cyclophosphamide Sandoz is a clear solution with a color from colorless to pale yellow, practically free from visible particles.
Cyclophosphamide Sandoz is in a vial made of colorless glass type I, closed with a stopper made of bromobutyl rubber type I, and protected with an aluminum seal with a dark orange, plastic flip-off cap.
Pack sizes:

• 1 multidose vial containing 5 mL of concentrate for solution for injection/infusion, equivalent to 500 mg of cyclophosphamide.
• 1 multidose vial containing 10 mL of concentrate for solution for injection/infusion, equivalent to 1000 mg of cyclophosphamide.
• 1 multidose vial containing 20 mL of concentrate for solution for injection/infusion, equivalent to 2000 mg of cyclophosphamide.

Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder
Sandoz Polska Sp. z o.o.
ul. Domaniewska 50C
02-672 Warsaw
phone: 22 209 70 00
Manufacturer
Fareva Unterach GmbH
Mondseestrasse 11
4866 Unterach Am Attersee
Austria

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

Denmark
Cyclophosphamide Sandoz
Austria
Cyclophosphamid Sandoz 100 mg/ml –Konzentrat zur Herstellung einer Injektions-
/Infusionslösung
Bulgaria
Cyclophosphamide Sandoz 100 mg/ mL concentrate for solution for injection/infusion
Poland
Cyclophosphamide Sandoz
Sweden
Cyclophosphamide Sandoz

Date of last update of the leaflet:

Logo Sandoz
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Information intended exclusively for professional medical personnel:
The medicinal product Cyclophosphamide Sandoz should only be administered by a doctor
with experience in the use of anticancer chemotherapy. The medicinal product
Cyclophosphamide Sandoz should only be administered in places where equipment is available
enabling regular monitoring of clinical, biochemical and hematological parameters both before, during and after administration, under the supervision of an oncology specialist.
Dosing and administration
The dose should be determined individually for each patient. Doses and duration of treatment and (or)
intervals between treatment cycles depend on the therapeutic indication, the scheme of combined therapy, the patient's overall health and organ function, as well as the results of laboratory tests
(in particular, blood cell count control).
In combined therapy with other cytostatics of similar toxicity, it may be necessary to reduce the dose or prolong the intervals between treatment cycles.
The use of hematopoietic stimulating factors (colony-stimulating factors and erythropoiesis-stimulating factors) may be considered to reduce the risk of complications associated with bone marrow suppression and (or) facilitate the administration of the intended dose.
To reduce the risk of toxic effects on the urinary tract, before, during, and immediately after administration of the medicinal product, the patient should be given an appropriate amount of fluid orally or by infusion to induce diuresis. Therefore, the medicinal product Cyclophosphamide Sandoz should be administered in the morning.
Handling of the medicinal product
Cyclophosphamide is inactive until activated by liver enzymes. However, as with all cytotoxic drugs, it is recommended that the medicinal product be prepared by trained medical personnel in a designated area.
Precautions to be taken before preparation or administration of the medicinal product
Persons preparing the medicinal product should wear protective gloves. Caution should be exercised to avoid contact of the medicinal product with the eyes. Pregnant or breastfeeding women should not have direct contact with this medicinal product.
The volume of solvent required to dilute the medicinal product Cyclophosphamide Sandoz, containing cyclophosphamide, depends on the route of administration.
Direct injection
If the medicinal product Cyclophosphamide Sandoz (containing cyclophosphamide) is to be used for direct intravenous injection, the concentrate with a concentration of 100 mg/mL should be diluted to a concentration of 20 mg/mL with an appropriate volume of one of the following diluents:

• sodium chloride solution with a concentration of 0.9%
• sodium chloride solution with a concentration of 0.45%
• glucose solution with a concentration of 5%
• a solution containing glucose at a concentration of 5% and sodium chloride at a concentration of 0.9%

Infusion
If the medicinal product Cyclophosphamide Sandoz (containing cyclophosphamide) is to be used for intravenous infusion, the concentrate with a concentration of 100 mg/mL should be diluted with an appropriate volume of one of the following diluents:

• sodium chloride solution with a concentration of 0.9%
• sodium chloride solution with a concentration of 0.45%
• glucose solution with a concentration of 5%
• a solution containing glucose at a concentration of 5% and sodium chloride at a concentration of 0.9%

The medicinal product Cyclophosphamide Sandoz (containing cyclophosphamide) reconstituted in water is hypotonic and should not be administered by direct injection.

Intravenous administration
The preferred method of intravenous administration is infusion.
The decision to use cyclophosphamide in accordance with applicable treatment guidelines is up to the doctor.
Example volumes of cyclophosphamide concentrate and diluents required to achieve a concentration in the range of 20 mg/mL (for direct injection) to 0.4 mg/mL (for infusion) are given in the table below as guidelines for a dose of 100 mg.

Table: Examples of volumes for diluting cyclophosphamide

Preparation of the infusion or injection solution
Step 1
The required number of vials of cyclophosphamide concentrate for preparation of the infusion solution should be left at a temperature of 20-25°C for 5 minutes.
Each milliliter of the medicinal product contains 100 mg of cyclophosphamide.
To achieve the dose intended for the patient, it may be necessary to use more than one vial of cyclophosphamide concentrate for preparation of the infusion solution with a concentration of 100 mg/mL. The required amount of cyclophosphamide concentrate for preparation of the infusion solution should be drawn up aseptically using a calibrated syringe. For example, a dose of 1000 mg of cyclophosphamide requires the withdrawal of 10.00 mL of concentrate.
Step 2
In the case of direct injection, the withdrawn concentrate should be diluted to a concentration of 20 mg/mL by drawing up an appropriate volume of sodium chloride solution with a concentration of 0.9%, sodium chloride solution with a concentration of 0.45%, glucose solution with a concentration of 5%, or a solution containing glucose at a concentration of 5% and sodium chloride at a concentration of 0.9%.
In the case of infusion, the required volume of cyclophosphamide concentrate for preparation of the infusion solution should be injected into an intravenous fluid bag containing sodium chloride solution with a concentration of 0.9%, sodium chloride solution with a concentration of 0.45%, glucose solution with a concentration of 5%, or a solution containing glucose at a concentration of 5% and sodium chloride at a concentration of 0.9%. The resulting infusion solution should have a minimum concentration of 0.4 mg/mL.
Step 3
Remove the syringe and, by shaking, manually mix the contents of the infusion bag or bottle.
Step 4
As with all parenteral medicinal products, the resulting infusion solution should be visually inspected for the presence of particulate matter and changes in color, to the extent that the solution and container permit. After dilution, the solution is clear and colorless to light yellow. Only clear solutions should be used. Since the infusion solution is supersaturated, it may crystallize over time. In such a case, the solution should not be used and should be discarded.
Step 5
To reduce the likelihood of adverse reactions that appear to be dependent on the rate of administration (e.g., facial edema, headache, nasal congestion, scalp burning), cyclophosphamide should be injected or administered by infusion very slowly.
The duration of the infusion (from 30 minutes to 2 hours) should be adjusted according to the volume and type of vehicle fluid administered.
The preparation and administration of the medicinal product Cyclophosphamide Sandoz must be carried out in accordance with the principles and regulations for the use of cytostatic drugs. Dilution should, if possible, be carried out in a safety cabinet with a laminar airflow. The person preparing the medicinal product must wear a protective mask and gloves.
In the event of spillage, the surface should be thoroughly rinsed with water.
Guidelines for safe handling of anticancer drugs
Pregnant women should not participate in the preparation of cytotoxic drugs. The medicinal product should be diluted by trained personnel. This should be done in a designated area. The work surface should be covered with a single-use absorbent paper with a plastic backing.
Appropriate protective gloves, masks, and clothing should be worn. Precautions should be taken to avoid accidental contact of the medicinal product with the skin or mucous membranes, and any exposed area should be thoroughly washed with soap and water. If accidental contamination of the eyes occurs, they should be immediately and thoroughly rinsed with water.
Luer-lock syringes and equipment should be used. The use of needles with a large opening is recommended to minimize pressure and the possibility of aerosol formation. The risk of aerosol formation can also be reduced by using a vented needle.
Any unused remnants of the drug should be disposed of. Appropriate precautions should be taken when disposing of equipment used for dilution of cyclophosphamide. Any remnants of the drug or contaminated materials should be placed in bags for high-risk products. Sharp objects (needles, syringes, vials, etc.) should be placed in an appropriate rigid container. Personnel involved in the collection and disposal of these wastes should be aware of the associated hazard.
The entire unused medicinal product or waste should be disposed of in accordance with local regulations for cytotoxic drugs.
Storage and shelf-life
After first opening:
A partially used vial should be stored in a refrigerator at a temperature between 2°C and 8°C. The medicinal product should be used within 28 days of first opening. Any remnants of the medicinal product should be discarded.
After dilution:
Chemical and physical stability of the diluted solution has been demonstrated in accordance with the table below.

Table: Storage of diluted cyclophosphamide solutions

From a microbiological point of view, the diluted medicinal product should be used immediately.
If the medicinal product is not used immediately, the user is responsible for the storage time and conditions prior to use, and this time should not normally exceed 24 hours at a temperature of 2°C - 8°C, unless the dilution has taken place in controlled and validated aseptic conditions.