Ciclophosphamide Accord

Leaflet accompanying the packaging: patient information

Cyclophosphamide Accord, 500 mg, powder for solution for injection/infusion

Cyclophosphamide Accord, 1000 mg, powder 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.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including any 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 Accord and what is it used for
• 2. Important information before using Cyclophosphamide Accord
• 3. How to use Cyclophosphamide Accord
• 4. Possible side effects
• 5. How to store Cyclophosphamide Accord
• 6. Contents of the packaging and other information

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

Cyclophosphamide Accord contains the active substance cyclophosphamide.
Cyclophosphamide is a cytotoxic medicine, also known as an anticancer medicine.
Its action involves destroying cancer cells, which is sometimes referred to as "chemotherapy".
Cyclophosphamide Accord is used in chemotherapy alone or in combination with other medicines in the following cases:

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

In addition, cyclophosphamide is used in preparation for bone marrow transplantation to treat various types of white blood cell cancer (acute lymphoblastic leukemia, chronic myeloid leukemia, and acute myeloid leukemia).
Occasionally, some doctors may prescribe cyclophosphamide to treat other non-cancerous diseases:

• 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 blood vessel inflammation).

2. Important information before using Cyclophosphamide Accord

When not to use Cyclophosphamide Accord

• if the patient is allergic to cyclophosphamide or any of its metabolites or any of the other ingredients of this medicine (listed in section 6);
• if the patient currently has any infection;
• if the patient has severe bone marrow disorders (especially after chemotherapy or radiation therapy). The doctor will recommend blood tests to check bone marrow function;
• if the patient has a urinary tract infection, which may cause pain when urinating (cystitis);
• if the patient has had kidney or bladder disorders in the past due to previous chemotherapy or radiation therapy;
• if the patient has problems with urination (urinary retention);
• if the patient is breastfeeding;
• if the patient has other non-cancerous diseases, except for life-threatening immune system disorders.

Warnings and precautions

Before using Cyclophosphamide Accord, the patient should discuss it with their doctor, pharmacist, or nurse:

• if the patient has a low blood cell count;
• if the patient has severe infections;
• if the patient has liver or kidney disease; the doctor will recommend blood tests to check liver and kidney function;
• if the patient has had their adrenal glands removed;
• if the patient has recently undergone or is undergoing radiation therapy or chemotherapy;
• if the patient has heart problems or has been irradiated in the chest area;
• if the patient has diabetes;
• if the patient is in poor general health or is weak;
• if the patient is elderly;
• if the patient has had surgery in the last 10 days.

Special caution is required when using Cyclophosphamide Accord:

• During cyclophosphamide treatment, potentially life-threatening allergic reactions (anaphylactic reactions) 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,
• 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 usually observed 5-10 days after starting treatment and remains low for several days after the end of the treatment cycle. In most people, the number of blood cells returns to normal within 21-28 days. If the patient has been treated with chemotherapy multiple times in the past, the period of normalization of blood cell count may take a little longer.
• During the time when the number of blood cells decreases, the patient may be more susceptible to infection. The patient should avoid close contact with people who are coughing, have a cold, or have other infections. If the doctor believes that the patient has an infection or is at risk of developing an infection, they will prescribe appropriate treatment.
• Before and during cyclophosphamide treatment, the doctor will check if the number of red blood cells, white blood cells, and platelets is sufficient. 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. The patient should take care to keep any cuts clean and dry and check if they are healing properly. It is essential to take care of gum health, as mouth ulcers and oral infections may occur. If in doubt, the patient should ask their doctor.
• Cyclophosphamide may damage the lining of 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.

Cyclophosphamide may cause hair loss or baldness. Hair should grow back normally, although it may have a different texture or color.

• Mesna is given in a short injection, can be added to the cyclophosphamide drip, or taken in tablet form. More information about mesna can be found in the patient leaflet prepared for the injection and tablet forms.
• Most people who receive cyclophosphamide with mesna do not have any problems with their 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.
• Cancer 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 or other chemotherapy medicines are used, or in elderly patients. During treatment, the doctor will closely monitor heart function.
• Cyclophosphamide may cause lung problems, such as non-infectious 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. If the patient experiences sudden weight gain, liver pain, and yellowing of the skin or whites of the eyes (jaundice), they should immediately inform their doctor.
• Cyclophosphamide may cause nausea or vomiting. This may last for about 24 hours after administration. The patient may need to take anti-emetic medicines. They should consult their doctor about this.

Cyclophosphamide Accord and other medicines

The patient should tell their doctor or pharmacist about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take. They should especially inform them about the use of the following medicines or types of therapy, as cyclophosphamide may interfere with their action.
The following medicines may reduce the effect of cyclophosphamide:

• aprepitant, ondansetron (anti-emetic medicine)
• bupropion (antidepressant medicine)
• busulfan, tiotepa (cancer medicines)
• ciprofloxacin, chloramphenicol, sulfonamides, such as sulfadiazine, sulfasalazine, sulfamethoxazole (antibacterial medicines)
• fluconazole, itraconazole (antifungal medicines)
• prasugrel (antiplatelet medicine)

The following medicines may increase the effect of cyclophosphamide:

• allopurinol (medicine for gout)
• azathioprine (medicine to suppress the immune system)
• chloral hydrate (medicine for insomnia)
• cimetidine (medicine to reduce stomach acid)
• disulfiram (medicine for alcoholism)
• aldehyde glicerynowy (used to treat warts)
• protease inhibitors (medicines for viral infections)
• dabrafenib (anticancer medicine)
• medicines that increase the activity of liver enzymes, such as:
• rifampicin (antibacterial medicine)
• phenobarbital, carbamazepine, phenytoin (antiepileptic medicines)
• St. John's Wort (herbal medicine for mild depression)
• glucocorticosteroids (medicines for inflammation)

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

• ACE inhibitors, thiazide diuretics, such as hydrochlorothiazide or chlorthalidone (used to treat high blood pressure or fluid retention)
• natalizumab (medicine for multiple sclerosis)
• paclitaxel (medicine for cancer)
• zidovudine (medicine for viral infections)
• clozapine (medicine for psychiatric disorders)

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

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

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

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

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

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

Cyclophosphamide Accord with food, drink, and alcohol

Drinking alcohol may increase the nausea and vomiting caused by cyclophosphamide.
The patient should not consume grapefruits (as fruit or juice) while taking cyclophosphamide.
They may interfere with the proper action of the medicine and change its effectiveness.

Contraception, pregnancy, breastfeeding, and fertility

Contraception in men and women
Women should not become pregnant while taking Cyclophosphamide Accord and for up to 12 months after the end of treatment.
Men should take appropriate precautions, including effective contraception, to avoid conceiving a child while taking Cyclophosphamide Accord and for up to 6 months after the end of treatment.
Pregnancy
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.
Cyclophosphamide may cause miscarriage or fetal harm. Given the available information, the use of cyclophosphamide is not recommended during pregnancy, especially during the first trimester, and the decision to use it will be made by the doctor.
Breastfeeding
Since cyclophosphamide passes into breast milk, women should not breastfeed during treatment.
See section 2 "When not to use Cyclophosphamide Accord".
Fertility
Cyclophosphamide may affect the ability to have children in the future and may cause infertility. The patient should consult their doctor about the possibility of cryopreservation (freezing) of sperm before treatment. Patients planning to have children after the end of treatment should discuss this with their doctor.
In young women with ovarian reserve, premature menopause may develop after cyclophosphamide treatment.

Driving and using machines

After receiving cyclophosphamide, the patient may experience side effects such as dizziness, blurred vision, and vision disturbances, which may affect their ability to drive vehicles and operate machines. The decision to drive or operate machines is made individually by the doctor.

3. How to use Cyclophosphamide Accord

Cyclophosphamide Accord will be administered to the patient by a doctor or nurse with experience in cancer chemotherapy.
The medicine is usually given intravenously. The administration time usually lasts from 30 minutes to 2 hours, depending on the administered volume.
Cyclophosphamide is often used with other anticancer medicines or in combination with radiation therapy.
Recommended dose
The doctor will decide on the amount of medicine to be administered to the patient and the time of administration.
The duration of treatment and/or breaks in treatment depend on the indication, the scheme of combined therapy, the patient's overall health, laboratory test results, and blood cell regeneration.
It is recommended to administer cyclophosphamide in the morning. It is essential to ensure that the patient receives sufficient fluids before, during, and after administration to prevent an adverse effect on the urinary tract.
If the patient has any questions about the use of this medicine, they should consult their doctor or pharmacist.

Administration of a higher dose of Cyclophosphamide Accord than recommended

Cyclophosphamide Accord is administered under the supervision of a doctor, so it is very unlikely that an excessive amount will be administered. However, if any side effects occur after administration, the patient should immediately inform their doctor. Emergency treatment may be necessary.
The symptoms of cyclophosphamide overdose include the side effects listed below in the "Side effects" section, but their severity may be greater.

Missing a dose of Cyclophosphamide Accord

If a dose is missed, the patient should immediately consult their doctor.
If the patient has any further doubts about the use of this medicine, they should consult their doctor or pharmacist.

4. Possible side effects

Like all medicines, Cyclophosphamide Accord can cause side effects, although not everybody gets them.

The patient should immediately consult their doctor if they experience:

• an allergic reaction; symptoms include 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 breathing difficulties or shock, even leading to death (anaphylactic shock, anaphylactic reaction, or pseudoanaphylactic 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 antibiotic treatment to fight the infection, hemolysis, low platelet count, and kidney failure (hemolytic-uremic syndrome).
• severe pallor, lethargy, and fatigue. These may be signs of a low red blood cell count (anemia). Usually, no treatment is necessary - the body will replenish the lack of red blood cells. Severe anemia may require blood transfusion.
• severe hypersensitivity reactions with (high) fever, red spots on the skin, joint pain, and/or eye infection (Stevens-Johnson syndrome), severe acute (hypersensitive) reaction with fever and blisters on the skin/exfoliation (toxic epidermal necrolysis).
• abnormal muscle breakdown, which can lead to kidney problems (rhabdomyolysis).
• various blood disorders (agranulocytosis).
• blood in the urine, pain when urinating, or decreased urine output.
• severe chest pain.
• symptoms such as weakness, vision loss, speech disorders, or loss of touch.

Other side effects may also occur:

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

• decrease in blood cell count (myelosuppression)
• decrease in white blood cell count, which is important for fighting infection (leukopenia, neutropenia)
• hair loss (alopecia)
• burning sensation or pain when urinating and frequent urination (cystitis)
• blood in the urine
• fever
• suppression of the immune system

Common: may occur in less than 1 in 10 people

• infections
• mucositis
• abnormal liver function
• male infertility
• chills
• fatigue
• general malaise
• low white blood cell count with fever (febrile neutropenia)

Uncommon: may occur in less than 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 (may be permanent)
• chest pain
• rapid heartbeat
• heart rhythm disorders
• changes in the results of some blood tests
• redness of the skin
• nerve damage, causing numbness, tingling, and weakness (neuropathy)
• nerve pain, which can also feel like pain or burning (neuralgia)
• loss of appetite
• hearing loss

Rare: may occur in less than 1 in 1000 people

• increased risk of developing white blood cell cancer (acute leukemia) and other cancers (bladder cancer, ureteral cancer)
• ineffective production of a certain type of blood cell (myelodysplastic syndrome)
• increased release of antidiuretic hormone by the pituitary gland, affecting the kidneys, causing low sodium levels in the blood (hyponatremia) and water retention, leading to brain edema 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
• azoospermia
• dizziness
• vision disturbances, blurred vision
• changes in nail and skin color
• dehydration
• seizures
• bleeding

Very rare: may occur in less than 1 in 10,000 people

• shock
• complications of cancer treatment due to the breakdown of cancer cells (tumor lysis syndrome)
• low sodium levels in the blood
• high blood pressure (hypertension)
• low blood pressure (hypotension)
• angina pectoris
• heart attack
• lung damage (acute respiratory distress syndrome)
• scarring of the lungs, causing shortness of breath (chronic interstitial lung disease)
• difficulty breathing with wheezing or cough (bronchospasm)
• shortness of breath (dyspnea)
• inadequate oxygen supply to one or more parts of the body (hypoxia)
• cough
• pain or ulcers in the mouth (stomatitis)
• nausea, vomiting, or diarrhea
• constipation
• inflammation of the intestine
• inflammation of the pancreas
• blood clots
• enlargement of the liver (hepatomegaly)
• yellowing of the eyes or skin
• redness of the skin (radiation recall)
• itching
• taste disturbances
• tingling, numbness, or burning sensations (paresthesia)
• smell disturbances
• muscle cramps
• urinary disorders
• kidney function disorders, including kidney failure
• headache
• multi-organ failure
• injection site reactions
• weight gain
• confusion
• conjunctivitis, eye swelling
• fluid accumulation in the abdominal cavity (ascites)

Frequency not known: cannot be estimated from the available data

• various types of cancer, such as blood cancer (non-Hodgkin's lymphoma), kidney cancer, thyroid cancer
• sarcoma
• various blood disorders (lymphopenia, decreased hemoglobin levels)
• excessive tearing
• tinnitus
• nasal congestion (stuffy nose)
• mouth and throat pain
• allergic symptoms or flu-like symptoms (runny nose)
• sneezing
• conditions that cause lung inflammation, which can cause shortness of breath, cough, and elevated temperature or lung scarring (non-infectious pneumonia, bronchiolitis obliterans, allergic alveolitis), fluid in the lungs or around the lungs (pleural effusion), chest pain
• bleeding in the stomach or intestines
• gastrointestinal disorders/blood clots
• liver function disorders
• rash, redness of the skin, blistering of the lips, eyes, or mouth, skin peeling (erythema multiforme, urticaria, rash)
• palmar-plantar erythrodysesthesia syndrome
• facial swelling
• excessive sweating
• skin hardening (scleroderma)
• muscle spasms and pain
• joint pain
• inflammation, scarring, and contraction of the bladder
• effect on the fetus, such as damage or death, fetal death, birth defects, delayed fetal development, carcinogenic effect on offspring
• changes in the results of some blood tests (glucose levels, hormone levels)
• effect on the brain (encephalopathy), a syndrome called reversible posterior leukoencephalopathy, which can cause headache, confusion, seizures, and vision loss, abnormal sensation (dysesthesia or hypoaesthesia), tremors, changes in taste (dysgeusia) or loss of taste (hypogeusia), smell disturbances
• decreased heart ability to pump enough blood in the body, which can be life-threatening (cardiogenic shock, heart failure, or cardiac arrest), rapid heartbeat (tachycardia), which can be life-threatening (ventricular tachycardia), slow heartbeat (bradycardia), fluid accumulation in the sac around the heart (pericardial effusion), abnormal heart rhythm (arrhythmia), which can be noticeable (palpitations)
• changes in menstrual frequency
• parotitis

Reporting side effects

If the patient experiences any side effects, including any not listed in this leaflet, they should inform their doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocides
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 gather more information on the safety of the medicine.

5. How to store Cyclophosphamide Accord

The medicine should be stored out of sight and reach of children.
Do not use Cyclophosphamide Accord after the expiration date (EXP) stated on the packaging. The expiration date refers to the last day of the specified month.
Store in a refrigerator (2°C - 8°C).
After preparation of the solution for injection
Chemical and physical stability of the reconstituted solution (concentration 20 mg/mL) and diluted solution (concentration 2 mg/mL) has been demonstrated for 48 hours at a temperature of 2°C to 8°C.
From a microbiological point of view, the product should be used immediately. If not used immediately, the in-use storage times and conditions are the responsibility of the user. Normally, the storage time should not exceed 24 hours at 2°C to 8°C, provided that the reconstitution has taken place in controlled and validated aseptic conditions.
Do not use this medicine if the quality of the medicinal product has deteriorated, i.e., sediment and visible particles have formed in the solution after reconstitution/dilution.
Medicines should not be disposed of via wastewater or household waste. 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 Accord contains

• The active substance is cyclophosphamide.
• The excipient is mannitol.

Each vial of Cyclophosphamide Accord, 500 mg, powder for solution for injection/infusion, contains 534.5 mg of cyclophosphamide monohydrate, equivalent to 500 mg of cyclophosphamide.
Each vial of Cyclophosphamide Accord, 1000 mg, powder for solution for injection/infusion, contains 1069.0 mg of cyclophosphamide monohydrate, equivalent to 1000 mg of cyclophosphamide.

What Cyclophosphamide Accord looks like and contents of the pack

Cyclophosphamide Accord 500 mg is a white powder or lyophilized form in a 30 mL glass vial.
Cyclophosphamide Accord 1000 mg is a white powder or lyophilized form in a 50 mL glass vial.
Pack size: 1 vial.

Marketing authorization holder

Accord Healthcare Polska Sp. z o.o.
ul. Taśmowa 7
02-677 Warsaw

Manufacturer/Importer

Accord Healthcare Polska Sp. z o.o.
ul. Lutomierska 50
95-200 Pabianice
Pharmadox Healthcare Ltd.
KW20A Kordin Industrial Park,
Paola, PLA3000
Malta
Laboratori Fundació Dau
C/ C, 12-14 Pol. Ind. Zona Franca
08040 Barcelona
Spain
Accord Healthcare B.V.
Winthontlaan 200
3526KV Utrecht
Netherlands

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

Date of last revision of the leaflet:

Information intended for healthcare professionals only:

Cyclophosphamide Accord should only be administered by a doctor with experience in the use of anticancer chemotherapy. It should only be administered in facilities where regular monitoring of clinical, biochemical, and hematological parameters is possible before, during, and after administration, under the supervision of an oncology specialist.
Dosage
The dose should be determined individually for each patient. The duration of treatment and/or breaks in treatment depend on the therapeutic indication, the scheme of combined therapy, the patient's overall health, and the results of laboratory tests and blood cell regeneration.
In combined therapy with other cytostatics with similar toxicity, it may be necessary to reduce the dose or prolong the intervals between treatment cycles.
The use of hematopoietic growth factors (colony-stimulating factors and erythropoiesis-stimulating factors) may be considered to reduce the risk of complications associated with bone marrow suppression and/or to facilitate the administration of the planned dose.
To reduce the risk of toxic effects on the urinary tract, the patient should be given sufficient fluids (orally or by infusion) before, during, or immediately after administration of the medicinal product to induce diuresis. Therefore, Cyclophosphamide Accord should be administered in the morning.
Cyclophosphamide is inactive until it is activated by liver enzymes. However, as with all cytotoxic medicines, reconstitution should be performed by trained personnel in a designated area.
Handling of the medicinal product
The choice of solvent for reconstitution of Cyclophosphamide Accord containing cyclophosphamide depends on the route of administration.

The medicinal product Cyclophosphamide Accord reconstituted in water is hypotonic and should not be administered by direct injection.

To the vial containing the medicinal product Cyclophosphamide Accord, powder for solution for injection/infusion, the following amounts of water for injection or sodium chloride solution at a concentration of 9 mg/mL (0.9%) should be added:
Vial with 500 mg of cyclophosphamide: 25 mL
Vial with 1000 mg of cyclophosphamide: 50 mL
Injection of the solvent into the vial causes the formation of high pressure, which disappears immediately after the introduction of a second sterile needle through the rubber stopper of the vial. Vigorous shaking of the vial causes the powder contained in it to dissolve easily and a clear solution to form. If the powder does not dissolve immediately, shaking of the vial should be continued for a few minutes until the powder is completely dissolved. The solution should be administered immediately after preparation.
Intravenous administration
The preferred method of intravenous administration is infusion.
If the medicinal product Cyclophosphamide Accord remains (e.g. during transport) at a temperature exceeding the maximum temperature, the cyclophosphamide it contains may melt. Vials with melted cyclophosphamide can be visually distinguished. Cyclophosphamide is a white powder, while the melted form creates a transparent or yellowish viscous liquid (most often in the form of droplets on the vial walls).
Vials with melted cyclophosphamide are not suitable for use.
Guidelines for safe handling of anticancer drugs

• Preparation and administration of the medicinal product Cyclophosphamide Accord must comply with the principles and guidelines for the use of cytostatic drugs.
• If possible, reconstitution of the medicinal product should be carried out in a room with laminar flow.
• Personnel preparing the medicinal product must wear a mask and protective gloves.
• In the event of a solution spill, the surface should be thoroughly rinsed with water. Pregnant or breastfeeding women should not participate in the preparation of cytotoxic drugs.
• The drug should be diluted by trained personnel. This should be done in a designated area.
• The work surface should be covered with an absorbent underlay with a waterproof film for single use.
• 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 remains of the drug should be disposed of. Proper precautions should be taken when disposing of equipment used to dilute the cyclophosphamide solution. Any remaining drug or contaminated materials should be placed in high-risk product bags. Sharp

objects (needles, syringes, vials, etc.) should be placed in an appropriate rigid container.
Personnel involved in collecting and disposing of these wastes should be warned of the hazard.

• Any unused remains of the medicinal product or its waste should be disposed of in accordance with local regulations regarding cytotoxic drugs.

Storage and shelf-life of the solution after reconstitution
Chemical and physical stability of the solution after reconstitution has been demonstrated for 48 hours at a temperature of
2°C to 8°C.
From a microbiological point of view, the drug should be used immediately. If it is not used immediately, the user is responsible for the time and conditions of storage before use, and the storage time should not normally exceed 24 hours at a temperature of 2°C to 8°C, unless reconstitution/dilution took place in controlled and validated aseptic conditions.