Cyclophosphamide Dr. Reddy's 500 mg/ml concentrate for solution for injection and for infusion: detailed information

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Cyclophosphamide Dr. Reddy 500 mg/ml concentrate for solution for injection and infusion

Read the entire leaflet carefully before you start using this medicine, because it contains important information for you.

Keep this leaflet, as you may need to read it again.
If you have any questions, consult your doctor, pharmacist or nurse.
This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
- If you experience any adverse reactions, consult your doctor, pharmacist or nurse, even if they are adverse reactions not listed in this leaflet. See section 4.

Leaflet contents

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

1. What Ciclofosfamida Dr. Reddys is and what it is used for

This medicine contains the active substance ciclofosfamida.

It belongs to a group of medicines known as cytotoxic or antineoplastic agents. It works by killing cancer cells, which is sometimes referred to as chemotherapy.

This medicine is used in chemotherapy alone or in combination with other medicines in the following conditions:

certain types of white blood cell cancer (acute lymphocytic 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 type of bone cancer),
small cell lung carcinoma,
treatment of metastatic or advanced central nervous system tumors (neuroblastoma).

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

Sometimes, doctors may prescribe ciclofosfamida for other conditions not related to cancer:

Life-threatening autoimmune diseases: severe progressive forms of lupus nephritis (kidney inflammation caused by an immune system disease) and granulomatosis with polyangiitis (a rare form of vasculitis).

2. What you need to know before Ciclofosfamida Dr. Reddys is administered to you

Do not use Ciclofosfamida Dr. Reddys:

if you are allergic to the active substance (cyclophosphamide), its metabolites, or any of the other ingredients of this medicine (listed in section 6). An allergic reaction may include difficulty breathing, wheezing, rash, itching, or swelling of the face and lips.
if you currently have an infection.
if your bone marrow is not functioning properly (especially if you have previously received chemotherapy or radiotherapy). Blood tests will be performed to check your bone marrow function.
if you have a urinary tract infection that may present with pain when urinating (cystitis).
if you have had kidney or bladder problems as a result of chemotherapy or radiotherapy.
if you have a disease that reduces your ability to urinate (urinary flow obstruction).
if you are breastfeeding.
if you are pregnant.
if you are under 18 years of age (child or adolescent).
if you are of Asian descent with a known mutation in the ALDH2 gene.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before starting to use this medicine:

if you have low blood cell counts,
if you have serious infections,
if you have liver or kidney problems. Your doctor will check, via blood tests, whether your liver and kidneys are functioning properly,
if you have had your adrenal glands removed,
if you are currently receiving or have recently received radiotherapy or chemotherapy,
if you have heart problems or have received radiotherapy to the area of the heart,
if you have diabetes,
if you are in poor general health or are frail, or if you are elderly,
if you have undergone surgery within the last 10 days.

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

Cyclophosphamide can 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, and
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 the medicine. 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. You may need to have your dose reduced or the next dose delayed.

Cyclophosphamide may impair normal wound healing. Keep cuts clean and dry and monitor them for normal healing. It is important to maintain good gum health, as infections and mouth ulcers may occur. Consult your doctor if you have any concerns.

Cyclophosphamide can 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 prescribe a medicine 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 included with the Mesna packaging.

Most people receiving cyclophosphamide with Mesna do not develop bladder problems, but your doctor may wish to test your urine for blood using a test strip or microscope. If you notice blood in your urine, inform your doctor immediately.

Cancer medicines and radiotherapy may increase the risk of developing other types of cancer; this may occur several years after treatment ends. Cyclophosphamide carries an increased risk of causing cancer in the area of the urinary bladder.

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 problems such as inflammation or pulmonary fibrosis.

This may occur more than six months after treatment ends. If you develop difficulty breathing, 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.

This medicine may cause nausea and vomiting. This may last approximately 24 hours after receiving the medicine. You may need to take medication to prevent nausea and vomiting. Discuss this with your doctor.

Other medicines and Ciclofosfamida Dr. Reddys

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines. In particular, inform them about the following medicines or treatments, as they may be incompatible with cyclophosphamide.

The following medicines may reduce the effectiveness of cyclophosphamide:

aprepitant (used to prevent nausea)
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 to thin the blood)
sulfonamides, such as sulfadiazine, sulfasalazine, sulfamethoxazole (used to treat bacterial infections)
ondansetron (used to prevent nausea).

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 (a cancer medicine).

Medicines that may increase the toxic effects of cyclophosphamide on your blood cells and immune system:

ACE inhibitors (used to treat high blood pressure)
natalizumab (used to treat multiple sclerosis)
paclitaxel (used to treat cancer)
thiazide diuretics such as hydrochlorothiazide or chlorthalidone (used to treat high blood pressure or fluid retention)
zidovudine (used to treat viruses)
clozapine (used to treat symptoms of certain psychiatric disorders).

Medicines that may increase the toxic effects of cyclophosphamide on your heart:

anthracyclines such as bleomycin, doxorubicin, epirubicin
mitomycin (used to treat cancer)
cytarabine, pentostatin, trastuzumab (used to treat cancer)
radiation to the area of your heart.

Medicines that may increase the toxic effects of cyclophosphamide on your lungs:

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

Medicines that may increase the toxic effects of cyclophosphamide on your kidneys:

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

Other medicines that may affect or be affected by cyclophosphamide 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)
ciclosporin (used to reduce immune system activity)
succinylcholine (used to relax muscles during medical procedures)
digoxin, β-acetyldigoxin (used to treat heart conditions)
vaccines
verapamil (used to treat high blood pressure, angina, or irregular heartbeats)
sulfonylurea derivatives (blood sugar levels may decrease if cyclophosphamide is used concomitantly with sulfonylurea derivatives).

Use of Ciclofosfamida Dr. Reddys with food, drinks, and alcohol

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

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

Pregnancy, breastfeeding, and fertility

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

If you are a woman, you must not become pregnant during treatment with this medicine and for a period of 12 months after treatment ends. If pregnancy occurs during treatment, genetic counselling should be provided.

If you are a man, you must use effective contraception during treatment with this medicine to ensure you do not father a child during treatment with cyclophosphamide and for a period of 6 months after treatment ends.

Pregnancy

This medicine may cause miscarriage or fetal harm. Cyclophosphamide must not be used during pregnancy.

Breastfeeding

Do not breastfeed while being treated with Ciclofosfamida Dr. Reddys. 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 risk of irreversible infertility caused by cyclophosphamide. If you are considering having children after treatment, consult your doctor.

Driving and use of machines

Some of the adverse effects of treatment with Ciclofosfamida Dr. Reddys may affect your ability to drive and operate machinery safely. Your doctor will decide whether it is safe for you to do so.

to ensure you do not father a child during your treatment with cyclophosphamide

Ciclofosfamida Dr. Reddys contains ethanol

The 1 ml vial of Ciclofosfamida Dr. Reddys 500 mg/ml concentrate for solution for injection and infusion (500 mg/1 ml)

This medicine contains 65% by volume of anhydrous ethanol (alcohol), i.e., 513.5 mg per vial, equivalent to 13 ml of beer or 6 ml of wine.

The 2 ml vial of Ciclofosfamida Dr. Reddys 500 mg/ml concentrate for solution for injection and infusion (1000 mg/2 ml)

This medicine contains 65% by volume of anhydrous ethanol (alcohol), i.e., 1027 mg per vial, equivalent to 26 ml of beer or 11 ml of wine.

The 4 ml vial of Ciclofosfamida Dr. Reddys 500 mg/ml concentrate for solution for injection and infusion (2000 mg/4 ml)

This medicine contains 65% by volume of anhydrous ethanol (alcohol), i.e., 2054 mg per vial, equivalent to 52 ml of beer or 21 ml of wine.

The alcohol content in this medicine is unlikely to have effects in adults.

The amount of alcohol in this medicine may alter the effect of other medicines. Consult your doctor if you are taking other medicines.

If you are pregnant or breastfeeding, consult your doctor before taking this medicine.

If you have alcohol addiction, consult your doctor before taking this medicine.

3. How to use Cyclophosphamide Dr. Reddy's

Method of administration

For intravenous use.

Cyclophosphamide will be administered by a physician or nurse experienced in the use of chemotherapy for cancer.

Cyclophosphamide is given as an injection and is usually added to a large bag of fluid, which is then slowly infused directly into the vein. The vein may be located in your arm, the back of your hand, or a large vein beneath the clavicle.

Depending on your dose, administration typically takes between 30 and 120 minutes as an infusion.

Cyclophosphamide is often administered in combination with other anticancer medicines or radiotherapy.

Recommended dose

Your doctor will decide how much medication you need and when it should be administered.

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 anticancer medicines or undergoing radiotherapy.

It is advisable to administer cyclophosphamide in the morning. Before, during, and after administration, it is important to maintain adequate fluid intake to prevent potential adverse effects on the urinary tract.

If you notice that Cyclophosphamide Dr. Reddy's is having too strong or too weak an effect, speak with your doctor or pharmacist. Your doctor may need to adjust your dose and monitor you more closely if:

you have liver or kidney problems
you are elderly.

Use in children and adolescents

The use of this alcoholic solution of cyclophosphamide is contraindicated in children and adolescents due to the availability of alternative non-alcoholic cyclophosphamide formulations.

If you use more Cyclophosphamide Dr. Reddy's than you should

Since cyclophosphamide is administered under the supervision of your doctor, it is highly unlikely that you will receive an excessive amount. However, if you experience any side effects after receiving cyclophosphamide, inform your doctor immediately or go to the nearest hospital's Accident and 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 91 562 04 20, stating the medication and the amount ingested.

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

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

4. Possible adverse effects

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

Tell your doctor immediately if you experience:

-allergic reactions. Signs may include difficulty breathing, wheezing, increased heart rate, low blood pressure, 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 indicate that your blood platelet levels are too low.

-severe infection or fever, mouth ulcers, cough, shortness of breath, signs of sepsis such as fever, rapid breathing, increased heart rate, confusion, and edema. This could indicate a reduction in your white blood cell count, and antibiotics may be needed to fight infections, collapse of red blood cells, decreased platelet count, and kidney failure.

-pallor, feeling of fatigue and tiredness. This could indicate low red blood cell levels (anemia). Treatment is usually not required, as your body will eventually replenish red blood cells. 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, loss of touch sensation.

The following adverse effects may also occur during treatment with this medicine.

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

reduction in blood cells (myelosuppression),
reduction in white blood cells important for fighting infections (leukopenia, neutropenia),
hair loss (alopecia),
burning sensation when urinating and frequent need to urinate (cystitis),
presence of blood in the urine,
fever,
suppression of the immune system.

Common (may affect up to 1 in 10 patients)

infections,
inflammation of mucous membranes (mucositis),
blood in the urine and painful urination (hemorrhagic cystitis),
appearance of blood in the urine (macrohematuria),
abnormal kidney function,
male sterility,
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 patients)

anemia (low red blood cell count) which may cause tiredness and drowsiness,
tendency to bruise due to thrombocytopenia (low platelet count),
lung inflammation (pneumonitis),
sepsis,
allergic reactions,
infertility in women (may be permanent),
chest pain,
rapid heartbeat,
heart problems,
changes in results of certain blood tests,
skin redness (rash),
nerve damage which may cause numbness, tingling, and weakness (neuropathy),
nerve pain (neuralgia),
anorexia,
deafness.

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

increased risk of white blood cell cancer (acute leukemia) and some other cancers (bladder cancer, ureter cancer),
ineffective production of certain blood cells (myelodysplastic syndrome),
increased release of antidiuretic hormone from 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 excess water in the blood. Signs may include headache, personality or behavioral changes, confusion, drowsiness,
changes in heartbeat,
liver inflammation,
skin rash,
skin inflammation,
absence of menstruation (periods),
absence of sperm,
dizziness,
vision problems, blurred vision,
changes in the color of your nails or skin,
dehydration,
seizures,
bleeding.

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

rupture of red blood cells and kidney failure (hemolytic uremic syndrome),
formation of blood clots in small blood vessels throughout the body (disseminated intravascular coagulation),
shock,
complications that may occur after cancer treatment caused by breakdown products of dying cancer cells (tumor lysis syndrome),
low sodium levels in 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 difficulty breathing (chronic interstitial pulmonary fibrosis),
difficulty breathing with wheezing or cough (bronchospasm),
respiratory failure (dyspnea),
a condition in which the body or a region of the body lacks adequate oxygen supply (hypoxia),
cough,
mouth ulcers (stomatitis),
nausea, vomiting, or diarrhea,
constipation,
intestinal inflammation,
inflammation of the pancreas,
blood clot in the liver (veno-occlusive liver disease),
liver enlargement (hepatomegaly),
yellowing of eyes or skin,
severe hypersensitivity reactions with fever (high), red skin spots, joint pain and/or eye infection (Stevens-Johnson syndrome),
sudden severe (hypersensitive) reaction with fever and skin blisters/peeling skin (toxic epidermal necrolysis),
radiation erythema,
itching,
altered sense of taste (dysgeusia, hypogeusia),
tingling, prickling, 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,
reactions at the injection or infusion site,
weight gain,
confusion,
conjunctivitis, eye swelling,
acute kidney failure with decreased red blood cells and platelets (hemolytic uremic syndrome),
fluid in the lungs or around them (pulmonary edema),
accumulation of fluid in the abdominal cavity (ascites).

Frequency not known (cannot be estimated from available data)

various types of cancer, e.g. blood cancer (non-Hodgkin lymphoma), kidney cancer, thyroid cancer,
sarcoma,
various types of blood disorders (agranulocytosis, lymphopenia, decreased hemoglobin),
blockage of a blood vessel due to a blood clot in the circulatory system (thromboembolic episodes), including possible blockage of pulmonary vessels (pulmonary embolism),
increased tearing,
tinnitus,
nasal passage blockage (nasal congestion),
oropharyngeal pain,
rhinorrhea,
sneezing,
veno-occlusive lung disease,
bronchiolitis obliterans,
allergic alveolitis,
pneumonitis,
pleural effusion,
abdominal pain,
bleeding in the stomach or intestines,
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 spasm and pain,
joint pain,
inflammation, scarring, and contraction of the bladder,
damage or death of the fetus,
changes in results of certain blood tests (glucose level, hormone levels),
brain disorder (encephalopathy), neurotoxicity manifested as a syndrome characterized by headache, confusion, seizures, and visual loss (posterior reversible encephalopathy syndrome), abnormal sensation (dysesthesia, hypoesthesia), tremor, altered sense of taste (dysgeusia, hypogeusia), impaired sense of smell (parosmia),
various types of cardiac disorders (ventricular tachycardia, cardiogenic shock, pericardial effusion, bradycardia, palpitations, QT interval prolongation on electrocardiogram),
infertility in women and men,
changes in menstrual frequency,
intrauterine death,
fetal malformation,
fetal growth retardation,
carcinogenic effect in offspring,
inflammation of the salivary glands (usually in the cheek area; parotid gland inflammation).

If any of the adverse reactions worsen or if you notice any adverse reactions not listed in this leaflet, inform your doctor or pharmacist.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect 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 Dr. Reddy's

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

Do not use this medicine after the expiry date stated on the label and the packaging after EXP. The expiry date refers to the last day of the month indicated.

Store in a refrigerator (2°C - 8°C).

After dilution for intravenous administration – for direct injection:

Chemical and physical in-use stability has been demonstrated for 24 hours at 25°C and for 6 days between 2°C and 8°C.

From a microbiological standpoint, the product should be used immediately. 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°C - 8°C, unless the dilution has been carried out under controlled and validated aseptic conditions.

For intravenous infusion:

Chemical and physical in-use stability has been demonstrated for 24 hours at 25°C and 6 days at 2°C - 8°C when diluted with 0.45% sodium chloride perfusion solution; for 24 hours at 25°C and 36 hours at 2°C - 8°C when diluted with 5% glucose perfusion solution (50 mg/ml); and for 24 hours at 25°C and 36 hours at 2°C - 8°C when diluted with 0.9% w/v sodium chloride and 5% w/v glucose in perfusion solution.

Medicines should not be disposed of via wastewater. Ask your pharmacist how to dispose of medicines and packaging no longer required. This will help protect the environment.

6. Contents of the pack and other information

Composition of Cyclophosphamide Dr. Reddys

The active substance is cyclophosphamide 500 mg/ml.

Cyclophosphamide Dr. Reddys 500 mg/ml concentrate for solution for infusion:

A 1 ml vial of concentrate for solution for infusion contains 500 mg of cyclophosphamide.

A 2 ml vial of concentrate for solution for infusion contains 1000 mg of cyclophosphamide.

A 4 ml vial of concentrate for solution for infusion contains 2000 mg of cyclophosphamide.

The other component (excipient) is anhydrous ethanol.

Appearance of the product and contents of the pack

Cyclophosphamide Dr. Reddys 500 mg/ml concentrate for solution for infusion is a clear, colourless to yellow solution in clear glass vials.

The 1 ml vial of Cyclophosphamide Dr. Reddys 500 mg/ml concentrate for solution for infusion (500 mg/1 ml) is packaged in cartons containing 1, 6, 10 or 50 clear, colourless type I tubular glass vials of 2 ml, closed with 13 mm Teflon-coated rubber stoppers and sealed with 13 mm red flip-off seals.

The 2 ml vial of Cyclophosphamide Dr. Reddys 500 mg/ml concentrate for solution for infusion (1000 mg/2 ml) is packaged in cartons containing 1, 6, 10 or 50 clear, colourless type I tubular glass vials of 2 ml, closed with 13 mm Teflon-coated rubber stoppers and sealed with 13 mm grey flip-off seals.

The 4 ml vial of Cyclophosphamide Dr. Reddys 500 mg/ml concentrate for solution for infusion (2000 mg/4 ml) is packaged in cartons containing 1, 6, 10 or 50 clear, colourless type I tubular glass vials of 5 ml, closed with 13 mm Teflon-coated rubber stoppers and sealed with 13 mm violet flip-off seals.

Only certain pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder

Reddys Pharma Iberia, S.A.

Avda. Josep Tarradellas nº 38

08029 Barcelona (Spain)

Manufacturer

betapharm Arzneimittel GmbH

Kobelweg 95,

86156 Augsburg

Germany

SC Rual Laboratories SRL

313, Splaiul Unirii, Building H, 1st floor, sector 3,

Bucuresti, 030138

Romania

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

Country	Name
Germany	Cyclophosphamid beta 500 mg/ml concentrate for the preparation of an injection/infusion solution Cyclophosphamid beta 1000 mg/2 ml concentrate for the preparation of an injection/infusion solution Cyclophosphamid beta 2000 mg/4 ml concentrate for the preparation of an injection/infusion solution
Austria	Cyclophosphamid Reddy 500 mg/ml concentrate for the preparation of an injection/infusion solution Cyclophosphamid Reddy 1000 mg/2 ml concentrate for the preparation of an injection/infusion solution Cyclophosphamid Reddy 2000 mg/4 ml concentrate for the preparation of an injection/infusion solution
Spain	Ciclofosfamida Dr. Reddys 500 mg/ml concentrate for injectable and perfusion solution Ciclofosfamida Dr. Reddys 1000 mg/2 ml concentrate for injectable and perfusion solution Ciclofosfamida Dr. Reddys 2000 mg/4 ml concentrate for injectable and perfusion solution
France	Cyclophosphamide Reddy Pharma 500 mg/1 mL, concentrated injectable solution for infusion Cyclophosphamide Reddy Pharma 1000 mg/2 mL, concentrated injectable solution for infusion Cyclophosphamide Reddy Pharma 2000 mg/4 mL, concentrated injectable solution for infusion
Italy	Ciclofosfamide Dr. Reddy’s 500 mg/ml concentrate for injectable or infusion solution Ciclofosfamide Dr. Reddy’s 1000 mg/2 ml concentrate for injectable or infusion solution Ciclofosfamide Dr. Reddy’s 2000 mg/4 ml concentrate for injectable or infusion solution
Romania	Ciclofosfamida Dr. Reddy’s 500 mg/1 ml concentrate for perfusion solution Ciclofosfamida Dr. Reddy’s 1000 mg/2 ml concentrate for perfusion solution Ciclofosfamida Dr. Reddy’s 2000 mg/4 ml concentrate for perfusion solution

Date of the most recent review of this summary: November 2021.

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:

This medicine must be administered exclusively under the supervision of a physician experienced in antineoplastic chemotherapy. This medicine should only be administered in facilities equipped for periodic monitoring of clinical, biochemical, and hematological parameters before, during, and after administration, and under the direction of a specialist oncology service.

Dosage and method of administration

Dosage must be individually adjusted for each patient. The duration and dose of treatment and/or treatment intervals depend on the therapeutic indication, the regimen of combination therapy, the patient's general health status, and laboratory test results (particularly blood cell monitoring).

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

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

Before, during, and immediately after administration, an adequate amount of fluid should be ingested or infused to promote diuresis, thereby reducing the risk of urinary tract toxicity. Therefore, this medicine should be administered in the morning.

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

Those handling the preparation must wear protective gloves. Care must be taken to avoid splashing material into the eyes. The material should not be handled by pregnant or breastfeeding women.

Preparation

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

For direct intravenous injection

Withdraw the prescribed amount of Cyclophosphamide Dr. Reddy's from the vial using a syringe and add it to the required volume of 0.9% sodium chloride solution to achieve a final concentration of 20 mg/ml of cyclophosphamide.

Table 1: Dilution for Direct Intravenous Injection

Dosage	Volume of Cyclophosphamide Dr. Reddy's concentrate to be withdrawn	Dilute with 0.9% sodium chloride to final volume	Cyclophosphamide concentration
500 mg/25 ml	1 ml	25 ml	20 mg/ml
1000 mg/50 ml	2 ml	50 ml
2000 mg/100 ml	4 ml	100 ml

For intravenous infusion

Withdraw the prescribed amount of Cyclophosphamide Dr. Reddys from the vial using a syringe and dilute to a minimum concentration of 2 mg per ml with one of the following diluents:

5% (50 mg/ml) glucose infusion solution
0.9% w/v sodium chloride and 5% w/v glucose infusion solution
0.45% sodium chloride infusion solution

Table 2: Dilution for Intravenous Infusion

Dosage	Volume of Cyclophosphamide Dr. Reddy's concentrate to be withdrawn	Dilute with diluent to final volume	Cyclophosphamide concentration
500 mg/1 ml	1 ml	250 ml	2 mg/ml
1000 mg/2 ml	2 ml	500 ml
2000 mg/4 ml	4 ml	1000 ml

The solution should be administered as soon as possible after reconstitution.

Only clear solutions should be used.

Intravenous route

Intravenous administration should preferably be performed as an infusion.

General guidelines for handling cytotoxic agents must be observed when reconstituting or handling cyclophosphamide. Reconstitution should, as far as possible, be carried out in a laminar airflow safety cabinet. The person handling the product must wear a protective mask and protective gloves. In case of spills, the area should be thoroughly rinsed with water.

Safe handling guidelines for antineoplastic agents

Cytotoxic preparations should not be handled by pregnant personnel. The medication should be diluted by trained personnel, and this should be performed in a designated area. The work surface should be covered with disposable absorbent paper with a plastic backing.

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

Use Luer-lock fittings on all syringes and administration sets. Large-bore needles are recommended to minimize pressure and the potential for aerosol formation. Aerosol formation may also be reduced by using a venting needle.

Any unused contents must be discarded. Adequate care and caution must be exercised when disposing of materials used to dilute cyclophosphamide. Any unused product or contaminated material must be placed in a high-risk waste bag. Sharp objects (needles, syringes, vials, etc.) must be placed in an appropriate rigid container. Personnel involved in the collection and disposal of such waste must be aware of the associated hazards. Any unused medicinal product or waste material must be disposed of in accordance with standardized procedures applicable to cytotoxic agents.

Storage and shelf life

Direct injection:

Chemical and physical in-use stability has been demonstrated for 24 hours at 25°C and for 6 days between 2°C and 8°C.

From a microbiological standpoint, the product should be used immediately. 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°C – 8°C, unless dilution has been carried out under controlled and validated aseptic conditions.

For intravenous infusion:

Chemical and physical in-use stability has been demonstrated for 24 hours at 25°C and 6 days at 2°C – 8°C when diluted with 0.45% sterile sodium chloride solution; for 24 hours at 25°C and 36 hours at 2°C – 8°C when diluted with 5% glucose infusion solution (50 mg/ml); and for 24 hours at 25°C and 36 hours at 2°C – 8°C when diluted with 0.9% w/v sodium chloride and 5% w/v glucose infusion solution.

From a microbiological standpoint, the medicinal product should be used immediately. 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°C – 8°C, unless reconstitution/dilution has taken place under controlled and validated aseptic conditions.

Diluent	Storage
Ambient Temperature	Refrigerated
Diluted Solution for Direct Intravenous Injection (20 mg/mL)
Sodium Chloride 0.9% Solution for Infusion	up to 24 hours	up to 6 days
Diluted Solutions for Intravenous Infusion (2 mg/mL)
Sodium Chloride 0.45% Solution for Infusion	up to 24 hours	up to 6 days
Glucose 5% (50 mg/mL) Solution for Infusion	up to 24 hours	up to 36 hours
Sodium Chloride 0.9% w/v and Glucose 5% w/v Solution for Infusion	up to 24 hours	up to 36 hours

Special storage precautions

Store in a refrigerator (between 2°C and 8°C).

For storage conditions after dilution of the medicinal product, see above.