CYCLOPHOSPHAMIDE Dr. Reddy's 500 mg/mL Concentrate for Solution for Injection and Infusion

Introduction

Package Leaflet: Information for the Patient

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

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

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.

• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

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

This medicine contains the active substance cyclophosphamide.

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

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

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

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

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

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

2. What you need to know before you are given Ciclofosfamida Dr. Reddys

Do not use Ciclofosfamida Dr. Reddys:

• if you are allergic to the active substance (cyclophosphamide), its metabolites, or any of the other components of this medicine (listed in section 6). An allergic reaction may include difficulty breathing, wheezing, skin rash, itching, or swelling of the face and lips.
• if you currently have an infection.
• if your bone marrow is not working properly (especially if you have previously undergone chemotherapy or radiation therapy). You will have blood tests to check your bone marrow function,
• if you have a urinary tract infection that can be recognized by pain when urinating (cystitis).
• if you have had kidney or bladder problems as a result of chemotherapy or radiation therapy.
• if you have a disease that reduces your ability to urinate (obstruction of urine flow).
• if you are breastfeeding.
• if you are pregnant
• if you are under 18 years old (child or adolescent)
• if you are Asian 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 severe infections,
• if you have liver or kidney problems. Your doctor will check through a blood test if your liver and kidneys are working properly,
• if you have had your adrenal glands removed,
• if you are receiving or have recently received radiation therapy or chemotherapy;
• if you have heart problems or have received radiation therapy in the heart area,
• if you have diabetes,
• if you are in poor general health or are a fragile person, or if you are an elderly person,
• if you have had surgery in the last 10 days.

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

Cyclophosphamide may have effects on your blood and immune system.

Blood cells are produced in your bone marrow. Three types of blood cells are produced:

• red cells, which carry oxygen in the body,
• white cells, which fight infections, and
• platelets, which allow blood to clot.

After receiving cyclophosphamide, the count of blood cells for all three types of cells will decrease. This is an inevitable side effect of the medicine. Your blood count will reach its lowest level approximately 5 to 10 days after starting to receive cyclophosphamide and will remain low for some days after the treatment cycle ends. Most people recover normal blood cell counts within 21 to 28 days. If you have received a large amount of chemotherapy in the past, it may take a little longer to return to normal.

You are more likely to get infections if your blood cell count is low. Try to avoid close contact with people who have coughs, colds, and other infections. Your doctor will treat you with the appropriate medicine if they think you have an infection or are at risk of getting one.

Your doctor will make sure that the number of red cells, white cells, and platelets is high enough before treatment with cyclophosphamide and during treatment. You may need to reduce the amount of medicine you receive or delay the next dose.

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

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

Mesna can be given as a short injection or mixed with cyclophosphamide in the infusion solution, or in tablets. You can find more information about Mesna in the package leaflet that comes with Mesna.

Most people who receive cyclophosphamide with Mesna do not develop bladder problems, but your doctor may want to check your urine for blood with a dipstick or microscope. If you notice blood in your urine, you must tell your doctor immediately.

Cancer medicines and radiation therapy may increase the risk of developing other types of cancer; this may happen several years after the end of your treatment. Cyclophosphamide carries a higher risk of causing cancer in the bladder area.

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

Cyclophosphamide may cause lung problems such as inflammation or scarring of the lungs.

This can happen more than six months after the end of treatment. If you start to have difficulty breathing, tell your doctor immediately.

Cyclophosphamide may have potentially life-threatening effects on your liver.

If you experience a sudden increase in weight, liver pain, and your skin or the whites of your eyes turn yellow (jaundice), tell your doctor immediately.

Loss of hair or baldness may occur. Your hair should grow back normally, although its texture and color may be different.

This medicine may cause nausea and vomiting. This can last for approximately 24 hours after taking the medicine. You may need to take medicines to stop feeling sick and vomiting. Consult your doctor about this.

Other medicines and Ciclofosfamida Dr. Reddys

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

The following medicines may reduce the effectiveness of cyclophosphamide:

• aprepitant (used to prevent 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 the activity of the immune system)
• chloral hydrate (used to treat insomnia)
• cimetidine (used to reduce stomach acid)
• disulfiram (used to treat alcoholism)
• glyceraldehyde (used to treat warts)
• protease inhibitors (used to treat viruses)
• medicines that increase liver enzymes such as rifampicin (used to treat bacterial infections), carbamazepine, phenobarbital, phenytoin (used to treat epilepsy), St. John's Wort (a herbal remedy for mild depression), corticosteroids (used to treat inflammation)
• dabrafenib (a cancer medicine).

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

• 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 water retention)
• zidovudine (used to treat viruses)
• clozapine (used to treat symptoms of some 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 heart area

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 the number of white blood cells 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 stop smoking)
• coumarins such as warfarin (used as a blood thinner)
• cyclosporin (used to reduce the activity of the immune system)
• succinylcholine (used to relax muscles during medical procedures)
• digoxin, ß-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 and sulfonylurea derivatives are used together).

Using Ciclofosfamida Dr. Reddys with food, drinks, and alcohol

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

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

Pregnancy, breastfeeding, and fertility

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

If you are a woman, you must not become pregnant during treatment with this medicine and for 12 months after the end of treatment. If you become pregnant during treatment, genetic counseling should be provided.

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

Pregnancy

This medicine may cause miscarriage or harm to the fetus. Cyclophosphamide should not be used during pregnancy.

If you are a woman, you must not become pregnant during treatment with this medicine and for 12 months after the end of treatment. If you become pregnant during treatment, genetic counseling should be provided.

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

Breastfeeding

Do not breastfeed while you are being treated with Ciclofosfamida Dr. Reddys. Ask your doctor for advice.

Fertility

Cyclophosphamide may affect your ability to have children in the future. Consult your doctor about cryopreservation (freezing) of sperm or eggs before treatment due to the possibility of irreversible infertility due to treatment with cyclophosphamide. If you are considering becoming a parent after treatment, consult your doctor.

Driving and using machines

Some of the side effects of treatment with Ciclofosfamida Dr. Reddys may affect your ability to drive or use machines safely. Your doctor will decide if 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% v/v 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% v/v 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% v/v of anhydrous ethanol (alcohol), i.e., 2054 mg per vial, equivalent to 52 ml of beer or 21 ml of wine.

It is unlikely that the alcohol in this medicine will have an effect on 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 a history of alcoholism, consult your doctor before taking this medicine.

3. How to use Cyclophosphamide Dr. Reddys

Form of administration

For intravenous use.

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

Cyclophosphamide is administered as an injection and is usually added to a large bag of liquid and injected (perfused) slowly directly into a vein. The vein may be in your arm, the back of your hand, or a large vein under your collarbone.

Depending on your dose, it will usually take between 30 and 120 minutes to administer as an infusion.

Cyclophosphamide is often administered in combination with other cancer medications or radiation therapy.

Recommended dose

Your doctor will decide the amount of medication you need and when it should be administered.

The amount of cyclophosphamide you will be given depends on:

• the type of disease you have
• your size (a combination of your height and weight)
• your general health
• if you are being given other cancer medications or if you are receiving radiation therapy.

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

If you notice that Cyclophosphamide Dr. Reddys is acting too strongly or too weakly, talk to your doctor or pharmacist. Your doctor may need to change the amount of medication you are given 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 because there are alternative cyclophosphamide medications without alcohol.

If you use more Cyclophosphamide Dr. Reddys than you should

Since cyclophosphamide is administered under the supervision of your doctor, it is very 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 Accidents and Emergencies at the nearest hospital. You may need urgent medical attention.

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

The symptoms of a cyclophosphamide overdose include the side effects listed below in the "Side Effects" section, but are generally more severe in nature.

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

4. Possible adverse effects

Like all medications, this medication can cause side effects, although not everyone will experience them.

Tell your doctor immediately if you experience:

• allergic reactions. The signs would be difficulty breathing, wheezing, increased heart rate, decreased blood pressure, rash, itching, or swelling of the face and lips. Severe allergic reactions could cause breathing difficulties or shock, with a possible fatal outcome (anaphylactic shock, anaphylactic/anaphylactoid reaction).
• appearance of bruises without being hit, or bleeding in the gums. This could be a sign that the levels of platelets in your blood are too low.
• severe infection or fever, ulcers in the mouth, cough, shortness of breath, signs of septicemia such as fever, rapid breathing, increased heart rate, confusion, and swelling. This could be a sign of a reduction in your white blood cell count and antibiotics may be needed to fight infections, red blood cell breakdown, decrease in platelet count, and kidney failure.
• pallor, feeling of fatigue and tiredness. This could be indicative of a low level of red blood cells (anemia). Normally, no treatment is required, as your body will replace the red blood cells over time. In case of severe anemia, you may need a blood transfusion.
• blood in the urine, pain when urinating, or reduced urine volume.
• severe chest pain.
• symptoms such as weakness, loss of vision, speech difficulties, loss of touch.

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

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

• reduction in the number of blood cells (myelosuppression),
• reduction in white blood cells that are important in fighting infections (leukopenia, neutropenia),
• hair loss (alopecia),
• burning sensations when urinating and frequent need to do so (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,
• sterility in males,
• chills,
• feeling of weakness,
• general feeling of discomfort,
• reduction in white blood cell count and fever (febrile neutropenia).

Uncommon (may affect up to 1 in 100 patients)

• anemia (low red blood cell count) that can cause fatigue and drowsiness,
• propensity to bruising due to low platelet count (thrombocytopenia),
• inflammation of the lungs (pneumonia),
• septicemia,
• allergic reactions,
• infertility in women (may be permanent),
• chest pain,
• rapid heartbeat,
• heart problems,
• changes in the results of some blood tests,
• redness of the skin (rash),
• nerve damage that can cause numbness, tingling, and weakness (neuropathy),
• nerve pain (neuralgia),
• loss of appetite,
• hearing loss.

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

• increased risk of white blood cell cancer (acute leukemia) and other cancers (bladder cancer, ureter cancer),
• ineffective production of a certain type of blood cells (myelodysplastic syndrome),
• increased release of antidiuretic hormone from the pituitary gland (inappropriate antidiuretic hormone secretion syndrome). This affects the kidneys, causing low sodium levels in the blood (hyponatremia) and water retention, resulting in brain swelling due to too much water in the blood. The signs of this may be headache, changes in personality or behavior, confusion, drowsiness
• changes in heart rhythm,
• inflammation of the liver,
• skin rash,
• skin inflammation,
• absence of menstruation (periods),
• absence of sperm,
• dizziness,
• vision problems, blurred vision,
• changes in nail or skin color
• dehydration,
• seizures,
• bleeding

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

• breakdown of red blood cells and kidney failure (hemolytic uremic syndrome)
• formation of blood clots in the small blood vessels of the body (disseminated intravascular coagulation)
• shock
• complications that may occur after cancer treatment caused by degradation products of dying cancer cells (tumor lysis syndrome),
• low sodium levels in the blood (hyponatremia)
• high blood pressure (hypertension)
• low blood pressure (hypotension)
• angina
• heart attack
• blockage of a blood vessel due to a blood clot in the circulatory system (thromboembolism)
• lung injury (acute respiratory distress syndrome)
• pulmonary fibrosis that causes breathing difficulties (chronic interstitial pulmonary fibrosis)
• difficulty breathing with wheezing or coughing (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
• inflammation of the intestine
• inflammation of the pancreas
• blood clot in the liver (hepatic veno-occlusive disease)
• enlargement of the liver (hepatomegaly)
• yellowing of the eyes or skin
• severe hypersensitivity reactions with fever (high), red spots on the skin, joint pain, and/or eye infection (Stevens-Johnson syndrome)
• sudden severe reaction (hypersensitive) with fever and blisters on the skin/desquamation of the skin (toxic epidermal necrolysis)
• radiation erythema)
• itching
• alteration of taste (dysgeusia, hypogeusia)
• tingling, tingling, pinching, or burning sensation (paresthesia)
• alteration of smell (parosmia)
• abnormal muscle breakdown that can cause kidney problems (rhabdomyolysis)
• muscle cramp
• 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 cell and platelet count (hemolytic uremic syndrome)
• fluid in the lungs or around them (pulmonary edema)
• fluid accumulation in the abdominal cavity (ascites)

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

• different types of cancer, e.g. blood cancer (non-Hodgkin's lymphoma), kidney cancer, thyroid cancer
• sarcoma
• different 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 the possibility of blockage of the pulmonary vessels (pulmonary embolism)
• increased tearing
• tinnitus
• nasal congestion
• oropharyngeal pain
• rhinorrhea
• sneezing
• veno-occlusive pulmonary disease
• obliterative bronchiolitis
• allergic alveolitis
• pneumonitis
• pleural effusion
• abdominal pain
• bleeding in the stomach or intestines
• intestinal problems/bleeding
• liver failure
• rash, redness of the skin, blisters on the lips, eyes, or mouth, skin desquamation (erythema multiforme, urticaria, erythema)
• hand-foot syndrome
• facial swelling
• increased sweating
• skin hardening (scleroderma)
• muscle spasms and pain
• joint pain
• fetal damage or death
• changes in the results of some 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, hypesthesia), tremor, alteration of taste (dysgeusia, hypogeusia), deterioration of smell (parosmia)
• different types of heart disorders (ventricular tachycardia, cardiogenic shock, pericardial effusion, bradycardia, palpitations, QT interval prolongation on the electrocardiogram)
• infertility in women and men
• changes in menstrual frequency
• intrauterine death
• fetal malformation
• fetal growth retardation
• cancer-causing effect on offspring

If any of the adverse reactions worsen or if you notice any adverse reaction not mentioned 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 that is not listed in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medication.

5. Conservation of Cyclophosphamide Dr. Reddys

Keep this medication out of sight and reach of children.

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

Store in the refrigerator (2°C - 8°C)

After dilution for intravenous administration - for direct injection:

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

From a microbiological point of view, the product must be used immediately. If not used immediately, the storage times and conditions before use are the responsibility of the user and normally would 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 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 infusion solution; 24 hours at 25°C and 36 hours at 2°C - 8°C when diluted with 5% glucose infusion solution (50 mg/ml); and 24 hours at 25°C and 36 hours at 2°C - 8°C when diluted with 0.9% sodium chloride and 5% glucose infusion solution.

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

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

6. Container Content and Additional Information

Composition of Cyclophosphamide Dr. Reddys

The active ingredient is cyclophosphamide 500 mg / ml.

Cyclophosphamide Dr. Reddys 500 mg/ml concentrate for solution for injection and 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 Container Content

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

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

The 2 ml vial of Cyclophosphamide Dr. Reddys 500 mg/ml concentrate for solution for injection and infusion (1000 mg/2 ml) is packaged in boxes containing 1, 6, 10 or 50 type I transparent and colorless glass tubular vials of 2 ml, closed with 13 mm Teflon-coated rubber stoppers and sealed with a 13 mm gray flip-off cap.

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

Only some pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Reddys Pharma Iberia, S.A.

Avda. Josep Tarradellas nº 38

08029 Barcelona (Spain)

Manufacturer

betapharm Arzneimittel GmbH

Kobelweg 95,

86156 Augsburg

Germany

or

SC Rual Laboratories SRL

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

Bucharest, 030138

Romania

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

Date of the last revision of this leaflet:November 2021.

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

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

This information is intended exclusively for healthcare professionals:

This medicinal product should be administered exclusively under the supervision of a doctor with experience in antineoplastic chemotherapy. This medicinal product should be administered only where there are facilities for periodic monitoring of clinical, biochemical, and hematological parameters before, during, and after administration, and under the direction of a specialist oncology service.

Posology and Method of Administration

Doses should be adjusted individually for each patient. The duration and dose of treatment and/or treatment intervals depend on the therapeutic indication, the scheme of combination therapy, the patient's general state of health, and laboratory test results (in particular, monitoring of blood cells).

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

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

Before, during, and immediately after administration, an adequate amount of fluids should be ingested or infused to force diuresis in order to reduce the risk of toxicity in the urinary tract. Therefore, this medicinal product should be administered in the morning.

Cyclophosphamide is inert until it is activated by enzymes in the liver. However, as with all cytotoxic agents, it is recommended that reconstitution be performed by trained personnel in a designated area.

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

Preparation

The choice of solvent for reconstituting this medicinal product containing cyclophosphamide depends on the route of administration used.

For direct intravenous injection

Extract the prescribed amount of Cyclophosphamide Dr. Reddys from the vial with a syringe and add to the required amount of 0.9% sodium chloride solution to obtain a final concentration of 20 mg/ml of cyclophosphamide.

Table 1: Dilution for Direct Intravenous Injection

For intravenous infusion

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

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

Table 2: Dilution for Intravenous Infusion

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

Only clear solutions should be used.

Intravenous route

Intravenous administration should be performed preferably as an infusion.

The guidelines for handling cytostatics in general should be reviewed when reconstituting or handling cyclophosphamide. Reconstitution should be performed, as far as possible, in a laminar flow safety cabinet. The person handling the product should wear a protective mask and gloves. In case of spills, the area should be rinsed well with water.

Guidelines for the Safe Handling of Antineoplastic Agents

Cytotoxic preparations should not be handled by pregnant personnel. Trained personnel should dilute the medicinal product. This should be done in a designated area. The work surface should be covered with absorbent paper with a plastic backing.

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; the affected area should be cleaned thoroughly with water and soap. If accidental contamination of the eyes occurs, they should be rinsed thoroughly with water immediately.

Luer-lock fittings should be used on all syringes and sets. Large-caliber needles are recommended to minimize pressure and possible aerosol formation. The latter can also be reduced by using a ventilation needle.

Any unused content should be discarded. Due care and caution should be taken when disposing of items used to dilute cyclophosphamide. Any unused product or contaminated material should be placed in a high-risk waste bag. Sharp objects (needles, syringes, vials, etc.) should be placed in a suitable rigid container. Personnel involved in the collection and disposal of these wastes should be aware of the hazard involved. Any unused medicinal product or waste material should be disposed of in accordance with the standardized procedures applicable to cytotoxic agents.

Storage and Shelf-Life

Direct injection:

Chemical and physical stability has been demonstrated for 24 hours at 25°C and 6 days at 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 before use are the responsibility of the user and would normally not exceed 24 hours at 2°C - 8°C, unless the dilution has been made in controlled and validated aseptic conditions.

For intravenous infusion

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

From a microbiological point of view, the medicinal product should be used immediately. If not used immediately, the in-use storage times and conditions before use are the responsibility of the user and would normally not exceed 24 hours at 2°C - 8°C, unless the reconstitution/dilution has taken place in controlled and validated aseptic conditions.

Special Precautions for Storage

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

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