Prospect: information for the patient

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

Read this prospect thoroughly before starting to use this medication, because it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor, pharmacist, or nurse.

- This medication has been prescribed to you alone, and you must not give it to other people, even if they have the same symptoms as you, as it may harm them.

• If you experience adverse effects, consult your doctor, pharmacist, or nurse, even if they do not appear in this prospect. See section 4.

This medication contains the active substance cyclophosphamide.

It belongs to the group of medications known as cytotoxic or antineoplastic medications. It acts by killing cancer cells, which is sometimes called chemotherapy.

This medication is used in chemotherapy alone or in combination with other medications in the following cases:

-certain types of white blood cell cancer (acute 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 type of bone cancer),

-microcytic lung carcinoma,

-in the treatment of metastatic or advanced central nervous system tumors (neuroblastoma).

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

In some cases, some doctors may prescribe cyclophosphamide for other conditions unrelated to cancer:

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

No use Ciclofosfamida Dr. Reddys:

-if you are allergic to the active ingredient (ciclofosfamida), its metabolites, or any of the other components of this medication (listed in section 6).A hypersensitivity 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 does not function properly (especially if you have previously undergone chemotherapy or radiation therapy). Blood tests will be performed to check the function of your bone marrow,

-if you have a urinary tract infection that can be recognized by pain while 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

Consult your doctor, pharmacist, or nurse before starting to use this medication:

-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 function correctly,

-if you have had your adrenal glands removed,

-if you are receiving or have recently received radiation or chemotherapy;

-if you have heart problems or have received radiation in the heart area,

-if you have diabetes,

-if you have a poor general health or are a fragile person, or if you are an elderly person,

-if you have undergone surgery less than 10 days ago.

Severe allergic reactions (anaphylactic reactions) may occur during treatment with ciclofosfamida.

Ciclofosfamida may affect your blood and immune system.

Cells in your bone marrow produce blood cells. There are three types of blood cells:

-red blood cells, which transport oxygen in the body,

-white blood cells, which fight infections, and

-platelets, which allow blood to clot.

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

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

Your doctor will ensure that the number of red blood cells, white blood cells, and platelets is high enough before starting treatment with ciclofosfamida and during treatment. You may need to reduce the amount of medication you receive or delay the next dose.

Ciclofosfamida may affect normal wound healing. Keep cuts clean and dry and check that they are healing normally. It is essential to maintain good oral health, as infections and mouth ulcers can occur. Consult your doctor if you have any doubts.

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

Mesna can be administered as a short injection or mixed with ciclofosfamida in the infusion solution, or in tablets. You can find more information about Mesna in the leaflet included in the Mesna packaging.

Most people who receive ciclofosfamida with Mesna do not develop bladder problems, but your doctor may want to analyze your urine to detect the presence of blood using a dipstick or microscope. If you observe blood in your urine, you must inform your doctor immediately.

Cancer treatments and radiation therapy may increase the risk of developing other types of cancer; this can occur several years after the completion of your treatment. Ciclofosfamida carries a higher risk of causing cancer in the urinary bladder area.

Ciclofosfamida may cause cardiac damage or affect the rhythm at which your heart beats. This effect is greater at higher doses of ciclofosfamida, if you are being treated with radiation or other chemotherapy medications, or if you are an elderly person. Your doctor will closely monitor your heart during treatment.

Ciclofosfamida may cause lung problems such as inflammation or pulmonary fibrosis.

This can occur more than six months after treatment completion. If you start experiencing difficulty breathing, inform your doctor immediately.

Ciclofosfamida may have potentially fatal effects on your liver.

If you experience sudden weight gain, liver pain, and the skin or white part of your eyes turn yellow (jaundice), inform your doctor immediately.

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

Ciclofosfamida may cause nausea and vomiting. This can last approximately 24 hours after taking the medication. You may need to take medication to prevent nausea and vomiting.Consult your doctor about this.

Other Medications and Ciclofosfamida Dr. Reddys

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication. In particular, inform them of the following medications or treatments because they may be incompatible with the use of ciclofosfamida.

Medications that may reduce the effectiveness of ciclofosfamida:

•aprepitant (used to prevent nausea)

•bupropion (an antidepressant)

•busulfan, tiotepa (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)

Medications that may increase the toxicity of ciclofosfamida:

•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)

•glyceraldehyde (used to treat warts)

•protease inhibitors (used to treat viruses)

•enzymes that increase liver enzymes such as: rifampicin (used to treat bacterial infections), carbamazepine, phenobarbital, phenytoin (used to treat epilepsy), St. John's Wort (a plant-based remedy for mild depression), corticosteroids (used to treat inflammation)

•dabrafenib (cancer medication)

Medications that may increase the toxic effects of ciclofosfamida 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)

•diuretics such as hydrochlorothiazide or clortalidona (used to treat high blood pressure or water retention)

•zidovudine (used to treat viruses)

•clozapine (used to treat certain psychiatric symptoms)

Medications that may increase the toxic effects of ciclofosfamida on your heart:

•anthracyclines such as bleomycin, doxorubicin, epirubicin

•mitomycin (used to treat cancer)

•citarabine, pentostatine, trastuzumab (used to treat cancer)

•radiation in the heart area

Medications that may increase the toxic effects of ciclofosfamida on your lungs:

•amiodarone (used to treat irregular heartbeats)

•hormones G-CSF, GM-CSF (used to increase white blood cell count after chemotherapy)

Medications that may increase the toxic effects of ciclofosfamida on your kidneys:

•amphotericin B (used to treat fungal infections)

•indomethacin (used to treat pain and inflammation)

Other medications that may affect or be affected by ciclofosfamida 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)

•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 used concurrently with ciclofosfamida and 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 ciclofosfamida.

Pomelo (in the form of fruit or juice) should not be consumed while taking this medication. It may interfere with the usual effect of your medication and alter its efficacy.

Pregnancy, breastfeeding, and fertility

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

If you are a woman, do not become pregnant during treatment with this medication and for a period of 12 months after treatment completion.If pregnancy occurs during treatment, genetic counseling should be provided.

If you are a man, you should use effective contraception during treatment with this medication,to ensure that you do not father children during your treatment with ciclofosfamidaand for a period of 6 months after treatment completion.

Pregnancy

This medication may cause miscarriage or fetal damage.Ciclofosfamida should not be used during pregnancy.

If you are a woman, do not become pregnant during treatment with this medication and for a period of 12 months after treatment completion.If pregnancy occurs during treatment, genetic counseling should be provided.

If you are a man, you should use effective contraception during treatment with this medication,to ensure that you do not father children during your treatment with ciclofosfamidaand for a period of 6 months after treatment completion.

Breastfeeding

Do not breastfeed your baby while undergoing treatment with Ciclofosfamida Dr. Reddys. Consult your doctor.

Fertility

Ciclofosfamida 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 ciclofosfamida. If you are considering having children after treatment, consult your doctor

Driving and operating machinery

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

to ensure that you do not father children during your treatment with ciclofosfamida

Ciclofosfamida Dr. Reddys contains ethanol

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

This medication 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 concentrated solution for injection and infusion (1000 mg/2 ml)

This medication 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 concentrated solution for injection and infusion (2000 mg/ 4 ml)

This medication 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.

It is unlikely that the alcohol in this medication will have an effect on adults.

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

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

If you have a history of alcohol addiction, consult your doctor before taking this medication.

Administration Form

For intravenous use.

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

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

The infusion typically takes between 30 and 120 minutes, depending on your dose.

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 receive depends on:

•the type of disease you have

•your size (a combination of your height and weight)

•your overall health

•whether you are receiving other cancer medications or radiation therapy.

It is recommended to administer cyclophosphamide in the morning. Before, during, and after administration, it is essential to receive adequate amounts of fluid to prevent possible adverse effects on the urinary tract.

If you notice that Cyclophosphamide Dr. Reddys is acting too strongly or too weakly, speak with your doctor or pharmacist. Your doctor may need to adjust the amount of medication you receive 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 cyclophosphamide medications without alcohol.

If You Take More Cyclophosphamide Dr. Reddys Than You Should

As you receive cyclophosphamide 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 emergency room. 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 cyclophosphamide overdose include the side effects listed 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.

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

Inform your doctor immediately if you experience:

-allergic reactions. Their signs would be difficulty breathing, wheezing, increased heart rate, decreased blood pressure, hives, itching, or inflammation of the face and lips. Severe allergic reactions could cause respiratory distress 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 your blood platelet levels are too low.

-severe infection or fever, mouth ulcers, cough, shortness of breath, signs of septicemia such as fever, rapid breathing, elevated heart rate, confusion, and edema. This could be a sign of a decrease in your white blood cell count and you may need antibiotics to fight infections, collapse of red blood cells, decrease in platelet count, and kidney failure.

-pallor, feeling of fatigue and tiredness. This could be indicative of low red blood cell levels (anemia). Normally, no treatment is required, as your body will replenish red blood cells over time. In case of severe anemia, you may need a blood transfusion.

-blood in the urine, painful urination, or reduced urine volume.

-severe chest pain.

-symptoms such as weakness, loss of vision, speech difficulties, loss of touch sensation.

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

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

-reduction in the number of blood cells (myelosuppression),

-reduction of white blood cells that are important in fighting infections (leucopenia, 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,

-mucous membrane inflammation (mucositis),

-blood in the urine and painful urination (hemorrhagic cystitis)

-appearance of blood in the urine (macrohematuria)

-abnormal kidney function,

-male infertility,

-chills,

-feeling of weakness,

-general feeling of discomfort,

-reduction in white blood cell count and fever (febrile neutropenia).

Rare (may affect up to 1 in 100 patients)

-anemia (low red blood cell count) that may cause fatigue and drowsiness,

-tendency to bruise due to thrombocytopenia (low platelet count),

-lung inflammation (pneumonia),

-septicemia,

-allergic reactions,

-female infertility (may be permanent),

-chest pain,

-rapid heart rate,

-cardiac problems,

-changes in some blood test results,

-skin redness (erythema),

-skin inflammation,

-loss of menstruation (periods),

-loss of sperm,

-dizziness,

-vision difficulties, blurred vision,

-changes in nail or skin color

-dehydration,

-convulsions,

-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 small blood vessels throughout the body (disseminated intravascular coagulation)

-shock

-complications that can occur after cancer treatment caused by products of cell death (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)

-chronic interstitial lung disease that causes difficulty breathing (fibrosis interstitial pulmonar crónica)

-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

-inflammation of the intestine

-inflammation of the pancreas

-blood clot in the liver (hepatic veno-occlusive disease)

-enlargement of the liver (hepatomegaly)

-yellow eyes or skin

-severe hypersensitivity reactions with fever (high), red skin patches, joint pain, and/or eye infection (Stevens-Johnson syndrome)

-severe (hypersensitive) reaction with fever and skin blisters or peeling (toxic epidermal necrolysis)

-radiation dermatitis)

-itching

-alteration of taste (dysgeusia, hypogeusia)

-tingling, numbness, pins and needles, or burning sensation (paresthesia)

-alteration of smell (parosmia)

-abnormal muscle deterioration that may cause kidney problems (rhabdomyolysis)

-muscle cramp

-urinary problems

-kidney problems, including kidney failure

-headache

-multi-organ failure

-reactions at the injection or infusion site

-weight gain

-confusion

-conjunctivitis, eye edema

-acute kidney failure with reduced red blood cell and platelet count (hemolytic-uremic syndrome)

-fluid in the lungs or around it (pulmonary edema)

-fluid accumulation in the abdominal cavity (ascites)

Frequency not known (cannot be estimated from available data)

-different types of cancer, e.g. blood cancer (non-Hodgkin 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)

-excessive tearing

-tinnitus

-nasal congestion

-oropharyngeal pain

-rhinorrhea

-sternutation

-veno-occlusive lung disease

-obliterative bronchiolitis

-allergic alveolitis

-neumonitis

-pleural effusion

-abdominal pain

-bleeding in the stomach or intestines

-gastrointestinal problems / bleeding

-liver insufficiency

-skin rash, redness of the skin, blisters on the lips, eyes, or mouth, skin peeling (erythema multiforme, urticaria, erythema)

-hand-foot syndrome

-facial edema

-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 some blood test results (glucose levels, hormone levels)

-brain disorder (encephalopathy), neurotoxicity manifested as a syndrome characterized by headache, confusion, convulsions, and loss of vision (posterior reversible encephalopathy syndrome), abnormal sensation (dysesthesia, hypoesthesia), tremor, alteration of taste (dysgeusia, hypogeusia), deterioration of smell (parosmia)

-different types of heart problems (ventricular tachycardia, cardiogenic shock, pericardial effusion, bradycardia, palpitations, prolongation of the QT interval on the electrocardiogram)

-infertility in women and men

-changes in menstrual frequency

-intrauterine death

-fetal malformation

-retardation of fetal growth

-cancer-causing effect on offspring

-inflammation of salivary glands (usually in the cheek area; inflammation of the parotid gland)

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 reactions

If you experience any type of adverse reaction, consult your doctor, pharmacist, or nurse even if it is a possible adverse reaction that does not appear in this leaflet. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use: https://www.notificaram.es. By reporting adverse reactions, you can contribute to providing more information on the safety of this medicine.

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

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

Store in refrigerator (2°C - 8°C)

After dilution for intravenous administration - for direct injection:

Chemical and physical stability has been demonstrated in use 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, storage times in use 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 was performed in controlled and validated aseptic conditions.

For intravenous infusion:

Chemical and physical stability has been demonstrated in use for 24 hours at 25°C and 6 days at 2°C - 8°C when diluted with 0.45% sodium chloride solution for infusion; 24 hours at 25°C and 36 hours at 2°C - 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 - 8°C when diluted with 0.9% sodium chloride solution and 5% glucose solution in infusion solution.

From a microbiological standpoint, the product should be used immediately. If not used immediately, storage times in use 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 was performed in controlled and validated aseptic conditions.

Medicines should not be disposed of through drains.Ask your pharmacist how to dispose of the containers and medicines that you no longer need. This will help protect the environment.

Composition of Cyclophosphamide Dr. Reddys

The active ingredient is cyclophosphamide 500 mg/ml.

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

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

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

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

The other component (excipient) is anhydrous ethanol.

Appearance of the product and contents of the package

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

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

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

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

Only some package sizes may be marketed.

Marketing authorization holder and responsible manufacturer

Marketing Authorization Holder

Reddys Pharma Iberia, S.A.

Avda. Josep Tarradellas nº 38

08029 Barcelona (Spain)

Responsible 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 with the following names:

Last review date of this leaflet:November 2021.

For detailed information on this medicinal product, please consult the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es.

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This information is intended solely for healthcare professionals:

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

Dosage and administration

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

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

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

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

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

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

Preparation

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

For direct intravenous injection

Withdraw 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

Withdraw 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:

•Glucose 5% solution for infusion (50 mg/ml)

•0.9% sodium chloride solution for infusion and glucose 5% 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 transparent solutions should be used.

Intravenous route

Direct intravenous administration should be performed preferably as an infusion.

The guidelines for the safe handling of antineoplastic agents should be reviewed in general for the management of cyclophosphamide. Reconstitution should be performed, if possible, in a laminar airflow safety cabinet. The person handling the product should wear a protective mask and protective gloves. In case of spills, the area should be thoroughly washed with water.

Guidelines for safe handling of antineoplastic agents

Cytotoxic preparations should not be handled by personnel in a state of pregnancy. 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 that can be disposed of.

Protective gloves, masks, and protective clothing should be used. Precautions should be taken to avoid accidental contact of the medicinal product with the skin or mucous membranes. The affected area should be thoroughly cleaned with water and soap. If accidental contamination of the eyes occurs, they should be flushed with water immediately.

Use Luer-lock accessories on all syringes and sets. Large-caliber needles are recommended to minimize pressure and the possible formation of aerosols. The latter can also be reduced by using a ventilation needle.

Any unused content should be discarded. Care and caution should be taken when disposing of the elements 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 waste materials should be aware of the risks involved. Any unused medicinal product or waste material should be disposed of in accordance with the standard procedures applicable to cytotoxic agents.

Storage and shelf life

Direct intravenous injection

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

From a microbiological point of view, the product should be used immediately. If not used immediately, storage times in use 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 performed 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 - 8°C when diluted with a sterile 0.45% sodium chloride solution; 24 hours at 25°C and 36 hours at 2°C - 8°C when diluted with glucose 5% solution for infusion (50 mg/ml); and 24 hours at 25°C and 36 hours at 2°C - 8°C when diluted with 0.9% sodium chloride solution for infusion and glucose 5% solution for infusion.

From a microbiological point of view, the medicinal product should be used immediately. If not used immediately, storage times in use 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 refrigerator (between 2°C and 8°C).

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