Cyclophosphane

Cyclophosphamide is a cytostatic drug that is widely used in oncology to treat various types of cancer, and in rheumatology and several other medical fields to treat immune and inflammatory diseases.

Indications Cyclophosphane

Cyclophosphan (Cyclophosphamide) is used in the treatment of various diseases, both malignant and immune. The main indications for its use include:

1. Oncology:

   • Lymphomas: Including Hodgkin's lymphoma and non-lymphatic lymphomas.
   • Leukemias: Including acute lymphoblasticleukemia, acute myeloblasticleukemia and chronic myeloidleukemia.
   • Bladder Cancer: Cyclophosphane can be used as part of combination chemotherapy.
   • Breast Cancer: As part of adjuvant or neoadjuvant therapy and for the treatment of metastatic breast cancer.
   • Ovarian Cancer: As part of combination therapy for the treatment of ovarian cancer.
   • Lung Cancer: Cyclophosphane can be used in combination with other drugs to treat lung cancer.
   • Other tumors: Including cervical cancer, head and neck cancer, sarcomas, etc.

2. Rheumatologic diseases:

   • Systemic Lupus erythematosus (SLE): Cyclophosphane is used to suppress disease activity and prevent organ damage.
   • Rheumatoid Arthritis: As part of combination therapy for severe disease activity.
   • Vasculitides: Including polyarteritis nodosa, granulomatous polyangiitis (formerly known as Wegener's), microscopic polyangiitis, etc.

3. Organ transplantation:

   • As an immunosuppressive agent to suppress rejection reactions in organ transplantation.

4. Other immune and inflammatory diseases:

   • Including systemic sclerosis, Still's syndrome, systemic lupus erythematosus, etc.

Release form

Cyclophosphane is available in several dosage forms depending on the method of administration and dosage. The main dosage forms include:

1. Tablets: Cyclophosphane is manufactured in the form of oral tablets. The tablets are available in different dosages, allowing the doctor to accurately select the best dose for each patient. These tablets are usually used to treat various diseases as part of chemotherapy.
2. Solution for injection: Cyclophosphane is also available in the form of a solution for injection. This solution is intended for intravenous administration and is usually used in an inpatient setting under the supervision of medical personnel. The solution for injection can be used to treat various types of cancer as well as rheumatologic and other diseases.
3. Oral suspension: In some cases, cyclophosphane may be available as an oral suspension. This may be a preferred option for patients who have difficulty swallowing tablets or for those who prefer this form of the drug.

Pharmacodynamics

Cyclophosphamide is a prodrug that is metabolized in the liver to form active metabolites, phosphoramide mustard and acrolein. These metabolites have the following actions:

• DNA alkylation: Phosphoramide mustard, the main active metabolite, alkylates DNA by forming cross-links between two DNA strands. This interferes with DNA separation and hence cell division, which is particularly effective against rapidly dividing cells such as cancer cells.
• Induction of apoptosis: DNA alkylation can also initiate processes leading to cell apoptosis.
• Immunosuppression: Cyclophosphamide suppresses the immune system by affecting lymphocytes, which is useful in treating autoimmune diseases and preventing rejection of transplanted organs.

Pharmacokinetics

Cyclophosphane pharmacokinetics describes how the body processes the drug after it is taken. Here are the main aspects of Cyclophosphane pharmacokinetics:

1. Absorption: Cyclophosphane is usually well absorbed after oral administration, but absorption may be variable and dependent on individual patient characteristics. The time to reach maximum concentration (Tmax) is usually 1 to 2 hours after tablet administration.
2. Metabolism: Cyclophosphan is metabolized in the liver to form the active metabolite 4-hydroxycyclophosphamide (4-OH-CPA), which is responsible for its therapeutic effect. Metabolism is carried out via cytochrome P450.
3. Distribution: Cyclophosphan is widely distributed in the body and penetrates into many tissues and organs. It is also able to penetrate the placental barrier and is excreted in breast milk.
4. Excretion: Excretion of cyclophosphane from the body occurs mainly by the kidneys in the form of metabolites. Approximately 10-50% of the dose is excreted unchanged through the kidneys and the remainder is excreted as metabolites through the urine.
5. Half-life: Thehalf-life of cyclophosphane is about 6-9 hours. This may be varied depending on the patient's condition, degree of functional activity of the liver and kidneys.
6. Interactions: Cyclophosphane may interact with other drugs, affecting their metabolism or pharmacokinetic parameters. Such interactions should be taken into account when prescribing combination therapy.

Dosing and administration

The route of administration and dosage of cyclophosphamide can vary considerably depending on the disease, stage of disease, treatment regimen (monotherapy or combination therapy), and individual patient characteristics such as weight, age, general health and renal function. It is important that treatment and dosage are always determined and monitored by a physician. The following are general recommendations for use and doses, but are not intended to replace medical advice from a specialist.

Oral administration:

• For adults: Dosage varies from 50 to 200 mg per day depending on the specific disease and treatment goal.
• For children: Dosage is usually calculated based on body surface area (mg/m²) or child weight (mg/kg).

Intravenous administration:

Cyclophosphamide is most commonly administered intravenously in the hospital setting, especially at high doses or in combination chemotherapy regimens. Doses for intravenous administration can vary considerably:

• High-dose therapy: May exceed 1 g/m² body weight, especially in preparation for bone marrow transplantation.
• Standard dosage: Varies depending on the treatment regimen, may be administered as a singledose or divided over several days.

Important aspects of the application:

• Hydration: To prevent cystitis caused by cyclophosphamide, patients are advised to increase fluid intake on the day of administration and on subsequent days.
• Mesna: Mesna may be prescribed for prophylaxis of hemorrhagic cystitis, especially with high doses of cyclophosphamide.
• Monitoring: Regular blood monitoring is necessary to monitor bone marrow function and kidney and liver function during treatment.

Use Cyclophosphane during pregnancy

The use of Cyclophosphane during pregnancy may pose serious risks to both mother and fetus. This drug is FDA (Food and Drug Administration) category D for use during pregnancy, which means that there is evidence of risks to the fetus, but the benefits of the drug may be justified in some cases under strict medical supervision.

The main risks of using cyclophosphane during pregnancy include:

1. Fetal toxicity: Cyclophosphane may penetrate the placental barrier and have toxic effects on the developing fetus, which may lead to various congenital anomalies and developmental disorders.
2. Loss of pregnancy: Use of cyclophosphane during pregnancy may increase the risk of pregnancy failure and fetal loss, especially when taken during the first trimester of pregnancy.
3. Ovarian disorders: Cyclophosphane may cause ovarian disorders in women and lead to infertility or temporary cessation of menstrual cycle.
4. Risk of disease in the child: Children born to mothers who took cyclophosphane during pregnancy may have an increased risk of developing cancer and other health problems.

Therefore, the use of cyclophosphane during pregnancy is usually considered only when absolutely necessary and after careful assessment of the benefits and risks to the mother and fetus.

Contraindications

Like any other drug, Cyclophosphane has a number of contraindications that should be considered before its prescription. It is important to conduct a thorough assessment of the patient's condition to avoid possible negative consequences. Here are the main contraindications to the use of cyclophosphamide:

Major contraindications:

1. Hypersensitivity: Patients with a known allergy to cyclophosphamide or any of its components should not receive this drug.
2. Pregnancy: Cyclophosphamide is classified as a Category D drug by the FDA, meaning that there is a confirmed risk of harm to the fetus if used during pregnancy. Cyclophosphamide may cause birth defects and/or fetal death and should not be used in pregnant women unless the potential benefit outweighs the potential risk.
3. Breastfeeding: Cyclophosphamide and its metabolites may pass into breast milk and cause harm to the infant. It is recommended that women receiving cyclophosphamide discontinue breastfeeding.
4. Severe bone marrow dysfunction: In patients with severely depressed bone marrow, the use of cyclophosphamide may result in further suppression of hematopoiesis.
5. Active infections: In patients with active, especially severe infections, the use of cyclophosphamide may worsen the condition because of its immunosuppressive properties.
6. Severe hepatic or renal impairment: Cyclophosphamide is metabolized in the liver and excreted by the kidneys, so patients with severe impairment of these organs may experience increased toxicity of the drug.

Relative contraindications:

Some relative contraindications include moderate impairment of liver or renal function, moderate suppression of cerebral hematopoiesis and controlled infections. In such cases, cyclophosphamide may be used with caution, with careful monitoring of the patient's condition.

Side effects Cyclophosphane

Cyclophosphane can cause a number of side effects that can be both temporary and more serious. Here are some of them:

1. Toxic effects on bone marrow: Cyclophosphane may inhibit blood formation in the bone marrow, resulting in decreased numbers of white blood cells, platelets, and red blood cells, which increases the risk of infections, bleeding, and anemia.
2. Toxic effects on the mucous membrane of the gastrointestinal tract: May manifest as nausea, vomiting, diarrhea, ulcers and other digestive disorders.
3. Renal impairment: Cyclophosphane may cause toxic effects on the kidneys, which may lead to impairment of their function and development of renal failure.
4. Urologic complications: Include cystitis, hemorrhagic cystitis, and other urinary tract complications.
5. Toxic effects on the liver: May cause liver damage and increased activity of liver enzymes.
6. Cardiovascular disorders: Include arterial hypertension, heart rhythm disturbances, cardiomyopathy and other cardiac complications.
7. Nervous System Damage: Includes peripheral neuropathy, neuropathy, paresis, and other neurologic complications.
8. Skin side effects: Include allergic reactions, rash, skin depigmentation, etc.
9. Immune disorders: Allergic reactions, autoimmune manifestations may occur.
10. Risk of developing secondary tumors: Long-term use of cyclophosphane may increase the risk of developing secondary tumors such as leukemia.

Overdose

An overdose of cyclophosphamide (Cyclophosphamide) can have serious consequences and may require medical attention. Overdose with this medication can occur due to unintentionally increasing the dose or due to improper use. Symptoms of overdose may include:

1. Toxic effects on bone marrow: This manifests as severe anemia, thrombocytopenia and leukopenia.
2. Digestive disorders: Severe nausea, vomiting, diarrhea and other digestive symptoms.
3. Kidney and liver damage: Increased activity of hepatic enzymes and impaired renal function.
4. Urologic complications: Hemorrhagic cystitis and other urinary tract complications.
5. Neurologic symptoms: Including peripheral neuropathy and other neurologic complications.
6. Cardiac complications: Heart rhythm disturbances, arterial hypertension and other cardiovascular symptoms.

Interactions with other drugs

Cyclophosphamide (Cyclophosphan) may interact with various drugs, which may affect their effectiveness or level of toxicity. Some of the most significant interactions are summarized below:

1. Drugs that increase the risk of myelosuppression: Use of cyclophosphane with other drugs that also cause myelosuppression, such as other cytostatics or antibiotics, may increase the risk of pancytopenia and other hematopoietic disorders.
2. Allopurinol: Allopurinol may slow the metabolism of cyclophosphane in the liver, which may increase its toxicity.
3. Medications that cause hemorrhagic cystitis: Use of cyclophosphane with other medications that contribute to hemorrhagic cystitis, such as methotrexate or furosemide, may increase the risk of developing it.
4. Drugsaffecting liver and kidney function: Drugs that affect liver or kidney function may alter the metabolism and excretion of cyclophosphane from the body, which may affect its efficacy or toxicity.
5. Drugsaffecting blood circulation: Drugs affecting blood circulation, such as anticoagulants or antiaggregants, may increase the risk of bleeding when used concomitantly with cyclophosphan.
6. Antifungal drugs: Some antifungal drugs, such as ketoconazole or fluconazole, may increase the toxicity of cyclophosphane.

Storage conditions

Storage conditions for Cyclophosphamide (Cyclophosphamide) may vary depending on the form of the drug (tablets, solution for injection, etc.) and the manufacturer. However, the following is generally recommended for all forms of release:

1. Storage Temperature: Cyclophosphamide is usually stored at room temperature between 20 and 25°C.
2. Protection from light: The drug should be stored in a place protected from light to prevent decomposition of the active ingredients by light.
3. Protection from moisture: Avoid moisture in the containers or packaging of the drug.
4. Storage out of reach of children: Preparations should be stored out of the reach of children or in places where they cannot be accidentally ingested by children.
5. Manufacturer's specific instructions: It is important to follow the instructions on the drug package and your doctor's instructions regarding storage and use of cyclophosphamide.
6. Use after expiration date: Do not use the product after the expiration date indicated on the package.

It is important to refer to the storage instructions that come with the specific package of cyclophosphamide and follow the directions of your doctor and pharmacist.