Bleomycin Bidiphar medicine for treatment of carcinoma, melanoma

ATC code: L01DC01

Pharmacological and mechanism of action:

BLEOYMIN is a soluble glycopeptide antibiotic mixture in water that has a toxic effect of cells, created by Streptomyces Verticillus, in which BLEOMYCIN A, and BLEOMYCIN B, are the main components. The mechanism of action of BLEOMYCIN is to break the DNA segment, partly due to the drug directly linked to DNA and partly due to the formation of free radicals. Due to inhibition of DNA synthesis, it inhibits the division and growth of tumor cells. The drug has a specific effect on DNA and does not affect the synthesis of RNA or protein of tumor cells.

The maximum effect in the cell cycle occurs in the M phase, and during the transition from the G1 phase to the S phase, but the G2 phase is also very sensitive to the Bleomycin.

BLEOYCIN has a high affinity for scales and especially achieves high concentrations in the skin, lungs, abdominal and lymphocytes.

Combination of radiation treatment has the effect of copper with drugs, especially when treating cancer in the head and neck. When treating carcinomometoma (scaled cells), the best effect in highly differentiated tumors.

In addition to the anti -tumor effect, BLEOMYCIN almost has no other effect. When intravenous injection, the drug may have the same effect as histamines on blood pressure and increase body temperature.

Dynamic pharmacokinetics

BLEOYCIN is poorly absorbed when used on the spot. Bleomycin is less absorbed by the gastrointestinal tract but is quickly absorbed through the injection, peritoneal and pleura. Born after intramuscular injection is 100%, peritoneal or pleura is 45%.

The ratio is attached to low plasma proteins. Blood medication can be measured by radioactive immunology.

After intravenous injection of 15 USP/m, the serum concentration reaches 10 - 10,000 millimeters of units. The distribution is about 0.27 ± 0.04 liters/kg; The clearance of 0.066 ± 0.018 liters/hour/kg.

Low cerebrospinal fluid concentration. After being injected, Bleomycin is distributed mainly in the skin, lungs, kidneys, peritoneal and lymphatic system. The concentration of the drug in the skin and lung tumor is higher than the hematoma. Low bone marrow concentration may be due to the concentration of the degenerative enzymes of BLeomycin in the high bone marrow.

BLEOYCIN is degenerated mainly in plasma, liver and some other organs, a few in the skin and lungs. The drug is inactive in tissues by the specific hydrolytic catalyst enzyme Bleomycinhydrolase, this enzyme has very little in the skin and lungs, these are two main toxic places of the drug.

After an intravenous injection, the drug is eliminated in 2 phases: the half -life of the first phase is 0.5 hours and the last phase is 4 hours. If the intravenous transmission is continuous, the elimination may be longer (1.3 and 9 hours). Two -thirds of the dose is eliminated in an unknown form, the rate of elimination is decided by the kidney function.

When intravenous injection, the drug is faster when intramuscularly. For patients with normal renal function, about 70% of the dose is excreted in the form of unchanged urine within 24 hours. In people with moderate kidney failure (clearing creatinine

Clinical safety data:

Animal tests shows BLEOMYCIN, as well as other cytotoxic toxins, capable of monitoring and mutations.

BLEOYCIN has been reported to cause atherosclerosis and kidney cancer in the mouse when subcutaneously injected.

BLEOYCIN has been reported to cause fetal defects in experimental animals (mice).

Bloomycin treatment patients must be checked with the lung X -ray at least 2 months after treatment. If there are signs of changes in the lungs, immediately use Bloomycin and glucocorticoid treatment and broad -spectrum antibiotic.

At least 50% of patients with erythematosus, horny and skin ulcers, especially in the pressed skin. These changes often begin to edematize and increase colds in the fingers and elbows.

The risk of toxicity with the lungs is often increased when the total dose of treatment is over 400 USP units, using the medication simultaneously with respiratory radiation, using simultaneously with other toxic pills with other lungs or lung disease. The risk of toxicity is also increased when using high oxygen concentrations during anesthesia with the elderly. Symptoms usually start with cough and shortness of breath, fever, appearing 1-3 months after the beginning of treatment. One of the reasons selectively toxic drugs on the lungs and skin seems to be due to the decrease in the Bleomycin Hydrolase in these tissues.

Some studies suggest that the subcutaneous infusion of Bleomycin can reduce toxicity to the lungs and even increase the anti -tumor effect of Bleomycin.

or using Bleomycin to constantly intravenously or subcutaneous infusion also decreased toxic to the lungs.

Monitor: Calculate the cumulative dose before and after each treatment. Monitor the temperature at the beginning, especially in patients with lymphoma. Assess the kidney function before taking the drug. The best lung monitoring is equal to the dispersion capacity of shrinkage and exertion. Lung function should be checked both before and during treatment. The detection characteristics on the X -ray, including changes, suggested the spread of spreading on both sides.

If there is difficulty breathing or contamination that cannot be attributed to tumors or lung diseases, the drug must be stopped immediately and for patients to treat corticosteroids and broad -spectrum antibiotics.

Side effects when injecting Bleomycin into the pleural cavity: chest pain and fever (can be used before injecting or lidocaine in the catheter to reduce pain; Lower blood pressure, nausea, vomiting, diarrhea, coughing blood, stasis, bacterial shock, rash, hair loss.

Be cautious when used

BLEOYCIN even when using low doses. The drug should be used under the supervision of the cancer specialist with experience in chemotherapy and treatment facilities with full diagnostic, treatment and interventions when complications. Patients who are receiving treatment with Bleomycin must be monitored carefully and regularly during and after treatment.

Lung toxicity:

This is the most serious toxicity related to the use of Bleomycin (See also the unwanted effect).

Patients being treated should be chest X-ray every 1-2 weeks, continue to monitor 04 weeks after completion of treatment. If observations are changed in the lungs, immediately stop treatment to determine whether the cause is related to the drug or not. Treatment of pneumonia should be conducted promptly with antibiotics and steroids. Repeated treatment is contraindicated for any patient showing signs of pneumonia or lung reduction.

Anesthesia: patients treated with BLEOMYCIN are at high risk of symptoms of post -surgical respiratory failure in adults 6-12 months after initial treatment. To minimize the risk in surgical patients who have been treated with Bleomycin, the recommended preventive measures are as follows:

(1): Use low -concentration oxygen (

(2): Avoid pulmonary edema by monitoring the infusion (using glue solution instead of using dissolved solution).

Lung cancer: BLEOMYCIN should be used extremely carefully in patients with lung cancer, because these patients show the rate of lung poisoning increases.

Elderly: Patients over 70 years of age should be strictly monitored with signs of lung toxicity caused by Bleomycin (See more unwanted effects), because of this risk of increasing toxicity.

Cumulative dose: Lung toxicity is more common in patients using a total dose of more than 400,000 IU (400 USP units).

Kidney or liver toxicity: Cases of kidney toxicity, began to impaired renal and liver function has been reported irregularly, but may occur at any time after the beginning of treatment.

Abnormal/special reactions: The reactions are not clear similar to anaphylactic shock that have been reported in lymphoma patients treated with Bleomycin. Because these symptoms usually occur after the first or second dose, careful monitoring should be monitored after using these doses.

Patients with lymphoma: All lymphoma patients need to be tested by the dose of Bleomycin before starting the full dose treatment, because of the possibility of anaphylaxis.

Renal failure: BLEOMYCIN should be used carefully with patients with renal failure.

impaired lung function due to non -malignant diseases: Bleomycin should be used very carefully because it is especially toxic to the lungs.

Cancer ability: Bleomycin's cancer ability in people is unknown. However, for cytotoxic agents, it is impossible to rule out the possibility of cancer.

The effect of the drug on the ability to drive and operate machinery

The operation of machinery and driving depends on the condition of the patient and should be considered by the doctor.

Use drugs for women during pregnancy and lactation

pregnancy:

BLEOYCIN has a teratogenic effect in animals and can be through the placenta.

BLEOYMINCIN is contraindicated for pregnant women.

If the patient is pregnant, the risk must be notified to the fetus.

breastfeeding period:

It is not clear whether the drug is excreted through breast milk or not. Patients with BLEOYCIN should not breastfeed.

reproductive ability:

BLEOYCIN has been shown to cause mutations in in vitro and in vivo; Momnicism. Impact on the unresolved fertility.

Women of reproductive age must avoid pregnancy during treatment with BLEOYCIN and 06 months after treatment.

Drug interaction

When BLEOYCIN is used as one of the valence medications in a combination regimen, it is necessary to pay attention to the toxicity of BLEOYCIN when choosing the same drug and the dosage of the same toxicity. The addition of other cytotoxic drugs may require changes in dosage. Increasing toxicity on the lungs has been recorded when using Bleomycin with cisplatin.

Methods of radiation first or at the same time chest area and/ or use of anti -tumor drugs (for example, cisplatin) are important factors that increase the frequency and severity of lung poisoning such as interstitial pneumonia or pulmonary fibrosis.

Radiation before or at the same time the head or neck is a factor that increases stomatitis and cracking of the corner of the corner may worsen.

It can cause pharyngitis mucosa leading to hoarseness.

Because Bleomycin is sensitive to lung tissue, patients who have been used Bleomycin before surgery are at risk of developing pulmonary toxicity when using oxygen in surgery, so the reduction of inhaled oxygen levels in and after surgery is recommended.

In patients with testicular cancer treatment patients with Bleomycin and coconut alkaloid, a syndrome has been reported similarly to Raynaud's disease, anemia can lead to necrosis of the peripheral parts of the body (fingers, toes, nose tip).

The cavalry of the drug:

BLEOYMINCIN is similar to valence cations II (especially copper) and compounds with sulfhydryl groups.

Do not mix the Bleomycin solution with essential amino acids, ascorbic acid, dexamethasone, aminophylin or furosemid.

No drug or dilute with glucose solutions (because of the inactivation).