Pharmorubicin

A semi-synthetic analogue of Doxorubicin, obtained by epimerization of its molecule, a cytostatic with an antibacterial effect, is used to treat malignant neoplasms of various genesis and localizations. The active ingredient (epicycline hydrochloride) belongs to the anthracycline series. Like all drugs used to stop tumor growth, it has cytotoxic properties and requires careful monitoring of treatment by an experienced oncologist.

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Indications Pharmorubicin

Intravenously for malignant neoplasms:

• localized in the face and neck area;
• breast, lung, ovary and prostate gland;
• lymph and blood - lymphogranulomatosis, leukemia, lymphoma and myeloma;
• soft tissues and bones – melanoma and sarcomas;
• organs involved in the digestive process: esophagus, stomach, lower intestines, pancreas.

Intra-arterial - malignant neoplasm of the liver (hepatocellular carcinoma).

Instillations are non-invasive malignant (in situ) neoplasms of the bladder.

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Release form

It is produced in the form of a red lyophilized powder or dense porous mass, packaged in transparent glass vials of 0.01 or 0.05 g of the active ingredient (epirubicin hydrochloride), with a solvent included - water for injection in five-milliliter ampoules.

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Pharmacodynamics

The drug prevents the division and development of tumor cells. The action of Farmorubicin is that its active component is embedded between two helices of the DNA molecule of a cancer cell, forming a defect in this place, thereby preventing its replication. In addition, epirubicin hydrochloride is able to inhibit the enzymatic activity of topoisomerase II, which catalyzes several processes of DNA replication (gene transcription, chromosomal segregation). The formation of a strong connection of the active component with the DNA of a cancer cell changes its structure, functions, reduces matrix activity and, ultimately, disrupts the production of nucleic acids, and the proliferation of malignant tumor cells stops.

The formation of free radicals during the activation of epirubicin by cellular microsomes also contributes to the death of cancer cells, in these places, separations (single and double) of the DNA helix are formed. However, the toxic effect of anthracyclines on the heart muscle is associated with this ability. Nevertheless, the cardiotoxicity of epirubicin is less pronounced than that of its predecessor Doxorubicin.

Pharmacokinetics

The active ingredient of the drug, administered intravenously, penetrates organs and tissues at a good rate, without overcoming the blood-brain barrier. The connection with serum albumins is 77% regardless of the level of epirubicin in the blood. Its metabolism (oxidation) occurs in the liver, the change in the serum level of epirubicinol (a metabolic product) occurs proportionally to the residual density of the unchanged active substance. The half-life of circulation of the active substance in the blood is about 40 hours. Its distribution in the tissues of the body is wide and uniform, as evidenced by the high purification coefficient (0.9 l / min). It is excreted mainly through the bile ducts, about 10% leaves the body through the kidneys.

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Dosing and administration

This drug can be prescribed independently or in combination with other drugs that inhibit cell proliferation processes; its dosage depends on the chosen therapeutic regimen, following special recommendations.

The solution is prepared as follows: a solvent (saline or sterile water for injection) is added to the contents of the vial at a rate of 10 mg of epirubicin/5 ml of solvent, then the vial is shaken until the dry substance is completely dissolved.

Intravenous infusions. For monotherapy, adult patients are recommended to dose the drug per cycle at a rate of 60-90 mg per square meter of body surface. The infusion cycle is carried out with a frequency of once every 21-28 days. The dose calculated for the cycle can be administered as a single infusion or divided into parts and infused by jet or drip for two or three days in a row.

When used in combination with drugs of similar action, the dosage of Farmorubicin is reduced accordingly.

If it is necessary to use large doses, the drug requirement per cycle is calculated at 90-120 mg per square meter of body surface and is administered once, observing an interval between infusions of three to four weeks.

Repeated infusions of Farmorubicin are carried out only in the absence of symptoms indicating the toxic effect of the previous course, with special attention being paid to the normalization of the blood count and the disappearance of dyspeptic disorders.

In patients with renal dysfunction, with plasma creatinine levels exceeding 5 mg/dL, the dosage of the drug is reduced.

In patients with liver dysfunction with a serum bilirubin density of 1.2 to 3.0 mg/dL and/or an AST value two to four times the upper limit of the norm, the infusion dose per cycle is halved compared to the standard dose; with a bilirubin value greater than 3.0 mg/dL or an AST value more than four times the upper limit of the norm, the infusion dose per cycle should be 1/4 of the standard dose.

For individuals with a history of treatment with cytostatics in high doses, as well as with tumor infiltration of the bone marrow, it is recommended to reduce the dosage or extend the time interval between cycles.

The dosage of the drug for initial therapy in elderly patients is carried out according to general standards.

The probability of thrombus formation and accidental drug penetration into nearby tissues can be reduced by injecting it into the infusion system tube during drip infusion of solutions - dextrose (5%) or physiological. The duration of the procedure depends on the dosage of Farmorubicin, the volume of the infused solution and ranges from three minutes to 1/3 hour.

Intravesical infusions. Therapeutic regimens for the treatment of non-invasive bladder tumors include eight weekly intravesical infusions of Farmorubicin. For this, 50 mg vials are used, the contents of which are dissolved in 25-50 ml of saline. Symptoms of local intoxication are manifested by chemical cystitis, the signs of which are the absence, delay or, conversely, frequent and abundant urination, nocturnal enuresis or frequent urge to urinate at night, all this can be accompanied by pain, burning and other discomfort above the pubis, microscopic or macroscopic hematuria. The presence of symptoms of intoxication with Farmorubicin should motivate a reduction in dosage to 30 mg.

If the malignancy of the neoplasm is unspecified (in situ) and the patient tolerates the drug well, the dosage can be increased to 80 mg.

To prevent recurrence, patients who have undergone transurethral removal of a superficial bladder tumor are usually given four intravesical infusions of 50 mg epirubicin (one per week), followed by similar treatments monthly for the rest of the year (11 treatments in total).

The drug is infused into the bladder using a catheter. Before the procedure, you should try not to drink anything for half a day to avoid diluting the injected solution with urine. The liquid is left inside for 60 minutes. During this time, the patient periodically turns from side to side so that the solution washes all areas of the mucous membrane evenly. After the procedure, the patient should urinate.

Introduction into the main hepatic artery. The purpose of this method is to provide intensive action of the drug directly at the site of the cancer tumor while reducing its systemic toxic effect. This type of infusion is recommended for the diagnosis of primary hepatocellular malignancy. For this procedure, the dosage of epirubicin per cycle is 60-90 mg per square meter of the patient's body surface, the time interval between infusions is maintained from three weeks to three months. Dosing of 40-60 mg per square meter is possible, procedures are carried out every four weeks to ensure and simultaneously reduce the general toxic effect.

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Use Pharmorubicin during pregnancy

This medicine can be prescribed to a woman carrying a child only for vital indications. Laboratory studies on animals allow the possibility of its teratogenic effect on the fetus. Studies involving this category of patients have not been conducted. Therefore, if it is necessary to prescribe a course of Farmorubicin during the period of bearing a child or if pregnancy is detected during treatment, the woman must be informed of the possibility of negative consequences for the development of the fetus.

Patients of childbearing age should be strongly advised to use reliable contraception during treatment with the drug.

Pharmarubicin therapy may lead to the absence of menstruation in women and early menopause.

Studies on the penetration of Epirubicin hydrochloride into breast milk have not been conducted, however, it is known that drugs of this series are found in breast milk. Therefore, to prevent the negative impact of the drug on the infant, breastfeeding is interrupted before starting therapy with Farmarubicin.

The use of this drug can lead to the appearance of chromosomal defects in male reproductive cells (spermatozoa), so men must use reliable protection during treatment. And if necessary, donate their sperm for storage before the start of treatment, since irreversible infertility can be a consequence of Farmorubicin therapy.

Contraindications

General: Known allergy to anthracyclines and anthracenediones. Pregnancy and breastfeeding.

For intravenous infusions:

• a significant decrease in the level of leukocytes and platelets in the blood (myelosuppression);
• severe forms of cardiac and renal organic lesions and functional disorders;
• heart rhythm disturbance;
• history of recent myocardial infarction;
• recent course of therapy with high doses of drugs belonging to the anthracycline or anthracenedione group.

For intravesical infusion:

• neoplasms that have grown into the lining of the bladder;
• infectious and inflammatory diseases of the urinary organs.

Side effects Pharmorubicin

Hematopoiesis disorders: a decrease in the quantitative indicators of blood cells - leukocytes, platelets, hemoglobin, neutrophils (usually temporary and reversible, the minimum is observed ten or two weeks after the administration of Farmarubicin; by the end of the third week the indicator is restored to normal).

Manifestations of toxicity to the heart muscle:

• acute (early) manifests itself in increased heart rate and heart rhythm, these symptoms may be accompanied by non-specific changes in the electrocardiogram in the ST segment and T wave, a slow pulse, bundle branch block or atrioventricular block may be observed (these symptoms do not usually foreshadow the development of delayed more serious manifestations of cardiotoxicity, have no clinical significance and do not suggest discontinuation of the course of treatment);
• delayed or late manifests itself as a decrease in systolic blood volume during contraction of the left ventricle; inflammation of the pericardium or myocardium is possible; thromboembolism, including pulmonary artery, which can result in the death of the patient; these signs can occur independently or be accompanied by symptoms of congestive heart failure (shortness of breath, gallop rhythm, pulmonary or lower extremity edema, enlargement of the heart and liver, decreased urine output, abdominal dropsy, exudative pleurisy) - the most severe side effect of taking Farmorubicin, limiting the required volume of the drug accumulation dose.

Digestive disorders: loss of appetite, inflammation of the gums, hyperpigmentation of the oral mucosa, nausea, vomiting, colitis, diarrhea, inflammation of the esophagus, abdominal pain (cutting and burning), erosive gastropathy, gastroduodenal bleeding.

Liver tests: increased ALT and AST levels, as well as bilirubin concentration.

Urinary disorders: red urine is observed in the first two days after administration of the drug; excess uric acid in the urine.

Eyes: inflammation of the outer shell and/or cornea.

Endocrine disorders: hot flashes, absence of menstruation, which usually returns after the end of therapy, however, there is a risk of early menopause; decreased volume of ejaculate, absence of sperm in it (sometimes after a fairly long period after the course of therapy, these indicators can return).

Skin: hair loss, urticaria, itching, hyperemia, increased pigmentation of the skin, sensitization to ultraviolet light, photoallergy.

General: weakness, fatigue, asthenic condition, fever, febrile condition, acute lymphocytic or myelogenous leukemia, anaphylaxis.

Local effects: a strip of erythematous rash may be observed along the venous vessel into which the solution was infused; over time, inflammation, sclerotic changes or thrombi may develop in the same vessel (especially after repeated infusion). If Farmorubicin enters past the venous blood flow, flows out of the vein onto the skin - there is a high probability of developing a local reaction of the affected tissues, up to their necrotic changes.

The introduction of the drug into the artery is fraught with negative consequences in the form of general intoxication and, in addition, ulceration of the mucous membranes of the digestive tract (stomach and duodenum), hypothetically as a result of backflow into the gastric artery and/or sclerosing inflammation of the bile ducts, manifested by their strictures.

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Overdose

Severe myelosuppressive symptoms, mainly a strong decrease in the quantitative indices of leukocytes and platelets; inflammatory-erosive lesions throughout the digestive tract from the oral cavity to the intestines; acute manifestations of toxic effects on the myocardium.

Therapeutic measures are coordinated with the symptoms that have appeared (the antidote to Farmorubicin is not known).

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Interactions with other drugs

Combination with other drugs that inhibit cell proliferation potentiates their mutual action and increases drug intoxication, especially with regard to the manifestation of myelosuppression and mucositis.

Combination with drugs toxic to the heart muscle, as well as with calcium channel blockers, requires careful monitoring of cardiac function throughout the course of treatment.

It is not recommended to use it simultaneously with cimetidine, since this combination reduces the rate of elimination of Farmorubicin from the body.

This drug must not be mixed with any other drugs, or with alkaline solutions (to avoid hydrolysis of the active ingredient).

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Storage conditions

Does not require special storage conditions. The prepared solution is stored for no more than two days in a cool (4-10℃) and dark place or at room temperature - no more than a day.

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Shelf life

The expiration date is indicated on the packaging (no more than 4 years).

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