5-fluorouracil 5% 20ml

Mechanism of action

Fluorouracil is an antimetabolite of uracil. The mechanism of action is due to the transformation of the drug in tissues into the active metabolite fluorouridine monophosphate, which is a competitive inhibitor of the enzyme thymidylate synthetase, which is involved in the synthesis of nucleic acids. Fluorouracil disrupts DNA synthesis and causes the formation of structurally imperfect RNA, inhibiting the division of tumor cells. Active metabolites are localized within the cell.

Pharmacokinetics

After intravenous administration, the drug is rapidly biotransformed and distributed in tumor tissues, intestinal mucosa, bone marrow, liver and other tissues. Easily penetrates the blood-brain barrier, falling into the cerebrospinal fluid and brain tissue. Metabolized mainly in the liver to form inactive metabolites. The half-life of fluorouracil depends on the dose administered and is 8–22 minutes. About 20% of the drug is excreted by the kidneys in unchanged form for 6 hours (90% of this amount is eliminated during the 1st hour) and 60-80% through the respiratory tract in the form of CO₂, a small amount is excreted in the bile.

Indications

- cancer of the colon and rectum;

- mammary cancer;

- esophageal carcinoma;

- stomach cancer;

- pancreas cancer;

- primary liver cancer;

- ovarian cancer;

- cervical cancer;

- bladder cancer;

- malignant tumors of the head and neck;

- prostate cancer;

- adrenal cancer;

- cancer of the penis;

- carcinoid.

Dosage and administration

Fluorouracil is a part of many Chemotherapy regimens, and therefore, in choosing the route of administration, regimen and doses in each individual case, one should be guided by the data of special literature.

The drug is injected into / in the streamer or by slow infusion, intraarterially, intracavitary.

The following doses and regimens are recommended:

500 mg / m² or 12-13.5 mg / kg daily for 3-5 days, the interval between courses is 4 weeks;

600 mg / m² or 15 mg / kg (the highest single dose of 1 g) once a week, 6-10 doses;

600 mg / m² on days 1 and 8 of the IV in combination with other cytostatics;

1 g / m² / day in / in drip in the form of a constant infusion over 96-120 h;

When used in combination with Calcium folinate, the dose of fluorouracil is usually reduced by 25-30%.

Side effect

From the side of blood-forming organs: leukopenia, neutropenia, rarely - thrombocytopenia, anemia. The most significant drop in the number of leukocytes is usually observed from 9 to 14 days (up to 25 days), platelets from 7 to 17 days of treatment.

Gastrointestinal: loss of appetite, nausea, vomiting, inflammation and ulceration of the mucous membranes of the gastrointestinal tract (including stomatitis), diarrhea, bleeding from the gastrointestinal tract, heartburn and a change in taste, impaired liver function.

Cardiovascular: very rarely - pain in the heart, arrhythmias, ischemia, myocardial infarction, angina pectoris, heart failure.

Nervous system: rarely - cerebellar ataxia, impaired sensitivity, disorientation, confusion, euphoria, nystagmus, retrobulbar neuritis, headache.

Special senses: irritation of the mucous membrane of the eyes, excessive tearing due to duct stenosis (10-25%), photophobia, cataracts, cortical blindness (at high doses), impaired vision.

From the reproductive system: reversible inhibition of the function of the gonads, leading to amenorrhea or azoospermia.

From the skin and skin appendages: alopecia (rarely), hyperpigmentation of the skin, dry and cracked skin, telangiectasia, palm-plantar erythrodisesthesia syndrome (tingling sensation in the hands and feet, followed by pain, hyperemia and swelling), change and convergence of the nail plates (rarely), photosensitization.

Allergic reactions: skin rash, dermatitis, urticaria, hyperemia of the skin of the palms and soles, bronchospasm, anaphylaxis (rare).

Other: fever (rarely), thrombophlebitis at the injection site, nosebleeds, cough, shortness of breath, hyperuricemia, weakness, the development of secondary infections.

Contraindications

- hypersensitivity to fluorouracil and / or any other component of the drug;

- pregnancy;

- lactation;

- severe leukopenia, neutropenia, thrombocytopenia;

- stomatitis;

- ulceration of the gastrointestinal mucosa;

- pseudomembranous enterocolitis.

WITH caution: renal and / or liver failure; acute infectious diseases of viral, fungal or bacterial nature (including tuberculosis, chicken pox, shingles); bone marrow infiltration by tumor cells; previous radiotherapy or chemotherapy.

Use during pregnancy and lactation

Contraindications: pregnancy; lactation.

Application for violations of the liver

WITH caution: liver failure.

The initial dose should be reduced by 1/3 or 1/2 in case of abnormal liver function.

Application for violations of kidney function

WITH caution: renal failure.

The initial dose should be reduced by 1/3 or 1/2 in case of renal dysfunction.

Special notes

Fluorouracil is a cytotoxic drug, so care must be taken when handling it.

When stomatitis or diarrhea appears, treatment with the drug should be stopped until these symptoms disappear.

The initial dose should be reduced by 1/3 or 1/2 in the following cases: weight loss, the postoperative period of at least 30 days after extensive surgery, insufficient bone marrow function, abnormal liver function or kidney function.

Care should be taken when prescribing to patients who have previously been exposed to high doses of radiation in the pelvic area or have received alkylating agents.

During the treatment period, it is necessary to monitor the total number of leukocytes, the absolute number of neutrophils, platelets, determine hematocrit, hemoglobin, liver function tests and bilirubin level, examine the patient's oral cavity for signs of stomatitis.

Men and women of childbearing age during treatment with fluorouracil and for at least 3 months. then you should use reliable methods of contraception.

Influence on ability to drive motor transport and control mechanisms

The side effects caused by taking fluorouracil may adversely affect driving a vehicle.

Overdosage

Symptoms: nausea, vomiting, diarrhea, ulcerative stomatitis and gastric bleeding, suppression of bone marrow function (thrombocytopenia, leukopenia and agranulocytosis).

In case of overdose, the function of blood formation in patients should be monitored for at least 4 weeks, and in the event of violations, symptomatic therapy is carried out. The specific antidote to fluorouracil is not known.

Drug interaction

Calcium folinate enhances the therapeutic and toxic effects of fluorouracil.

When used in combination with other cytostatics and interferon-alpha, there can also be an increase in both the antitumor effect and the toxicity of fluorouracil.

With prolonged joint use with mitomycin C, hemolytic uremic syndrome was observed.

When taken concurrently with sorivudin, a marked leukopenia was noted, in some cases resulting in a lethal outcome.

Fluorouracil should not be used after and in conjunction with therapy with aminophenazone, phenylbutazone and sulfonamide.

Chlordiazooxide, disulfiram, Griseofulvin and isoniazid can enhance the activity of fluorouracil.

Fluorouracil may reduce the immunological response to vaccination. When administered simultaneously with a live vaccine, severe antigen reactions can develop.

Terms and conditions of storage

List A.

In the dark place at a temperature of no higher than 25 ° C.

Note: In case of formation of a precipitate under the influence of low temperatures, the solution should be heated to 60 ° C before use, shaking vigorously and then cooled to room temperature.

Keep out of the reach of children!

Shelf life 2 years.

Do not use after the expiration date printed on the package.

Pharmacy sales terms

On prescription.