Fluorouracil - instructions for use, doses, side effects, contraindications

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

Pharmacokinetics:

After intravenous administration, the preparation is rapidly biotransformed to the active metabolite of fluorouridine monophosphate and distributed in tumor tissues, mucous membranes shell of the intestine, the bone marrow, liver and other tissues. Easily penetrates the blood-brain barrier, getting into the cerebrospinal fluid and brain tissue. Metabolized mainly in the liver with the formation of 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 unchanged for 6 hours (90% of this amount is excreted within 1 hour) and 60-80% - through the respiratory tract in the form of CO2, a small amount is excreted with bile.

Indications:

cancer of the colon and rectum;
mammary cancer;
esophageal carcinoma;
stomach cancer;
pancreas cancer;
primary liver cancer;
ovarian cancer;
cervical cancer;
cancer of the bladder;
malignant tumors of the head and neck;
prostate cancer;
adrenal cancer;
cancer of the vulva;
cancer of the penis;
carcinoid.

Contraindications:

Hypersensitivity to fluorouracil and / or any other component of the drug.
Combination with inhibitors of dihydropyrimidine dehydrogenase (DPD) (brivudine, sorivudine).
Pregnancy and lactation.
Severe leukopenia, neutropenia, thrombocytopenia, stomatitis, ulceration of the gastrointestinal mucosa (GI tract), pseudomembranous enterocolitis.

The postoperative period is less than 30 days after extensive surgical intervention.
Childhood (effectiveness and safety not proven).

Carefully:

renal and / or hepatic insufficiency, acute infectious diseases of a viral, fungal or bacterial nature (including tuberculosis, chicken pox, shingles), bone marrow infiltration by tumor cells, previously intensive radiation therapy or chemotherapy.

Dosing and Administration:

Fluorouracil is included in many chemotherapy regimens, therefore, when choosing the route of administration, regimen and dosage in each individual case, one should be guided by the data of the special literature.

The drug is administered intravenously struino 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 - 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 intravenously in combinations with other cytostatics;
1 g / m²/ day intravenously drip in the form of a constant infusion for 96-120 hours.

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

Side effects:

From the hematopoiesis: 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. Very rarely - pancytopenia, agranulocytosis.

From the digestive system: anorexia, nausea, vomiting, inflammation and / or ulceration of the mucous membranes of the digestive tract (including stomatitis), diarrhea, bleeding from the gastrointestinal tract, heartburn and taste change, glossitis, pharyngitis, esophagitis, mucositis, impaired liver function, cholecystitis.

From the cardiovascular system: very rarely - pain in the heart, arrhythmias, myocardial ischemia, myocarditis, myocardial infarction, angina pectoris, heart failure, cardiomyopathy, cardiogenic shock, lowering blood pressure.

From the nervous system: rarely - cerebellar ataxia, impaired sensitivity, disorientation, confusion, euphoria, nystagmus, retrobulbar neuritis, asthenia, headache.

FROMabout the sides of the sense organs: conjunctivitis, irritation of the mucous membrane of the eyes, lacrimation due to stenosis of lacrimal ducts, photophobia, cataract, cortical blindness (at high doses), diplopia, visual impairment.

On the part of the reproductive system: reversible oppression of the sexual glands, leading to amenorrhea or azoospermia.

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

Allergic reactions: skin rash, dermatitis, urticaria, bronchospasm, anaphylactic shock (rarely).

Other: "tide" of blood to the face, fever (rare), thrombophlebitis at the site of injection, epistaxis, cough, shortness of breath, hyperuricemia, weakness, development of secondary infections

Overdose:

Signs and symptoms of an overdose include nausea, vomiting, diarrhea, ulcerative stomatitis and gastric bleeding, suppression of bone marrow function (thrombocytopenia, leukopenia and agranulocytosis). In case of an overdose, hematopoietic function should be monitored for at least 4 weeks, symptomatic therapy should be performed if abnormalities occur.

The specific antidote to fluorouracil is not known.

Interaction:

Calcium folinate enhances the therapeutic and toxic effects of fluorouracil.

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

At long joint application with mitomycin C the appearance of a hemolytic-uremic syndrome was observed.

Simultaneous use of anticoagulants, coumarin derivatives, such as warfarin, can increase the anticoagulant effect.

Thiazide diuretics can enhance the myelosuppressive effects of antitumor drugs.

When used in combination with levamisole, the degree of hepatotoxicity significantly increases (an increase in the activity of alkaline phosphatase is often accompanied by an increase in serum transaminases or bilirubin).

Simultaneous use of fluorouracil with drugs that suppress the enzyme DPD, responsible for the catabolism of endogenous and fluorinated pyrimidines (brivudine, sorivudine) significantly increases the toxicity of fluorouracil.

With the simultaneous reception with the drug sorivudine marked leukopenia, in some cases, led to death.

Fluorouracil should not be used after and with therapy with aminophenazone, phenylbutazone and sulfonamides.

Chlordiazepoxide, disulfiram, griseofulvin and isoniazid may enhance the activity of fluorouracil.

In connection with the suppression of natural defense mechanisms in the treatment of fluorouracil, it is possible to intensify the replication of the vaccine virus or to reduce the production of antibodies in response to vaccine administration when vaccinated with live or inactivated vaccines, so the interval between the end of the drug application and vaccination with live or inactivated vaccines is from 3 months to 1 of the year.

Special instructions:

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

When stomatitis or diarrhea occurs, the drug should be discontinued until the symptoms disappear.

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

The period of treatment is necessary to control the total number of leukocytes, 'absolute neutrophil count, platelet count, to determine the hematocrit, hemoglobin, activity "liver" transaminases and bilirubin, inspect the mouth cavity of the patient for signs of stomatitis.

Due to the toxicity of fluorouracil together with drugs that suppress the enzyme DPD, a break before taking the drug Fluorouracil for - the restoration of activity of endogenous and fluorinated pyrimidines.

Men and women of childbearing age during treatment with fluorouracil and at least 3 months after should be taken reliable methods of contraception.

During the treatment period it is necessary to refrain from driving the car and practicing potentially dangerous activities that require an increased concentration attention and speed of psychomotor reactions.

When working with the drug must comply with the rules for handling cytotoxic substances. Unused drug residues and all tools and materials used in the preparation of infusion solutions and drug administration, including gloves, must be disposed of in accordance with the approved cytotoxic waste disposal procedure.

Effect on the ability to drive transp. cf. and fur:During the treatment period it is necessary to refrain from driving the car and practicing potentially dangerous activities that require an increased concentration attention and speed of psychomotor reactions.

Form release / dosage:Solution for intravascular and intracavitary administration of 250 mg / 5 ml, 500 mg / 10 ml, 1000 mg / 20 ml (50 mg / ml).

Packaging:

For 5 ml in ampoules of light-protective glass or ampoules from tubular glass of brown color of the 1st hydrolytic class.

5 ml in the ampoule. For 10 ampoules together with the instruction for use and scarifier ampullum in a pack of cardboard. When you pack the ampoules with a colored break ring, the attachment of the ampullar scarifier is excluded.

5 ml, 10 ml, 20 ml each in brown glass bottles, sealed with rubber stoppers with aluminum caps or with caps combined of aluminum and plastic.

For 5 ml, 10 ml or 20 ml in a vial, 1 bottle or 10 bottles of 5 ml, 10 ml, 20 ml together with instructions for use in a pack of cardboard. It is allowed to wrap in a film of 10 packs of 1 bottle of 5 ml, 10 ml or 20 ml.

Storage conditions:

Store in a dark place at a temperature of 15 ° C to 25 ° C.

Do not freeze!

Note: When storing the drug at lower temperatures, precipitation may occur. In this case, the ampoule (vial) should be heated to a temperature of 60 ° C with vigorous shaking, after which the preparation must be cooled to a temperature of 35 ° C. If the precipitate dissolves and the solution becomes clear, the drug is usable.

Keep out of the reach of children.

Shelf life:

2 years.

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

Terms of leave from pharmacies:On prescription

Registration number:LP-001443

Date of registration:18.01.2012

The owner of the registration certificate:FARM STANDART, OJSC FARM STANDART, OJSC Russia

Manufacturer: & nbsp

PHARMSTANDART-BIOOLEK, PAO Ukraine

FARMSTANDART-UFAVITA, JSC Russia

Information update date: & nbsp09.11.2015

Illustrated instructions

Instructions

Fluorouracil (Fluorouracil)