Instructions for use Fluorouracil Medak solution for injection 50 mg/ml bottle 100 ml No. 1
Composition
active ingredient: fluorouracil;
1 ml of solution contains 50 mg of fluorouracil;
Excipients: sodium hydroxide, water for injections.
Dosage form
Solution for injection.
Main physicochemical properties: transparent, colorless or almost colorless liquid.
Pharmacotherapeutic group
Antineoplastic agents. Antimetabolites. Structural pyrimidine analogues.
ATX code L01B C02.
Pharmacological properties
Pharmacodynamics.
Fluorouracil is an analog of uracil, a component of ribonucleic acid. The drug is believed to function as an antimetabolite. After intracellular conversion to the active deoxynucleotide, it interferes with DNA synthesis by blocking the conversion of deoxyuridylic acid to thymidylic acid by the cellular enzyme thymidylate synthetase. Fluorouracil may also interfere with RNA synthesis.
Pharmacokinetics.
Absorption Fluorouracil is absorbed with very high variability in the gastrointestinal tract after oral administration by first-pass metabolism caused by varying levels of dihydropyrimidine dehydrogenase (DPD), the first enzyme in the catabolic transformation of fluorouracil.
Distribution After intravenous administration, fluorouracil is distributed to all body fluids and is eliminated from the blood within 3 hours. It is mainly absorbed by actively proliferating tissues and tumors after conversion to the nucleotide. Fluorouracil readily crosses the blood-brain barrier and brain tissue.
Biotransformation Dihydropyrimidine dehydrogenase is the initial enzyme in the catabolism of fluorouracil, which catabolizes more than 85% of the administered dose to dihydrofluorouracil. Dihydrofluorouracil is then converted to fluoro-β-ureidopropionate, and further to fluoro-β-alanine. Enzyme deficiency in this process can lead to severe and even life-threatening fluorouracil toxicity. In case of hepatic insufficiency, the metabolism of fluorouracil is slowed down, which may require dose adjustment.
Intracellularly, fluorouracil is converted by a number of enzymes into the active metabolites fluorodeoxyuridine monophosphate, fluorodeoxyuridine triphosphate, and fluorouridine triphosphate.
Elimination After intravenous administration, the plasma half-life of fluorouracil is approximately 10-20 minutes and depends on the dose administered. After a single intravenous administration of fluorouracil, approximately 15% of the dose is excreted unchanged in the urine within 6 hours; more than 90% of the dose is excreted from the body within the first hour. The remainder is metabolized mainly in the liver by the body's normal mechanisms for uracil.
Indication
- treatment of metastatic colorectal cancer;
- adjuvant therapy for colon and rectal cancer;
- treatment of advanced stomach cancer;
- treatment of advanced pancreatic cancer;
- treatment of advanced esophageal cancer;
- treatment of advanced or metastatic breast cancer;
- adjuvant therapy of operable primary invasive breast cancer;
- treatment of inoperable locally advanced squamous cell carcinoma of the head and neck in previously untreated patients;
- treatment of locally recurrent or metastatic squamous cell carcinoma of the head and neck.
Contraindication
Fluorouracil is contraindicated in the following cases:
- hypersensitivity to fluorouracil or to any of the excipients;
- bone marrow suppression after radiation therapy or after treatment with other anticancer agents;
- should not be used to treat benign tumors;
- severe liver dysfunction;
- severe infectious diseases (herpes zoster, chickenpox);
- a state of severe exhaustion;
- Fluorouracil is absolutely contraindicated during breastfeeding.
- complete deficiency of dihydropyrimidine dehydrogenase (DPD) (see section "Special instructions for use");
- recent or concomitant treatment with brivudine (see sections “Special warnings and precautions for use” and “Interaction with other medicinal products and other types of interactions”).
Interaction with other medicinal products and other types of interactions
Brivudin
A clinically significant interaction has been described between brivudine and fluoropyrimidines (e.g. capecitabine, fluorouracil, tegafur) resulting from inhibition of dihydropyrimidine dehydrogenase by brivudine. The interaction, which leads to increased fluoropyrimidine toxicity, is potentially fatal. For this reason, an interval of at least 4 weeks should be observed between the administration of fluorouracil and brivudine, sorivudine and their analogues. Treatment with brivudine can be started 24 hours after the last dose of fluorouracil.
The biochemical effects of various drugs on the antitumor efficacy or toxicity of fluorouracil have been noted. Known drugs such as methotrexate, metronidazole, folinic acid, interferon alpha, and allopurinol can affect the efficacy of fluorouracil.
Fluorouracil enhances the effects of other cytostatics and radiotherapy. In combination with other myelosuppressive drugs, dose adjustment is necessary.
The cardiotoxicity of anthracyclines may be increased.
Radiation therapy
With simultaneous or previous radiotherapy, a reduction in the dose of fluorouracil is required.
Folinic acid
The efficacy and toxicity of fluorouracil may be increased when used with folinic acid. Side effects may be more severe and severe diarrhea may occur. Life-threatening diarrhea has been reported when 600 mg/m² of fluorouracil (IV bolus once weekly) was administered with folinic acid.
Phenytoin
Increased plasma levels of phenytoin have been reported with concomitant use of phenytoin and fluorouracil, leading to symptoms of phenytoin intoxication.
Cimetidine, metronidazole, interferon
Cimetidine, metronidazole or interferon may increase the concentration of fluorouracil in the blood plasma and enhance toxic effects.
Thiazide diuretics, cyclophosphamide, methotrexate
In patients receiving cyclophosphamide, methotrexate, and 5-fluorouracil, the addition of thiazide diuretics resulted in a more pronounced decrease in granulocyte counts compared with patients not receiving thiazides. In patients with breast cancer, combination therapy with cyclophosphamide, methotrexate, 5-fluorouracil, and tamoxifen has been reported to increase the risk of thromboembolic events.
Warfarin Marked increases in prothrombin time and international normalized ratio (INR) have been reported in several patients stabilized on warfarin therapy after initiation of fluorouracil.
Levamisole: Hepatotoxicity (increased alkaline phosphatase, transaminases, or bilirubin) is commonly observed in patients receiving fluorouracil in combination with levamisole.
Clozapine The use of fluorouracil in combination with clozapine should be avoided due to an increased risk of agranulocytosis.
Anthracyclines
The cardiotoxicity of anthracyclines may be increased.
Tamoxifen In patients with breast cancer, combination therapy with cyclophosphamide, methotrexate, fluorouracil, and tamoxifen increases the risk of thromboembolic complications.
Vinorelbine in combination with fluorouracil may cause inflammation of the mucous membranes.
Live vaccines
Vaccination with live vaccines should be avoided in immunocompromised patients.
Cisplastin
An increased incidence of cerebral infarction has been reported in patients with oropharyngeal cancer treated with fluorouracil and cisplatin.
Application features
Fluorouracil treatment is carried out under the supervision of a qualified oncologist experienced in the use of antimetabolites, in a hospital setting and with facilities for regular monitoring of clinical, biochemical and hematological effects during and after use.
All patients should be admitted to hospital for initial therapy. The difference between therapeutic and toxic doses is small. It is unlikely that a therapeutic dose can be achieved.
effect without some toxicity, therefore, it is necessary to carefully select patients for therapy and adjust the doses. In case of severe toxicity, treatment should be discontinued
Hematotoxicity
With adequate treatment with fluorouracil, leukopenia usually develops. The minimum number of leukocytes is usually noted between the 7th and 14th day of the first course of treatment, but sometimes the minimum can be observed after 20 days. The number of leukocytes usually normalizes by the 30th day.
It is recommended to monitor platelet and leukocyte counts daily and discontinue treatment if platelet counts fall below 100,000/mm3 and leukocytes below 3,500/mm3. If leukocytes fall below 2,000/mm3, especially in the presence of granulocytopenia, it is recommended to hospitalize the patient in a hospital isolation ward and take measures to prevent the development of systemic infections.
Toxic effect on the gastrointestinal tract
Treatment should also be discontinued at the first signs of stomatitis or oral mucosal ulcers, severe diarrhea, gastrointestinal ulcers, gastrointestinal bleeding, as well as bleeding and hemorrhages of any location.
Cardiotoxicity
Cardiotoxicity, including myocardial infarction, angina pectoris, arrhythmias, myocarditis, cardiogenic shock, sudden cardiac death, stress cardiomyopathy (Takotsubo syndrome), and electrocardiographic changes (including very rare cases of QT prolongation) have been associated with fluoropyrimidine therapy. These adverse events occur more frequently in patients receiving continuous fluorouracil infusion rather than bolus injections. A history of coronary artery disease is a risk factor for cardiovascular adverse reactions. Therefore, caution should be exercised in patients who complain of chest pain during treatment and in patients with a history of cardiac disease. Cardiac function should be monitored regularly during fluorouracil therapy. Treatment should be discontinued if severe cardiotoxicity occurs.
From post-marketing experience, cases of encephalopathy (including hyperammonemic encephalopathy, leukoencephalopathy), posterior reversible encephalopathy syndrome have been reported in association with fluorouracil treatment. Signs and symptoms of encephalopathy include altered mental status, confusion, disorientation, coma or ataxia. If a patient develops any of these symptoms, treatment should be discontinued immediately and serum ammonia levels should be monitored. In the event of elevated serum ammonia levels, measures should be taken to lower serum ammonia levels. Caution should be exercised when administering fluorouracil to patients with renal and/or hepatic impairment, as they are at increased risk of hyperammonemia and hyperammonemic encephalopathy.
Hyperammonemic encephalopathy often occurs simultaneously with lactic acidosis.
Tumor lysis syndrome
Cases of tumor lysis syndrome have been reported in post-marketing experience with fluorouracil. Patients at increased risk of tumor lysis syndrome (e.g., patients with renal insufficiency, hyperuricemia, high tumor burden, rapid disease progression) should be closely monitored. Preventive measures (e.g., hydration, correction of high uric acid levels) may be appropriate.
Dihydropyrimidine dehydrogenase (DPD) deficiency
DPD activity is the rate-limiting factor in the catabolism of fluorouracil, and therefore patients with DPD deficiency are at increased risk of fluoropyrimidine-related toxicity, including, for example, stomatitis, diarrhea, mucosal inflammation, neutropenia, and neurotoxicity.
Toxicity associated with DPD deficiency usually occurs during the first cycle of treatment or after dose increases.
Complete DPD deficiency.
Complete DPD deficiency is rare (0.01-0.5% of Caucasians). Patients with complete DPD deficiency are at increased risk of life-threatening or fatal toxicity and should not receive fluorouracil Medac.
Partial deficiency of DPD.
Partial DPD deficiency occurs in 3–9% of Caucasians. Patients with partial DPD deficiency are at increased risk of severe and potentially life-threatening toxicity. To reduce this toxicity, a reduction in the starting dose should be considered. DPD deficiency should be considered as a parameter to be considered in conjunction with other routine dose reduction measures. A reduction in the starting dose may affect the efficacy of treatment. In the absence of serious toxicity, subsequent doses may be increased with careful monitoring.
Testing to determine DPD deficiency.
Phenotypic and/or genotypic testing is recommended prior to initiating treatment with fluorouracil Medac, although there is uncertainty regarding the optimal testing methods prior to initiating treatment. Appropriate clinical guidelines should be considered.
Genotypic characteristics of DPD deficiency.
Preliminary testing for rare mutations in the DPYD gene allows the identification of patients with DPD deficiency. Four DPYD variants c.1905+1G>A (also known as DPYD*2A), c.1679T>G (DPYD*13), c.2846A>T and c.1236G>A/HapB3 can cause complete absence or reduction of DPD enzymatic activity. Other rare variants may also be associated with an increased risk of severe or life-threatening toxicity.
It is known that some homozygous and compound heterozygous mutations in the DPYD gene locus (for example, combinations of four variants with at least 1 allele c.1905+1G>A or c.1679T>G) cause complete or almost complete absence of DPD enzymatic activity.
Patients with certain heterozygous DPYD variants (including c.1905+1G>A, c.1679T>G, c.2846A>T, and c.1236G>A/HapB3 variants) are at increased risk of severe toxicity when treated with fluoropyrimidines.
The frequency of the heterozygous genotype p.1905+1G>A in the DPYD gene in representatives of the Caucasian race is approximately 1%, p.2846A>T – 1.1%, p.1236G>A/HapB3 – 2.6–6.3%, p.1679T>G – 0.07–0.1%.
Data on the frequency of the four DPYD variants in races other than European are limited. Currently, four DPYD variants (c.1905+1G>A, c.1679T>G, c.2846A>T and c.1236G>A/HapB3) are considered virtually absent in people of African or Asian descent.
Phenotypic characteristics of DPD deficiency.
For phenotypic characterization of DPD deficiency, measurement of the level of the endogenous DPD substrate, uracil (U), in blood plasma is recommended.
Elevated pretreatment uracil concentrations are associated with an increased risk of uracil toxicity. Although there is uncertainty regarding the DPD thresholds that define complete or partial DPD deficiency, blood DPD levels ≥ 16 ng/mL and < 150 ng/mL should be considered indicative of partial DPD deficiency and associated with an increased risk of fluoropyrimidine toxicity. Blood uracil levels ≥ 150 ng/mL should be considered indicative of complete DPD deficiency and associated with life-threatening or fatal fluoropyrimidine toxicity.
Therapeutic drug monitoring of fluorouracil.
Therapeutic drug monitoring of fluorouracil may improve clinical outcomes in patients receiving regular fluorouracil infusions, reduce toxicity, and increase efficacy. The AUC is expected to be 20 to 30 mg×h/L.
Fluorouracil Medac should not be used with brivudine. Fatalities have been reported due to this drug interaction. For this reason, an interval of at least 4 weeks should be observed between the administration of fluorouracil and brivudine. Treatment with brivudine can be started 24 hours after the last dose of fluorouracil. When brivudine is used in patients treated with fluorouracil, effective measures should be taken to reduce the toxicity of fluorouracil. Immediate hospitalization is recommended. All measures should be aimed at preventing systemic infections and dehydration.
Phenytoin
Patients taking phenytoin concomitantly with fluorouracil should be monitored regularly, as there is a possibility of increased plasma concentrations of phenytoin. Patients are advised not to stay in the sun for long periods due to the risk of photosensitization. Fluorouracil Medak should be used with caution in patients who have received high doses of radiotherapy to the pelvis.
Impaired kidney or liver function
Fluorouracil should be used with caution in patients with reduced renal or hepatic function or jaundice.
Photosensitivity
Patients are not recommended to stay in the sun for long periods of time due to the risk of photosensitization.
Radiation therapy to the pelvic area.
The drug should be used with caution in patients who have received high doses of radiation therapy to the pelvis.
Vaccination with live vaccines
Vaccination with live vaccines should be avoided in patients receiving fluorouracil due to the possibility of severe or fatal infections. Contact with individuals who have recently been vaccinated with polio vaccine should be avoided.
Combination of fluorouracil and folinic acid
The toxicity profile of fluorouracil may be increased or altered by concomitant use of folinic acid. The most common manifestations are leukopenia, mucositis, stomatitis and/or diarrhoea, which may be dose-limiting. When fluorouracil and folinic acid are used in combination, the dose of fluorouracil should be reduced more if toxicity develops than when fluorouracil is used alone. The toxic effects observed in patients receiving this combination are qualitatively similar to those observed in patients receiving fluorouracil monotherapy.
Gastrointestinal toxicity is more common and may be more severe or even life-threatening (especially stomatitis and diarrhea). In severe cases, fluorouracil and folinic acid should be discontinued and supportive intravenous therapy should be initiated. Patients should be instructed to notify their physician immediately if stomatitis (mild to moderate ulcers) and/or diarrhea (watery stools) occur.
Sodium
Fluorouracil Medak contains the following amount of sodium depending on the packaging:
5 ml of solution contains 1.79 mmol (41.19 mg)/dose sodium, contains less than 1 mmol (23 mg)/dose sodium, i.e. essentially sodium-free.
10 ml of solution contains 3.58 mmol (82.37 mg)/dose sodium. Caution should be exercised when administering to patients on a controlled sodium diet.
20 ml of solution contains 7.16 mmol (164.75 mg) of sodium. Caution should be exercised when administering to patients on a controlled sodium diet.
100 ml of solution contains 35.82 mmol (823.75 mg) of sodium. Caution should be exercised when administering to patients on a controlled sodium diet.
Use during pregnancy or breastfeeding
Pregnancy There are no adequate and well-controlled studies in pregnant women; however, fetal malformations and miscarriages have been reported in women exposed to fluorouracil during pregnancy. Women of childbearing potential should be advised to avoid pregnancy and to use effective contraception during treatment with fluorouracil and for at least 6 months after treatment. If fluorouracil is used during pregnancy or if the patient becomes pregnant while taking the drug, she should be informed of the potential hazard to the fetus and the need for genetic counseling.
Fluorouracil should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Breast-feeding
It is not known whether fluorouracil passes into breast milk, therefore, if women use fluorouracil, breastfeeding should be discontinued.
Fertility
Men receiving fluorouracil are advised to use reliable contraception during therapy and for 3 months after its discontinuation. The question of sperm cryopreservation should be decided before starting treatment because of the possibility of irreversible infertility due to fluorouracil therapy.
Ability to influence reaction speed when driving vehicles or other mechanisms
Studies on the effects on the ability to drive and use machines have not been conducted. Fluorouracil may cause side effects such as nausea and vomiting. It may also have adverse effects on the nervous system and vision, which may interfere with driving or operating heavy machinery.
Method of administration and doses
Fluorouracil Medak should only be used under the supervision of a qualified physician with extensive experience in the field of anticancer chemotherapy. The patient's condition should be closely and frequently monitored during treatment. The risks and benefits for each individual patient should be weighed before treatment.
Adults
The selection of the appropriate dose and treatment regimen depends on the patient's condition, the type of cancer to be treated, and whether fluorouracil is used as monotherapy or in combination with other therapies. The number of cycles to be used should be determined by the physician based on local treatment protocols and guidelines, taking into account the effectiveness of the treatment and tolerability of the drug.
Treatment must be started in a hospital setting.
A dose reduction is recommended for patients in the following cases:
- cachexia;
- major surgery in the previous 30 days;
- deterioration of bone marrow function;
- the presence of liver or kidney dysfunction.
In adult and elderly patients receiving fluorouracil, hematological (platelet, leukocyte and granulocyte counts), gastrointestinal (stomatitis, diarrhea, gastrointestinal bleeding), and neurological toxicity should be monitored before each dose and, if necessary, the dose of fluorouracil should be reduced or treatment discontinued.
The need for dose adjustment or discontinuation of the drug depends on the occurrence of adverse reactions. In case of hematological toxicity, such as a decrease in the number of leukocytes (≤ 3500/mm³) and/or platelets (≤ 100,000/mm³), treatment may be discontinued. The question of resuming treatment should be decided by the doctor depending on the clinical situation.
Colorectal cancer
Fluorouracil is used to treat colon and rectal cancer in a number of regimens. Fluorouracil is used primarily in combination with folinic acid. Often, regimens combine fluorouracil and folinic acid with other chemotherapy drugs, such as irinotecan, oxaliplatin, or both.
Fluorouracil is usually administered in a dose range of 200–2600 mg/m2 body surface area. The dose also varies depending on the route of administration, either intravenous bolus or continuous intravenous infusion.
The dosage regimen also depends on the chemotherapy regimen. The dose of fluorouracil can be administered once a week, once every two weeks, or once a month. The number of cycles depends on the treatment regimen used, as well as on clinical judgment, which is based on the effectiveness of the treatment and tolerability.
Stomach and gastroesophageal junction cancer
Intraoperative chemotherapy with the following regimen is recommended for patients with potentially curable gastric cancer: epirubicin, cisplatin, fluorouracil. The recommended dose of fluorouracil in this regimen is 200 mg/m² body surface area per day as a continuous intravenous infusion for 3 weeks. 6 cycles are recommended, but this depends on the effectiveness of the treatment and the patient's tolerability of the drug.
For patients with incurable locally advanced or metastatic cancer, fluorouracil is usually used in combination with cisplatin and with or without epirubicin or docetaxel.
Esophageal cancer
Fluorouracil is usually used in combination with cisplatin, or with cisplatin and epirubicin, or with epirubicin and oxaliplatin. The dose of the drug varies in the range of 200–1000 mg/m2 of body surface area per day and is administered as a continuous infusion; the course of treatment is several days and is repeated cyclically depending on the treatment regimen.
Intraoperative chemotherapy with the following regimen is recommended for the treatment of lower esophageal cancer: epirubicin, cisplatin, fluorouracil. The recommended dose of fluorouracil with this regimen is 200 mg/m² body surface area per day as a continuous intravenous infusion for 3 weeks, repeated cyclically.
Pancreatic cancer
Fluorouracil is mainly used in combination with folinic acid or gemcitabine. The dose varies in the range of 200-500 mg/m2 body surface area per day and is administered, depending on the treatment regimen, as an intravenous bolus injection or intravenous infusion, which is repeated cyclically.
Breast cancer
Fluorouracil is often used in chemotherapy in combination with cyclophosphamide and methotrexate, or with epirubicin and cyclophosphamide, or with methotrexate and leucovorin (MFL). The recommended dose is 500–600 mg/m² body surface area and is administered as an intravenous bolus, repeated every 3–4 weeks if necessary.
The duration of adjuvant therapy for primary invasive breast cancer is 6 cycles.
Head and neck cancer
Fluorouracil is used mainly in combination with cisplatin or carboplatin. The dose varies in the range of 600-1200 mg/m2 of body surface area per day and is administered as a continuous intravenous infusion over several days. It is repeated cyclically depending on the treatment regimen.
Kidney or liver failure
The drug Fluorouracil Medak is used with caution in patients with renal or hepatic insufficiency; if necessary, the dose is reduced.
Elderly patients
No dose adjustment is required.
Fluorouracil is usually administered intravenously as a bolus injection, an infusion over several hours, or a continuous infusion over several days to several weeks. It is very important to strictly adhere to the duration of the injection/infusion and the chosen treatment regimen.
Elderly patients
No dose adjustment is required.
Children.
There are no recommendations for the treatment of children, so the drug should not be used in pediatric practice.
Overdose
Symptoms Symptoms and signs of fluorouracil overdose are qualitatively similar to adverse reactions, but are usually more pronounced. In particular, the following adverse reactions may occur: nausea, vomiting, diarrhea, gastrointestinal ulcers, mucositis, bleeding, bone marrow depression (including thrombocytopenia, leukopenia, and agranulocytosis).
Treatment Treatment consists of discontinuation of the drug and supportive measures. There is no specific antidote. Patients should have blood tests for at least 4 weeks after overdose. If pathological changes occur, appropriate therapy should be used.
Side effects
The most common side effects are gastrointestinal disorders: diarrhea, nausea and mycoses. Leukopenia is also very common. The undesirable effects are described below.
Frequency estimate: very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1000, < 1/100), rare (≥ 1/10,000, < 1/1000), very rare (< 1/10,000), frequency unknown (cannot be estimated from the available data).
Infections and infestations: very common – infections; uncommon – sepsis.
Blood and lymphatic system: very common - myelosuppression (onset: 7–10 days, resolution: 9–14 days, recovery: 21–28 days), neutropenia, leukopenia, granulocytopenia, thrombocytopenia, agranulocytosis, anemia, pancytopenia; common - fibrillary neutropenia.
Immune system: very common - immunosuppression; rare - generalized allergic reactions, anaphylactic reactions, anaphylactic shock.
Endocrine disorders: rarely - increased total thyroxine (T4), increased total triiodothyronine (T3).
Metabolism and nutrition disorders: very common – hyperuricemia, uncommon – dehydration, frequency unknown – lactic acidosis, tumor lysis syndrome.
Mental disorders: rare – euphoria, uncommon – confusion, very rare – disorientation.
Nervous system disorders: uncommon - nystagmus, headache, dizziness, Parkinson's symptoms, pyramidal signs, drowsiness, optic neuritis; rare - extrapyramidal disorders, cerebral disorders, cortical disorders, peripheral neuropathy; very rare - leukoencephalopathies, including ataxia, acute cerebellar disorders, dysarthria, confusion, disorientation, myasthenia gravis, aphasia, convulsions or coma in patients; frequency unknown - hyperammonemic encephalopathy, posterior reversible encephalopathy syndrome.
Organs of vision: common – conjunctivitis; uncommon – increased lacrimation, blurred vision, eye movement disorder, diplopia, decreased visual acuity, photophobia, blepharitis, ectropion, dacryostenosis.
Cardiac disorders: very common - ischemic ECG changes; common - angina-like chest pain; uncommon - arrhythmia, myocardial infarction, myocarditis, heart failure, dilated cardiomyopathy, acute heart failure; very rare - cardiac arrest, sudden cardiac death; frequency unknown - pericarditis, stress cardiomyopathy (Takotsubo syndrome).
Vascular disorders: uncommon – hypotension; rare – vasculitis, cerebral ischemia, ventricular ischemia, peripheral ischemia, Raynaud's phenomenon, vasculitis, thrombophlebitis, thromboembolism.
Respiratory system: very common – bronchospasm, epistaxis; uncommon – dyspnea.
Gastrointestinal disorders: very common – gastrointestinal side effects that may be life-threatening: inflammation of the mucous membrane (stomatitis, esophagitis, pharyngitis, proctitis), anorexia, watery diarrhea, nausea, vomiting; uncommon – gastric ulcer, gastrointestinal bleeding; frequency unknown – pneumatosis intestinalis.
Liver disorders: uncommon – hepatocellular disorders; very rare – liver necrosis (fatal cases), biliary sclerosis, cholecystitis.
Skin and subcutaneous tissue disorders: very common – alopecia, palmar-plantar erythrodysesthesia syndrome was observed with prolonged and continuous infusion of high doses of the drug. The syndrome began with dysesthesia of the palms and soles, which progressed to pain and tenderness. In parallel, edema and erythema of the hands and feet developed.
Uncommon: dermatitis, skin changes (dry skin, cracks, erythema, pruritic maculopapular rash, hyperpigmentation, hypopigmentation), exanthema, urticaria, striated hyperpigmentation or depigmentation near veins (e.g. diffuse superficial blue pigmentation, hyperpigmentation, nail dystrophy, nail bed pain and thickening, paronychia) and onycholysis, rebound phenomenon. Frequency unknown: cutaneous lupus erythematosus.
Renal and urinary disorders: uncommon – renal failure.
General disorders and administration site conditions: very common – slow wound healing, fever, general weakness, fatigue, asthenia.
Reports of adverse drug reactions.
Reporting adverse reactions after the registration of a medicinal product is important. This allows monitoring of the benefit/risk ratio when using this medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all cases of suspected adverse reactions and lack of efficacy of the medicinal product via the Automated Information System for Pharmacovigilance at the link: https://aisf.dec.gov.ua.
Expiration date
2 years.
Storage conditions
Store in original packaging at a temperature not exceeding 25 ° C. Keep out of the reach of children.
Do not freeze.
Incompatibility.
Incompatible with folinic acid, calcium folinate, carboplatin, cisplatin, cytarabine, diazepam, doxorubicin, droperidol, filgrastim, gallium nitrate, methotrexate, metoclopramide, morphine, ondansetron, parenteral nutrition products, vinorelbine, other anthracyclines.
The prepared solutions are alkaline, so it is not recommended to mix them with medications that have acidic properties.
Due to the lack of compatibility studies, this medicinal product should not be mixed with other medicinal products.
Special precautions for disposal.
The pH of the fluorouracil solution is 8.9. The drug has maximum stability at pH 8.6-9.4. Fluorouracil is an irritant, so contact with the skin and mucous membranes should be avoided.
Packaging
5 ml, 10 ml, 20 ml, 100 ml of the drug in a bottle. 1 bottle is placed in a cardboard box.
Vacation category
According to the recipe.
Producer
Medak Gezelshaft fur kliniche Specialpreparate mbH.
Location.
Theaterstrasse 6, 22880 Wedel, Germany.
