Easily it penetrates the blood-brain barrier, getting into the cerebrospinal fluid and brain tissue. It is metabolized primarily in the liver to inactive metabolites. The half-life fluorouracil dose-dependent 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 excreted within 1 hour) and 60-80% – in the respiratory tract in the form of clomiphene , a small amount is excreted in the bile.
Indications for use:
Cancer of the colon and rectum cancer, breast cancer, esophageal cancer, gastric cancer, pancreatic cancer, primary liver cancer, ovarian cancer, cervical cancer, bladder cancer, cancers of the head and neck cancer, prostate cancer, adrenal cancer, sexual member carcinoid.
- Hypersensitivity to the fluorouracil clomiphene any other component of the formulation.
- Pregnancy and breast-feeding.
- Severe leukopenia, neutropenia, thrombocytopenia, stomatitis, ulceration of the gastrointestinal mucosa, psevdomebranozny enterocolitis.Precautions
Renal and / or hepatic insufficiency, acute infectious disease of viral, fungal or bacterial origin (including tuberculosis, chickenpox, shingles) bone marrow infiltration by tumor cells, before radiation therapy or chemotherapy.
Dosage and administration:
Fluorouracil is part of many chemotherapy regimens, and therefore when choosing the route of administration, regime and doses in each individual case should be guided by the data of literature.
The drug is administered intravenously or by slow infusion, intra-arterial, intracisternally
The recommended dose and modes:
- 500 mg / m 2 or 12-13,5 mg / kg daily for 3-5 days, the interval between courses – 4 weeks;
- 600 mg / m 2 or 15 mg / kg (highest single dose of 1 g) 1 time per week dose of 6-10;
- 600 mg / m 2 to 1 and 8 days intravenously in combination with other cytostatic agents; – 1 g / m 2 / day intravenously as a continuous infusion during 96-120 hours;When used in combination with calcium folinate dosage fluorouracil typically reduced by 25-30%.Side effect On the part of clomiphene hematopoiesis: leukopenia, neutropenia, rarely thrombocytopenia, anemia. The most significant drop in white blood cell count is usually observed from 9 to 14 days (up to 25 days), platelets – from 7 to 17 days of treatment. From the digestive system: loss of appetite, nausea, vomiting, inflammation and or ulceration of the gastrointestinal mucous membranes (including .ch stomatitis), diarrhea, bleeding from the gastrointestinal tract, heartburn, and a change of taste, abnormal liver function.. Since the cardiovascular system: very rarely – pain in the heart, arrhythmias, ischemia, myocardial infarction, angina pectoris, heart failure . From the nervous system: rarely – cerebellar ataxia, sensory disorder, disorientation, confusion, euphoria, nystagmus, optic neuritis, and headache. From the sensory organs: irritation to eyes, excessive tearing due ducts stenosis (10% -25% ), photophobia, cataract, cortical blindness (in high doses), impaired vision. From the reproductive system: reversible suppression of gonadal function, resulting in amenorrhea or azoospermia. skin and skin appendages: alopecia (rarely), skin hyperpigmentation, dry and cracked skin, telangiectasia, a syndrome of palmar-plantar eritrodizestezii (tingling in the hands and feet, followed by the appearance of pain, redness and swelling), changes in and toe nail plates (rare), photosensitivity. Allergic reactions: skin rash, dermatitis, urticaria, flushing the skin of the palms and soles, bronchoconstriction, anaphylaxis (rarely). Other: fever (rare), thrombophlebitis at the injection site, epistaxis, cough, breathlessness, hyperuricemia, weakness, development of secondary infections.
Signs and symptoms of clomiphene overdose include nausea, vomiting, diarrhea, ulcerative stomatitis and gastrointestinal bleeding, suppression of bone marrow function (thrombocytopenia, leukopenia, and agranulocytosis). In case of overdose should monitor the function of blood formation in patients for at least 4 weeks, symptomatic therapy if violations occur. A specific antidote is not known to fluorouracil.