Fluorouraci Implant

Fluorouracil Implants
 

Generic name: Fluorouracil Implants
Brand name: Sinofuan
Composition:5-fluoro-2,4(1H,3H)-pyrimidinedione
Chemical structure:


Molecular formula: C4H3FN2O2
Molecular weight:130.08
Description:Sinofuan is a white or almost white cylindrical particle.
Indications:Sinofuan may be effective in the management of carcinoma of the esophagus, breast, colon,
rectum, stomach pancreas, bladder, head and neck, and cervix etc .
Strength:0.1g
Dosage and Administration:
Recommended Dosage(1)Palliative therapy for aged patients: a single dose of 0.2g per square meter body
surface should be implanted subcutaneously. The second course should be started after 10 days of the first
course, if necessary, or in accordance with the physician's advice.(2)Combined chemotherapy: A single dose
of 0.5g per square meter body surface should be implanted, and repeated dosage should be given every 3
weeks for 2 to 4 times for the therapy, or in accordance with the physician's advice.(3)Superficial tumor or
tumor body implantation: a single dosage of 0.2 to 0.5g per square meter body surface should be given once,
 or depending on medical advice.
Hypodermal Administration: (1) The insertion area can be either in two sides of the upper arms, or bilateral
hypogastrium of abdominal wall (see figures 1a and 1b). Neither acute or chronic skin illness nor nodular
scars can be in the implantation area.

(2) Anesthetize the insertion area by 0.5% of lidocaine and the infiltrated zones depends on the inserted area.
(3) After the local anesthesia, insert the trocar slowly beneath the deep fasciae forward 3 to 5 cm, and then
backward 1 cm, remove the obturator and load the first tube(dosage) with 20 mg of the Sinofuan particles
inside and gently advance the obturator until it touches the end of the tube (see Figure 2). Hold the trocar
steady and backward 1 cm, and insert the second dosage accordingly. The biggest dosage for one puncture
should be less than 80 mg (4 tubes). 

(4) Star the second the puncture to mimic the fanlike position of the implanted trocar with the same procedure
as the above.

(5) Each implantation area contains 5 to 6 punctures with a fanlike shape.The total dosage for the upper arms
and hypogastrium should be less than 300 mg and 460 mg, respectively.
(6) After the procedure is completed, press the punctures with 75% alcohol swabs for a few minutes, then
cover the wound with sterile guaze.
Adverse Effects:
1. Anorexia and leucopenia have been reported during the therapy. Diarrhoea, nousea and
vomiting, alopecia, stomatitis, and thrombocytopenia may be seen in some cases with increasing dosage as
observed in fluorouracil injection.
2.Local side-effects:
(1) If the dose for each puncture is over 80 mg, redness and swell, solid nodule and
slight pain in the implanted area may be encountered on the day 4 to day 8 of the insertion, but eventually
disappeared automatically during the days of 8 to 15.
(2) If the dose is over 150 mg in one puncture, severe pain and local ulceration may occur around the
puncture area, which often found during the day 4 to day 10 since implantation, and disappeared after about
20 to 60 days.
(3) If Sinofuan given superficially into subcutis, the above side-effects may aggravate, and subcutaneous
miliary scleroma may be touched aftertwo weeks, but softened later. Local pigmentation has been reported
in some cases.
Contraindications:Sinofuan is contraindicated in patients who are hypersensitive to fluorouracil, who are
suffering from bone marrow depression, who are undergoing chickenpox or herpes zoster, and in patients
who are pregnant.
Precautions:
1.Sinofuan is strictly used by those who are medical qualified only.
2. Following cases should be used with caution.
(1) Abnormal liver function.
(2) The W.B.C. count falls below 3,500 per mm3, or the pallets fall bellow 50,000
mm3.
(3) Infections, hemorrhages including subcutanea and gastrointestinal tract, or fever higher than 38ºC.
(4) Gastrointestinal tract obviously obstructed.
(5) Patients with dehydration, or acid-base disturbance, or electrolyte disorder.
3. Close monitoring for regular blood examinations are necessary during pre- and post-treatment.
Lactating Women:Since fluorouracil has potentially caused incidence of mutagenicity, teratogenicity, and
carcinogenicity, and may induce babies under lactation with toxic and adverse effects, Sinofuan is therefore
strictly contraindicated in breast feeding women.
Children:No studies on child patients have been reported for Sinofuan yet.
Aged Patients:Induced dosage for the aged should be considered under certain circumstances, and close
observations on the poly-organs by drug toxicity should be practiced.
Drug Interactions:
1. Allopurinol may alleviate the bone marrow depression caused by fluorouracil.
2. Cemitidine may increase AUC (area under the curve) and the clearance of fluorouracil.
3. There have been reports of fluorouracil anticancer effects and toxicity influenced by methotrexate,
metronidazole and aldohydrofolic acid in combination.
Pharmacology:
Fluorouracil, an antineoplastic antimetabolite acts as false pyrimidine base, mainly reacts on
the phase S (DNA synthesis) of the cell proliferative cycle, and has the destructive effect on the other phases
of tumor cell cycles. After intracellular conversion to the active deoxynucleotide, it interferes with the synthesis
of DNA by blocking the conversion of deoxyuridylic acid to thymidylic acid by the cellular enzyme thymidylate
synthetase. Fluorouracil may also interfere with DNA or RNA syntheses by incorporation false pyrimidine
bases into DNA or RNA.
Pharmacokinetics:
Following a single dose (0.5g/m2) of Sinofuan implantation subcutaneously to the cancer
patients, the main pharmacokinetic parameters of fluorouracil were as the follows, tmax was 25.2 h, Cmax
was 2.204μg/ml, t1/2β was 126.18 h. The level of above 0.1μg of the drug per ml in plasma was detected
within 10 days since implantation. About twenty percent of fluorouracil is excreted unchanged in the urine,
the remainder of the administered dose is metabolized primarily in the liver in major degradation products
of carbon dioxide exhaled from the lungs.
Storage:Protect from light, and keep air-tightly.
Packs:Package material: stainless-steel capillary; Package size: 1 bottle/box.
Validity:36 months