Fluorac

Fluorac Uses, Dosage, Side Effects, Food Interaction and all others data.

5-Fluorouracil works by inhibiting the enzyme thymidylate kinase which results in reduced formation of thymidine and thus DNA. The active metabolite FdUMP appears to form a stable complex with the folate cofactor N-5, 10-methylene tetrahydrofolate which inactivates thymidylate kinase. 5-Fluril as FdUMP is also incorporated into RNA which results in fluorination of RNA. The effect of fluorouracil on living cells is limited mainly to those in the proliferative phase but while cells in the G2 and S phase are most affected there may be effects at any stage of the cell cycle.

Fluorouracil is an antineoplastic anti-metabolite. Anti-metabolites masquerade as purine or pyrimidine - which become the building blocks of DNA. They prevent these substances from becoming incorporated into DNA during the "S" phase (of the cell cycle), stopping normal development and division. Fluorouracil blocks an enzyme which converts the cytosine nucleotide into the deoxy derivative. In addition, DNA synthesis is further inhibited because Fluorouracil blocks the incorporation of the thymidine nucleotide into the DNA strand.

Fluorac
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Fluorac
Generic	Fluorouracil + diclofenac sodium
Type	Cream
Therapeutic Class
Manufacturer
Available Country	United States
Last Updated:	September 19, 2023 at 7:00 am

Uses

Rheumatology: Inflammatory and degenerative forms of rheumatism, chronic involutive, polyarthritis, ankylosing spondylarthritis, osteoarthritis, spondylarthroses, acute gout, peri-articular rheumatic disorders.Surgery and Traumatology: Sprain, bruises, dislocations ... Read more

5-Fluorouracil is used alone or in combination for carcinoma of the colon or rectum, carcinoma of the stomach and exocrine pancreas, carcinoma of the liver, carcinoma of the breast (an especially aggressive form of breast cancer), carcinoma of the bladder, carcinoma of the lung, epithelial ovarian carcinoma andcervical carcinoma.

Fluorac is also used to associated treatment for these conditions: Actinic Keratosis (AK), Breast Cancer, Malignant Neoplasm of Colon, Malignant Neoplasm of Pancreas, Malignant Neoplasm of Stomach, Rectal Carcinoma, Superficial Basal Cell Carcinoma, Warts, Hyperkeratotic actinic keratosis

How Fluorac works

The precise mechanism of action has not been fully determined, but the main mechanism of fluorouracil is thought to be the binding of the deoxyribonucleotide of the drug (FdUMP) and the folate cofactor, N5–10-methylenetetrahydrofolate, to thymidylate synthase (TS) to form a covalently bound ternary complex. This results in the inhibition of the formation of thymidylate from uracil, which leads to the inhibition of DNA and RNA synthesis and cell death. Fluorouracil can also be incorporated into RNA in place of uridine triphosphate (UTP), producing a fraudulent RNA and interfering with RNA processing and protein synthesis.

Dosage

Fluorac dosage

Diclofenac FC Tablet: Adults: 75-150 mg daily in 2 to 3 divided doses, preferably after food. Dose should be reduced in long term use. Diclofenac SR Tablet: Adult: 1 tablet daily, taken whole with liquid, preferably at meal times. If necessary, the daily dose can be increased to 150 mg by supplementation with conventional tablets. Children: 1-3 mg of diclofenac/kg body wt. daily in divided doses. Elderly patients: In elderly or debilitated patients, the lowest effective dosage is recommended, although the pharmacokinetics of diclofenac sodium is not impaired to any clinically relevant extent in elderly patients. Diclofenac Dispersible Tablet: Adults: The recommended daily dosage is 2-3 tablets and the maximum daily dose is 150 mg. In milder cases, 2 tablets of Diclofenac DT per day are sufficient. Diclofenac DT should preferably be taken before meals. Children: Diclofenac is not recommended in children for other indications except juvenile rheumatoid arthritis where the recommended dose is 1-3 mg/kg body weight. Diclofenac DT is to be dropped into a half-glass of water and the liquid is to be stirred to aid dispersion before swallowing. There is no information on the use of Diclofenac DT for more than 03 months. Diclofenac TR Capsule: One capsule daily. Diclofenac TR should be taken preferably after mealtimes.Diclofenac Suppository: For adults: 50 mg suppository 2-3 times daily. Maximum daily dose is 150 mg.Diclofenac injection: For adults the usual dose is 1 ampoule daily. In serious cases this dose may be increased up to 2 ampoules daily.Diclofenac Gel: For external use only. Depending on the size of area to be treated, 2-4 g of Diclofenac gel should be applied to the skin 3-4 times daily. To the affected area gel should be rubbed in lightly. This gel may also be given in addition to further treatment with other dosage forms of Diclofenac.

Various protocols exist-

500 mg/m2 IV on Days 1-5, OR
450-600 mg/m2 IV weekly, OR
200-400 mg/m2 IV continuous infusion qD
Not to exceed 800 mg/day

The commonest schedules being 500 mg/m2 daily for 5 days repeated at 4-weekly intervals.

Intravenous 5-FU can be delivered by rapid intravenous bolus injection or slow infusion. The vial contents can rapidly be injected directly into a peripheral vein. Slow intravenous infusion requires the drug to be diluted in 500 mL of dextrose 5% solution, then infused over 2-3 hours on 5 successive days.

Side Effects

Diclofenac Sodium is generally well tolerated. Adverse effects are mild, rare and transient. At the starting of the treatment, however, patients may be sometimes complaining of epigastric pain, eructation, nausea and diarrhea or dizziness or headache. These effects are usually mild in nature. Peripheral edema and skin reactions, such as rash and eczema have also been encountered. Diclofenac Sodium Gel may cause local irritation and reddening of the skin and skin rash.

Mild to moderate cardiac effects, hepatic effects, hematological effects, neurological effects, allergic reaction, decreased bone marrow function, hand-foot syndrome, severe vomiting, diarrhoea, frequent bowel movements or watery stools, sores in the mouth or throat may occur.

Toxicity

LD₅₀=230mg/kg (orally in mice)

Precaution

In rare instances where peptic ulceration or gastrointestinal bleeding occurs in patients under treatment with Diclofenac. In patients with advanced age should be kept under close observation. Diclofenac Sodium Gel should not be allowed to come in contact with the eyes or mucus membranes, after application the hands should be washed properly and not to be taken by mouth.

Dose should be reduced in patients with compromised liver function. For intra-arterial infusion, 5000 U of L.M. heparin should be added to 1 L of 5% dextrose in water together with the daily dose of fluorouracil. Ulcer-like pain or other significant gastrointestinal symptoms are indications to discontinue intra-arterial therapy, as hemorrhage or perforation may occur. Precipitation may occur when leucovorin and fluorouracil are mixed in the same bag.

Interaction

Diclofenac Sodium may have the following drug interactions:Lithium and digoxin: Diclofenac may increase plasma concentrations of lithium and digoxin.Anticoagulants: There are isolated reports of an increased risk of haemorrhage with the combined use of diclofenac and anticoagulant therapy, although clinical investigations do not appear to indicate any influence on anticoagulant effect.Antidiabetic agents: Clinical studies have shown that diclofenac can be given together with oral antidiabetic agents without influencing their clinical effect.Cyclosporin: Cases of nephrotoxicity have been reported in patients receiving cyclosporin and diclofenac concomitantly.Methotrexate: Cases of serious toxicity have been reported when methotrexate and NSAIDs are given within 24 hours of each other.Quinolone antimicrobials: Convulsions may occur due to an interaction between quinolones and NSAIDs. Therefore, caution should be exercised when considering concomitant therapy of NSAID and quinolones.Other NSAIDs and steroids: Co-administration of diclofenac with other systemic NSAIDs and steroids may increase the frequency of unwanted effects. With aspirin, the plasma levels of each is lowered, although no clinical significance is known.

Pre-treatment with cimetidine for 4 weeks lead to increased plasma concentrations of fluorouracil following intravenous and oral administration. The effect was probably due to a combination of hepatic enzyme inhibition and reduced hepatic blood flow.

Its use should be avoided in patients receiving drugs known to modulate dihydropyrimidine dehydrogenase (such as the antiviral drug sorivudine). It may also increase the INR and prothrombin times in patients on warfarin. Fluoruracil's efficacy is decreased when used alongside allopurinol which can be used to decrease fluoruracil induced stomatitis through use of allopurinol mouthwash.

Elimination Route

28-100%

Half Life

10-20 minutes

Elimination Route

Seven percent to 20% of the parent drug is excreted unchanged in the urine in 6 hours; of this over 90% is excreted in the first hour. The remaining percentage of the administered dose is metabolized, primarily in the liver.

Pregnancy & Breastfeeding use

During pregnancy, Diclofenac should be employed only for compelling reasons. The lowest effective dose should be used. These types of drugs are not recommended during the first trimester of pregnancy. In view of insufficient clinical data, Diclofenac Sodium Gel is not recommended during pregnancy. A very insignificant quantity of Diclofenac may be detected in breast milk but no undesirable effects on the infant to be expected.

Pregnancy category D. There are no data on the excretion of fluorouracil into human milk. Because fluorouracil inhibits DNA, RNA and protein synthesis, mothers should not nurse while receiving this drug.

Contraindication

Contraindicated to the patients hypersensitive to any ingredient of the products. Peptic ulcer, hypersensitivity to Diclofenac like other non-steroid anti-inflammatory agents, Diclofenac is also contra-indicated in asthmatic patient in whom attack with asthma, urticaria or acute rhinitis are precipitated by acetylsalicylic acid or by other drugs with prostaglandin synthetase inhibitor. This Gel should not be used under occlusive airtight dressings.

It is contraindicated in patients that are severely debilitated or in patients with bone marrow suppression due to either radiotherapy or chemotherapy. It is likewise contraindicated in pregnant or breastfeeding women. It should also be avoided in patients that do not have malignant illnesses.

Acute Overdose

There is very little difference between the minimum effective dose and maximum tolerated dose of 5-FU, and the drug exhibits marked individual pharmacokinetic variability. Therefore, an identical dose of 5-FU may result in a therapeutic response with acceptable toxicity in some patients and unacceptable and possibly life-threatening toxicity in others. Both overdosing and underdosing are of concern with 5-FU, although several studies have shown that the majority of colorectal cancer patients treated with 5-FU are underdosed based on today's dosing standard, body surface area (BSA). The limitations of BSA-based dosing prevent oncologists from being able to accurately titer the dosage of 5-FU for the majority of individual patients, which results in sub-optimal treatment efficacy or excessive toxicity.

Numerous studies have found significant relationships between concentrations of 5-FU in blood plasma and both desirable or undesirable effects on patients. Studies have also shown that dosing based on the concentration of 5-FU in plasma can greatly increase desirable outcomes while minimizing negative side effects of 5-FU therapy. One such test that has been shown to successfully monitor 5-FU plasma levels and which "may contribute to improved efficacy and safety of commonly used 5-FU-based chemotherapies" is the My 5-FU test.