Fluorouracil: Medical Uses, Administration, Contraindications, Adverse Effects, Interactions and Pharmacology

Sold under the brand name Adrucil, it is a drug used to treat cancer.

It is a standard chemotherapeutic for treating different malignant tumors, including gastrointestinal tract carcinomas, breast, and skin.

The rate-limiting enzyme in the catabolic pathway is dihydropyrimidine dehydrogenase (DPD), and studies have shown that decreased dihydropyrimidine dehydrogenase activity leads to less drug clearance and increased toxicity.

Injection into a vein is used for colon cancer, esophageal cancer, stomach cancer, pancreatic cancer, breast cancer, and cervical cancer. It is used for actinic keratosis and basal cell carcinoma as a cream.

When used by injection, most people develop side effects. Common side effects include inflammation of the mouth, loss of appetite, low blood cell count, hair loss, and skin inflammation.

When used as a cream, it can irritate the application site. Using any of the forms in pregnancy can harm the baby. Fluorouracil is in the antimetabolite and pyrimidine analog drug families.

It is not entirely clear, but it is believed to involve blocking the action of thymidylate synthase and thus stopping DNA production.


Fluorouracil was patented in 1956 and entered medical use in 1962. On the World Health Organization’s Essential Medicines List, it is the most effective and safest medicine needed in a health system.

The wholesale cost in the developing world is approximately $ 1.18 to $ 3.40 per 500 mg vial. In the UK, this amount costs the National Health Service around £ 6.40. In the United States, it costs about $ 18.71.

Medical uses

Fluorouracil has been administered systemically for anal, breast, colorectal, esophageal, stomach, pancreas, and skin cancers (especially head and neck cancers).

Also administered topically (on the skin), topical Fluorouracil is used to treat actinic keratosis and superficial basal and squamous cell skin cancers. The medicine destroys skin cells damaged by the sun.

But it can also damage normal skin it comes in contact with or causes skin irritation, and it has also been used for Bowen’s disease and as eye drops for treating squamous neoplasia of the ocular surface.

Other uses include ocular injections into a previously created trabeculectomy bleb to inhibit healing and cause tissue scarring, thus allowing adequate aqueous humor flow to reduce intraocular pressure.

How does it work

Fluorouracil is part of a group of chemotherapy drugs known as antimetabolites. Anti metabolites are similar to normal body molecules but with slightly different structures.

These differences mean that antimetabolites stop cancer cells from working properly.

Fluorouracil (5-FU) is a type of chemotherapy that exerts its anticancer effect by preventing the production of DNA in the cell. The lack of functional DNA prevents the cancer cell from reproducing and making vital proteins, which in turn causes the cell to die.

More quickly, they stop the cells that make and repair DNA. Cancer cells need to create and repair DNA to grow and multiply.


You can take Fluorouracil through a drip or use a small pump that you carry with you for several days.

Fluorouracil is also available as an ointment called Efudix for skin cancer. When used as an ointment, it does not cause the usual side effects, but it can cause temporary irritation and inflammation in the treated areas of the skin.

Topical Fluorouracil (5-FU) comes as a topical cream, available in 2 strengths. Your healthcare provider will determine which force is appropriate for your condition and tell you how often to use it (usually 1 to 2 times a day).

Most patients will use the cream for 2-12 weeks, depending on the condition being treated and the response to treatment. To apply the cream:

  • Wash the area to be treated with plain water and pat dry. Wait 10 minutes.
  • Wear a glove when applying the medication or use a non-metal applicator to apply it.
  • If your hands come in contact with Fluorouracil, wash them right away.
  • Use a sufficient amount to cover the injuries being treated.
  • If you need to cover the area, use only an absorbent gauze dressing that allows the site to “breathe.”
  • Do not apply to the eye, vagina, or mucous membranes.
  • Possible side effects of topical Fluorouracil.

Fluorouracil is usually prescribed as part of a multi-cycle course of treatment. You generally have up to 6 treatment cycles. Each cycle lasts 3 or 4 weeks.

You receive continuous treatment through a small portable pump. The nurse connects you to your central line. This means you can go home with it. She regularly returns to the hospital for the nurse to change her pump and see her progress.


It is contraindicated in severely debilitated patients or patients with bone marrow suppression due to radiation therapy or chemotherapy. It is also contraindicated in pregnant or lactating women. It should also be avoided in patients who do not have malignancies.

Adverse effects

The toxic effects of systemic exposure include diarrhea, stomatitis, mucositis, pancytopenia, sepsis, cardiotoxicity, and, in some cases, death.

Treatment for actinic keratosis includes cryotherapy, topical Fluorouracil, topical imiquimod, topical diclofenac, photodynamic therapy, and surgical excision.

There are very few reports of severe adverse reactions from topical Fluorouracil, but reactions include allergic contact dermatitis and inflammatory colitis. Only one known case of life-threatening toxicity from topical Fluorouracil has been reported.

For years, topical Fluorouracil has been a standard gold treatment, especially with multiple lesions. Topical Fluorouracil’s most common side effects include skin irritation with associated erythema, dryness, and burning.

During systemic use

Diarrhea is severe, dose-limiting, and aggravated by calcium folinate co-treatment. Neutropenia tends to peak 9 to 14 days after starting treatment.

The thrombocytopenia tends to peak about 7-17 days after the treatment and recover about ten days after the rise.

Cardiotoxicity is a reasonably common side effect, but generally, this cardiotoxicity is simply angina or symptoms associated with coronary artery spasms. Still, about 0.55% of those taking the drug will develop life-threatening cardiotoxicity.

Life-threatening cardiotoxicity includes arrhythmias, ventricular tachycardia, and cardiac arrest secondary to transmural ischemia.

Neurological damage

Even in small doses, Fluorouracil injection and topical application cause acute central nervous system (CNS) damage and progressive worsening of delayed central nervous system degeneration in mice.

The latter effect is caused by fluorouracil-induced damage to oligodendrocytes produced by insulating myelin sheaths.

The United States package insert notes that acute cerebellar syndrome has been observed after fluorouracil injection and may persist after cessation of treatment. Symptoms include ataxia, nystagmus, and dysmetria.

There are several things you can do to manage the side effects of topical Fluorouracil. Talk to your care team about these recommendations. They can help you decide what will work best for you. These are some of the most common side or significant effects:

Skin changes

The treatment area will usually have a burning sensation, and after several days of treatment, it will become red and crusty. The site will look worse than before treatment, which will likely continue for a few weeks after treatment ends.

You may experience any of the following symptoms in the treated area: darkening of the skin color, pain, irritation, redness, itching, scarring, rash, and ulcerations on the skin.

Sun sensitivity

This medicine can make your skin more sensitive to the sun, leading to severe burns or a rash. Sun sensitivity can last even after chemotherapy is completed. Avoid the sun between 10 and 2 pm, when it is most vital.

Wear sunscreen (at least sun protection factor 30 with UVA / UVB protection) every day and reapply when in the sun for extended periods; wear sunglasses with UVA / UVB protection, a hat, and long sleeves/pants to protect your skin and seek shade whenever possible.

Other side effects

The amount of medicine absorbed into the blood is limited with topical use, but some people have a deficiency in the DPD enzyme needed to break down Fluorouracil. These patients can develop severe toxicity.

If you experience diarrhea, stomach pain, fever, chills, vomiting, or mouth sores, tell your healthcare provider immediately or if you have a known or family history of DPD enzyme deficiency.

Reproductive problems

Exposure of a fetus to this drug can cause congenital disabilities, so you should not become pregnant or have a child while taking this drug.

Effective birth control is necessary during treatment. Even if your menstrual cycle stops or you think you are not producing sperm, you could still be fertile and conceive. It would help if you did not breastfeed while receiving this medicine.

Potential overdose

There is very little difference between the minimum effective dose and the maximum tolerated dose of Fluorouracil, and the drug exhibits marked individual pharmacokinetic variability.

Therefore, an equivalent dose of Fluorouracil can result in a therapeutic response with acceptable toxicity in some patients and unacceptable and possibly fatal toxicity in others.

Both overdose and underdose are of concern with Fluorouracil. However, several studies have shown that most colorectal cancer patients treated with Fluorouracil are dosed based on the current dosing standard, body surface area.

Dosing limitations based on body surface area prevent oncologists from accurately assessing fluorouracil dosing for most individual patients, resulting in suboptimal treatment efficacy or excessive toxicity.

Numerous studies have found significant relationships between blood plasma fluorouracil concentrations and desirable or unwanted effects in patients.

Studies have also shown that dosing based on plasma fluorouracil concentration can significantly increase desirable results and minimize adverse side effects of fluorouracil therapy.

One such test has been shown to successfully control plasma fluorouracil levels and “may contribute to improving the efficacy and safety of commonly used fluorouracil-based chemotherapies” is the Myfluorouracil test.


Its use should be avoided in patients receiving drugs known to modulate dihydropyrimidine dehydrogenase (such as the antiviral drug sorivudine). It can also increase the international normalized ratio and prothrombin times in warfarin patients.

The effectiveness of Fluorouracil is decreased when used in conjunction with allopurinol, which can be used to reduce fluorouracil-induced stomatitis through the use of allopurinol mouthwash.



The enzyme dihydropyrimidine dehydrogenase (DPD) is responsible for the detoxifying metabolism of fluoropyrimidines, a class of drugs that includes 5-fluorouracil, capecitabine, and tegafur.

Genetic variations within the dihydropyrimidine dehydrogenase (DPYD) gene can lead to reduced or absent dihydropyrimidine dehydrogenase activity.

And individuals who are heterozygous or homozygous for these variations may have a partial or complete dihydropyrimidine dehydrogenase deficiency; It is estimated that 0.2% of individuals have absolute dihydropyrimidine dehydrogenase deficiency.

Those with partial or complete dihydropyrimidine dehydrogenase deficiency have a significantly increased risk of severe or even fatal drug toxicity when treated with fluoropyrimidines; examples of toxicities include myelosuppression, neurotoxicity, and hand-foot syndrome.

Mechanism of action

Fluorouracil acts in several ways, but primarily as a thymidylate synthase (TS) inhibitor. Interrupting the action of this enzyme blocks the synthesis of pyrimidine thymidine, which is a nucleoside required for DNA replication.

Thymidylate synthase methylates deoxyuridine monophosphate (dUMP) to form thymidine monophosphate (dTMP).

Fluorouracil administration causes a shortage of thymidine monophosphate, whereby rapidly dividing cancer cells undergo cell death by death without thymine.

Calcium folinate provides an exogenous source of reduced follicles and thus stabilizes the fluorouracil-thymidylate synthase complex, increasing the cytotoxicity of Fluorouracil.


In 1954 Abraham Cantarow and Karl Paschkis discovered that liver tumors absorbed radioactive uracil more quickly than average liver cells.

Charles Heidelberger, who had previously discovered that the fluorine in trifluoroacetic acid inhibited a vital enzyme, asked Robert Duschinsky and Robert Schnitzer at Hoffman-La Roche to synthesize Fluorouracil.

Some credit Heidelberger and Duschinsky with discovering that 5-fluorouracil markedly inhibited tumors in mice.

The original 1957 report in Nature has Heidelberger as the lead author, along with NK Chaudhuri , Peter Danneberg , Dorothy Mooren , Louis Griesbach , Robert Duschinsky , RJ Schnitzer , E. Pleven, and J. Scheiner .

Natural analogs

In 2003, scientists isolated closely related compounds of 5-fluorouracil derivatives from the marine sponge, Phakellia Fusca, collected around Yongxing Island of the Xisha Islands in the South China Sea.

This is significant because fluorine-containing organic compounds rarely exist, and synthetic anticancer drugs with natural analogs are often not found.