Verrunex

Verrunex 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.

Salicylic acid has a potent keratolytic action and a slight antiseptic action when applied topically. It softens and destroys the stratum corneum by increasing endogenous hydration which causes the horny layer of the skin to swell, soften, and then desquamate. At high concentrations, salicylic acid has a caustic effect. It also possesses weak antifungal and antibacterial activity.

Salicylic acid treats acne by causing skin cells to slough off more readily, preventing pores from clogging up. This effect on skin cells also makes salicylic acid an active ingredient in several shampoos meant to treat dandruff. Use of straight salicylic solution may cause hyperpigmentation on unpretreated skin for those with darker skin types (Fitzpatrick phototypes IV, V, VI), as well as with the lack of use of a broad spectrum sunblock. Subsalicylate in combination with bismuth form the popular stomach relief aid known commonly as Pepto-Bismol. When combined the two key ingredients help control diarrhea, nausea, heartburn, and even gas. It is also very mildly anti-biotic.

Verrunex
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	Verrunex
Generic	fluorouracil + salicylic acid
Type	Cream
Therapeutic Class
Manufacturer
Available Country	United States
Last Updated:	September 19, 2023 at 7:00 am

Uses

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.

6% Salicylic Acid: This topical preparations treat the following common scaly conditions:

Chronic atopic dermatitis
Lichen simplex
Psoriasis
Seborrhoeic dermatitis
Ichthiosis

12% Salicylic Acid: This topical preparations treat the following common scaly conditions:

Warts (small excessive growths of skin caused by a type of virus. Warts often occur on the fingers or on the back of the hands).
Verruca (occurs only on the sole of the feet and can be painful. It often looks like a small white ring of skin with a black dot in the centre).
Corns and Calluses (are hard, thick pads of skin caused by pressure and friction. They usually occur on the feet due to poorly fitting shoes and can occur on the hands).

Verrunex 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 keratosisAcne, Actinic Keratosis (AK), Alopecia Areata (AA), Atopic Dermatitis (AD), Blackheads, Chronic Eczema, Chronic cutaneous lupus erythematosus, Corns, Dandruff, Dermatitis, Contact, Dermatitis, Eczematous, Dermatitis, Eczematous of the scalp, Discoid Lupus Erythematosus (DLE), Foot Callus, Fungal skin infection, Furuncle, Hand Eczema, Hyperkeratosis, Hyperkeratosis follicularis et parafollicularis, Infections, Fungal, Infections, Fungal of the Skin Folds, Infections, Fungal of the face, Infections, Fungal of the feet, Infections, Fungal of the hand, Keratosis Palmaris et Plantaris, Lichen, Lichen Plano-Pilaris, Lichen Planus (LP), Lichen simplex chronicus, Molluscum Contagiosum, Musculoskeletal Pain, Neurodermatitis, Palmo-Plantar Pustulosis, Plantar Warts, Pruritus, Psoriasis, Psoriasis Vulgaris (Plaque Psoriasis), Psoriasis of the scalp, Rash, Ringworm of the Skin, Ringworm of the scalp, Seborrheic Dermatitis, Seborrhoeic Dermatitis of the Scalp, Skin Infections, Bacterial, Verrucous Psoriasis, Warts, Calluses, Corticosteroid-responsive dermatoses, Keratinization disorders, Scaling, Scaling of skin, Scalp seborrhea, Superficial Fungal skin infection, Keratolysis

How Verrunex 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.

Salicylic acid directly irreversibly inhibits COX-1 and COX-2 to decrease conversion of arachidonic acid to precursors of prostaglandins and thromboxanes. Salicylate's use in rheumatic diseases is due to it's analgesic and anti-inflammatory activity. Salicylic acid is a key ingredient in many skin-care products for the treatment of acne, psoriasis, calluses, corns, keratosis pilaris, and warts. Salicylic acid allows cells of the epidermis to more readily slough off. Because of its effect on skin cells, salicylic acid is used in several shampoos used to treat dandruff. Salicylic acid is also used as an active ingredient in gels which remove verrucas (plantar warts). Salicylic acid competitively inhibits oxidation of uridine-5-diphosphoglucose (UDPG) with nicotinamide adenosine dinucleotide (NAD) and noncompetitively with UDPG. It also competitively inhibits the transferring of the glucuronyl group of uridine-5-phosphoglucuronic acid (UDPGA) to a phenolic acceptor. Inhibition of mucopoly saccharide synthesis is likely responsible for the slowing of wound healing with salicylates.

Dosage

Verrunex dosage

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.

Topical/Cutaneous (Adult)-

Hyperkeratotic and scaling skin conditions: As 1.8-3% preparation: Apply to affected area of the skin and/or scalp 1-4 times daily.

Acne: As 0.5-2% preparation: Apply thinly to affected area 1-3 times daily, reduce to once daily or every other day if dryness or peeling occur.

Warts and calluses:

As 12-40% plaster: Fit over the wart/callus for 48 hr, repeat process 48 hrly as needed until wart/callus is removed (up to 12 wk for warts or up to 14 days for calluses).
As 5-17% preparation in collodion-like vehicle: Apply a small amount to sufficiently cover wart/callus and allow to dry. Repeat 1-2 times daily until wart/callus is removed (up to 12 wk for warts or up to 14 days for calluses).
As 15% preparation in karaya gum-glycol plaster vehicle: Smoothen warts with emery board and place a drop of warm water prior to application. Apply the plaster in the evening and leave in place for at least 8 hr to be removed in the morning. Repeat process 24 hrly, if necessary up to 12 wk.

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

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.

An allergic reaction (shortness of breath, closing of the throat, swelling of the lips, face or tongue or hives) or severe skin irritation.

Toxicity

LD₅₀=230mg/kg (orally in mice)

Oral rat LD50: 891 mg/kg. Inhalation rat LC50: > 900 mg/m3/1hr. Irritation: skin rabbit: 500 mg/24H mild. Eye rabbit: 100 mg severe. Investigated a mutagen and reproductive effector.

Precaution

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.

For external use only. Avoid contact with eyes and other mucous membranes.

Interaction

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.

Do not use other topical preparations on the treated area unless otherwise directed by your healthcare provider. They may interfere with treatment or increase skin irritation.

Volume of Distribution

The volume of distribution is about 170 mL/kg of body weight.

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.

About 10% is excreted unchanged in the urine.

Pregnancy & Breastfeeding use

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.

Pregnancy Category C. If used by nursing mothers, it should not be used on the chest area to avoid accidental contamination of the child.

Contraindication

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.

It should not be used in any patient known to be sensitive to Salicylic Acid or any other listed ingredients.

Special Warning

Salicylic Acid is used in children over 2 years.

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.

An overdose of Salicylic Acid topical is unlikely to occur. If you do suspect an overdose or if the medication has been ingested, call a poison control center or emergency room for advice.