Cantharidin: A Comprehensive Review

Drug Overview

Molluscum contagiosum, or molluscum bumps, is a viral skin infection that creates raised, pearl-like skin bumps in adults and children two years and older. Cantharidin is used to treat this condition. Topical Cantharidin was the first molluscum contagiosum (molluscum) medication recognized by the Food and Drug Administration on July 21, 2023, for adults and pediatric patients two years of age and older.

Drug Group:

Cantharidin belongs to a group of drugs known as vesicants.

Available Doses and Dosage Forms:

Each milliliter of topical solution of Cantharidin has seven milligrams (0.7 percent) of Cantharidin.

For Patients:

What Is Molluscum Contagiosum?

The molluscum contagiosum virus (pox) is the source of molluscum contagiosum, a skin infection. Usually, it causes a benign, moderate skin illness called Mollusca, characterized by tiny, elevated sores. These growths typically have a diameter of two to five millimeters and can occur anywhere on the body. They are about the size of a pencil eraser or a pinhead. Mollusca have a pearly look because of their central pit or dimple, which might be flesh-colored, pink, white, or another color. They are firm and soft upon touch.

Molluscum contagiosum usually disappears without leaving scars after six to 12 months, although it might take up to four years for the lesions to vanish completely. Rarely do the lesions appear on the palms of the hands or the soles of the feet, though they occasionally become itchy, painful, red, and swollen. Mollusca can be seen on the face, neck, arms, legs, abdomen, and genitalia, among other body parts. They could appear either singly or in clusters.

What Are the Things to Inform the Doctor Before Taking Cantharidin?

• Patients should disclose any allergies they may have to Cantharidin topical solution, other drugs, or any of the constituents of the solution.

• Additionally, patients should disclose any vitamins, nutritional supplements, herbal items, and prescription and over-the-counter medications that they presently use or intend to take.

• Any prior or current skin issues should be disclosed to the doctor as they may affect topical Cantharidin application.

• Patients must inform their doctor if they are expecting or already pregnant. They should also inform their doctor if they become pregnant during the treatment regime.

• In patients who are nursing or intend to start nursing, the physician will avoid topical Cantharidin application on skin areas that the infant may come into touch with.

• Smokers should be advised that topical Cantharidin is combustible and should abstain from smoking until the drug has been removed from their skin.

How Is Cantharidin Administered?

• Cantharidin is available as a liquid solution and is applied by healthcare practitioners in a clinical environment like doctor's offices or clinics. This solution is applied directly to the skin in regions affected by molluscum bumps. It is applied usually once every three weeks or as frequently as needed.

• It is best to wait up to five minutes for the medication to dry completely on the skin before leaving the doctor's office. The patient should wash the treated skin region with soap and water 24 hours after applying the medication. Avoid rubbing the skin too hard or washing it with a washcloth or anything abrasive.

• It is recommended that topical Cantharidin be applied only to the skin, avoiding contact with the nose, mouth, eyes, or genitalia.

• After applying topical Cantharidin, wait 24 hours or until the drug has been rinsed off from the skin before touching the treated regions or allowing it to come into contact with the mouth or eyes.

• If topical Cantharidin gets in the eyes, it could result in serious eye damage, such as ulcers and scarring. It can also lead to irreversible blindness. Get emergency medical attention and flush the affected eye for at least fifteen minutes if topical Cantharidin gets in the eyes.

• After treatment, for 24 hours, or until the medicine is removed from the skin, topical products (for example, creams, lotions, sunscreen, or steroids) should not be applied to the treated area. Furthermore, bandaging or wrapping the treated regions is not advised.

• Blisters and severe discomfort at the application site are possible adverse effects of topical Cantharidin. If a serious reaction appears less than 24 hours after application, it is advised to call the doctor and wash the affected area with soap and water. For symptom relief, Acetaminophen, an over-the-counter pain reliever, may be suggested.

• Topical Cantharidin is combustible, even after it has dried on the skin. Until the drug is completely removed, treated skin should not be exposed to fire or open flames either during or after treatment.

Precautions and Overview While Applying the Medicine:

• When Applying Cantharidin:

  • Put on vinyl or nitrile gloves and safety goggles before preparing and applying.

  • Use no more than two Cantharidin applicators in a single application to cover any lesion.

  • Twenty-four hours following treatment, wash the area treated with soap and water and repeat every three weeks if necessary.

  • Bandaging cured lesions is not advised.

  • Remove Cantharidin before 24 hours if extreme blistering, discomfort, or other serious reactions occur.

• About the Cantharidin Break Tool and Applicator:

  • Make only one use of each applicator.

  • Avoid modifying or using an obstructed applicator.

  • Breaking the glass ampule before removing the applicator cap is not advised.

  • Discard applicators appropriately in a sharps container per medical advice if there is damage or leakage.

Dietary Instructions:

Sticking to the regular diet is usually advised unless the doctor instructs the patient otherwise.

Side Effects:

• Cantharidin applied topically may cause side effects like:

  • The color of the skin changes at the application site. It becomes either lighter or darker.

  • Redness, irritation, dryness, or scabbing where the application was made.

  • One must notify their physician if any of these symptoms worsen or continue.

• Topical Cantharidin may cause major adverse effects. Notifying the physician right away is essential if the below-mentioned symptoms occur:

  • Blisters, pain, or swelling where Cantharidin was applied.

  • At the site of the application of Cantharidin, the skin may break down, deteriorate, or have lesions.

  • Red, painful eyes or irritating eyes. If topical Cantharidin gets in the eyes, it may cause blindness.

• If a person or child accidentally swallows topical Cantharidin or if Cantharidin comes into contact with their mouth or they exhibit any of the below-mentioned symptoms, they should contact their physician right away or seek emergency medical attention.

  • Seizures.

  • Trouble in swallowing and difficulty in talking (slurring of speech).

  • Reduced frequency of urination.

  • Nausea, vomiting, and diarrhea.

  • Unusual weakness.

  • Swelling occurs in the lower legs, arms, face, feet, ankles, and hands.

  • Cramps and pain in the abdomen.

  • Presence of blood or mucus in the stools.

  • Unexpected bruises and bleeding.

  • Urine becomes discolored, or blood may be present in the urine.

Missed Dose:

Applied as and when needed or once in three weeks.

Overdose:

Cantharidin, when used orally, can cause major side effects such as flaccid paralysis (muscle tone decreases resulting in paralysis or muscle weakness), severe gastrointestinal damage, blistering, coagulopathy (disease of blood clotting), and renal (kidney) failure. If Cantharidin topical solution is consumed, prompt medical intervention is necessary. If patients need more advice on controlling overdosage, they should get in touch with a medical toxicologist or a poison center.

Supply and Storage:

Cantharidin is packaged as a single-use applicator in a tiny glass container called an ampule. It is protected in a paperboard sleeve. Each ampule has roughly 0.45 mL (milliliters) of 0.7 percent Cantharidin solution. This indicates that there are seven milligrams of Cantharidin per milliliter of Cantharidin.

For Doctors:

Indication:

Molluscum contagiosum is treated with Cantharidin in adults and children two years of age and above.

Contraindication:

No contraindications were reported.

What Are the Pharmacological Aspects of Cantharidin?

• Description - Cantharidin topical solution is a light violet to deep purple, somewhat viscous liquid with no visible particles intended for topical use. The solution includes seven milligrams (mg) of Cantharidin (0.7 percent) per milliliter (mL), an active component with a lipophilic character. Cantharidin appears as a white to off-white solid at room temperature and has little water solubility.

• Ingredients -

  • Active Component - Cantharidin.

  • Inactive Substances - Camphor, gentian violet, hydroxypropyl cellulose, acetone, nitrocellulose, castor oil, ethanol, and denatonium benzoate (a bittering agent).

  • Denatonium benzoate is a bittering ingredient that prevents young children from inadvertently placing it in their mouths and ingesting it.

• Mechanism of Action - Cantharidin's exact mechanism of action in the treatment of molluscum contagiosum remains unclear.

• Pharmacodynamics - Molluscum contagiosum is treated with Cantharidin due to its vesicant qualities. However, the precise pharmacodynamics that underlie this treatment's effectiveness are yet unknown.

• Pharmacokinetics -

  • In a trial with sixteen participants two years of age and above with at least twenty-one molluscum contagiosum lesions at baseline, the pharmacokinetics of Cantharidin were assessed. Cantharidin solution was applied topically to each lesion once for every participant. Subjects receiving exposure therapy had 47.4 lesions treated on average (median of 35.0).

  • In the plasma of 15 out of 16 patients, Cantharidin was undetectable. At two hours post-dose, there was only one patient with a detectable plasma level of Cantharidin (3.391 nanograms per milliliter).

Toxicity (Carcinogenesis, Mutagenesis, and Infertility)

• There is no research on Cantharidin's carcinogenicity.

• Cantharidin showed no mutagenic characteristics in an Ames bacterial reverse mutation assay. An in vitro test for chromosomal abnormality in human lymphocytes yielded unclear results. Furthermore, Cantharidin demonstrated positive results in an in vitro micronucleus experiment using TK6 cells, mostly through an aneugenic pathway.

• It is unknown how Cantharidin affects fertility.

Warnings and Precautions:

• Toxicities Associated with Inappropriate Administration - Cantharidin is only meant to be applied topically. It is not recommended for use in the eyes, mucosal areas, or oral administration. If Cantharidin is taken orally, it can cause serious, possibly fatal consequences. Oral intake can result in coagulopathy, paralysis, convulsions, gastrointestinal damage, and renal failure as side effects. It is important to advise patients and caregivers not to put Cantharidin in their mouths and to get medical help right away if they do accidentally eat it.

Furthermore, Cantharidin can cause ocular toxicity if it gets in the eyes. Ocular perforations, severe ocular injuries, and corneal necrosis are examples of adverse reactions. As a result, it is essential to refrain from putting Cantharidin in or near the eyes. It is advisable to seek medical attention and cleanse the eyes with water for at least 15 minutes if Cantharidin gets in the eyes.

• Local Skin Reactions - As a vesicant, Cantharidin produces blisters where it is applied. Ninety-seven percent of participants in clinical studies reported having local skin reactions, including erythema, pruritus, vesiculation, and pain. It should not be used near mucosal tissues, the eyes, or nearby healthy skin. Contact should be removed immediately if it comes into contact with healthy skin or other unwanted surfaces. To avoid spreading and unfavorable responses, wait 24 hours after Cantharidin therapy before applying other topical medications to the treated regions. Cantharidin should be removed by washing with soap and water before the suggested 24-hour period if there is extreme blistering, discomfort, or other negative responses.

• Flammability - Even after drying, Cantharidin remains combustible. Until Cantharidin is eliminated from the body, keeping smoke, flames, and fire away from the treated lesion or lesions during and after application is crucial.

Drug Interaction:

No research has been done to evaluate Cantharidin's possible interactions with other medicines.

Clinical Studies:

Five hundred twenty-eight patients with molluscum contagiosum participated in the two-phase three trials (trial 1 and trial 2) that evaluated Cantharidin. In these double-blind, randomized, placebo-controlled trials, participants were randomly assigned to receive either vehicle therapy or Cantharidin. Most patients had one 24-hour dermal application of Cantharidin or a vehicle for each lesion, which could be repeated up to four times every three weeks.

Due to treatment-emergent adverse events, 35 percent of trial participants treated with Cantharidin solution and 21 percent of trial participants treated with vehicles had their treatment stopped before the 24-hour time point. During both investigations, the most commonly reported side effects were local skin responses at the application site, occurring in 97 percent of the people treated with Cantharidin. No significant side effects were noted in any of these trials.

Among participants treated with Cantharidin, the rate of discontinuation owing to adverse responses was 2.3 percent, whereas, among those treated with vehicles, it was 0.5 percent.

Specific Considerations:

• Pregnancy - Since there is no data on Cantharidin use in pregnant women, there is no information on possible drug-associated risks of serious birth abnormalities, miscarriage, or unfavorable outcomes for the mother or fetus. Studies on Cantharidin and animal reproduction have not been carried out. Maternal use is unlikely to expose the fetus to Cantharidin, nevertheless, because systemic exposure to the medication after topical treatment is minimal. It is noteworthy that there is a lack of clarity regarding the background risk of serious birth abnormalities and miscarriages in the general community. The estimated background risk of significant birth abnormalities and miscarriage in clinically recognized pregnancies in the general U.S. population is between two percent to four percent and 15 percent to 20 percent, respectively. Thus, there is a background risk associated with every pregnancy that could result in miscarriage, birth abnormalities, or other unfavorable consequences.

• Lactation - Keep Cantharidin topical solution away from areas where a nursing infant could eat it or be exposed to it through their eyes. As Cantharidin has low systemic absorption after topical administration, breastfeeding is not expected to result in significant drug exposure for the child, even though there are no data on the effects of Cantharidin on the breastfed infant or the production of milk, whether it is present in human or animal milk. However, in addition to the mother's clinical requirement for Cantharidin topical solution and any potential negative effects on the nursing child from the medicine or the underlying maternal disease, it is crucial to take into account the developmental and health benefits of breastfeeding.

• Pediatric Patients - Cantharidin is safe and effective for treating molluscum contagiosum in pediatric patients two years of age and above. Results from adequate and carefully monitored trials, including patients in this age range, support this. It is noteworthy that there is no demonstrated safety or effectiveness when using Cantharidin for longer than 12 weeks.

• Geriatric Patients - Data on the effect of Cantharidin on the older population is not available.