A Comprehensive Review of Dapsone Therapy in Leprosy Management

Overview

First studied in 1937 as an antibiotic, Dapsone is known by several other names, such as Diaminodiphenyl sulfone (DDS) and 4,4’-sulfonyldianiline (SDA). It was extensively studied and explored in 1937 and has made its way to the list of essential medicines in the World Health Organization (WHO). Dapsone is used with Rifampicin and Clofazimine to treat Hansen’s disease or leprosy.

It also treats other diseases such as acne vulgaris, pneumocystis pneumonia, toxoplasmosis, etc. This medication can be used orally or topically, depending on the disease for which it is prescribed. Like other medicines, Dapsone is also associated with certain side effects. This medication should be taken per the doctor's prescription to avoid the recurrence of leprosy.

How Does Dapsone Work?

Leprosy, otherwise known as Hansen’s disease, is caused by the slow-growing, rod-shaped bacterium, Mycobacterium leprae, usually known as M. leprae. These bacterial cells must proliferate in number to create genetic material. Folic acid is needed for the production of genetic material. However, unlike human cells, bacteria cannot absorb folic acid from the diet. Instead, they create it from scratch. Dapsone functions by halting or inhibiting the bacteria's production of folate. Thus, these bacteria cannot create genetic material without folate, which prevents them from proliferating. Therefore, Dapsone hinders the spread of Mycobacterium leprae infection. The immune system also plays a role by eliminating the remaining bacteria.

Uses of Dapsone

This medication is used to treat several conditions, such as -

• Used to treat leprosy.

• Acne vulgaris.

• Pneumocystis pneumonia.

• Toxoplasmosis.

Dosage and Administration

It is dispensed in the form of tablets and is administered orally. The dosage varies for adults and children.

• Adults and Teenagers - 50 to 100 milligrams once a day.

• Children - 1.4 milligrams per kilogram of body weight, once a day.

Missed Dose: Patients should take the missed dose as soon as they remember. However, they should avoid taking two doses at the same time. Additionally, patients can skip the missed dose if it is almost time for the subsequent dose.

Warnings and Precautions:

• Since Dapsone makes the skin sensitive to light, patients should also take measures to avoid prolonged or unnecessary sunlight exposure to reduce the chances of unwanted complications. They can achieve this by wearing sunscreen, protective clothing, and sunglasses.

• Patients should continue using the drug until the disease has cleared up completely to prevent its recurrence. Results may take a few weeks to several months. In some instances, it can take several years as well.

• Patients should avoid missing the scheduled doses as Dapsone works best when there is a steady and constant level in the blood. Hence, the doses should also be taken simultaneously every day.

• Patients should inform the health care professional of all medical conditions, especially the ones mentioned below, as using Dapsone may exacerbate or worsen these conditions.

• Glucose-6-phosphate dehydrogenase (G6PD) deficiency.

• A severe form of anemia.

• Any form of liver disease.

• Methemoglobin reductase deficiency.

• Women should inform the health care professional if they are pregnant or plan to become pregnant. Lactating patients should also consult a physician before using Dapsone to prevent unnecessary harm to the infant. When patients become pregnant while consuming Dapsone, the healthcare professional should be immediately intimated.

Use in Specific Groups:

1. Allergies:

Patients should inform the physician about the present or past history of any unusual or allergic reaction to this medication or other medications. They should also discuss the history of allergies to foods, preservatives, dyes, or animals.

2. Pediatric Population:

Due to the limited availability of studies with the pediatric population, a thorough risk assessment should be made while prescribing this drug to the pediatric population.

3. Geriatric Population:

Studies have yet to be done with this group specifically. Hence, a thorough risk assessment should be made before prescribing Dapsone to this population.

4. Breastfeeding Population:

Due to the limited availability of studies involving this population, women should weigh the potential benefits and risks before taking this medication while breastfeeding.

Drug Interactions

Administration of Dapsone with the following drugs can exacerbate the side effects -

• Atazanavir.

• Fosamprenavir.

• Rifabutin.

• Rifapentine.

• Amprenavir.

Certain medications cannot be used together to avoid interactions; however, in some cases, sometimes these medications are prescribed by changing the dose and or taking the necessary precautions required. Dose modification might be required for the following medicines when they are administered with Dapsone -

• Zidovudine.

• Warfarin.

Other Interactions

Patients should avoid alcohol and tobacco while taking Dapsone since it can lead to interactions and unnecessary complications. Dapsone is also known to cause stomach disturbances, hence should always be consumed with food or milk.

For Patients

What Is Leprosy?

Leprosy is a long-term bacterial infection that affects the skin, resulting in severe health complications. It is caused by a slow-growing, rod-shaped bacterium - Mycobacterium leprae, commonly called M. leprae. The exact mode of transmission is unclear, but scientists believe it is transmitted via droplets expelled in the air when an infected person coughs or sneezes. Individuals that are immunosuppressed are at a higher risk of contracting leprosy.

This disease affects the skin and the peripheral nerves, eyes, and surfaces of the upper respiratory tract.

If left untreated, the disease can be debilitating, resulting in muscle weakness, permanent nerve damage in arms and legs, and loss of sensation in the body. It is known to occur at all ages, ranging from early infancy to old age. It is common in tropical and sub-tropical Asia, Africa, and Central and South America. Primarily, there are two common forms of leprosy, namely - tuberculoid and lepromatous. Although both these leprosy forms produce skin lesions, the lepromatous form is more severe and highly contagious. Usually, it leads to the additional formation of large bumps and lumps in the body.

What Are the Signs and Symptoms Associated With Leprosy?

The incubation period for Leprosy varies and can range anywhere between six months to 20 years. This disease affects the nerves, skin, and moist and soft surfaces present inside the body.

The various signs and symptoms associated with leprosy include the following -

• Discolored skin patches.

• Bulby growths on the skin, tubercular or nodular.

• Dry skin.

• Thick and stiff skin.

• Loss of eyelashes.

• Loss of eyebrows.

• Swelling on the earlobes and face, which are usually painless.

• Ulcers on feet.

• Numbness in the skin, especially in the affected region.

• Muscle pain and weakness.

• Paralysis of the hands and feet.

• Visual problems such as blurred or diminished vision.

• Enlarged nerves, are usually seen at the lateral aspect of the neck.

• Nose bleeds.

• Stuffy or runny nose.

What Is Dapsone and How Does It Work?

Dapsone is a prescription drug used to treat various diseases, including leprosy, also known as Hansen’s disease. The slow-growing, rod-shaped bacterium causes leprosy, Mycobacterium leprae, usually known as M. leprae. These bacterial cells must proliferate in number to create genetic material. Folic acid is needed for the production of genetic material. However, unlike human cells, bacteria cannot absorb folic acid from the diet. Instead, they create it from scratch. Dapsone functions by halting or inhibiting the bacteria's production of folate. Thus, these bacteria cannot create genetic material without folate, which prevents them from proliferating. Therefore, Dapsone hinders the spread of Mycobacterium leprae infection. The immune system also plays a role by eliminating the remaining bacteria.

How Should Dapsone Be Used?

This medication is administered orally and should be taken per the doctor's instructions. It is typically taken once daily but can also be taken thrice weekly, based on the patient's condition. Patients should consult their physician before modifying the dose. It is dispensed in the form of tablets. The dosage varies for adults and children.

• Adults and Teenagers - 50 to 100 milligrams once a day.

• Children - 1.4 milligrams per kilogram of body weight, once a day.

Missed Dose: Patients should take the missed dose as soon as they remember. However, they should avoid taking two doses at the same time. Additionally, patients can skip the missed dose if it is almost time for the subsequent dose.

What Special Dietary Considerations Should Be Taken Into Account?

Dapsone tends to cause stomach disturbances and hence, should be taken with food or milk.

What Are the Side Effects of Dapsone?

Every medication is associated with certain side effects. The side effects of Dapsone include the following -

• Stomach disturbances, such as an upset stomach.

• Fever.

• Vomiting.

• Nausea.

• Skin rash.

• Yellowing of the skin and eyes.

• Unusual and unexplained bruising of the skin.

• Sore throat.

How Is Dapsone Stored and Discarded?

This medication should be stored in its original packaging and kept away from pets and children. It should also be protected from direct sunlight and excess moisture. Dapsone has a good shelf life when stored at room temperature.

Who Should Not Use Dapsone?

• Patients allergic to Dapsone should avoid using it.

Individuals having the following conditions should also avoid using it -

• Glucose-6-phosphate dehydrogenase (G6PD) deficiency.

• A severe form of anemia.

• Any form of liver disease.

• Methemoglobin reductase deficiency.

What Should Be Done in the Case of an Overdose?

An overdose of Dapsone usually precipitates in the form of syncope, loss of consciousness, nasal congestion, and hallucinations. Patients should rush to the hospital when such symptoms are elicited.

What Should Be Informed to the Healthcare Provider Before Using Dapsone?

Patients should ensure the following before starting the course of Dapsone:

1. They should inform the health care professional about the present and past history of allergies to Dapsone.

2. They should also inform about allergies associated with

• Sulfa drugs.

• Phenylhydrazine.

• Naphthalene.

• Niridazole.

• Nitrofurantoin.

• Primaquine, or any other drugs.

3. Patients should also inform the health care professional about all the non-prescription and prescription drugs, medications, vitamins, and other supplements they have been taking.

Special emphasis should be made on the following -

• Aminobenzoate potassium.

• Aminobenzoic acid.

• Clofazimine.

• Didanosine.

• Probenecid.

• Pyrimethamine.

• Rifampin.

• Trimethoprim.

4. Patients should inform the health care professional of all medical conditions, especially the ones mentioned below, as using Dapsone may exacerbate or worsen these conditions.

• Glucose-6-phosphate dehydrogenase (G6PD) deficiency.

• A severe form of anemia.

• Any form of liver disease.

• Methemoglobin reductase deficiency.

5. Women should inform the health care professional if they are pregnant or plan to become pregnant. Lactating patients should also consult a physician before using Dapsone to prevent unnecessary harm to the infant. When patients become pregnant while consuming Dapsone, the healthcare professional should be immediately intimated.

For Doctors:

Indications of Dapsone:

1. FDA-approved indications include -

• Leprosy.

• Dermatitis herpetiformis.

2. Non-FDA-approved indications include -

• Linear IgA bullous dermatosis.

• Chronic bullous dermatosis of childhood.

• Bullous systemic lupus erythematosus.

• Erythema elevatum diutinum.

• Autoimmune bullous dermatoses like cicatricial pemphigoid, bullous pemphigoid, IgA pemphigus, pemphigus vulgaris, subcorneal pustular dermatosis, pemphigus foliaceous, and epidermolysis bullosa acquisita.

• Vasculitic dermatoses like eukocytoclastic vasculitis and urticarial vasculitis.

• Neutrophilic dermatoses like pyoderma, gangrenosum, and Behcet syndrome.

• Other dermatoses like subacute cutaneous lupus erythematosus, granuloma annulare, loxoscelism, granuloma faciale, relapsing polychondritis, rosacea, nodulocystic acne, panniculitis, pustular psoriasis, and rhinosporidiosis

Contraindications of Dapsone:

The use of Dapsone is contraindicated in individuals having the following conditions -

• Allergies to Dapsone.

• Liver diseases.

• Severe anemia.

• Glucose-6-phosphate dehydrogenase (G6PD) deficiency.

• Methemoglobin reductase deficiency.

Pharmacology of Dapsone:

Mechanism of Action:

Dapsone is bacteriostatic against Mycobacterium leprae when used to treat leprosy at doses between 1 and 10 mg/L. It works by blocking the folic acid pathway. Competitive antagonism explicitly stops the bacteria from using para-aminobenzoic acid (PABA) to synthesize folic acid. It inhibits dihydropteroate synthase efficiently.

The Half-Life of Dapsone: Although it ranges from 10 to 50 hours, at a steady state, Dapsone has a half-life of 28 hours.

Administration: Dapsone is dispensed as oral tablets and is administered orally.

Adverse Effects of Dapsone:

The adverse effects of Dapsone include the following -

• Stomach disturbances, such as upset stomach.

• Fever.

• Vomiting.

• Nausea.

• Skin rash.

• Yellowing of the skin and eyes.

• Unusual and unexplained bruising of the skin.

• Sore throat.

Pharmacokinetics of Dapsone -

• Absorption: Following its oral administration, Dapsone has a bioavailability ranging from 70 to 80 percent.

• Metabolism: Dapsone primarily metabolizes via hepatic routes, specifically mediated via CYP2E1 enzymes.

• Elimination: Dapsone is eliminated via renal routes.