Dapsone, also known as 4,4'-sulfonyldianiline (SDA) or diaminodiphenyl sulfone (DDS), is an
antibiotic
An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of ...
commonly used in combination with
rifampicin and
clofazimine
Clofazimine, sold under the brand name Lamprene, is a medication used together with rifampicin and dapsone to treat leprosy. It is specifically used for multibacillary (MB) leprosy and erythema nodosum leprosum. Evidence is insufficient to sup ...
for the treatment of
leprosy
Leprosy, also known as Hansen's disease (HD), is a long-term infection by the bacteria ''Mycobacterium leprae'' or ''Mycobacterium lepromatosis''. Infection can lead to damage of the nerves, respiratory tract, skin, and eyes. This nerve damag ...
.
It is a second-line medication for the treatment and prevention of
pneumocystis pneumonia and for the prevention of
toxoplasmosis
Toxoplasmosis is a parasitic disease caused by ''Toxoplasma gondii'', an apicomplexan. Infections with toxoplasmosis are associated with a variety of neuropsychiatric and behavioral conditions. Occasionally, people may have a few weeks or months ...
in those who have
poor immune function
Immunosuppression is a reduction of the activation or efficacy of the immune system. Some portions of the immune system itself have immunosuppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reacti ...
.
[ Additionally, it has been used for ]acne
Acne, also known as ''acne vulgaris'', is a long-term skin condition that occurs when dead skin cells and oil from the skin clog hair follicles. Typical features of the condition include blackheads or whiteheads, pimples, oily skin, and ...
, dermatitis herpetiformis
Dermatitis herpetiformis (DH) is a chronic autoimmune blistering skin condition, characterised by intensely itchy blisters filled with a watery fluid. DH is a cutaneous manifestation of coeliac disease, although the exact causal mechanism is not k ...
, and various other skin conditions. Dapsone is available both topically and by mouth.
Severe side effects may include a decrease in blood cells, red blood cell breakdown especially in those with glucose-6-phosphate dehydrogenase deficiency
Glucose-6-phosphate dehydrogenase deficiency (G6PDD), which is the most common enzyme deficiency worldwide, is an inborn error of metabolism that predisposes to red blood cell breakdown. Most of the time, those who are affected have no symptoms. ...
(G-6-PD), or hypersensitivity.[ Common side effects include nausea and loss of appetite.][ Other side effects include liver inflammation, methemoglobinemia, and a number of types of skin rashes.][ While the safety of use during pregnancy is not entirely clear some physicians recommend that it be continued in those with leprosy.][ It is of the ]sulfone
In organic chemistry, a sulfone is a organosulfur compound containing a sulfonyl () functional group attached to two carbon atoms. The central hexavalent sulfur atom is double-bonded to each of two oxygen atoms and has a single bond to each of ...
class.[
Dapsone was first studied as an antibiotic in 1937.][ Its use for leprosy began in 1945.][ It is on the ]World Health Organization's List of Essential Medicines
The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health ...
. The form, which is taken by mouth, is available as a generic drug and not very expensive.[
]
Medical uses
Infections
Dapsone is commonly used in combination with rifampicin and clofazimine
Clofazimine, sold under the brand name Lamprene, is a medication used together with rifampicin and dapsone to treat leprosy. It is specifically used for multibacillary (MB) leprosy and erythema nodosum leprosum. Evidence is insufficient to sup ...
for the treatment of leprosy
Leprosy, also known as Hansen's disease (HD), is a long-term infection by the bacteria ''Mycobacterium leprae'' or ''Mycobacterium lepromatosis''. Infection can lead to damage of the nerves, respiratory tract, skin, and eyes. This nerve damag ...
.[ It is also used to both treat and prevent pneumocystis pneumonia (PCP).] It is also used for toxoplasmosis
Toxoplasmosis is a parasitic disease caused by ''Toxoplasma gondii'', an apicomplexan. Infections with toxoplasmosis are associated with a variety of neuropsychiatric and behavioral conditions. Occasionally, people may have a few weeks or months ...
in people unable to tolerate trimethoprim
Trimethoprim (TMP) is an antibiotic used mainly in the treatment of bladder infections. Other uses include for middle ear infections and travelers' diarrhea. With sulfamethoxazole or dapsone it may be used for ''Pneumocystis'' pneumonia in peo ...
with sulfamethoxazole.
Dapsone by mouth was one of the first medications used to treat moderate to severe acne vulgaris, and is still occasionally prescribed for the treatment of severe cases. A topical form of dapsone is also effective with potentially less side effects.
It is unclear if the combination with pyrimethamine
Pyrimethamine, sold under the brand name Daraprim among others, is a medication used with leucovorin (leucovorin is used to decrease side effects of pyrimethamine; it does not have intrinsic anti-parasitic activity) to treat the parasitic dise ...
is useful in the prevention of malaria
Malaria is a mosquito-borne infectious disease that affects humans and other animals. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. S ...
.
Autoimmune disease
*Cutaneous lupus erythematosis. Dapsone is effective and safe in persons with moderate, severe, or refractory cutaneous lupus erythematosis.
*Idiopathic thrombocytopenic purpura. Dapsone is effective and safe for adjunctive glucocorticoid-sparing treatment of persons with idiopathic thrombocytopenic purpura and is preferred over danazol or interferon alpha in those people with antinuclear antibodies.
*Chronic spontaneous urticaria. Dapsone is effective and safe for treatment of second-line therapy for people with chronic spontaneous urticaria in those for whom antihistamines and other first-line agents have failed.
*Relapsing polychondritis. There are no clinical trials but there are many case reports that dapsone is effective at doses of 25 mg/day to 200 mg/day for treatment of relapsing polychondritis.
Other
Dermatitis herpetiformis
Dermatitis herpetiformis (DH) is a chronic autoimmune blistering skin condition, characterised by intensely itchy blisters filled with a watery fluid. DH is a cutaneous manifestation of coeliac disease, although the exact causal mechanism is not k ...
in combination with a gluten-free diet
A gluten-free diet (GFD) is a nutritional plan that strictly excludes gluten, which is a mixture of proteins found in wheat (and all of its species and hybrids, such as spelt, kamut, and triticale), as well as barley, rye, and oats. The incl ...
.[
Dapsone may be used to treat ]brown recluse spider
The brown recluse (''Loxosceles reclusa''), Sicariidae (formerly placed in a family "Loxoscelidae") is a recluse spider with necrotic venom. Similar to those of other recluse spiders, their bites sometimes require medical attention. The brown r ...
bites that become necrotic
Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated dige ...
.
Dapsone is the recommended treatment for erythema elevatum diutinum
Erythema elevatum diutinum is a form of vasculitis.
It has been described as a paraneoplastic syndrome.
See also
* Cutaneous small-vessel vasculitis
* List of cutaneous conditions
Many skin conditions affect the human integumentary syst ...
, as a review found that using oral dapsone alone was effective in 80% of early cases of the disease. However, dapsone can potentially cause severe side effects, meaning that sometimes steroids or other antibiotics should be used instead, although these alternative treatments are much less effective.
An August 2015 review notes that dapsone is reported to be effective against generalized granuloma annulare
Generalized granuloma annulare is a skin condition of unknown cause, tending to affect women in the fifth and sixth decades, presenting as a diffuse but symmetrical, papular or annular eruption of more than ten skin lesions, and often hundreds.
...
.
Dapsone has been used as a monomer in the design of dye adsorbent polymers.
Contraindications and precautions
People with porphyria
Porphyria is a group of liver disorders in which substances called porphyrins build up in the body, negatively affecting the skin or nervous system. The types that affect the nervous system are also known as acute porphyria, as symptoms are ra ...
, anemia
Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, th ...
, cardiac disease, lung disease, HIV
The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune ...
infection, G6PD deficiency
Glucose-6-phosphate dehydrogenase deficiency (G6PDD), which is the most common enzyme deficiency worldwide, is an inborn error of metabolism that predisposes to red blood cell breakdown. Most of the time, those who are affected have no symptoms. ...
, and liver impairment are at higher risks of adverse effects when using dapsone.
Adverse effects
Hypersensitivity reactions occur in 1.4% of persons treated with dapsone, and can be fatal in medical settings with low resources. It is a form of severe cutaneous adverse reactions
Severity or Severely may refer to:
* ''Severity'' (video game), a canceled video game
* "Severely" (song), by South Korean band F.T. Island
See also
*
*
{{disambig ...
(SCARs) in which a SCARs disorder, primarily the DRESS syndrome
Drug reaction with eosinophilia and systemic symptoms (DRESS), also termed drug-induced hypersensitivity syndrome (DIHS), is a rare reaction to certain medications. It involves primarily a widespread skin rash, fever, swollen lymph nodes, and c ...
or a DRESS syndrome-like reaction occurs.
Blood
Hemolysis
Hemolysis or haemolysis (), also known by several other names, is the rupturing (lysis) of red blood cells (erythrocytes) and the release of their contents (cytoplasm) into surrounding fluid (e.g. blood plasma). Hemolysis may occur in vivo o ...
is the most prominent side-effect, occurring in about 20 % of patients treated with dapsone, although it is dose-related. It may lead to hemolytic anemia
Hemolytic anemia or haemolytic anaemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells (RBCs), either in the blood vessels (intravascular hemolysis) or elsewhere in the human body (extravascular). This most commonly ...
and methemoglobinemia. The side-effect is more common and severe in those with glucose-6-phosphate dehydrogenase deficiency
Glucose-6-phosphate dehydrogenase deficiency (G6PDD), which is the most common enzyme deficiency worldwide, is an inborn error of metabolism that predisposes to red blood cell breakdown. Most of the time, those who are affected have no symptoms. ...
, leading to the dapsone-containing antimalarial combination Lapdap being withdrawn from clinical use. A case of hemolysis in a neonate from dapsone in breast milk has been reported. Agranulocytosis
Agranulocytosis, also known as agranulosis or granulopenia, is an acute condition involving a severe and dangerous lowered white blood cell count (leukopenia, most commonly of neutrophils) and thus causing a neutropenia in the circulating blood. ...
occurs rarely when dapsone is used alone but more frequently in combination regimens for malaria prophylaxis. Abnormalities in white blood cell
White blood cells, also called leukocytes or leucocytes, are the cell (biology), cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and de ...
formation, including aplastic anemia
Aplastic anemia is a cancer in which the body fails to make blood cells in sufficient numbers. Blood cells are produced in the bone marrow by stem cells that reside there. Aplastic anemia causes a deficiency of all blood cell types: red blood ...
, are rare, yet are the cause of the majority of deaths attributable to dapsone therapy.
Methemoglobinemia occurs in about 15 % of patients treated with long-term dapsone at standard doses (100 mg/day). Only special multi-wawelength oximeters (CO-oximeter
A CO-oximeter is a device that measures the oxygen carrying state of hemoglobin in a blood specimen, including oxygen-carrying hemoglobin (O2Hb), non-oxygen-carrying but normal hemoglobin (HHb) (formerly, but incorrectly, referred to as 'reduced' ...
s) can detect methemoglobinemia directly. When there is a "saturation gap" between a low ordinary pulse oximeter
Pulse oximetry is a noninvasive method for monitoring a person's oxygen saturation. Peripheral oxygen saturation (SpO2) readings are typically within 2% accuracy (within 4% accuracy in 95% of cases) of the more accurate (and invasive) reading o ...
reading and a high arterial blood gas analysis
A blood gas test or blood gas analysis tests blood to measure blood gas tension values, it also measures blood pH, and the level and base excess of bicarbonate. The source of the blood is reflected in the name of each test; arterial blood ga ...
result, methemoglobinemia may be suspected.
Liver
Toxic hepatitis
Hepatitis is inflammation of the liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes (jaundice), poor appetite, vomiting, tiredness, abdominal pa ...
and cholestatic jaundice have been reported by the manufacturer. These toxic reactions may also occur as part of the dapsone hypersensitivity syndrome (a form of SCARs-see above) or dapsone syndrome (see below).[ Dapsone is metabolized by the ]Cytochrome P450
Cytochromes P450 (CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are ...
system, specifically isozymes In biochemistry, isozymes (also known as isoenzymes or more generally as multiple forms of enzymes) are enzymes that differ in amino acid sequence but catalyze the same chemical reaction. Isozymes usually have different kinetic parameters (e.g. dif ...
CYP2D6
Cytochrome P450 2D6 (CYP2D6) is an enzyme that in humans is encoded by the ''CYP2D6'' gene. ''CYP2D6'' is primarily expressed in the liver. It is also highly expressed in areas of the central nervous system, including the substantia nigra.
CYP2D ...
, CYP2B6
Cytochrome P450 2B6 is an enzyme that in humans is encoded by the ''CYP2B6'' gene. CYP2B6 is a member of the cytochrome P450 group of enzymes. Along with CYP2A6, it is involved with metabolizing nicotine, along with many other substances.
Funct ...
, CYP3A4
Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine. It oxidizes small foreign organic molecules (xenobiotics), such as toxins or drugs, so that they can be removed from t ...
, and CYP2C19
Cytochrome P450 2C19 (abbreviated CYP2C19) is an enzyme protein. It is a member of the CYP2C subfamily of the cytochrome P450 mixed-function oxidase system. This subfamily includes enzymes that catalyze metabolism of xenobiotics, including some p ...
. Dapsone metabolites produced by the cytochrome P450 2C19 isozyme are associated with the methemoglobinemia side effect of the drug.
Skin
When used topically, dapsone can cause mild skin irritation, redness, dry skin, burning, and itching. When used together with benzoyl peroxide products, temporary yellow or orange skin discolorations can occur.
Dapsone hypersensitivity syndrome
Hypersensitivity
Hypersensitivity (also called hypersensitivity reaction or intolerance) refers to undesirable reactions produced by the normal immune system, including allergies and autoimmunity. They are usually referred to as an over-reaction of the immune s ...
reactions occur in some patients. This reaction may be more frequent in patients receiving multiple-drug therapy.
The reaction always involves a rash
A rash is a change of the human skin which affects its color, appearance, or texture.
A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cr ...
, may also include fever
Fever, also referred to as pyrexia, is defined as having a body temperature, temperature above the human body temperature, normal range due to an increase in the body's temperature Human body temperature#Fever, set point. There is not a single ...
, jaundice, and eosinophilia, and is likely to be one manifestation of the SCARs reaction viz., the DRESS syndrome
Drug reaction with eosinophilia and systemic symptoms (DRESS), also termed drug-induced hypersensitivity syndrome (DIHS), is a rare reaction to certain medications. It involves primarily a widespread skin rash, fever, swollen lymph nodes, and c ...
(see above).[ In general, these symptoms will occur within the first six weeks of therapy or not at all, and may be ameliorated by ]corticosteroid
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are involv ...
therapy.
Other adverse effects
Other adverse effects include nausea
Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...
, headache
Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches.
Headaches can occur as a result ...
, and rash
A rash is a change of the human skin which affects its color, appearance, or texture.
A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cr ...
(which are common), and insomnia
Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...
, psychosis
Psychosis is a condition of the mind that results in difficulties determining what is real and what is not real. Symptoms may include delusions and hallucinations, among other features. Additional symptoms are incoherent speech and behavior ...
, and peripheral neuropathy
Peripheral neuropathy, often shortened to neuropathy, is a general term describing disease affecting the peripheral nerves, meaning nerves beyond the brain and spinal cord. Damage to peripheral nerves may impair sensation, movement, gland, or or ...
. Effects on the lung
The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of t ...
occur rarely and may be serious, though are generally reversible.
Mechanism of action
As an antibacterial
An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of ...
, dapsone inhibits bacteria
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
l synthesis of dihydrofolic acid
Dihydrofolic acid (conjugate base dihydrofolate) (DHF) is a folic acid ( vitamin B9) derivative which is converted to tetrahydrofolic acid by dihydrofolate reductase. Since tetrahydrofolate is needed to make both purines and pyrimidines, which ar ...
, via competition with para-aminobenzoate for the active site of dihydropteroate synthase
Dihydropteroate synthase is an enzyme classified under . It produces dihydropteroate in bacteria, but it is not expressed in most eukaryotes including humans. This makes it a useful target for sulfonamide antibiotics, which compete with the PA ...
, thereby inhibiting nucleic acid synthesis. Though structurally distinct from dapsone, the sulfonamide group of antibacterial drugs also work in this way.
As an anti-inflammatory
Anti-inflammatory is the property of a substance or treatment that reduces inflammation or swelling. Anti-inflammatory drugs, also called anti-inflammatories, make up about half of analgesics. These drugs remedy pain by reducing inflammation as o ...
, dapsone inhibits the myeloperoxidase-H2O2-halide-mediated cytotoxic system in polymorphonucleocytes. As part of the respiratory burst
Respiratory burst (or oxidative burst) is the rapid release of the reactive oxygen species (ROS), superoxide anion () and hydrogen peroxide (), from different cell types.
This is usually utilised for mammalian immunological defence, but also play ...
that neutrophil
Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying ...
s use to kill bacteria, myeloperoxidase converts hydrogen peroxide () into hypochlorous acid
Hypochlorous acid (HClO, HOCl, or ClHO) is a weak acid that forms when chlorine dissolves in water, and itself partially dissociates, forming hypochlorite, ClO−. HClO and ClO− are oxidizers, and the primary disinfection agents of chlorine so ...
(HOCl). HOCl is the most potent oxidant generated by neutrophils, and can cause significant tissue damage during inflammation. Dapsone arrests myeloperoxidase in an inactive intermediate form, reversibly inhibiting the enzyme. This prevents accumulation of hypochlorous acid, and reduces tissue damage during inflammation. Myeloperoxidase inhibition has also been suggested as a neuron-sparing mechanism for reducing inflammation in neurodegenerative diseases such as Alzheimer's disease
Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...
and stroke.
Dapsone's anti-inflammatory
Anti-inflammatory is the property of a substance or treatment that reduces inflammation or swelling. Anti-inflammatory drugs, also called anti-inflammatories, make up about half of analgesics. These drugs remedy pain by reducing inflammation as o ...
and immunomodulatory effects are thought to be its mechanism of action in treating dermatitis herpetiformis
Dermatitis herpetiformis (DH) is a chronic autoimmune blistering skin condition, characterised by intensely itchy blisters filled with a watery fluid. DH is a cutaneous manifestation of coeliac disease, although the exact causal mechanism is not k ...
.
Dapsone is an odorless white to creamy-white crystalline powder with a slightly bitter taste.
History
Discovery
In the early 20th century, the German chemist Paul Ehrlich
Paul Ehrlich (; 14 March 1854 – 20 August 1915) was a Nobel Prize-winning German physician and scientist who worked in the fields of hematology, immunology, and antimicrobial chemotherapy. Among his foremost achievements were finding a cure ...
was developing theories of selective toxicity based largely on the ability of certain dyes to kill microbe
A microorganism, or microbe,, ''mikros'', "small") and ''organism'' from the el, ὀργανισμός, ''organismós'', "organism"). It is usually written as a single word but is sometimes hyphenated (''micro-organism''), especially in olde ...
s. Gerhard Domagk
Gerhard Johannes Paul Domagk (; 30 October 1895 – 24 April 1964) was a German pathologist and bacteriologist. He is credited with the discovery of sulfonamidochrysoidine (KL730) as an antibiotic for which he received the 1939 Nobel Prize in Phy ...
, who would later win a Nobel Prize
The Nobel Prizes ( ; sv, Nobelpriset ; no, Nobelprisen ) are five separate prizes that, according to Alfred Nobel's will of 1895, are awarded to "those who, during the preceding year, have conferred the greatest benefit to humankind." Alfr ...
for his efforts, made a major breakthrough in 1932 with the discovery of the antibacterial prontosil red (sulfonamidochrysoidine). Further investigation into the involved chemicals opened the way to sulfa drug and sulfone therapy, first with the discovery of sulfanilamide
Sulfanilamide (also spelled sulphanilamide) is a sulfonamide antibacterial drug. Chemically, it is an organic compound consisting of an aniline derivatized with a sulfonamide group. Powdered sulfanilamide was used by the Allies in World War II ...
, the active agent of prontosil, by Daniel Bovet
Daniel Bovet (23 March 1907 – 8 April 1992) was a Swiss-born Italian pharmacologist who won the 1957 Nobel Prize in Physiology or Medicine for his discovery of drugs that block the actions of specific neurotransmitters. He is best known for hi ...
and his team at Pasteur Institute
The Pasteur Institute (french: Institut Pasteur) is a French non-profit private foundation dedicated to the study of biology, micro-organisms, diseases, and vaccines. It is named after Louis Pasteur, who invented pasteurization and vaccines f ...
(1935), then with that of dapsone independently by Ernest Fourneau
Ernest Fourneau (4 October 1872 – 5 August 1949) was a French pharmacist graduated in Pharmacy 1898 for the Paris university specialist in medicinal chemical and pharmacology who played a major role in the discovery of synthetic local anesthetic ...
in France and Gladwin Buttle in the United Kingdom.[ (1937)]
Proposed use in antimalarial drugs
The spread of drug-resistant malaria
Malaria is a mosquito-borne infectious disease that affects humans and other animals. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. S ...
in Africa has encouraged the development of new, low-cost antimalarial drugs. ''Plasmodium falciparum
''Plasmodium falciparum'' is a Unicellular organism, unicellular protozoan parasite of humans, and the deadliest species of ''Plasmodium'' that causes malaria in humans. The parasite is transmitted through the bite of a female ''Anopheles'' mosqu ...
'', one of the ''Plasmodium
''Plasmodium'' is a genus of unicellular eukaryotes that are obligate parasites of vertebrates and insects. The life cycles of ''Plasmodium'' species involve development in a blood-feeding insect host which then injects parasites into a vert ...
'' species that causes malaria, has developed resistance both to chloroquine
Chloroquine is a medication primarily used to prevent and treat malaria in areas where malaria remains sensitive to its effects. Certain types of malaria, resistant strains, and complicated cases typically require different or additional medi ...
and sulfadoxine/pyrimethamine, two of the most common treatments for malaria. Artemisinin
Artemisinin () and its semisynthetic derivatives are a group of drugs used in the treatment of malaria due to '' Plasmodium falciparum''. It was discovered in 1972 by Tu Youyou, who shared the 2015 Nobel Prize in Physiology or Medicine for her ...
, another antimalarial drug, had been developed in the 1980s but was too expensive for large-scale use. This led GlaxoSmithKline
GSK plc, formerly GlaxoSmithKline plc, is a British multinational pharmaceutical and biotechnology company with global headquarters in London, England. Established in 2000 by a merger of Glaxo Wellcome and SmithKline Beecham. GSK is the ten ...
to develop Lapdap
Chlorproguanil/dapsone (sold commercially as Lapdap) was a fixed dose antimalarial combination containing chlorproguanil and dapsone, which act synergistically against malaria. The drug was withdrawn in 2008 following increasing evidence of toxici ...
, a combination drug consisting of chlorproguanil and dapsone. Lapdap was licensed in the United Kingdom starting in October 2003.[
One advantage of Lapdap was that chlorproguanil and dapsone are both low-cost drugs. Another was that by virtue of being a combination drug, it was less likely to cause drug resistance. However, because dapsone causes hemolytic anemia in patients with G6PD deficiency, and because G6PD deficiency affects 10-25% of the population of sub-Saharan Africa, it was discovered that Lapdap is not safe for use in Africa. It was available in many African countries for four years before GlaxoSmithKline took it off the market in February 2008.][
]
Dapsone gel
Dapsone had been reported in a few cases to effectively treat acne, but the risk of hemolytic anemia kept it from being widely used for this purpose. For many years scientists attempted to develop a topical formulation of dapsone that would be as effective against acne as oral dapsone, but without the hemolysis side effect. This was difficult to accomplish because dapsone is highly insoluble in aqueous solvents. In the early 2000s QLT USA developed Aczone, a 5% dapsone gel that was shown to be effective against acne without causing clinically significant declines in hemoglobin levels, even in subjects with G6PD deficiency. In February 2016, the FDA approved a 7.5% dapsone gel. This higher strength has the advantage of a once-daily application, versus twice-daily application of the 5% formulation.
Other uses
Dapsone also find uses as a curing agent in the manufacture of paints, adhesives, composites, powder coats, printed circuit boards, and imine-based vitrimers.
See also
*Promin
Promin, or sodium glucosulfone is a sulfone drug that was investigated for the treatment of malaria, tuberculosis and leprosy. It is broken down in the body to dapsone, which is the therapeutic form.
History
The first synthesis of Promin is some ...
, a more-soluble derivative
References
External links
*
{{Authority control
AbbVie brands
Anilines
Anti-acne preparations
Antileprotic drugs
Benzosulfones
Dihydropteroate synthetase inhibitors
German inventions
Wikipedia medicine articles ready to translate
World Health Organization essential medicines