Sulphonylbisbenzamine – Indications, Contraindication Sulphonylbisbenzamine/Dapsone is a synthetic derivative of diamino-sulfone with anti-inflammatory and anti-bacterial properties. As a structural analog of p-aminobenzoic acid (PABA), dapsone inhibits dihydropteroate synthase (DHPS), an enzyme important in folate synthesis, resulting in a depletion of the folate pool and a reduction in the amount of thymidylate available for DNA synthesis. Although the exact mechanism through which dapsone exerts its anti-inflammatory activity has yet to be fully elucidated, this agent interferes with the activation and oxidative damage of myeloperoxidase in neutrophils and inhibits the integrin-mediated adherence and chemotaxis of neutrophils. Dapsone’s anti-inflammatory activities may contribute to the effects seen upon topical administration. Dapsone is a sulfonamide related drug used for the therapy of leprosy and dermatitis herpetiformis. Dapsone has been linked with rare cases of idiosyncratic liver injury, similar to that seen with the sulfonamides. Dapsone is a sulfone that is diphenyl sulfone in which the hydrogen atom at the 4 positions of each of the phenyl groups is substituted by an amino group. It is active against a wide range of bacteria but is mainly employed for its actions against Mycobacterium leprae, being used as part of multidrug regimens in the treatment of all forms of leprosy. It has a role as an antimalarial, a leprostatic drug, an anti-infective agent and an anti-inflammatory drug. It is a sulfone and a substituted aniline. It derives from a diphenyl sulfone. Another name Bis(p-aminophenyl) sulfone DADPS Dapsona Dapsone Dapsonum DDS Diaphenylsulfone p-aminophenyl sulfone p,p-sulphonylbisbenzamine p,p-sulphonylbisbenzenamine p,p’-diaminodiphenyl sulfone Mechanism of Action of Dapsone Dapsone acts against bacteria and protozoa in the same way as sulphonamides, which is by inhibiting the synthesis of dihydrofolic acid through competition with para-amino-benzoate for the active site of dihydropteroate synthetase. The anti-inflammatory action of the drug is unrelated to its antibacterial action and is still not fully understood. Dapsone is a structural analog of para-aminobenzoic acid (PABA) and a competitive inhibitor of dihydropteroate synthase (folP1P2) in the folate pathway. The effect on this evolutionarily conserved pathway also explains why dapsone is a broad-spectrum agent with antibacterial, anti-protozoal, and antifungal effects. The anti-inflammatory effects of dapsone occur via inhibition of tissue damage by neutrophils. First, dapsone inhibits neutrophil myeloperoxidase activity and respiratory burst. Second, it inhibits the activity of neutrophil lysosomal enzymes. Third, it may also act as a free radical scavenger, counteracting the effect of free radicals generated by neutrophils. Fourth, dapsone may also inhibit the migration of neutrophils to inflammatory lesions. Indications of Dapsone Gel Anti-Infective Agents; Antimalarials; Folic Acid Antagonists; Leprostatic Agents For the treatment and management of leprosy and dermatitis herpetiformis. Dapsone is a sulfonamide related drug used for the therapy of leprosy and dermatitis herpetiformis. Dapsone has been linked with rare cases of idiosyncratic liver injury, similar to that seen with the sulfonamides. Acne Vulgaris Bullous Systemic Lupus Erythematosus Bullous dermatitis herpetiformis Hansen’s Disease Pemphigus Vulgaris (PV) Relapsing Polychondritis Mild Pneumocystis pneumonia Dermatitis Herpetiformis Bullous Pemphigoid Leprosy Leprosy, Lepromatous Leprosy, Tuberculoid Leukocytoclastic Vasculitis Linear IgA Disease Pemphigoid Pemphigus Pneumocystis Pneumonia Pneumocystis Pneumonia Prophylaxis Toxoplasmosis, Prophylaxis Mild Toxoplasma gondii encephalitis Moderate Pneumocystis pneumonia Moderate Toxoplasma gondii encephalitis Refractory Idiopathic thrombocytopenic purpura The anti-inflammatory effects are the basis for a therapy for pemphigoid, dermatitis herpetiformis, linear IgA bullous disease, relapsing chondritis, and ulcers caused by the brown recluse spider Dapsone is approved for use in dermatitis herpetiformis and leprosy. It is particularly useful in the treatment of linear immunoglobulin (IgA) dermatosis, bullous systemic lupus erythematosus, erythema elevatum diutinum, and subcorneal pustular dermatosis It was effective in chronic adjuvant arthritis & cotton pellet granuloma. Antipyretic & analgesic effects were similar to those of phenylbutazone. Results showed that dapsone produced clearing of skin lesions within 2-3 days in a 53-yr-old woman who was completely controlled on dapsone 150 mg/day. Dapsone is used for the treatment of dermatitis herpetiformis. The non-FDA approved indications include the following:[rx] Linear IgA bullous dermatosis, chronic bullous dermatosis of childhood, bullous systemic lupus erythematosus, and erythema elevatum diutinum Autoimmune bullous dermatoses such as bullous pemphigoid, cicatricial pemphigoid, IgA pemphigus, subcorneal pustular dermatosis, pemphigus Vulgaris, pemphigus foliaceous, and epidermolysis bullosa acquisita Vasculitic dermatoses such as leukocytoclastic vasculitis and urticarial vasculitis Neutrophilic dermatoses such as Sweet syndrome, pyoderma gangrenosum, and Behcet syndrome Other dermatoses such as subacute cutaneous lupus erythematosus, relapsing polychondritis, granuloma annulare, loxoscelism, granuloma faciale, rosacea, panniculitis, pustular psoriasis, nodulocystic acne, and rhinosporidiosis Autoimmune disease Cutaneous lupus erythematosus. Dapsone is effective and safe in persons with moderate, severe, or refractory cutaneous lupus erythematosus.[rx] 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.[rx] Chronic spontaneous urticaria. Dapsone is effective and safe for the treatment of second-line therapy for people with chronic spontaneous urticaria in those for whom antihistamines and other first-line agents have failed.[rx][rx] Relapsing polychondritis. There are no clinical trials but there are many cases reports that dapsone is effective at doses of 25 mg/day to 200 mg/day for treatment of relapsing polychondritis. Contraindications of Dapsone Gel glucose-6-phosphate dehydrogenase (G6PD) deficiency deficiency of the blood enzyme cytochrome b5 reductase significant anemia liver problems Anemia from Pyruvate Kinase and G6PD Deficiencies Absolute contraindications to the use of dapsone are prior hypersensitivity to dapsone or its derivatives including agranulocytosis and hypersensitivity syndrome. Deaths from agranulocytosis, aplastic anemia, and other blood dyscrasias have been reported with dapsone administration. Relative contraindications to the use of dapsone include allergy to sulfonamide antibiotics, significant cardiopulmonary disease, significant liver or renal function impairment, or pre-existing peripheral neuropathy. For the treatment of women who are pregnant, dapsone is a category C drug. Therefore, it should be used with caution only if benefits outweigh risks. According to the American Academy of Pediatrics, dapsone is listed as a “maternal medication usually compatible with breastfeeding.” Allergies to Sulfone Dosage of sulphonylbisbenzamine Strengths: 100 mg; 25 mg Leprosy – Lepromatous 50 to 100 mg orally once a day for 2-5 years. Leprosy – Tuberculoid 100 mg orally once a day for 6 months. Rifampin is additionally recommended to reduce the incidence of dapsone resistance. If the disease relapses, this regimen should be repeated. Dermatitis Herpetiformis 50 mg orally once a day continued on a life-long basis. Dosage may be advanced to 300 mg/day. Dosage reduction to a minimum maintenance level as soon as possible is recommended. Pneumocystis Pneumonia 100 mg orally once a day for 14 to 21 days. Used in combination with trimethoprim. Pneumocystis Pneumonia Prophylaxis 100 mg orally twice a week. Therapy should be continued on a life-long basis. The addition of pyrimethamine appears to significantly increase the activity of dapsone for PCP prophylaxis. Toxoplasmosis – Prophylaxis 100 mg orally twice a week continued on a life-long basis. Pediatric Dose for Leprosy 1 to 2 mg/kg (up to 100 mg) orally once a day. Pediatric Dose for Pneumocystis Pneumonia Prophylaxis 1 month 2 mg/kg/day (up to 100 mg) orally once a day. Alternate dosing > 1 month 4 mg/kg orally once weekly. Maximum dose = 200 mg. Pediatric Dose for Toxoplasmosis > 1 month g2 mg/kg/day (or 15 mg/m2) orally once a day. Maximum dose = 25 mg. Dapsone should be administered as part of combination therapy for prophylaxis of toxoplasmosis. Side Effects of sulphonylbisbenzamine More common easy bruising itching, dryness, redness, scaling, or peeling of the skin loss of hair numbing or tingling sensation in the hands or feet signs of depression (e.g., poor concentration, changes in weight, changes in sleep, decreased interest in activities) signs of infections (e.g., fever or chills, sore throat) signs of liver problems (e.g., nausea, vomiting, diarrhea, loss of appetite, weight loss, yellowing of the skin or whites of the eyes, dark urine, pale stools) unusual tiredness or weakness Back, leg, or stomach pains bluish fingernails, lips, or skin difficult breathing fever loss of appetite pale skin skin rash unusual tiredness or weakness Common Hematologic: Hemolytic anemia, methemoglobinemia, leukopenia, and agranulocytosis Cutaneous hypersensitivity reactions: Mebilliform eruption, exfoliative erythroderma, drug-induced lupus erythematosus, and toxic epidermal necrolysis Neurologic: Peripheral neuropathy, predominantly motor loss Psychiatric: Psychosis and insomnia Eyes: Blurred vision Ear, nose, and throat: Tinnitus and vertigo Cardiac: Tachycardia Pulmonary: Pulmonary Eosinophilia Hepatic: Hepatitis, dapsone syndrome, cholestatic jaundice, and hypoalbuminemia without proteinuria Gastrointestinal: Nausea, vomiting, abdominal pain, anorexia, and pancreatitis Renal: Nephrotic syndrome, albuminur signs of anemia (low red blood cells; e.g., dizziness, pale skin, unusual tiredness or weakness, shortness of breath) signs of infection (fever, severe chills, sore throat, mouth ulcers) signs of an allergic reaction (e.g., rash, hives, swelling of the lips or face, difficulty breathing) Rare severe vomiting signs of methemoglobinemia (e.g., headache, fatigue, dizziness, shortness of breath, grey or bluish skin colour, especially of lips, mouth and nail beds) signs of pancreatitis (e.g., abdominal pain on the upper left side, back pain, nausea, fever, chills, rapid heartbeat, swollen abdomen) Itching, dryness, redness, scaling, or peeling of the skin, or loss of hair mood or other mental changes numbness, tingling, pain, burning, or weakness in hands or feet sore throat unusual bleeding or bruising yellow eyes or skin blurred vision dizziness fast heartbeat fatigue headache loss of appetite nausea or vomiting skin rash or itch trouble sleeping Drug Interactions of sulphonylbisbenzamine azole antifungals (e.g., fluconazole, itraconazole, ketoconazole, voriconazole) anti-malarial medications (e.g., chloroquine, hydroxychloroquine, primaquine) benzoyl peroxide celecoxib flutamide nitrates (e.g., isosorbide dinitrate, isosorbide mononitrate, nitroglycerin) lidocaine metoclopramide phenazopyridine phenobarbital chloroquine clarithromycin didanosine hydroxychloroquine mefloquine nicardipine probenecid proguanil protease inhibitors; anti-HIV medications (lopinavir, ritonavir, saquinavir) St. John’s wort sodium nitrite sulfadiazine sulfamethoxazole sulfasalazine tetracaine trimethoprim sulfisoxazole If you are taking any of these medications, speak with your doctor or pharmacist. Depending on your specific circumstances, your doctor may want you to: stop taking one of the medications, change one of the medications to another, change how you are taking one or both of the medications, or leave everything as is. Pregnancy Category of sulphonylbisbenzamine Pregnancy This medication should not be used during pregnancy unless the benefits outweigh the risks. If you become pregnant while taking this medication, contact your doctor immediately. Breast-feeding This medication passes into breast milk. If you are a breast-feeding mother and are taking dapsone, it may affect your baby. Talk to your doctor about whether you should continue breast-feeding. This medication should not be used for children less than 1-month-old. The safety and effectiveness of using this medication have not been established for children less than 12 years old. References DrugBank https://www.drugbank.ca/legal/terms_of_use http://www.drugbank.ca/drugs/DB00250 http://www.drugbank.ca/drugs/DB00250#targets http://www.drugbank.ca/drugs/DB00250 https://www.drugs.com/mtm/dapsone.html https://pubchem.ncbi.nlm.nih.gov/compound/Dapsone https://pubchem.ncbi.nlm.nih.gov/compound/Dapsone-hydroxylamin FDA Pharm Classes https://www.fda.gov/about-fda/about-website/website-policies#linking https://dailymed.nlm.nih.gov/dailymed/browse-drug-classes.cfm https://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/ucm162549.htm LiverTox https://www.ncbi.nlm.nih.gov/books/n/livertox/Dapsone/ NCI Thesaurus (NCIt) https://www.cancer.gov/policies/copyright-reuse https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&ns=NCI_Thesaurus&code=C415 EPA DSSTox https://www.epa.gov/privacy/privacy-act-laws-policies-and-resources https://comptox.epa.gov/dashboard/DTXSID4020371 HSDB https://pubchem.ncbi.nlm.nih.gov/source/hsdb/5073 Sanford-Burnham Center for Chemical Genomics https://pubchem.ncbi.nlm.nih.gov/bioassay/1996#section=Data-Table ChemIDplus https://chem.nlm.nih.gov/chemidplus/sid/0000080080 https://chem.sis.nlm.nih.gov/chemidplus/ DTP/NCI https://dtp.cancer.gov/dtpstandard/servlet/dwindex?searchtype=NSC&outputformat=html&searchlist=756716 https://dtp.cancer.gov/dtpstandard/servlet/dwindex?searchtype=NSC&outputformat=html&searchlist=6091 European Chemicals Agency (ECHA) https://echa.europa.eu/web/guest/legal-notice https://echa.europa.eu/substance-information/-/substanceinfo/100.001.136 https://echa.europa.eu/information-on-chemicals/cl-inventory-database/-/discli/details/57234 ClinicalTrials.gov https://clinicaltrials.gov/ct2/about-site/terms-conditions#Use https://clinicaltrials.gov/ DailyMed https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=DAPSONE Drug Gene Interaction database (DGIdb) http://www.dgidb.org/drugs/DAPSONE EPA Chemical and Products Database (CPDat) https://www.epa.gov/privacy/privacy-act-laws-policies-and-resources https://comptox.epa.gov/dashboard/DTXSID4020371#exposure https://www.epa.gov/chemical-research/chemical-and-products-database-cpdat EU Clinical Trials Register https://www.clinicaltrialsregister.eu/ EU REGULATION (EC) No 1272/2008 https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=uriserv%3AOJ.L_.2018.115.01.0001.01.ENG Hazardous Chemical Information System (HCIS), Safe Work Australia http://hcis.safeworkaustralia.gov.au/HazardousChemical/Details?chemicalID=1149 NITE-CMC http://www.safe.nite.go.jp/english/ghs/08-mhlw-0009e.html FDA Orange Book https://www.fda.gov/about-fda/about-website/website-policies#linking https://www.fda.gov/Drugs/InformationOnDrugs/ucm129662.htm FDA/SPL Indexing Data https://www.fda.gov/about-fda/about-website/website-policies#linking https://www.fda.gov/ForIndustry/DataStandards/SubstanceRegistrationSystem-UniqueIngredientIdentifierUNII/ NIST Mass Spectrometry Data Center http://www.nist.gov/srd/nist1a.cfm MassBank of North America (MoNA) https://mona.fiehnlab.ucdavis.edu/documentation/license http://mona.fiehnlab.ucdavis.edu/spectra/browse?inchikey=MQJKPEGWNLWLTK-UHFFFAOYSA-N SpectraBase https://spectrabase.com/spectrum/5KssvTfXUvu https://spectrabase.com/spectrum/6h9HC6bYhaC https://spectrabase.com/spectrum/3Oss9682gEu https://spectrabase.com/spectrum/IooHj7U67r8 https://spectrabase.com/spectrum/7a9pC0azatx https://spectrabase.com/spectrum/LZ0kCLOJJTS https://spectrabase.com/spectrum/7edrZTKsc27 https://spectrabase.com/spectrum/AI3YeXFrwD3 https://spectrabase.com/spectrum/DhCwTAqcY7 https://spectrabase.com/spectrum/Gd9mE0Byvai https://spectrabase.com/spectrum/2KVU90bmOyW https://spectrabase.com/spectrum/CPh9PmrjrDu https://spectrabase.com/spectrum/KNps2LhAJUo NIPH Clinical Trials Search of Japan https://rctportal.niph.go.jp/en/ Springer Nature https://pubchem.ncbi.nlm.nih.gov/substance/341140379 Thieme Chemistry https://creativecommons.org/licenses/by-nc-nd/4.0/ WHO ATC https://www.whocc.no/copyright_disclaimer/ https://www.whocc.no/atc/ https://www.whocc.no/atc_ddd_index/ Wikipedia https://en.wikipedia.org/wiki/Dapsone https://www.webmd.com/drugs/2/drug-6744/dapsone-oral/details/list-contraindications https://www.ncbi.nlm.nih.gov/books/NBK470552/ https://chealth.canoe.com/drug/getdrug/aczone https://chealth.canoe.com/drug/getdrug/dapsone Wiley https://pubchem.ncbi.nlm.nih.gov/substance/?source=wiley&sourceid=110875 MeSH https://www.ncbi.nlm.nih.gov/mesh/68003622 http://www.nlm.nih.gov/mesh/meshhome.html https://www.ncbi.nlm.nih.gov/mesh/68005493 https://www.ncbi.nlm.nih.gov/mesh/68000962 https://www.ncbi.nlm.nih.gov/mesh/68007917 https://www.ncbi.nlm.nih.gov/mesh/68000890 https://pubchem.ncbi.nlm.nih.gov Show More