Interacting drugs- summary

+ Dapsone-

Charcoal                                                                                                                       activated charcoal decrease dapsones GI absoprtion and enterohepatic recycling

Didanosine                                                                                                                       possible therapeutic failure of dapsone, leading to an increase in infection

Folic acid                                                                                                                          Pyrimethamine increase hematological reactions antagonist weekly concomittant use has caused agranulocytosis during the second and third months of therapy.

Para-amino benzoic acid                                                                                      antagonise effect of dapsone, by interfering with benzoic acid the primary mechanism of action.

Probenecid                                                                                                           probenecid reduces urinary excretion of dapsone metabolites increasing plasma concentrations

Rifampin                                                                                                                    rifampin lowers dapsone levels seven to tenfold, by accelerating plasma clearance.

Trimethoprim                                                                                                             increased serum levels of both drugs appear, increasing the Dapsone pharmologic and toxic effects of each drug Dapsone 

Multibacillary leprosy

Hematologic

dose related hemolysis is the most common adverse effect, including hemolytic anemia (in patients with or without G-6_PF deficiency). Hemolysis development in almost every individua treated with 200 to 300mg dapsone every day.

Dermatologic

drug induced lupus erythematosus , phototoxicity CNS- peripheral neuropathy, haeadache, psychosis, insomnia, vertigo, paresthesia GI- nausea, vomiting, abdominal pain, anorexia.

Renal- albuminuria, the nephrotic synsdrome, renal papilllary necrosis Miscellaneous- blurred vision, tinnitus, fever, infertility, tachycardia, an infectious mononucleosis-like syndrome,pancreatitis, pulmonary eosinophilia

Severe G6PD deficiency, sulphone allergy, severe anaemia, porphyria Special precautions: Mild to moderate G6PD deficiency, sulponamide allergy, moderate anaemia, cardiac and pulmonary diseases, lactation.

Monitoring- perform blood counts weekly for the first month, monthly for 6 months and semi-annually thereafter.

Hemolysis- Give dapsone with caution to patients exposed to other conditions such as infection or diabetic ketosis capable of producing hemolysis.

Hepatic effects- toxic hepatitis and cholestatic jaundice have been reported early in therapy If abnormal, discontinue dapsone until the source of abnormality is established. Peripheral neuropathy- is an unusual complication in neoleprosy patients. Monitor loss is predominant.

Photosensitivity- photosensyivity may occur. Caution patients to take protective measures against exposure to ultraviolet or sunlight.

Warnings- Hemotologic effects- deaths associated with dapsone administration have been reported from agranulocytosis,aplastixc anemia, and other blood dyscrasias. Sore throat or jaundice may occur.

Severe anemia- treat prior to initiation of therapy and monitor hemoglobin.

Hypersensitivity- cutaneous reactions (especially bullous) include exfoliative dermatitis, toxic erythema, erythema multiforme, toxic epidermal necrolysis, morbilliform and scarlatiniform reactions, urticaria and eryerma nodosum.

Sulfone syndrome- is an unusual and potentialy fatal hypersensitivity reaction. It consists of fever, malaise, jaundice, with hepatic necrosis, exfoliative dermatitis.

Carcinogenesis- dapsone is carcinogenic in small animals.

Pregnancy- because of lack of controlled studies , use during pregnancy only if necessary.

Lactation- Because of the potential for tumerigenicity shown in animal stidies , discontune nursing or discontinue the drug.

Multibacillary leprosy Dosage:

Start with 50mg daily in adults. If full control is not acheived within the range of 50 to 300mg. higher dose may be tried.

Children- Recommended dose 1 to 2mg/kg/day for a minimum of 3 years. Maximum is usual adult dose of 100mg/day.

Overdosage- Symptoms Nausea, vomiting, hyperexcitability, can appear a few minutes andup to 24 hrs after ingestion of an overdose. Methoglobin-induced depression, convulsions, and severe cyanosis require prompt treatment Treatment

1. Empty stomach by lavage.

2. In normal and methogobin reductase deficient patients, methylene blue , 1 to 2mg/kg given slowly IV is the treatment of choice.

3. For nonemergencies, if treatment isneeded methylene blue may be given orally in doses of 3 to 5mg/kg every 4 to 6 hrs.

4. Methylene blue reduction on G-6-PD, do not give to fully expressed G-6-PD deficient patients.

Missed dose

1. If you miss a dose of this medicine, take it as soon as possible.

2. However, if it is almost time for next dose, skip the missed dose and go back to your regular dosing schedule.

3. Do not double doses.

Hemolytic anemia ( in G6PD deficiency )  Drugs causing adverse reactions- ( 585 )

1. Antimalarials ( Primaquine )

2. Chlramphenicol

3. Dapsone

4. Nalidixic acid

5. Nitrofurantoin

6. Sulfonamides

7. Aspirin

8. Phenacetin

9. P-amino salicylic acid

10. Quinidine

11. Vitamin C

12. Vitamin K

13. Cotrimoxazole

14. Probenecid

15. Procainamide

May cause photosensitivity; avoid prolonged exposure to sunlight or sunlamps.

1. Allergies- Tell your doctor if you have ever had any unusual or allergic reactions to dapsone or sulfonamidfes or other related medicines. Also tell your doctor if your are allergic to any other substances such as foods, preservatives or dyes.

2. Pregnancy- dapsone has not been shown to cause birth defects or other problems.

3. Breast feeding- not recommended

4. Children- has not shown to casue different side effects or problems than it does in adults.

5. Elderly- no specific information comparing use of dantrolene in the elderly in other age groups

6. Other medicines- tell your doctor if you are taking any of the following- Acetohydroxamic or Antidiabetes or Furazolidine or Methyldopa or Nitrofurantoin or Primaquine or Procainamide or Quinidine or Quinine or Sulfonamide or Vitamin K - use of dapsone with these medicines may increase the chance of side effects affecting the blood Dideoxyinosine - use of dideoxyinosine with dapsone may increase the effectiveness of dapsone

7. Other medical problems- tell your doctor if you have any other medical problems- Anemia or Glucose -6-phosphate dehydrogenase (G6PD ) deficiency or Metthemoglobin reductase deficiency - increased risk of severe blood disorders and a decrease in red blood cell survival Liver disease - dapsone may on rare occasion cause liver damage

8. Missed dose- If you miss a dose of this medicine take it as soon as possible. However if it is almost time for your next dose go back to your regular dosing schedule. Do not double doses.

Pharmacology:

Dapsone(4,4-diaminodiphenylsulphone- DDS) a sulfone, is bactericidal as well as as bacteriostatic against Mycobacterium leprae.

Pharmacokinetics:

Dapsone is rapidly and completely absorbed frommthe GI tract; peak plasma concentratins are reached in 4 to 8 hours. Dapsone is acetylated in the liver and the plasma half-life ranges from 10 to 50 hours. Excretion of drug is slow and a constant blood level can be maintained with the usual dosage.

Reports not available

Pregnancy Use during pregnancy only if clearly needed.

Lactation: Do not administer to nursing woman Children: Safety and efficacy in children have not been established