Dapsone Flashcards
What is Dapsone?
A sulfone drug
An antibiotic with antiinflammatory actions
Bioavailability of Dapsone
80%
Peak plasma conc = 2 - 6 hours
Where is Dapsone metabolised and exrected?
Metabolised in the liver
Excreted in the urine
MoA of Dapsone
Inhibits neutrophil myeloperoxidase, thus reduces damage from neutrophil respiratory burst mediated by this enzyme
Inhibits neutrophil chemotaxis
**IgA adherance is also inhibited **
**Inhibits Eosinophil myleoperoxidase **
Dose of Dapsone?
Available in 25 and 100mg tablets.
Initial = 50mg / day
Up to 200 mg / day
Major side effects of dapsone
Common: P
- Haemolysis
- Methaemaglobinaemia
Uncommon:
- GI: dyspepsia, nausea
Rare: L
- agranulocytosis (occur 3 -12 weeks post)
- peripheral motor neuropathy
- Dapsone hypersensitivity
Idiosyncratic (labelled *
pharmacologic = dose dependent (labelled P)
What is dapsone hypersensitivty sydrome?
Rare, idosyncratic reaction
Fever,
Hepatitis (can lead to liver failure)
Generalised cutaneous eruption (morbilliform –> TEN)
Hypothyroidism
May be fatal
Predictor of dapsone hypersensitivty syndrome?
HLA B13: 01
esp in chinese populations
Indications for dapsone?
Consistent efficacy
○ DH
○ Linear IgA dermatosis/bullous dermatosis of childhood
○ Bullous eruption in SLE
○ Leprosy (as combination therapy)
○ EED
Variable:
Neutrophillic dermatoses
- Sweets
- Bechets
- PG
Immunobullous disease
- BP
- PV, PF,
- IgA pemphigus
- Bullous eruption of SLE
- MMP
CSVV
Granuloma faciale
Contraindications to Dapsone?
Prior hypersensitivty to dapsone
Low G6PD level
Significant cardiopulmonary disease
Dapsone and pregnancy
Category B3 (insufficent data)
Can be used if benefits outweigh the risks
Dapsone and lactation
Dapsone is found in breast milk and can cause hemolytic anemia in breastfed infants;
Therefore best avoided, can be used if benefits outweight risks.
Drugs that may increase dapsone levels (and side effects)?
Probenecid
(via decreased renal clearance),
Trimethoprim,
other folate antagonists such as methotrexate.
Sulfonamides and hydroxychloroquine
increase the oxidative stress on RBCs and may worsen hemolysis.
Pre-treatment Ix of Dapsone
G6PD
HLA B13:01 - in asian
FBC, film
UEC
LFT
Consider B12, folate and iron studies if anaemic
Monitoring bloods for dapsone
FBE + film weekly for 4 weeks, then every 2 weeks until 12 weeks, then every 3-4 months (or sooner with significant dose increases)
Reticulocyte count - up to 12% is acceptable
Methaemoglobin
UEC, LFTs, Urinalysis, CMP
Acceptable reticulocyte value for Dapsone?
12%
Paeds dosing of Dapsone?
0.5 - 1 mg / kg / day
Significance of methaemoglobinaemia
Dose-related
Symptoms: headache, lethargy, SOB, cyanosis, cardiopulmonary symptoms
**Cannot **accurately predict the amount of methaemoglobin based on degree of cyanosis
Percentage of methaemoglobin may not reflect clinical significance
* 10% methaemoglobin and total Hb of 150 = functional Hb of 135
* 10% methaemoglobin and total Hb of 100 = 100 functional Hb of 90 and will likely develop symptoms of anaemia
* Patients with significant cardiac or pulmonary disease are less able to tolerate low levels of methaemoglobin
How to treat methaemoglobinaemia?
Emergency management:
* oral methylene blue 100-300 mg daily (contraindicated in G6PD deficiency)
* plasma exchange
Cimetidine 400mg TDS: may reduce methaemoglobin
