Published: 3 March 2022

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Out of the blue: Dapsone-induced methaemoglobinaemia

Published 3 March 2022
Prescriber Update 43(1): 7–8
March 2022

Methaemoglobinaemia is a known adverse effect of dapsone

Dapsone is a sulfone antibiotic that inhibits folic acid synthesis to prevent microbial replication. Oral dapsone is indicated for the treatment of leprosy, dermatitis herpetiformis and actinomycotic mycetoma.¹ Topical dapsone is indicated for the treatment of acne vulgaris.²

Methaemoglobinaemia is a known adverse effect of dapsone.^2,3 Varying degrees of dose-related methaemoglobinaemia occur in most individuals at daily oral doses of 200 mg or more but may occur at lower doses.³ Methaemoglobinaemia has also been reported with the use of topical dapsone.²

Methaemoglobin is formed when the iron present in haemoglobin has been altered by oxidation from the ferrous (Fe²⁺) to the ferric (Fe³⁺) state.⁴ Ferric iron is unable to bind to oxygen. Furthermore, the presence of ferric iron in the haemoglobin molecule increases the affinity of ferrous iron for oxygen, resulting in a left shift in the oxygen dissociation curve. There is usually a small amount of methaemoglobin in the blood – approximately 1 percent of total haemoglobin. An increase in the proportion of methaemoglobin leads to reduced oxygen delivery to the tissues. At high concentrations, methaemoglobin causes hypoxia and cyanosis.^4,5 Some medicines, including dapsone, have oxidative properties that can increase the proportion of methaemoglobin.⁴

Symptoms and signs of methaemoglobinaemia

The symptoms and signs of methaemoglobinaemia typically correlate with the level of methaemoglobin in the blood. Early symptoms and signs may include cyanosis and skin discolouration, dyspnoea, headache, light-headedness, fatigue, tachycardia, irritability, and lethargy. Severe methaemoglobinaemia may cause respiratory depression, change in mental status, seizures, loss of consciousness and death.⁴

Management of dapsone-induced methaemoglobinaemia

Consider the possibility of methaemoglobinaemia in patients taking dapsone who present with symptoms or signs of hypoxia. Methaemoglobinaemia is confirmed with a blood test. Consult the local laboratory for testing requirements and reference values.

Note that standard pulse-oximetry may be misleading in patients with methaemoglobinaemia.⁴ Assessment of oxygen saturation usually requires arterial blood gas analysis.

If methaemoglobinaemia occurs, discontinue treatment with dapsone.^2,3 Management of methaemoglobinaemia may also include use of oxygen and administration of methylene blue.⁶ Severe cases may require blood transfusion.

When prescribing dapsone, inform the patient or caregiver about the risk of methaemoglobinaemia and the symptoms and signs to look out for. Advise patients taking dapsone to seek medical attention urgently if they experience symptoms or signs of methaemoglobinaemia.

New Zealand case reports

Up until 31 December 2021, the Centre for Adverse Reactions Monitoring (CARM) had received 15 reports of methaemoglobinaemia, of which 5 were associated with dapsone.

References

1. New Zealand Formulary (NZF). 2022. NZF v115: Dapsone 1 January 2022. URL: nzf.org.nz/nzf_3258 (accessed 14 January 2022).
2. Allergan New Zealand Ltd. 2018. Aczone New Zealand Data Sheet 6 September 2018. URL: medsafe.govt.nz/profs/Datasheet/a/aczonegel.pdf (accessed 18 January 2022).
3. Link Pharmaceuticals Ltd. 2020. Dapsone New Zealand Data Sheet 14 September 2020. URL: medsafe.govt.nz/profs/datasheet/d/DapsoneLinktab.pdf (accessed 14 January 2022).
4. Prchal J. 2021. Methemoglobinemia. In: UpToDate 05 November 2021. URL: uptodate.com/contents/methemoglobinemia (accessed 14 January 2022).
5. The Royal College of Pathologists of Australia (RCPA). 2019. Methaemoglobin 10 January 2019. URL: rcpa.edu.au/Manuals/RCPA-Manual/Pathology-Tests/M/Methaemoglobin (accessed 18 January 2022).
6. Clinect NZ Pty Limited. 2021. Proveblue Methylene Blue New Zealand Data Sheet 7 September 2021. URL: medsafe.govt.nz/profs/Datasheet/p/proveblueinj.pdf (accessed 18 January 2022).