Toxicity Management

• DMARDs require monitoring for the duration of treatment. Therefore, they are prescribed under a shared care protocol, in which the initial monitoring and drug prescribing occurs in secondary care, and is later passed to the GP¹.

• Regarding hydroxychloroquine, the current NICE guidelines state that no routine laboratory monitoring is required as the incidence of toxicity with this particular DMARD is relatively low². Contrary to this, international guidelines advise that a baseline blood screen should be performed before commencing treatment³. Ultimately, this decision is at the clinician's discretion and will vary between patients.

• All patients should undergo a baseline ophthalmic examination and Optical Coherence Tomography (OCT) scan during their first year of taking hydroxychloroquine^2,3.

• However, those taking hydroxychloroquine for a prolonged period (over 5 years) should undergo an additional annual eye assessment. These are used to detect the development of retinopathy^2,3.

• The American Association of Ophthalmology (AAO) guidelines stipulate that monitoring should be performed based on the patient's risk factors of developing retinopathy, such as their ethnicity³. The AAO also suggest to perform a wider range of screening tests including visual field tests, spectral domain OCT (SD-OCT), multi-focal electroretinogram (mfERG), and fundus autofluorescence (FAF)³.

Many adverse effects, particularly dermatological and ENT changes, improve upon cessation or dose reduction of hydroxychloroquine⁴. However, patients who have overdosed on a significant amount of hydroxychloroquine may need to be intubated and ventilated. They should also undergo cardiovascular monitoring⁴.

To manage cardiovascular toxicity, several treatment interventions can be implemented.

• Adrenaline and/or diazepam may be administered for hypotension, dysrhythmias, QRS widening or circulatory collapse induced by hydroxychloroquine (diazepam may also be given for seizures).

• QRS widening and hypotension can be treated with sodium bicarbonate as it is alkaline. This treats the sodium channel blockage^4,5.

Type 1A antiarrhythmics should always be avoided following hydroxychloroquine overdose⁴. Emetics should be avoided as toxicity may be associated with seizures, abnormal mentation, dysrhythmias, and hypotension which increases the risk of aspiration⁵.

Regarding gastrointestinal toxicity, activated charcoal can be given to decontaminate the gastrointestinal system after hydroxychloroquine overdose. When given during the first five minutes after intake, activated charcoal absorbs aminoquinoline in the gastrointestinal tract with a 95-99% binding rate^5,6.

References:

1. NICE. What are the general principles of managing DMARDs? [Online]. 2021. [Date accessed 14/11/2021]. Available from: https://cks.nice.org.uk/topics/dmards/management/hydroxychloroquine/.

2. NICE. What monitoring is required for hydroxychloroquine?. [Online]. 2021. [Date accessed 14/11/2021]. Available from: https://cks.nice.org.uk/topics/dmards/management/hydroxychloroquine/.

3. American Academy of Ophthalmology. Recommendations on screening for Chloroquine and Hydroxychloroquine retinopathy-2016 [Online]. 2016. [Date accessed: 21/11/2021]. Available from: https://www.aao.org/clinical-statement/revised-recommendations-on-screening-chloroquine-h#top

4. Marquardt K, Albertson TE. Treatment of hydroxychloroquine overdose. Therapeutics. 2001;19(5):420-424.

5. Porta A, Bornstein K, Coye A, Montrief T, Long B, Paris M. Acute chloroquine and hydroxychloroquine toxicity: A review for emergency clinicians. American Journal of Emergency Medicine. 2020;38(10), 2209-2217.

6.Kivisto K., Neuvonen P. Activated charcoal for chroloquine poisoning. BMJ, 1993; 307(6911).