Published: 2 September 2015

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Risks of Hydroxychloroquine

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Prescriber Update 36(3): 36–37
September 2015

The Centre for Adverse Reactions Monitoring (CARM) receives several reports each year of serious adverse reactions to hydroxychloroquine. Healthcare professionals are encouraged to report all suspicions of adverse reactions to hydroxychloroquine and other medicines to CARM (https://nzphvc.otago.ac.nz/).

Hydroxychloroquine, originally used as an antimalarial agent, has beneficial effects on mucocutaneous symptoms in systemic lupus erythematosus. It is also used for the skin rash of discoid lupus erythematosus. A number of rare but serious adverse reactions can occur with its use and are usually associated with long-term therapy.

Ophthalmological Reactions

In the last two years, CARM has received two reports of ophthalmological reactions associated with hydroxychloroquine. Of the two reports, one report was of scotoma and one report was of retinal disorder.

Retinopathy is a serious adverse reaction due to the progressive and irreversible nature of the changes¹. Retinopathy is usually associated with long-term use (greater than five years), although it can occur earlier.

Other risk factors include high dose (both daily dose and cumulative dose), an age greater than 60 years, and renal or hepatic dysfunction¹. Patients with a history of retinopathy or pre-existing maculopathy should not be treated with hydroxychloroquine.

Corneal changes can also occur with hydroxychloroquine use, although these often subside following a dose reduction or discontinuation of the medicine².

All patients should have an ophthalmological examination prior to treatment initiation and at least six monthly thereafter². Local guidance of monitoring requirements should also be considered.

Any indication of abnormality in the visual field or retinal macular areas, or any visual symptoms which are not fully explainable by difficulties of accommodation or corneal opacities require immediate discontinuation of hydroxychloroquine and the patient closely observed for possible progression^1,2.

There is some evidence that early detection means that retinal changes reverse upon discontinuation of the medicine².

Cardiomyopathy and QT Prolongation

CARM have received reports of cardiac arrest, cardiac failure, cardiomyopathy, endocarditis and myocarditis associated with hydroxychloroquine treatment.

Long-term use and high doses of hydroxychloroquine are risk factors for the development of cardiomyopathy. Cardiac failure, conduction disorders (including QT prolongation and Torsades de Pointes) and sudden cardiac death are consequences of the cardiomyopathy.

Diagnosis of cardiomyopathy can be difficult due to the lack of specificity of symptoms and concurrent cardiovascular involvement of the underlying disease³.

When detected early, hydroxychloroquine induced cardiomyopathy may be reversible⁴. Therefore, patients requiring long-term therapy should be appropriately monitored. If cardiac complications due to hydroxychloroquine are suspected, treatment should be discontinued.

In patients with risk factors for QT prolongation, hydroxychloroquine should be used with care. Reassessment of treatment should occur should any new risk factors for QT prolongation be identified for individual patients. Further information on risk factors for QT prolongation is available in a previous issue of Prescriber Update⁵.

Haematological Reactions

Two cases of blood dyscrasias requiring hospital treatment have been reported to CARM in the last two years.

Hydroxychloroquine treatment can cause bone marrow depression, anaemia, aplastic anaemia, leucopenia, thrombocytopenia, agranulocytosis, and porphyria exacerbation.

Risk factors include use of high doses and long-term use. Periodic full blood counts are recommended for patients on long-term therapy. Treatment should be discontinued if hydroxychloroquine treatment is identified as the cause of any of these serious blood dyscrasias².

Neurological and Neuromuscular Reactions

In New Zealand, there have been two reports of peripheral neuropathy associated with hydroxychloroquine use since 1 January 2010. In one report, the patient’s symptoms improved after the drug was discontinued.

Reports of neuromyopathy in the literature generally involve proximal muscle weakness in the lower extremities together with diminished tendon reflexes³. Muscle weakness may be progressive and atrophy of the proximal muscles can occur². The manifestations of neuromyopathy are reversible on discontinuation of treatment^2,3.

All patients on long-term therapy should be questioned and examined periodically for muscle weakness². Testing should include knee and ankle reflex response².

References

1. Rodriguez-Caruncho C, Bielsa Marsol I. 2014. Antimalarials in dermatology: mechanism of action, indications, and side effects. Actas Dermosifiliograficas 105(3): 243–252.
2. Sanofi-Aventis NZ Ltd. 2014. Plaquenil Data Sheet. URL: www.medsafe.govt.nz/profs/datasheet/p/Plaqueniltab.pdf (accessed 30 July 2015).
3. Tonnesmann E, Kandolf R, Lewalter T. 2013. Chloroquine cardiomyopathy — a review of the literature. Immunopharmacology and Immunotoxicology 35(3): 434–442.
4. Yogasundaram H, Putko BN, Tien J, et al. 2014. Hydroxychloroquine-Induced Cardiomyopathy: Case Report, Pathophysiology, Diagnosis and Treatment. Canadian Journal of Cardiology 30: 1706–1715.
5. Medsafe. 2010. Drug-induced QT prolongation and Torsades de pointes — the facts. Prescriber Update 31(4): 27–29. URL: www.medsafe.govt.nz/profs/PUArticles/DrugInducedQTProlongation.htm (accessed 6 Aug 2015).