Side Effects of Chloroquine and Hydroxychloroquine on Skeletal Muscle: a Narrative Review

Abstract

Purpose of Review Concerning adverse neuromuscular effects, there are quite a few reports about the incidence and prevalence of chloroquine (CQ) and hydroxychloroquine (HCQ) myopathy. Given the above, I decided to explore the relationships of these drugs with skeletal muscle in an attempt to clarify how they affect the muscle now and in the future, as millions of people are using CQ and HCQ. Recent Findings The literature review identified 28 publications about CQ/HCQ myopathy, totaling 56 patients, from 1963 to 2020. A compilation of all patients was carried out by computing demographic features, clinical aspects, laboratory exams, and clinical evolution. All articles but two represented a large series about incidence and prevalence of the myopathy. Fifty-nine percent used QC, mean daily dose was 393 mg per day, and mean duration of treatment was 37 months. The predominant underlying diseases were rheumatoid arthritis (42.8%) and lupus erythematosus (26.8%). Respiratory distress was present in 12.5% in patients with proximal muscle weakness (87.2%). Dysphagia and cervical and axial weakness were observed in a smaller percentage. Creatine kinase was elevated in 60.7%, and EMG showed a myopathic pattern in 54%. Muscle biopsy showed a vacuolar pattern in 53.7%, and curvilinear bodies (CB) were the predominant ultrastructural finding (86.8%). After drug withdrawal, 85.4% of patients improved, and 12.7% died from other causes than myopathy. Summary CQ and HCQ myopathy has been known for a long time, but the incidence is low, being described only with long-term use. The use of these drugs for a short period has not been reported, although a prolonged elimination half-life of these drugs actually exists.

Chloroquine and Hydroxychloroquine Myopathy: Clinical Spectrum and Treatment Outcomes

“…Herein, we showed that longer exposure and higher cumulative doses are associated with higher disability and more common swallowing and cardiac involvement. Neuromuscular complications seem to be a late complication, as none of our patients and only very rare cases reported by others developed a myopathy with <6 months of exposure to CQ or HCQ ( 6 , 15 ). Hence, it would be less likely for a brief exposure to these drugs, such as when used during a viral infection, to cause a myopathy.…”

“…The clinical phenotype associated with CQ/HCQ myopathy has been mainly described in the literature as a proximal myopathy ( 5 , 8 , 15 ). In this study, we demonstrate that CQ/HCQ myopathy is associated with a wide spectrum of clinical presentations consisting of one or a combination of the following: proximal limb, swallowing, respiratory, and axial muscle weakness.…”

“…There is a major gap in understanding the mechanism of action of CQ and HCQ, their safety profile, and recommended dosing ( 15 ). Herein, we showed that longer exposure and higher cumulative doses are associated with higher disability and more common swallowing and cardiac involvement.…”

Putative mechanisms explaining neuro-COVID

“…From remdesivir, ritonavir, and lopinavir it is known that they occasionally trigger rhabdomyolysis ( Ghasemiyeh et al, 2020 ). From chloroquine it is well known that it may cause toxic myopathy ( Carvalho, 2020 ). Known side effects of tocilizumab include arterial hypertension, hyperlipidemia, obesity, infections, bowel ulceration, and heart failure ( Saito et al, 2020 ), which may secondarily cause cerebrovascular disease.…”

SARS-CoV-2 as Well as Anti-COVID-19 Treatment May Cause Rhabdomyolysis

“… 3 From chloroquine it is known that it can be myotoxic and can cause permanent myopathy. 4 Steroids can induce mitochondrial myopathy. Tocilizumab has been reported to occasionally induce myositis.…”