How are antimalarials used in the treatment of rheumatic diseases such as RA or SLE?
Antimalarials are the least toxic of all DMARDs and can be safely combined with other DMARDs. They are particularly effective in early treatment or add-on therapy of RA patients with mild to moderate disease manifestations. HCQ is the main antimalarial used.
Dosage:
- HCQ (Plaquenil), 200 to 400 mg/day (<5 mg/kg actual body weight).
- Chloroquine (Aralen), 250 mg/day (≤3.0 mg/kg ideal body weight).
- Quinacrine (Atabrine), 100 to 200 mg/day. Made by a compounding pharmacy. Can be used in dose of 50 to 100 mg/day as adjunctive therapy with HCQ and chloroquine without increasing retinal toxicity.
- There is no effect of food on absorption of antimalarials. About 50% is excreted in urine. Patients with renal insufficiency (<30 mL/minute) should receive a reduced dose, plasma levels (HCQ) monitored, and receive a close evaluation for side effects (ocular, myopathy, cardiomyopathy). Antimalarials are not effectively dialyzable.
Side effects (hydroxychloroquine):
- • Nausea and vomiting (5%): this is less likely to occur if start at half dose and titrate up over 2 to 4 weeks.
- • Retinal toxicity: The risk is proportional to the dose and length of exposure for HCQ. When dosed at <5 mg/kg (actual weight), the risk is <2% at 10 years, but can be up to 20% after 20 years. After 20 years, the annual risk is approximately 4%. There is increased risk with renal insufficiency and tamoxifen use.
- • Central nervous system effects (2%): these can include headache, dizziness, and tinnitus.
- • Myopathy and neuropathy: a neuromyopathy can rarely occur usually after prolonged use or in patients with renal insufficiency. Creatine phosphokinase can be normal or slightly elevated. The muscle pathology shows a vacuolar myopathy with the classic findings of curvilinear and/or myeloid bodies. A cardiomyopathy with similar histologic features presenting as congestive heart failure can also occur in this setting. Patients on antimalarials for over 5 to 10 years may benefit from periodic cardiac troponin I and brain natriuretic peptide testing to pick up early toxicity.
- • Aplastic anemia (quinacrine): this may be heralded by a lichen planus rash.
- • Hemolysis: this is rare unless the patient has a glucose-6-phosphate dehydrogenase (G6PD) deficiency.
- • Rash: an acute erythroderma-like reaction can happen but is rare. This might be more common in patients with psoriasis or dermatomyositis. Hyperpigmentation of the skin (gray-black with HCQ and chloroquine, yellow with quinacrine) is common with long-term use. Bleaching of hair has been described.
Monitoring: a baseline retinal examination including automated visual fields plus spectral-domain optical coherence tomography (SDOCT) is recommended. Low-risk patients may have follow-up retinal screening at year 5 and then yearly. However, some experts recommend yearly examinations regardless of risk
