Hydroxychloroquine (Plaquenil) and chloroquine (Ara-len) are 4-aminoquinoline antimalarial drugs that pos-sess modest DMARD activity. They are indicated for the treatment of rheumatoid arthritis and systemic lu-pus erythematosus; The onset of action of these drugs is longer than that of other DMARDs, and their side ef-fects are relatively mild. Because of this, these agents show promise as ingredients of combination therapies for rheumatoid arthritis.
Hydroxychloroquine and chloroquine are similar in ac-tivity; however, hydroxychloroquine has a lower inci-dence of ocular side effects and is used more frequently. These drugs are weak bases that enter and interfere with the functioning of lysosomes and other subcellular compartments of T- and B-lymphocytes, monocytes, and macrophages. This in turn inhibits the ability of these cells to produce and release inflammatory cytokines and hydrolytic enzymes.
Skin rashes and pruritus are common adverse effects of the 4-aminoquinoline antimalarials, as are GI effects. The incidence of the most serious toxic reaction, irre-versible retinopathy with resultant blindness, is dose re-lated and can be minimized by maintaining a daily dose of hydroxychloroquine less than 6.5 mg/kg or chloro-quine less than 4 mg/kg. Eye examinations should be performed regularly during treatment with these drugs. Severe hematological toxicity (neutropenia, thrombo-cytopenia, aplastic anemia) is rare. Reversible side ef-fects observed during high-dose, long-term therapy with the aminoquinolines include lichenoid skin lesions, leukopenia, neuromyopathy, hair loss, sensitivity to sun-burn, and changes in the electrocardiogram.
The aminoquinolines accumulate in lung, kidney, and liver; thus, any preexisting pathology in these tissues contraindicates their use. Similarly, any ocular pathol- ogy precludes their use. Psoriasis and porphyria are fre-quently exacerbated by the administration of the aminoquinolines.
Aminoquinolines can increase plasma concentra-tions of penicillamine, hence the potential for serious hematological or renal toxicity. Similarly, aminoquino-lines can increase digoxin levels. Gold and an amino-quinoline probably should not be administered concur-rently because of the propensity of each to produce dermatitis.