Antimalarials

Indications

Hydroxychloroquine (Plaquenil) and chloroquine (Aralen) are 4-aminoquinoline antimalarial drugs that possess modest DMARD activity. They are indicated for the treatment of rheumatoid arthritis and systemic lupus erythematosus. The onset of action of these drugs is longer than that of other DMARDs, and their side effects are relatively mild. Because of this, these agents show promise as ingredients of combination therapies for rheumatoid arthritis.

Pharmacology

Hydroxychloroquine and chloroquine are similar in activity; however, hydroxychloroquine has a lower incidence 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.

Side effects

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, irreversible retinopathy with resultant blindness, is dose related and can be minimized by maintaining a daily dose of hydroxychloroquine less than 6.5 mg/kg or chloroquine less than 4 mg/kg. Eye examinations should be performed regularly during treatment with these drugs. Severe hematological toxicity (neutropenia, thrombocytopenia, aplastic anemia) is rare. Reversible side effects observed during high-dose, long-term therapy with the aminoquinolines include lichenoid skin lesions, leukopenia, neuromyopathy, hair loss, sensitivity to sunburn, and changes in the electrocardiogram.

Precautions

The aminoquinolines accumulate in lung, kidney, andliver; thus, any preexisting pathology in these tissuescontraindicates their use. Similarly, any ocular pathologyprecludes their use. Psoriasis and porphyria are frequentlyexacerbated by the administration of theaminoquinolines.
Aminoquinolines can increase plasma concentrationsof penicillamine, hence the potential for serioushematological or renal toxicity. Similarly, aminoquinolinescan increase digoxin levels. Gold and an aminoquinolineprobably should not be administered concurrentlybecause of the propensity of each to producedermatitis.

Raw materials

Preparation Products