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.
