What is known about impaired hearing or tinnitus as an adverse effect of hydroxychloroquine? Is it

Fråga: What is known about impaired hearing or tinnitus as an adverse effect of hydroxychloroquine? Is it a reversible effect? The question concerns a patient with Sjogren´s syndrome, who also has impaired hearing and tinnitus. The patient´s rheumatologist wants to introduce hydroxychloroquine (Plaquenil) treatment. The question comes from the otologist.

Sammanfattning: Hearing disorders, such as impaired hearing and tinnitus, have been reported for hydroxychloroquine as well as for chloroquine. Cases of both reversible and irreversible hearing loss have been published.

Svar: Hydroxychloroquine is a 4-hydroxyamino derivative, which is used as an antimalarial and anti-inflammatory drug. It is closely related both structurally and pharmacologically to chloroquine. Both drugs have a long terminal half-life (1). Questions about chloroquine induced hearing loss have previously been documented in Drugline. Both reversible and irreversible cases of hearing disorders after chloroquine treatment have been published. Hearing disorders have been reported after treatment for inflammatory diseases as well as for malaria prophylaxis or -treatment (2,3,4). It is known that both chloroquine and hydroxychloroquine is accumulated in melanin containing tissues, such as the stria vascularis in the inner ear (1). This accumulation might cause a vascular damage, which in turn may alter endolymph composition and consequently the receptor cells of the audiovestibular system (5).

A literature search revealed four cases of hearing disorders in connection to hydroxychloroquine treatment. One report describes two cases of irreversible deafness. The first patient noticed reduced hearing after daily treatment for five years with hydroxychloroquine (400 mg/day) for systemic lupus erythematosus (SLE). Audiogram showed bilateral sensineuronal hearing loss, 20-40 dB on the right side and 20-50 dB on the left. No improvement was seen after withdrawal of treatment. The other patient had been treated for periods of three months during three years (400 mg/day) for connective tissue disease. Later the dose was changed to continuous treatment of 200 mg daily due to diagnosis of SLE. Within a month he noticed reduced hearing. Hydroxychloroquine treatment continued, and two years later his hearing loss was 5-15 dB on the right side and 5-35 dB on the left. Treatment was stopped, but his hearing was not improved eight months later (6). Another report describes a woman with rheumatoid arthritis, who five months after initiation of therapy with hydroxychloroquine (400 mg/day) had reduced hearing and tinnitus. The hearing loss was 10-35 dB on the right side and 10-25 dB on the left. Two weeks after hydroxychloroquine was discontinued her tinnitus disappeared, and two months later her hearing had improved with a normal pure tone audiogram (7). The last report is of a 7-year old girl, treated with hydroxychloroquine (200 mg/day) for idiopathic pulmonary haemosiderosis for the past two years, who developed unilateral sensineuronal hearing loss (8).

In the Swedish adverse drug reaction register there are six reports of hearing disorders (of a total of 63 reports) related to hydroxychloroquine treatment. Of these are four impaired hearing, one deafness and one dysacusis. For chloroquine the number is 22 (out of a total of 325 reports). The reactions have appeared both after treatment of rheumatoid arthritis and malaria prophylaxis. Cases have been described, which probably will be irreversible (9).