Hydroxychloroquine

Cardiomyopathy resulting in cardiac failure, sometimes fatal, has been reported (symptoms may present as atrioventricular block, pulmonary hypertension, sick sinus syndrome, or as cardiac complications), and may appear during acute or chronic therapy. Monitor for signs/symptoms of cardiac compromise; discontinue treatment promptly if signs and symptoms of cardiomyopathy occur. In a scientific statement from the American Heart Association, hydroxychloroquine has been determined to be an agent that may either cause direct myocardial toxicity or exacerbate underlying myocardial dysfunction (magnitude: major) (AHA [Page 2016]). Consider chronic toxicity if conduction disorders (eg, bundle branch block, atrioventricular heart block) as well as biventricular hypertrophy are diagnosed. May also be associated with QT interval prolongation; ventricular arrhythmia and torsades de pointes have been reported (avoid concurrent use of other medications which may prolong the QT interval).

Skin reactions to hydroxychloroquine may occur; use with caution in patients on concomitant medications with a propensity to cause dermatitis.

Bone marrow suppression (eg, agranulocytosis, anemia, aplastic anemia, leukopenia, thrombocytopenia) have been reported; periodically monitor CBC during prolonged therapy. Discontinue treatment if signs/symptoms of severe blood disorder not attributable to the underlying disease occur.

Severe hypoglycemia, including life-threatening loss of consciousness, has been reported in patients with and without concomitant use of antidiabetic agents. Advise patients of risk of hypoglycemia and associated signs/symptoms; discontinue use in patients who develop severe hypoglycemia.

Proximal myopathy or neuromyopathy, leading to progressive weakness, proximal muscle atrophy, depressed tendon reflexes, and abnormal nerve conduction may occur, especially with long-term therapy. Curvilinear bodies and muscle fiber atrophy with vacuolar changes have been noted on muscle or nerve biopsy. Muscle strength (especially proximal muscles) and reflexes should be assessed periodically during long term therapy.

Suicidal behavior has been reported rarely.

Retinal toxicity, potentially causing irreversible retinopathy, is predominantly associated with high daily doses and a duration of >5 years of use of chloroquine or hydroxychloroquine in the treatment of rheumatic diseases. Other major risk factors include concurrent tamoxifen use, renal impairment, lower body weight, and the presence of macular disease. Daily hydroxychloroquine (base) doses >5 mg/kg actual body weight were associated with an ~10% risk of retinal toxicity within 10 years of treatment and an almost 40% risk after 20 years of therapy. Risk is most accurately assessed on the basis of duration of use relative to daily dose/body weight (Marmor [AAO 2016]; Melles 2014). Based on these risks, the American Academy of Ophthalmology (AAO) recommends not exceeding a daily hydroxychloroquine dosage of 5 mg/kg using actual body weight. Previous recommendations to use ideal body weight are no longer advised; very thin patients in particular were at increased risk for retinal toxicity using this practice. Current AAO guidelines do not specifically address dosing in obese patients. AAO also recommends baseline screening for retinal toxicity and annual screening beginning after 5 years of use (or sooner if major risk factors are present) (Marmor [AAO 2016]). If ocular toxicity is suspected, discontinue and monitor closely; retinal changes and visual disturbances may progress after discontinuation. A baseline ocular exam is recommended within the first year of initiating hydr

Although the manufacturer's labeling recommends hydroxychloroquine be used with caution in patients with G6PD deficiency due to a potential for hemolytic anemia, there is limited data to support this risk. Many experts consider hydroxychloroquine, when given in usual therapeutic doses to WHO Class II and III G6PD deficient patients, to probably be safe (Cappellini 2008; Glader 2017; Luzzatto 2016; Youngster 2010). Safety in Class I G6PD deficiency (ie, severe form of the deficiency associated with chronic hemolytic anemia) is generally unknown (Glader 2017). In a retrospective chart review, no incidence of hemolytic anemia was found among the 11 patients identified with G6PD deficiency receiving hydroxychloroquine therapy, despite >700 months of exposure (all patients were African-American and located in the US) (Mohammad 2017). In addition, the ACR Rheumatology guidelines do not mention the need to evaluate G6PD levels prior to initiation of therapy (Singh 2015).

Use with caution in patients with gastrointestinal disorders.

Use with caution in patients with hepatic impairment, alcoholism, or concurrent therapy with hepatotoxic agents.

Use with extreme caution in patients with porphyria; may exacerbate or precipitate disease.

Use with extreme caution in patients with psoriasis; may exacerbate or precipitate disease.

Use with caution in patients with renal impairment; dosage reduction may be needed. Special populations:

Pediatric patients have an increased sensitivity to aminoquinolones. Safety and efficacy have not been established for chronic use in children for juvenile idiopathic arthritis or for systemic lupus erythematosus. Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.