Chloroquine

Cases of cardiomyopathy resulting in cardiac failure (sometimes fatal) have been reported during long term therapy at high doses. Monitor for signs and symptoms of cardiomyopathy; discontinue if cardiomyopathy develops. Consider chronic toxicity and discontinue chloroquine if conduction disorders (bundle branch block/AV block) are diagnosed. QT prolongation, torsade de pointes, and ventricular arrhythmias (some fatal) have been reported; risk is increased with high doses. Use with caution in patients with cardiac disease, history of ventricular arrhythmias, uncorrected hypokalemia and/or hypomagnesemia, or bradycardia, and during concomitant administration with QT interval prolonging agents due to potential for QT prolongation. In a scientific statement from the American Heart Association, chloroquine has been determined to be an agent that may either cause direct myocardial toxicity or exacerbate underlying myocardial dysfunction (magnitude: major) (AHA [Page 2016]).

Acute extrapyramidal disorders may occur, usually resolving after discontinuation of therapy and/or symptomatic treatment.

Rare hematologic reactions including reversible agranulocytosis, aplastic anemia, neutropenia, pancytopenia, and thrombocytopenia have been reported; monitor CBC during prolonged therapy. Consider discontinuation if severe blood disorders occur that are unrelated to disease.

Severe hypoglycemia, including loss of consciousness, has been reported in patients treated with or without antidiabetic agents. Counsel patients about risk of hypoglycemia and associated signs and symptoms.

Skeletal muscle myopathy or neuromyopathy, leading to progressive weakness and atrophy of proximal muscle groups have been reported; muscle strength (especially proximal muscles) should be assessed periodically during prolonged therapy; discontinue therapy if weakness occurs.

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 potentially the presence of macular disease. 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 chloroquine phosphate dosage of 2.3 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]). Disease-related concerns:

Use with caution in patients with preexisting auditory damage; discontinue immediately if hearing defects are noted.

Although the manufacturer’s labeling recommends chloroquine 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 chloroquine, 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 trial conducted in West Africa involving 74 G6PD deficient patients (predominantly Class III deficiency), there were no cases of hemolysis reported following exposure to usual doses of chloroquine (Mandi 2005). 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 hepatic impairment, alcoholism, or concurrent therapy with hepatotoxic agents.

Use with caution in patients with porphyria; may exacerbate disease symptoms.

Use with caution in patients with psoriasis; may exacerbate disease symptoms.

Use with caution in patients with a history of seizure disorder; may cause seizures. 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. Other warnings/precautions:

Chloroquine does not prevent relapses in patients with vivax or ovale malaria (not effective against exoerythrocytic forms); additional treatment with an antimalarial effective against these forms (eg, an 8-aminoquinoline) is required for the treatment of infections with P. vivax and P. ovale. Do not use for the treatment of complicated malaria (high-grade parasitemia and/or complications [eg, cerebral malaria, acute renal failure]).

Chloroquine is not effective against chloroquine- or hydroxychloroquine-resistant strains of Plasmodium species. Chloroquine resistance is widespread in P. falciparum and is reported in P. vivax. Prior to initiation of chloroquine for prophylaxis, it should be determined if chloroquine is appropriate for use in the region to be visited; do not use for malaria prophylaxis in areas where chloroquine resistance occurs. Patients should be treated with another antimalarial if patient is infected with a resistant strain of plasmodia.