Side Effects of Aralen (chloroquine)

Aralen (chloroquine) is an anti-malarial drug hydroxychloroquine (Plaquenil), and is useful in treating several forms of malaria as well as amebiasis that has spread outside of the intestines. 

Some experts think chloroquine might be effective against COVID-19 coronavirus, but this is unproven.

Its mechanism of action is unknown; however, malarial parasites invade human red blood cells, and Aralen may prevent malarial parasites from breaking down (metabolizing) hemoglobin in human red blood cells.  

Aralen is effective against the malarial parasites Plasmodium vivax, P. malariae, P. ovale, and susceptible strains of P. falciparum. Aralen does not prevent malaria. It suppresses malaria infection, stops acute attacks, and lengthens the time between treatment and relapse. Aralen is used off-label to treat porphyria cutanea tarda.

Common side effects of Aralen include:

• irreversible damage to the retina,
• deafness,
• ringing in the ears,
• reduced hearing,
• increased liver enzymes,
• loss of appetite,
• nausea,
• vomiting, and
• diarrhea.

Serious side effects of Aralen include:

• personality changes,
• depression,
• low blood pressure (hypotension),
• polyneuritis,
• extrapyramidal disorders,
• psychosis,
• pancytopenia,
• aplastic anemia,
• thrombocytopenia,
• serious allergic reactions,
• muscle damage,
• hepatitis, and
• maculopathy and macular degeneration.

Drug interactions of Aralen include antacids and kaolin, which can reduce absorption of Aralen.  

Cimetidine can block the breakdown of Aralen, increasing its blood levels.

Aralen significantly reduces blood levels of ampicillin.

Aralen may increase cyclosporine blood levels.

Combining Aralen and mefloquine may increase the risk of seizures.

Aralen can reduce the antibody response to primary immunization with intradermal human diploid-cell rabies vaccine.

There are no studies evaluating the safety and efficacy of Aralen during pregnancy. Aralen should be avoided during pregnancy unless it is necessary and the benefit outweighs the risk. Aralen is excreted in breast milk. Consult your doctor before breastfeeding. 

Common side effects include

• Irreversible damage to the retina
• Deafness
• Tinnitus (ringing in the ears)
• Reduced hearing
• Increased liver enzymes
• Anorexia
• Nausea
• Vomiting
• Diarrhea

Other, rare side effects

• Rash
• Itching
• Photosensitivity
• Hair loss and bleaching of hair
• Neutropenia
• Seizures
• Headache
• Delirium
• Anxiety
• Agitation
• Insomnia
• Confusion
• Hallucinations

Possible serious effects

• Personality changes
• Depression
• Hypotension
• Polyneuritis
• Extrapyramidal disorders
• Psychosis
• Pancytopenia
• Aplastic anemia
• Thrombocytopenia
• Serious allergic reactions
• Muscle damage (myopathy)
• Hepatitis
• Maculopathy and macular degeneration

Other adverse reactions and side effects of Aralen

• There have been rare reports of severe skin reactions such as erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, and exfoliative dermatitis.
• Chloroquine may precipitate a severe attack of psoriasis in patients with psoriasis and may worsen porphyria. Chloroquine should not be used in these conditions unless the benefit to the patient outweighs the potential risks.
• People with retinal or visual field changes should not use chloroquine unless it is absolutely necessary.
• Some strains of P. falciparum are resistant to chloroquine and hydroxychloroquine. Chloroquine resistance is widespread.
• Chloroquine should not be used for treatment of P. falciparum infections from areas of chloroquine resistance or malaria occurring in patients where chloroquine prophylaxis has failed.
• Patients infected with a resistant strains of plasmodia should be treated with another antimalarial drug.
• Retinopathy, maculopathy, irreversible retinal damage, as well as macular degeneration have been reported. Retinopathy from chloroquine may be dose related. Initial and periodic eye examinations are recommended during prolonged treatment. Chloroquine should be discontinued immediately if there are changes in vision.
• Chloroquine may cause acute extrapyramidal disorders (abnormal, uncontrollable body movements) that usually resolve after treatment is stopped.
• Patients should be observed for evidence of muscular weakness. If weakness occurs treatment should be stopped.
• Fatalities have occurred in children from accidental ingestion of small doses of chloroquine. Chloroquine should be kept out of the reach of children.

Special Senses

Ocular

Maculopathy and macular degeneration have been reported and may be irreversible; irreversible retinal damage in patients receiving long-term or high-dosage 4-aminoquinoline therapy; visual disturbances (blurring of vision and difficulty of focusing or accommodation); nyctalopia; scotomatous vision with field defects of paracentral, pericentral ring types, and typically temporal scotomas, e.g., difficulty in reading with words tending to disappear, seeing half an object, misty vision, and fog before the eyes. Reversible corneal opacities have also been reported.

Auditory

Nerve type deafness; tinnitus, reduced hearing in patients with preexisting auditory damage.

Musculoskeletal system

Skeletal muscle myopathy or neuromyopathy leading to progressive weakness and atrophy of proximal muscle groups, which may be associated with mild sensory changes, depression of tendon reflexes and abnormal nerve conduction, have been noted.

Gastrointestinal system

Hepatitis, increased liver enzymes, anorexia, nausea, vomiting, diarrhea, abdominal cramps.

Skin and appendages

Rare reports of erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis and similar desquamation-type events. Pleomorphic skin eruptions, skin and mucosal pigmentary changes; lichen planus-like eruptions, pruritus, urticaria, anaphylactic/anaphylactoid reaction including angioedema; drug rash with eosinophilia and systemic symptoms (DRESS syndrome); photosensitivity and hair loss and bleaching of hair pigment.

Hematologic system

Rarely, pancytopenia, aplastic anemia, reversible agranulocytosis, thrombocytopenia and neutropenia.

Nervous system

Convulsive seizures, mild and transient headache, polyneuritis. Acute extrapyramidal disorders (such as dystonia, dyskinesia, tongue protrusion, torticollis). Neuropsychiatric changes including psychosis, delirium, anxiety, agitation, insomnia, confusion, hallucinations, personality changes, and depression.

Cardiac system

Rarely, hypotension, electrocardiographic change (particularly, inversion or depression of the T-wave with widening of the QRS complex), and cardiomyopathy.

Antacids and kaolin: Antacids and kaolin can reduce absorption of chloroquine; an interval of at least 4 hours between intake of these agents and chloroquine should be observed.

Cimetidine

Cimetidine can inhibit the metabolism of chloroquine, increasing its plasma level. Concomitant use of cimetidine should be avoided.

Ampicillin

In a study of healthy volunteers, chloroquine significantly reduced the bioavailability of ampicillin. An interval of at least two hours between intake of this agent and chloroquine should be observed.

Cyclosporine

After introduction of chloroquine (oral form), a sudden increase in serum cyclosporine level has been reported. Therefore, close monitoring of serum cyclosporine level is recommended and, if necessary, chloroquine should be discontinued.

Mefloquine

Co-administration of chloroquine and mefloquine may increase the risk of convulsions.

The blood concentrations of chloroquine and desethylchloroquine (the major metabolite of chloroquine, which also has antimalarial properties) were negatively associated with log antibody titers. Chloroquine taken in the dose recommended for malaria prophylaxis can reduce the antibody response to primary immunization with intradermal human diploid-cell rabies vaccine.