Side Effects of Plaquenil (hydroxychloroquine)

Hydroxychloroquine (Plaquenil) is an anti-malarial drug used to treat several forms of malaria as well as lupus erythematosus and rheumatoid arthritis. Its mechanism of action is unknown. 

Malarial parasites invade human red blood cells. Hydroxychloroquine may prevent malarial parasites from breaking down hemoglobin in human red blood cells. Hydroxychloroquine is effective against the malarial parasites Plasmodium vivax, P. malariae, P. ovale, and susceptible strains of P. falciparum. 

Hydroxychloroquine also prevents inflammation caused by lupus erythematosus and rheumatoid arthritis. Hydroxychloroquine and its sister drug chloroquine (Aralen) are under investigation for treatment of the COVID-19 coronavirus disease but their effectiveness is currently unproven.

Common side effects of hydroxychloroquine include:

• irritability,
• headache,
• weakness,
• hair lightening or loss,
• stomach upset,
• nausea,
• dizziness,
• muscle pain,
• rash, and
• itching.

Serious side effects of hydroxychloroquine include:

• possible worsening of psoriasis,
• reduced white blood cells (leukopenia) or platelets (thrombocytopenia) and abnormal red blood cells (anemia),
• serious eye toxicity that can lead to color blindness and loss of vision, and
• in certain patients who are genetically deficient in a certain enzyme severe anemia can occur.

Drug interactions of hydroxychloroquine include penicillamine, which may increase penicillamine levels, increasing the risk of penicillamine side effects.

Combining telbivudine and hydroxychloroquine may increase the risk of unexplained muscle pain, tenderness, or weakness because both drugs cause such side effects.

Hydroxychloroquine suppresses the immune system and should not be combined with drugs that also suppress the immune system or live vaccines.

Hydroxychloroquine should only be used in pregnant women for malaria prophylaxis or treatment.

Hydroxychloroquine may be secreted in breast milk and may cause side effects in the infant. Consult your doctor before breastfeeding. 

WARNING

PHYSICIANS SHOULD COMPLETELY FAMILIARIZE THEMSELVES WITH THE COMPLETE CONTENTS OF THE PRESCRIBING INFORMATION BEFORE PRESCRIBING HYDROXYCHLOROQUINE.

Side effects include:

• irritability,
• headache,
• weakness,
• hair lightening or loss,
• stomach upset,
• nausea,
• dizziness,
• muscle pain,
• rash and
• itching.

Rarely, hydroxychloroquine can affect the bone marrow leading to reduced white blood cells (leukopenia) or platelets (thrombocytopenia) and abnormal red blood cells (anemia).

Rare but potentially serious eye toxicity can occur. This toxicity affects a part of the eye called the retina and can lead to color blindness and even loss of vision. An ophthalmologist (eye specialist) often can detect changes in the retina that suggest toxicity before serious damage occurs. Therefore, regular eye examinations, even when there are no symptoms, are mandatory.

Patients who are genetically deficient in a certain enzyme, called G6PD, can develop severe anemia resulting from the rupture of red blood cells. This enzyme deficiency is more common in persons of African descent and can be evaluated by blood testing. Hydroxychloroquine may worsen psoriasis.

The following adverse reactions have been identified during post-approval use of Plaquenil or other 4-aminoqunoline compounds. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Blood and lymphatic system disorders: Bone marrow failure, anemia, aplastic anemia, agranulocytosis, leukopenia, and thrombocytopenia. Hemolysis reported in individuals with glucose-6- phosphate dehydrogenase (G-6-PD) deficiency.

Cardiac disorders: Cardiomyopathy which may result in cardiac failure and in some cases a fatal outcome. Plaquenil prolongs the QT interval. Ventricular arrhythmias and torsade de pointes have been reported in patients taking Plaquenil.

Ear and labyrinth disorders: Vertigo, tinnitus, nystagmus, nerve deafness, deafness.

Eye disorders: Irreversible retinopathy with retinal pigmentation changes (bull's eye appearance), visual field defects (paracentral scotomas) and visual disturbances (visual acuity), maculopathies (macular degeneration), decreased dark adaptation, color vision abnormalities, corneal changes (edema and opacities) including corneal deposition of drug with or without accompanying symptoms (halo around lights, photophobia, blurred vision).

Gastrointestinal disorders: Nausea, vomiting, diarrhea, and abdominal pain.

General disorders and administration site conditions: Fatigue.

Hepatobiliary disorders: Liver function tests abnormal, hepatic failure acute.

Immune system disorders: Urticaria, angioedema, bronchospasm

Metabolism and nutrition disorders: Decreased appetite, hypoglycemia, porphyria, weight decreased.

Musculoskeletal and connective tissue disorders: Sensorimotor disorder, skeletal muscle myopathy or neuromyopathy leading to progressive weakness and atrophy of proximal muscle groups, depression of tendon reflexes and abnormal nerve conduction.

Nervous system disorders: Headache, dizziness, seizure, ataxia and extrapyramidal disorders such as dystonia, dyskinesia, and tremor have been reported with this class of drugs.

Psychiatric disorders: Affect/emotional lability, nervousness, irritability, nightmares, psychosis, suicidal behavior.

Skin and subcutaneous tissue disorders: Rash, pruritus, pigmentation disorders in skin and mucous membranes, hair color changes, alopecia. 

Dermatitis bullous eruptions including erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), photosensitivity, dermatitis exfoliative, acute generalized exanthematous pustulosis (AGEP).

AGEP has to be distinguished from psoriasis, although Plaquenil may precipitate attacks of psoriasis. It may be associated with pyrexia and hyperleukocytosis.

To report suspected adverse reactions, contact Concordia Pharmaceuticals Inc. at 1- 877-370-1142 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

• Administration of hydroxychloroquine with penicillamine (Cuprimine, Depen) may increase penicillamine levels, increasing the risk of penicillamine side effects. The mechanism is unknown.
• Combining telbivudine (Tyzeka) and hydroxychloroquine may increase the risk of unexplained muscle pain, tenderness, or weakness because both drugs cause such side effects.
• Hydroxychloroquine suppresses the immune system and should not be combined with drugs that also suppress the immune system or live vaccines.

Digoxin

Concomitant Plaquenil and digoxin therapy may result in increased serum digoxin levels: serum digoxin levels should be closely monitored in patients receiving combined therapy.

Insulin Or Antidiabetic Drugs

As Plaquenil may enhance the effects of a hypoglycemic treatment, a decrease in doses of insulin or antidiabetic drugs may be required.

Drugs That Prolong QT Interval And Other Arrhythmogenic Drugs

Plaquenil prolongs the QT interval and should not be administered with other drugs that have the potential to induce cardiac arrhythmias. Also, there may be an increased risk of inducing ventricular arrhythmias if Plaquenil is used concomitantly with other arrhythmogenic drugs.

Mefloquine And Other Drugs Known To Lower The Convulsive Threshold

Plaquenil can lower the convulsive threshold. Co-administration of Plaquenil with other antimalarials known to lower the convulsion threshold (e.g., mefloquine) may increase the risk of convulsions.

Antiepileptics

The activity of antiepileptic drugs might be impaired if co-administered with Plaquenil.

Methotrexate

Combined use of methotrexate with Plaquenil has not been studied and may increase the incidence of adverse effects.

Cyclosporin

An increased plasma cyclosporin level was reported when cyclosporin and Plaquenil were co-administered.

The following interactions have been observed on treatment with the structurally related substance chloroquine phosphate, and therefore cannot be ruled out for hydroxychloroquine.

Praziquantel

Chloroquine has been reported to reduce the bioavailability of praziquantel.

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.