hydroxychloroquine sulfate

Hydroxychloroquine sulfate is a medication used to prevent and treat uncomplicated malaria, and for treatment of autoimmune disorders, rheumatoid arthritis and lupus erythematosus. Hydroxychloroquine sulfate belongs to a class of drugs known as 4-aminoquinoline, derived from the chemical quinoline, known for its antimalarial properties. Hydroxychloroquine sulfate kills the malarial parasite, and in addition, also has immunomodulatory and anti-inflammatory effects, although the precise mechanisms of action are not known.

Hydroxychloroquine sulfate is an alkaline chemical compound that increases pH levels and neutralizes acid. Hydroxychloroquine accumulates inside the malarial parasite’s lysosomes, organelles inside cells that contain digestive enzymes, and raise the pH levels. With the digestive acids neutralized, the malarial parasites lose their ability to break down hemoglobin and draw the nutrition that they require to survive and grow. Hydroxychloroquine is effective only against the blood stage of the malarial parasite and not the liver stage forms.

Hydroxychloroquine sulfate also accumulates inside the organelles of human cells, which prevents the cells from presenting the unique proteins (antigens) that autoimmune antibodies recognize and attack in autoimmune disorders. This reduces inflammatory activity, including activation of killer T-cells and release of inflammatory proteins (cytokines). Hydroxychloroquine was initially granted emergency use authorization (EUA) for COVID-19, but the FDA has since revoked it based on data that it is unlikely to be effective for COVID.

The uses of hydroxychloroquine sulfate include:

FDA-approved:

• Treatment of uncomplicated malaria due to Plasmodium falciparum, Plasmodium malariae, Plasmodium ovale, and Plasmodium vivax in adult and pediatric patients
• Prophylaxis of malaria in geographic areas where chloroquine resistance is not reported in adult and pediatric patients
• Treatment of rheumatoid arthritis in adults
• Treatment of systemic lupus erythematosus in adults
• Treatment of chronic discoid lupus erythematosus in adults

Off-label:

• Dermatomyositis with cutaneous disease
• Porphyria cutanea tarda
• Primary Sjogren syndrome (extraglandular manifestations)
• Q fever (Coxiella burnetii)
• Sarcoidosis with joint disease (arthropathy)
• Sarcoidosis, with extensive cutaneous disease

• Do not use hydroxychloroquine sulfate in patients who are hypersensitive to any component of the formulation or 4-aminoquinoline derivatives.
• Hydroxychloroquine sulfate can cause life-threatening or fatal heart muscle disease (cardiomyopathy) and cardiac rhythm disturbances, including QT prolongation.
  • Do not use hydroxychloroquine sulfate to treat patients with congenital or acquired QT prolongation.
  • Do not use in patients with risk factors for QT prolongation including:
    • Pre-existing heart disease such as heart failure or myocardial infarction
    • Irregular heart rhythm disorders (arrhythmias)
    • History of ventricular arrhythmia
    • Taking medications that prolong QT interval
    • Uncorrected hypokalemia or hypomagnesemia
  • Correct electrolyte imbalances before starting hydroxychloroquine sulfate.
  • Monitor the patient's cardiac function and discontinue hydroxychloroquine sulfate if the patient develops signs and symptoms of cardiotoxicity.
• Hydroxychloroquine sulfate can cause irreversible retinal damage. In patients of Asian descent, retinal damage may first start outside the macula, the central part of retina.
  • Risk increases with use of high doses for periods longer than 5 years, pre-existing macular disease, kidney function impairment or concurrent use of drugs such as tamoxifen.
  • Perform eye examinations within the first year of starting hydroxychloroquine sulfate. Thereafter, monitor retinal health every year in patients at high risk for retinal damage. Eye examinations may be deferred for 5 years in patients without significant risk factors.
  • In case of suspected retinal damage, discontinue hydroxychloroquine and continue monitoring the patient, because retinal changes and visual disturbances can progress even after discontinuation of treatment.
• Hydroxychloroquine sulfate can cause severe skin reactions including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), and acute generalized exanthematous pustulosis (AGEP). Monitor patients for signs and symptoms, advise patients to report skin reactions, and discontinue treatment in case of severe skin reactions.
• Avoid use of hydroxychloroquine sulfate in patients with psoriasis, an autoimmune skin disorder or porphyria, a group of inherited disorders that causes buildup of porphyrin, unless benefits outweigh risks, because it can worsen these conditions.
• Hydroxychloroquine sulfate can suppress bone marrow function. Monitor patient’s blood count periodically and discontinue hydroxychloroquine if the patient develops treatment-related myelosuppression.
• Hydroxychloroquine sulfate has been associated with premature destruction of red blood cells (hemolysis) in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, a genetic disorder that leads to hemolysis with the use of certain medications. Monitor patients for hemolytic anemia.
• There have been reports of skeletal muscle disease (myopathy) and nerve disease (neuropathy) with the use of hydroxychloroquine sulfate. Periodically assess the patient’s muscle strength and deep tendon reflexes, and discontinue treatment if the patient develops muscle weakness.
• Hydroxychloroquine sulfate can cause life-threatening hypoglycemia in diabetic patients taking antidiabetic treatment.
  • Assess blood glucose levels in patients who develop hypoglycemia symptoms and adjust antidiabetic medication dosages, if required.
  • Advise patients to monitor their blood glucose levels, be aware of hypoglycemia symptoms and seek medical attention if such symptoms occur.
• Suicidal behavior has been reported in patients treated with hydroxychloroquine sulfate. Caution the patient, their family, and caregivers about this risk, and advise them to be alert for and report any emergence or worsening of depression or suicidal thoughts, or unusual changes in mood and behavior. Assess risks and benefits of continued treatment in patients who develop such symptoms.

Common side effects of hydroxychloroquine sulfate include:

• Heart muscle disease (cardiomyopathy)
• Cardiac failure
• Heart rhythm disorders including:
  • QT-interval prolongation
  • Ventricular tachycardia
  • Torsades de pointes
  • Atrioventricular block
  • Bundle branch block
  • Sick sinus syndrome
• High pressure in the pulmonary blood vessels (pulmonary hypertension)
• Retinal disease (retinopathy)
• Pigmentation changes in the retina
• Degeneration of macula, the central part of the retina
• Swelling of cornea (corneal edema)
• Corneal opacity
• Visual field defects
• Decreased darkness adaptation
• Uncontrolled eye movements (nystagmus)
• Vertigo
• Ringing in the ears (tinnitus)
• Hearing loss
• Bone marrow depression
• Blood disorders including:
  • Low red blood cell count (anemia)
  • Anemia due to lack of new red cell growth (aplastic anemia)
  • Low count of leukocyte immune cells (leukopenia)
  • Low count of granulocyte immune cells (agranulocytosis)
  • Low platelet count (thrombocytopenia)
• Nausea
• Vomiting
• Diarrhea
• Abdominal pain
• Loss of appetite (anorexia)
• Weight loss
• Low blood glucose (hypoglycemia)
• Fatigue
• Abnormal liver function tests
• Liver injury and failure (fulminant hepatic failure)
• Disease of skeletal muscles (proximal myopathy)
• Depressed tendon reflexes
• Muscle weakness and muscle loss (atrophy)
• Abnormal nerve conduction
• Headache
• Dizziness
• Impaired balance, coordination and speech (ataxia)
• Tremor
• Seizure
• Drug-related movement disorder (extrapyramidal disorder)
• Irritability
• Mood swings
• Nervousness
• Nightmares
• Psychosis
• Suicidal ideation and behavior
• Hypersensitivity reactions including:
  • Hives (urticaria)
  • Bronchospasm
  • Swelling of tissue beneath the skin and mucous membranes (angioedema)
• Skin reactions including:
  • Rash
  • Itching (pruritus)
  • Hair color changes
  • Hair loss (alopecia)
  • Light sensitivity (photosensitivity)
  • Hyperpigmentation
• Severe skin reactions including:
  • Exacerbation of psoriasis
  • Erythema multiforme
  • Exfoliative dermatitis
  • Acute generalized exanthematous pustulosis (AGEP)
  • Drug rash with eosinophilia and systemic symptoms (DRESS)
  • Stevens-Johnson syndrome (SJS)
  • Toxic epidermal necrolysis (TEN)

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Tablet

• 200 mg

Adult:

Malaria

Prophylaxis

• Indicated for prophylaxis of malaria in geographic areas where chloroquine resistance is not reported
• 400 mg (310 mg base) orally weekly, starting 2 weeks before exposure and continued for 4 weeks after departure from endemic area OR
• Weight-based dosing: 6.5 mg/kg (5 mg/kg base) orally once weekly, not to exceed 400 mg (310 mg base), starting 2 weeks before exposure and continued for 4 weeks after leaving the endemic area

Acute treatment

• Indicated for treatment of uncomplicated malaria due to P. falciparum, P. malariae, P. ovale, and P. vivax
• 800 mg (620 mg base) orally, then 400 mg (310 mg base) orally at 6 hours, 24 hours, and 48 hours after initial dose
• Weight-based dosing: 13 mg/kg (10 mg/kg base), not to exceed 800 mg (620 mg base) followed by 6.5 mg/kg (5 mg/kg base), not to exceed 400 mg (310 mg base), orally at 6 hours, 24 hours, and 48 hours after initial dose  

trong>Rheumatoid Arthritis

• Indicated for treatment of acute and chronic rheumatoid arthritis
• 400-600 mg/day (310-465 mg base/day) orally once or twice daily
• When a good response is obtained, reduce dosage by 50% and continue maintenance dose of 200-400 mg/day (155-310 mg base/day) orally once or twice daily; not to exceed 600 mg or 6.5 mg/kg (5 mg/kg base) per day, whichever is lower, as the incidence of retinopathy has been reported to be higher when this maintenance dose is exceeded
• Use corticosteroids and salicylates in conjunction with hydroxychloroquine; gradually decrease dosage or eliminate after a maintenance dose has been achieved

Systemic Lupus Erythematosus

• Indicated for treatment of chronic discoid lupus erythematosus and systemic lupus erythematosus
• 200-400 mg/day (155-310 mg base/day) orally as a single daily dose or in two divided doses
• Doses higher than 400 mg/day are not recommended
• Incidence of retinopathy has been reported to be higher when this maintenance dose is exceeded

Porphyria Cutanea Tarda (Off-label)

• 100-200 mg (77.5-155 mg base) orally 2-3 times/week

Pediatric:

Malaria

Prophylaxis

• Indicated for prophylaxis of malaria in geographic areas where chloroquine resistance is not reported.
• 6.5 mg/kg (5 mg/kg base) PO once weekly, not to exceed 400 mg (310 mg base), starting 2 weeks before exposure and continued for 4 weeks after leaving the endemic area

Acute treatment

• Indicated for treatment of uncomplicated malaria due to P. falciparum, P. malariae, P. ovale, and P. vivax
• 13 mg/kg (10 mg/kg base), not to exceed 800 mg (620 mg base) followed by 6.5 mg/kg (5 mg/kg base), not to exceed 400 mg (310 mg base), orally at 6 hours, 24 hours, and 48 hours after initial dose

Porphyria Cutanea Tarda (Off-label)

• Dosing schedules not well established in children
• A case report describes 3 mg/kg orally twice weekly over 14 months reported as safe and effective in a child aged 4 years

Dosing Considerations

• A reduction in dosage may be necessary for patients with hepatic or renal disease
• Before prescribing hydroxychloroquine for treatment or prophylaxis of malaria, consult the Centers for Disease Control and Prevention (CDC) Malaria website (link http://www.cdc.gov/malaria)

Limitations of use in malaria

• Not recommended for treatment of complicated malaria
• Not effective against chloroquine or hydroxychloroquine-resistant strains of Plasmodium species
• Not recommended for treatment of malaria acquired in geographic areas where chloroquine resistance occurs or when the Plasmodium species has not been identified
• Not recommended for malaria prophylaxis in geographic areas where chloroquine resistance occurs
• Does not prevent relapses of P. vivax or P. ovale because it is not active against the hypnozoite forms of these parasites
• For radical cure of P. vivax and P. ovale infections, concomitant therapy with an 8-aminoquinoline compound is necessary

Overdose

• Hydroxychloroquine sulfate overdose can cause central nervous system depression, visual disturbances, transient loss of vision, seizures, coma, low blood potassium (hypokalemia), life-threatening low blood pressure (hypotension), serious irregular heart rhythms, cardiac arrest and death.
• Overdose treatment includes gastrointestinal decontamination procedures, if it is within one hour after ingestion, respiratory support if required, normalization of blood potassium levels and other supportive measures as required.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Severe interactions of hydroxychloroquine sulfate include:
  • lefamulin
• Hydroxychloroquine sulfate has serious interactions with at least 210 different drugs.
• Hydroxychloroquine sulfate has moderate interactions with at least 27 different drugs.
• Mild interactions of hydroxychloroquine sulfate include:
  • chloroquine
  • praziquantel
  • yellow fever vaccine

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

• No animal reproductive studies have been conducted with hydroxychloroquine sulfate. Prolonged clinical experience and available data on the use of hydroxychloroquine sulfate in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal, or fetal outcomes.
• Untreated or increased disease activity from malaria, rheumatoid arthritis and systemic lupus erythematosus during pregnancy is associated with maternal and fetal risks.
• Hydroxychloroquine is present in breastmilk in low concentrations. No adverse effects or growth and developmental abnormalities have been reported in breastfed infants. There is no information on its effects on milk production.
• Decision to breastfeed should be based on the nursing mother’s clinical need for hydroxychloroquine sulfate, health and developmental benefits of breastfeeding, and the risks to the breastfed infant from exposure to the drug or the mother’s underlying condition.

• Take hydroxychloroquine sulfate exactly as prescribed, with food or milk, and swallow whole.
• Report to your treating physician if you experience:
  • Heart-related symptoms such as irregular or rapid heartbeat, dizziness, lightheadedness or fainting
  • Eye symptoms such as decrease in vision or adaptation to darkness
  • Severe skin reactions such as blisters, itching or burning with or without fever
  • Muscle weakness
• Monitor your blood sugar levels and seek immediate medical attention if you experience any symptoms of low blood sugar, which include weakness, dizziness, shakiness, sweating, nausea, rapid heartbeat, confusion, blurred vision, and fainting.
• Hydroxychloroquine sulfate may induce or worsen depression and suicidal thoughts and behavior. Seek support from family, friends and your healthcare provider if you feel depressed.
• If you are a family member or caregiver of a patient taking hydroxychloroquine sulfate, be alert for signs and symptoms of depression in the patient and contact the treating physician if you notice unusual changes in the patient’s mood or behavior.
• Store hydroxychloroquine sulfate safely out of reach of children.
• In case of overdose, seek immediate medical help or contact Poison Control.