Hydroxychloroquine is a 4-aminoquinoline with immunosuppressive, antiautophagy, and antimalarial activities. Although the precise mechanism of action is unknown, hydroxychloroquine may suppress immune function by interfering with the processing and presentation of antigens and the production of cytokines. As a lysosomotropic agent, hydroxychloroquine raises intralysosomal pH, impairing autophagic protein degradation; hydroxychloroquine-mediated accumulation of ineffective autophagosomes may result in cell death in tumor cells reliant on autophagy for survival. In addition, this agent is highly active against the erythrocytic forms of P. vivax and malaria and most strains of P. falciparum but not the gametocytes of P. falciparum.
Hydroxychloroquine (HCQ) is a lupus erythematosus (chronic discoid or systemic) and acute or chronic rheumatoid arthritis drug is a medication used for the prevention and treatment of certain types of malaria.
Mechanism of Action of Hydroxychloroquine
Although the exact mechanism of action is unknown, it may be based on the ability of hydroxychloroquine to bind to and alter DNA. Hydroxychloroquine has also has been found to be taken up into the acidic food vacuoles of the parasite in the erythrocyte. This increases the pH of the acid vesicles, interfering with vesicle functions and possibly inhibiting phospholipid metabolism. In suppressive treatment, hydroxychloroquine inhibits the erythrocytic stage of development of plasmodia. In acute attacks of malaria, it interrupts erythrocytic schizogony of the parasite. Its ability to concentrate in parasitized erythrocytes may account for their selective toxicity against the erythrocytic stages of plasmodial infection. As an antirheumatic, hydroxychloroquine is thought to act as a mild immunosuppressant, inhibiting the production of rheumatoid factor and acute phase reactants. It also accumulates in white blood cells, stabilizing lysosomal membranes and inhibiting the activity of many enzymes, including collagenase and the proteases that cause cartilage breakdown.
Indications of Hydroxychloroquine
- Rheumatoid Arthritis
- Juvenile idiopathic arthritis (in children)
- Discoid and systemic lupus erythematosus (a disease of the skin or the internal organs)
- Skin problems which are sensitive to sunlight
- Lyme Disease, Arthritis
- Dermatomyositis
- Malaria
- Systemic Lupus Erythematosus
- Malaria Prevention
- Sjogren’s Syndrome
- Undifferentiated Connective Tissue Disease
- Discoid Lupus Erythematosus
- Malaria caused by Plasmodium malaria
- Malaria caused by Plasmodium ovale
- Malaria caused by plasmodium vivax
- Porphyria Cutanea Tarda
- Q Fever
- Sjögren’s Syndrome
- Systemic Lupus Erythematosus
Contra-Indications of Hydroxychloroquine
- Hyper sense. to drug class common.
- Retinal or visual field changes
- Concurrent hepatotoxic agent use
- Hepatic impairment
- Alcoholism
- Pediatric pts
- Psoriasis
- Porphyria
- Electrolyte abnormalities
- Congenital long QT syndrome
- QT prolongation
- QT prolongation family hx
- Ventricular arrhythmias
- Bradycardia
Dosage of Hydroxychloroquine
Strength: 200 mg, 400 mg
Lupus Erythematosus
-
Typical starting dosage: 400 mg taken once or twice per day.
-
Typical maintenance dosage: 200–400 mg per day.
Rheumatoid Arthritis
- Initial dose: 400 to 600 mg (310 to 465 mg base) orally once a day to optimum response (usually 4 to 12 weeks)
- Maintenance dose: 200 to 400 mg (155 to 310 mg base) orally once a day
- Dose adjustment: The dose may need to be reduced temporarily if adverse side effects occur; after 5 to 10 days the dose may gradually be increased to the optimum response level.
- Maintenance dose: 200 to 400 mg (155 mg to 310 mg base) orally daily
Arthritis
- Typical starting dosage: 400–600 mg per day for 5–10 days.
- Dosage increases: Your doctor may increase your dosage based on how well the medication is working for you.
- Maintenance dosage: 4–12 weeks after your starting dose, your doctor may lower your dosage to 200–400 mg per day.
Malaria
Adult dosage (ages 18 years and older)
- The typical starting dose is 800 mg. This is followed by 400 mg three times: 6 hours after the first dose, 24 hours after the first dose, and 48 hours after the first dose.
Side Effects of Hydroxychloroquine
The more common side effects
- stomach pain, especially if it comes along with fever and diarrhea or constipation
- yellowing of the skin or eyes
- loss of appetite
- Constipation
- sleepiness or unusual drowsiness
- clumsiness or unsteadiness
- dizziness
- drowsiness
- dry mouth
- false sense of well-being
- increased watering of mouth
- lightheadedness
- constipation;
- vision changes;
- breast swelling (in men or women); or
- decreased sex drive, impotence, or difficulty having an orgasm.
- blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
- restless muscle movements in your eyes, tongue, jaw, or neck;
Common
- Drowsiness and lightheadedness the day after taking the medicine.
- Confusion.
- Numbed emotions.
- Visual disturbances such as blurred vision or double vision.
- Shaky movements and unsteady walk (ataxia).
- Loss of memory (amnesia).
- Muscle weakness.
- Dizziness.
- Headache.
- Skin rashes.
- Disturbances of the gut such as diarrhoea, constipation, nausea, vomiting or abdominal pain.
- Difficulty in passing urine (urinary retention).
- Changes in sex drive.
- Low blood pressure (hypotension).
- Blood disorders.
- Jaundice.
- Unexpected aggression, restlessness or irritability (tell your doctor if you experience this).
- Nightmares or hallucinations (tell your doctor if you experience this).
Rare
- agitation
- anxiety
- behavioural changes, including aggressiveness, angry outbursts, bizarre behaviour, or decreased inhibitions
- confusion
- increased trouble sleeping
- memory problems
- muscle spasms
- shortness of breath
Drug Interactions of Hydroxychloroquine
Hydroxychloroquine may interact with following drugs, supplements, & may change the efficacy of drugs
- abatacept
- anakinra
- anti-tumour necrosis factor agents (e.g., adalimumab, etanercept, infliximab, )
- azathioprine
- “azole” antifungals (e.g., itraconazole, ketoconazole, voriconazole)
- beta-blockers (e.g., carvedilol, metoprolol, propranolol)
- carbamazepine
- clonidine
- clozapine
- corticosteroids (e.g.dexamethasone, hydrocortisone, prednisone)
- cyclosporine
- diltiazem
- imatinib
- macrolide antibiotics (e.g., clarithromycin, erythromycin)
- methotrexate
- methyldopa
- mycophenolate
- phenobarbital
- phenytoin
- rituximab
- tacrolimus
- verapamil
Hydroxychloroquine additional drug interaction
- Some antibiotics used for infections (such as gentamicin, neomycin or tobramycin)
- Cimetidine – used for stomach ulcers
- Neostigmine and pyridostigmine – used for muscle weakness (myasthenia gravis)
- Medicines that may affect the kidneys or liver
- Medicines that affect the skin or the eyes
- Halofantrine, mefloquine – used for malaria
- Amiodarone – used for heart problems
- Moxifloxacin – used to treat infections
- Medicines used for epilepsy
Pregnancy & Lactation
FDA Pregnancy Category D
Pregnancy
Use of chloroquine and other 4-aminoquinolines in high doses and for prolonged durations has been associated with neurological disturbances and interference with hearing, balance, and vision in the fetus. There are no controlled data in human pregnancy. Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage.
Lactation
Infants exposed to hydroxychloroquine during breastfeeding receive only small amounts of the drug in breastmilk. In a small number of infants up to at least 1 year of age, careful follow-up found no adverse effects on growth, vision or hearing. International experts indicate that hydroxychloroquine is acceptable during breastfeeding.
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