Oxiklorin
Oxiklorin Uses, Dosage, Side Effects, Food Interaction and all others data.
Oxiklorin is a 4-aminoquinoline antimalarial with actions similar to those of chloroquine but is mainly used in the treatment of SLE and rheumatoid arthritis. It interferes with digestive vacuole function within susceptible malarial parasites by increasing pH and interrupting with lysosomal degradation of Hb thus impeding normal cell function of sensitive parasites.
Oxiklorin affects the function of lysozomes in humans as well as plasmodia. Altering the pH of the lysozomes reduces low affinity self antigen presentation in autoimmue diseases and interferes with the ability of plasmodia to proteolyse hemoglobin for their energy requirements. Oxiklorin has a long duration of action as it may be taken on a weekly basis for some indications. Oxiklorin may lead to severe hypoglycemia and so diabetic patients are advised to monitor their blood glucose levels. Oxiklorin is not effective against malaria in areas where chloroquine resistance has been reported.
| Trade Name | Oxiklorin |
| Availability | Prescription only |
| Generic | Hydroxychloroquine |
| Hydroxychloroquine Other Names | Hidroxicloroquina, Hydroxychloroquine, Hydroxychloroquinum, Oxichlorochine, Oxichloroquine |
| Related Drugs | Humira, aspirin, amoxicillin, prednisone, doxycycline, methotrexate, clindamycin, ceftriaxone, dexamethasone, triamcinolone |
| Type | |
| Formula | C18H26ClN3O |
| Weight | Average: 335.872 Monoisotopic: 335.176440176 |
| Protein binding | The S enantiomer of hydroxychloroquine is 64% protein bound in plasma. It is 50% bound to serum albumin and 29% bound to alpha-1-acid glycoprotein. The R enantiomer is 37% protein bound in plasma. It is 29% bound to serum albumin and 41% bound to alpha-1-acid glycoprotein. In total, hydroxychloroquine is 50% protein bound in plasma. |
| Groups | Approved |
| Therapeutic Class | Anti-malarial drugs, Disease-modifying antirheumatic drugs (DMARDs), Drugs used for Rheumatoid Arthritis |
| Manufacturer | |
| Available Country | Finland, South Korea |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Acute lupus erythematosus, Kawasaki disease and dermatomyositis sarcoidosis, Lyme disease, Malaria, Porphyria cutanea tarda, Q fever, Rheumatoid arthritis, Sjogren’s syndrome, Systemic lupus erythematosus (SLE)
Oxiklorin is also used to associated treatment for these conditions: Discoid Lupus Erythematosus (DLE), Plasmodium Infections, Porphyria Cutanea Tarda, Q Fever, Rheumatoid Arthritis, Sjögren's Syndrome, Systemic Lupus Erythematosus (SLE), Uncomplicated Malaria caused by Plasmodium Vivax, Uncomplicated Malaria caused by Plasmodium malariae, Uncomplicated Malaria caused by Plasmodium ovale, Uncomplicated Malaria caused by Plasmodium falciparum
How Oxiklorin works
The exact mechanisms of hydroxychloroquine are unknown. It has been shown that hydroxychloroquine accumulates in the lysosomes of the malaria parasite, raising the pH of the vacuole. This activity interferes with the parasite's ability to proteolyse hemoglobin, preventing the normal growth and replication of the parasite. Oxiklorin can also interfere with the action of parasitic heme polymerase, allowing for the accumulation of the toxic product beta-hematin.
Oxiklorin accumulation in human organelles also raise their pH, which inhibits antigen processing, prevents the alpha and beta chains of the major histocompatibility complex (MHC) class II from dimerizing, inhibits antigen presentation of the cell, and reduces the inflammatory response. Elevated pH in the vesicles may alter the recycling of MHC complexes so that only the high affinity complexes are presented on the cell surface. Self peptides bind to MHC complexes with low affinity and so they will be less likely to be presented to autoimmune T cells. Oxiklorin also reduces the release of cytokines like interleukin-1 and tumor necrosis factor, possibly through inhibition of Toll-like receptors.
The raised pH in endosomes, prevent virus particles (such as SARS-CoV and SARS-CoV-2) from utilizing their activity for fusion and entry into the cell.
Oxiklorin inhibits terminal glycosylation of ACE2, the receptor that SARS-CoV and SARS-CoV-2 target for cell entry. ACE2 that is not in the glycosylated state may less efficiently interact with the SARS-CoV-2 spike protein, further inhibiting viral entry.
Dosage
Oxiklorin dosage
Acute malaria:
- Adult: Initially, 800 mg followed by 400 mg 6-8 hr later, then a further 400 mg on each of the succeeding 2 days.
- Child: 13 mg/kg; followed by 6.5 mg/kg 6 hr later and repeat dose on the 2nd and 3rd days.
Prophylaxis of malaria:
- Adult: 400 mg every 7 days. Begin 2 wk before exposure, continue for 4-6 wk after leaving the endemic area.
- Child: 6.5 mg/kg once wkly. Max: 400 mg/dose.
Rheumatoid arthritis, Systemic lupus erythematosus:
- Adult: Initially, 400 mg daily in divided doses. Maintenance: 200-400 mg/day. Max: 6.5 mg/kg/day or 400 mg/day whichever is lower.
- Child: Up to 6.5 mg/kg/day or 400 mg/day whichever is lower. Lowest effective dose should be used.
Side Effects
Generally Oxiklorin Sulphate is well tolerated. However, few side effects like nausea, vomiting, stomach upset, loss of appetite, diarrhea, tiredness, weakness or headache and visual problem may occur the first several days.
Toxicity
Patients experiencing an overdose may present with headache, drowsiness, visual disturbances, cardiovascular collapse, convulsions, hypokalemia, rhythm and conduction disorders including QT prolongation, torsades de pointes, ventricular tachycardia, and ventricular fibrillation. This may progress to sudden respiratory and cardiac arrest. Overdose should be treated with immediate gastric lavage and activated charcoal at a dose of at least 5 times the hydroxychloroquine dose within 30 minutes. Parenteral diazepam may be given to treat cardiotoxicity, transfusion may reduce serum concentrations of drug, patients should be monitored for at least 6 hours, fluids should be given, and ammonium chloride should be given to acidify urine and promote urinary excretion. Patients may also be given epinephrine.
Precaution
Impaired liver or renal function, severe GI disorders, porphyria, psoriasis, neurological disorders especially a history of epilepsy, myasthenia gravis, glucose-6-phosphate dehydrogenase deficiency, pregnancy, lactation. Monitor CBC in patients receiving prolonged therapy. Perform baseline and periodic 6-mth eye exams, test periodically for muscle weakness.
Interaction
Cimetidine may increase serum levels of hydroxychloroquine. Its absorption may be decreased by kaolin or Mg trisilicate. Avoid digoxin and alcohol. Increased risk of ventricular arrhythmias when used with halofantrine. Concurrent use with mefloquine may increase the risk of convulsions.
Food Interaction
- Take with food. Take with a meal or glass of milk.
[Moderate] GENERALLY AVOID: Theoretically, grapefruit and grapefruit juice may increase the plasma concentrations of hydroxychloroquine or chloroquine and the risk of toxicities such as QT interval prolongation and ventricular arrhythmias.
The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruit.
Following coadministration with cimetidine, a weak to moderate CYP450 3A4 inhibitor, a 2-fold increase in chloroquine exposure occurred.
Since chloroquine and hydroxychloroquine have similar structures and metabolic elimination pathways, a similar interaction may be observed with hydroxychloroquine.
In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands.
Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition.
Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.
MANAGEMENT: Although clinical data are lacking, it may be advisable to avoid the consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract during hydroxychloroquine or chloroquine therapy.
Oxiklorin Drug Interaction
Moderate: duloxetine, duloxetine, pregabalin, pregabalinUnknown: aspirin, aspirin, omega-3 polyunsaturated fatty acids, omega-3 polyunsaturated fatty acids, levothyroxine, levothyroxine, cyanocobalamin, cyanocobalamin, ascorbic acid, ascorbic acid, ergocalciferol, ergocalciferol, cholecalciferol, cholecalciferol, cetirizine, cetirizine
Oxiklorin Disease Interaction
Major: oculotoxicity, porphyriaModerate: arrhythmias, bone marrow suppression, ototoxicity, seizures, glucose-6-PD deficiency, hepatotoxicity, myasthenia gravis, psoriasis, diabetes, heart disease, renal impairment
Volume of Distribution
Oxiklorin has a volume of distribution of 5522L from blood and 44,257L from plasma.
Elimination Route
Oxiklorin is 67-74% bioavailable. Bioavailability of the R and S enantiomers were not significantly different. Following a 200mg oral dose, hydroxychloroquine reached a Cmax of 129.6ng/mL with a Tmax of 3.26h in the blood and a Cmax of 50.3ng/mL with a Tmax of 3.74h in the plasma. Following 155mg and 310mg intravenous doses, Cmax in the blood ranged from 1161-2436ng/mL with an average of 1918ng/mL.
Half Life
Oral hydroxychloroquine has an absorption half life of 3-4 hours. A 200mg oral dose of hydroxychloroquine has a half life of 537 hours or 22.4 days in blood, and 2963 hours or 123.5 days in plasma. A 155mg intravenous dose has a half life of 40 days.
Clearance
The clearance of hydroxychloroquine is 96mL/min.
Elimination Route
40-50% of hydroxychloroquine is excreted renally, while only 16-21% of a dose is excreted in the urine as unchanged drug. 5% of a dose is sloughed off in skin and 24-25% is eliminated through the feces.
Pregnancy & Breastfeeding use
Pregnancy category C. During pregnancy, this drug should be used only if clearly needed. Since small amounts of this medication are found in breast milk consult your doctor before medication.
Contraindication
Retinal or visual field changes, known hypersensitivity. Long-term use in children.
Acute Overdose
Symptoms of overdose consist of headache, drowsiness, visual disturbances, cardiovascular collapse, and convulsions, followed by sudden and early respiratory and cardiac arrest. Gastric lavage until the stomach is completely emptied.
Treatment should be prompt and symptomatic as symptoms appear quickly
Storage Condition
Store below 30° C.
Innovators Monograph
You find simplified version here Oxiklorin
Oxiklorin contains Hydroxychloroquine see full prescribing information from innovator Oxiklorin Monograph, Oxiklorin MSDS, Oxiklorin FDA label
FAQ
What is Oxiklorin used for?
Oxiklorin is used to treat autoimmune diseases, such as systemic lupus erythematosus and rheumatoid arthritis. Oxiklorin is a medication used to prevent and treat malaria in areas where malaria remains sensitive to chloroquine.
How safe is Oxiklorin?
It's safe for most adults and kids to take Oxiklorin. Your doctor will use your weight to get the right dose. Studies show it's safe to take Oxiklorin if you're pregnant or breastfeeding. Always talk to your doctor about what drugs you're taking.
How does Oxiklorin work?
Oxiklorin works by killing the organisms that cause malaria.
What are the common side effects of Oxiklorin?
Common side effects of Oxiklorin are include:
- headache.
- dizziness.
- loss of appetite.
- nausea.
- diarrhea.
- stomach pain.
- vomiting.
- rash.
Is Oxiklorin safe during pregnancy?
Oxiklorin is generally considered to be safe for the treatment of autoimmune rheumatic conditions during pregnancy.
Is Oxiklorin safe during breastfeeding?
Infants exposed to Oxiklorin during breastfeeding receive only small amounts of the drug in breastmilk. In 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 Oxiklorin is acceptable during breastfeeding.
Can I drink alcohol with Oxiklorin?
There's no known interaction between alcohol and Oxiklorin.
Can I drive after taking Oxiklorin?
Avoid driving or hazardous activity until you know how this Oxiklorin will affect you.
When should be taken of Oxiklorin?
Oxiklorin dose is usually taken once a week on exactly the same day of each week.
How many time can I take Oxiklorin daily?
Oxiklorin is usually taken once or twice a day. If you are taking Oxiklorin to treat rheumatoid arthritis, it is usually taken once or twice a day.
How long does Oxiklorin take to work?
Oxiklorin stays in your body for about 3 months.
Can I take Oxiklorin for long term?
Oxiklorin therapy is safe for long-term use at doses <5 mg/kg/day.
Can I take Oxiklorin daily?
Oxiklorin is usually taken twice daily. The dose are 200-mg. The usual dose is 1 or 2 dose daily.
How long can I stay on Oxiklorin?
You may continue to get better for up to 1 year. Most people who take Plaquenil also take other medicines for pain and stiffness.
Who should not take Oxiklorin ?
If you have low amount of magnesium in the blood, low amount of potassium in the blood you should not used Oxiklorin. Stop taking Oxiklorin and call your doctor at once if you have blurred vision, trouble focusing, distorted vision, blind spots, trouble reading, changes in your color vision, increased sensitivity to light.
What happens if I overdose?
Seek emergency medical attention. An overdose of hydroxychloroquine can be fatal, and must be treated quickly. Overdose symptoms may include drowsiness, vision changes, seizure, slow heart rate, weak pulse, pounding heartbeats, sudden dizziness, fainting, shortness of breath, or slow breathing (breathing may stop).
What happen If I missed a dose of Oxiklorin?
If you forgot your Oxiklorin for the day altogether, do not take an extra dose the next day; just resume your regular dose. As long as this does not happen regularly, you will likely not feel any ill effects.
What happen If I stop taking Oxiklorin?
Stopping prevention or treatment too soon may lead to infection or a return of the infection. Tell your doctor if your condition lasts or gets worse. It may take several weeks or months to see improvement if you are taking this for lupus or arthritis. Oxiklorin may not prevent malaria in all cases.
Can Oxiklorin affect my kidneys?
Oxiklorin was associated with a longer time-to-the occurrence of renal damage.
Can Oxiklorin affects my liver?
Oxiklorin induced liver injury is a very rarely reported side effect of this medication.
Is Oxiklorin hard on my heart?
Oxiklorin can cause dangerous effects on your heart, especially if you also use certain other medicines. Seek emergency medical attention if you have fast or pounding heartbeats and sudden dizziness (like you might pass out).
