Difosfato de Cloroquina
Difosfato de Cloroquina Uses, Dosage, Side Effects, Food Interaction and all others data.
Difosfato de Cloroquina is used for malarial prophylaxis (as a suppressive) and in managing acute attacks of malaria. It is highly active against erythrocytic forms of P. vivax, P. malariae and P. falciparum. It influences Hb digestion by increasing intravesicular pH in malaria parasite cells and interferes with the nucleoprotein synthesis of the patient. It is also effective in extra intestinal amoebiasis. In RA chloroquine and more effectively hydroxychloroquine have a disease-modifying effect.
Difosfato de Cloroquina inhibits the action of heme polymerase, which causes the buildup of toxic heme in Plasmodium species. It has a long duration of action as the half life is 20-60 days. Patients should be counselled regarding the risk of retinopathy with long term usage or high dosage, muscle weakness, and toxicity in children.
| Trade Name | Difosfato de Cloroquina |
| Availability | Prescription only |
| Generic | Chloroquine |
| Chloroquine Other Names | Chloraquine, Chlorochin, Chloroquina, Chloroquine, Chloroquinium, Chloroquinum, Cloroquina |
| Related Drugs | doxycycline, metronidazole, clindamycin, hydroxychloroquine, Flagyl, Plaquenil, Cleocin, Vibramycin, tinidazole |
| Type | |
| Formula | C18H26ClN3 |
| Weight | Average: 319.872 Monoisotopic: 319.181525554 |
| Protein binding | Chloroquine is 46-74% bound to plasma proteins. (-)-chloroquine binds more strongly to alpha-1-acid glycoprotein and (+)-chloroquine binds more strongly to serum albumin. |
| Groups | Approved, Investigational, Vet approved |
| Therapeutic Class | Anti-malarial drugs |
| Manufacturer | |
| Available Country | Brazil |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Difosfato de Cloroquina Phosphate is used for the treatment of malaria, prophylaxis and suppression of malaria, amoebic hepatitis and abscess, discoid and systemic and systemic lupus erythematosus, rheumatoid arthritis
Difosfato de Cloroquina is also used to associated treatment for these conditions: Discoid Lupus Erythematosus (DLE), Extraintestinal Amebiasis, Plasmodium Infections, Polymorphic Light Eruption (PLE), Porphyria Cutanea Tarda, Rheumatoid Arthritis, Sarcoidosis, Acute, uncomplicated Malaria
How Difosfato de Cloroquina works
Difosfato de Cloroquina inhibits the action of heme polymerase in malarial trophozoites, preventing the conversion of heme to hemazoin. Plasmodium species continue to accumulate toxic heme, killing the parasite.
Difosfato de Cloroquina passively diffuses through cell membranes and into endosomes, lysosomes, and Golgi vesicles; where it becomes protonated, trapping the chloroquine in the organelle and raising the surrounding pH. The raised pH in endosomes, prevent virus particles from utilizing their activity for fusion and entry into the cell.
Difosfato de Cloroquina does not affect the level of ACE2 expression on cell surfaces, but 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
Difosfato de Cloroquina dosage
Acute malaria:
- Adult: As base: Initially, 600 mg followed by 300 mg 6-8 hr later on day 1. On days 2 and 3, single doses of 300 mg/day.
- Child: Initially, 10 mg base/kg (max 600 mg base) followed by 5 mg base/kg (max 300 mg base) after 6 hrs. Single doses of 5 mg base/kg on days 2 and 3.
Hepatic amoebiasis:
- Adult: As base: 600 mg daily for 2 days then 300 mg daily for 2 or 3 wk given with emetine or dehydroemetine.
- Child: 6 mg/kg daily. Max dose: 300 mg daily.
Rheumatoid arthritis:
- Adult: As base: 150 mg daily. Max: 2.5 mg/kg daily. Discontinue treatment if there is no improvement after 6 mth.
- Child: Up to 3 mg/kg/day. Discontinue treatment if there is no improvement after 6 mth.
Discoid and systemic lupus erythematosus:
- Adult: As base: Initially, 150 mg once daily, reduce gradually after maximal response. Max dose: 2.5 mg/kg daily.
- Child: 3 mg/kg daily.
Prophylaxis of malaria:
- Adult: As base: 300 mg once wkly, starting 1 wk before exposure, continuing throughout on a wkly basis and for at least 4 wk after exposure.
- Child: 5 mg/kg weekly.
Side Effects
Retinopathy, hair loss, photosensitivity, tinnitus, myopathy (long-term therapy). Psychosis, seizures, leucopenia and rarely aplastic anaemia, hepatitis, GI upsets, dizziness, hypokalaemia, headache, pruritus, urticaria, difficulty in visual accommodation.
The most serious toxic hazard of prolonged therapy with doses is the occasional development of irreversible retinal damage. For this reason considerable caution is needed in the use of choroquine for long-term high dosage therapy and such use should only be considered when no other drug is available. Defects in visual accommodation may occur on first taking choloquine and patients should be warned regarding driving or operating machinery.
Toxicity
Patients experiencing an overdose may present with headache, drowsiness, visual disturbances, nausea, vomiting, cardiovascular collapse, shock, convulsions, respiratory arrest, cardiac arrest, and hypokalemia. Overdose should be managed with symptomatic and supportive treatment which may include prompt emesis, gastric lavage, and activated charcoal.
Precaution
Psoriasis, diseases of the haematopoietic or CNS systems, myasthenia gravis, hepatic or renal impairment, G6PD deficiency, epilepsy, childn. Pregnancy and lactation. Slow infusion is used upon IV admin to prevent cardiotoxicity.
Interaction
Concomitant therapy with phenylbutazone predisposes to dermatitis, antagonises effect of neostigmine and pyridostigmine, reduces bioavailability of ampicillin. Cimetidine inhibits metabolism of chloroquine raising plasma levels.
Food Interaction
- Take with food. Food reduces irritation and increases bioavailability.
[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.
Difosfato de Cloroquina Drug Interaction
Major: ciprofloxacin, ciprofloxacinModerate: celecoxib, celecoxib, pregabalin, pregabalinUnknown: amoxicillin / clavulanate, amoxicillin / clavulanate, diphenhydramine, diphenhydramine, esomeprazole, esomeprazole, acetaminophen, acetaminophen, cyanocobalamin, cyanocobalamin, ascorbic acid, ascorbic acid, cholecalciferol, cholecalciferol
Difosfato de Cloroquina Disease Interaction
Major: oculotoxicity, porphyriaModerate: arrhythmias, bone marrow suppression, ototoxicity, seizures, glucose-6-PD deficiency, hepatotoxicity, myasthenia gravis, psoriasis
Volume of Distribution
The volume of distribution of chloroquine is 200-800L/kg.
Elimination Route
Difosfato de Cloroquina oral solution has a bioavailability of 52-102% and oral tablets have a bioavailability of 67-114%. Intravenous chloroquine reaches a Cmax of 650-1300µg/L and oral chloroquine reaches a Cmax of 65-128µg/L with a Tmax of 0.5h.
Half Life
The half life of chloroquine is 20-60 days.
Clearance
Difosfato de Cloroquina has a total plasma clearance of 0.35-1L/h/kg.
Elimination Route
Difosfato de Cloroquina is predominantly eliminated in the urine. 50% of a dose is recovered in the urine as unchanged chloroquine, with 10% of the dose recovered in the urine as desethylchloroquine.
Pregnancy & Breastfeeding use
Pregnancy Category C. Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.
Contraindication
Hypersensitivity, known or suspected resistant P. falciparum infection, porphyria, retinal damage, concurrent hepatotoxic drugs.
Acute Overdose
Symptoms: Headache, drowsiness, visual disturbances, nausea and vomiting, CV collapse, shock and convulsions followed by sudden and early respiratory and cardiac arrest. ECG may reveal atrial standstill, nodal rhythm, prolonged intraventricular conduction time and progressive bradycardia leading to ventricular fibrillation and/or arrest.
Management: Treatment is symptomatic and should be prompt with immediate evacuation of the stomach by emesis or gastric lavage. Finely powdered, activated charcoal may be used within 30 min after ingestion of the antimalarial to reduce intestinal absorption of the drug. To be effective, the dose of activated charcoal should be at least five times the estimated dose of chloroquine ingested.
Storage Condition
Store at 15-30° C.
Innovators Monograph
You find simplified version here Difosfato de Cloroquina
Difosfato de Cloroquina contains Chloroquine see full prescribing information from innovator Difosfato de Cloroquina Monograph, Difosfato de Cloroquina MSDS, Difosfato de Cloroquina FDA label
FAQ
What is Difosfato de Cloroquina used for?
Difosfato de Cloroquina is a cephalosporin antibiotic used to treat infections caused by bacteria.
How safe is Difosfato de Cloroquina?
Difosfato de Cloroquina is a medication primarily used to prevent and treat malaria in areas where malaria remains sensitive to its effects. Certain types of malaria, resistant strains, and complicated cases typically require different or additional medication.
How does Difosfato de Cloroquina work?
The major action of Difosfato de Cloroquina is to inhibit the formation of hemozoin (Hz) from the heme released by the digestion of hemoglobin (Hb).
What are the common side effects of Difosfato de Cloroquina?
Common side effects of Difosfato de Cloroquina are include:
- headache
- nausea
- loss of appetite
- diarrhea
- upset stomach
- stomach pain
- rash
- itching
- hair loss
Is Difosfato de Cloroquina safe during pregnancy?
There is no evidence that Difosfato de Cloroquina is harmful to an unborn baby, although more information about its use in pregnancy ideally needs to be collected. If you are travelling to certain regions you may be advised to take Difosfato de Cloroquina. You should not avoid taking Difosfato de Cloroquina because you are pregnant.
Is Difosfato de Cloroquina safe during breastfeeding?
Difosfato de Cloroquina is safe for mothers to breastfeed their infants when undergoing treatment for malaria with Difosfato de Cloroquina.
Can I drink alcohol with Difosfato de Cloroquina ?
Results from this study indicate that concomitant consumption of alcoholic beverages and oral administration of CQ tablets may aggravate the puritogenic effect of Difosfato de Cloroquina since more Difosfato de Cloroquina will be available for distribution to skin and skeletal muscle.
Can I drive after taking Difosfato de Cloroquina?
Difosfato de Cloroquina may cause vision problems. It may also make you dizzy or lightheaded. Do not drive or do anything else that could be dangerous until you know how this medicine affects you.
What time should I take Difosfato de Cloroquina?
Difosfato de Cloroquina works best when you take it on a regular schedule. If you are taking it once a week to prevent malaria, it is best to take it on the same day of each week.
How long does Difosfato de Cloroquina take to work?
Difosfato de Cloroquina may be 12 weeks or longer before you notice any benefit.
How long does Difosfato de Cloroquina stay in the system?
Difosfato de Cloroquina is extensively distributed with an enormous total apparent volume of distribution (Vd) more than 100 L/kg, and a terminal elimination half-life of 1 to 2 months.
How many time can I take Difosfato de Cloroquina daily?
The dose for an adult is two tablets once a week, on the same day of the week.
Can I take Difosfato de Cloroquina long-term?
Taking Difosfato de Cloroquina long-term or at high doses may cause irreversible damage to the retina of your eye that could progress to permanent vision problems. You may not be able to use Difosfato de Cloroquina if you have a history of vision changes or damage to your retina.
What happens if I take too much Difosfato de Cloroquina?
An overdose of Difosfato de Cloroquina 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).
Who should not take Difosfato de Cloroquina?
You should not use this medicine if you are allergic to Difosfato de Cloroquina or hydroxychloroquine. You may not be able to use Difosfato de Cloroquina if you have ever had vision changes or damage to your retina.
What happens if I overdose?
Seek emergency medical attention. An overdose of chloroquine 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 happens if I miss a dose?
In the instance that you miss a dose, take it as soon as possible that day. For daily regimes, if you miss the dose completely for that day, skip the missed dose entirely and continue with your next dose. Never take a double dose to make up for a missed dose.
What happen If I suddenly stop taking Difosfato de Cloroquina?
It is important to continue taking this for the length of time prescribed. 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. Difosfato de Cloroquina may not prevent malaria in all cases.
Can Difosfato de Cloroquina affects my heart ?
Difosfato de Cloroquina 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).
Can Difosfato de Cloroquina affect my kidneys?
It is concluded that Difosfato de Cloroquina administration impairs kidney function, resulting in inappropriate Na+ and Cl- retention. This effect is likely to be mediated via Difosfato de Cloroquina -induced increases in plasma aldosterone concentration and lowering of GFR.
Can Difosfato de Cloroquina affect my liver?
Difosfato de Cloroquina prevents ischemic liver damage at the early phase, but aggravates liver damage at the late phase in liver I/R injury.
Can Difosfato de Cloroquina affect my fertility?
In the in-vitro studies, more than 80% os spermatozoa were immotile in all concentrations of chloroquine tested. These results suggest that Difosfato de Cloroquina brings about its antifertility effect by decreasing sperm motility.
