Malarex (Chloroquine)

Uses

Malarex (Chloroquine) 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

Malarex (Chloroquine) 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 Malarex (Chloroquine) works

Malarex (Chloroquine) 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.

Malarex (Chloroquine) 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.

Malarex (Chloroquine) 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

Malarex (Chloroquine) 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.

Malarex (Chloroquine) 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

Malarex (Chloroquine) 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

Malarex (Chloroquine) oral solution has a bioavailability of 52-102% and oral tablets have a bioavailability of 67-114%. Intravenous chloroquine reaches a C_max of 650-1300µg/L and oral chloroquine reaches a C_max of 65-128µg/L with a T_max of 0.5h.

Half Life

The half life of chloroquine is 20-60 days.

Clearance

Malarex (Chloroquine) has a total plasma clearance of 0.35-1L/h/kg.

Elimination Route

Malarex (Chloroquine) 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.

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