QUININE SULPHATE TABLETS BP 300 MG

Indications

• Severe falciparum malaria
• Chloroquine-resistant malaria
• Malaria prophylaxis in high-risk areas

Dosage

Children: Child (body-weight 45 kg and above): Loading dose 20 mg

Adults: Loading dose: 20 mg/kg (max. 1.4 g) infused over 4 hours. Maintenance: 10 mg/kg every 8 hours (max. per dose 700 mg). For non-falciparum malaria, 600 mg every 8 hours for 5–7 days, in combination with doxycycline or clindamycin.

Mechanism of action

Quinine and related antimalarial drugs are theorized to be toxic to malaria parasites by interfering with their ability to digest hemoglobin. This leads to starvation of the parasite and accumulation of toxic levels of partially degraded hemoglobin. Quinine acts as a blood schizonticide and has been shown to inhibit heme polymerase, resulting in increased levels of cytotoxic heme within the parasite.

Pharmacodynamics

Quinine is particularly effective against chloroquine-resistant strains of Plasmodium falciparum. It acts as a blood schizonticide and possesses gametocytocidal activity against Plasmodium vivax and Plasmodium malariae. It is a weak base and becomes concentrated in the food vacuoles of the parasite, which enhances its antimalarial efficacy. Due to its side effects and toxicity, its use is generally reserved for severe cases of malaria.

Pharmacokinetics

Quinine is administered intravenously or orally, with a half-life that can vary based on the route of administration and the patient's renal function. Peak plasma concentrations are typically achieved within 1 to 3 hours of intravenous administration. It is metabolized in the liver and excreted primarily through urine. Dosing must be adjusted in cases of renal impairment to avoid toxicity.

Adverse effects

• alopecia
• angioedema
• bone marrow disorders
• choleostasis
• constipation
• diarrhoea
• fever
• gastric disorders
• megaloblastic anaemia
• oral disorders
• skin reactions
• vasculitis

Interactions

• quinine + digoxin: Moderate (increases concentration)
• hiv-protease inhibitors + quinine: Unknown (affects exposure)
• cimetidine + quinine: Unknown (increases exposure)
• rifampicin + quinine: Unknown (decreases exposure)

Precautions

• history of seizures-avoid large loading doses
• predisposition to folate deficiency

Pregnancy

Benefit of prophylaxis in malaria outweighs risk. Adequate folate supplements should be given to the mother.

Breast-feeding

Quinine is excreted in breast milk, caution is advised.

Storage

Store in a cool, dry place. Protect from light.

Formulations

• Quinine hydrochloride
• Quinine dihydrochloride
• Quinine sulfate

Mechanism of action

The theorized mechanism of action for quinine and related anti-malarial drugs is that these drugs are toxic to the malaria parasite. Specifically, the drugs interfere with the parasite's ability to break down and digest hemoglobin. Consequently, the parasite starves and/or builds up toxic levels of partially degraded hemoglobin in itself. Quinine has a local anesthetic action and analgesic, antipyretic, and oxytocic effects. Quinine also has cardiovascular effects similar to those of quinidine.

Pharmacodynamics

Quinine is used parenterally to treat life-threatening infections caused by chloroquine-resistant Plasmodium falciparum malaria. Quinine acts as a blood schizonticide although it also has gametocytocidal activity against P. vivax and P. malariae. Because it is a weak base, it is concentrated in the food vacuoles of P. falciparum. It is thought to act by inhibiting heme polymerase, thereby allowing accumulation of its cytotoxic substrate, heme. As a schizonticidal drug, it is less effective and more toxic than chloroquine. However, it has a special place in the management of severe falciparum malaria in areas with known resistance to chloroquine.