Kinin Dak

Uses

Kinin Dak Sulfate, is an antimalarial drug used only for treatment of uncomplicated Plasmodium falciparum malaria. Kinin Dak sulfate has been shown to be effective in geographical regions where resistance to chloroquine has been documented

Kinin Dak Sulfate oral capsules are not approved for:

• Treatment of severe or complicated P. falciparum malaria.
• Prevention of malaria.
• Treatment or prevention of nocturnal leg cramps

Kinin Dak Dihydrochloride is used for the acute treatment of malaria. It may also be used in the treatment of Babesiosis in conjunction with clindamycin.

Kinin Dak is also used to associated treatment for these conditions: Malaria caused by Plasmodium falciparum

How Kinin Dak works

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.

Dosage

Kinin Dak dosage

Intravenous:

• Adult: Initially, 20 mg/kg to max 1.4 g over 4 hr with maintenance infusion started after 8 hr. Maintenance infusions: 10 mg/kg to max 700 mg over 4 hr 8 hrly. Loading dose should not be given if patient has received quinine, quinidine, halofantrine or mefloquine during the previous 24 hr.
• Child:≤5 mg/kg/hr by slow IV infusion.

Oral:

• Adult: 648 mg given every 8 hr for 7 days.
• Child: ≥8 yr10 mg/kg 8 hrly for 7 days.

Should be taken with food. Take with food to minimise GI discomfort.

Reconstitutions

Dilute in NaCl 0.9% to a concentration of diHCl 60-100 mg/mL.

Side Effects

Headache, nausea, disturbed vision, impaired hearing, tinnitus, abdominal pain, vomiting, diarrhoea, vertigo; flushing skin with intense pruritus, urticaria; fever, dyspnoea, agranulocytosis, palpitations, rashes; myalgia, muscle weakness, asthma, asthenia, disorientation, angioedema; haemoglobinuria; hypoprothrombinaemia, hypoglycaemia, hypotension, renal failure.

Toxicity

Kinin Dak is a documented causative agent of drug induced thrombocytopenia (DIT). Thrombocytopenia is a low amount of platelets in the blood. Kinin Dak induces production of antibodies against glycoprotein (GP) Ib-IX complex in the majority of cases of DIT, or more rarely, the platelet-glycoprotein complex GPIIb-IIIa. Increased antibodies against these complexes increases platelet clearance, leading to the observed thrombocytopenia.

Precaution

Patients with cardiac conduction defects, heart block or AF. Pregnancy and lactation.

Interaction

Reduced renal clearance of amantadine. Reduced clearance with cimetidine. Increased anticoagulant effect of warfarin and other anticoagulants. Reduced plasma levels of ciclosporin. Increased plasma levels of digoxin. Increased risk of myopathy and rhabdomyolysis with atorvastatin. May enhance hypoglycaemic effects of oral antidiabetics.

Food Interaction

• Take with food. Food reduces irritation.

[Minor] Coadministration with grapefruit juice does not appear to affect the pharmacokinetics of quinine in a clinically relevant manner.

Although grapefruit juice is an inhibitor of CYP450 3A4 and quinine is metabolized by this pathway to its major metabolite, 3-hydroxyquinine, a study of ten healthy volunteers found no significant differences in quinine peak plasma concentration (Cmax), time to reach Cmax (Tmax), terminal elimination half-life, systemic exposure (AUC), or apparent oral clearance (Cl

Relative to the control period, the apparent renal clearance of quinine was markedly increased by 81% during treatment with half-strength grapefruit juice.

However, since renal clearance accounts for approximately 6% of the total clearance of quinine, this change would likely have minimal clinical impact.

The lack of a significant interaction is probably due to the fact that grapefruit juice primarily inhibits intestinal rather than hepatic CYP450 3A4, and quinine is not known to undergo significant presystemic metabolism as evidenced by its relatively high oral bioavailability (76% to 88%).

Nevertheless, excessive consumption of grapefruit juice and tonic water (which contains quinine) was suspected as the cause of torsade de pointes arrhythmia in a patient with a history of asymptomatic long QT syndrome.

Treatment with magnesium sulfate and metoprolol had no effect, but the arrhythmia resolved spontaneously 48 hours after discontinuation of the drinks.

Based on current data, moderate grapefruit juice consumption is probably safe for the majority of patients taking quinine.

Kinin Dak Drug Interaction

Moderate: fluticasone / salmeterol, duloxetine, budesonide / formoterolUnknown: aspirin, diphenhydramine, calcium / vitamin d, celecoxib, rosuvastatin, omega-3 polyunsaturated fatty acids, fluticasone nasal, atorvastatin, pregabalin, esomeprazole, acetaminophen, levothyroxine, acetaminophen, cyanocobalamin, ascorbic acid, cholecalciferol, cetirizine

Kinin Dak Disease Interaction

Major: QT prolongation, G-6-PD deficiency, myasthenia gravis, ocular toxicity, thrombocytopenia, tinnitusModerate: liver impairment, renal impairment

Volume of Distribution

• 1.43 ± 0.18 L/kg [Healthy Pediatric Controls]
• 0.87 ± 0.12 L/kg [P. falciparum Malaria Pediatric Patients]
• 2.5 to 7.1 L/kg [healthy subjects who received a single oral 600 mg dose]

Elimination Route

76 - 88%

Half Life

Approximately 18 hours

Clearance

• 0.17 L/h/kg [healthy]
• 0.09 L/h/kg [patients with uncomplicated malaria]
• 18.4 L/h [healthy adult subjects with administration of multiple-dose activated charcoal]
• 11.8 L/h [healthy adult subjects without administration of multiple-dose activated charcoal]
• Oral cl=0.06 L/h/kg [elderly subjects]

Elimination Route

Kinin Dak is eliminated primarily via hepatic biotransformation. Approximately 20% of quinine is excreted unchanged in urine.

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 to quinine, mefloquine or quinidine. Patients with nocturnal leg cramps; prolonged QT interval, tinnitus or optic neuritis, myasthenia gravis, G6PD deficiency, haemolysis and who had suffered from blackwater fever. Concomitant use with ritonavir, mefloquine, rifampicin, class IA and class III antiarrhythmic agents, neuromuscular blocking agents, other drugs known to cause QT prolongation, and Al- and/or Mg-containing antacids.

Special Warning

Renal Impairment:

• Oral:Severe: Initially, 648 mg followed after 12 hr by maintenance doses of 324 mg 12 hrly.
• Intravenous: Severe: Reduce maintenance dose to 5-7 mg/kg of quinine salt 8 hrly.

Hepatic Impairment:

• Mild to moderate: No dosage adjustment needed.
• Intravenous: Severe: Reduce maintenance dose to 5-7 mg/kg of quinine salt 8 hrly.

Acute Overdose

Symptoms: GI effects, CNS disturbances, oculotoxicity, cardiotoxicity,; tinnitus, abdominal pain, diarrhoea, vertigo, pulmonary oedema, hypotension, sweating, flushing, nausea, vomiting, headache, slightly disturbed vision, deafness, vasodilatation and adult resp distress syndrome.

Management: Administer multiple dose of activated charcoal within 1 hr or perform gastric lavage. Symptomatic (e.g. maintaining BP, respiration and renal function, treating arrhythmias) and supportive treatment.

Storage Condition

Store between 20-25° C. Protect from light.

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