The suitable dosage for each patient should be prescribed by a doctor.

Method of Administration:

by SLOW Infusion (or deep IM inj)**.
**If IV infusion is not possible, quinine dihydrochloride has been given IM route. This can be an irritant, cause pain (quinine dihydrochloride are acidic (pH 2)), focal necrosis and abscess formation, and fatal tetanus has developed in some patients, and there have been concerns regarding its safety and efficacy. The IM route should only be used as a last resort.

IV infusion: The solution should be diluted before administration infused slowly over 4 hours.
Hypotension and cardiac arrest may result from rapid intravenous injection. Intravenous quinine should be given only by infusion, never injection.

Loading dose: max.< 1400mg และ Maintenance dose: max. < 700mg

Quinine causes an approximately 10% prolongation of the electrocardiograph QT interval – mainly as a result of slight QRS widening. The effect on ventricular repolarization is much less than that with quinidine.

This medication should be taken with or after meals to minimize gastrointestinal irritation.

Usual adult and adolescent dose

Malaria, Plasmodium falciparum , severe (treatment):
Loading dose: 20 mg/kg up to a maximum of 1400 mg given slowly by infusion over 4 hours. Commence the maintenance doses 8 to 12 hours after loading dose.

Maintenance dose: 10 mg/kg up to a maximum of 700 mg over 4 hours given slowly by infusion. Repeat every 8 - 12 hours if necessary.

A loading dose is not required if anti-malarials have been given during the previous 24 hours.
If parenteral therapy is required for more than 48 hours, the maintenance dose of quinine should be reduced by one third to one half to 5 mg/kg to avoid accumulation and drug level monitoring is important.

Alternatively, in Intensive Care Units or if an infusion pump is available, an initial loading dose of 7mg/kg may be given over 30 minutes followed immediately by the first of the maintenance infusions.

Note: The two dosage regimens listed above are equally effective.
Either regimen should be administered in conjunction with doxycycline, clindamycin, or sulfadoxine/pyrimethamine combination.
Treatment should be switched to oral quinine sulfate when the patient can swallow, to complete a seven-day treatment course.

Children Dosage:

Paediatric - Intravenous – 10 mg per kg diluted and infused slowly at a rate not exceeding 0.5 mg per minute, preferably with ECG monitoring.

Antiprotozoal—The precise mechanism of action of quinine in malaria has not been determined but may be based on its ability to concentrate in parasitic acid vesicles, causing an elevation of pH in intracellular organelles. This is thought to disrupt the intracellular transport of membrane components and macromolecules, and phospholipase activity. Quinine has a schizonticidal action. Its ability to concentrate in parasitized erythrocytes may account for its selective toxicity against the erythrocytic stages of the four malarial parasites, including Plasmodium falciparum strains resistant to chloroquine. The drug is also gametocidal against Plasmodium vivax and Plasmodium malariae.

Antimyotonic—Quinine increases the refractory period of skeletal muscle by direct action on the muscle fiber and the distribution of calcium within the muscle fiber, thereby diminishing the response to tetanic stimulation. It also decreases the excitability of the motor end-plate region, reducing the responses to repetitive nerve stimulation and to acetylcholine.

Patients hypersensitive to quinidine may be hypersensitive to this medication also.
Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).

Risk-benefit should be considered when the following medical problems exist
» Blackwater fever, history of (interrupted or recurrent quinine therapy in patients with Plasmodium falciparum infections may predispose them to the complications of blackwater fever, including anemia and hemolysis with renal failure)

Cardiac arrhythmias, history of, or QT prolongation (a prolonged QT interval has been noted in patients being treated for cerebral malaria, without correlation with plasma quinine concentration; patients with a history of cardiac arrhythmias or QT prolongation may be at risk for arrhythmias while taking quinine)

Glucose-6-phosphate dehydrogenase (G6PD) deficiency (hemolysis or hemolytic anemia may occur in G6PD-deficient patients; however, quinine has been given safely in therapeutic doses to patients with G6PD deficiency)

» Hypersensitivity to quinine or quinidine
» Hypoglycemia (quinine stimulates release of insulin from the pancreas; hypoglycemia may also be a complication of severe P. falciparum malaria, especially in children and during pregnancy)

» Myasthenia gravis (quinine may exacerbate muscle weakness in myasthenia gravis due to its neuromuscular blocking effects)

» Purpura, thrombocytopenic, or history of (quinine may cause thrombocytopenic purpura, especially in highly sensitive patients or in patients with a previous history of this reaction to quinine)

Check for hypersensitivity to quinine or quinidine BEFORE administration. It is important that when given intravenously it should be given by SLOW infusion and the patient observed closely for signs of cardiotoxicity.

Pulse and blood pressure should be closely monitored and the rate of infusion attenuated if dysrhythmias occur, and blood glucose concentrations should be monitored. Therapy should be changed to oral administration as soon as possible.

If intravenous infusion is not possible, quinine dihydrochloride has been given intramuscularly. This can be an irritant, cause pain, focal necrosis and abscess formation, and fatal tetanus has developed in some patients, and there have been concerns regarding its safety and efficacy. The intramuscular route should only be used as a last resort.

Haemolysis

QUININE DIHYDROCHLORIDE should be stopped immediately and supportive measures instituted if signs of haemolysis appear. Haemolysis with a potential for haemolytic anaemia has been reported when given to patients with G6PD deficiency.

Prothrombin Formation

QUININE DIHYDROCHLORIDE is capable of causing hypoprothrombinaemia and may enhance the effect of anticoagulants.

Atrial Fibrillation

Patients with this condition should be digitilised before receiving quinine as otherwise it may cause an increase in the ventricular rate.

Hypersensitivity

Reactions include cutaneous flushing, pruritis, rash, fever, facial oedema, GI distress, dyspnoea, tinnitus, and impairment of vision. The most frequently reported hypersensitivity reaction is extreme flushing of the skin with intense pruritis. If evidence of hypersensitivity occurs, quinine therapy should be discontinued.
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The use of anti-malarials for the treatment of life threatening malaria during pregnancy is acceptable, because the small risk to the fetus is outweighed by the benefits to the mother and fetus.

In high doses, quinine causes fetal injuries in the form of deafness, development disturbances, and malformation of the extremities and cranium. It has the ability to induce uterine contractions and constitutes a risk of abortion.

Quinine is distributed into breast milk in small amounts. One study suggests that a breast-fed infant will receive approximately 1.5 to 3 mg per day of quinine base from maternal therapy. Problems in humans have not been documented.

ยาขับออกทางน้ำนมได้ แต่ไม่พบว่าทำให้เกิดอันตรายต่อทารก จึงสามารถให้นมบุตรในระหว่างที่ใช้ Quinine ได้ แต่ควรเฝ้าระวังภาวะเลือดออกหรือดีซ่านในทารก โดยเฉพาะในเด็กที่คลอดก่อนกำหนดหรือมีอายุน้อยกว่า 1 เดือน และห้ามใช้ในทารกที่มีภาวะพร่องเอนไซม์ G-6-PD

Gastrointestinal disturbances (abdominal or stomach cramps or pain; diarrhea; nausea; vomiting)
Note: Symptoms of gastrointestinal disturbances, such as nausea and vomiting, may be related to central nervous system (CNS) effects of quinine.

When quinine is given repeatedly, a group of symptoms known as cinchonism occurs. Cinchonism symptoms include tinnitus, impaired
hearing, headache, nausea, disturbed vision, vomiting, abdominal pain, diarrhoea, and vertigo.

Blood dyscrasias such as agranulocytosis, leukopenia, and/or thrombocytopenia (black, tarry stools; blood in urine or stools; cough or hoarseness; fever or chills; lower back or side pain; painful or difficult urination; pinpoint red spots on skin; sore throat; unusual bleeding or bruising; unusual tiredness or weakness)

hypoglycemia (anxiety; behavior change, similar to drunkenness; blurred vision; cold sweats; confusion; convulsions or coma; cool pale skin; difficulty in concentrating; drowsiness; excessive hunger; fast heartbeat; headache; nausea; nervousness; nightmares; restless sleep; shakiness; slurred speech; unusual tiredness or weakness)

Note: Hypoglycemia, which may be severe and recurrent, has been reported in some patients with severe malaria caused by Plasmodium falciparum who received quinine therapy, and there was some evidence that quinine-induced insulin secretion may have been one of several possible precipitating factors.

hypersensitivity reactions (abdominal pain; difficulty in breathing and/or swallowing; fever; hives; nausea; reddening of the skin, especially around ears; swelling of eyes, face, or inside of nose; unusual tiredness or weakness)

hypoprothrombinemia (unusual bleeding or bruising) visual disturbances (blurred vision; disturbed color perception; double vision; night blindness)

Note: Hemolytic uremic syndrome (HUS) is a multi-system disorder that is characterized by hemolytic anemia, thrombocytopenia, disseminated intravascular coagulation (DIC), and acute renal failure . This reaction may occur within hours of a single ingestion of quinine. Several case reports have been published describing patients who have had an acute hypersensitivity reaction to quinine that resulted in adult HUS.

Hypoprothrombinemia may be reversed with vitamin K administration.