Quinine Dosage

Usual Adult Dose for Malaria

Qualaquin (R):
Treatment of uncomplicated Plasmodium falciparum malaria: 648 mg orally every 8 hours for 7 days

Per Centers for Disease Control and Prevention (CDC) guidelines:
542 mg base (650 mg sulfate salt) orally 3 times a day for 3 to 7 days

Treatment of uncomplicated malaria due to chloroquine-resistant (or unknown resistance) P falciparum (or species not identified) infection should be in conjunction with one of the following: doxycycline, tetracycline, or clindamycin. In pregnant women, quinine sulfate plus clindamycin is recommended.

Treatment of uncomplicated malaria due to chloroquine-resistant P vivax infection should be in conjunction with either doxycycline or tetracycline plus primaquine phosphate. In pregnant women, quinine sulfate alone for 7 days is recommended.

Usual Pediatric Dose for Malaria

Qualaquin (R):
Treatment of uncomplicated P falciparum malaria:
16 years or older: 648 mg orally every 8 hours for 7 days

Per CDC guidelines:
8.3 mg base/kg (10 mg sulfate salt/kg) orally 3 times a day for 3 to 7 days; pediatric dose should never exceed adult dose

Less than 8 years:
Treatment of uncomplicated malaria due to chloroquine-resistant (or unknown resistance) P falciparum (or species not identified) infection should be combined with clindamycin.

Treatment of uncomplicated malaria due to chloroquine-resistant P vivax infection should be combined with primaquine phosphate.

8 years or older:
Treatment of uncomplicated malaria due to chloroquine-resistant (or unknown resistance) P falciparum (or species not identified) infection should be in conjunction with one of the following: doxycycline, tetracycline, or clindamycin.

Treatment of uncomplicated malaria due to chloroquine-resistant P vivax infection should be in conjunction with either doxycycline or tetracycline plus primaquine phosphate.

Renal Dose Adjustments

Qualaquin (R):
Mild and moderate renal dysfunction: Data not available

Severe chronic renal failure not on dialysis:
Loading dose: 648 mg orally once followed 12 hours later by maintenance dose
Maintenance dose: 324 mg orally every 12 hours

Liver Dose Adjustments

Qualaquin (R):
Mild to moderate hepatic dysfunction (Child-Pugh A and B): No adjustment recommended. Patients should be closely monitored for side effects associated with quinine.

Severe hepatic dysfunction (Child-Pugh C): Data not available

Precautions

Quinine is contraindicated in patients with prolonged QT interval, myasthenia gravis, glucose-6-phosphate dehydrogenase (G6PD) deficiency, and optic neuritis.

Quinine is contraindicated in patients with known hypersensitivity to mefloquine or quinidine due to documented cross-sensitivity. Quinine is contraindicated in patients with a history of potential hypersensitivity reactions associated with prior quinine use including (but not limited to) thrombotic thrombocytopenic purpura (TTP) or hemolytic uremic syndrome (HUS), thrombocytopenia, and blackwater fever.

Quinine use for the treatment or prevention of nocturnal leg cramps may result in serious and life-threatening hematological reactions (including thrombocytopenia and HUS/TTP) as well as hypersensitivity reactions, QT prolongation, serious cardiac arrhythmias (including torsades de pointes), and other serious side effects requiring medical intervention and hospitalization. The risk associated with the administration of quinine in the absence of evidence of its effectiveness for treatment or prevention of nocturnal leg cramps, outweighs any potential benefit in treating and/or preventing this benign, self-limiting condition.

Severe cases of thrombocytopenia (fatal or life-threatening) have been reported with quinine, including cases of HUS/TTP. In general, thrombocytopenia resolves within a week following quinine discontinuation; however, if quinine is not stopped, there is a risk for fatal hemorrhage. Reexposure to quinine (from any source) in patients with quinine-dependent antibodies could result in thrombocytopenia that is more rapid in onset and more severe than the original episode.

Serious hypersensitivity reactions reported with quinine include anaphylactic shock, anaphylactoid reactions, urticaria, serious skin rashes, including Stevens-Johnson syndrome and toxic epidermal necrolysis, angioedema, facial edema, bronchospasm, and pruritus. Several other serious adverse reactions reported with quinine (including TTP and HUS, thrombocytopenia, immune thrombocytopenic purpura, blackwater fever, disseminated intravascular coagulation, leukopenia, neutropenia, granulomatous hepatitis, and acute interstitial nephritis) may also be due to hypersensitivity reactions. Other hypersensitivity reactions have been observed following a single small dose of quinine. These have included cutaneous flushing, visual disturbance, fever, gastric distress, dyspnea, tinnitus, or hemoglobinuria. Quinine should be stopped in case of any signs or symptoms of hypersensitivity.

QT interval prolongation has been a consistent finding in studies which evaluated electrocardiographic changes with oral or parenteral quinine use, regardless of age, clinical status, or severity of disease. The maximum increase in QT interval has been shown to correspond with peak quinine plasma concentration. Quinine therapy has been rarely associated with potentially fatal cardiac arrhythmias, including torsades de pointes, and ventricular fibrillation. Quinine should not be administered with other drugs known to prolong the QT interval (including Class IA and III antiarrhythmic agents). Quinine should also be avoided in patients with known QT interval prolongation, in elderly patients, and in patients with clinical conditions known to prolong the QT interval (such as uncorrected hypokalemia, bradycardia, and certain cardiac conditions).

Quinine therapy should be used with caution in patients with atrial fibrillation or atrial flutter. A paradoxical increase in ventricular response rate may occur with quinine, similar to that observed with quinidine. Caution should be exercised when administering quinine therapy to patients with a history of atrial fibrillation, cardiac conduction problems, or heart block.

Hemolysis and hemolytic anemia can occur in patients with G6PD deficiency who receive quinine therapy. Quinine should be discontinued immediately upon the appearance of evidence of hemolysis.

Cinchonism may occur as a result of high quinine serum levels or overdose. The clinical presentation includes a cluster of symptoms (temporary deafness, tinnitus, headache, dizziness, rash, mental dullness, depression, confusion, and nausea) on repeated normal doses. Cardiac and nervous systems involvement is seen at high doses.

Safety and effectiveness of Qualaquin (R) have not been established in pediatric patients less than 16 years of age.

Dialysis

Data not available

Other Comments

The US FDA requires a Risk Evaluation and Mitigation Strategy (REMS) for quinine. It includes a Medication Guide and a communication plan. Additional information is available at www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm111350.htm.

Qualaquin (R) should be administered with food to minimize gastric upset.

Per CDC guidelines:
The US manufactured quinine sulfate capsule is available in a 324 mg dosage; therefore, 2 capsules should be sufficient for adult dosing. Due to the unavailability of non-capsule forms of quinine, pediatric dosing may be difficult.

Quinine treatment should be continued for 7 days if malaria infection was acquired in Southeast Asia, or for 3 days if acquired elsewhere.

In pregnant women diagnosed with uncomplicated malaria due to chloroquine-resistant P falciparum or chloroquine-resistant P vivax infection, doxycycline or tetracycline may be given with quinine if other treatment options are not tolerated or are not available, and the benefit outweighs the risks.

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