Quinine Sulfate - Drug Monograph

Introduction

Quinine sulfate is an antimalarial alkaloid derived from the bark of the Cinchona tree. Historically used for centuries to treat malaria, it remains an important therapeutic agent in specific clinical scenarios. While its use has declined with the development of newer antimalarials, quinine sulfate continues to have clinical relevance in malaria treatment and certain off-label applications.

Mechanism of Action

Quinine exerts its antimalarial effects through several mechanisms. The primary action involves accumulation in the acidic food vacuoles of Plasmodium species, where it inhibits heme polymerase. This enzyme normally detoxifies hematin produced during hemoglobin digestion; inhibition leads to accumulation of toxic heme products that kill the malaria parasite. Additionally, quinine may interfere with carbohydrate metabolism and DNA replication in plasmodia. Its muscle relaxant properties in nocturnal leg cramps are thought to result from increased refractory period and decreased excitability of motor end plates.

Indications

• Treatment of uncomplicated Plasmodium falciparum malaria (in combination with other antimalarials)
• Treatment of chloroquine-resistant Plasmodium falciparum malaria

• Nocturnal leg cramps (though FDA has restricted this use due to risk-benefit concerns)
• Babesiosis (in combination with clindamycin)

Dosage and Administration

• 648 mg (2 capsules) every 8 hours for 7 days
• Always administered in combination with doxycycline, tetracycline, or clindamycin

• CrCl 10-50 mL/min: Administer every 8-12 hours
• CrCl <10 mL/min: Administer every 24 hours

• Use with caution; consider dose reduction in severe impairment

• 30 mg/kg/day divided every 8 hours for 7 days
• Maximum dose: 2 g/day

• Administer with food to minimize gastrointestinal upset
• Do not crush or break capsules

Pharmacokinetics

Contraindications

• Hypersensitivity to quinine or related compounds (quinidine, mefloquine)
• Glucose-6-phosphate dehydrogenase (G6PD) deficiency
• Myasthenia gravis
• Optic neuritis
• Tinnitus or history of quinine-induced tinnitus
• Pregnancy (except for treatment of chloroquine-resistant malaria)
• Prolonged QT interval or concomitant drugs that prolong QT interval

Warnings and Precautions

• Serious hematologic reactions including thrombocytopenia, hemolytic uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP), and disseminated intravascular coagulation (DIC)
• QT prolongation and serious arrhythmias including torsades de pointes

• Cinchonism (tinnitus, hearing loss, nausea, visual disturbances) may occur
• Hypoglycemia (especially in pregnancy and severe malaria)
• Use with extreme caution in patients with cardiac conditions
• Monitor for signs of hemolysis in all patients
• Risk of thrombocytopenia (monitor platelet counts)

Drug Interactions

• CYP3A4 inhibitors (ketoconazole, ritonavir): ↑ quinine levels
• CYP3A4 inducers (rifampin, carbamazepine): ↓ quinine levels
• Drugs that prolong QT interval (antiarrhythmics, antipsychotics, antidepressants): ↑ risk of torsades de pointes
• Digoxin: ↑ digoxin levels
• Warfarin: ↑ anticoagulant effect
• Neuromuscular blocking agents: ↑ neuromuscular blockade

• Antacids: ↓ quinine absorption
• Mefloquine: ↑ risk of ECG abnormalities and convulsions

Adverse Effects

• Cinchonism (tinnitus, hearing decreased, headache, nausea, visual disturbances)
• GI upset (nausea, vomiting, diarrhea)
• Hypoglycemia

• Thrombocytopenia
• Hemolytic uremic syndrome
• QT prolongation and torsades de pointes
• Severe hypersensitivity reactions
• Hepatitis
• Acute kidney injury
• Blindness (with overdose)

Monitoring Parameters

• CBC with platelets
• Electrolytes, renal and hepatic function
• ECG (QT interval)
• Blood glucose
• G6PD status (if not previously documented)

• Daily platelet counts during initial treatment
• ECG monitoring if high dose or cardiac risk factors
• Blood glucose monitoring (especially in pregnancy)
• Signs/symptoms of cinchonism
• Audiometric and ophthalmologic exams if prolonged therapy

• Target plasma concentration: 8-15 mg/L for malaria
• Trough levels recommended in renal impairment

Patient Education

• Take with food to reduce stomach upset
• Complete full course of therapy even if feeling better
• Immediately report any signs of bleeding, bruising, palpitations, dizziness, or hearing/vision changes
• Avoid grapefruit juice during therapy
• Be aware of possible hypoglycemia symptoms (sweating, shaking, hunger)
• Do not use for leg cramps without explicit physician recommendation
• Inform all healthcare providers of quinine use before any new medications

References

1. FDA Prescribing Information: Qualaquin (quinine sulfate). 2020 2. World Health Organization. Guidelines for the treatment of malaria. 3rd edition. 2015 3. Liles NW, Page EE. Quinine: a review of its clinical use and toxicity. Journal of Emergency Medicine. 2018;54(2):215-223 4. Rosenthal PJ. Antimalarial drug discovery: old and new approaches. Journal of Experimental Biology. 2003;206(Pt 21):3735-3744 5. Tan KR, Magill AJ, Parise ME, et al. Doxycycline for malaria chemoprophylaxis and treatment: report from the CDC expert meeting on malaria chemoprophylaxis. American Journal of Tropical Medicine and Hygiene. 2011;84(4):517-531 6. Tracy JW, Webster LT. Drugs used in the chemotherapy of protozoal infections. In: Hardman JG, Limbird LE, eds. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 12th ed. McGraw-Hill; 2011:1423-1468