Introduction
Qualaquin (quinine sulfate) is an antimalarial medication derived from the bark of the cinchona tree. While historically significant as the first effective treatment for malaria, its current FDA-approved use is limited to the treatment of uncomplicated Plasmodium falciparum malaria. Quinine has also been used off-label for nocturnal leg cramps, though this use carries significant risks and is no longer recommended due to safety concerns.
Mechanism of Action
Quinine exerts its antimalarial effects through several mechanisms. The primary action involves inhibition of hemozoin polymerization in the plasmodium parasite, leading to accumulation of toxic heme products that are lethal to the organism. Additionally, quinine may interfere with parasite carbohydrate metabolism and DNA replication. The drug also possesses mild antipyretic, analgesic, and skeletal muscle relaxant properties, though the exact mechanisms for these effects are not fully understood.
Indications
FDA-approved indication:
- Treatment of uncomplicated Plasmodium falciparum malaria
Note: Quinine is not recommended for:
- Malaria prophylaxis
- Treatment of severe or complicated malaria (IV artesunate is preferred)
- Nocturnal leg cramps (due to risk-benefit profile)
Dosage and Administration
Adult dosing for malaria:- 648 mg (2 capsules) orally every 8 hours for 3-7 days
- Typically administered with doxycycline, tetracycline, or clindamycin
- 10 mg/kg (maximum 600 mg) orally every 8 hours for 3-7 days
- Renal impairment: Dose reduction required for CrCl <50 mL/min
- Hepatic impairment: Use with caution; consider dose reduction
- Geriatric patients: Initiate at lower end of dosing range
Pharmacokinetics
Absorption: Rapidly absorbed from GI tract with peak concentrations in 1-3 hours Distribution: Widely distributed throughout body tissues; crosses placenta and blood-brain barrier Protein binding: Approximately 70-85% bound to plasma proteins Metabolism: Extensively metabolized hepatically via CYP3A4 and CYP2C19 Elimination: Half-life of 8-14 hours; primarily renal excretion (20% as unchanged drug) Special considerations: Bioavailability may be reduced with food; antacids may decrease absorptionContraindications
- Hypersensitivity to quinine, quinidine, or mefloquine
- History of quinine-induced thrombocytopenia
- History of blackwater fever
- Prolonged QT interval or congenital long QT syndrome
- Myasthenia gravis
- G6PD deficiency (relative contraindication)
Warnings and Precautions
Black Box Warning:- Qualaquin is not indicated for the treatment or prevention of nocturnal leg cramps due to potential for serious hematologic reactions
- Cinchonism: Tinnitus, hearing loss, visual disturbances, nausea, and dizziness may occur
- Hematologic toxicity: Thrombocytopenia, hemolytic anemia, disseminated intravascular coagulation
- Cardiotoxicity: QT prolongation, ventricular arrhythmias, torsades de pointes
- Hypoglycemia: Particularly in pregnant women and patients with severe malaria
- Neurologic effects: Headache, seizures, confusion
- Hepatic toxicity: Monitor liver function tests
Drug Interactions
Major interactions:- CYP3A4 inhibitors (ketoconazole, ritonavir): Increased quinine levels
- CYP3A4 inducers (rifampin, carbamazepine): Decreased quinine levels
- Other QT-prolonging agents (antiarrhythmics, antipsychotics, antidepressants): Additive QT prolongation
- Digoxin: Quinine may increase digoxin levels
- Warfarin: Enhanced anticoagulant effect
- Neuromuscular blocking agents: Enhanced neuromuscular blockade
Adverse Effects
Common (≥1%):- Cinchonism (tinnitus, hearing loss, blurred vision, nausea)
- Headache
- Dizziness
- Rash
- GI disturbances (nausea, vomiting, diarrhea)
- Thrombocytopenia
- Hemolytic uremic syndrome/thrombotic thrombocytopenic purpura
- Ventricular arrhythmias
- Severe hypoglycemia
- Acute kidney injury
- Hepatitis
- Stevens-Johnson syndrome
Monitoring Parameters
- Complete blood count with platelets (baseline and regularly during therapy)
- Electrolytes, especially potassium and magnesium
- ECG for QT interval monitoring (baseline and during therapy)
- Blood glucose monitoring (especially in pregnant patients)
- Liver function tests
- Renal function
- Signs and symptoms of cinchonism
- Therapeutic drug monitoring (target concentration 8-15 mg/L) in severe cases
Patient Education
- Take with food to minimize gastrointestinal upset
- Do not crush or chew capsules
- Report immediately: ringing in ears, hearing changes, vision changes, unusual bleeding or bruising, palpitations, dizziness, or fever
- Avoid grapefruit juice during therapy
- Understand that this medication is for malaria treatment only, not for leg cramps
- Complete the full course of therapy even if feeling better
- Use effective contraception during treatment (teratogenic risk)
- Be aware of potential dizziness and avoid driving or operating machinery if affected
References
1. FDA Qualaquin Prescribing Information (2022) 2. Guidelines for the Treatment of Malaria (4th edition). World Health Organization, 2022 3. Griffith KS, Lewis LS, Mali S, et al. Treatment of malaria in the United States: a systematic review. JAMA. 2007;297(20):2264-2277 4. Tan KR, Magill AJ, Parise ME, et al. Doxycycline for malaria chemoprophylaxis and treatment: report from the CDC expert meeting on malaria chemoprophylaxis. Am J Trop Med Hyg. 2011;84(4):517-531 5. Liles NW, Page EE, Liles AL, et al. Diversity and severity of adverse reactions to quinine: a systematic review. Am J Hematol. 2016;91(5):461-466 6. Eperon G, Schmid C, Loutan L, et al. Treatment of imported malaria in adults: a systematic review and meta-analysis. Antimicrob Agents Chemother. 2014;58(2):654-663
This information is intended for educational purposes only and should not replace professional medical advice. Always consult with a healthcare provider for personalized medical guidance.