Quinine Sulfate

Approved Indications:

• Treatment of Uncomplicated Malaria
• Specifically caused by Plasmodium falciparum, including chloroquine-resistant strains
• Typically used in combination with a second agent (e.g., doxycycline or clindamycin)

Clinically Accepted Off-Label Uses:

• Babesiosis
• Used in combination with clindamycin in mild-to-moderate cases where atovaquone-based therapy is unsuitable
• Nocturnal Leg Cramps (off-label use not recommended)
• Previously used, but now discouraged due to serious adverse effects including thrombocytopenia and arrhythmias
• Malaria due to other Plasmodium species
• May be used if first-line therapies (e.g., artemisinin derivatives) are unavailable or contraindicated

Route of Administration: Oral

Administer with food to reduce gastrointestinal side effects. Swallow capsules/tablets whole.

Adults:

• Uncomplicated P. falciparum Malaria:
• Quinine Sulfate 648 mg orally every 8 hours for 7 days
• Combine with one of the following:
• Doxycycline 100 mg orally twice daily for 7 days, or
• Clindamycin 300–600 mg orally every 8 hours for 7 days

Pediatrics (Off-label):

• Children ≥8 years:
• 10 mg/kg orally every 8 hours for 7 days
• Use in combination with doxycycline or clindamycin
• Maximum per dose: 648 mg

Elderly:

• Use standard adult dosage, but monitor closely due to higher risk of cardiac and CNS side effects.

Renal Impairment:

• CrCl < 10 mL/min: Extend dosing interval to every 12 hours
• Monitor ECG and serum quinine levels (if available)

Hepatic Impairment:

• Use cautiously; consider dose adjustment
• Monitor for signs of toxicity (cinchonism, visual changes)

Quinine acts by disrupting the parasite’s heme detoxification pathway inside red blood cells. Plasmodium species digest hemoglobin and release toxic heme. Normally, the parasite converts heme to non-toxic hemozoin. Quinine interferes with this polymerization process, causing toxic heme accumulation, leading to oxidative stress, membrane damage, and eventual parasite death. It is active only against the asexual erythrocytic stage of malaria parasites.

• Absorption: Rapid and nearly complete after oral administration
• Bioavailability: Approximately 88%
• Time to Peak: ~1 to 3 hours post-dose
• Distribution: Wide tissue distribution; 70% plasma protein binding
• Metabolism: Extensively metabolized in the liver via CYP3A4, CYP2C9, and CYP2C19 pathways
• Active Metabolites: None with significant therapeutic effect
• Half-life: ~11 hours (may be prolonged in renal impairment or severe malaria)
• Excretion: Primarily via the urine (~20% unchanged); remainder as inactive metabolites

• Pregnancy:
• FDA Pregnancy Category C
• Crosses the placenta; animal studies show fetal toxicity, but quinine is considered safe for treating malaria in all trimesters, as the benefits outweigh potential risks
• Monitor for hypoglycemia, especially in the third trimester
• Lactation:
• Excreted in small amounts in breast milk
• Generally considered compatible with breastfeeding
• Monitor breastfed infants for irritability, vomiting, or hearing changes if maternal therapy is prolonged

• Primary Class: Antimalarial
• Subclass: Cinchona Alkaloid
• Pharmacological Action: Blood schizonticide with mild analgesic and antipyretic effects

• Hypersensitivity to quinine, quinidine, mefloquine, or other cinchona alkaloids
• History of quinine-induced thrombocytopenia, hemolytic anemia, or hypersensitivity reactions
• Myasthenia gravis
• Optic neuritis or preexisting severe visual impairment
• Prolonged QT interval or known ventricular arrhythmias
• Concomitant use with drugs that significantly prolong QT interval
• Use for nocturnal leg cramps is contraindicated due to serious safety risks

• Black Box Warning:
• Not approved for nocturnal leg cramps due to life-threatening risks: thrombocytopenia, hemolytic uremic syndrome (HUS), and fatal arrhythmias
• Cardiac Risk:
• Risk of QT prolongation and torsades de pointes
• Avoid use with other QT-prolonging agents
• ECG monitoring recommended in patients with heart disease
• CNS Toxicity:
• High plasma levels can cause cinchonism: tinnitus, headache, blurred vision, dizziness, confusion
• Seizures and coma possible at toxic doses
• Hematologic Toxicity:
• Risk of immune-mediated thrombocytopenia, agranulocytosis, or DIC
• Discontinue immediately if blood dyscrasia is suspected
• Hypoglycemia:
• Stimulates pancreatic insulin release
• Monitor glucose closely, especially in pregnancy or severe malaria
• Visual Effects:
• Prolonged use or overdose may lead to retinal damage, optic neuritis, or blindness

Common Adverse Effects:

• Neurologic: Tinnitus, dizziness, headache, blurred vision
• Gastrointestinal: Nausea, vomiting, abdominal pain, diarrhea
• Musculoskeletal: Leg cramps, muscle weakness
• General: Sweating, flushing, fatigue

Serious/Rare Adverse Effects:

• CNS: Confusion, seizures, severe cinchonism
• Cardiovascular: QT prolongation, torsades de pointes, ventricular fibrillation
• Hematologic: Thrombocytopenia, HUS, hemolytic anemia
• Ocular: Optic neuritis, visual loss (rare, dose-related)
• Allergic: Anaphylaxis, angioedema

• QT-Prolonging Agents (e.g., amiodarone, fluoroquinolones, macrolides):
  ↑ Risk of torsades de pointes
• Antacids (aluminum or magnesium):
  ↓ Quinine absorption – separate doses by ≥2 hours
• CYP3A4 Inhibitors (e.g., ketoconazole, ritonavir):
  ↑ Quinine plasma levels – ↑ toxicity risk
• CYP3A4 Inducers (e.g., rifampin, phenytoin, carbamazepine):
  ↓ Quinine effectiveness – adjust dose or monitor response
• Digoxin:
  May increase digoxin levels – monitor for toxicity
• Warfarin:
  Potentially enhanced anticoagulant effect – monitor INR closely
• Neuromuscular Blocking Agents:
  Potentiated effects when used concurrently
• Alcohol:
  May exacerbate CNS depression or increase cinchonism risk

• FDA Safety Update:
• Reinforced restriction against use for nocturnal leg cramps
• Highlighted risks of thrombocytopenia, cardiac toxicity, and drug-induced TTP/HUS
• CDC Malaria Guidelines:
• Quinine remains a second-line therapy for chloroquine-resistant P. falciparum
• Recommended to be used in combination with doxycycline, tetracycline, or clindamycin for full parasite clearance
• WHO Recommendations:
• Quinine acceptable in all trimesters of pregnancy
• Preferable when artemisinin-based therapies are unavailable or contraindicated

• Store at a controlled room temperature of 20°C to 25°C (68°F to 77°F)
• Allowable temperature range: 15°C to 30°C
• Protect from light and moisture
• Store in tightly closed containers
• Do not refrigerate or freeze
• No reconstitution or special handling required for oral capsules/tablets