What is the recommended treatment and dosage of quinine (quinine) for uncomplicated malaria caused by Plasmodium falciparum?

Quinine Treatment for Uncomplicated Plasmodium falciparum Malaria

For uncomplicated P. falciparum malaria, quinine is a third-line treatment option that should only be used when artemisinin-based combination therapies (ACTs) and atovaquone-proguanil are contraindicated or unavailable, and must be combined with doxycycline or clindamycin for 7 days. 1, 2

Position in Treatment Algorithm

Quinine has been relegated to third-line status in current guidelines because:

• Artemether-lumefantrine or dihydroartemisinin-piperaquine are first-line treatments with cure rates of 96-98.4% and superior tolerability 1, 3, 2
• Atovaquone-proguanil is the preferred second-line option when ACTs are contraindicated 1, 3
• Quinine is inferior to artesunate in preventing red blood cell sequestration, making it suboptimal for severe disease 1

Dosing Regimen

When quinine must be used for uncomplicated malaria:

Oral Quinine Dosing

• 648 mg (two capsules) every 8 hours for 7 days 4
• Must be taken with food to minimize gastric upset 4
• Total treatment duration of 7 days is appropriate when combined with doxycycline or clindamycin 1

Combination Therapy Requirements

Quinine monotherapy has unacceptably high failure rates, requiring combination with:

• Quinine 750 mg salt (3 tablets) three times daily for 7 days PLUS doxycycline 100 mg twice daily for 7 days 1, 2
• Alternative: Quinine 750 mg salt three times daily for 7 days PLUS clindamycin 20 mg/kg every 8 hours for 7 days 1, 2

The combination with tetracycline for 7 days achieved 100% cure rates in multidrug-resistant malaria, while 5-day quinine courses had significantly lower efficacy (87% cure rate) 5. Clindamycin combinations also achieved 100% cure rates and are particularly valuable when tetracyclines are contraindicated 6.

Dose Adjustments

Renal Impairment

• Severe chronic renal impairment: One loading dose of 648 mg, then 324 mg every 12 hours starting 12 hours after the loading dose 4
• If IV quinine is continued >48 hours with renal failure, reduce dose by one-third 1

Hepatic Impairment

• Mild to moderate (Child-Pugh A or B): No dose adjustment required, but monitor closely for adverse effects 4
• Severe (Child-Pugh C): Do not administer quinine 4

Critical Adverse Effects and Monitoring

Cinchonism

• Tinnitus, vertigo, headache, and acute hearing loss occur commonly 1, 2
• These effects contributed to poor patient compliance in studies, particularly with 7-day regimens 5

Hypoglycemia

• Quinine stimulates insulin release, causing potentially severe hypoglycemia 1
• Monitor glucose levels, especially in severe malaria 7

Cardiac Effects

• QTc prolongation is a significant risk 1, 2
• Avoid in patients at risk for QTc prolongation or taking medications that prolong QTc 2
• QTc prolongation occurred in 23% of patients in one study (3 of 13 patients) 8

Other Adverse Effects

• Nausea, vomiting, and gastrointestinal distress are common 1, 5, 6
• Doxycycline adds risk of skin rash and esophagitis 1
• Clindamycin adds risk of diarrhea and C. difficile infection 1

Specific Contraindications and Warnings

• Do not use against P. falciparum acquired in Southeast Asia due to resistance 1, 2
• Not recommended in patients with neuropsychiatric history when mefloquine alternatives exist 1, 2
• Quinine can be used in all trimesters of pregnancy (unlike doxycycline, which is contraindicated) 1, 2

Pharmacokinetic Considerations

• Plasma concentrations consistently exceed 10 mg/L with standard dosing 9
• Clearance and volume of distribution are significantly reduced in severe malaria compared to uncomplicated disease 9
• Renal clearance accounts for approximately 20% of total clearance 9
• Parasite clearance correlates directly with area under the concentration-time curve 7

Common Pitfalls to Avoid

• Never use quinine monotherapy for 7 days - cure rates drop to 87% without combination therapy 5, 6
• Do not shorten quinine course to 5 days even with 7-day tetracycline, as this significantly reduces cure rates 5
• Do not forget to take with food - this minimizes gastric upset 4
• Do not overlook glucose monitoring - hypoglycemia can be life-threatening 1, 7