Drug reference

Quinine

Antimalarial · Antimalarial, Skeletal Muscle Relaxant

Also known as quinine hydrochloride, quinine dihydrochloride, quinine sulfate, quinine bisulfate

AntimalarialAntimalarial, Skeletal Muscle Relaxant

CDSCO approvedSchedule H

EXCRETION

—

not curated

INTERACTIONS

12 major

SEVERE in our sources

PREGNANCY

FDA category + note

Top interactionssee all 12 →

AdenosineSevereDatabaseDDInter
AmiodaroneSevereDatabaseDDInter
AmisulprideSevereDatabaseDDInter
AnagrelideSevereDatabaseDDInter

Mechanism

Quinine, the chief alkaloid of cinchona bark, is a blood schizonticide that accumulates in the acidic food vacuole of Plasmodium parasites, where it binds to heme (ferriprotoporphyrin IX) released during hemoglobin digestion. This prevents the parasite's detoxification of heme into insoluble hemozoin, causing accumulation of toxic free heme that disrupts membranes and kills the parasite. Quinine also depresses skeletal muscle excitability by increasing the refractory period — the basis for its use in nocturnal leg cramps.

Indications

Nocturnal leg cramps (unlicensed indication)Non-falciparum malariaFalciparum malariatreatment of uncomplicated p. falciparum malariaparenteral treatment of severe illness due to drug-resistant strains of p. falciparumcombined with tetracycline, doxycycline, or clindamycinSevere babesiosis (in combination with clindamycin)abolish nocturnal leg crampsP. falciparum (most chloroquine and multidrug-resistant strains)acute attack of falciparum malariacomplicated/severe falciparum malaria (parenteral route)nocturnal muscle crampsmyotonia congenitaUncomplicated CQ-resistant malaria (oral, as alternative to S/P-ACT)Complicated and severe malaria including cerebral malaria (i.v., historically drug of choice)Severe falciparum malaria during 1st trimester of pregnancy (i.v., when artemisinins are not available)

Dosing

Adult: Nocturnal leg cramps: 200–300 mg once daily by mouth, to be taken at bedtime. Malaria (Non-falciparum, or Falciparum if IV needed): 10 mg/kg every 8 hours (max. per dose 700 mg) by intravenous infusion over 4 hours; reduce dose to 5–7 mg/kg if parenteral treatment is required for more than 48 hours. Change to oral chloroquine as soon as patient’s condition permits.
Pediatric: Falciparum malaria: 10 mg/kg every 8 hours (max. per dose 600 mg) by mouth for 7 days.
Max dose: 700 mg per dose (IV for malaria), 300 mg daily (oral for nocturnal leg cramps)

Pharmacokinetics

Onset

3 to 8 h

Half-life

about 11 h (may increase to 18h in severe malaria)

Bioavailability

76 ± 11%

Protein binding

N-A: ∼85–90%; M-A: 93–95%

Metabolism

metabolized extensively by hepatic CYP3A4 (major metabolite: 3-hydroxyquinine)

Excretion

about 20% in unaltered form in urine (more rapid with acidic urine)

Contraindications

hypersensitivity
tinnitus
optic neuritis
cardiac dysrhythmias
history of blackwater fever
thrombocytopenic purpura
thrombocytopenia associated with quinine or quinidine use
many cardiac conduction defects and arrhythmias
myasthenia gravis
corticosteroids (useless, may be harmful in poisoning)

Side effects

Common

cinchonism (tinnitus, high-tone deafness, visual disturbances, headache, dysphoria, nausea, vomiting, postural hypotension)gastrointestinal upset (nausea, vomiting, abdominal pain, diarrhea)flushingsweatingrashangioedemahyperinsulinemiasevere hypoglycemiaCardiac effects (prolonged QT interval)cramps (as idiosyncrasy)diarrhoea (as idiosyncrasy)purpura (as idiosyncrasy)asthma (as idiosyncrasy)vascular collapse (as idiosyncrasy)cinchonism (ringing in ears, nausea, vomiting, headache, mental confusion, vertigo, difficulty in hearing, visual defects, diarrhoea, flushing, marked perspiration)gastric irritationepigastric discomfortcinchonism (tinnitus, high-tone deafness, headache, dysphoria, nausea, vomiting, abdominal pain, visual disturbances, postural hypotension)hypoglycemia

Serious

fatal oral dose (2 to 8 g)
life-threatening hypoglycemia
hypotension (with rapid iv infusions)
cardiac dysrhythmias (sinus arrest, junctional rhythms, atrioventricular block, ventricular tachycardia and fibrillation)
severe hemolysis (hypersensitivity)
hemoglobinuria
asthma
blackwater fever (massive hemolysis, hemoglobinemia, hemoglobinuria leading to anuria, renal failure, death)
hypoprothrombinemia
leukopenia
agranulocytosis
thrombotic thrombocytopenic purpura
alarming respiratory distress
dysphagia (in myasthenia gravis)
Oculotoxicity and hearing loss/tinnitus associated with unbound concentrations >2 µg/mL.
haemolysis (in G-6PD deficient individuals)
aggravates weakness in myasthenics
delirium (in poisoning)
fever (in poisoning)
tachypnoea (in poisoning)
respiratory depression (in poisoning)
pulmonary edema (in poisoning)
hypoglycaemia (in poisoning, or rapid IV injection)
marked weakness (in poisoning)
prostration (in poisoning)
hypotension (with rapid intravenous injection)
cardiac arrhythmias (with rapid intravenous injection)
q-t prolongation (during intravenous infusion, stop if exceeds 25%)
purpura (in hypersensitivity)
rashes (in hypersensitivity)
itching (in hypersensitivity)
angioedema of face (in hypersensitivity)
bronchoconstriction (in hypersensitivity)
haemolysis (especially in pregnant women and falciparum malaria patients)
haemoglobinuria (black water fever, especially in pregnant women and falciparum malaria patients)
kidney damage (especially in pregnant women and falciparum malaria patients)
Hypoglycaemia (due to hyperinsulinemia)
deafness
hemolytic anemia
arrhythmias
hypotension