quinine (Rx)

<1%

Flushing of the skin

Anginal symptoms

Fever

Rash

Pruritus

Hypoglycemia

Epigastric pain

Hemolysis in G6PD deficiency

Thrombocytopenia

Hepatitis

Nightblindness

Diplopia

Optic atrophy

Impaired hearing

Hypersensitivity reaction

Frequency Not Defined

Severe headache

Nausea

Vomiting

Diarrhea

Blurred vision

Tinnituscinchonism (risk of cinchonism is directly related to dose and duration of therapy)

Contraindications

Prolonged QT interval

Hypersensitivity; cross-sensitivity with mefloquine or quinidine

G6PD deficiency

Optic neuritis, tinnitus, history of quinine-associated blackwater fever and thrombocytopenic purpura

Thrombocytopenia

Hemolytic uremic syndrome

Blackwater fever

Myasthenia gravis

Optic neuritis

Cautions

FDA warns against unapproved use for leg cramps because of unpredictable serious and life-threatening hematologic reactions including thrombocytopenia and hemolytic-uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP)

Quinine stimulates release of insulin from the pancreas, and patients, especially pregnant women, may experience clinically significant hypoglycemia

QT prolongation

• Concentration-dependent prolongation of the PR and QRS interval observed
• At particular risk are patients with underlying structural heart disease and preexisting conduction system abnormalities, elderly patients with sick sinus syndrome, patients with atrial fibrillation with slow ventricular response, patients with myocardial ischemia or patients receiving drugs known to prolong the PR interval (eg, verapamil) or QRS interval (eg, flecainide or quinidine)

Pregnancy

No evidence that quinine causes uterine contractions at doses recommended for malaria treatment

May stimulate the pregnant uterus at doses several-times higher than those used to treat malaria

There are extensive published data but few well-controlled studies of quinine sulfate in pregnant women

Published data on over 1,000 pregnancy exposures to quinine did not show an increase in teratogenic effects over the background rate in the general population; however, the majority of these exposures were not in the first trimester

Used during pregnancy only if the potential benefit justifies the potential risk to the fetus

Clinical considerations

• Treatment of malaria in pregnancy is important
• P falciparum malaria carries a higher risk of morbidity and mortality in pregnant women than in the general population
• Pregnant women with P falciparum malaria have an increased incidence of fetal loss (including spontaneous abortion and stillbirth), preterm labor and delivery, intrauterine growth retardation, low birth weight, and maternal death
• Hypoglycemia, due to increased pancreatic secretion of insulin, associated with quinine use, particularly in pregnant women

Lactation

Low levels of quinine in breastmilk; amounts ingested by infant are small and would not be expected to cause any adverse effects

Dosage in milk is far below those required to treat an infant for malaria

Do not use in mothers with an infant who is glucose-6-phosphate dehydrogenase (G6PD) deficient

Relatively small amounts of quinine in tonic water ingested by breastfeeding women have caused hemolysis in G6PD-deficient infants

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of action

Unknown; may disrupt Plasmodium DNA transcription/replication

Pharmacokinetics

Absorption: readily, mainly from upper small intestine

Protein Bound: 70-95%

Metabolism: primarily hepatic

Half-life elimination: children: 6-12 hr; adults: 8-14 hr

Peak Plasma Time: 1-3 hr

Excretion: feces & saliva; urine (<5% as unchanged drug)

Oral Administration

Take with food to minimize gastric upset

Missed dose: Instruct patient not to double the next dose; if >4 hr has elapsed since missed dose, patient should wait and take the next dose as previously scheduled

IV Administration

Was administered by slow IV infusion as the dihydrochloride; however, a parenteral dosage form of the drug no longer is available in the US

Storage

Capsules: Store at 20-25°C (68-77°F)