quinine

Quinine is a naturally occurring compound (alkaloid) derived from the bark of the cinchona tree. Quinine is used to treat malaria, a disease with high fevers, shaking chills, and flu-like illness. Malaria is caused by microscopic unicellular parasites belonging to the Plasmodium species, and malaria caused by Plasmodium falciparum is the type most likely to result in severe infections that can even lead to death, if not promptly treated. Malaria can, however, be prevented by taking precautions against mosquito bites in malaria-endemic regions.

Malaria is transmitted by the bite of infective female Anopheles mosquitos. Malarial parasites grow and multiply in the human liver first and then get into red blood cells and multiply further. The parasites grow inside the red blood cells, eventually rupturing them and releasing daughter parasites that invade other blood cells. The blood stage parasites cause malarial symptoms in humans, though the mosquito itself suffers no ill consequences from the parasite.

When a female Anopheles mosquito bites an infected human, the blood stage parasites get into the mosquito. Certain forms of the parasites known as gametocytes, occur in male and female forms, which mate in the mosquito’s gut. After 10 to 18 days, the parasites, in the form of sporozoites, migrate to the mosquito’s saliva, and this is the mosquito’s infective stage. The parasite is transmitted when the mosquito bites another human, to continue the cycle.

Quinine interferes with the ability of the parasites to break down the hemoglobin in the red blood cells for the oxygen and carbohydrates they need to grow and multiply. Consequently, the parasite starves and hemoglobin builds up to toxic levels within the parasite, killing it. Quinine also gets inserted into the parasite’s DNA and disrupts DNA transcription and replication. Quinine works only on the blood stage of the P. falciparum parasites.

Quinine has been used for centuries to treat malaria and is useful in treating malarial infections that are resistant to other antimalarial agents such as chloroquine. Quinine is approved by the FDA for the treatment of uncomplicated P. falciparum malaria. Quinine cannot be used for preventing malaria or to treat severe or complicated P. falciparum malaria. Quinine is also used off-label to treat babesiosis, caused by a tick-borne parasite that infects red cells. 

• Do not use quinine in patients with the following conditions:
  • Prolonged QT interval, an abnormality in the heart’s electrical conduction; quinine can exacerbate it and may lead to irregular cardiac rhythms (arrhythmia)
  • Glucose-6-phosphate dehydrogenase (G6PD) deficiency, a genetic disorder; quinine can cause destruction of red cells (hemolysis) in G6PD deficiency
  • Myasthenia gravis, a neuromuscular disorder; quinine may worsen muscle weakness
  • Optic neuritis; quinine may exacerbate active optic neuritis
• Do not use quinine to treat patients who have had hypersensitivity reactions to quinine including the following:
  • Low platelet count (thrombocytopenia) and related conditions such as idiopathic thrombocytopenic purpura (ITP) and thrombotic thrombocytopenic purpura (TTP)
  • Hemolytic uremic syndrome (HUS), a condition that affects the kidney’s blood vessels
  • Blackwater fever, a serious complication of chronic malaria and quinine treatment that leads to extensive red cell destruction and kidney failure
• Do not use quinine to treat nocturnal leg cramps; quinine has negligible benefit and can adversely affect almost every system; can cause unpredictable, serious side effects including life-threatening blood reactions, cardiac arrhythmias and kidney failure
• Quinine can cause QT prolongation; patients with underlying heart diseases have a higher risk; avoid simultaneous use with other drugs that can cause QT prolongation
• Quinine can destroy red blood cells; monitor hemoglobin and hematocrit levels closely during treatment; discontinue if the patient develops acute hemolytic anemia
• Quinine stimulates release of insulin from the pancreas; monitor blood glucose levels, especially in pregnant women
• Quinine can cause severe hypersensitivity reactions including anaphylactic shock and serious skin reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis

The most common side effects of quinine are a cluster of symptoms known as cinchonism. Symptoms of mild cinchonism include:

• Headache
• Dilation of blood vessels (vasodilation)
• Sweating
• Nausea
• Ringing in the ears (tinnitus)
• Hearing impairment
• Dizziness
• Vertigo
• Blurred vision
• Double vision (diplopia)
• Visual disturbances
• Diminished visual fields
• Disturbance in color perception

Symptoms of severe cinchonism include:

• Vomiting
• Diarrhea
• Abdominal pain
• Deafness
• Optic nerve inflammation (optic neuritis)
• Night blindness
• Blindness
• Disturbances in cardiac rhythm or conduction

Less common side effects of quinine include:

• Fever
• Chills
• Flushing
• Weakness (asthenia)
• Lupus-like syndrome
• Hypersensitivity reactions
• Blood disorders including:
  • Low count of granulocyte immune cells (agranulocytosis)
  • Deficiency of blood-clotting substance prothrombin (hypoprothrombinemia)
  • Low platelet count (thrombocytopenia)
  • Easy bruising and bleeding due to thrombocytopenia (idiopathic thrombocytopenic purpura)
  • Formation of blood clots in small vessels (thrombotic thrombocytopenic purpura)
  • Blood clotting disorder (coagulopathy)
  • Widespread blood clotting (disseminated intravascular coagulation)
  • Anemia from red cell destruction (hemolytic anemia)
  • Hemolytic uremic syndrome
  • Anemia due to reduced red cell production (aplastic anemia)
  • Hemorrhage
  • Black water fever
  • Low count of neutrophil immune cells (neutropenia)
  • Low count of leukocyte immune cells (leukopenia)
  • Low count of all types of blood cells (pancytopenia)
  • Production of autoimmune antibodies (lupus anticoagulants)
  • Purple spots and discoloration of skin from bleeding under the skin
• Asthma
• Shortness of breath (dyspnea)
• Fluid in the lungs (pulmonary edema)
• Cardiovascular effects including:
  • Chest pain
  • Vasodilatation
  • Low blood pressure (hypotension)
  • Postural hypotension
  • Rapid heart rate (tachycardia)
  • Slow heart rate (bradycardia)
  • Palpitations
  • Fainting (syncope)
  • Atrioventricular block
  • Atrial fibrillation
  • Irregular rhythms
  • Unifocal premature ventricular contractions
  • QT prolongation
  • Ventricular fibrillation
  • Ventricular tachycardia
  • Torsades de pointes, a type of ventricular tachycardia
  • Cardiac arrest
• Gastric irritation
• Inflammation of the esophagus (esophagitis)
• Loss of appetite (anorexia)
• Low blood glucose levels (hypoglycemia)
• Abnormal liver function tests
• Liver inflammation (hepatitis)
• Jaundice
• Hemoglobin in the urine (hemoglobinuria)
• Kidney impairment
• Acute inflammation in the spaces between the kidney tubules (interstitial nephritis)
• Kidney failure
• Skin reactions including:
  • Skin rashes
  • Hives (urticaria)
  • Itching (pruritus)
  • Bullous dermatitis
  • Exfoliative dermatitis
  • Erythema multiforme
  • Stevens-Johnson syndrome
  • Toxic epidermal necrolysis
  • Fixed drug eruption
  • Photosensitivity reactions
  • Allergic contact dermatitis
  • Black discoloration of skin on extremities (acral necrosis)
  • Inflammation of blood vessels in the skin (cutaneous vasculitis)
• Muscle pain (myalgia)
• Muscle weakness
• Impaired coordination, balance and speech (ataxia)
• Involuntary muscle contractions (dystonic reaction)
• Difficulty with language and communication (aphasia)
• Confusion
• Altered mental status
• Disorientation
• Restlessness
• Tremors
• Seizures
• Coma
• Suicide

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug.

Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Capsule

• 324 mg

Adult:

Malaria

Uncomplicated (P. falciparum)

• 648 mg orally every 8 hours for 7 days

Chloroquine-Resistant (P. falciparum)

• 648 mg orally every 8 hours for 3-7 days concomitant tetracycline, doxycycline, or clindamycin

Chloroquine-Resistant (P. vivax)

• 648 mg orally every 8 hours for 3-7 days concomitant doxycycline (or tetracycline) and oral primaquine

Babesiosis (Off-label)

• 648 mg orally every 8 hours, with concomitant orally or intravenously clindamycin

Dosage Modifications

Renal impairment

• Severe: 648 mg orally once, then 324 mg orally every 12 hours

Hepatic impairment

• Mild or moderate (Child-Pugh A or B): No dosage adjustment required; monitor closely
• Severe (Child-Pugh C): Do not administer

Limitations of use

• Not approved for
  • Treatment of severe or complicated P. falciparum malaria
  • Prevention of malaria
  • Treatment or prevention of nocturnal leg cramps

Pediatric:

Malaria

Uncomplicated (P. falciparum)

• 30 mg/kg/day orally divided three times daily for 3-7 days

Chloroquine-Resistant (P. falciparum)

• 30 mg/kg/day orally divided three times daily for 3-7 days, with concomitant doxycycline, tetracycline, or clindamycin

Chloroquine-Resistant (P. vivax)

• 30 mg/kg/day orally three times daily for 3-7 days, with concomitant doxycycline and oral primaquine

Dosage Modifications

Should not exceed the usual adult oral dosage

Babesiosis (Off-label)

• 25 mg/kg/day orally divided three times daily for 7 days, with concomitant oral clindamycin

Administration

• Should be swallowed whole to avoid bitter taste and taken with food to minimize gastric upset

• Quinine overdose can cause serious complications including visual impairment or loss of vision, ringing in the ears or hearing loss, gastrointestinal symptoms, nervous system disorders, hypoglycemia, hypotension, circulatory collapse, respiratory distress, cardiac arrhythmias, and death.
• Quinine overdose is managed with symptomatic and supportive care. Quinine is rapidly absorbed and gastric lavage may not be effective. Multiple doses of activated charcoal may reduce quinine concentration in blood.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Severe interactions of quinine include:
  • dronedarone
  • eliglustat
  • lefamulin
  • pimozide
  • thioridazine
• Quinine has serious interactions with at least 89 different drugs.
• Quinine has moderate interactions with at least 182 different drugs.
• Quinine has minor interactions with at least 65 different drugs.

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

Pregnancy

• There are extensive published data but few well-controlled studies of quinine use in pregnant women; published data do no show evidence of fetal harm, however, a majority of these exposures were not in the first trimester
• In some animal studies, there were central nervous system and ear abnormalities, and fetal death occurred with 1 to 4 times human clinical doses
• P. falciparum malaria carries a higher risk of morbidity and mortality in pregnant women than in general population, with an increased risk of fetal loss, preterm labor and delivery, intrauterine growth retardation, low birth weight, and maternal death
• Treatment of malaria in pregnancy is important; quinine may be used to treat chloroquine-resistant uncomplicated malaria during all trimesters of pregnancy; quinine should be used if potential benefits to the mother outweighs potential risks to the fetus
• Quinine can cause hypoglycemia, particularly in pregnant women; blood glucose levels should be monitored

Labor and delivery

• There is no evidence that quinine in recommended doses for malaria treatment causes uterine contraction; substantially high doses may stimulate the pregnant uterus
• If congenital malaria is suspected after delivery, the infant should be evaluated and treated appropriately

Breastfeeding

• Quinine is present in breast milk; limited studies show no evidence of toxicity in the breastfed infant; use quinine with caution in nursing women
• Plasma quinine levels may not be therapeutic in infants of nursing mothers receiving quinine; if malaria is suspected in the infant, it should be treated appropriately