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{{drugbox
{{DrugProjectFormSinglePage
| IUPAC_name = (2-ethenyl-4-azabicyclo[2.2.2]oct-5-yl)- (6-methoxyquinolin-4-yl)-methanol
|authorTag={{AJ}}
| image = Quinine-2D-skeletal.png
|genericName=[[Quinine Sulfate]]
| image2 = Quinine-3D-balls.png
|aOrAn=a
| size = 250px
|drugClass=[[cinchona alkaloid]], [[antimalarial]] and  [[anti-Infective]] Agent,
| CAS_number = 130-95-0
|indicationType=treatment
| ATC_prefix = M09
|indication=of uncomplicated [[Plasmodium falciparum]] [[malaria]]
| ATC_suffix = AA01
|hasBlackBoxWarning=Yes
| ATC_supplemental = {{ATC|P01|BC01}}
|adverseReactions=[[cinchonism]] include [[headache]], [[vasodilation]] and [[sweating]], [[nausea]], [[tinnitus]], [[hearing impairment]], [[vertigo]] or [[dizziness]], [[blurred vision]], and disturbance in [[color perception]].
| PubChem = 8549
|blackBoxWarningTitle=WARNING
| DrugBank = APRD00563
|blackBoxWarningBody=* Quinine sulphate use for the treatment or prevention of nocturnal leg cramps may result in serious and life-threatening hematologic reactions, including thrombocytopenia and hemolytic uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP). Chronic renal impairment associated with the development of TTP has been reported. The risk associated with Quinine sulphate use in the absence of evidence of its effectiveness in the treatment or prevention of nocturnal leg cramps outweighs any potential benefit
| C = 20 |H = 24 |N = 2 |O = 2
 
| molecular_weight = 324.417 [[Gram|g]]/[[Mole (unit)|mol]]
<!--FDA-Labeled Indications and Dosage (Adult)-->
| bioavailability = 76 to 88%
|fdaLIADAdult=* Quinine sulphate is an [[antimalarial drug]] indicated only for treatment of uncomplicated [[P. falciparum malaria|Plasmodium falciparum malaria]]. Quinine sulfate has been shown to be effective in geographical regions where resistance to [[chloroquine]] has been documented.
| protein_bound = ~70%
 
| metabolism = [[Liver|Hepatic]] (mostly [[CYP3A4]] and [[CYP2C19]]-mediated)
* Quinine sulphate oral capsules are not approved for:
| elimination_half-life = ~18 hours
 
| excretion = [[Kidney|Renal]] (20%)
:* Treatment of severe or complicated [[P. falciparum malaria]].
| pregnancy_category = X <small>([[United States of America|USA]])</small>, D <small>([[Australia|Au]])</small>
:* Prevention of [[malaria]].
| legal_status =
:* Treatment or prevention of [[nocturnal]] [[leg cramps]]  
| routes_of_administration = Oral, [[intravenous therapy|intravenous]]
 
| melting_point = 177
====Dosing Information====
}}
 
{{SI}}
* Treatment of Uncomplicated [[P. falciparum malaria]]
{{CMG}}
* For treatment of uncomplicated [[P. falciparum malaria]] in adults: Orally, 648 mg (two capsules) every 8 hours for 7 days.
 
* Quinine sulphate should be taken with food to minimize [[gastritis|gastric upset]].
 
=====Renal Impairment=====


{{EH}}
* In patients with acute uncomplicated [[malaria]] and severe [[CRF|chronic renal impairment]], the following dosage regimen is recommended: one loading dose of 648 mg Quinine sulphate followed 12 hours later by maintenance doses of 324 mg every 12 hours.


==[http://www.wikidoc.org/index.php?title=Quinine_(Patient_information)&action=edit click here for Quinine patient information]==
* The effects of mild and moderate [[renal impairment]] on the safety and [[pharmacokinetic]]s of quinine sulfate are not known.


'''Quinine''' ({{IPAEng|ˈkwaɪnaɪn, kwɪˈniːn, ˈkwiːniːn}}) is a natural white [[crystal]]line [[alkaloid]] having [[antipyretic]] (fever-reducing), anti-smallpox, [[analgesic]] (painkilling), and [[anti-inflammatory]] properties and a bitter taste. It is a [[stereoisomer]] of [[quinidine]].
=====Hepatic Impairment=====


Quinine was the first effective treatment for [[malaria]] caused by [[Plasmodium falciparum|P falciparum]], appearing in therapeutics in the 17th century. It remained the antimalarial drug of choice until the 1940s, when other drugs took over. Since then, many effective antimalarials have been introduced, although quinine is still used to treat the disease in certain critical situations. Quinine is available with a prescription in the [[United States of America|United States]]. Quinine is also used to treat [[Cramps#Nocturnal leg cramps|nocturnal leg cramps]] and [[arthritis]], and there have been attempts (with limited success) to treat [[prion]] diseases. It was once a popular [[heroin]] [[adulterant]].
* Adjustment of the recommended dose is not required in mild ([[Child-Pugh A]]) or moderate ([[Child-Pugh B]]) [[hepatic impairment]], but patients should be monitored closely for adverse effects of quinine. Quinine should not be administered in patients with severe ([[Child-Pugh C]]) [[hepatic impairment]].
|offLabelAdultGuideSupport=There is limited information regarding off-label use and dosage for adults.
|offLabelAdultNoGuideSupport=* [[Babesiosis]]
* [[Malaria]], Uncomplicated, [[Plasmodium vivax]]


==Mechanism of action==
The [[theory|theorized]] mechanism of action for quinine and related anti-malarial drugs is that these drugs are toxic to the [[malaria]] [[Wiktionary:parasite|parasite]]. Specifically, the drugs interfere with the parasite's ability to break down and digest [[hemoglobin]]. Consequently, the parasite starves and/or builds up toxic levels of partially degraded hemoglobin in itself.


==Sources of quinine==
Quinine was extracted from the bark of the [[South America]]n [[cinchona]] tree and was isolated and named in [[1817]] by French researchers [[Pierre Joseph Pelletier]] and [[Joseph Bienaimé Caventou]]. The name was derived from the original [[Quechua]] (Inca) word for the cinchona tree bark, "Quina" or "Quina-Quina", which roughly means "bark of bark" or "holy bark". Prior to 1820, the bark was first dried, ground to a fine powder and then mixed into a liquid (commonly wine) which was then drunk.


Large scale use of quinine as a prophylaxis started around [[1850]], although it had been used in un-extracted form by Europeans since at least the early [[1600s]]. Quinine was first used to treat malaria in Rome in 1631. During the 1600s, malaria was endemic to the [[swamp]]s and [[marsh]]es surrounding the city of [[Rome]]. Over time, malaria was responsible for the death of several [[Pope]]s, many [[Cardinal (Catholicism)|Cardinal]]s and countless common citizens of Rome. Most of the [[priest]]s trained in Rome had seen malaria victims and were familiar with the [[shivering]] brought on by the cold phase of the disease. In addition to its anti-malarial properties, quinine is an effective muscle relaxant, long used by the [[Quechua]] Indians of [[Peru]] to halt shivering brought on by cold temperatures. The [[Jesuit]] Brother Agostino Salumbrino (1561-1642), an [[apothecary]] by training and who lived in [[Lima]], observed the Quechua using the quinine-containing bark of the [[cinchona]] tree for that purpose. While its effect in treating malaria (and hence malaria-induced shivering) was entirely unrelated to its effect in controlling shivering from cold, it was still the correct medicine for malaria. At the first opportunity, he sent a small quantity to Rome to test in treating malaria. In the years that followed, cinchona bark became one of the most valuable commodities shipped from Peru to Europe.
<!--FDA-Labeled Indications and Dosage (Pediatric)-->
|fdaLIADPed=There is limited information regarding FDA-Labeled Use of Quinine sulphate in pediatric patients.
|offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Quinine sulphate in pediatric patients.


Quinine also played a significant role in the colonization of Africa by Europeans. As the dawn of modern pharmacology, Quinine was the prime reason why Africa ceased to be the white man's grave. According to Clifford D. Conner in "A People's History of Science", "It was quinine's efficacy that gave colonist fresh opportunities to swarm into the Gold Coast, Nigeria and other parts of west Africa and seize fertile agricultural lands, introduce new livestock and crops, build roads and railways, drive natives into mines, and introduce all the disruptions to traditional lifestyles that cash economies brought."(Conner pp 95-96) also cites Porter, "The Greatest Benefit to Mankind, pp. 465-466) 
<!--Non–Guideline-Supported Use (Pediatric)-->
|offLabelPedNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Quinine sulphate in pediatric patients.


===Synthetic quinine===
<!--Contraindications-->
:''Main article: [[quinine total synthesis]]''
|contraindications=Quinine sulphate is [[contraindicated]] in patients with the following:
Cinchona trees remain the only practical source of quinine. However, under wartime pressure, research towards its artificial production was undertaken. A formal chemical synthesis was accomplished in [[1944]] by American chemists [[Robert Burns Woodward|R.B. Woodward]] and [[W.E. Doering]].<ref name="Woodward1944">
{{cite journal | author = Woodward R, Doering W | title = The Total Synthesis of Quinine | journal = [[Journal of the American Chemical Society|J Am Chem Soc]] | volume = 66 | issue = 849 | year = 1944}}</ref> Since then, several more efficient [[quinine total synthesis|quinine total syntheses]] have been achieved <ref>see review article in Angewandte Chemie, Int. Ed., 2005, 44, p. 854 ff</ref> , but none of them can compete in economic terms with isolation of the alkaloid from natural sources.


==Dosing==
=====Prolonged QT interval:=====
Quinine is a basic amine and is therefore always presented as a salt.  Various preparations that exist include the [[hydrochloride]], dihydrochloride, [[sulfate]], bisulfate and [[gluconate]].  This makes quinine dosing very complicated, because each of the salts has a different weight.
* One case of a [[fatal]] [[ventricular arrhythmia]] was reported in an elderly patient with a [[prolonged QT interval]] at baseline, who received quinine sulfate [[intravenously]] for [[P. falciparum malaria]].


The following amounts of each form are equal:
=====Glucose-6-phosphate dehydrogenase deficiency(G6PD):=====
* [[Hemolysis]] can occur in patients with [[G6PD deficiency]] receiving quinine.


* quinine base 100 mg
=====Known hypersensitivity reactions to quinine:=====
* quinine bisulfate 169 mg
* These include, but are not limited to, the following:
* quinine dihydrochloride 122 mg
:* [[Thrombocytopenia]]
* quinine hydrochloride 122 mg
:* [[Idiopathic thrombocytopenia purpura]] ([[ITP]]) and [[Thrombotic thrombocytopenic purpura]] ([[TTP]])
* quinine sulfate 121 mg
[[Hemolytic uremic syndrome]] (HUS)
* quinine gluconate 160 mg.
:* [[Blackwater fever]] ([[acute intravascular hemolysis]], [[hemoglobinuria]], and [[hemoglobinemia]])
:* Known [[hypersensitivity]] to [[mefloquine]] or [[quinidine]]: cross-sensitivity to quinine has been documented.
:* [[Myasthenia gravis]]. Quinine has [[neuromuscular]] blocking activity, and may exacerbate muscle weakness.
:* [[Optic neuritis]]. Quinine may exacerbate active [[optic neuritis]]
|warnings=====Use of Quinine for Treatment or Prevention of Nocturnal Leg Cramps:====
* Quinine sulphate may cause unpredictable serious and life-threatening [[hematologic]] reactions including [[thrombocytopenia]] and [[hemolytic-uremic syndrome]]/[[thrombotic thrombocytopenic purpura]] ([[HUS]]/[[TTP]]) in addition to [[hypersensitivity]] reactions, [[QT prolongation]], serious [[cardiac arrhythmias]] including [[torsades de pointes]], and other serious adverse events requiring medical intervention and hospitalization. Chronic [[renal impairment]] associated with the development of [[TTP]], and fatalities have also been reported. The risk associated with the use of Quinine sulphate in the absence of evidence of its effectiveness for treatment or prevention of nocturnal [[leg cramps]], outweighs any potential benefit in treating and/or preventing this benign, self-limiting condition.


All quinine salts may be given orally or [[Intravenous therapy|intravenous]]ly (IV); quinine gluconate may also be given [[intramuscular injection|intramuscular]]ly (IM) or rectally (PR).<ref name="Barennes1996">{{cite journal | author=Barennes H, ''et al.'' | title=Efficacy and pharmacokinetics of a new intrarectal quinine formulation in children with Plasmodium falciparum malaria  | journal=Brit J Clin Pharmacol | volume=41 | pages=389 | year=1996
=====Thrombocytopenia=====
| doi=10.1046/j.1365-2125.1996.03246.x | issue=5 }}</ref><ref name="Barennes2006">{{cite journal | Barennes H, Balima-Koussoubé T, Nagot N, Charpentier J-C, Pussard E | title=Safety and efficacy of rectal compared with intramuscular quinine for the early treatment of moderately sever malaria in children: randomised clinical trial | journal=Brit Med J | volume=332 | issue=7549 | pages=1055&ndash;57 }}</ref>  The main problem with the rectal route is that the dose can be expelled before it is completely absorbed, but this can be rectified by giving half dose again.
* Quinine-induced [[thrombocytopenia]] is an immune-mediated disorder. Severe cases of [[thrombocytopenia]] that are fatal or life threatening have been reported, including cases of [[HUS]]/[[TTP]]. Chronic [[renal impairment]] associated with the development of [[TTP]] has also been reported. [[Thrombocytopenia]] usually resolves within a week upon discontinuation of quinine. If quinine is not stopped, a patient is at risk for fatal [[hemorrhage]]. Upon re-exposure to quinine from any source, a patient with quinine-dependent [[antibodies]] could develop [[thrombocytopenia]] that is more rapid in onset and more severe than the original episode.


The IV dose of quinine is 8 mg/kg of quinine base every eight hours; the IM dose is 12.8 mg/kg of quinine base twice daily; the PR dose is 20 mg/kg of quinine base twice daily. Treatment should be given for seven days.
=====QT Prolongation and Ventricular Arrhythmias:=====
* [[QT interval prolongation]] has been a consistent finding in studies which evaluated [[electrocardiographic]] changes with oral or [[parenteral]] quinine administration, regardless of age, clinical status, or severity of disease. The maximum increase in [[QT interval]] has been shown to correspond with peak quinine [[plasma|plasma concentration]]. Quinine sulfate has been rarely associated with potentially fatal [[cardiac arrhythmias]], including [[torsades de pointes]], and [[ventricular fibrillation]].


The preparations available in the UK are quinine sulfate (200 mg or 300 mg tablets) and quinine hydrochloride (300 mg/ml for injection).  Quinine is not licensed for IM or PR use in the [[United Kingdom|UK]]. The adult dose in the UK is 600 mg quinine dihydrochloride IV or 600 mg quinine sulfate orally every eight hours.
* Quinine sulphate has been shown to cause concentration-dependent [[First degree AV block|prolongation of the PR]] and [[Intraventricular conduction delay|QRS interval]]. At particular risk are patients with underlying [[structural heart disease]] and preexisting [[Bradycardia|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 [[prolongation of the PR|PR interval]] (e.g. [[verapamil]]) or [[Intraventricular conduction delay|QRS interval]] (e.g. [[flecainide]] or [[quinidine]]).


In the United States quinine sulfate is available as 324 mg tablets under the brand name Qualaquin; the adult dose is two tablets every eight hours.  There is no injectable preparation of quinine licensed in the U.S.: [[quinidine]] is used instead.<ref>{{cite journal | author=Center for Disease Control | title=Treatment with Quinidine Gluconate of Persons with Severe ''Plasmodium falciparum'' Infection: Discontinuation of Parenteral Quinine | journal=Morb Mort Weekly Rep | year=1991 | volume=40 | issue=RR-4 | pages=21&ndash;23 | url=http://www.cdc.gov/mmwr/preview/mmwrhtml/00043932.htm | accessdate=2006-05-06 }}</ref><ref>{{cite journal | journal=New Engl J Med | volume=353 | pages=335&ndash;337 | year=2005 | issue=4 | title=Making Antimalarial Agents Available in the United States | author=Magill A, Panosian C }}</ref>
* Quinine sulphate is not recommended for use with other drugs known to cause [[Long QT syndrome|QT prolongation]], including [[antiarrhythmic agents|Class IA antiarrhythmic agents]] (e.g., [[quinidine]], [[procainamide]], [[disopyramide]]), and [[antiarrhythmic agents|Class III antiarrhythmic agent]]s (e.g., [[amiodarone]], [[sotalol]], [[dofetilide]]).


Quinine is not recommended for malaria prevention ([[Wiktionary:prophylaxis|prophylaxis]]) because of its side effects and poor tolerability, not because it is ineffective. When used for prophylaxis, the dose of quinine sulphate is 300&ndash;324mg once daily, starting one week prior to travel and continuing for four weeks after returning.
* The use of [[macrolide]] [[antibiotic]]s such as [[erythromycin]] should be avoided in patients receiving Quinine sulphate. [[Fatal]] [[torsades de pointes]] was reported in an [[elderly]] patient who received concomitant quinine, [[erythromycin]], and [[dopamine]]. Although a causal relationship between a specific drug and the arrhythmia was not established in this case, [[erythromycin]] is a [[CYP3A4 inhibitor]] and has been shown to increase quinine plasma levels when used concomitantly. A related [[macrolide]] [[antibiotic]], [[troleandomycin]], has also been shown to increase quinine exposure in a [[pharmacokinetic]] study.


==Side effects==
* Quinine may inhibit the [[metabolism]] of certain drugs that are [[CYP3A4]] substrates and are known to cause [[Long QT syndrome|QT prolongation]], e.g., [[astemizole]], [[cisapride]], [[terfenadine]], [[pimozide]], [[halofantrine]] and [[quinidine]]. [[Torsades de pointes]] has been reported in patients who received concomitant quinine and [[astemizole]]. Therefore, concurrent use of Quinine sulphate with these medications, or drugs with similar properties, should be avoided.
:''See: [[cinchonism]]''
It is usual for quinine in therapeutic doses to cause [[cinchonism]]; in rare cases, it may even cause death (usually by [[pulmonary edema]]). The development of mild cinchonism is not a reason for stopping or interrupting quinine therapy and the patient should be reassured. Blood glucose levels and electrolyte concentrations must be monitored when quinine is given by injection; the patient should also ideally be in cardiac monitoring when the first quinine injection is given (these precautions are often unavailable in developing countries where malaria is most a problem).


Cinchonism is much less common when quinine is given by mouth, but oral quinine is not well tolerated (quinine is exceedingly bitter and many patients will vomit up quinine tablets): other drugs such as Fansidar® ([[sulfadoxine]] (sulfonamide antibiotic) with [[pyrimethamine]]) or Malarone® ([[proguanil]] with [[atovaquone]]) are often used when oral therapy is required. Blood glucose, electrolyte and cardiac monitoring are not necessary when quinine is given by mouth.
* Concomitant administration of Quinine sulphate with the [[antimalarial drug]]s, [[mefloquine]] or [[halofantrine]], may result in [[electrocardiographic]] abnormalities, including [[Intraventricular conduction delay|QT prolongation]], and increase the risk for [[torsades de pointes]] or other serious [[ventricular arrhythmias]]. Concurrent use of Quinine sulphate and [[mefloquine]] may also increase the risk of [[seizure]]s.


In [[1994]], the [[USA|U.S.]] [[Food and Drug Administration]] (FDA), banned the use of [[Over-the-counter drug|over-the-counter]] (OTC) quinine as a treatment for nocturnal leg cramps. [[Pfizer]] [[Pharmaceuticals]] had been selling the brand name Legatrin® for this purpose.  This soon followed disallowing even [[Medical prescription|prescription]] quinine for leg cramps, and all OTC sales of the drug for malaria.  From [[1969]] to [[1992]], the FDA received 157 reports of health problems related to quinine use, including 23 which had resulted in death.[http://www.fda.gov/fdac/departs/695_updates.html]
* Quinine sulphate should also be avoided in patients with known [[Long QT syndrome|prolongation of QT interval]] and in patients with clinical conditions known to [[Long QT syndrome|prolong the QT interval]], such as uncorrected [[hypokalemia]], [[bradycardia]], and certain [[cardiac]] conditions.
Quinine can cause paralysis if accidentally injected into a nerve.  It is extremely toxic in overdose and the advice of a [[toxicology|poisons specialist]] should be sought immediately.


===Quinine and pregnancy===
=====Concomitant Use of Rifampin:=====
In very large doses, quinine also acts as an [[abortifacient]]; in the United States quinine is classed as a Category X [[teratogen]] by the Food and Drug Administration, meaning that it can cause [[birth defect]]s (especially [[deafness]]) if taken by a woman during [[pregnancy]].  In the UK, the recommendation is that pregnancy is ''not'' a contra-indication to quinine therapy for [[Plasmodium falciparum|falciparum]] malaria (which directly contradicts the US recommendation), although it should be used with caution; the reason for this is that the risks to the pregnancy are small and theoretical, as opposed to the very real risk of death from falciparum malaria. Futher research, conducted in Sweden's Consug University hospital, has found a weak but significant correlation between dosage increase in pregnancy and Klebs-Loeffler bacillus infections in neonates.
* Treatment failures may result from the concurrent use of [[rifampin]] with Quinine sulphate, due to decreased [[plasma]] concentrations of quinine, and concomitant use of these medications should be avoided.


===Quinine and interactions with other diseases===
=====Concomitant Use of Neuromuscular Blocking Agents:=====
Quinine can cause [[hemolysis]] in [[G6PD deficiency]], but again this risk is small and the physician should not hesitate to use quinine in patients with [[G6PD deficiency]] when there is no alternative. Quinine can also cause [[drug-induced]] [[immune thrombocytopenic purpura]] (ITP).
* The use of [[neuromuscular blocking agent]]s should be avoided in patients receiving Quinine sulphate. In one patient who received [[pancuronium]] during an operative procedure, subsequent administration of quinine resulted in [[respiratory depression]] and [[apnea]]. Although there are no clinical reports with [[succinylcholine]] or [[tubocurarine]], quinine may also potentiate [[Neuromuscular-blocking drugs|neuromuscular blockade]] when used with these drugs.


Quinine can cause abnormal heart rhythms and should be avoided if possible in patients with [[atrial fibrillation]], [[conduction defects]] or [[heart block]].
=====Hypersensitivity=====
* Serious [[hypersensitivity]] reactions reported with quinine sulfate include [[anaphylactic shock]], [[anaphylactoid reactions]], [[urticaria]], serious [[skin]] [[rashes]], including [[Stevens-Johnson syndrome]] and [[toxic epidermal necrolysis]], [[angioedema]], [[facial edema]], [[bronchospasm]], and [[pruritus]].


Quinine must not be used in patients with [[hemoglobinuria]], [[myasthenia gravis]] or [[optic neuritis]], because it worsens these conditions.
* A number of other serious adverse reactions reported with quinine, including [[thrombotic thrombocytopenic purpura]] ([[TTP]]) and [[hemolytic uremic syndrome]] ([[HUS]]), [[thrombocytopenia]], [[immune thrombocytopenic purpura]] ([[ITP]]), [[blackwater fever]], [[disseminated intravascular coagulation]], [[leukopenia]], [[neutropenia]], [[granulomatous hepatitis]], and [[acute interstitial nephritis]] may also be due to [[hypersensitivity]] reactions.


===Quinine and hearing impairment===
* Quinine sulphate should be discontinued in case of any signs or symptoms of [[hypersensitivity]].
Some studies have related the use of quinine and [[hearing impairment]], which can cause some high-frequency loss, but it has not been conclusively established whether such impairment is temporary or permanent.<ref>{{cite journal | author=Department of Clinical Pharmacology, Huddinge University Hospital, Sweden | title=The concentration-effect relationship of quinine-induced hearing impairment | journal=Clin Pharmacol Ther | year=1994 | volume=55 | issue=3 | pages=317&ndash;323 | pmid = 8143397  | accessdate=2006-05-06 }}</ref>


==Non-medical uses of quinine==
=====Atrial Fibrillation and Flutter:=====
[[Image:Tonic water uv.jpg|thumb|left|Tonic water, in normal light and UV.]]
* Quinine sulphate should be used with caution in patients with [[atrial fibrillation]] or [[atrial flutter]]. A paradoxical increase in ventricular response rate may occur with quinine, similar to that observed with quinidine. If [[digoxin]] is used to prevent a rapid ventricular response, serum [[digoxin]] levels should be closely monitored, because [[digoxin]] levels may be increased with use of quinine.
Quinine is a flavour component of [[tonic water]], [[bitter lemon]], and [[vermouth]]. According to tradition, the bitter taste of anti-malarial quinine tonic led British colonials in [[India]] to mix it with [[gin]], thus creating the [[gin and tonic]] cocktail, which is still popular today in both India and [[United Kingdom]], and in many English speaking countries.


In the [[United States]], the [[Food and Drug Administration]] limits tonic water quinine to 83 [[parts per million]], which is one-half to one-quarter the concentration used in therapeutic tonic.
=====Hypoglycemia=====
* Quinine stimulates release of [[insulin]] from the [[pancreas]], and patients, especially [[pregnant]] women, may experience clinically significant [[hypoglycemia]].
|clinicalTrials=====Overall====


In [[France]], quinine is an ingredient of an [[apéritif]] known as [[Quinquina]].
* Quinine can adversely affect almost every body system. The most common adverse events associated with quinine use are a cluster of symptoms called "[[cinchonism]]", which occurs to some degree in almost all patients taking quinine. Symptoms of mild [[cinchonism]] include headache, [[vasodilation]] and [[sweating]], [[nausea]], [[tinnitus]], [[hearing impairment]], [[vertigo]] or [[dizziness]], [[blurred vision]], and disturbance in color perception. More severe symptoms of [[cinchonism]] are [[vomiting]], [[diarrhea]], [[abdominal pain]], [[deafness]], [[blindness]], and disturbances in [[cardiac rhythm]] or conduction. Most symptoms of [[cinchonism]] are reversible and resolve with discontinuation of quinine.


Quinine is often added to street drugs [[cocaine]] or [[ketamine]] in order to "[[cutting agent|cut]]" the product and make more profit.
* The following ADVERSE REACTIONS have been reported with quinine sulfate. Most of these reactions are thought to be uncommon, but the actual [[incidence]] is unknown:


Because of its relatively constant and well-known [[fluorescence]] quantum yield, quinine is also used in photochemistry as a common fluorescence standard.
=====General:=====


In the United States, quinine is an ingredient in the [[Howling monkey energy drink]].
* [[Fever]], [[chills]], [[sweating]], [[flushing]], [[asthenia]], [[Systemic lupus erythematosus|lupus-like syndrome]], and [[hypersensitivity]] reactions.


In Canada, quinine is an ingredient in the carbonated [[chinotto]] beverage called Brio.
=====Hematologic:=====
* [[Agranulocytosis]], [[hypoprothrombinemia]], [[thrombocytopenia]], [[DIC|disseminated intravascular coagulation,]] [[hemolytic anemia]]; [[hemolytic uremic syndrome]], [[thrombotic thrombocytopenic purpura]], [[idiopathic thrombocytopenic purpura]], [[petechiae]], [[ecchymosis]], [[hemorrhage]], [[coagulopathy]], [[blackwater]] [[fever]], [[leukopenia]], [[neutropenia]], [[pancytopenia]], [[aplastic anemia]], and [[lupus anticoagulant]].


In the United Kingdom, quinine is an ingredient in the carbonated and caffeinated beverage, [[Irn-Bru]].
=====Neuropsychiatric:=====
* [[Headache]], [[diplopia]], [[confusion]], [[altered mental status]], [[seizures]], [[coma]], [[disorientation]], [[tremors]], [[restlessness]], [[ataxia]], [[acute dystonic reaction]], [[aphasia]], and [[suicide]].


In South Africa and Europe, quinine is an ingredient in the carbonated beverage called [[Schweppes]].
=====Dermatologic:=====
* [[rash|Cutaneous rashes]], including [[urticarial]], [[papular]], or [[rash|scarlatinal rashes]], [[pruritus]], [[bullous]] [[dermatitis]], [[exfoliative dermatitis]], [[erythema multiforme]], [[Stevens-Johnson syndrome]], [[toxic epidermal necrolysis]], [[fixed drug eruption]], [[photosensitivity]] reactions, [[allergic contact dermatitis]], [[acral necrosis]], and [[Cutaneous small vessel vasculitis|cutaneous vasculitis]].


==References==
=====Respiratory:=====
<references/>
* [[Asthma]], [[dyspnea]], [[pulmonary edema]].


==See also==
=====Cardiovascular:=====
*[[Pharmacology]]
* [[Chest pain]], [[vasodilatation]], [[hypotension]], [[postural hypotension]], [[tachycardia]], [[bradycardia]], [[palpitations]], [[syncope]], [[atrioventricular block]], [[atrial fibrillation]], [[irregular rhythm]], [[premature ventricular contractions|unifocal premature ventricular contractions]], [[nodal escape beats]], [[U waves]], [[QT prolongation]], [[ventricular fibrillation]], [[ventricular tachycardia]], [[torsades de pointes,]] and [[cardiac arrest]].
*[[Luis Jerónimo Fernández de Cabrera]] and [[Jesuit's bark]], for the story of its introduction into Europe
Jeffrey I. Seeman, ''The Woodward-Doering/Rabe-Kindler Total Synthesis of Quinine: Setting the Record Straight'' ''Angew. Chem. Int. Ed. Eng''. '''2007''', ''9'', 1373.


==External links==
=====Gastrointestinal:=====
* [http://www.companymagazine.org/v144/powder.html Jesuits' Powder]
* [[Nausea]], [[vomiting]], [[diarrhea]], [[abdominal pain]], [[gastric irritation]], and [[esophagitis]].
* [http://www.intox.org/databank/documents/pharm/quinine/ukpid13.htm From intox databank]
* [http://www.inchem.org/documents/pims/pharm/pim464.htm From inchem]
* [http://www.rain-tree.com/quinine.htm Database file on Quinine from rain-tree.com]
* [http://www.organic-chemistry.org/Highlights/2004/01November.shtm Catalytic Asymmetric Synthesis of Quinine and Quinidine]
* [http://pubs.acs.org/cen/coverstory/83/8325/8325quinine.html Summary article on history of Quinine in Chemical and Engineering News]
* [http://historyofalcoholanddrugs.typepad.com/alcohol_and_drugs_history/quinine/index.html Quinine news page] - [[Alcohol and Drugs History Society]]


{{Antimalarials}}
=====Hepatobiliary:=====
[[ca:Quinina]]
* [[Granulomatous hepatitis]], [[hepatitis]], [[jaundice]], and abnormal [[liver function tests]].
[[cs:Chinin]]
[[da:Kinin]]
[[de:Chinin]]
[[es:Quinina]]
[[eo:Kinino]]
[[fr:Quinine]]
[[ko:퀴닌]]
[[it:Chinino]]
[[he:כינין]]
[[nl:Kinine]]
[[ja:キニーネ]]
[[no:Kinin]]
[[pt:Quinina]]
[[ru:Хинин]]
[[sk:Chinín]]
[[fi:Kiniini]]
[[sv:Kinin]]
[[zh:奎寧]]


=====Metabolic:=====
* [[Hypoglycemia]] and [[anorexia]].


[[Category:Ethers]]
=====Musculoskeletal:=====
[[Category:Nitrogen heterocycles]]
* [[Myalgias]] and [[muscle weakness]].
[[Category:Quinine]]
[[Category:Teratogens]]
[[Category:Antimalarial agents]]
[[Category:Quinolines]]
[[Category:Drugs]]


[[pl:Chinina]]
=====Renal:=====
[[tr:Kinin]]
* [[Hemoglobinuria]], [[renal failure]], [[renal impairment]], and [[acute interstitial nephritis]].


{{jb1}}
=====Special Senses:=====
{{WH}}
* Visual disturbances, including [[blurred vision]] with [[scotomata]], sudden [[loss of vision]], [[photophobia]], [[diplopia]], [[night blindness]], diminished [[visual fields]], fixed [[pupillary dilatation]], disturbed [[color vision]], [[optic neuritis]], [[blindness]], [[vertigo]], [[tinnitus]], [[hearing impairment]], and [[deafness]].
{{WikiDoc Sources}}
|postmarketing=There is limited information regarding <i>Postmarketing Experience</i> of Quinine sulphate in the drug label.
|alcohol=Alcohol-Quinine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
}}

Latest revision as of 16:00, 3 March 2015

Quinine
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Adeel Jamil, M.D. [2]

Disclaimer

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Black Box Warning

WARNING
See full prescribing information for complete Boxed Warning.
* Quinine sulphate use for the treatment or prevention of nocturnal leg cramps may result in serious and life-threatening hematologic reactions, including thrombocytopenia and hemolytic uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP). Chronic renal impairment associated with the development of TTP has been reported. The risk associated with Quinine sulphate use in the absence of evidence of its effectiveness in the treatment or prevention of nocturnal leg cramps outweighs any potential benefit

Overview

Quinine is a cinchona alkaloid, antimalarial and anti-Infective Agent, that is FDA approved for the treatment of of uncomplicated Plasmodium falciparum malaria. There is a Black Box Warning for this drug as shown here. Common adverse reactions include cinchonism include headache, vasodilation and sweating, nausea, tinnitus, hearing impairment, vertigo or dizziness, blurred vision, and disturbance in color perception..

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

  • Quinine sulphate oral capsules are not approved for:

Dosing Information

  • Quinine sulphate should be taken with food to minimize gastric upset.
Renal Impairment
  • In patients with acute uncomplicated malaria and severe chronic renal impairment, the following dosage regimen is recommended: one loading dose of 648 mg Quinine sulphate followed 12 hours later by maintenance doses of 324 mg every 12 hours.
Hepatic Impairment

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding off-label use and dosage for adults.

Non–Guideline-Supported Use

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding FDA-Labeled Use of Quinine sulphate in pediatric patients.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Quinine sulphate in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Quinine sulphate in pediatric patients.

Contraindications

Quinine sulphate is contraindicated in patients with the following:

Prolonged QT interval:
Glucose-6-phosphate dehydrogenase deficiency(G6PD):
Known hypersensitivity reactions to quinine:
  • These include, but are not limited to, the following:

Hemolytic uremic syndrome (HUS)

Warnings

WARNING
See full prescribing information for complete Boxed Warning.
* Quinine sulphate use for the treatment or prevention of nocturnal leg cramps may result in serious and life-threatening hematologic reactions, including thrombocytopenia and hemolytic uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP). Chronic renal impairment associated with the development of TTP has been reported. The risk associated with Quinine sulphate use in the absence of evidence of its effectiveness in the treatment or prevention of nocturnal leg cramps outweighs any potential benefit

Use of Quinine for Treatment or Prevention of Nocturnal Leg Cramps:

Thrombocytopenia
  • Quinine-induced thrombocytopenia is an immune-mediated disorder. Severe cases of thrombocytopenia that are fatal or life threatening have been reported, including cases of HUS/TTP. Chronic renal impairment associated with the development of TTP has also been reported. Thrombocytopenia usually resolves within a week upon discontinuation of quinine. If quinine is not stopped, a patient is at risk for fatal hemorrhage. Upon re-exposure to quinine from any source, a patient with quinine-dependent antibodies could develop thrombocytopenia that is more rapid in onset and more severe than the original episode.
QT Prolongation and Ventricular Arrhythmias:
Concomitant Use of Rifampin:
  • Treatment failures may result from the concurrent use of rifampin with Quinine sulphate, due to decreased plasma concentrations of quinine, and concomitant use of these medications should be avoided.
Concomitant Use of Neuromuscular Blocking Agents:
Hypersensitivity
  • Quinine sulphate should be discontinued in case of any signs or symptoms of hypersensitivity.
Atrial Fibrillation and Flutter:
  • Quinine sulphate should be used with caution in patients with atrial fibrillation or atrial flutter. A paradoxical increase in ventricular response rate may occur with quinine, similar to that observed with quinidine. If digoxin is used to prevent a rapid ventricular response, serum digoxin levels should be closely monitored, because digoxin levels may be increased with use of quinine.
Hypoglycemia

Adverse Reactions

Clinical Trials Experience

Overall

  • The following ADVERSE REACTIONS have been reported with quinine sulfate. Most of these reactions are thought to be uncommon, but the actual incidence is unknown:
General:
Hematologic:
Neuropsychiatric:
Dermatologic:
Respiratory:
Cardiovascular:
Gastrointestinal:
Hepatobiliary:
Metabolic:
Musculoskeletal:
Renal:
Special Senses:

Postmarketing Experience

There is limited information regarding Postmarketing Experience of Quinine sulphate in the drug label.

Drug Interactions

There is limited information regarding Quinine Drug Interactions in the drug label.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): There is no FDA guidance on usage of Quinine in women who are pregnant.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Quinine in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Quinine during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Quinine in women who are nursing.

Pediatric Use

There is no FDA guidance on the use of Quinine in pediatric settings.

Geriatic Use

There is no FDA guidance on the use of Quinine in geriatric settings.

Gender

There is no FDA guidance on the use of Quinine with respect to specific gender populations.

Race

There is no FDA guidance on the use of Quinine with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Quinine in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Quinine in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Quinine in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Quinine in patients who are immunocompromised.

Administration and Monitoring

Administration

There is limited information regarding Quinine Administration in the drug label.

Monitoring

There is limited information regarding Quinine Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Quinine and IV administrations.

Overdosage

There is limited information regarding Quinine overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

Pharmacology

There is limited information regarding Quinine Pharmacology in the drug label.

Mechanism of Action

There is limited information regarding Quinine Mechanism of Action in the drug label.

Structure

There is limited information regarding Quinine Structure in the drug label.

Pharmacodynamics

There is limited information regarding Quinine Pharmacodynamics in the drug label.

Pharmacokinetics

There is limited information regarding Quinine Pharmacokinetics in the drug label.

Nonclinical Toxicology

There is limited information regarding Quinine Nonclinical Toxicology in the drug label.

Clinical Studies

There is limited information regarding Quinine Clinical Studies in the drug label.

How Supplied

There is limited information regarding Quinine How Supplied in the drug label.

Storage

There is limited information regarding Quinine Storage in the drug label.

Images

Drug Images

{{#ask: Page Name::Quinine |?Pill Name |?Drug Name |?Pill Ingred |?Pill Imprint |?Pill Dosage |?Pill Color |?Pill Shape |?Pill Size (mm) |?Pill Scoring |?NDC |?Drug Author |format=template |template=DrugPageImages |mainlabel=- |sort=Pill Name }}

Package and Label Display Panel

{{#ask: Label Page::Quinine |?Label Name |format=template |template=DrugLabelImages |mainlabel=- |sort=Label Page }}

Patient Counseling Information

There is limited information regarding Quinine Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Quinine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Quinine Brand Names in the drug label.

Look-Alike Drug Names

There is limited information regarding Quinine Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

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