Summary for UKPID


    Kathryn Pughe, BSc (Hons) MRPharmS

    National Poisons Information Service (Newcastle Centre)
    Regional Drug & Therapeutics Centre
    Wolfson Building
    Claremont Place
    Newcastle upon Tyne
    NE1 4LP

    This monograph has been produced by staff of a National Poisons
    Information Service Centre in the United Kingdom.  The work was
    commissioned and funded by the UK Departments of Health, and was
    designed as a source of detailed information for use by poisons
    information centres.

    Peer review group: Directors of the UK National Poisons Information



         quinine sulphate
         quinine bisulphate
         quinine hydrochloride
         quinine dihydrochloride

    Chemical group/family

         BNF 5.4.1

    Reference number

         (CAS) 130-95-0 (anhydrous quinine)


         Cox Arthur H & Co Ltd
         Whiddon Valley
         North Devon EX32 8NS

         Tel: 01271 311200
         Fax: 01271 46106


         quinine sulphate 125 mg, 200 mg, 300 mg
         quinine bisulphate 200 mg, 300 mg
         quinine hydrochloride 300 mg
         quinine dihydrochloride 300 mg
         produced in various pack sizes e.g. 100,1000

         injection 300 mg/ml also available from Martindale

    Physico-chemical properties (Dollery)


    Molecular Weight

         quinuclidinyl group      4.1
         quinolone group          8.5

         in water                 very low
         in alcohol               1 in 1



         prophylaxis and treatment of malaria
         prevention of nocturnal muscle cramps

    Therapeutic Dosage (BNF)

         Adults         malaria        300 mg - 600 mg daily
                        muscle cramps  200 mg - 300 mg daily

         Children       malaria        30 mg/kg daily


    Hypersensitivity to quinine and other cinchona alkaloids.
    Concurrent use with cimetidine, amiodarone, digoxin and other
    digitalis glycosides.
    Therapeutic administration of mefloquine within the preceding 14 days.
    Optic neuritis


    Caution should be used in patients with history of asthma, serious
    heart disease or tinnitus.
    Quinine may stimulate pancreatic insulin release and should be used
    cautiously in hypoglycaemic persons.
    Quinine may cause thrombocytopenia purpura and should be used
    cautiously in patients with a history of this reaction, or in highly
    sensitive patients.


    Oral absorption                              >80%
    Presystemic metabolism                       >10%
    Volume of distribution (healthy subjects)    1.5 Lkg-1
         (severe malaria)                        1.2 Lkg-1
    Plasma half life
         range (healthy subjects)                7 - 11 hr
         (severe malaria)                        6 - 47 hr
         mean (healthy subjects)                 8.7 hr
         mean (severe malaria)                   18.2 hr

    Toxicokinetics (Bateman DN et al, 1985)

    At toxic levels elimination half life is reported to be 26.5 +/- 5.8

    Adverse effects

    Cinchonism, including tinnitus, headache, hot and flushed skin,
    nausea, abdominal pain, rashes, visual disturbances (including
    temporary blindness), confusion.

    Hypersensitivity reactions including angioedema, blood disorders
    (including thrombocytopenia and intravascular coagulation) and acute
    renal failure.

    Hypoglycaemia (especially after parenteral administration).


    Quinine is used mainly in the treatment of chloroquine resistant
    malaria. There have been a large number of case reports of
    malformations following quinine ingestion in human pregnancy. Many of
    these pregnancies involved large doses of quinine used as an
    abortifacient. The most frequently reported abnormality following
    quinine exposure during early pregnancy is hypoplasia of the auditory
    nerve with resultant deafness. Other major malformations involving
    most organ systems have been reported also. However, the Perinatal
    Collaborative Study reported no association between first trimester
    exposure to quinine and birth defects. In general, there has been no
    proven association between quinine at doses used for malarial
    prophylaxis and an increased risk of malformations.

    Third trimester exposure to quinine does not appear to adversely
    effect uterine contractility. However, an increase in insulin
    secretion associated with hypoglycaemia has been reported. Therefore,
    monitoring of blood or serum glucose levels during quinine therapy is

    Breast milk

    Quinine is excreted into breast milk. Following 300 and 640 mg oral
    doses in six patients, milk concentrations varied up to 2.2 mcg/ml,
    with an average level of 1 mcg/ml at 3 hours. No adverse effects in
    breast fed babies were reported. Quinine is thought to be
    compatible with breast feeding (Bennet PN, 1988).

    Interactions (BNF)

    Anti-arrhythmic          plasma concentration of flecainide increased

    Antihistamines           increased risk of ventricular arrythmias with
                             astemizole and terfenadine

    Cardiac glycosides       plasma concentration of digoxin increased -
                             halve digoxin maintenance dose (includes use
                             of quinine for cramps)

    Ulcer-healing drugs      cimetidine inhibits quinine metabolism
                             (increased plasma quinine concentration)

    Other antimalarials      Increased risk of arryhthmias with
                             halofantrine and mefloquine



    Type of product: For treatment of malaria and leg cramps.

    Quinine salt         Tablet size (mg)    Quinine base content (mg)
    Sulphate             125                 103
                         200                 165
                         300                 248
    Dihydrochloride      300                 246
    Hydrochloride        300                 246


    Highly toxic.

    There is a higher risk of visual loss and cardiac complications when
    plasma concentrations of quinine exceed 15 mg/l at any stage of

    The average fatal dose for an adult is about 8 g although deaths have
    been reported from as little as 1.5 g in an adult and 900 mg in a

    General features

    Quinine causes nausea, vomiting, tremor, tinnitus and deafness.

    Visual features

    Blurred vision may proceed to complete blindness within a few hours.
    As vision is lost the pupils become dilated and unresponsive to light.
    Initially only narrowing of the retinal arterioles may be seen on
    fundoscopy but after 3 days retinal oedema may appear.

    Cardiac features

    Tachycardia, dysrhythmias, hypotension and ECG conduction
    abnormalities may precede cardiac arrest.

    Other features

    Oliguria and acute renal failure from intravascular haemolysis. Coma
    and convulsions (especially in children)


    1. Monitor cardiac conduction and rhythm.

    2. Supportive measures from coma and convulsions.

    3. Empty the stomach if within 4 hours of ingestion.

    4. Repeated dose oral activated charcoal has been shown to increase
    quinine elimination in volunteers, and should therefore be used in

    5. Severe impairment of vision cannot be treated. The evidence that
    stellate ganglion block, retro-bulbar injections or vasodilators are
    effective is poor and based on wrong assumptions about the mode of
    toxicity of quinine. Discuss with the doctor on call.

    Some recovery of vision can be expected but permanent, severe
    restriction of the visual fields may occur. Optic atrophy may appear

    6. Methods to enhance elimination of quinine from the body (other than
    oral activated charcoal) are of doubtful value. This is particularly
    true of forced acid diuresis, exchange transfusion, haemodialysis and
    charcoal haemoperfusion. The value or otherwise of resin
    haemoperfusion is yet to be demonstrated.

    Serious poisoning should be discussed with the doctor on call.


    Wolf LR et al. Cinchonism: two case reports and review of acute
    quinine toxicity and treatment. J Emerg Med 1992;10:295-301.

    Schonwald and Shannon M. Unsuspected quinine intoxication presenting
    as acute deafness and mutism. Am J Emerg Med 1991;9:318-320.

    Canning CR, Hague S. Ocular quinine toxicity. Br J Opthalmol

    Bateman DN. Quinine toxicity. Adv Drug React Ac Pois Rev 1986;4:215-

    Dyson EH, et al. Quinine amblopia: is current management appropriate ?
    Clin Toxicol 1985-86;23:571-578.

    Bateman DN et al. Pharmacokinetics and clinical toxicity of quinine
    overdosage: lack of efficacy of techniques intended to enhance
    elimination. Q J Med 1985;ns54,no214:125-131.

    Murray SB, Jay JL. Loss of sight after self-poisoning with quinine. Br
    Med J 1983;287:1700.



    Quinine has class 1A antiarrhythmic effects, but is less potent than
    its stereoenantiomer quinidine. These effects include sodium channel
    blockade, slowed phase o depolarisation, conduction delay and
    prolonged repolarisation. Quinine also has alpha agonist action and
    may have oxytocic actions.

    Range of toxicity (Poisindex)

    The adult toxic dose may be as little as 2g, although usually greater
    than 3 to 4g.

    Toxic Levels

    Plasma concentrations over 5 mcg/ml causes cinchonism
    Plasma concentrations above 10 mcg/ml are associated with visual
    Plasma concentrations above 15 mcg/ml are associated with cardiac

    Fatal Level

    Death was reported in a patient with an initial quinine level of 22.2
    mcg/ml. A peak level of 17.8 mcg/ml was reported in a fatal case
    (Wenstone et al 1989).



    Quinine overdose either intentionally or accidentally has been
    reported to result in signs and signs and symptoms including headache,
    deafness, tachycardia, depression of atrial, atrioventricular and
    ventricular conduction arrhythmias, hypotension, heart failure
    syncope, respiratory arrest, paraesthesia, coma and death.


    Visual field constriction may progress to sudden blindness with
    non-reactive dilated pupils.

    Fixed dilated pupils are seen frequently in children following quinine
    overdosage (Grattan-Smith et al,1987).

    In addition to cinchonism quinine is thought to have a direct toxic
    effect on the retina, causing constricted fields that can progress to
    blindness with dilated non reactive pupils (Dyson et al,1985).

    Central vision usually recovers first. Complete recovery of vision may
    take several months; pupils may remain dilated after recovery of

    Blindness following quinine overdosage is typically delayed in onset
    usually for more than 12 hours (Smilkstein et al, 1987).

    Plasma concentrations associated with the visual deficits usually
    exceed 15mg/l in less than 10 hours post-ingestion and greater than 10
    mg/l after 10 hours. However, plasma concentrations appear to be
    inadequate to predict the extent of visual deficit.


    Transient tinnitus and eighth bilateral nerve damage have been
    observed after overdose.

    Deafness and mutism occurred in a 14 year old who ingested
    approximately 6.5 to 7.8 g of quinine sulphate. Symptoms lasted for
    approximately 3 days (Schonwald & Shannon, 1991).


    Cardiotoxicity typically appears within 8 hours following ingestion of
    quinine, but delayed cardiotoxicity up to 25 hours after ingestion
    have been reported (Bodenhamer & Smilkstein, 1993).

    Sinoatrial, atrioventricular and His-ventricular depression of
    conduction may occur along with ventricular tachycardia and
    ventricular fibrillation. Syncope is usually related to transient
    torsade de pointes ventricular tachycardia (Bauman et al, 1984).

    Hypotension occurs frequently. Heart failure may result. Toxic ECG
    abnormalities include prolongation of the PR, QRS and QT intervals. ST
    depression and T wave inversion may also occur.


    Respiratory depression may occur. Adult respiratory distress syndrome
    has been reported in one fatal case (Wenston et al, 1989).


    Ataxia, paresthesias. Convulsions may follow an overdose.

    Central nervous system toxicity seems to be more marked in children
    than adults. Children frequently present with seizures following and
    overdose (Grattan-Smith et al, 1987).


    Nausea and vomiting are common side effects of quinine.


    Hepatic granulomas have been reported with quinidine as well as
    reversible hypersensitivity-related hepatitis.


    Hypokalaemia may occur secondary to quinine induced electrolyte
    fluxes. Aggressive treatment is not recommended.


    Haemolytic anaemia may occur in patients with G6PD deficiency.
    Thrombocytopenia (immune mechanism)


    Therapeutic use of quinine and overdosage has resulted in severe
    hypoglycaemia (Wenstone et al, 1989).


    Photosensitivity reactions may occur

    Chronic toxicity

    No information



    Repeated doses of oral activated charcoal should be started as soon as
    possible since their is some evidence that this shortens the half life
    which is otherwise about 26 hours after over dosage. 50 - 100g (25g in
    children) should be given initially followed by 25 g 2 hourly or 50 g
    4 hourly (12g in children). 20ml of lactulose should be given with
    each dose of charcoal.

    Supportive care

    There is no evidence that stellete ganglion block, retro-bulbar
    injections or vasodilators are effective. Evidence is based on wrong
    assumptions about the mode of toxicity of quinine. They are not

    Fluid and electrolyte monitoring and repeated evaluations of renal
    function should be performed


    Monitor vital signs - pulse, blood pressure, respiration
    Careful monitoring of ECG and ventilation should be instituted.
    Blood for evaluation of plasma quinine level may useful to asses
    Renal function
    Blood gases if patient is unconscious
    Blood sugar


    There are no effective antidotes

    Elimination techniques

    Measures to enhance the elimination of quinine have been generally
    ineffective (Bateman et al, 1985). The natural history of quinine
    amblyopia is such that elimination procedures may not critically alter
    its course (Heath,1985).

    Forced diuresis has not been found not to produce a sufficiently rapid
    reduction in plasma concentration or to have a substantial effect on
    visual disturbances. (Bateman DN at al 1985).

    Peritoneal dialysis is less effective than normal renal excretion, but
    has been used occasionally in patients with renal failure (Markham et
    al, 1967).

    Haemodialysis, charcoal haemoperfusion and exchange transfusion have
    similarly been found to be ineffective in increasing quinine
    elimination (Bateman DN et al 1985).

    Haemodialysis combined with resin haemoperfusion may be effective in
    the treatment of quinine blindness refractory to the usual therapy
    (Gibbs JL,1985). However these data have yet to be corroborated
    (Bateman DN, 1985).


    On admission blood should be drawn for a full blood count, blood
    sugar, prothrombin time, renal function tests, urinalysis and

    Periodic eye examinations should include visual acuity. Other
    techniques that may be used in the longer term assessment of patients
    with quinine ambylopia include electroretinography, electrooculogram,
    visual evoked potentials, dark adaptations, and colour testing.

    Periodic ECGs as indicated.

    Management controversies

    Most recent evidence has shown that enhancement of elimination of
    quinine by forced acid diuresis, peritoneal dialysis, haemodialysis,
    charcoal haemoperfusion are ineffective (Bateman DN et al 1985).

    The evidence that stellate ganglion block, retro-bulbar injections or
    vasodilators are effective is poor and based on wrong assumptions
    about the mode of toxicity of quinine. This technique should,
    therefore, not be used.


    1. Bodenhamer & Smilkstein (1993) reported delayed cardiotoxicity
    following ingestion of 16.25g of quinine in a 49 year old female.
    Symptoms appeared 11.5 hours following ingestion, with conduction
    abnormalities, ectopy and torsades de pointes occurring 25 hours after

    2. Notelovitz et al (1970) report a case of a 21 year old female who
    ingested 90g of quinine during her 8th week of pregnancy to induce
    abortion. The patient subsequently became drowsy with dark red urine
    which was positive for blood and albumin. The patient became oliguric
    and her blood urea rose to 2080 g/l. The patient was treated with
    diuretics, blood transfusion and haemodialysis with improvement and
    discharge within 72 hours.

    3.Visual damage occurred following overdose of quinine in 2 patients (
    a 38 year old male who ingested 2g of quinine and a 60 year old woman
    who ingested 4g of quinine). The vision loss was only partially
    reversible (Murray & Jay 83). A 26 year old male developed bilateral
    loss of vision after ingesting 20 quinine tablets and an unknown
    quantity of alcohol (Drake & Hiorns 1994).

    4. A 17 year old man ingested 5 g of quinine and developed deafness
    within several hours. Upon presentation he was noted to have broad
    complex tachycardia, which normalised over 8 hours. The case was
    complicated with hypokalaemia (2.2 mmol/l) and hypoglycaemia (2.7
    mmol/l). Later chest x-ray revealed non-cardiogenic pulmonary oedema.
    He was treated with antibiotics and inotropic agents. Renal
    dysfunction developed on the ninth day and the patient died from
    hypoxic cardiac arrest on the twelfth day. Necropsy revealed ARDS. The
    peak quinine level was 17.8 mg/l (Wenston et al 1989).

    5. Goldenberg AM & Wexler LF (1988) report a case of a 24 year old man
    who ingested 8 g of quinine sulphate in a suicide attempt. The patient
    presented within 2 hours and was given a stomach washout. Despite
    haemoperfusion which was started 10 hours after ingestion, the patient
    suffered a fatal asystolic cardiac arrest.

    6. A case of unsuspected quinine overdose is reported in a 14 year old
    girl who presented with symptoms including deafness and mutism
    (Schonwald S & Shannon M, 1991). Diagnosis was delayed for
    approximately 4 hours because of the absence of an accurate history.
    The patient took upto 7.8g of quinine, and the serum level 6-8 hours
    postingestion was 4.5mg/L. Hearing gradually returned on the third day
    after admission and later that day the patients mutism resolved

    7. Two cases of acute quinine toxicity are reported by Wolf LR et al
    (1992). Both patients presented with acute bilateral blindness. They
    also experienced the classic symptoms of sinchinism, including nausea,
    vomiting, and tinnitus. Prolongation of the Q-T interval developed in
    both patients. Serum quinine levels were 5.3 mg/l and 13 mg/l.
    Although their visual acuity improved, both patients has some residual
    deficit at follow up.


    Plasma quinine levels can be performed with a modification of the test
    used to measure quinidine levels using high performance liquid
    chromatography. (Dyson EH et al 1985 BMJ1985)


    Kathryn Pughe, BSc (Hons) MRPharmS

    National Poisons Information Service (Newcastle Centre)
    Regional Drug & Therapeutics Centre
    Wolfson Building
    Claremont Place
    Newcastle upon Tyne
    NE1 4LP

    This monograph was produced by the staff of the Newcastle Centre of
    the National Poisons Information Service in the United Kingdom. The
    work was commissioned and funded by the UK Departments of Health, and
    was designed as a source of detailed information for use by poisons
    information centres.

    Peer review was undertaken by the Directors of the UK National Poisons
    Information Service.

    Last updated March 1996


    Bateman DN, Blain PG, Woodhouse KW, Rawlins MD, Dyson H, Heyworth R,
    Prescott LF, Proudfoot AT. Q J Med N Ser. 1985;54:125-131.

    Bauman JL, Baurenfiend RA, Strasberg B. Torsades de pointes due to
    quinidine; observation in 31 patients. Am Heart J 1984;107:4125-4230.

    Bennett PN and the WHO Group, Drugs and Human Lactation, Elsevier

    Bodenhamer JE & Smilkstein MJ. Delayed cardiotoxicity following
    quinine overdosage: A case report. J Emerg Med. 1993;11:279-285.

    British National Formulary. Number 30 (September 1995). British
    Medical Association and Royal Pharmaceutical Society.

    Drake WM and Hiorns MP. Quinine overdose: review of toxicity and
    treatment. Clin Cardiol. 1988;11:726-718.

    Dollery C. Therapeutic Drugs. Churchill Livingstone. 1991.

    Dyson EH, Proudfoot AT, Prescott LF, Heyworth R. Death and blindness
    due to overdose of quinine. Br Med J 1985;291:31-33.

    Gibbs JL, Trafford A, Sharpstone P. Quinine amblyopia treated by
    combined haemodialysis and activated resin haemoperfusion. Lancet

    Goldenberg AM & Wexler LF. Quinine overdose: review of toxicity and
    treatment. Clin Cardiol. 1988;11:716-718.

    Grattan-Smith TM, Gillis J, Killham H. Quinine poisoning in children.
    Med J Aust. 1987;147:93-95.

    Heath A. Resin haemoperfusion for quinine poisoning. Lancet

    Markhan TN, Dodson VN, Eckberg DL. Peritoneal dialysis in quinine
    sulphate intoxication. JAMA 1967;202:1102-1103.

    Murray SB and Jay JL. Loss of sight after self poisoning with quinine.
    Br Med J 1983;287:1700.

    Notelovitz M. Acute renal failure following quinine poisoning. So Afr
    Med J 1970;44:649.

    Poisindex System(R), Micromedex, inc, Denver Colorado, Edition Expires

    Schonwald S & Shannon M. Unsuspected quinine intoxication presenting
    as acute deafness and mutism. Am J Emerg Med. 1991;9:318-320.

    Smilkstein MJ, Kulig KW, Rumack BH. Acute toxic blindness:
    Unrecognised quinine poisoning. Ann Emerg Med. 1987;16:98-101.

    Wenstone R, Bell ME, Mostafa SM. Fatal adult respiratory distress
    syndrome after quinine overdose (letter). Lancet 1989;1:1143-1144

    Wolf LR, Otten EJ, Spadafora MP. Cinchonism: Two case reports and
    review of acute quinine toxicity and treatment. J Emerg Med.