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QUININE BISULFATE TABLETS BP 300MG

Active substance(s): QUININE BISULFATE / QUININE BISULFATE

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1.

NAME OF THE MEDICINAL PRODUCT
Quinine Bisulfate Tablets BP 300mg

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains quinine bisulfate 300mg
For excipients, see 6.1

3.

PHARMACEUTICAL FORM

Film-coated tablet
A white, biconvex film-coated tablet

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
For the treatment of falciparum malaria
Treatment and prevention of nocturnal leg cramps in adults and the elderly, when cramps
cause regular disruption of sleep (see section 4.2 and Section 4.4)

4.2

Posology and method of administration
For falciparum malaria
Adults: the adult dosage regimen by mouth is 600mg of quinine sulfate given every 8
hours for 7 days.
The elderly: as for adults
Children: the dosage regimen for children by mouth is 10mg of quinine sulfate per kg
body weight given every 8 hours for 7 days.
Note
If quinine resistance is known or suspected in the patient, then supplementary
treatment with another recommended antimalarial drug is necessary.
If part or all of the dose is vomited within 1 hour of administration, then the same
amount must be administered immediately.
For the treatment and prevention of nocturnal leg cramps:

Adults (including elderly):
The recommended dose is 300mg at bedtime.
A reduction in frequency of leg cramps may take up to 4 weeks to become apparent.
Patients should be monitored closely during the early stages of treatment for
adverse effects. After an initial trial of 4 weeks, treatment should be stopped if there
is no benefit. Treatment should be interrupted at approximately three monthly
intervals to reassess the benefit of treatment.

4.3

Contraindications
-Hypersensitivity to the active substance(s) or to any of the excipients listed in section
6.1.
-Optic neuritis
-Tinnitus
-Myasthenia gravis, quinine may cause severe respiratory distress and dysphagia in
these patients
-Haemoglobinuria

4.4

Special warnings and precautions for use
Cinchonism
Administration of quinine may give rise to cinchonism, which is generally more
severe in overdose, but may also occur in normal therapeutic doses. Patients should be
warned not to exceed the prescribed dose, because of the possibility of serious,
irreversible side effects in overdose. Treatment for night cramps should be stopped if
symptoms of cinchonism emerge. Such symptoms include tinnitus, impaired hearing,
headache, nausea, and disturbed vision (see sections 4.8 and 4.9).
Hypersensitivity
Hypersensitivity to quinine may also occur with symptoms of cinchonism together
with urticaria, flushing, pruritus, rash, fever, angioedema, dyspnoea and asthma.
Serious hypersensitivity reactions including Stevens-Johnson syndrome have been
reported with quinine.
Cardiac disorders
Quinine should be used with caution in patients with atrial fibrillation, conduction
defects and heart block or other serious heart disease. It may cause
hypoprothrombinaemia.
Glucose-6-Phosphate Dehydrogenase (G-6-PD) Deficiency
The administration of quinine to a patient who has previously been suffering from a
chronic and inadequately controlled malarial infection may precipitate an attack of
blackwater fever. However, in some cases deficiency of glucose-6-phosphate

dehydrogenase may have been involved. Glucose-6-phosphate dehydrogenase
deficient patients with malaria or taking quinine to treat leg cramps may be at an
increased risk of haemolytic anaemia during quinine therapy.
Quinine should not be withheld from pregnant women who have life threatening
malaria (see section 4.6).
Treatment should be monitored in all patients in case signs of resistance develop.
Before use for nocturnal leg cramps, the risks, which include significant adverse
effects and interactions (see above and sections 4.5 and 4.8), should be carefully
considered relative to the potential benefits. These risks are likely to be of particular
concern in the elderly. Quinine should only be considered when cramps are very
painful or frequent, when other treatable causes of cramp have been ruled out, and
when non-pharmacological measures have not worked. Quinine bisulfate should not
be used for this indication during pregnancy (see section 4.6).
Quinine may cause unpredictable serious and life-threatening thrombocytopenia,
which is thought to be an idiosyncratic hypersensitivity reaction. Quinine should not
be prescribed or administered to patients who have previously experienced any
adverse reaction to quinine, including that in tonic water or other beverages. Patients
should be instructed to stop treatment and consult a physician if signs of
thrombocytopenia such as unexplained bruising or bleeding occur.
Patients with rare hereditary problems of galactose intolerance, the LAPP lactase
deficiency or glucose-galactose malabsorption should not take this medicine, as it
contains lactose.
Reduce the dosage (or increase intervals between doses) in renal or hepatic disease.
4.5

Interaction with other medicinal products and other forms of interaction
Effect of other drugs on quinine
CYP3A4 substrate
Quinine is metabolised via hepatic oxidative cytochrome P450 pathways,
predominantly by CYP3A4. There is the potential for increased quinine toxicity with
concurrent use of potent CYP3A4 inhibitors, which include azole antifungal drugs and
HIV protease inhibitors.
Sub-optimal quinine serum levels may result from concomitant use of CYP3A4
inducers such as rifampicin, barbiturates, carbamazepine and phenytoin.
Care should be taken when quinine is used in combination with other CYP3A4
substrates, especially those causing prolongation of the QT interval.
Effect of quinine on other drugs
The plasma concentration of mefloquine may be increased.
Amantidine: Quinine can reduce the renal clearance of amantadine

If quinine is administered the maintenance dose of digoxin should be halved.
Ciclosporin: Quinine can decrease serum plasma concentrations of ciclosporin
Cardiac glycosides: Quinine increases plasma concentrations of cardiac
glycosides and
reduced dosage of concomitant cardiac glycosides such
as digoxin to half the maintenance dose may be necessary.

Other drug interactions
Drug caused QT prolongation
There is an increased risk of ventricular arrhythmias with other drugs which prolong
the QT interval, including amiodarone, moxifloxacin, pimozide thioridazine and
halofantrine, and therefore concomitant use with these products should be avoided
Antiarrhythmics: Concomitant use of amiodarone should be avoided due to the
increased risk of ventricular arrhythmias. The plasma concentration of
flecainide is increased by quinine. Concomitant use of quinidine may
increase the possibility of
cinchonism.
Antibacterials; There is an increased risk of ventricular arrhythmias when
moxifloxacin is given with quinine. Rifampicin can reduce the serum levels of
quinine, therefore reducing its therapeutic effect.
Anticoagulants: Quinine may cause hypoprothrombinaemia and thereby enhance the
effect of anticoagulants.
Antihistamines: Concomitant use of terfenadine should be avoided due to the
increased risk of ventricular arrhythmias.
Antimalarials: According to the manufacturer of artemether with lumefantrine
concomitant use should be avoided. There is an increased risk of convulsions
when
given with mefloquine. Chloroquine and quinine appear to be
antagonistic when
given together for P falciparum malaria. There is a decrease in plasma
concentrations
of primaquine.
Antipsychotics: There is an increased risk of ventricular arrhythmias and concomitant
use should be avoided with pimozide or thioridazine.
Hypoglycaemics: Concurrent use with oral hypoglycaemics may
increase the risk of
hypoglycaemia.
Suxamethonium: Quinine enhances the neuromuscular effects of
suxamethonium.

Ulcer healing drugs: Cimetidine inhibits quinine metabolism leading to increased
plasma quinine concentrations.
Chloroquine and quinine appear to be antagonistic when given together for P
falciparum malaria.
Concomitant use of artemether and lumefantrine should be avoided.
4.6

Fertility, pregnancy and lactation

Pregnancy:
Quinine may cause congenital abnormalities of the CNS and extremities. Following
administration of large doses during pregnancy, phototoxicity and deafness have been
reported in neonates. Quinine bisulfate should not be used during pregnancy unless
the benefits outweigh the risks.
Treatment of chloroquine-resistant strains of falciparium malaria: Pregnancy in a
patient with malaria is not generally regarded as a contraindication to the use of
quinine. As malaria infection is potentially serious during pregnancy and poses a
threat to the mother and foetus, there appears to be little justification in withholding
treatment in the absence of a suitable alternative.
Prophylaxis of nocturnal leg-cramps: Quinine bisulfate should not be used during
pregnancy to treat cramps.
Breast-feeding:
Quinine bisulfate is excreted in breast milk, but no problems in humans have been
reported. However, quinine bisulfate should not be given to nursing mothers unless
the benefits outweigh the risks.
4.7

Effects on ability to drive and use machines
Quinine may cause visual disturbances and vertigo, hence patients should be advised that if
affected they should not drive or operate machinery

4.8

Undesirable effects

Cinchonism is more common in overdose, but may occur even after normal doses of
quinine. In its mild form symptoms include tinnitus, impaired hearing, rashes,
headache, nausea and disturbed vision. In more severe manifestations, symptoms may
include gastrointestinal symptoms, oculotoxicity, CNS disturbances, cardiotoxicity
and death (see section 4.9). Visual disorders may include blurred vision, defective
colour perception, visual field constriction and total blindness.

MedDRA system organ class

Adverse Reaction

Blood and lymphatic system
disorders

Thrombocytopenia, intravascular coagulation,
hypoprothrombinaemia, Haemoglobinuria, oliguria,
haemolytic uraemic syndrome, pancytopenia,
haemolysis, agranulocytosis, thrombocytopenic
purpura

Immune system disorders

Reports have been received of eczematous
dermatitis, oedema, erythema and lichen planus.
Hypersensitivity reactions such as asthma,
angioneurotic oedema, photosensitivity, hot and
flushed skin, fever, pruritus, thrombocytopenic
purpura and urticaria have also been reported.

Metabolism and nutritional
disorders

Hypoglycaemia may occur after oral administration
although it is more common after parenteral
administration

Psychiatric disorders

Agitation, confusion

Nervous system disorders

Reports of Headache, Vertigo, excitement, loss of
consciousness, coma and death have been received.

Eye disorders

Blurred vision, defective colour perception, visual
field constriction,

Ear and labyrinth disorders

Tinnitus, impaired hearing

Cardiac disorders

Atrioventricular conduction disturbances, a fall in
blood pressure coupled with a feeble pulse,
prolongation of the QT interval, widening of the
QRS complex and T wave flattening have been
noted with therapeutic doses.
Bronchospasm, dyspnoea may occur

Respiratory, thoracic and
mediastinal disorders

Gastrointestinal Disorders

Nausea, vomiting, diarrhoea, abdominal pain may
occur after long term administration of quinine,

Skin and subcutaneous tissue
disorders

Flushing, rash, urticaria, eczematous dermatitis,
oedema, erythema, lichen planus, pruritus,
photosensitivity, Stevens-Johnson syndrome

Musculoskeletal and
connective tissue disorders

Muscle weakness may occur, aggravation of
myasthenia gravis

Renal and urinary disorders
R
e
p
Reproductive
system and
o
breast
disorders
r
t
ing of suspe

Renal insufficiency, and acute renal failure may be
due to an immune mechanism or to circulatory
failure.
Toxic doses of quinine may induce abortion, but it is
unwise to withhold the drug if less toxic
antimalarials are not available.

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is
important. It allows continued monitoring of the benefit/risk balance of the medicinal
product. Healthcare professionals are asked to report any suspected adverse reactions via the
Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

4.9

Overdose
Symptoms
Quinine overdosage may lead to serious side effects including irreversible visual loss and can
be fatal. In acute overdosage, symptoms of cinchonism may occur, including convulsions,
nausea, vomiting, tinnitus, deafness, headache, vasodilation and visual disturbance.
Features of a significant overdose include convulsions, impairment of consciousness, coma,
respiratory depression, QT prolongation, ventricular arrhythmia, cardiogenic shock and renal
failure. Fatalities have been reported in adults after doses of 2-8g. High doses are teratogenic
and may cause miscarriage. Hypokalaemia and hypoglycaemia may also occur.
Treatment:
Children (< 5 years) who have ingested any amount should be referred to hospital.
Older children and adults should be referred to hospital if more than 30mg/kg of quinine base
has been taken.
Note: Each quinine bisulfate 300mg tablet is equivalent to 178mg of quinine base
Quinine is rapidly absorbed. Consider activated charcoal (50g for adults; 1g/kg for children)
if the patient presents within 1 hour of ingestion of more than 30mg/kg quinine base or any
amount in a child under 5 years. Multiple dose activated charcoal will enhance quinine
elimination.
Observe patients for at least 12 hours after ingestion. Monitor cardiac conduction and rhythm,
serum electrolytes, blood glucose and visual acuity.
Other treatment is symptomatic to maintain blood pressure, respiration, renal function and to
treat arrhythmia, convulsions, hypoglycaemia and acidosis.

5.1

Pharmacodynamic properties

ATC Code: P01B C01. Quinine alkaloid (antimalarials, methanolquinolines).

Quinine is a cinchona alkaloid and a 4-methanolquinoline antimalarial agent which is
a rapidly acting blood schizontocide with activity against Plasmodium falciparum, P.
vivax, P. ovale and P. malariae. It is active against the gametocytes of P. malariae
and P. vivax but not against mature gametocytes of P. falciparum. Since it has no
activity against exoerythrocyctic forms, quinine does not produce a radical cure in
vivax or ovale malarias.
Quinine has effects on the motor end-plate of skeletal muscle and prolongs the
refractory period. Like quinidine, quinine is a sodium channel blocker and, therefore,
has local anaesthetic, and both anti- and proarrhythmic activity.
The precise mechanism of action of quinine is unclear but it may interfere with
lysosome function or nucleic acid synthesis in the malaria parasite.
Quinine increases the refractory period of muscle so that the tetanic stimulation is
diminished. It also affects a number of other body systems including the central
nervous system, the cardiovascular system, the gastrointestinal tract and the pancreas.
In addition, quinine exhibits local anaesthetic action and a local irritant action. As an
antimalarial drug it acts primarily as a schizontocide. It is more toxic and less
effective than chloroquine, but is especially useful for treatment of chloroquineresistant strains of malarial infection.
5.2

Pharmacokinetic properties

The pharmacokinetics of quinine are altered significantly by malaria infection, the
major effects being reductions in both its apparent volume of distribution and its
clearance.
Absorption: Quinine is rapidly and almost completely absorbed from the GI tract and
peak concentrations in the circulation are attained about 1-3 hours after oral
administration of the sulfate.
Distribution: Plasma protein binding is about 70% in healthy subjects and rises to
90% or more in patients with malaria. Quinine is widely distributed throughout the
body. Concentrations attained in the CSF of patients with cerebral malaria have been
reported to be about 2-7% of those in the plasma.
Metabolism: Quinine is extensively metabolised in the liver and rapidly excreted
mainly in the urine. Estimates of the proportion of unchanged quinine excreted in the
urine vary from less than 5% to 20%. The pharmacokinetics of quinine are altered
significantly by malaria infection, with reductions in both the apparent volume of
distribution and clearance.
Elimination: Excretion is increased in acid urine. The elimination half-life is about 11
hours in healthy subjects but may be prolonged in patients with malaria. Small
amounts of quinine also appear in the bile and saliva.
Quinine crosses the placenta and is excreted in the breast milk.
5.3

Preclinical safety data

Preclinical information has not been included because the safety profile
of quinine

bisulfate has been established after many years of clinical use. Please refer to Section
4.
6.1

Excipients

Lactose
Microcrystalline cellulose
Povidone K30
Ethanol
Sodium starch glycollate
Talc
Colloidal anhydrous silica
Magnesium stearate
Pregelatinised maize starch
Coating Components/Tablet
Purified Water
Isopropyl Alcohol
Hydroxypropylmethylcellulose
Diethyl phthalate
Opadry Y-1-7000 (containing hydroxypropylmethylcellulose, titanium dioxide,
polyethylene glycol 400)
Carnauba wax
6.2.

Incompatibilities

Not Applicable.

6.3

Shelf life

AL/PVC Blister packs: 48 months
Polypropylene tablet containers: 36 months

6.4.

Special precautions for storage

Store in a dry place below 25°C.

6.5.

Nature and content of container

Polypropylene tablet containers with polyethylene caps and option use of polyethylene ullage
fillers.
PVC (285 μm)/aluminium (25 μm) foil blisters.

Pack sizes: 5, 7, 10, 14, 15, 20, 21, 25, 28, 30, 56, 60, 84, 90, 100, 112, 120, 168, 180, 250,
500.
Not all pack sizes may be marketed.

6.6.

Special precautions for disposal
No special requirements.

7.

MARKETING AUTHORISATION HOLDER
Strides Pharma UK Ltd
Unit 4 Metro Centre
Tolpits Lane
Watford
Hertfordshire
WD18 9SS
Trading as: Co-pharma
8.

MARKETING AUTHORISATION NUMBER(S)

PL: 13606/0058.

9.
DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
18/02/1998 / 11/10/2004.

10

DATE OF REVISION OF THE TEXT
26/06/2017

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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