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QUININE SULFATE 200MG TABLETS

Active substance(s): QUININE SULFATE / QUININE SULFATE / QUININE SULFATE

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SUMMARY OF PRODUCT CHARACTERISTICS
1

NAME OF THE MEDICINAL PRODUCT
Quinine Sulfate 200mg Tablets

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains quinine sulfate 200mg
For excipients, see 6.1.

3

PHARMACEUTICAL FORM
Film-coated tablet.
A white, biconvex film-coated tablet, plain on both sides.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
For the treatment of chloroquine resistant falciparum malaria in adults and children
aged 5 years or older (and ≥ 20kg)
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 chloroquine resistant falciparum malaria
Adults and adolescents (> 12 years of age): the adult dosage regimen by
mouth is 600mg of quinine sulfate given every 8 hours for 7 days. The dose
may depend upon the size of the patient, severity of infection, and evidence of
renal or liver disease (when the intervals should be increased), due to a
prolonged half-life of the drug.
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. Quinine sulfate
200mg tablets are not suitable for children weighing less than 20kg or less
than 5 years old.

Note
If quinine resistance is known or suspected on completion of the course, then
supplementary treatment with another recommended antimalarial drug is
necessary. Official guidance should be adhered to.
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 200mg at bedtime. Maximum dose is 300mg.
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.
Method of administration:
Oral

4.3

Contraindications
-

4.4

Hypersensitivity to quinine or any of the other ingredients in the tablet
Tinnitus
Optic neuritis
Acute haemoglobinuria
Myasthenia gravis (quinine may cause severe respiratory distress in these
patients)

Special warnings and precautions for use
Chinchonism
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.
Use for nocturnal leg cramps

Before use for nocturnal leg cramps, the risks, which include significant
adverse effects and interactions (see 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 sulphate should not be used for this indication during pregnancy (see
section 4.6).
Thrombocytopenia
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.
Cardiac disorders
Quinine should be used with caution in patients with atrial fibrillation or other
serious heart disease. It may cause hypoprothrombinaemia.
Glucose-6-Phosphate Dehydrogenase (G-6-PD) Deficiency
Patients with glucose 6-phosphate dehydrogenase (G6PD) deficiency may
develop acute haemolytic anaemia. 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 haemolysis
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.
Reduce the dosage (or increase intervals between doses) in renal or hepatic
disease.
Quinine can affect the results of certain urine tests for alkaloids and steroids.
It may also interfere with tests for plasma catecholamines as well as slowing
the erythrocyte sedimentation rate.
Excessive amounts of beverages containing quinine should not be consumed
while taking quinine, as this may increase the risk of adverse reactions and
toxicity.

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.

4.5

Interaction with other medicinal products and other forms of interaction
Effect of other drugs on quinine
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 flecainide, digoxin and mefloquine may be
increased.
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.
There is an increased risk of convulsions when quinine is given with
mefloquine.
Quinine can decrease serum plasma concentrations of ciclosporin
Other drug interactions
There is an increased risk of ventricular arrhythmias when quinine is given in
combination with other drugs that prolong the QT interval, including
amiodarone, moxifloxacin, pimozide, thioridazine, terfenadine and
halofantrine and therefore concomitant use with these products should be
avoided. 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.
Co-administration of other drugs known to alter cardiac conduction (e.g. antiarrhythmic or ß-adrenergic blocking agents, calcium channel blockers, some
antihistamines or H1-blocking agents, tricyclic antidepressants and
antipsychotics) might also contribute to a prolongation of the QT interval.
There is an increased risk of ventricular arrhythmias when moxifloxacin is
given with quinine. There is increased risk of ventricular arrhythmias when
quinine is given with artemether/lumefantrine. Concomitant use of artemether
and lumefantrine should be avoided.

Rifampicin can reduce the serum levels of quinine, therefore reducing its
therapeutic effect.
Concurrent use with oral hypoglycaemics may increase the risk of
hypoglycaemia.
Quinine may cause hypoprothrombinaemia and thereby enhance the effect of
anticoagulants.
Quinine enhances the neuromuscular effects of suxamethonium.
Concurrent use of quinidine may increase the possibility of cinchonism.
Chloroquine and quinine appear to be antagonistic when given together for P
falciparum malaria. There is a decrease in plasma concentrations of
primaquine.
Quinine can reduce the renal clearance of amantadine. Concomitant use of
amatadine should be avoided.
Cimetidine, which inhibits metabolism, may cause increased plasma quinine
concentrations.

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 sulphate 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 sulphate should not be used
during pregnancy to treat cramps.
Lactation:
Quinine sulfate is excreted in breast milk, but no problems in humans have
been reported. However, quinine sulphate should not be given to nursing
mothers unless the benefits outweigh the risks.
Fertility:
The effects of quinine on fertility are unknown.

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)

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

Generalised hypersensitivity reactions including
angioedema and fever

Metabolism and nutritional
disorders

Hypoglycaemia

Psychiatric disorders

Agitation and confusion, excitement

Nervous system disorders

Headache, Vertigo, loss of consciousness, coma
and death

Eye disorders

Blurred vision, defective colour perception,
visual field constriction, total blindness

Ear and labyrinth disorders

Tinnitus, hearing impaired

Cardiac disorders

Atrioventricular conduction disturbances,
hypotension, prolongation of the QT interval,
widening of the QRS complex and T wave
flattening
Bronchospasm, dyspnoea, asthma

Respiratory, thoracic and
mediastinal disorders

Gastrointestinal Disorders

Nausea, vomiting, diarrhoea, abdominal pain,

Skin and subcutaneous
tissue disorders

Flushing, rash, urticaria, eczematous dermatitis,
oedema, erythema, lichen planus, pruritus,
photosensitivity

Musculoskeletal and
connective tissue disorders

Muscle weakness, aggravation of myasthenia
gravis

Renal and urinary disorders

Renal insufficiency, acute renal failure

Reproductive system and
breast disorders

Toxic doses of quinine may induce abortion

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; website:
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.
Symptoms include nausea, vomiting, tinnitus, deafness, headache and visual
disturbance.
Features of a significant overdose include convulsions, impairment of
consciousness, respiratory depression, QT prolongation, ventricular
arrhythmia, cardiogenic shock and renal failure. High doses of quinine are
teratogenic and may cause miscarriage. Hypokalaemia and hypoglycaemia
may also occur. Fatalities have been reported in adults after doses of 2-8g.
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 sulfate 200mg tablet is equivalent to 165mg of quinine base.
Consider activated charcoal (50g for adults; 4g/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

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
ATC Code: P01BC01
Quinine 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. malariar and P. vivax but not against P. falciparum
gametocytes. Since it has no activity against exoerythrocyctic forms, quinine
does not produce a radical cure in vivax or ovale malarias. It is more toxic and
less effective than chloroquine, but it is especially useful for treatment of
chloroquine-resistant strains of malarial infection.
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. Since it has
no activity against exoerythrocytic forms, quinine does not produce a radical
cure in vivax or ovale malarias.

5.2

Pharmacokinetic properties
Quinine is rapidly and almost completely absorbed from the gastrointestinal
tract. Peak concentrations in the circulation are attained about 1-3 hours after
ingestion and about 70% is bound to proteins in the plasma in healthy subjects
rising to about 90% in patients with malaria. Quinine is widely distributed
throughout the body. Concentrations attained in the CSF are about 2-7% of
those in the plasma. Quinine is extensively metabolised in the liver and
excreted in the urine. Estimates of the proportion of unchanged quinine
excreted in the urine vary from less than 5% to 20%. 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. The pharmacokinetics of quinine
are altered significantly by malaria infection, with reductions in both the
apparent volume of distribution and clearance.
Quinine crosses the placenta and is excreted in the breast milk.

5.3

Preclinical safety data
No data of relevance to the prescriber, which is additional to that included in
other sections of the SPC.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Lactose
Microcrystalline cellulose
Maize starch
Colloidal anhydrous silica
Purified talc
Magnesium stearate
Sodium starch glycollate
Coating Components/Tablet
Methylhydroxypropylcellulose
Opadry white Y-1-7000 (containing methylhydroxypropylcellulose, titanium
dioxide, polyethylene glycol 400)
Carnauba wax

6.2

Incompatibilities
Not applicable

6.3

Shelf life
36 months

6.4

Special precautions for storage
This medicinal product does not require any special storage conditions.

6.5

Nature and contents of container
PVC (285µm)/aluminium (25µm) foil blisters

Pack sizes: 5, 7, 10, 14, 15, 20, 21, 25, 28, 30, 56, 60, 84, 90, 100, 112, 120,
168, 180, 250 and 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 13606/0200

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
25/10/2016

10

DATE OF REVISION OF THE TEXT
28/04/2017

Expand Transcript

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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