Quinine Bisulphate Tablets 300 Mg
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Quinine Bisulphate Tablets 300mg
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains Quinine Bisulphate 300mg For excipients, see 6.1
3 PHARMACEUTICAL FORM
White, sugar coated deep convex tablet
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Quinine sulphate tablets are indicated for the following:
1. Treatment of Falciparum malaria infection
2. Treatment of malaria where the infective species is not known or is mixed.
3. 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
Route of administration: Oral Treatment of malaria
Adults and Children over 12 years: 2g daily in divided dose Children: 4 - 6 years: 300 - 500mg in 2-3 divided doses.
7 - 12 years: 0.5 - 1.0g in 2-3 divided doses.
Not suitable for children up to 3 years.
The above doses are usually administered for 7 days and, if quinine resistance is known or suspected, then treatment should be followed with an appropriate course of pyrimethamine/sulfadoxine or doxycycline.
Elderly: dosage as for adults.
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 quinine or any of the other ingredients
Haemoglobinuria
Optic neuritis
Tinnitus
Myasthenia gravis
4.4 Special warnings and precautions for use
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 to quinine may also occur with symptoms of cinchonism together with urticaria, flushing, pruritus, rash, fever, angioedema, dyspnoea and asthma.
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).
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.
Quinine should be used with caution in patients with atrial fibrillation or other serious heart disease. It may cause hypoprothrombinaemia.
Patients with glucose 6-phosphate dehydrogenase (G6PD) deficiency may develop acute haemolytic anaemia.
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, which include 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 can decrease plasma concentrations of ciclosporin.
Other drug interactions
There is an increased risk of ventricular arrhythmias with other drugs which prolong the QT interval, including amiodarone, moxifloxacin, pimozide, thioridazine and halofantrine.
Concurrent use with oral hypoglycaemics may increase the risk of hypoglycaemia.
Quinine may cause hypoprothrombinaemia and enhance the effects of anticoagulants.
Quinine enhances the neuromuscular effects of suxamethonium.
Concomitant use of quinidine may increase the possibility of cinchonism.
Chloroquine and quinine appear to be antagonistic when given together for P falciparum malaria.
4.6 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 should not be used during pregnancy unless the benefits outweigh the risks.
Treatment of chloroquine-resistant strains of falciparum malaria: Pregnancy in a patient with malaria is not generally regarded as a contra-indication 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 should not be used during pregnancy to treat cramps.
Lactation
Quinine is excreted in breast milk, but no problems in humans have been reported. However, quinine should not be given to nursing mothers unless the benefits outweigh the risks.
Effects on ability to drive and use machines
4.7
Quinine may cause visual disturbances and vertigo, hence patients should be advised that if affected they should not drive or operate machinery.
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4.8 Undesirable effects | |
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MedDRA system organ class |
Adverse Reaction |
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Blood and lymphatic system disorders |
Thrombocytopenia, intravascular coagulation, hypoprothrombinaemia, haemoglobinuria, oliguria, haemolytic-uremic syndrome, pancytopenia, haemolysis, agranulocytosis, thrombocytopenic purpura |
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Immune system disorders |
Generalised hypersensitivity reactions including angioneurotic oedema and fever |
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Metabolism and nutrition disorders |
Hypoglycaemia |
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Psychiatric disorders |
Agitation, confusion |
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Nervous system disorders |
Headache, vertigo |
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Eye disorders |
Blurred vision, defective colour perception, visual field constriction |
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Ear and labyrinth disorders |
Tinnitus, impaired hearing |
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Cardiac disorders |
Atrioventricular conduction disturbances, hypotension, prolongation of the QT interval, widening of the QRS complex and T wave flattening |
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Respiratory, thoracic and mediastinal disorders |
Bronchospasm |
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Gastrointestinal disorders |
Nausea, vomiting, diarrhoea, abdominal pain |
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Skin and subcutaneous tissue disorders |
Flushing, rash, urticaria, eczematous dermatitis, oedema, erythema, lichen planus, pruritis, photosensitivity |
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Musculoskeletal and connective tissue disorders |
Muscle weakness, aggravation of myasthenia gravis |
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Renal and urinary disorders |
Renal insufficiency, acute renal failure |
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4.9 Overdose |
Symptoms
Quinine overdosage may lead to serious side effects including irreversible visual loss, and can be fatal. Symptoms include 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 tetrogenic 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.
Each 300mg Quinine bisulphate tablet is equivalent to 178mg quinine base.
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 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: P01B C01
Quinine is a highly active blood schizonticide and suppresses the asexual cycle of development of malarial parasites in the erythrocyte. It is believed to act by interfering with DNA. It has gametocidal action against P. Vivax, P. Ovale and P. Malariae. Quinine affects a large variety of biological systems and has been called “general protoplasmic poison”. It is toxic to many bacteria and other unicellular organisms. It has local anaesthetic action, sensory nerves are briefly stimulated and then paralysed. Slightly higher concentrations than those necessary for anaesthesia are likely to cause oedema, pain and reactive fibrosis.
In therapeutic doses the effects on the CNS are analgesia and antipyresis. Lowering of the blood pressure is the main cardiovascular effect. Quinine affects the skeletal muscle, it not only increases the tension response to a single maximal stimulus but it also increases the refractory period of muscle so that the response to tetanic stimulation is diminished.
Quinine may lower blood glucose concentrations apparently by stimulating insulin secretion by pancreatic islet cells.
5.2 Pharmacokinetic properties
Following oral administration, quinine is almost completely and rapidly absorbed from the gastrointestinal tract. Absorption occurs mainly from the upper small intestine and is almost complete even in patient with marked diarrhoea.
Peak concentration in the circulation is attained about 1 to 3 hours after ingestion and approximately 70 per cent is bound to plasma proteins. Plasma concentration appears to be in the range 3-7 mcg/ml during therapy with oral doses of 500 to 650mg three times daily. It is degraded in the body, mainly in the liver.
Malarial infection inhibits hepatic metabolism and thus plasma concentrations resulting from a given dose will vary according to the severity of the infection. Plasma half-life of quinine is 6-9 hours, which is increased up to 15 hours in malarial infection and decreased to about 3 to 4 hours in patients being treated with antiepileptic drugs. Following termination of quinine therapy, the plasma level falls rapidly and only a negligible concentration is detectable after 24 hours.
Quinine is excreted mainly in the urine as hydroxyl derivatives, but trace amounts also appear in the faeces, gastric juice, bile and saliva. Renal excretion of quinine is twice as rapid when the urine is acidic as when it is alkaline.
5.3 Preclinical safety data
There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Pregelatinised starch
Powdered cellulose
Crospovidone
Magnesium stearate
Anhydrous colloidal silica
Shellac
Povidone
Dextrin
Sucrose
Kaolin
Talc
Titanium dioxide (E171)
6.2 Incompatibilities
None known
6.3 Shelf life
Opaque plastic containers: 36 months Blister packs: 24 months
6.4 Special precautions for storage
Protect from heat, light and moisture
6.5 Nature and contents of container
1. Opaque plastic containers with plastic caps in pack sizes of 28, 42, 50, 56, 84, 100, 112, 250, 500 and 1000.
2. Opaque plastic container composed of either high density polypropylene or high density polyethylene with a tamper evident or child resistant tamper evident closure composed of high density polyethylene for all pack sizes (28, 42, 50, 56, 84, 100, 112, 250, 500 and 1000) packaging inclusion: polyether foam or polyethylene or polypropylene made filler.
3. Blister packs of aluminium/opaque PVC subsequently packed in printed cartons in pack sizes of 28, 42, 56, 84 and 112.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
No special instructions
7 MARKETING AUTHORISATION HOLDER
Auden McKenzie (Pharma Division) Ltd
McKenzie House
Bury Street
Ruislip
Middlesex
HA4 7TL
UK
8 MARKETING AUTHORISATION NUMBER(S)
PL 17507/0178
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
08/03/2004
10 DATE OF REVISION OF THE TEXT
14/07/2010