Quinine Sulphate Tablets Bp 300mg
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Quinine Sulphate Tablets BP 300 mg
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 300mg Quinine Sulphate BP.
3. PHARMACEUTICAL FORM
Tablets.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Quinine sulphate tablets are indicated for the treatment of falciparum malaria and for the 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 oral administration only.
For falciparum malaria Adults
The adult dosage regimen for Quinine by mouth is: 600mg of Quinine Sulphate given every 8 hours for 7 days.
Elderly
The dosage regimen for Quinine by mouth for the elderly is: as for adults.
Children
The dosage regimen for Quinine by mouth for children is: 10mg of Quinine Sulphate 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 nocturnal cramps
One tablet to be taken 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 3 monthly intervals to reassess the benefit of treatment.
Note: Quinine (anhydrous base) 100 mg is equivalent to 121 mg of Quinine Sulphate.
4.3 Contraindications
Quinine sulphate tablets are contraindicated for use in:
• patients hypersensitive to quinine or any of the excipients in the tablet.
• patients with tinnitus or optic neuritis or acute haemoglobinuria or 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).
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.
Glucose-6-phosphate dehydrogenase deficient patients with malaria are at increased risk of haemolysis during quinine therapy. Treatment should be monitored in all patients in case signs of resistance develop.
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.
Hypersensitivity to quinine may also occur with symptoms of cinchonism together with urticaria, flushing, pruritus, rash, fever, angioedema, dyspnoea and asthma.
Quinine sulphate tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
4.5 Interaction with other medicinal products and other forms of interaction
Effect of other drugs on quinine
Quinine is metabolised via heptic 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 conjunction 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
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 the 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 sulphate 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.
Effects on ability to drive and use machines
4.7
Visual disturbance and vertigo may occur and therefore, patients should be warned that quinine may cause impairment in the ability to drive and operate machinery.
4.8 Undesirable effects
|
MedDRA system organ class |
Adverse reaction |
|
Blood and lymphatic system disorders |
Thrombocytopenia, intravascular coagulation, hypoprothrombonaemia, haemoglobinuria, oliguria, haemolytic-uremic syndrome, pancytopenia, haemolysis, agranulocytosis, thrombocytopenic purpura |
|
Immune system disorders |
Generalised hypersensitivity reactions including angioneurotic oedema and fever |
|
Metabolism and nutrition disorders |
Hypoglycaemia |
|
Psychiatric disorders |
Agitation, confusion |
|
Nervous system disorders |
Headache, vertigo |
|
Eye disorders |
Blurred vision, defective colour perception, visual field constriction |
|
Ear and labyrinth disorders |
Tinnitus, impaired hearing |
|
Cardiac disorders |
Atrioventricular conduction disturbances, hypotension, prolongation of the QT interval, widening of the QRS complex and T wave flattening |
|
Respiratory, thoracic and mediastinal disorders |
Bronchospasm |
|
Gastrointestinal disorders |
Nausea, vomiting, diarrhoea, abdominal pain |
|
Skin and subcutaneous tissue disorders |
Flushing, rash, urticaria, eczematous dermatitis, oedema, erythema, lichen planus, pruritis, photosensitivity |
|
Musculoskeletal and connective tissue disorders |
Muscle weakness, aggravation of myasthenia gravis |
|
Renal and urinary disorders |
Renal insufficiency, acute renal failure |
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 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 30 mg/kg of quinine base has been taken.
[Each Quinine sulphate 300 mg tablet is equivalent to 248 mg quinine base.]
Consider activated charcoal (50 g for adults; 1 g/kg for children) if the patient presents within 1 hour of ingestion of more than 30 mg/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
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. malariae 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.
Quinine is used orally for the treatment of uncomplicated attacks of falciparum malaria due to chloroquine or multidrug resistant strains and parenterally for severe or complicated malaria. Quinine is usually given by mouth as the sulphate or bisulphate and by infusion as the dihydrochloride, although other salts are used.
5.2 Pharmacokinetic properties
Quinine is rapidly and almost completely absorbed from the gastro-intestinal tract. Peak concentrations in the circulation are attained about 1 to 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% to 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
There are no preclinical safety data of relevance to the prescriber which are additional to those already included in other sections of the SmPC.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
The tablet contains microcrystalline cellulose, lactose, maize starch, colloidal anhydrous silica, purified talc, magnesium stearate and sodium starch glycollate. The tablet coating contains hypromellose (E464), titanium dioxide (E171), lactose monohydrate, macrogol 4000 and carnauba wax.
6.2 Incompatibilities
None known.
6.3 Shelf life
5 years (polypropylene containers). 36 months (PVC/Al blisters).
6.4 Special precautions for storage
Store in a dry place below 25°C.
6.5 Nature and contents of container
Polypropylene containers with polyethylene caps and optional use of polyethylene ullage fillers or PVC/Aluminium foil blisters. Each pack type is available in pack sizes of 5, 7, 10, 14, 15, 20, 21, 25, 28, 30, 56, 60, 84, 90, 100, 112, 120, 168, 180, 250 and 500 tablets.
6.6. Special Precautions for Disposal
None.
7 MARKETING AUTHORISATION HOLDER
Generics [UK] Ltd t/a Mylan
Station Close
Potters Bar
Herts
EN6 1TL
8. MARKETING AUTHORISATION NUMBER
PL 04569/0089
9. Date of First Authorisation/Renewal of Authorisation
Date MA granted: 2 February 1985 Last renewal granted: 11 June 2005
10 DATE OF REVISION OF THE TEXT
27/07/2010