Consumer medicine information

NEW ZEALAND DATA SHEET
Q300
Quinine sulfate 300mg tablets

Presentation
Q300 Tablets: Clear film coated white biconvex tablet, 7/16” diameter, imprinted Q300 on one side. Each Q300 tablet contains 300mg of quinine sulfate. Actions
Quinine sulfate 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. The precise mechanism of action of quinine in malaria has not been determined but may be based on its ability to concentrate in parasitic acid vesicles causing an elevation of pH and thereby disrupting intracellular activity. Quinine increases the refractory period of skeletal muscle by direct action on the muscle fibre thereby diminishing the response to tetanic stimulation. It also decreases the excitability of the motor end-plate region, reducing the responses to repetitive nerve stimulation and to acetylcholine. Pharmacokinetics
Quinine is rapidly and almost completely absorbed from the gastrointestinal 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. Indications
Quinine is indicated concurrently with tetracycline or clindamycin or pyrimethamine plus sulphadiazine or sulphadoxine in the treatment of chloroquine-resistant malaria caused by Plasmodium falciparum. Quinine is indicated in the treatment of myotonia. Dosage and Administration
Q300 may be taken with or after meals to minimise gastrointestinal irritation. Usual Adult and Adolescent Dose
For chloroquine-resistant Plasmodium falciparum malaria: Oral, 600 to 650mg every eight hours for at least three days in most areas of the world (seven days in Southeast Asia) with concurrent or consecutive administration of 250mg of tetracycline every six hours for seven days; or concurrent administration of 1.5 grams of sulfadoxine and 75mg of pyrimethamine combination as a single dose; or concurrent or consecutive administration of 900mg of clindamycin three times a day for three days. Antimyotonic
Oral, 300 to 650mg two or three times a day. Usual Paediatric Dose
For chloroquine-resistant Plasmodium falciparum malaria: Oral, 8.3mg per kg of body weight every eight hours for at least three days in most areas of the world (seven days in Southeast Asia) with concurrent or consecutive administration of 5mg per kg of body weight of tetracycline every six hours for seven days in children over 8 years of age; or concurrent or consecutive administration of 6.7 to 13.3mg per kg of body weight of clindamycin three times a day for three days; or concurrent administration of 1.25mg per kg of body weight of pyrimethamine in combination with 25mg per kg of body weight of sulfadoxine as a single dose. Antimyotonic
Contraindications
Quinine is contraindicated in patients with a history of hypersensitivity to quinine, in the presence of haemolysis, and in patients with tinnitus or optic neuritis. It should be used with caution in patients with atrial fibrillation or other serious heart disease. Quinine may cause hypoprothrombinaemia and enhance the effects of anticoagulants. Quinine may aggravate the symptoms of myasthenia gravis and should be used with care if at all in such patients. Pregnancy in a patient with malaria is not generally regarded as a contraindication to the use of quinine. Risk-benefit should be considered when the following medical problems exist:  a history of Blackwater fever  glucose-6-phosphate dehydrogenase (G6PD) deficiency hypoglycemia Warnings and Precautions
Quinine should be used with caution in patients with atrial fibrillation or other serious heart disease. Quinine should be avoided in patients with myasthenia gravis as it may aggravate their condition and cause severe respiratory distress and dysphasia. 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. 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. Such symptoms include tinnitus, impaired hearing, headache, nausea and disturbed vision. Patients hypersensitive to quinidine may be hypersensitive to this medication also. Hypersensitivity to quinine may also occur with symptoms of cinchonism together with urticaria, flushing pruritus, rash, fever, angioedema, dyspnoea and asthma. Q300 tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine. 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 sulfate should not be used during pregnancy unless the benefits outweigh the risks. 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. Breastfeeding
Quinine sulfate is excreted in breast milk, but no problems in humans have been reported. However, quinine sulfate should not be given to nursing mothers unless the benefits outweigh the risks. Use in Children
Appropriate studies with quinine for use as an antimyotonic have not been performed in the paediatric population. Antimalarial studies performed to date have shown that children have a decreased elimination half-life and volume of distribution; however, paediatrics-specific problems that would limit the usefulness of quinine in children have not been documented. Effects on ability to drive
Quinine may cause visual disturbances and vertigo, hence patients should be advised that if affected they should not drive or operate machinery. Adverse 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. Its more serious manifestation symptoms may include gastrointestinal symptoms, oculotoxicity, CNS disturbances, cardiotoxicity and death. Visual disorders may include blurred vision, defective colour perception, visual field constriction and total blindness. lymphatic
disorders:
hypoprothrombinaemia, haemoglobinuria, oliguria, haemolytic-uremic syndrome, pancytopenia, haemolysis agranulocytosis and thrombocytopenic purpura have all been reported. 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, pruritis, thrombocytopenic purpura and urticaria have also been reported.
Metabolism and nutrition 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: There may be 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 has
been noted with therapeutic doses.
Respiratory, thoracic and mediastinal disorders: bronchospasm, dyspnoea may occur.
Gastrointestinal disorders: diarrhoea, nausea, vomiting and abdominal pain may occur after long term
administration of quinine.
Skin and subcutaneous tissue disorders: flushing, rash, urticaria, eczematous, dermatitis, oedema,
erythema, lichen planus, pruritis, photosensitivity.
Musculoskeletal, connective tissue and bone disorders: muscle weakness may occur, aggrevation of
Myasthenia gravis.
Renal and urinary disorders: renal insufficiency and acute renal failure may be due to an immune
mechanism or to circulatory failure.
Reproductive system and breast disorders: toxic doses of quinine may induce abortion, but it is unwise to
withhold the drug if less toxic antimalarials are not available.
Interactions
The following drug interactions have been noted with quinine sulfate. Combinations containing any of the following medications depending on the amount present may also interact with quinine sulfate. Effect of other medicines 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, barbituates, 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 medicines
The plasma concentration of flecainide, digoxin and mefloquine may be increased. Amantadine: Quinine can reduce the renal clearance of amantadine. 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 medicine interactions
There is an increased risk of ventricular arrhythmias with other medicines which prolong the QT interval, including amiodarone, moxifloxacin, pimozide, thiorizine and halofantrine. Antiarrhythmics: Concomitiant 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. Concurrent use of quinidine may increase the possibility of cinchonism. 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 mefloquinine. 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: There is an increased risk of hypoglycaemia when taken concurrently. Suxamethonium: Quinine enhances the neuromuscular effects of suxamethonium. Ulcer-healing medicines: Cimetidine, which inhibits metabolism, may cause increased plasma-quinine concentrations. Quinine sulfate has been observed to interfere with Urinary 17-ketogenic steroid determinations. Overdosage
Quinine overdosage may lead to serious and irreversible side effects and can be fatal. In acute overdosage, symptoms of cinchonism may occur, including convulsions, nausea, vomiting, tinnitus, deafness, headache, vasodilatation and disturbed vision. The visual disorders may be severe and there may be impaired consciousness, coma, respiratory depression, arrhythmia and cardiogenic shock. Fatalities have been reported in adults after doses of 2-8g. High doses of quinine are teratogenic and may cause miscarriage. The effects of oculotoxicity may include blurred vision, defective colour perception, visual field constriction and total blindness. The onset of symptoms may vary from a few hours to a day or more after ingestion. Visual disturbances are usually slowly reversible but there may be residual damage. The effects associated with cardiovascular toxicity include conduction abnormalities, ventricular dysrhythmias, anginal symptoms and hypotension leading to cardiac arrest and circulatory failure. Hypokalaemia and hypoglycaemia may also occur. Treatment
Quinine is rapidly absorbed. In patients who present within one hour of ingestion an overdose gastric lavage may be considered, but the risk of aspiration must be considered, especially if there is CNS depression or drowsiness. Multiple doses of activated charcoal may be considered. Other treatment is mostly symptomatic to maintain blood pressure, respiration, renal function and treating arrhythmia, convulsions, hypoglycaemia and acidosis. For further advice on management of overdose please contact the National Poisons Information Centre
(0800 POISON or 0800 764 766).
Pharmaceutical Precautions
Medicine Classification
Package Quantities
Further Information
Quinine Sulfate is (8S,9R)-6’-methoxycinchonan-9-ol sulfate dihydrate. It has a molecular weight of 783.0 and a formula of (C20H24N2O2) 2, H2SO4, 2H2O. Each Q300 tablet contains 300mg of active ingredient, quinine sulfate. It also contains lactose, magnesium stearate, povidone, sodium starch glycollate and carnauba wax. The film coating contains ethanol, diethyl phthalate, purified water and hypromellose. Q300 is gluten free. Name and Address
Mylan New Zealand Ltd PO Box 11-183 Ellerslie AUCKLAND Telephone: 09-579-2792 Date of Preparation

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