Consumer medicine information

Quinate

Quinine sulfate dihydrate

BRAND INFORMATION

Brand name

Quinate

Active ingredient

Quinine sulfate dihydrate

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Quinate.

SUMMARY CMI

QUINATE tablets

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using QUINATE?

QUINATE contains the active ingredient quinine (as quinine sulfate).

QUINATE is used to treat malaria, an infectious disease spread by female mosquitoes. It belongs to a group of medicines called antimalarials. This medicine works by stopping the growth of the organisms which cause malaria.

For more information, see Section 1. Why am I using QUINATE? in the full CMI.

2. What should I know before I use QUINATE?

Do not use if you have ever had an allergic reaction to quinine sulfate, tonic water or bitter lemon drinks which contain quinine, or any of the ingredients listed at the end of the CMI.

For more information, see Section 2. What should I know before I use QUINATE? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with QUINATE and affect how it works. Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use QUINATE?

  • Your doctor will tell you how much QUINATE to take.
  • QUINATE tablets must be swallowed whole with a full glass of water. Do not chew the tablets.
  • More instructions can be found in Section 4. How do I use QUINATE? in the full CMI.

5. What should I know while using QUINATE?

Things you should do
  • Tell your doctor if you become pregnant while taking QUINATE.
  • Tell any doctors, dentists, and pharmacists who are treating you that you are taking QUINATE.
Things you should not do
  • Do not take QUINATE to treat any other complaint unless your doctor says so.
  • Do not give this medicine to anyone else, even if their symptoms are similar to yours
  • Do not stop taking QUINATE, or lower the dosage, even if you are feeling better, without first checking with your doctor.
Driving or using machines
  • Be careful driving or operating machinery until you know how QUINATE affects you.
Looking after your medicine
  • Keep QUINATE tablets in a cool dry place where the temperature is below 30°C.

For more information, see Section 5. What should I know while using QUINATE? in the full CMI.

6. Are there any side effects?

There are a number of side effects associated with this medicine. It is important to be aware of them so that you can identify any symptoms if they occur (see the full CMI for more details). The serious side effects are: signs of allergy; severely disturbed vision; chest pain; changes in heartbeats; diarrhoea; reduction in the amount of urine or reddish colour in urine; bruising or bleeding more easily than normal; symptoms of liver disease with yellowing of the eyes or skin (jaundice) and dark urine; confusion; loss of consciousness, coma, death.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

QUINATE tablets

Active ingredient(s): Quinine Sulfate Dihydrate

Consumer Medicine Information (CMI)

This leaflet answers some common questions about Quinate. It does not contain all the available information.

It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor or pharmacist has weighed the risks of you taking Quinate against the benefits they expect it will have for you.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine.

You may need to read it again.

Where to find information in this leaflet:

1. Why am I using QUINATE?
2. What should I know before I use QUINATE?
3. What if I am taking other medicines?
4. How do I use QUINATE?
5. What should I know while using QUINATE?
6. Are there any side effects?
7. Product details

1. Why am I using QUINATE?

Quinate contains quinine (as quinine sulfate) as the active ingredient.

Quinate is used to treat malaria, an infectious disease spread by female mosquitoes. It belongs to a group of medicines called antimalarials.

This medicine works by stopping the growth of the organisms which cause malaria.

Ask your doctor if you have any questions about why Quinate has been prescribed for you.

Your doctor may have prescribed it for another purpose.

This medicine is only available with a doctor's prescription.

There is no evidence that it is addictive.

2. What should I know before I use QUINATE?

Warnings

Do not take Quinate if you have ever had an allergic reaction to:

  • quinine sulfate
  • tonic water or bitter lemon drinks which contain quinine
  • Any of the tablet ingredients listed at the end of this leaflet.

Symptoms of an allergic reaction may include shortness of breath, wheezing, or difficulty in breathing; swelling of the face, lips, tongue or any other parts of the body; rash, itching or hives on the skin.

Do not take Quinate if you have had a reaction to it before.

Highly sensitive reactions to quinine can include bleeding or bruising more easily than normal, bloody diarrhoea and stomach pains.

Do not take Quinate if you have:

  • myasthenia gravis, a disease of the muscles.
  • Glucose-6-phosphate dehydrogenase, a genetic disorder mainly affecting red blood cells
  • Tinnitus, ringing in the ears
  • Optic neuritis, an inflammation of the optic nerve
  • A history of blackwater fever, a form of malaria characterized by kidney damage resulting in dark urine
  • a disorder affecting the red blood
  • cells (haemolysis)
  • a rare hereditary problems of galactose intolerance, total lactose deficiency or glucose-galactose
  • malabsorption.

Do not take Quinate after the expiry date (EXP) printed on the label.

If you take this medicine after the expiry date has passed, it may not work as well.

Do not take it if the bottle shows signs of tampering, or if the tablets don't look quite right.

Check with your doctor or pharmacist if you:

  • are allergic to any other medicines or any foods, dyes or preservatives.
  • have or have had any medical conditions, especially the following: Heart problems; Blood problems including anaemia and haemophilia; Nervous system disorder.

If you have not told your doctor about any of these things, tell them before you take Quinate.

You should not take more than the prescribed dose as a condition called ‘cinchonism’ may occur, even with normal doses. Symptoms of cinchonism include abdominal pain, diarrhoea, disturbed vision (blurred vision, changes in colour perception or field of vision, total blindness), headache, feeling or being sick, ringing in the ears or impaired hearing, rashes, loss of consciousness, fits, shock due to heart problems, irregular heartbeats, death. Tell your doctor if you experience any of them.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Do not take Quinate if you are pregnant or plan to become pregnant unless you and your doctor have discussed the risks and benefits involved.

Quinine sulphate should not be used during pregnancy to treat leg cramps.

Do not take it if you are breast feeding or plan to breast feed.

It is not recommended for use while breastfeeding as it is found in breast milk.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any that you buy without a prescription from a pharmacy, supermarket or health food shop.

Some medicines may interfere with QUINATE. These include:

  • glycosides (e.g. digoxin and digitoxin), medicines used to heart failure.
    It is recommended that regular bold tests be performed when glycosides and Quinate are taken at the same time.
  • antacids containing aluminium
  • warfarin, a medicine used to prevent blood clots
  • pancuronium, succinylcholine, and tubocurarine, medicines used for anaesthesia
  • mefloquine, a medicine used for treating malaria
  • cimetidine, a medicine used for ulcers
  • muscle relaxant drugs
  • flecainide, quinidine or amiodarone (used to treat irregular heartbeats)
  • ciclosporin (used as an immunosuppressant medication)
  • urinary alkalinisers (e.g. sodium bicarbonate and acetazolamide), medicines used for bladder infections
  • quinine-containing beverages eg. tonic water, bitter lemon.
  • barbiturates, carbamazepine or phenytoin (medicines to treat epilepsy)
  • amantadine (to treat Parkinsons Disease or some viral infections)
  • medicines to treat diabetes
  • moxifloxacin, rifampicin or antifungals (used to treat infections)
  • astemizole or terfenadine (for allergic reactions)
  • pimozide or thioridazine (used to treat some mental disorders)
  • levacetylmethadol (a pain killer).

These medicines may be affected by Quinate or may affect how well it works. You may need different amounts of your medicine or you may need to take different medicines. Your doctor or pharmacist has a more complete list of medicines to be careful with or avoid while taking QUINATE.

4. How do I use QUINATE?

How much to take

Your doctor will tell you how much Quinate to take.

The dose will depend on the condition being treated and your response to the treatment.

When to take / use QUINATE

Follow all directions given to you by your doctor carefully.

These directions may differ from the information contained in this leaflet.

How to take QUINATE?

Swallow the tablet whole with a full glass of water.

Do not chew the tablets.

Quinate has a special coating to mask the bitter taste of the tablet.

Continue taking Quinate for as long as your doctor tells you.

Do not stop taking it, or lower the dosage, even if you are feeling better, without first checking with your doctor.

If you forget to use QUINATE

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to. Otherwise, take it as soon as you remember, and then go back to taking your medicine as you would normally.

Do not take a double dose to make up for the dose that you missed.

This may increase the chance of you getting an unwanted side effect.

If you are not sure what to do, ask your doctor or pharmacist.

If you use too much QUINATE

Immediately telephone your doctor or the Poisons Information Centre (telephone 13 11 26) for advice, or go to Accident and emergency at your nearest hospital, if you think that you or anyone else may have taken too much Quinate. Do this even if there are no signs of discomfort or poisoning.

You may need urgent medical attention.

Symptoms of an overdose may include:

  • tinnitus (ringing in the ears)
  • deafness
  • disturbed vision
  • Dizziness
  • Skin rash
  • Intestinal cramping and
  • Vomiting
  • Headache
  • Fever
  • apprehension and confusion
  • Convulsions.

5. What should I know while using QUINATE?

Things you should do

Take Quinate exactly as your doctor has prescribed.

Tell any other doctors, dentists, and pharmacists who are treating you that you are taking Quinate, especially if you are being started on any new medicine.

Tell your doctor, surgeon or dentist that you are taking Quinate if you are about to undergo surgery or an operation requiring a general anaesthetic.

Tell your doctor immediately if you become pregnant while taking Quinate.

Things you should not do

Do not give this medicine to anyone else, even if they have the same condition as you.

Do not take Quinate to treat any other complaints unless your doctor tells you to.

Do not stop taking it, or lower the dosage, even if you are feeling better, without first checking with your doctor.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how QUINATE affects you.

Looking after your medicine

Keep your tablets in the bottle until it is time to take them.

If you take the tablets out of the bottle they may not keep as well.

Keep your tablets in a cool dry place, protected from light, where the temperature stays below 30°C.Do not store QUINATE, or any other medicine, in the bathroom or near a sink.

Do not leave medicines in the car or on window sills. Heat and dampness can destroy some medicines.

Keep your medicines where children cannot reach them. A locked cupboard at least one-and-a-half metres (1.5 m) above the ground is a good place to store medicines.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

Less serious side effects

Less serious side effectsWhat to do
  • tinnitus (ringing in the ears)
  • headache
  • nausea
  • Slightly disturbed vision
Speak to your doctor or pharmacist if you have any of these less serious side effects and they worry you.
These side effects are usually mild and short-lived.

Serious side effects

Serious side effectsWhat to do
  • severely disturbed vision
  • chest pain
  • changes in the way your heart beats for example if you notice it beating faster.
  • hypersensitivity, for example, flushing or rash of the skin, itching, fever, and swelling.
  • shortness of breath, difficulty in breathing
  • diarrhoea or cramps
  • distinct reduction in the amount of urine or a reddish colour in the urine.
  • bruising or bleeding more easily than normal
  • symptoms of liver disease with yellowing of the eyes or skin (jaundice) and dark urine.
  • confusion
  • loss of consciousness, coma, death.
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.
Stop taking QUINATE and tell your doctor immediately or go to Accident and Emergency at your nearest hospital if you notice any unexplained signs of bruising or swelling.

Some side effects can only be detected by your doctor. So it is important to visit your doctor for regular check-ups.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Do not be alarmed by this list of possible side effects.

You may not experience any of them.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is available with a doctor's prescription.

What QUINATE contains

Active ingredient
(main ingredient)		quinine sulfate dihydrate
Other ingredients
(inactive ingredients)

QUINATE tablets contain:

  • lactose monohydrate,
  • magnesium stearate
  • maize starch,
  • povidone,
  • sodium starch glycollate
  • Opadry complete film coating system White Y-1-7000.
Potential allergensThe tablets contain sugars as lactose.

Quinate tablets do not contain gluten, sucrose, tartrazine or any other azo dyes.

Do not take this medicine if you are allergic to any of these ingredients.

What QUINATE looks like

Quinate tablets are plain white, round, biconvex and film coated.

Available in bottles of 50 tablets. (AUST R 50707).

Who distributes QUINATE

Arrotex Pharmaceuticals Pty Ltd
15-17 Chapel St
Cremorne VIC 3121
www.arrotex.com.au

This leaflet was prepared in June 2024

Published by MIMS August 2024

BRAND INFORMATION

Brand name

Quinate

Active ingredient

Quinine sulfate dihydrate

Schedule

S4

 

1 Name of Medicine

Quinine sulfate dihydrate.

2 Qualitative and Quantitative Composition

Quinate tablets contain 300 mg of quinine sulfate dihydrate.

Excipients with known effect.

Contains sugars as lactose.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Quinate tablets are white, round, biconvex film coated tablets.

4 Clinical Particulars

4.1 Therapeutic Indications

Treatment of malaria due to strains of P. falciparum resistant to chloroquine and the related 4-aminoquinolines.

4.2 Dose and Method of Administration

Adults.

Quinine sulfate dihydrate 600 mg (adult < 50 kg: 450 mg) orally after a meal, 8 hourly for 7 to 14 days and pyrimethamine 75 mg + sulfadoxine 1500 mg as a single dose on the second day of the treatment.

Children.

Quinine sulfate dihydrate 10 mg/kg bodyweight (up to 600 mg) orally, 8 hourly for 7 to 10 days, in combination with appropriate single dose of pyrimethamine/ sulfadoxine.

4.3 Contraindications

Patients hypersensitive to quinine, mefloquine or quinidine or any of the excipient listed in Section 6.1.
Patients with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency.
Since thrombocytopenia, which may be fatal, and haemolytic uraemic syndrome with acute renal failure may follow the administration of quinine in highly sensitive patients, a history of this occurrence associated with previous quinine ingestion contraindicates its further use. Recovery usually occurs following withdrawal of the medication and appropriate therapy.
Myasthenia gravis (see Section 4.8 Adverse Effects (Undesirable Effects)), quinine may cause severe respiratory distress and dysphagia in these patients.
Tinnitus; optic neuritis or in patients with a history of blackwater fever.
Haemolysis or Haemoglobinuria.
Prolongation of QT interval (see Section 4.4 Special Warnings and Precautions for Use).

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. Symptoms of cinchonism include tinnitus, impaired hearing, nausea, and disturbed vision (see Section 4.8 Adverse Effects (Undesirable Effects); Section 4.9 Overdose).

Haemolysis.

Quinine should be stopped immediately if haemolysis occurs and supportive measures instituted.

Prothrombin formation.

Quinine is capable of causing hypoprothrombinaemia (i.e. depresses the formation of prothrombin) and may enhance the effects of anticoagulants. The simultaneous administration of vitamin K counteracts the prolongation of the prothrombin time.

Cardiac disorders.

Quinine has dose-dependent QT-prolonging effects. Caution is recommended in patients with conditions which predispose to QT-prolongation and in patients with atrioventricular block.
Quinine should be used with caution in patients with heart block, other cardiac conduction defects or other serious heart disease.
Patients with atrial fibrillation should be digitalised before receiving quinine, because quinine may otherwise cause an increase in the ventricular rate.

Hypersensitivity reactions.

Serious hypersensitivity reactions reported with quinine sulfate include anaphylactic shock, anaphylactoid reactions, serious skin rashes including Stevens-Johnson syndrome and toxic epidermal necrolysis, angioedema, bronchospasm and pruritus. A number of other serious adverse reaction reported with quinine, including thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS), thrombocytopenia, immune thrombocytopenic purpura (ITP), blackwater fever, disseminated intravascular coagulation, leukopenia, neutropenia, granulomatous hepatitis, and acute interstitial nephritis may also be due to hypersensitivity reactions.
Hypersensitivity reactions, including cutaneous flushing, pruritus, rash (urticarial, papular, scarlatinal), fever, facial oedema, gastrointestinal distress, dyspnoea, tinnitus and impairment of vision have been reported with quinine. Extreme flushing of the skin with intense, generalised pruritus is the most frequently reported hypersensitivity reaction to the drug. Haemoglobinuria and asthma have also been reported rarely. If evidence of hypersensitivity occurs during quinine therapy, the drug should be discontinued.

Thrombocytopenia.

Quinine-induced thrombocytopenia is an immune-mediated disorder. Severe cases of thrombocytopenia that are fatal or life threatening have been reported, including cases of HUS/TTP. Chronic renal impairment associated with the development of TTP has also been reported. Thrombocytopenia usually resolves within a week upon discontinuation of quinine. If quinine is not stopped, a patient is at risk for fatal hemorrhage. Upon re-exposure to quinine from any source, a patient with quinine-dependent antibodies could develop thrombocytopenia that is more rapid in onset and more severe than the original episode.
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.

Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency.

Quinine has been implicated in precipitating blackwater fever when given for prolonged periods, although in some cases, glucose-6-phosphate dehydrogenase deficiency may be at increased risk of haemolysis during quinine therapy and may develop acute haemolytic anaemia. Quinine should not be withheld from pregnant women who have life threatening malaria (see Section 4.6 Fertility, Pregnancy and Lactation).
Treatment with quinine should be monitored in case signs of resistance develop.
Patients with rare hereditary problems of galactose intolerance, total lactose deficiency or glucose-galactose malabsorption should not take this medicine.

Hypoglycemia.

Quinine stimulates release of insulin from the pancreas, and patients, especially pregnant women, may experience clinically significant hypoglycemia.

Musculoskeletal.

Quinine has neuromuscular blocking activity, and may exacerbate myasthenia gravis.

Renal impairment.

Clearance of quinine is decreased in patients with severe chronic renal failure; reduce the dosage (or increase interval between doses) in renal diseases.

Hepatic impairment.

Close monitoring is recommended for patients with impaired liver function, as this may result in increased exposure to quinine. Reduce the dosage (or increase interval between doses) in hepatic diseases.

Use in the elderly.

No data available.

Paediatric use.

No data available.

Effects on laboratory tests.

Quinine may produce an elevated value for urinary 17-ketogenic steroids when the Zimmerman method is used.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Effect of other drugs on quinine.

Quinine is metabolised via hepatic oxidative cytochrome P450 pathways, predominantly by CYP3A4. Other enzymes, including CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP2E1 may contribute to the metabolism of quinine. There is the potential for increased quinine toxicity with concurrent use of potent CYP3A4 inhibitors, which includes cyclosporine, azole antifungal drugs macrolide antibiotics including erythromycin and clarithromycin, antidepressants (e.g. nefazodone), 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.
Caution is advised when administering quinine with drugs which could prolong the QT interval.
Quinine may increase the levels of phenobarbital and of carbamazepine. Patients should be monitored closely during concomitant use of quinine with these agents.

Effect of quinine on other drugs.

Results of in vivo drug interaction studies suggest that quinine has the potential to inhibit the metabolism of drugs that are substrates of CYP3A4 and CYP2D6. Quinine inhibits P-gp and has the potential to affect the transport of drugs that are P-gp substrates.

Astemizole (CYP3A4 substrate).

Elevated plasma astemizole concentrations were reported in a subject who experienced torsades de pointes after receiving three doses of quinine sulfate for nocturnal leg cramps concomitantly with chronic astemizole 10 mg/day. The concurrent use of quinine with astemizole and other CYP3A4 substrates with QT prolongation potential (e.g. cisapride, terfenadine, halofantrine, pimozide and quinidine) should also be avoided (see Section 4.4 Special Warnings and Precautions for Use, Cardiac disorders).

Atorvastatin (CYP3A4 substrate).

Rhabdomyolysis with acute renal failure secondary to myoglobinuria was reported in a patient taking atorvastatin administered with a single dose of quinine. Quinine may increase plasma concentrations of atorvastatin, thereby increasing the risk of myopathy or rhabdomyolysis. Thus, clinicians considering combined therapy of quinine with atorvastatin or other HMG-CoA reductase inhibitors ("statins") that are CYP3A4 substrates (e.g. simvastatin, lovastatin) should carefully weigh the potential benefits and risks of each medication. If quinine is used concomitantly with any of these statins, lower starting and maintenance doses of the statin should be considered. Patients should also be monitored closely for any signs or symptoms of muscle pain, tenderness, or weakness, particularly during initial therapy. If marked creatine phosphokinase (CPK) elevation occurs or myopathy (defined as muscle aches or muscle weakness in conjunction with CPK values > 10 times the upper limit of normal) is diagnosed or suspected, atorvastatin or other statin should be discontinued.
The plasma concentration of flecainide, digoxin and mefloquine may be increased.

Amantadine.

Quinine can reduce the renal clearance of amantadine toxicity (including headache, nausea, dizziness).

Mefloquine.

The concomitant administration of mefloquine and quinine may produce electrocardiographic abnormalities (including QTc prolongation) and may increase the risk of seizures (see Section 4.4 Special Warnings and Precautions for Use).

Analgesics.

Increased risk of ventricular arrhythmias with levacetylmethanol (avoid concomitant use).

Ciclosporin.

Quinine can decrease serum plasma concentrations of ciclosporin.

Cardiac glycosides.

Increased plasma levels of digoxin have been demonstrated in individuals after concomitant quinine administration. Increased plasma levels of digitoxin have been demonstrated in individuals after concomitant quinidine administration. It is therefore recommended that plasma levels of digoxin or digitoxin be determined periodically for those individuals taking either of these glycosides and quinine concomitantly.

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. Caution is advised when administering quinine with drugs which could prolong the QT interval.

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 quinine may increase the possibility of cinchonism.

Antibacterials.

Rifampicin can reduce the serum levels of quinine, therefore reducing its therapeutic effect.

Anticoagulants.

Quinine may cause hypoprothrombinaemia and the effects of anticoagulants may be enhanced (see Section 4.4 Special Warnings and Precautions for Use). Cinchona alkaloids, including quinine, may have the potential to depress hepatic enzyme synthesis of vitamin K-dependent coagulation pathway proteins and may enhance the action of warfarin and other oral anticoagulants. Quinine may also interfere with the anticoagulant effect of heparin. Thus, in patients receiving these anticoagulants, the prothrombin time (PT), partial thromboplastin time (PTT), or international normalization ratio (INR) should be closely monitored as appropriate, during concurrent therapy with quinine.

Antihistamines.

Concomitant use of astemizole and terfenadine should be avoided due to the increased risk of ventricular arrhythmias.

Antimalarials.

There may be an increased risk of side effects if quinine is used with other antimalarials, for example, chloroquine, halofantrine and mefloquine (increased risk of convulsions), although this should not prevent their use in severe cases. Quinine may increase the plasma concentration of mefloquine. Chloroquine and quinine appear to be antagonistic when given together for P. falciparum malaria. There is an increased risk of ventricular arrhythmias with halofantrine.

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 enhance the neuromuscular effects of suxamethonium.

Ulcer-healing drugs.

Cimetidine has been reported to decrease the clearance and prolong the elimination half-life of quinine following concomitant use in healthy adults leading to increased plasma-quinine concentrations. The clinical significance of this interaction is unknown. Concurrent use of aluminium containing antacids may delay or decrease absorption of quinine.
Cinchona alkaloids, including quinine, have the potential to depress the hepatic enzyme system that synthesises the vitamin K dependent factors. The resulting hypoprothrombinaemic effect may enhance the action of warfarin and other anticoagulants.
Excessive quantities of quinine containing beverages should not be consumed while taking quinine as this may increase the risk of adverse reactions and toxicity.
The effects of neuromuscular blocking agents (particularly pancuronium, succinylcholine and tubocurarine) may be potentiated with quinine, and result in respiratory difficulties.
In view of the known effects of quinine in patients with myasthenia gravis it may potentiate the effect of both depolarising and nondepolarising muscle relaxants.
Urinary alkalinisers (such as acetazolamide and sodium bicarbonate) may increase quinine blood levels with potential for toxicity.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category D)
The use of antimalarials in the treatment of life threatening malaria is accepted because the small risk to the foetus is outweighed by the benefits to the mother and foetus. Prophylaxis in high risk situations is also justified.
In high doses, quinine causes foetal injuries in the form of deafness, phototoxicity development disturbances and malformations of the CNS extremities and cranium in both animals and humans. Its ability to induce uterine contractions also constitutes a risk of abortion.
Hypoglycemia, due to increased pancreatic secretion of insulin, has been associated with quinine use, particularly in pregnant women.
Quinine sulfate should not be used during pregnancy to treat cramps.
 Caution should be exercised when quinine is given to nursing mothers because quinine is excreted in breast milk (in small amounts). Infants at risk for glucose-6-phosphate dehydrogenase deficiency should not be breastfed until this disease can be ruled out. Quinine 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 Adverse Effects (Undesirable Effects)

Cinchonism is the term given to a group of symptoms which usually occurs when quinine is given repeatedly in full doses. Cinchonism has certain features in common with salicylate poisoning. Mildest forms consist of tinnitus, headache, nausea and slightly disturbed vision. If the medication is continued or in overdose, symptoms involve the gastrointestinal tract, CNS and CVS and the skin. In some individuals, small doses of quinine cause toxic manifestations.
The following adverse reactions have been reported with quinine in therapeutic or excessive doses.
(Individual or multiple symptoms may represent cinchonism or hypersensitivity.)

Blood and lymphatic system disorders.

Thrombocytopenia, disseminated intravascular coagulation, hypoprothrombinaemia, haemoglobinuria, oliguria, hemolytic anemia, haemolytic-uremic syndrome, pancytopenia, haemolysis agranulocytosis, thrombotic thrombocytopenic purpura, idiopathic thrombocytopenic purpura, petechiae, ecchymosis, hemorrhage, coagulopathy, blackwater fever, leukopenia, neutropenia, aplastic anemia.

Immune system disorders.

Eczematous dermatitis, oedema, erythema and lichen planus, hypersensitivity reactions such as asthma, angioneurotic oedema, photosensitivity, hot and flushed skin, fever, chills, sweating, pruritus, lupus-like syndrome, thrombocytopenic purpura and urticaria have also been reported.

Metabolism and nutrition disorders.

Hypoglycaemia and anorexia.

Psychiatric disorders.

Agitation, confusion.

Nervous system disorders.

Headache, diplopia, confusion, altered mental status, seizures, vertigo, excitement, loss of consciousness, coma, death, disorientation, tremors, restlessness, ataxia, acute dystonic reaction, aphasia, and suicide.

Eye disorders.

Visual disturbances, including blurred vision with scotomata, sudden loss of vision, photophobia, diplopia, night blindness, diminished visual fields, optic neuritis, blindness, fixed pupillary dilatation and disturbed colour vision. Although visual disturbances are generally reversible following discontinuation of the drug, in severe cases, optic atrophy may result.

Ear and labyrinth disorders.

Tinnitus, vertigo, deafness and impaired hearing.

Cardiovascular disorders.

Anginal symptoms, chest pain, conduction disturbances, ventricular tachycardia, ventricular fibrillation, fall in blood pressure coupled with feeble pulse, bradycardia, palpitations, syncope, atrioventricular block, atrial fibrillation, irregular rhythm, unifocal premature ventricular contractions, nodal escape beats, U waves, torsades de pointes, and cardiac arrest. Atrioventricular conduction disturbances, prolongation of the QT interval, widening of the QRS complex and T wave flattening, vasodilatation, hypotension, postural hypotension.

Respiratory disorders.

Asthmatic symptoms, pulmonary oedema, bronchospasm, dyspnoea.

Gastrointestinal disorders.

Nausea, vomiting (may be CNS related), epigastric pain, hepatitis, diarrhoea, abdominal pain*, gastric irritation, and esophagitis.

Skin and subcutaneous tissues disorders.

Flushing, rashes, (urticarial, the most frequent type of allergic reaction, papular or scarlatinal), eczematous dermatitis, oedema, bullous dermatitis, exfoliative dermatitis, erythema multiforme, lichen planus, pruritus, photosensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis, fixed drug eruption, sweating, occasional oedema of the face, allergic contact dermatitis, acral necrosis, and cutaneous vasculitis.

Musculoskeletal and connective tissue disorders.

Muscle weakness, myalgia and aggravation of myasthenia gravis.

Renal and urinary disorders.

Anuria, uraemia and haemoglobinuria, renal insufficiency, acute renal failure (may be due to an immune mechanism or to circulatory failure), acute interstitial nephritis, oliguria.

Hepatobiliary disorders.

Granulomatous hepatitis, hepatitis, jaundice, and abnormal liver function tests.

Reproductive system and breast disorders.

Abortion**.

General disorders and administration site conditions.

Cinchonism***.
* May occur after long term administration of quinine
** Toxic doses of quinine may induce abortion, but it is unwise to withhold the drug if less toxic antimalarials are not available.
*** 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 severe manifestation symptoms may include gastrointestinal symptoms, oculotoxicity, CNS disturbance, cardiotoxicity and death (see Section 4.9 Overdose). Visual disorders (blurred vision, defective colour perception, visual field constriction and total blindness).
Quinine can cause thrombocytopenia which may be fatal. There have been reports of haemolytic uraemic syndrome and acute renal failure following a single dose of 300 mg of quinine. Acute haemolytic anaemia is rare and normally disappears on discontinuation of the drug.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration 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 at www.tga.gov.au/reporting-problems.

4.9 Overdose

The most common signs and symptoms of overdosage are tinnitus, deafness, visual disturbances, dizziness, skin rash and gastrointestinal disturbances (intestinal cramping). With higher doses, cardiovascular and CNS effects may occur, including headache, fever, vomiting, apprehension, confusion and convulsions. Abortion, low blood pressure and renal failure are also possible results of overdosage. Other effects are listed in Section 4.8 Adverse Effects (Undesirable Effects).
Fatalities have been reported from a single dose of 2-8 g of quinine and a single fatality reported with a 1.5 g dose (which may reflect an idiosyncratic effect). Several cases of blindness following large overdoses of quinine, with partial recovery of vision in each instance, have been reported. Tinnitus and impaired hearing may occur at plasma quinine concentration of over 10 microgram/mL. This level would not be normally attained with the dose of 1-2 quinine tablets a day, but in hypersensitive patients, as little as 0.3 g of quinine may produce tinnitus.
Treatment for overdosage with Quinate should consist of general supportive measures including monitoring of vital signs and observation of the clinical status of the patient together with careful monitoring of ECG, respiratory status and central nervous system toxicity. There is no specific antidote for overdose with Quinate. Administration of activated charcoal may also be used to aid in removal of unabsorbed drug.
Patients should be warned of possible blindness but reassured that some recovery of sight frequently occurs. Stellate block has been used effectively for quinine associated blindness. Residual visual impairment occasionally yields to vasodilators.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Quinine affects a large variety of biological systems. From the therapeutic viewpoint, the following are most relevant.

Central nervous system.

Quinine exerts a slight antipyretic effect, and an analgesic action resembling that of the salicylate group, especially on joint and muscle pain. Although quinine acts centrally, it is ineffective against severe pain.

Cardiovascular system.

Quinine acts in a similar qualitative manner on cardiac muscle as does its isomer quinidine, the anti-arrhythmic drug. However, therapeutic doses of quinine have little or no effect on the normal cardiovascular system in man.

Smooth muscle.

Quinine has a mild stimulatory effect on the pregnant uterus which is an oxytocic stimulation. It also passes the placental barrier. Quinine may also cause the smooth muscle in the spleen to contract producing lymphocytosis, sometimes observed after therapeutic doses of the drug.

Skeletal muscle.

Quinine has a dual action in skeletal muscle: it acts directly on the muscle fibre, increasing the tension response, and also increases the refractory period; it affects neuromuscular transmission by increasing the threshold of excitability of the motor endplate.

Antimalarial action.

Quinine is also effective in malaria. Although the exact mechanism of action is not known, quinine appears to interfere with plasmodial DNA.

Other actions.

Quinine has a strong prostaglandin antagonistic action and a weak agonistic activity. The antagonistic effect is clearly demonstrated at concentrations attained therapeutically. Quinine has a slight local anaesthetic activity. The anaesthesia may last for many hours or days.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Absorption occurs readily when given orally, and occurs mainly in the upper small intestine. Plasma concentrations after single oral doses are approximately the same as after comparable intravenous doses. Peak plasma concentrations occur within 1-3 hours after a single oral dose. Quinine sulfate is 70% bound to plasma proteins.

Metabolism.

Metabolism occurs largely in the liver, with less than 5% excreted unaltered in the urine.

Excretion.

After cessation of quinine therapy, the plasma level falls rapidly, and only a negligible concentration is present after 24 hours. No accumulation in body tissues occurs with continued administration. The inactive metabolites are excreted mainly in the urine.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Quinate tablet contain the excipients lactose monohydrate, maize starch, povidone, sodium starch glycollate, magnesium stearate and Opadry complete film coating system white Y-1-7000.
See Section 2 Qualitative and Quantitative Composition.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 30°C.

6.5 Nature and Contents of Container

Quinate tablets are available in HDPE bottles of 50.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Quinine sulfate is the sulfate of an alkaloid obtained from the bark of species of Cinchona. It contains not less than 99.0 per cent and not more than 101.0 per cent of total alkaloid salt, calculated as (C20H24N2O2)2.H2SO4, on the anhydrous basis. It is a white or almost white or colourless, fine, crystalline solid.

Chemical structure.

Quinine sulfate dihydrate has the following structural formula:
Molecular weight: 783.0.

CAS number.

CAS Registry Number: 6119-70-6.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Medicine.

Summary Table of Changes