Consumer medicine information

Quinine Dihydrochloride 6%

Quinine dihydrochloride

BRAND INFORMATION

Brand name

Quinine Dihydrochloride 6% (Phebra) Sterile Concentrate

Active ingredient

Quinine dihydrochloride

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Quinine Dihydrochloride 6%.

What is in this leaflet

This leaflet answers some common questions about Quinine Dihydrochloride 6%. It does not contain all the available information. It does not take the place of talking to your doctor.

All medicines have risks and benefits. Your doctor has weighed the risks of you being given Quinine Dihydrochloride 6% against the benefits they expect it will have for you.

If you have any concerns about being given this medicine, ask your doctor.

Keep this leaflet. You may need to read it again.

What Quinine Dihydrochloride 6% is used for

Quinine Dihydrochloride 6% is a concentrated solution and must be diluted before use. This medicine is used for the treatment of severe malaria or when the patient is unable to take medication by mouth.

It is also used in the treatment of Babesiosis, a rare disease caused by an infection carried by ticks.

Ask your doctor if you have any questions about why Quinine Dihydrochloride 6% has been prescribed for you. Your doctor may have prescribed it for another reason.

Before you are given Quinine Dihydrochloride 6%

When you must not be given it

You must not be given Quinine Dihydrochloride 6% if you have an allergy to quinine or quinidine.

Some of the symptoms of an allergic reaction may include:

  • shortness of breath.
  • wheezing or difficulty breathing.
  • swelling of the face, lips, tongue or other parts of the body.
  • rash, intense itching, flushing or hives on the skin.
  • ringing in the ears.
  • changes in vision.
  • fever.
  • stomach pain or upset.

You must not be given Quinine Dihydrochloride 6% if you have any of the following medical conditions:

  • glucose-6-phosphate-dehydrogenase deficiency (an inherited condition)
  • a history of blackwater fever
  • haemolysis (destruction of red blood cells)
  • tinnitus (buzzing, whistling, ringing or other persistent noises in the ear)
  • inflammation of the optic nerve
  • diabetes

You should not be given this medicine if you are also taking medicine used to prevent blood clots such as Warfarin.

You should not be given this medicine if the solution is discoloured, cloudy, turbid, or particles or a precipitate is present. The solution is normally a clear and colourless to light yellow solution.

You should not be given this medicine if, when diluted with another solution, it causes the solution to precipitate, become cloudy, turbid, discolour, or particles are visible.

You should not be given this medicine after the expiry date printed on the pack, or if the packaging is torn or shows signs of tampering. If you are given this medicine after the expiry date has passed, it may not work as well.

If you are not sure whether you should be given this medicine, talk to your doctor.

Before you are given it

Tell your doctor if you have allergies to any other medicines, foods, preservatives, or dyes.

Tell your doctor if you have or have had any of the following medical conditions:

  • irregular heart beat.
  • liver disease and/or hepatitis.
  • kidney disease.

Tell your doctor if you are pregnant or plan to become pregnant or are breast-feeding. Your doctor will discuss with you the risks and benefits involved.

If you have not told your doctor about any of the above, tell him/her before you are given Quinine Dihydrochloride 6% Sterile concentrate.

Taking other medicines

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

Some medicines and Quinine Dihydrochloride 6% may interfere with each other. These include:

  • medicines used to treat the symptoms of urinary tract infections such as ammonium chloride, acetazolamide, sodium bicarbonate.
  • cimetidine a medicine often used to treat reflux and ulcers.
  • digoxin, a medicine used for heart conditions.
  • medicines used to prevent blood clots such as Warfarin, Coumarin, or Indanedione derivatives
  • other medicines used to treat malaria such as pyrimethamine, mefloquinine and quinidine.
  • lithium, a medicine used to treat a mental illness - bipolar disorder.
  • medicines used to treat myasthenia gravis.
  • medicines that help relax the muscles during the use of general anaesthetics called neuromuscular blocking agents such as tubocurarine chloride and doxacurium chloride.
  • medicines which increase the effects of neuromuscular blocking agents (see point above) when taken at the same time such as:
    - magnesium salts
    - salbutamol
    - some general anaesthetics
    - ganglion blockers such as trimethaphan
    - calcium channel blockers such as nifedipine and verapamil
    - antibacterials such as vancomycin
    - diuretics such as frusemide and mannitol
    - antiarrhythmics such as lignocaine and verapamil
    - anticholinesterases such as neostigmine
    - antineoplastics such as tamoxifen.

These medicines may be affected by Quinine Dihydrochloride 6% 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 and pharmacist have more information on medicines you need to be careful with, or avoid, while being given this medicine.

How Quinine Dihydrochloride 6% is given

Quinine Dihydrochloride 6% must only be given by a doctor or nurse.

Quinine Dihydrochloride 6% is a concentrated solution and must be diluted before use. It will be infused slowly into a vein only after dilution into an intravenous (IV) solution.

If Quinine Dihydrochloride 6% cannot be infused into a vein, it may be injected into a muscle.

Your doctor will decide what dose of Quinine Dihydrochloride 6% you will receive and for how long you will receive it. This depends on your medical condition and other factors including your weight.

If you are given too much (overdose)

Quinine Dihydrochloride 6% is given by a doctor or nurse so an overdose is not likely to occur.

Immediately contact your doctor or go to the Emergency Department at the nearest hospital if you notice the symptoms of an overdose. Symptoms of an overdose are similar to the symptoms of the side effects experienced with this medicine and are listed under Side Effects section.

While you are being given Quinine Dihydrochloride 6%

Things you must do

If you are about to be started on any new medicine, remind your doctor and pharmacist, that you have been given Quinine Dihydrochloride 6%.

Tell any other doctors, dentists, and pharmacists, who treat you that you have been given this medicine.

If you are going to have surgery, tell the surgeon or anaesthetist that you have been given this medicine. It may affect other medicines used during surgery.

If you become pregnant while being given this medicine, tell your doctor immediately.

Keep all of your doctor’s appointments so that your progress can be checked. Your doctor may do some tests from time to time to make sure the medicine is working and to prevent unwanted side effects.

Things to be careful of

If you feel light headed or faint when getting out of bed or standing up, get up slowly. Standing up slowly, especially when you get up from beds or chairs, will help your body get used to the change in position and blood pressure. If this problem continues to get worse talk to your doctor.

Side Effects

Tell your doctor or nurse as soon as possible if you do not feel well while you are being given Quinine Dihydrochloride 6%. This medicine may have unwanted side effects in a few people. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

Do not be alarmed by the following list of side effects. You may not experience any of them.

Ask your doctor to answer any questions you may have.

Tell your doctor or nurse if you notice any of the following and they worry you:

  • ringing in the ears or difficulty hearing.
  • headache, confusion.
  • disturbed vision.
  • nausea, vomiting, diarrhoea, stomach pain.
  • dizziness.

The above list includes the more common side effects of your medicine.

If any of the following happen tell your doctor or nurse immediately or go to the Emergency Department at your local hospital:

  • skin rash, itching, swelling of the face, flushing of the skin.
  • wheezing, difficulty breathing.
  • irregular heart beat, chest pain
  • symptoms of liver disease such as yellowing of the eyes and skin.
  • reduced or no urine produced or discoloured urine.
  • increase in bruising or bleeding.
  • muscle weakness
  • fainting.

The above list includes some very serious side effects. You may need urgent medical attention or hospitalisation. These side effects are very rare.

Tell your doctor or nurse if you notice anything that is making you feel unwell.

Other side effects not listed above may also occur in some people.

Some of the side effects can only be found when your doctor does tests from time to time to check your progress.

After being given Quinine Dihydrochloride 6%

Storage

Quinine Dihydrochloride 6% will usually be stored in the doctor’s surgery, pharmacy, or clinic. The medicine is kept in a cool dry place where the temperature stays below 25°C. It should be protected from light.

Quinine Dihydrochloride 6% will be opened for use on you. It will be used only once and then it will be discarded. It will never be stored after it is opened or used for more than one person.

Product description

What it looks like

Quinine Dihydrochloride 6% is a clear and colourless to light yellow solution in a 10 mL clear glass vial sealed with a grey rubber stopper and aluminium seal with a white plastic flip off cap.

Ingredients

Quinine Dihydrochloride 6% contains 60 mg/mL of quinine dihydrochloride in water for injections.

This medicine does not contain lactose, sucrose, gluten, tartrazine dyes or any preservatives.

Manufacturer

Quinine Dihydrochloride 6% is made in Australia by:

Phebra Pty Ltd
19 Orion Road
Lane Cove West, NSW 2066
Australia
Telephone: 1800 720 020

Quinine Dihydrochloride 6%
10 mL vial
AUST R 23101

Phebra product code:

INJ043: 10 mL x 10 vials in a carton

INJ209: 10 mL x 5 vials in a carton

Not all pack sizes may be marketed.

Date of most recent amendment:
16 Feb 2021

Phebra and the Phi symbol are trademarks of Phebra Pty Ltd, 19 Orion Road, Lane Cove West, NSW 2066, Australia.

Published by MIMS April 2021

BRAND INFORMATION

Brand name

Quinine Dihydrochloride 6% (Phebra) Sterile Concentrate

Active ingredient

Quinine dihydrochloride

Schedule

S4

 

1 Name of Medicine

Quinine dihydrochloride.

2 Qualitative and Quantitative Composition

Quinine Dihydrochloride 6% contains 600 mg quinine dihydrochloride in 10 mL of water for injections.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Quinine Dihydrochloride 6% is a sterile concentrated solution for injection which has a faint straw coloured appearance. Dilute before administration.

4 Clinical Particulars

4.1 Therapeutic Indications

Quinine Dihydrochloride 6% Sterile Concentrate 600 mg in 10 mL solution for injection is indicated for the acute treatment of malaria. It may also be used in the treatment of Babesiosis in conjunction with clindamycin.

4.2 Dose and Method of Administration

The solution should be diluted before administration and contains no antimicrobial preservative. Quinine Dihydrochloride 6% should be used in one patient on one occasion only and unused solution should be discarded.
Wherever possible, patients should be transferred to oral therapy as soon as possible.

For intravenous injection.

Adults.

The following doses may be used as a guide, Quinine Dihydrochloride 6% must be diluted in 500 mL of glucose 5% preferably, or sodium chloride 0.9% (usually 600 mg in 500 mL) and infused slowly over 4 hours.

Loading dose.

20 mg/kg up to a maximum of 1400 mg given slowly by infusion over 4 hours. Commence the maintenance doses 8 to 12 hours after loading dose.

Maintenance dose.

10 mg per kg up to a maximum of 700 mg over 4 hours given slowly by infusion. Repeat every 8-12 hours if necessary.
A loading dose is not required if antimalarials have been given during the previous 24 hours.
If parenteral therapy is required for more than 48 hours, the maintenance dose of quinine should be reduced by one-third to one-half to 5 mg/kg to avoid accumulation and drug level monitoring is important. See Section 4.4 Special Warnings and Precautions for Use.
Alternatively, in intensive care units only, an initial loading dose of 7 mg per kg may be given over 30 minutes followed immediately by the first of the maintenance infusions.

Paediatric.

Intravenous.

10 mg per kg diluted and infused slowly at a rate not exceeding 0.5 mg per minute, preferably with ECG monitoring.

Intramuscular injection.

See Section 4.4 Special Warnings and Precautions for Use.

Compatible solutions.

Glucose 5%, sodium chloride 0.9%.

4.3 Contraindications

Quinine Dihydrochloride 6% is contraindicated in the following situations:
Hypersensitivity to quinine or quinidine.
Glucose-6-phosphate dehydrogenase (G6PD) deficiency.
History of blackwater fever.
Patients with tinnitus or optic neuritis.
It should not be used in the presence of haemolysis or in the presence of concurrent anticoagulant therapy.
It should not be used in patients with diabetes.

4.4 Special Warnings and Precautions for Use

Check for hypersensitivity to quinine or quinidine before administration. It is important that when given intravenously it should be given by slow infusion and the patient observed closely for signs of cardiotoxicity.
Pulse and blood pressure should be closely monitored and the rate of infusion attenuated if dysrhythmias occur, and blood glucose concentrations should be monitored. Therapy should be changed to oral administration as soon as possible.
If intravenous infusion is not possible, quinine dihydrochloride has been given intramuscularly. This can be an irritant, cause pain, focal necrosis and abscess formation, and fatal tetanus has developed in some patients, and there have been concerns regarding its safety and efficacy. The intramuscular route should only be used as a last resort.

Haemolysis.

Quinine Dihydrochloride 6% should be stopped immediately and supportive measures instituted if signs of haemolysis appear. Haemolysis with a potential for haemolytic anaemia has been reported when given to patients with G6PD deficiency.

Prothrombin formation.

Quinine Dihydrochloride 6% is capable of causing hypoprothrombinaemia and may enhance the effect of anticoagulants.

Atrial fibrillation.

Patients with this condition should be digitilised before receiving quinine as otherwise it may cause an increase in the ventricular rate.

Hypersensitivity.

Reactions include cutaneous flushing, pruritus, rash, fever, facial oedema, GI distress, dyspnoea, tinnitus, and impairment of vision. The most frequently reported hypersensitivity reaction is extreme flushing of the skin with intense pruritus. If evidence of hypersensitivity occurs, quinine therapy should be discontinued.

Use in hepatic impairment.

The half-life of quinine is prolonged in hepatitis and moderate chronic liver disease.

Use in the elderly.

No data available.

Paediatric use.

See Section 4.2 Dose and Method of Administration, Paediatric.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Urinary alkalinisers.

Such as acetazolamide and sodium bicarbonate increases blood quinine levels by decreasing renal clearance of quinine.

Urinary acidifiers.

Such as ammonium chloride and some other drugs, decrease the pH of the urine and therefore increase the excretion of quinine, resulting in lower quinine blood levels.

Cimetidine.

If used concurrently, it may reduce the clearance of quinine.

Digoxin.

If used concurrently, it may result in increased serum digoxin concentrations and increased digoxin effect. Serum digoxin concentrations should be monitored and dosage adjustments made when necessary.

Anticoagulants.

Hypoprothrombinaemic effects may be increased when quinine is used with warfarin, coumarin or indanedione derivatives.

Pyrimethamine.

Antimalarials such as this drug may displace quinine from protein binding sites resulting in excessive free quinine levels and possible toxicity.

Neuromuscular blocking agents.

Including pancuronium bromide, atracurium besylate, suxamethonium chloride, mivacurium chloride, pipecuronium bromide, rapacuronium bromide, alcuronium chloride, cisatracurium besylate, doxacurium chloride, gallamine triethiodide, metocurine iodide, decamethonium bromide or diiodide, rocuronium bromide, vecuronium chloride and tubocurarine chloride are known to or may interact with quinine causing respiratory difficulties.
Agents which add to an enhancement of neuromuscular blockading drugs must be monitored with concurrent usage. These include:

Antiarrhythmics.

Lignocaine, procainamide, quinidine, nifedipine and verapamil which all have neuromuscular blocking activity and may exacerbate neuromuscular block.

Anticholinesterases.

Neostigmine and edrophonium may enhance neuromuscular block.

Diuretics.

Frusemide and mannitol.

Antineoplastics.

Caution should be used with antioestrogenic drugs such as tamoxifen.

Antibacterials.

Some antibacterials in high concentration may produce a muscle paralysis which may be additive to or synergistic with that produced by neuromuscular blockers. This may be enhanced in patients with intracellular potassium deficiency or low plasma calcium concentration following large doses or renal impairment. The agents most commonly implicated are: aminoglycosides, lincosamides, polymyxins, vancomycin and rarely, tetracyclines. These should be used with care with quinine or monitored very closely.

Calcium channel blockers.

Nifedipine and verapamil enhance the effect of neuromuscular blockade.

Ganglion blockers.

Prolonged neuromuscular blockade has been reported in patients receiving neuromuscular blockers and trimetaphan.

General anaesthetics.

Neuromuscular blockers are potentiated in a dose dependent manner by inhalation anaesthetics especially with competitive blockers. The greatest potentiation is from isoflurane, enflurane, desflurane and sevoflurane followed by halothane and cyclopropane.

Magnesium salts.

Parenteral magnesium salts may potentiate the effects of neuromuscular blockade.

Sympathomimetics (salbutamol).

Intravenous salbutamol has been reported to enhance the blockade obtained with pancuronium and vecuronium.

Other.

Antimyasthenics, haemolytics, neurotoxic medication, ototoxic medication, mefloquine, lithium and quinidine.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
The use of antimalarials for the treatment of life threatening malaria during pregnancy is acceptable, because the small risk to the fetus is outweighed by the benefits to the mother and fetus. In high doses, quinine causes fetal injuries in the form of deafness, development disturbances, and malformation of the extremities and cranium. It has the ability to induce uterine contractions and constitutes a risk of abortion.
 Quinine is excreted in breast milk in small concentrations and caution should be exercised during breastfeeding.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

When quinine is given repeatedly, a group of symptoms known as cinchonism occurs. Cinchonism symptoms include tinnitus, impaired hearing, headache, nausea, disturbed vision, vomiting, abdominal pain, diarrhoea and vertigo.

Haematological.

Acute haemolysis, thrombocytopenic purpura, agranulocytosis and hypoprothrombinaemia.

CNS.

Visual disturbances, blurred vision with scotomata, photophobia, diplopia, mydriasis, constricted visual fields, night blindness and disturbed colour perception. In severe cases the following adverse effects may also occur: tinnitus, vertigo, deafness, headache, confusion, syncope and optic atrophy (which may result in blindness).

Dermatological.

Rashes, urticaria, pruritus, flushing of the skin, oedema of the face, photosensitivity.

Respiratory.

Asthma precipitation.

Cardiovascular.

Disturbance in cardiac rhythm on conduction, widening of the QRS complex, hypotension, ventricular tachycardia, angio-oedema, and angina symptoms in sensitive patients. Severe or even fatal cardiovascular toxicity can result from rapid intravenous administration of quinine.

Gastrointestinal.

Nausea, vomiting, epigastric pain.

Musculoskeletal.

It may aggravate myasthenia gravis.

Hepatic.

Hepatoxicity.

Renal.

Anuria, uraemia, haemoglobinuria (rarely).

Hypoglycaemia.

It may aggravate hypoglycaemia. Quinine may cause thrombocytopenia which may be fatal.

Reporting suspected adverse reactions.

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

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.

The exact mechanism of action of quinine in malaria is uncertain, but its actions appear to interfere with the function of plasmodial DNA. It inhibits protein synthesis by preventing strand separation and therefore DNA replication and transcription to RNA. Its primary action is schizonticidal, and no lethal effect is exerted on sporozoites or pre-erythrocytic tissue forms. It is gametocytocidal for P. vivax and P. malariae.

CNS.

Quinine has slight analgesic and antipyretic activity. It has indifferent action on fevers except malarial fever.

Cardiovascular.

The central action of quinine and its isomer quinidine on cardiac muscle, are qualitatively similar. However, normal therapeutic doses have small effect on normal cardiovascular systems. Toxic doses may cause myocardial depression and vasodilatation.

Smooth muscle.

Quinine has a slight oxytocic action on the gravid uterus. The spleen may contract by action on the musculature of its capsule, thus producing a lymphocytosis.

Skeletal muscle.

Quinine has a dual action on skeletal muscle. It acts directly on muscle fibres, increasing the tension response and refractory period. It can have a curare-like effect on skeletal muscle.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

No data available.

Distribution.

The pharmacokinetics are altered significantly by malarial infection, the major effect being reduction in both its apparent volumes of distribution and its clearance.

Metabolism.

Quinine is metabolised in the liver and rapidly excreted mainly in the urine.

Excretion.

Excretion is increased in acid urine and decreased in alkaline urine.
Plasma protein binding is about 70% in healthy subjects, and rises to about 90% or more in patients with malaria. The elimination half life in healthy patients is 11 hours but may be prolonged in patients with malaria. This suggests that during malaria there is impaired hepatic metabolism of quinine.

5.3 Preclinical Safety Data

Genotoxicity.

No available data.

Carcinogenicity.

No available data.

6 Pharmaceutical Particulars

6.1 List of Excipients

Water for injections. It contains no antimicrobial preservative.

6.2 Incompatibilities

Incompatible with amiodarone, pancuronium bromide, atracurium besylate, suxamethonium chloride, mivacurium chloride, pipecuronium bromide, rapacuronium bromide, alcuronium chloride, cisatracurium besylate, doxacurium chloride, gallamine triethiodide, metocurine iodide, decamethonium bromide or diiodide, rocuronium bromide, vecuronium chloride and tubocurarine chloride, diuretics especially frusemide, mannitol, heparin, intravenous ketamine.
Also see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions; Section 4.4 Special Warnings and Precautions for Use.

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)1. The expiry date can be found on the packaging.
1 AUST R 23101.

6.4 Special Precautions for Storage

Store below 25°C and protect from light.

6.5 Nature and Contents of Container

10 mL vial supplied in a carton containing of 10 vials.
Phebra product code - INJ043.
10 mL vial supplied in a carton containing 5 vials.
Phebra product code - INJ209.
Not all pack sizes may be marketed.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Chemical name: (8S, 9R)-6'-methoxycinchonan-9-ol dihydrochloride.
The molecular weight of the compound is 397.3. The molecular formula is C20H24N2O2.2HCl.

Chemical structure.


CAS number.

60-93-5.

7 Medicine Schedule (Poisons Standard)

Schedule 4 - Prescription Only Medicine.

Summary Table of Changes