Chinina chloride Galenica Senese: detailed information

Patient Information Leaflet: Information for the User

Chinina cloridrato GALENICA SENESE 500 mg/2 ml concentrate for solution for infusion

Chinina cloridrato
Generic Medicine
Please read this leaflet carefully before you use this medicine because it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor or nurse.
If you experience any side effects, including those not listed in this leaflet, contact your doctor or nurse. See section 4.

Contents of this leaflet:

What CHININA CLORIDRATO GALENICA SENESE is and what it is used for
What you need to know before using CHININA CLORIDRATO GALENICA SENESE
How to use CHININA CLORIDRATO GALENICA SENESE
Possible side effects
How to store CHININA CLORIDRATO GALENICA SENESE
Contents of the pack and other information

1. What CHININA CLORIDRATO GALENICA SENESE is and what it is used for

CHININA CLORIDRATO GALENICA SENESE contains quinine, a medicine used to treat
malaria, an illness caused by parasites (protozoa of the genus Plasmodium).
This medicine is used for:

The treatment of severe cases of malaria (due to strains of Plasmodium falciparum);
The treatment of other types of severe infections (mixed infections from unknown species).

2. What you need to know before using CHININA CLORIDRATO GALENICA SENESE

Do not use CHININA CLORIDRATO GALENICA SENESE

if you are allergic to quinine, to similar medicines (quinine derivatives), or to any of the other ingredients of this medicine (listed in section 6): in this regard, cross-reactions between quinine and quinidine, used in the treatment of heart problems (cardiac arrhythmias), should be considered;
if you have myasthenia gravis, a disease causing muscle weakness and fatigue: quinine may worsen muscle weakness;
if you have low levels of a particular substance (the enzyme glucose-6-phosphate dehydrogenase), because serious blood problems may occur (hemolysis and hemolytic anemia);
if you have a heart condition (prolongation of the QT interval);
if you have eye problems (optic neuritis);
if you have previously experienced allergic reactions (hypersensitivity) after using this medicine; such reactions include, sometimes severe, blood and kidney problems (thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, thrombocytopenia, hemoglobinuric fever with acute intravascular hemolysis, hemoglobinuria and hemoglobinemia);
If you are being treated with the following medicines: amiodarone, astemizole, terfenadine, thioridazine, pimozide, droperidol, halofantrine, cisapride, levacetylmethadol (see section "Other medicines and CHININA CLORIDRATO GALENICA SENESE").

Warnings and precautions
Consult your doctor or nurse before using CHININA CLORIDRATO GALENICA SENESE.
This medicine will be administered to you with great caution if you have:

serious heart problems such as cardiac rhythm disturbances (atrial fibrillation, conduction defects, blocks);
breathing difficulties (asthma);
presence of hemoglobin in the urine (hemoglobinuria);
inflammation of the optic nerve (optic neuritis);
a disease characterized by ringing in the ears (tinnitus);
liver or kidney problems (hepatic or renal insufficiency), as these may alter the effects and elimination of the medicine.

During administration of CHININA CLORIDRATO GALENICA SENESE, the following may occur:

a drastic reduction in blood glucose levels, sometimes even fatal (severe hypoglycemia), due to increased production of a hormone called insulin, especially if you are pregnant or have severe and prolonged infections. For this reason, your blood glucose levels (glycemia) will be closely monitored; additionally, preventive administration of a glucose-containing medicine (glucose solution) may be necessary.
a rare and serious allergic reaction (hypersensitivity reaction) called hemoglobinuric fever, characterized by severe blood cell problems (massive destruction of red blood cells (hemolysis), high levels of hemoglobin in blood plasma (hemoglobinemia), and presence of hemoglobin in urine (hemoglobinuria), which may cause serious kidney problems (renal failure), even fatal. This condition occurs more frequently in pregnant women.

Administration of CHININA CLORIDRATO GALENICA SENESE together with mefloquine may increase the risk of involuntary muscle contractions (convulsions) and disturbances in heart rhythm (arrhythmias) (see section "Other medicines and CHININA CLORIDRATO GALENICA SENESE").

Other medicines and CHININA CLORIDRATO GALENICA SENESE
Inform your doctor or nurse if you are taking, have recently taken, or might take any other medicine.
The use of this medicine must be avoided if you are taking the following medicines, as they may increase the risk of ventricular arrhythmias:

amiodarone, used to treat heart disorders (cardiac arrhythmias);
astemizole and terfenadine, used as antihistamines;
thioridazine, pimozide, droperidol, used to treat mental illnesses;
halofantrine, used to treat malaria;
cisapride, used for stomach (gastroesophageal reflux) and intestinal problems;
levacetylmethadol, used to treat opioid dependence.

This medicine will be administered to you with great caution if you are taking the following medicines, as quinine hydrochloride may interfere with these medicines:

mefloquine, used to treat malaria;
erythromycin, troleandomycin, and rifampicin, used to treat bacterial infections (antibiotics);
saquinavir and ritonavir, antiviral medicines used to treat AIDS;
ketoconazole, used to treat fungal infections;
cimetidine and ranitidine, used to regulate gastric acid secretion (gastric ulcer);
carbamazepine, phenobarbital, and phenytoin, used to treat a disease characterized by loss of consciousness and uncontrolled muscle movements (epilepsy);
theophylline and aminophylline, used for respiratory problems;
atorvastatin, used to lower blood cholesterol levels;
desipramine, used to treat depression;
antacids containing aluminium and/or magnesium, used for stomach acidity;
acetazolamide, a diuretic medicine;
sodium bicarbonate, an alkalizing agent;
urine acidifying medicines, used for kidney problems;
digoxin, used for heart problems (congestive heart failure);
iloperidone and pimozide, used to treat mental illnesses;
lapatinib, used to treat breast cancer;
sunitinib, used to treat kidney cancer;
quinidine and flecainide, used to treat heart disorders (cardiac arrhythmias);
pancuronium, succinylcholine, and tubocurarine, used for muscle relaxation during surgery;
cyclosporine, used to reduce the risk of transplant rejection;
metformin, used for diabetes;
warfarin and similar medicines (oral anticoagulants), heparin, used for blood clotting disorders;
methadone, used in the treatment of drug addiction.

Interference with laboratory tests
During administration of CHININA CLORIDRATO GALENICA SENESE, changes in the following laboratory parameters may occur:

urine color, which may appear darkened;
measurement of quinidine in blood, which may show a false increase;
ESR (erythrocyte sedimentation rate), which may show a false decrease;
determination of certain substances in urine (17-hydroxycorticosteroids, 17-ketosteroids, and catecholamines), which may show a false increase.

CHININA CLORIDRATO GALENICA SENESE with food and drinks
During administration of CHININA CLORIDRATO GALENICA SENESE, do not consume grapefruit juice, as it may increase its toxicity.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor or nurse before this medicine is administered to you.

Pregnancy
Avoid taking this medicine during pregnancy, as it may cause serious harm both to you, such as decreased blood glucose levels (hypoglycemia) or a rare and serious allergic reaction characterized by severe blood cell problems (hemoglobinuric fever), and to the fetus, particularly hearing problems that may lead to deafness (hypoplasia of the acoustic nerve).
In cases of absolute necessity, your doctor will evaluate whether this medicine can be administered, weighing the benefit to you against the risk to your baby.

Breastfeeding
Quinine passes into breast milk. Avoid taking this medicine while breastfeeding, as it may cause serious blood disorders in the newborn (severe hemolysis).

Driving and using machines
After administration of this medicine, visual disturbances may occur. If this happens, avoid driving vehicles or operating machinery.

3. How to use CHININA CHLORIDE GALENICA SENESE

This medicine will be administered to you by specialized healthcare personnel.
If you have any doubts, consult your doctor or nurse.
The doctor will determine the dose according to your age and health condition, both in adults and children.
CHININA CHLORIDE GALENICA SENESE will be administered by slow intravenous infusion; otherwise, a sudden and severe drop in blood pressure (severe hypotension) may occur.

If you use more CHININA CHLORIDE GALENICA SENESE than you should
Since this medicine will be administered by specialized personnel, it is unlikely that you will receive an excessive dose.
However, if an overdose of this medicine is administered, the following symptoms may occur:

vision problems (visual disturbances and impaired color perception, blurred vision, blindness);
reduction in blood glucose levels (hypoglycemia);
serious heart and circulatory problems (cardiac arrhythmia, drop in blood pressure (hypotension), circulatory collapse, sinus tachycardia, PR interval prolongation, T wave inversion, bundle branch block and QT interval prolongation, worsening of myocardial depression due to reduced coronary perfusion, cardiogenic shock and circulatory collapse, ventricular arrhythmia, ventricular tachycardia, ventricular fibrillation, idioventricular rhythm, torsades de pointes, bradycardia and atrioventricular block, reduced rate of depolarization and conduction, increased action potential and refractory period);
drowsiness, loss of consciousness, loss of muscle coordination (ataxia), and uncontrolled muscle movements (convulsions), coma, death;
breathing problems (respiratory depression, pulmonary edema, and adult respiratory distress syndrome).

Administration of CHININA CHLORIDE GALENICA SENESE, even at therapeutic doses, may lead to a clinical condition known as cinchonism, which in mild forms is characterized by hearing problems (tinnitus, deafness), headache (cephalalgia), nausea, vision problems (blurred vision, scotomas, photophobia, altered color perception), dizziness, difficulty breathing (dyspnea), sweating, and fever. With continued treatment or after high single doses, additional symptoms may appear, including gastrointestinal problems (vomiting, abdominal pain, diarrhea), heart problems (sinus arrest, junctional rhythm, atrioventricular block, ventricular tachycardia and fibrillation), skin reactions (hot and flushed skin, skin rashes), respiratory depression, mental confusion, involuntary muscle contractions (convulsions), and worsening of visual disturbances (including temporary blindness).

In case of accidental ingestion/overdose of CHININA CHLORIDE GALENICA SENESE, contact your doctor immediately or go to the nearest hospital.
If you have any doubts about the use of this medicine, consult your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Frequency not known (frequency cannot be estimated from the available data)

heart problems, even serious ones (angina pectoris, torsades de pointes, ventricular arrhythmias, atrial fibrillation, atrio-ventricular conduction disturbances) and problems with blood circulation;
a sudden and severe drop in blood pressure (severe hypotension), particularly after rapid infusion;
skin disorders (erythema multiforme, skin rashes, facial oedema, transient skin redness, itching, photosensitivity, excessive sweating, toxic epidermal necrolysis also known as Lyell's syndrome);
vasculitis;
thrombotic thrombocytopenic purpura;
reduction in blood glucose levels (hypoglycaemia) (see section “Warnings and precautions”);
difficulty in swallowing (dysphagia), stomach (epigastric) and abdominal pain, nausea and vomiting;
reduction in the number of blood cells (pancytopenia, thrombocytopenia, leucopenia, agranulocytosis), inherited blood disorder (porphyria), destruction of red blood cells (haemolysis),

blood clotting disorders (coagulopathy, disseminated intravascular coagulation),
deficiency of a blood substance called prothrombin (hypoprothrombinaemia), a condition characterised
by problems in oxygen transport in the blood (methaemoglobinaemia), reduced bone marrow function (myelosuppression);

severe liver damage (cholestatic hepatitis and granulomatous hepatitis);
immune system disorders*, allergic reactions (hypersensitivity reactions), itching and skin redness (urticarial, papular, scarlatiniform skin rashes), swelling (angioedema, especially of the face), skin sensitivity to light (photosensitivity);
diseases of the immune system (lupus anticoagulant);
muscle weakness and fatigue (myasthenia gravis);
nervous system disorders, restlessness, confusion, headache (migraine, cephalalgia), agitation, anxiety, loss of consciousness (syncope), dizziness, involuntary muscle contractions (seizures);
vision problems (abnormal colour vision, blurred vision, diplopia, nystagmus, photophobia, scotoma, visual disturbances, narrowing of the visual field, night blindness, temporary blindness, mydriasis and, rarely, blindness);
hearing problems (ototoxicity, tinnitus, hypoacusis, and hearing loss, usually reversible);
kidney problems, even severe ones (haemoglobinuric fever, haemolytic-uraemic syndrome, interstitial nephritis, nephrotoxicity, haemoglobinuria, acute renal failure)* (see section “Warnings and precautions”);
breathing problems (asthma, pulmonary infiltrate, respiratory depression, dyspnoea)*;
superficial inflammation of the veins (thrombophlebitis) at the site of administration;
cinchonism, a condition characterised by various symptoms affecting vision and hearing, heart, stomach and intestine, breathing difficulties, and nervous system problems (see section “If you use more CHININA CLORIDRATO GALENICA SENESE than you should”);
reactions at the site of administration – quinine is a highly irritating substance: thrombophlebitis may occur after intravenous infusion.
*Hypersensitivity reactions - The most frequently observed reaction is skin redness accompanied by intense generalised itching. Other less frequent reactions include: skin rashes (urticarial, papular, scarlatiniform), angioedema (especially of the face) and asthma, haematological alterations, acute renal failure, fever, haemoglobinuric fever.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist.
You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store CHININA CHLORIDE GALENICA SENESE

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the packaging after "Exp". The expiry date refers to the last day of that month.
Store this medicine in its original packaging and protect it from light. Use this medicine immediately after opening the vial. After dilution, the medicine must be used immediately; any remaining solution must be discarded.
This medicine in solution is a clear, colourless or slightly straw-coloured liquid.
Do not use if the appearance has changed.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Package contents and other information

What CHININA CLORIDRATO GALENICA SENESE 500 mg/2 ml concentrate for
solution for infusion contains

The active substance is chinina cloridrato. One 2 ml vial contains 500 mg of chinina cloridrato.
The other component is water for injections.

Description of the appearance of CHININA CLORIDRATO GALENICA SENESE and contents of the
pack Pack containing 1 or 5 glass vials of 2 ml.
Marketing Authorization Holder and Manufacturer
Industria Farmaceutica Galenica Senese S.r.l. - Via Cassia Nord, 351- 53014 Monteroni d'Arbia (SI) - Italy

The following information is intended exclusively for physicians or healthcare professionals

Dosage and administration
The dosage of quinine dihydrochloride is calculated according to body weight in both adults and children.
The initial loading dose is 20 mg/kg (up to a maximum dose of 1.4 g) infused over 4 hours.
The loading dose must not be administered to patients who have taken quinine (or quinidine) or mefloquine within the preceding 24 hours.
After an interval of 8–12 hours, treatment continues with a maintenance dose of 10 mg/kg (up to a maximum dose of 700 mg) infused over 4 hours, repeated at 8–12 hour intervals until the patient's condition allows oral administration.
The maintenance dose should be reduced to 5–7 mg/kg in patients with renal impairment or when parenteral treatment is required for more than 48 hours.
In intensive care units, the loading dose may alternatively be administered as 7 mg/kg infused over 30 minutes, immediately followed by 10 mg/kg over 4 hours.
After an interval of 8–12 hours, maintenance dosing continues as described.
The concentrate must not be administered undiluted but only after appropriate dilution with at least 10 volumes of physiological saline solution. Administer only by slow intravenous infusion. Rapid infusion may cause severe hypotension.
Parenteral administration should be replaced by oral administration as soon as the patient's condition permits.
Quinine administration must be discontinued immediately in case of haemolysis.
Any unused diluted solution must not be reused and should be discarded.

Combinations requiring special precautions or dosage adjustments
Urinary acidifiers – Increased renal clearance, reduced half-life and plasma concentration of quinine.
Urinary alkalinizers – (e.g. acetazolamide, sodium bicarbonate) Reduced clearance of quinine, increased half-life and plasma concentration of quinine.
Antimalarials – Mefloquine: increased risk of seizures and arrhythmias; this does not preclude the use of intravenous quinine in severe cases (see sections 4.2 and 4.4).
Peptic ulcer drugs – Cimetidine: inhibits metabolism and increases plasma concentration of quinine.
Antiarrhythmics – Increased plasma concentration of flecainide.
Anticoagulants – Inhibition of vitamin K-dependent coagulation factors, resulting in enhanced activity of warfarin and other vitamin K antagonists.
Cardiac glycosides – Increased plasma concentration of digoxin.
Muscle relaxants – (e.g. pancuronium, succinylcholine, tubocurarine) Enhanced muscle relaxant effect and increased risk of respiratory muscle paralysis.
Urinary acidification increases renal excretion of quinine, but in the presence of haemoglobinuria increases the risk of renal obstruction.

Treatment of overdose symptoms
Most reactions are dose-related; however, some reactions may be idiosyncratic, with variability among patients in response to quinine effects. A lethal dose of quinine has not yet been established; however, fatal outcomes have been reported following ingestion of 2–8 grams in adults.
Quinine, like quinidine, has class I antiarrhythmic properties. Quinine cardiotoxicity is due to its negative inotropic effect and its effect on cardiac conduction, causing reduced depolarization and conduction rates, and increased action potential and refractory period.
ECG changes observed in quinine overdose include sinus tachycardia, PR interval prolongation, T-wave inversion, bundle branch block and QT interval prolongation.
Due to its alpha-blocking activity, quinine may cause hypotension and worsen myocardial depression by reducing coronary perfusion.
Quinine is rapidly absorbed, and attempts to remove it from the stomach via gastric lavage may not be effective. Multiple doses of activated charcoal have reduced plasma concentrations of quinine. Forced acidic diuresis, haemodialysis, charcoal hemoperfusion and plasma exchange have not been significantly effective in enhancing quinine elimination.
Urinary acidification increases renal excretion of quinine, but in the presence of haemoglobinuria increases the risk of renal obstruction.

Incompatibilities
The medicinal product must not be mixed with alkalis.

For further information, consult the Summary of Product Characteristics.

Chinina chloride Galenica Senese