Quinine hydrochloride S.A.L.F.: detailed information

Package leaflet: Information for the user

Chinina cloridrato S.A.L.F. 500 mg/2 ml concentrate for solution for infusion

Quinine dihydrochloride
Generic Medicine
Read all of this leaflet carefully before using 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 get any side effects, including those not listed in this leaflet, tell your doctor or nurse. See section 4.

Contents of this leaflet:

What CHININA CLORIDRATO S.A.L.F. is and what it is used for
What you need to know before using CHININA CLORIDRATO S.A.L.F.
How to use CHININA CLORIDRATO S.A.L.F.
Possible side effects
How to store CHININA CLORIDRATO S.A.L.F.
Contents of the pack and other information

1. What CHININA CLORIDRATO S.A.L.F. is and what it is used for

CHININA CLORIDRATO S.A.L.F. contains the active substance quinine, a medicine used to combat 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 S.A.L.F.

Do not use CHININA CLORIDRATO S.A.L.F.

if you are allergic to quinine or to any of the other ingredients of this medicine (listed in section 6): in this regard, it is important to consider the possibility of cross-reactions between quinine and quinidine, used in the treatment of heart problems (cardiac arrhythmias);
if you suffer from myasthenia gravis, a disease causing muscle weakness and fatigue: quinine may worsen muscle weakness;
if levels are low of a particular substance (the enzyme glucose-6-phosphate-dehydrogenase) because serious blood problems may occur (hemolysis and hemolytic anemia);
if you suffer from a heart problem called long QT syndrome;
if you suffer from eye problems (optic neuritis);
if you have previously experienced allergic reactions (hypersensitivity) after using this medicine; such reactions involve, sometimes serious, 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, unless otherwise prescribed by your doctor (see section Other medicines and CHININA CLORIDRATO S.A.L.F.)

Warnings and precautions
Talk to your doctor or nurse before using CHININA CLORIDRATO S.A.L.F.
This medicine will be administered to you with great caution if you suffer from:

serious heart problems such as disturbances in heart rhythm (atrial fibrillation, conduction defects, blocks);
breathing difficulties (asthma);
a blood disorder called 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).

During administration of CHININA CLORIDRATO S.A.L.F., 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-based medicine (glucose solution) may be necessary.
a rare and serious allergic reaction (hypersensitivity reaction) called hemoglobinuric fever, characterized by serious problems with blood cells (massive hemolysis, hemoglobinemia and hemoglobinuria), which may cause severe kidney problems (renal failure), even fatal. This condition occurs more frequently in pregnant women.

The administration of CHININA CLORIDRATO S.A.L.F. together with mefloquine may increase the risk of involuntary muscle contractions (seizures) and disturbances in heart rhythm (arrhythmias). (see section Other medicines and CHININA CLORIDRATO S.A.L.F.)
During administration of CHININA CLORIDRATO S.A.L.F., changes in the following laboratory test parameters may occur:

urine color, which may appear darkened;
quinidine blood levels, 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.

Other medicines and CHININA CLORIDRATO S.A.L.F.
Inform your doctor or nurse if you are taking, have recently taken, or might take any other medicine.
The administration of this medicine is not recommended if you are taking the following medicines:

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 problems (gastroesophageal reflux);
levacetylmethadol, used to treat opioid dependence.

This medicine will be administered to you with great caution if you are taking the following medicines:

mefloquine, used to treat malaria;
erythromycin, troleandomycin, and rifampicin, used to treat bacterial infections (antibiotics);
saquinavir and ritonavir, used to treat AIDS;
ketoconazole, used to treat fungal infections;
cimetidine and ranitidine, used for stomach problems (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 breathing problems;
atorvastatin, used to treat high blood cholesterol;
desipramine, used to treat depression;
antacid medicines containing aluminium and/or magnesium, used for stomach acidity;
acetazolamide, sodium bicarbonate, used for kidney problems;
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.

CHININA CLORIDRATO S.A.L.F. with food and drinks
During administration of CHININA CLORIDRATO S.A.L.F., do not consume grapefruit juice, as it may increase its toxicity.

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

Pregnancy
Avoid taking this medicine if you are pregnant, 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 auditory nerve).
Your doctor will assess whether this medicine can be administered to you, weighing the benefit to you against the risk to the fetus.

Breastfeeding
Avoid taking this medicine if you are 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 CLORIDRATO S.A.L.F.

This medicine will be administered to you by trained 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 CLORIDRATO S.A.L.F. will be administered by slow intravenous infusion;
otherwise, a sudden drop in blood pressure (severe hypotension) may occur.
If you use more CHININA CLORIDRATO S.A.L.F. than you should
Since this medicine will be administered by trained medical personnel, it is unlikely that you will receive an excessive dose.
However, if an excessive dose of this medicine is administered, the following symptoms may occur:

vision problems (visual disturbances and impaired color perception, blurred vision, blindness);
decreased blood glucose levels (hypoglycemia);
serious heart and circulatory problems (cardiac arrhythmia, hypotension, circulatory collapse, sinus tachycardia, prolongation of the PR interval, 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), uncontrolled muscle movements (convulsions), coma, death;
respiratory problems (respiratory depression, pulmonary edema, and adult respiratory distress syndrome).

Administration of CHININA CLORIDRATO S.A.L.F., even at therapeutic doses, may lead to a clinical condition known as cinchonism. In mild forms, this is characterized by hearing disturbances (tinnitus), headache (cephalalgia), nausea, visual disturbances (blurred vision, scotomata, photophobia, altered color perception), dizziness, difficulty breathing (dyspnea), and fever. With continued treatment or after high single doses, additional symptoms may appear, including gastrointestinal disturbances (vomiting, abdominal pain, diarrhea), cardiac effects (sinus arrest, junctional rhythm, atrioventricular block, ventricular tachycardia and fibrillation), skin reactions (warm, flushed skin, skin rashes), respiratory depression, mental confusion, involuntary muscle contractions (convulsions), and worsening of visual disturbances (including temporary blindness).

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 everyone experiences them.
Frequency not known (frequency cannot be estimated from the available data)

heart problems, even severe ones (angina pectoris, torsades de pointes, ventricular arrhythmias, atrial fibrillation, atrioventricular conduction disturbances) and blood circulation problems (vasculitis);
a drastic decrease in blood pressure (severe hypotension);
skin disorders (erythema multiforme, skin rashes, facial edema, angioedema, transient skin redness, pruritus, photosensitivity, excessive sweating, toxic epidermal necrolysis also known as Lyell's syndrome, thrombotic thrombocytopenic purpura);
reduced levels of glucose in the blood (hypoglycaemia);
difficulty swallowing (dysphagia), stomach (epigastric) and abdominal pain, nausea and vomiting;
reduced number of blood cells (pancytopenia, thrombocytopenia, leucopenia, agranulocytosis), inherited blood disorders (porphyria), destruction of red blood cells (haemolysis), blood coagulation problems (coagulopathy, disseminated intravascular coagulation), deficiency of a blood substance called prothrombin (hypoprothrombinaemia), a condition characterised by impaired 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 rashes), swelling (angioedema, especially of the face), skin sensitivity to light (photosensitivity), immune system disorders (lupus anticoagulant);
muscle weakness and fatigue (myasthenia gravis), nervous system disorders, anxiety, confusion, headache (migraine, cephalalgia), agitation, restlessness, 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 generally reversible deafness);
kidney problems, even severe ones (haemoglobinuric fever, haemolytic-uraemic syndrome, interstitial nephritis, nephrotoxicity, haemoglobinuria, acute renal failure);
breathing problems (asthma, pulmonary infiltrate, respiratory depression, dyspnoea);
superficial inflammation of veins (thrombophlebitis) at the site of administration;
cinchonism, a condition characterised by various symptoms affecting vision and hearing, heart, stomach and intestines, breathing difficulties, and nervous system problems (See section “If you use more CHININA CLORIDRATO S.A.L.F. than you should”)

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or nurse.
You can also report side effects directly via the national reporting system at 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 CLORIDRATO S.A.L.F.

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after "Exp". The expiry date refers to the last day of that month.
Store this medicine in the original packaging to protect it from light.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Chinina cloridrato S.A.L.F. 500 mg/2 ml concentrate for infusion solution contains

The active substance is quinine dihydrochloride. Each 2 ml vial contains 500 mg of quinine dihydrochloride.
The other component is water for injections.

Description of the appearance of CHININA CLORIDRATO S.A.L.F. and pack contents
Pack containing 10 glass vials of 2 ml each.
Marketing Authorization Holder and Manufacturer
S.A.L.F. S.p.A. Laboratorio Farmacologico - Via Marconi, 2 - Cenate Sotto (BG) - Tel. 035 - 940097

The following information is intended exclusively for physicians or healthcare professionals

Dosage and administration:
The dosage of chloroquine hydrochloride 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 intervals of 8–12 hours 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 a dose of 10 mg/kg over 4 hours.
After an interval of 8–12 hours, the maintenance dose 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.
Any unused diluted solution must not be reused and should be discarded.

Management of overdose symptoms:
Most reactions are dose-related; however, some reactions may be idiosyncratic, with variability among patients in response to the effects of quinine. A lethal dose of quinine has not yet been identified; however, fatal outcomes have been reported following ingestion of 2–8 grams in adults.
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 acid diuresis, hemodialysis, hemoperfusion with a charcoal column, and plasma exchange have not been significantly effective in increasing quinine elimination.
Acidification of urine increases renal excretion of quinine, but in the presence of hemoglobinuria, it increases the risk of renal tubular obstruction.

Incompatibilities:
The medicinal product must not be mixed with alkalis.

Shelf life:
3 years when the packaging is intact.

Special precautions for storage:
Store in the original packaging to protect the medicinal product from light. No special storage conditions regarding temperature are required.
The solution should be clear, colourless or slightly yellowish, and free from visible particles.

For further information, consult the Summary of Product Characteristics.

Quinine hydrochloride S.A.L.F.