Quinine hydrochloride Agenzia Industrie Difesa

CHININA CHLORIDE AGENCY INDUSTRIE DIFESA
500 mg/2 ml
QUALITATIVE AND QUANTITATIVE COMPOSITION
Each vial contains
Active substance:
Quinine dihydrochloride 500 mg
Excipients:
Water for injections q.s. to 2 ml
PHARMACEUTICAL FORM
Concentrate for solution for infusion.
THERAPEUTIC PHARMACOLOGICAL CATEGORY
Antiprotozoal chemotherapeutic agents. Antimalarials.
MARKETING AUTHORIZATION HOLDER
Agenzia Industrie Difesa - Stabilimento Chimico Farmaceutico Militare
via XX Settembre 123/A
00187 Rome
MANUFACTURED AND CONTROLLED BY
Agenzia Industrie Difesa - Stabilimento Chimico Farmaceutico Militare
via Reginaldo Giuliani, 201
50141 Florence
or by
S.A.L.F. SpA Via Marconi, 2 - 24069 Cenate Sotto (Bergamo)
and by
BIOLAB SpA
Via Bruno Buozzi, 2 – 20090 Vimodrone (Milan)
for sterility control of the finished product
THERAPEUTIC INDICATIONS
Treatment of severe cases of malaria due to Plasmodium falciparum, mixed infection, or infection by unknown species.
Parenteral administration should be replaced by oral administration as soon as the patient's condition allows.
CONTRAINDICATIONS
Quinine should be administered with caution in cases of suspected or confirmed hypersensitivity to quinine or similar drugs (e.g., quinidine), especially in the presence of cutaneous, visual, auditory, or angioedematous reactions; in patients with severe myasthenia gravis; and in patients with glucose-6-phosphate dehydrogenase deficiency.
Concomitant use with amiodarone, astemizole, terfenadine, thioridazine, pimozide, droperidol, halofantrine, cisapride, or levacetilmetadol is contraindicated.
PRECAUTIONS FOR USE
Discontinue administration if severe symptoms of cinchonism (see "Undesirable effects") or hemolysis occur. Avoid rapid infusion due to the risk of severe hypotension. Avoid concomitant use of mefloquine with quinine due to increased risk of seizures and arrhythmias. Mefloquine intake should occur at least 12 hours after the last dose of quinine; conversely, quinine infusion after mefloquine may be dangerous due to the long half-life of mefloquine.
DRUG INTERACTIONS AND OTHER INTERACTIONS
The following pharmacological interactions of quinine are known:

• Urinary acidifiers and alkalinizers: accelerate or slow down, respectively, the clearance of quinine;
• Antimalarials: mefloquine increases the risk of arrhythmias and seizures;
• Muscle relaxants: increased muscle relaxant effect and consequent risk of respiratory muscle impairment;
• Cimetidine: reduces renal clearance of quinine;
• Cardiac glycosides: increased plasma levels of digoxin;
• Anticoagulants: inhibition of vitamin K-dependent coagulation factors, leading to enhanced activity of warfarin and other vitamin K antagonists.

Quinine may darken the color of urine and interfere with certain tests measuring urinary alkaloids and steroids, as well as plasma catecholamines.
SPECIAL WARNINGS
Hypersensitivity to quinine most commonly manifests as skin redness and intense generalized pruritus. Cinchonism (see "Undesirable effects") and hemoglobinuric fever ("blackwater fever": a triad comprising massive hemolysis, hemoglobinemia, and hemoglobinuria) may occur. The latter is a rare hypersensitivity reaction that can lead to renal failure, potentially fatal, and is more frequent in pregnant women.
Hemolysis, mild or moderate, may occur in subjects with glucose-6-phosphate dehydrogenase deficiency.
Quinine may cause severe, potentially life-threatening hypoglycemia due to stimulation of insulin secretion, particularly during pregnancy or in severe and prolonged infections. Blood glucose levels should be checked before administration and carefully monitored during treatment; preventive administration of glucose solution may be advisable.
Due to the potential exacerbation of postural hypotension associated with malaria by quinine, it is advisable to avoid transporting pediatric patients in an upright position after drug infusion.
Administration during pregnancy requires constant monitoring of blood glucose. Quinine is excreted in breast milk at concentrations lower than plasma levels; in infants with glucose-6-phosphate dehydrogenase deficiency, it may cause severe hemolysis.
DOSAGE, METHOD AND DURATION OF ADMINISTRATION
Before administration, the concentrate must be appropriately diluted with at least 10 volumes of physiological saline solution.
The initial loading dose is 20 mg/kg (up to a maximum dose of 1.4 g) infused over 4 hours.
After an interval of 8–12 hours, treatment continues with a maintenance dose of 10 mg/kg (up to a maximum of 700 mg) infused over 4 hours, repeated every 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 10 mg/kg over 4 hours.
After an 8–12 hour interval, the maintenance dose proceeds as described.
Antimalarial therapy lasts from 3 to 7 days, depending on the geographical resistance profile of the parasite.
During infusion, monitor arterial pressure, ECG trace (optional in non-cardiac patients), and blood glucose. If the pharmacologically corrected QT interval prolongs by more than 25%, the infusion rate should be slowed. Administration should be suspended in case of severe complications such as hypoglycemia, hypotension, or ECG changes.
OVERDOSAGE
Quinine overdose may cause cinchonism (see "Undesirable effects") with complications; in particular, auditory and visual disturbances predominate, and blindness may develop in over 40% of cases, sometimes permanently. Cardiotoxic manifestations may occur, such as arrhythmias, atrioventricular block, and tachycardia, requiring discontinuation of infusion and therapeutic intervention. In cases of overdose toxicity, efforts should be made to maintain arterial pressure, renal function, and electrolyte balance; artificial ventilation may be necessary if required. Treat angioedema with adrenaline, corticosteroids, and antihistamines.
Methods to enhance elimination of absorbed drug include forced diuresis, hemodialysis, plasmapheresis, and peritoneal dialysis. Activated charcoal hemoperfusion is considered a clinically effective alternative. Urinary acidification increases renal excretion of quinine, but in the presence of hemoglobinuria, it increases the risk of renal tubular obstruction.
UNDESIRABLE EFFECTS
Repeated therapeutic doses or a single overdose of quinine may cause "cinchonism": a syndrome characterized by auditory disturbances (tinnitus, high-tone hearing loss, tinnitus), visual disturbances (photophobia, altered color perception, reduced visual field, scotomas, mydriasis), nausea and vomiting, headache. These symptoms may worsen (deafness, vertigo, blindness) and may be associated with cardiovascular effects (QT interval prolongation and other conduction disturbances), dermatological reactions (rashes, erythema, angioedema, hyperhidrosis), central nervous system effects (pruritus, hyper- and hypothermia, mental confusion, agitation, delirium, seizures), gastrointestinal complications (abdominal pain, diarrhea), and respiratory effects (dyspnea, asthma). After at least 24 hours of treatment, quinine may cause hyperinsulinemic hypoglycemia, particularly dangerous during pregnancy. Thrombophlebitis may occur after intravenous infusion, and deep intramuscular administration may cause sterile abscesses.
For drug hypersensitivity reactions, see "Special Warnings".
Patients are advised to inform their physician or pharmacist of any adverse effects, even if not listed here.
EXPIRY DATE
Warning: do not use the medicinal product after the expiry date stated on the packaging.
SPECIAL STORAGE PRECAUTIONS
Store the product protected from light.
Keep in the original packaging.
Use immediately and do not reuse the diluted solution.
Keep out of reach of children.
OF HEALTH: 09/05/2008