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Circonyl

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Indications:

Treatment of uncomplicated Plasmodium falciparum malaria.

Contraindications:

Blackwater fever; pregnancy (except Qualaquin ); hypersensitivity to any component of the product; G-6-PD deficiency; history of thrombocytopenia; optic neuritis; tinnitus. Qualaquin Prolonged QT interval; myasthenia gravis.

Adverse reactions:

Cardiovascular Angina, atrioventricular block, bradycardia, cardiac arrest, chest pain, disturbances in cardiac rhythm or conduction, hypotension, irregular rhythm, nodal escape beats, palpitations, postural hypotension, QT prolongation, syncope, tachycardia, torsades de pointes, unifocal premature ventricular contractions, U waves, vasodilation, ventricular tachycardia. CNS Acute dystonic reaction, aphasia, apprehension, ataxia, altered mental status, asthenia, coma, confusion, disorientation, dizziness, headache, restlessness, seizures, suicide, tremor, vertigo. Dermatologic Acrinal necrosis, allergic contact dermatitis, bullous dermatitis, cutaneous rash (including popular, scarlatinal, or urticarial rashes), cutaneous vasculitis, erythema multiforme, exfoliative dermatitis, facial edema, fixed drug eruption, photosensitivity reactions, pruritus, Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN), urticaria. EENT Blindness, burred vision, deafness, diminished visual fields, diplopia, disturbances in color perception, fixed papillary dilatation, hearing impairment, night blindness, optic neuritis, photophobia, sudden loss of vision, tinnitus, visual impairment (including blurred vision with scotomata). GI Abdominal pain, diarrhea, epigastric pain, esophagitis, gastric irritation, nausea, vomiting. Genitourinary Acute interstitial nephritis, hemoglobinuria, renal failure, renal impairment. Hematologic-Lymphatic Acute hemolysis, agranulocytosis, aplastic anemia, blackwater fever, coagulopathy, DIS, ecchymosis, hemolytic anemia, hemolytic uremic syndrome, hemorrhage, hypoprothrombinemia, idiopathic thrombocytopenic purpura, leukopenia, lupus anticoagulant, neutropenia, pancytopenia, petechiae, thrombocytopenia, thrombotic thrombocytopenic purpura. Hepatic Abnormal LFTs, granulomatous hepatitis, hepatitis, jaundice. Hypersensitivity Hypersensitivity reactions. Metabolic-Nutritional Anorexia; hypoglycemia. Musculoskeletal Myalgia, muscle weakness. Respiratory Asthma, dyspnea, pulmonary edema. Miscellaneous Chills, fever, flushing, lupus-like syndrome, sweating.

Interactions:

Aluminum/Magnesium-containing antacids Causes delayed or decreased quinine absorption. Anticoagulants, oral (eg, warfarin) May cause depression of hepatic enzyme system that synthesizes vitamin K–dependent clotting factors and may enhance action of oral anticoagulants. Carbamazepine, phenobarbital Plasma concentrations of these drugs may be elevated, increasing the pharmacologic effects and risk of adverse reactions. Cimetidine, ranitidine May reduce quinine’s Cl and prolong its half-life. CYP1A2 substrates (aminophylline, theophylline) Plasma concentrations of these agents may be reduced, decreasing the efficacy. CYP2D6 (eg, debrisoquine, desipramine, dextromethorphan, flecainide, metoprolol, mexiletine, tolterodine) and CYP3A4 (eg, atorvastatin, zolpidem) substrates Quinine may inhibit the metabolism of these substrates, increasing the pharmacologic effects and risk of adverse reactions. Digoxin May cause increased digoxin serum concentration. Erythromycin, ketoconazole Quinine metabolism may be inhibited, increasing the risk of adverse reactions. Mefloquine May cause ECG abnormalities or cardiac arrest and may increase risk of convulsions. Do not use concurrently. Delay administration 12 h after last dose of quinine. Neuromuscular blocking agents May potentiate neuromuscular blockade and may result in respiratory difficulties. Phenobarbital, phenytoin, rifampin Quinine metabolism may be increased, reducing plasma concentrations and decreasing the efficacy. QT-prolonging drugs (eg, amiodarone, cisapride, disopyramide, dofetilide, halofantrine, levofloxacin, macrolide antibiotics [eg, clarithromycin, erythromycin], mefloquine, paroxetine, pimozide, procainamide, propafenone, quinidine, sotalol) Risk of life-threatening arrhythmias, including torsades de pointes, may be increased; coadministration of quinine is not recommended. Tetracycline Quinine plasma concentrations may be elevated, increasing the risk of adverse reactions. Urinary alkalinizers May increase quinine serum concentrations and potentiate toxicity.

Warnings:

Monitor Monitor patients with hepatic impairment for adverse reactions. Pregnancy Category X . Qualaquin Category C . Lactation Excreted in breast milk. Children Safety and efficacy not established in children younger than 16 yr of age. Elderly Studies did not include sufficient numbers of subjects older than 65 yr of age to determine if they respond differently from younger subjects. Hypersensitivity Serious hypersensitivity reactions, including anaphylactic and anaphylactoid reactions, angioedema, Stevens-Johnson syndrome, and TEN, have been reported. Renal Function Adjust dose in patients with severe chronic renal failure. Effects of mild and moderate renal impairment are not known. Hepatic Function Use with caution. Atrial fibrillation Use with caution. Cardiac disease Patients with cardiac arrhythmias may have exacerbation of symptoms with quinine, which acts similarly to quinidine. May cause cardiotoxicity. In patients with atrial fibrillation, quinine requires the same precautions as for quinidine. Hemolysis Has been associated with G-6-PD deficiency. Discontinue immediately if hemolysis appears. Hypoglycemia Release of insulin from the pancreas may be stimulated, increasing the risk of hypoglycemia, especially in pregnant women. Interrupted therapy May predispose patients to serious complications of blackwater fever, including anemia, RBC destruction, and renal failure. Myasthenia gravis Muscle weakness may be exacerbated. QT prolongation Unpredictable, serious, and life-threatening hypersensitivity reactions may occur. Potentially fatal cardiac arrhythmias, including torsades de pointes and ventricular fibrillation. Avoid use in patients with known QT interval prolongation or conditions know to prolong the QT interval (eg, bradycardia, certain cardiac conditions, uncorrected hypokalemia).

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