Furosemide_en

LAVOISIER FUROSEMIDE 20 mg/2 ml, injectable solution (IM-IV)
QUALITATIVE AND QUANTITATIVE COMPOSITION
WARNINGS AND SPECIAL PRECAUTIONS FOR USE
FUROSEMIDE.. 20.00 mg
Warnings
Accidental administration of furosemide may be conducive to hypovolemia associated with Sodium hydroxide …………. . s.q. pH 8.5 -9.5 Water for injectable preparations ……. . s.q. 2.00 ml In patients with hepatocellular insufficiency, treatment will be administered with great caution, undertaking strict electrolyte assessments because of the potential for hepatic encephalopathy (see Special warnings and special precautions for use). Discontinuance of treatment should then be PHARMACEUTICAL FORM
Cerebral vascular attack, often manifested by sudden hypertension is not an indication to antihypertensor treatment in emergency. Decision must be made depending on the presence of THERAPEUTIC INDICATIONS
short-term forecasting of life-threatening visceral complications. Hypertension associated with short-term forecasting of life-threatening visceral involvement (hypertensive emergency) particularly during: Special warnings and precautions for use
Each ampoule of this drug contains 7.35 mg of sodium (i.e. 3.68 mg of sodium per ml): to be taken left ventricular depression with pulmonary oedema. into account in patients with strict low-salt diet. Cardiologic emergencies: acute lung oedema, asystolic cardiac arrest. Severe sodium retention of cardiac, renal origin or in cirrhosis. Electrolyte balance
X-rays of lower urinary tract and ' wash out' test with Furosemide. Can be used in paediatric resuscitation. Natremia should be monitored prior to initiation of treatment, then at frequents intervals. Any diuretics therapy may in fact cause hyponatremia leading to complications sometimes to severe. POSOLOGY AND ADMINISTRATION
The decrease of natremia, initially asymptomatic, must be monitored routinely and even more often In hypertensive emergency, dose adjustment must be achieved so that fall in blood pressure does not in populations at risk like elderly patients, all the more malnourished, and in cirrhotics (see Adverse exceed 25% of initial level within an hour after onset of injection: a too abrupt fall in blood pressure may lead to myocardic, cerebral or renal ischaemia. The major risk of Loop diuretics is potassium depletion inducing hypokalaemia. Onset of Parenteral route: 2 to 3 ampoules daily by slow I.V. injection:
hypokalaemia (< 3.5 mmol/l) must be prevented in certain populations at risk like elderly patients Injection may be repeated for the treatment of acute lung oedema if a satisfactory response does and/or malnourished and/or polymedicated, cirrhotics with oedemas and ascites, patients with The switch to oral use can be achieved at any time of treatment 3 hours after an injection of Hypokalaemia increases digitalis cardiac toxicity and the risk of arrhythmias. In patients with prolonged QT interval in EKG caused by congenital or medication-related factors, Children
hypokalaemia increases onset of severe arrhythmia, especially torsades de pointe (TdP) potentially IV injection: 0.5 to 1 mg/kg daily.
life-threatening, especially when associated with bradycardia. In any case, kalaemia must be more often assessed. The first assessment of plasma potassium CONTRA-INDICATIONS
must be performed in the week after initiation of treatment. This drug should never be used in patients with: Mild hyperglysemic effect. However, in patients with diabetes, glycemia should be measured obstruction in urinary tract in patients with oliguria, Sodium depletion induced by Furosemide diminishes excretion of uric acid in urine. In patients with hyperuricemia may be more susceptible to gout attacks. Caution should be exercized in patients In patients hemodialysed and with severe renal impairment, hepatitis with progression of the disease and severe hepatocellular insufficiency will be excluded, as in associated renal insufficiency, the major Preparation of solutions
excretion path is through bile duct and accumulation may then occur. LAVOISIER FUROSEMIDE 20 mg/2 ml injectable solutions have a pH of 9 but no buffer value. A This drug is generally not recommended for use in pregnancy and in association with lithium or precipitate may form if Furosemide is introduced into a solution with a pH lower than 7. sultopride (see Interactions with other drugs and other forms of interactions). LAVOISIER FUROSEMIDE 20 mg/2 ml, injectable solution (IM-IV) Sportsmen
In congestive cardiac insufficiency, initiate very low dose of ACE inhibitors or inhibitor of Attention should be drawn to sportsmen that this speciality contains an active ingredient likely to induce angiotensin II, possibly after reducing the dose associated with hypokaliemiant diuretics. a positive reaction in the tests performed in anti-doping controls. In any case, renal function (dosage of creatininemia) must be monitored in the first weeks of treatment with ACE inhibitors or inhibitor of angiotensin II. Neonates and premature infants
In newborn and premature babies, high posology and prolonged treatment of Furosemide inducing a
♦ Drugs inducing torsades de pointe (TdP) (except sultopride) are: antiarrythmics drugs
risk of renal calcification, renal echographic monitoring is recommended. of class Ia (quinidine, hydroquinidine, disopyramide), and of class III (amiodarone,
sotalol, ibutilide, dofetilide), certain neuroleptics: phenothiazinic (chlorpromazine,
INTERACTIONS WITH OTHER DRUGS AND OTHER FORMS OF INTERACTIONS
cyamemazine, levomepromazine, thioridazine, trifluoperazine), benzamides (amisulpride,
CONTRAINDICATED INTERACTIONS
sulpiride, tiapride), butyrophenones (droperidol, haloperidol), other neuroleptics
(pimozide), others: bepridil, cisapride, diphemanil, erythromycine IV, mizolastine,
Lithium: increase of lithemia with signs of overdosage, like in low-sodium diet (diminished excretion
halofantrine, sparfloxacine, pentamidine, vincamine IV, moxifloxacine…
If coadministration is absolutely necessary, lithemia should be strictly monitored and dose Higher risk of ventricular arrhythmia, especially torsades de pointe (TdP) (hypokalaemia
is a predisposing factor).
♦ Sultopride: increased risk of ventricular arrhythymias, especially torsades de pointe (TdP)
Correct any hypokalaemia prior to use and clinical evaluation, (electrolyte) assessments and (hypokalaemia is a predisposing factor). Clinical evaluation, laboratory determinations and EKG monitoring. ♦ Metformin: lactic acidosis caused by metformin and triggered by possible functional renal
Associations to be used with precaution:
failure from diuretics especially Loop diuretics. ♦ NSAIDs (enteral route), including COX-2 selective inhibitors, acetylsalicylic acid…): acute
Metformine should not be used when creatinemia exceeds 15 mg/l (135 µmoles/l) for men and renal failure in patients at risk (elderly patients and/or dehydrated) with diminished glomerular filtration (inihibition of vasodilatator prostaglandins due to NSAIDs). Hydrate the patient, control of the renal function at initiation of treatment. ♦ Iodine contrast products: in case of dehydration by diuretics, increased risk of acute renal
insufficiency, especially when high dose of iodized contrast products are given. ♦ Other hypokalemiants: amphotericine B (IV injection), gluco and mineralocorticoids (enteral
Rehydration prior to use of iodized contrast product. route), tetracosactide, stimulant laxatives: higher risk of hypokalaemia (additional effect).
Kalaemia monitoring and correction, if need be: to be taken in consideration particularly with
♦ Baclofene: enhanced antihypertensor effect.
digitalis therapy. Administration of laxatives (not stimulative). Blood pressure monitoring and dose adjustment of antihypertensors if necessary. Digitalis: hypokalaemia increasing digitalis toxicity. Kalaemia monitoring and possibly EKG.
Associations requiring extreme caution:
♦ Hyperkalemiant diuretics (amiloride, canrenoate of potassium, spironolactone, triamterene):
♦ Corticoids, tetracosactide (enteral route) (except hydrocortisone used as adjuvant treatment
A rational combination therapy, useful in some patients should not exclude onset of hypokalaemia in Addison’s disease): diminished antihypertensor effect (sodium retention of corticoids). or, especially in patients with renal insufficiency and diabetes, of hyperkalemia. Kaliema monitoring, possibly EKG and, if need be, reconsider treatment strategies. ♦ Neuroleptics, imipraminic antidepressants (tricyclic): Antihypertensor effect and higher
risk of orthostatic hypotension (additional effect). ♦ Aminosides (parenteral route): increased nephrotoxic and ototoxic risks of aminosides (functional
renal impairment due to dehydration by diuretics). Coadministration may be achieved with ♦ Amifostine: Increased antihypertensor effect.
monitoring of hydration status, renal and cochleo-vestibular functions and plasma concentrations of ♦ Calcium (salts): Risk of hypercalcemia with diminished excretion of calcium in urine.
♦ Ciclosporine: increased risk of creatinemia with no change in ciclosporine plasma
♦ Phenytoine: diminished diuretic effect up to 50%.
concentrations, even whith no sodium depletion. ♦ Carbamazepin: risk of symptomatic hyponatremia.
PREGNANCY AND LACTATION
Clinical monitoring and laboratory determinations. If possible, use another class of diuretics. Use in Pregnancy
♦ Angiotensin converting enzyme (ACE) inhibitors, antagonists of angiotensin II: risk of sudden
Studies in animals have shown a teratogenic effect. hypotension and/or acute renal insufficiency when initiating a treatment with ACE inhibitors or an In clinical trials, no current data are available for pertinent evaluation of possible malformative or inhibitor of angiotensin II, in case of preexisting sodium depletion. foetotoxic effects of furosemide in pregnancy. In hypertensive patients, when previous diuretic treatment may have caused sodium depletion, it is Furosemide should generally be avoided in pregnancy and never be prescribed in physiological oedemas of pregnancy (requiring no treatment). Diuretics may in fact cause foetoplacentar - either to discontinue treatment during 3 days before initiating treatment with ACE inhibitors or ischaemia, with risk of foetal hypotrophy. inhibitor of angiotensin II , and re-administer hypokalemiant diuretics if necessary. - or to administer reduced initial dose of ACE inhibitors or inhibitor of angiotensin II and keep up Diuretics (for oral administration) remain however, a key element in the treatment of oedemas resulting from cardiac, hepatic and renal insufficiency, occurring in pregnant women. LAVOISIER FUROSEMIDE 20 mg/2 ml, injectable solution (IM-IV) Lactation:
Furosemide does not modify glomerular filtration (this latter was shown to be higher in certain Furosemide is excreted in the maternal milk. Loop diuretics diminish lacteous secretions and lactation conditions). Saliuretic action raises accordingly with the doses administered and persists in patients is inhibited from a single dose of 40 mg. Consequently, the use of this drug should be avoided in lactation. Antihypertensive action and other actions:
ADVERSE REACTION
Hemodynamic action is characterized by the decrease of the pulmonary capillary pressure even Sometimes, a mild increase of uricemia (about 10 to 30 mg/l) may occur during treatment, exceptionally prior to onset of diuresis, and the increase of the capacity storage of venous vascular bed shown by plethysmography (Studies of these properties were mainly focused on IV administration). Elevated glycemia is sometimes observed, most often in intensive and short-duration treatment, Furosemide treats all forms of sodium retention with response proportional to dosage. especially by intravenous injection. In very rare instances, decreased tolerance to glucose was Furosemide exerts antihypertensive action, resulting both from sodium depletion and hemodynamic Electrolyte disturbances may be observed in relation to the action of the product: dehydration, hyperazotemia, hyponatremia, hypovolemia manifested by orthostatic hypotension and justifiying Pharmacokinetics
discontinuance of treatment or reduced dosage. A very strict low-salt diet contributes to electrolyte After parenteral infusion, the major excretion path is in urine. Saliuretic action is observed within the first 5 minutes after intravenous injection. Some hypokalaemias whether associated or not with metabolic alkalosis may be observed. They occur Average elimination half-life is about one hour. This half-life is increased in premature infants. usually with high doses or in cirrhotics, patients malnourished and those with cardiac insufficiency (see Increased digestive elimination (biliary) in patients with renal insufficiency. There is then no Special warnings and precautions for use). These hypokalaemias may be very severe in patients with cardiac insufficiency and also be conducive to severe arrhythmias, especially torsades de pointe (TdP) (potentially life-threatening) principally when associated with antiarrythmics drugs of the quinidine PHARMACEUTICAL DATA
In very rare instances, renal calcifications associated with hypercalciuria were observed in very great premature infants treated by high doses of furosemide injections for congenital cardiopathy with cardiac Incompatibilities
LAVOISIER FUROSEMIDE 20 mg/2 ml, injectable solution should not be mixed with other substances in the same intravenous line (a precipitate may form by acidification of the solution). In patients with hepatocellular insufficiency, possible onset of hepatic encephalopathy. (see Contraindications and Special warnings and precautions for use). Shelf life: 2 years
Allergic reactions may occasionally occur sometimes bullous reactions, lumbar pains, leucopenias and Storage special precautions
Store ampoules in outer packaging, in a dark place. Nature and contents of container
Very high doses of injectable Furosemide - (especially when recommended rates of injection (4 to 6 minutes for direct IV injection or 4 mg per minute for perfusion) have not been observed) - may induce reversible hearing impairment, and exceptional cases of irreversible impairment when associated with Safety and drug handling instructions: Discard ampoule if any brown discoloration.
antibiotics of aminosides class with otoxic effects. PACKAGING AND PRODUCT LICENSE NUMBER
OVERDOSAGE
Hospital Packaging:
Hypovolemia by dehydration with electrolyte disturbances may occur in case of overdosage. Treatment with electrolyte rebalance should then be instituted. MA 561 856-1: 2 ml ampoule bottle (type I glass) – 100 units pack – Approved for institutions.
CLINICAL PHARMACOLOGY
CONDITIONS OF DELIVERY
List II
Pharmacodynamics
DATE OF REVISION
Saliuretic action:
With the usual therapeutic doses, Furosemide has an action primarily on the upper limb of Henle’s Loop, inhibiting first the reabsorption of chlorine, then of sodium. Furosemide exerts a minor action on CDM LAVOISIER
Furosemide potentiates renal blood flow to the benefit of the cortical zone. This propriety is of particular Laboratoires Chaix et Du Marais - 7, rue Labie - 75017 PARIS - FRANCE
interest in association with beta-blockers which may produce the reverse effect. Tel: +33 1 55 37 83 83 E-mail: [email protected] Fax: +33 1 55 37 83 84
LAVOISIER FUROSEMIDE 20 mg/2 ml, injectable solution (IM-IV)

Source: http://www.lavoisier.com/fic_bdd/pdf_en_fichier/12133477740_Furosemide_En.pdf