New Zealand Data Sheet 23 August 2018 Lasix and Lasix High Dose- furosemide (frusemide) DATA SHEET 1 PRODUCT NAME Lasix Oral solution 10mg/mL Lasix High Dose Solution for infusion 10mg/mL 2 QUALITATIVE AND QUANTITATIVE COMPOSITION Furosemide (frusemide) Oral solution 10mg/mL Furosemide (frusemide) High Dose Solution for infusion 10mg/mL in water for injection (without solubiliser, pH about 9) Chemical Structure CAS Number 54-31-9 For the full list of excipients, see section 6.1. 3 PHARMACEUTICAL FORM Lasix is an anthranilic acid derivative. Chemically, it is 4-chloro-N-furfuryl-5- sulfamoylanthranilic acid. Furosemide (Frusemide) is a white to off-white odourless crystalline powder. It is practically insoluble in water, sparingly soluble in alcohol, freely soluble in dilute alkali solutions and insoluble in dilute acids. lasix-lasix-high-dose-ccdsv12-dsv16-23aug18 Page 1 New Zealand Data Sheet 23 August 2018 Lasix and Lasix High Dose- furosemide (frusemide) 4 CLINICAL PARTICULARS 4.1 THERAPEUTIC INDICATIONS Oedema Lasix is indicated in adults, infants and children for the treatment of oedema associated with congestive heart failure, cirrhosis of the liver and renal disease including the nephrotic syndrome. Lasix is particularly useful when an agent with greater diuretic potential than that of those commonly employed is desired. Parenteral therapy should be reserved for patients unable to take oral medication or for patients in emergency clinical situations. Lasix Injection is also indicated as adjunctive therapy in acute pulmonary oedema and cerebral oedema where intense and rapid onset of diuresis is desired. If gastrointestinal absorption is impaired or oral medication is not practical for any reason, Lasix is indicated by the intravenous route. Parenteral use should be replaced with oral Lasix as soon as practical. Hypertension Oral Lasix may be used in adults for the treatment of hypertension alone or in combination with other antihypertensive agents. Hypertensive patients who cannot be adequately controlled with thiazides will probably also not be adequately controlled with Lasix alone. 4.2 DOSE AND METHOD OF ADMINISTRATION Lasix Oral Administration Oedema Therapy should be individualised according to patient's response. This therapy should be titrated to gain maximal therapeutic response with the minimum dose possible to maintain that diuretic response. Adults: The usual initial daily dose is 20 to 80 mg given as a single dose. If the diuretic response to a single dose of 20 to 80 mg is not satisfactory, increase this dose by increments of 20 to 40 mg, not sooner than 6 to 8 hours after the previous dose, until the desired diuretic effect is obtained. This individually determined dose should be given once or twice (e.g. at 8 am and 2 pm) daily. The dose of Lasix may be carefully titrated up to 400 mg/day (except in advanced renal failure) in those patients with severe clinical oedematous states. The mobilisation of oedema may be most efficiently and safely accomplished by giving Lasix on 2 to 4 consecutive days each week. When doses exceeding 80 mg/day are given for prolonged periods, careful clinical laboratory observations are particularly advisable. lasix-lasix-high-dose-ccdsv12-dsv16-23aug18 Page 2 New Zealand Data Sheet 23 August 2018 Lasix and Lasix High Dose- furosemide (frusemide) Infants and Children: The usual initial dose of oral Lasix for infants and children is 2mg/kg body weight given as a single dose. If the diuretic response is not satisfactory, the dose may be increased by 1 to 2 mg/kg no sooner than 6 to 8 hours after the previous dose. Doses of greater than 6 mg/kg body weight are not recommended. For maintenance therapy in infants and children, the dose should be adjusted to the minimum effective level. Hypertension Therapy should be individualised according to the patient's response. This therapy should be titrated to gain maximal therapeutic response with the minimum dose possible to maintain that therapeutic response. Adults: The usual initial daily dose of Lasix for hypertension is 80 mg, usually divided into 40 mg twice a day. Dosage should then be adjusted according to response. If response is not satisfactory, add other antihypertensive agents. Changes in blood pressure must be carefully monitored when Lasix is used with other antihypertensive drugs, especially during initial therapy. To prevent an excessive drop in blood pressure, the dosage of other agents should be reduced by at least 50% when Lasix is added to the regimen. As the blood pressure falls under the potentiating effect of Lasix, a further reduction in dosage or even discontinuation of other antihypertensive drugs may be necessary. Lasix High Dose Parenteral Administration The high dosage preparations are intended exclusively for administration to patients with greatly reduced glomerular filtration rate (GFR less than 20 mL/min but greater than 5 mL/min). Normal doses of Lasix are usually adequate in patients with greatly reduced GFR if functional oliguria or anuria is observed. Thus, test a normal dose of Lasix first, before administering Lasix High Dose. Furosemide (frusemide) is given intravenously only when oral administration is not feasible or is ineffective or if rapid effect is required. If intravenous therapy is used, it is recommended that transfer to oral therapy be carried out as soon as possible. To achieve optimum efficacy and suppress counter-regulation, a continuous furosemide (frusemide) infusion is generally preferred to repeated bolus injections. Before treatment of patients in shock is started, hypovolaemia and hypotension should be dealt with by suitable measures. Similarly, disturbed serum electrolytes and acid-base balance should first be corrected. lasix-lasix-high-dose-ccdsv12-dsv16-23aug18 Page 3 New Zealand Data Sheet 23 August 2018 Lasix and Lasix High Dose- furosemide (frusemide) When treating patients with conditions likely to interfere with micturition, such as prostatic hypertrophy or disturbed consciousness, it is absolutely essential to ensure free urinary drainage. Because of the wide and unpredictable individual variations in responsiveness it is important to adjust dosage and route of administration to individual needs. Once the desired rise in urinary output has begun, exact balance of water intake and water output must be maintained throughout the course of treatment so as to avoid hypovolaemia or hypotension. Careful electrolyte replacement is also necessary. The dosage of high strength furosemide (frusemide) given below is for adults only. The dosage regimen for children has not yet been determined. The administration of large doses of furosemide (frusemide) in children has been associated with permanent deafness (see Section 4.4). Lasix High Dose - Intravenous Infusion If a test dose of 40 to 80 mg Lasix, injected slowly IV over about 2 to 5 minutes, does not lead to increased diuresis within 30 minutes, infusion treatment with Lasix High Dose 250 mg is indicated. Infusion fluid Lasix High Dose for IV use is a mildly buffered alkaline solution. Lasix High Dose can be added to 5% Dextrose in water Isotonic Saline or Lactated Ringer's Injection when mixed as directed and prepared immediately before use. Furosemide (Frusemide) may precipitate in, and therefore is incompatible with, solutions in which the pH of the resulting mixture is less than 5.5. Furosemide (frusemide) should not be added into the tubing of a running infusion solution. Also, it should not be mixed with any other drugs in the infusion bottle. Initial dose The contents of one ampoule (250 mg/25 mL) are infused together with 250 mL of neutral to alkaline isotonic solution. The rate of infusion should not exceed 4 mg/minute, otherwise there is a risk of ototoxicity (see Section 4.4). Thus the duration of infusion should be about 60 minutes. The diuresis should start during the infusion. Additional dose Should the initial dose fail to produce an adequate increase (at least 40 to 50 mL/hour) in urinary output, a second infusion of 500 mg (appropriately diluted) may be given 1 hour after completion of the first. The duration of this infusion is determined by the maximum rate of furosemide (frusemide) 4 mg/minute. A maximum daily dose of 1000 mg should not be exceeded. For hypervolaemic patients, it is advisable to give the high-dosage formulation of furosemide (frusemide) undiluted, or in a suitable volume (e.g. 250 mg in 50 mL) of infusion fluid, so as to avoid the risk of over-hydration. IV infusions of the undiluted solution must be given with the aid of a motordriven precision syringe, so as to make sure that the upper limit of furosemide (frusemide) 4 mg (0.4mL) /minute is not exceeded. lasix-lasix-high-dose-ccdsv12-dsv16-23aug18 Page 4 New Zealand Data Sheet 23 August 2018 Lasix and Lasix High Dose- furosemide (frusemide) If a satisfactory diuretic response is achieved (40 to 50 mL/hour), the effective dose can be repeated every 24 hours. Use in Children High dose Lasix preparations should not be used in children. However, normal doses of Lasix may be used (refer above). 4.3 CONTRAINDICATION Known hypersensitivity to furosemide (frusemide) or sulfonamides or any of the inactive ingredients. Patients allergic to sulfonamides (e.g. sulfonamide antibiotics or sulfonylureas) may show cross-sensitivity to Lasix. Lasix Complete renal shutdown, impaired renal function or anuria. If increasing azotaemia and oliguria occur during treatment of severe progressive renal disease, discontinue furosemide (frusemide). Severe hypokalaemia, (see Section 4.8), hyponatraemia, hypovolaemia, dehydration or hypotension must be regarded as contraindications until serum electrolytes, fluid balance and blood pressure have been restored to normal levels. In hepatic coma or precoma and conditions producing electrolyte depletion, furosemide (frusemide) therapy should not be instituted until the underlying conditions have been corrected or ameliorated. Breast-feeding or pregnant women. Do not administer furosemide (frusemide) to newborns presenting jaundice or to infants with conditions which might induce hyperbilirubinaemia or kernicterus (e.g.