LASIX

LASIX ® is a diuretic which is an anthranilic acid derivative. LASIX tablets for oral administration contain furosemide as the active ingredient and the following inactive ingredients: lactose monohydrate NF, magnesium stearate NF, starch NF, talc USP, and colloidal silicon dioxide NF. Chemically, it is 4-chloro-N-furfuryl-5-sulfamoylanthranilic acid. LASIX is available as white tablets for oral administration in dosage strengths of 20, 40 and 80mg. Furosemide is a white to off-white odorless crystalline powder. It is practically insoluble in water, sparingly soluble in alcohol, freely soluble in dilute alkali solutions and insoluble in dilute acids. The CAS Registry Number is 54-31-9. The structural formula is as follows: The structural formula for LASIX® is a diuretic which is an anthranilic acid derivative. LASIX tablets for oral administration contain furosemide as the active ingredient and the following inactive i

Edema LASIX is indicated in adults and pediatric patients for the treatment of edema 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 is desired. 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.

Edema Therapy should be individualized according to patient response to gain maximal therapeutic response and to determine the minimal dose needed to maintain that response. Adults -- The usual initial dose of LASIX is 20 mg to 80mg given as a single dose. Ordinarily a prompt diuresis ensues. If needed, the same dose can be administered 6 to 8 hours later or the dose may be increased. The dose may be raised by 20 mg or 40mg and given not sooner than 6 to 8 hours after the previous dose until the desired diuretic effect has been obtained. The individually determined single dose should then be given once or twice daily (e.g., at 8 am and 2 pm). The dose of LASIX may be carefully titrated up to 600 mg/day in patients with clinically severe edematous states. Edema may be most efficiently and safely mobilized by giving LASIX on 2 to 4 consecutive days each week. When doses exceeding 80 mg/day are given for prolonged periods, careful clinical observation and laboratory monitoring are particularly advisable ( s ee PRECAUTIONS: Laboratory Test ) . Geriatric patients -- In general, dose selection for the elderly patient should be cautious, usually starting at the low end of the dosing range ( see PRECAUTIONS: Geriatric Use ). Pediatric patients -- The usual initial dose of oral LASIX in pediatric patients is 2 mg/kg body weight, given as a single dose. If the diuretic response is not satisfactory after the initial dose, dosage may be increased by 1 or 2 mg/kg no sooner than 6 to 8 hours after the previous dose. Doses greater than 6 mg/kg body weight are not recommended. For maintenance therapy in pediatric patients, the dose should be adjusted to the minimum effective level. Hypertension Therapy should be individualized according to the patient’s response to gain maximal therapeutic response and to determine the minimal dose needed to maintain the therapeutic response. Adults -- The usual initial dose of LASIX for hypertension is 80mg, usually divided into 40mg 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 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. Geriatric patients -- In general, dose selection and dose adjustment for the elderly patient should be cautious, usually starting at the low end of the dosing range (see PRECAUTIONS: Geriatric Use ).

LASIX is contraindicated in patients with anuria and in patients with a history of hypersensitivity to furosemide.

Adverse reactions are categorized below by organ system and listed by decreasing severity. Gastrointestinal System Reactions 1. hepatic encephalopathy in patients with hepatocellular insufficiency 6. oral and gastric irritation 7. cramping 2. pancreatitis 8. diarrhea 3. jaundice (intrahepatic cholestatic jaundice) 9. constipation 4. increased liver enzymes 10. nausea 5. anorexia 11. vomiting Systemic Hypersensitivity Reactions 1. Severe anaphylactic or anaphylactoid reactions (e.g., with shock) 3. interstitial nephritis 4. necrotizing angiitis 2. systemic vasculitis Central Nervous System Reactions 1. tinnitus and hearing loss 5. headache 2. paresthesias 6. blurred vision 3. vertigo 7. xanthopsia 4. dizziness Hematologic Reactions 1. aplastic anemia 5. leukopenia 2. thrombocytopenia 6. anemia 3. agranulocytosis 7. eosinophilia 4. hemolytic anemia Dermatologic-Hypersensitivity Reactions 1. toxic epidermal necrolysis 7. bullous pemphigoid 2. Stevens-Johnson Syndrome 3. erythema multiforme 8. purpura 9. photosensitivity 4. drug rash with eosinophilia and systemic symptoms 10. rash 11. pruritis 5. acute generalized exanthematous pustulosis 6. exfoliative dermatitis 12. urticaria Cardiovascular Reaction 1. Orthostatic hypotension may occur and be aggravated by alcohol, barbiturates, or narcotics. 2. Increase in cholesterol and triglyceride serum levels Other Reactions 1. hyperglycemia 6. restlessness 2. glycosuria 7. urinary bladder spasm 3. hyperuricemia 8. thrombophlebitis 4. muscle spasm 9. fever 5. weakness Whenever adverse reactions are moderate or severe, LASIX dosage should be reduced or therapy withdrawn. To report SUSPECTED ADVERSE REACTIONS, contact Validus Pharmaceuticals LLC at 1-866-982-5438 (1-866-9VALIDUS) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

LASIX may increase the ototoxic potential of aminoglycoside antibiotics, especially in the presence of impaired renal function. Except in life-threatening situations, avoid this combination. LASIX should not be used concomitantly with ethacrynic acid because of the possibility of ototoxicity. Patients receiving high doses of salicylates concomitantly with LASIX, as in rheumatic disease, may experience salicylate toxicity at lower doses because of competitive renal excretory sites. There is a risk of ototoxic effects if cisplatin and LASIX are given concomitantly. In addition, nephrotoxicity of nephrotoxic drugs such as cisplatin may be enhanced if LASIX is not given in lower doses and with positive fluid balance when used to achieve forced diuresis during cisplatin treatment. LASIX has a tendency to antagonize the skeletal muscle-relaxing effect of tubocurarine and may potentiate the action of succinylcholine. Lithium generally should not be given with diuretics because they reduce lithium’s renal clearance and add a high risk of lithium toxicity. LASIX combined with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers may lead to severe hypotension and deterioration in renal function, including renal failure. An interruption or reduction in the dosage of LASIX, angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers may be necessary. Potentiation occurs with ganglionic or peripheral adrenergic blocking drugs. LASIX may decrease arterial responsiveness to norepinephrine. However, norepinephrine may still be used effectively. Simultaneous administration of sucralfate and LASIX tablets may reduce the natriuretic and antihypertensive effects of LASIX. Patients receiving both drugs should be observed closely to determine if the desired diuretic and/or antihypertensive effect of LASIX is achieved. The intake of LASIX and sucralfate should be separated by at least two hours. In isolated cases, intravenous administration of LASIX within 24 hours of taking chloral hydrate may lead to flushing, sweating attacks, restlessness, nausea, increase in blood pressure, and tachycardia. Use of LASIX concomitantly with chloral hydrate is therefore not recommended. Phenytoin interferes directly with renal action of LASIX. There is evidence that treatment with phenytoin leads to decreased intestinal absorption of LASIX, and consequently to lower peak serum furosemide concentrations. Methotrexate and other drugs that, like LASIX, undergo significant renal tubular secretion may reduce the effect of LASIX. Conversely, LASIX may decrease renal elimination of other drugs that undergo tubular secretion. High-dose treatment of both LASIX and these other drugs may result in elevated serum levels of these drugs and may potentiate their toxicity as well as the toxicity of LASIX. LASIX can increase the risk of cephalosporin-induced nephrotoxicity even in the setting of minor or transient renal impairment. Concomitant use of cyclosporine and LASIX is associated with increased risk of gouty arthritis secondary to LASIX-induced hyperurecemia and cyclosporine impairment of renal urate excretion. High doses (>80mg) of furosemide may inhibit the binding of thyroid hormones to carrier proteins and result in transient increase in free thyroid hormones, followed by an overall decrease in total thyroid hormone levels. One study in six subjects demonstrated that the combination of furosemide and acetylsalicylic acid temporarily reduced creatinine clearance in patients with chronic renal insufficiency. There are case reports of patients who developed increased BUN, serum creatinine and serum potassium levels, and weight gain when furosemide was used in conjunction with NSAIDs. Literature reports indicate that coadministration of indomethacin may reduce the natriuretic and antihypertensive effects of LASIX (furosemide) in some patients by inhibiting prostaglandin synthesis. Indomethacin may also affect plasma renin levels, aldosterone excretion, and renin profile evaluation. Patients receiving both indomethacin and LASIX should be observed closely to determine if the desired diuretic and/or antihypertensive effect of LASIX is achieved.