UDSx Medicated System

INDICATIONS AND USAGE Edema Furosemide tablets are 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. Furosemide tablets are particularly useful when an agent with greater diuretic potential is desired. Hypertension Oral furosemide 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 furosemide alone. Use First aid antiseptic to help prevent the risk of infection in minor cuts, scrapes and burns

DOSAGE AND ADMINISTRATION 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 furosemide tablets is 20 to 80 mg 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 or 40 mg 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 furosemide tablets 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 furosemide tablets 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 (see PRECAUTIONS: Laboratory Tests ). 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 furosemide 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 furosemide tablets 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 furosemide tablets are 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 percent when furosemide tablets are added to the regimen. As the blood pressure falls under the potentiating effect of furosemide tablets, 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 ). Directions • Tear open packet • Unfold and clean the affected area • Discard after single use

CONTRAINDICATIONS Furosemide tablets are contraindicated in patients with anuria and in patients with a history of hypersensitivity to furosemide.

WARNING Furosemide is a potent diuretic which, if given in excessive amounts, can lead to a profound diuresis with water and electrolyte depletion. Therefore, careful medical supervision is required and dose and dose schedule must be adjusted to the individual patient's needs (see DOSAGE AND ADMINISTRATION ). WARNINGS In patients with hepatic cirrhosis and ascites, furosemide therapy is best initiated in the hospital. In hepatic coma and in states of electrolyte depletion, therapy should not be instituted until the basic condition is improved. Sudden alterations of fluid and electrolyte balance in patients with cirrhosis may precipitate hepatic coma; therefore, strict observation is necessary during the period of diuresis. Supplemental potassium chloride and, if required, an aldosterone antagonist are helpful in preventing hypokalemia and metabolic alkalosis. If increasing azotemia and oliguria occur during treatment of severe progressive renal disease, furosemide should be discontinued. Cases of tinnitus and reversible or irreversible hearing impairment and deafness have been reported. Reports usually indicate that furosemide ototoxicity is associated with rapid injection, severe renal impairment, the use of higher than recommended doses, hypoproteinemia or concomitant therapy with aminoglycoside antibiotics, ethacrynic acid, or other ototoxic drugs. If the physician elects to use high dose parenteral therapy, controlled intravenous infusion is advisable (for adults, an infusion rate not exceeding 4 mg furosemide per minute has been used) (see PRECAUTIONS: Drug Interactions ). Warnings For external use only. For Professional and Hospital use only. Do not • use in the eyes • apply over large areas of the body. Consult a doctor in case of deep or puncture wounds, animal bites, or serious burns. Stop use and consult a doctor if the condition persists or gets worse. Do not use longer than 1 week unless directed by a doctor. Keep out of reach of children. If swallowed, get medical help or contact a Poison Control Center right away.

Drug Interactions Furosemide may increase the ototoxic potential of aminoglycoside antibiotics, especially in the presence of impaired renal function. Except in life-threatening situations, avoid this combination. Furosemide should not be used concomitantly with ethacrynic acid because of the possibility of ototoxicity. Patients receiving high doses of salicylates concomitantly with furosemide, 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 furosemide are given concomitantly. In addition, nephrotoxicity of nephrotoxic drugs such as cisplatin may be enhanced if furosemide is not given in lower doses and with positive fluid balance when used to achieve forced diuresis during cisplatin treatment. Furosemide 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. Furosemide 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 furosemide, angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers may be necessary. Potentiation occurs with ganglionic or peripheral adrenergic blocking drugs. Furosemide may decrease arterial responsiveness to norepinephrine. However, norepinephrine may still be used effectively. Simultaneous administration of sucralfate and furosemide tablets may reduce the natriuretic and antihypertensive effects of furosemide. Patients receiving both drugs should be observed closely to determine if the desired diuretic and/or antihypertensive effect of furosemide is achieved. The intake of furosemide and sucralfate should be separated by at least two hours. In isolated cases, intravenous administration of furosemide within 24 hours of taking chloral hydrate may lead to flushing, sweating attacks, restlessness, nausea, increase in blood pressure, and tachycardia. Use of furosemide concomitantly with chloral hydrate is therefore not recommended. Phenytoin interferes directly with renal action of furosemide. There is evidence that treatment with phenytoin leads to decreased intestinal absorption of furosemide, and consequently to lower peak serum furosemide concentrations. Methotrexate and other drugs that, like furosemide, undergo significant renal tubular secretion may reduce the effect of furosemide. Conversely, furosemide may decrease renal elimination of other drugs that undergo tubular secretion. High-dose treatment of both furosemide and these other drugs may result in elevated serum levels of these drugs and may potentiate their toxicity as well as the toxicity of furosemide. Furosemide can increase the risk of cephalosporin-induced nephrotoxicity even in the setting of minor or transient renal impairment. Concomitant use of cyclosporine and furosemide is associated with increased risk of gouty arthritis secondary to furosemide-induced hyperuricemia and cyclosporine impairment of renal urate excretion. High doses (> 80 mg) 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 co-administration of indomethacin may reduce the natriuretic and antihypertensive effects of 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 furosemide should be observed closely to determine if the desired diuretic and/or antihypertensive effect of furosemide is achieved.

ADVERSE REACTIONS 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 2. systemic vasculitis 4. necrotizing angiitis 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 8. purpura 3. erythema multiforme 9. fever 4. drug rash with eosinophilia and systemic symptoms 10. rash 5. acute generalized exanthematous pustulosis 11. pruritus 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, furosemide dosage should be reduced or therapy withdrawn. To report SUSPECTED ADVERSE REACTIONS, contact Solco Healthcare US, LLC at 1-866-257-2597 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Pregnancy Furosemide has been shown to cause unexplained maternal deaths and abortions in rabbits at 2, 4 and 8 times the maximal recommended human dose. There are no adequate and well-controlled studies in pregnant women. Furosemide should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Treatment during pregnancy requires monitoring of fetal growth because of the potential for higher birth weights. The effects of furosemide on embryonic and fetal development and on pregnant dams were studied in mice, rats and rabbits. Furosemide caused unexplained maternal deaths and abortions in the rabbit at the lowest dose of 25 mg/kg (2 times the maximal recommended human dose of 600 mg/day). In another study, a dose of 50 mg/kg (4 times the maximal recommended human dose of 600 mg/day) also caused maternal deaths and abortions when administered to rabbits between Days 12 and 17 of gestation. In a third study, none of the pregnant rabbits survived a dose of 100 mg/kg. Data from the above studies indicate fetal lethality that can precede maternal deaths. The results of the mouse study and one of the three rabbit studies also showed an increased incidence and severity of hydronephrosis (distention of the renal pelvis and, in some cases, of the ureters) in fetuses derived from the treated dams as compared with the incidence in fetuses from the control group.