Frusemide

complete drug profile of Frusemide

1. Drug Profile Of FUROSEMIDE Presented By : JAWERIA AZDEE

2. INTRODUCTION Furosemide is a loop diuretic (water pill) that prevents body from absorbing too much salt, allowing the salt to instead be passed in urine. Furosemide treats fluid retention (edema) in people with congestive heart failure, liver disease, or a kidney disorder such as nephrotic syndrome. This medication is also used to treat high blood pressure (hypertension).

3. Brand Manufacturer Dosage Form ROA Strength Retail Price LASIX Aventis Tabs,inj PO,IV Tabs:20/40cc Inj:Per 2ml amp:20mg 244.78 FRUSINOX Abbott Tablets Orally Frusemide:40mg 110.86 EPHAMIDE Epharm Inj IV 20mg per 2ml amp 13.00 FRUSEMIDE Nawabsons Tablets Orally Frusemide:40mg 60.00 LAXIDE Munawar pharma Tablets Orally Frusemide:40mg 147.06

4. CHEMISTRY OF THE DRUG This compound belongs to the class of organic compounds known as aminobenzenesulfonamides . These are organic compounds containing a benzenesulfonamide moiety with an amine group attached to the benzene ring. Organoleptic properties Color: White Taste: Metallic taste Shape: Round, elliptical or oval Physical properties Melting Point: 206 ⁰C Solubility: poorly water soluble, binary mixtures of ethanol, propylene glycol, and glycerol from 0% to 100% cosolvent concentrations at 25 ⁰C. Molecular Weight: 330.7

5. PHARMACOKINETICS Absorption : 60–67% absorbed after oral administration (↓ in acute HF and in renal failure); also absorbed from IM sites. Distribution: Crosses placenta, enters breast milk. Protein Binding: 91–99%. Metabolism: Minimally metabolized by liver, some nonhepatic metabolism . Excretion: via kidney by glomerular filtration of tubular secretion . Half-life: 30–60 min (↑ in renal impairment).

6. TIME/ACTION PROFILE (diuretic effect) Route Onset Peak Duration PO 30-60min 1-2hr 6-8hr IM 10-30min Unknown 4-8hr IV 5min 30min 2hr

7. Mechanism of Action Furosemide , a loop diuretic, inhibits water reabsorption in the nephron by blocking the sodium-potassium-chloride cotransporter (N/K/2Cl) in the thick ascending limb of the loop of Henle . This is achieved through competitive inhibition at the chloride binding site on the cotransporter , thus preventing the transport of sodium from the lumen of the loop of Henle into the basolateral interstitium . Consequently, the lumen becomes more hypertonic while the interstitium becomes less hypertonic, which in turn diminishes the osmotic gradient for water reabsorption throughout the nephron . Because the thick ascending limb is responsible for 25% of sodium reabsorption in the nephron , furosemide is a very potent diuretic.

8. Actions

9. INDICATIONS For the treatment of edema associated with congestive heart failure, cirrhosis of the liver, and renal disease, including the nephrotic syndrome. Also for the treatment of hypertension alone or in combination with other antihypertensive agents. Duration: Diuresis effect persists 6-8 hrs following oral administration, while approximately 2 hrs following IV administrations.

10. Contraindications

11. PRECAUTIONS

12. Special Considerations FDA’s pregnancy category Furosemide has been shown to cause unexplained maternal deaths and abortions in rabbits at 2, 4 and 8 times the maximal recommended human dose. -the lowest dose of 25 mg/kg((2 times the maximal recommended human dose of 600 mg/day) -dose of 50 mg/kg (4 times the maximal recommended human dose of 600 mg/day) Treatment during pregnancy requires monitoring of fetal growth because of the potential for higher birth weights.

13. Nursing mothers Because it appears in breast milk, caution should be exercised when Furosemide is administered to a nursing mother. Furosemide may inhibit lactation .

14. Pediatric Use In premature infants furosemide may precipitate nephrocalcinosis / nephrolithiasis . If furosemide is administered to premature infants during the first weeks of life, it may increase the risk of persistence of patent ductus arteriosus Geriatric Use Controlled clinical studies of furosemide did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In general, dose selection for the elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection and it may be useful to monitor renal function.

15. WARNINGS 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

16. Route/Dosage IM: IV: (Adults)20-40mg q 1-2hr and increase by 20mg every 1-2hr IM: IV: Children 1-2mg/kg/dose q 6-12hrs CI-0.05mg/kg/hr IM: IV: Neonates 1-2mg/kg/dose q 12-24hr Orally IM IV

17. Route/Dosage

18. Route/Dosage

19. Patients with renal failure: For selected patients with advanced chronic renal failure, diuretic therapy may be started with furosemide orally. If conventional doses ( 80 to 160 mg orally ) fail to produce an adequate diuresis , a single dose of 250 mg is given as a starting dose. If a satisfactory diuresis does not ensue within 4 to 6 hours, the initial dose may be doubled to 500 mg . Dose adjustment in special population

20. Patients with hypervolemia : For hypervolemic patients, it is advisable to give the high-dosage formulation of furosemide undiluted, or in a suitable volume (e.g., 250 mg in 50 mL ) of infusion fluid so as to avoid the risk of overhydration . I.V. infusions of the undiluted solution must be given with the aid of a motor-driven precision syringe so as to make sure that the upper limit of furosemide 4 mg (0.4 mL )/minute is not exceeded. Dose adjustment in special population

21. Drug-Drug Interactions

22. Drug-Drug Interactions ↑ risk of hypotension with antihypertensives , nitrates , or acute ingestion of alcohol . Hypokalemia may ↑ risk of digoxin toxicity and ↑ risk of arrhythmia in patients taking drugs that prolong the QT interval. ↓ lithium excretion, may cause lithium toxicity. May ↑ risk of methotrexate toxicity. ↓ effects of furosemide when given at same time as sucralfate , cholestyramine ,or colestipol . ↑ risk of salicylate toxicity (with use of high-dose salicylate therapy).

23. Drug-Disease Interactions The use of loop diuretics is contraindicated in patients with anuria . therapy should be initiated in the hospital under strict observation in patients with liver cirrhosis and ascites . Sudden alteration of fluid and electrolyte balance may precipitate hepatic encephalopathy The use of loop diuretics, is commonly associated with loss of electrolytes, incl K,Na,Cl,Mg,Ca , may lead to cardiac arrhythmias and cardiac arrest. Other complications incl metabolic alkalosis and hyponatremia , weight loss, dehydration and hypovolemia

24. Contn ….. Impaired effectiveness and possible delayed excretion of loop diuretics may occur in patients with severe renal dysfunction. The use of furosemide has been associated with exacerbation or activation of systemic lupus erythematosus . Loop diuretics may decrease the rate of uric acid excretion. Hyperuricemia can occur but is usually asymptomatic and rarely leads to clinical gout except in patients with a history of gout or chronic renal failure.

25. Drug-Food Interactions But with caution…… Avoid alcohol. Avoid excess salt/sodium unless otherwise instructed by your physician. Increase potassium intake; add a banana or orange juice; unless instructed otherwise. Take with food to reduce irritation. Food does not appear to affect diuretic effect. Furosemide and ethanol may have additive effects in lowering your blood pressure. You may experience headache, dizziness, lightheadedness, fainting, and/or changes in pulse or heart rate.

26. Pharmaceutical Incompatibilities Acid solutions including other parenteral medications ( eg , labetalol , ciprofloxacin, amrinone , milrinone ): do not add to furosemide solution precipitate forms. Thus furosemide is unsuitable for Y-site coadministration with amiodarone hydrochloride, esmolol hydrochloride, labetalol hydrochloride, dobutamine hydrochloride, diltiazem hydrochloride, dopamine hydrochloride, and magnesium sulfate at their standardized concentrations causes precipitation formation.

27. Adverse Reactions CNS: blurred vision, dizziness, headache, vertigo EENT: hearing loss, tinnitus CV: hypotension GI: anorexia, constipation, diarrhea, dry mouth, dyspepsia, ↑ liver enzymes, nausea, pancreatitis, vomiting GU: ↑ BUN, excessive urination, nephrocalcinosis Derm : ERYTHEMA MULTIFORME, STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS , photosensitivity, pruritis , rash, urticaria Endo: hypercholesterolemia, hyperglycemia, hypertriglyceridemia , hyperuricemia Metab : dehydration , hypocalcemia , hypochloremia , hypokalemia , hypomagnesemia , hyponatremia , hypovolemia , metabolic alkalosis Hemat : APLASTIC ANEMIA, AGRANULOCYTOSIS , hemolytic anemia, leukopenia , thrombocytopenia MS: muscle cramps Neuro : paresthesia Misc: fever

28. Toxicology Signs & Symptoms: Dehydration, electrolyte imbalance, hypochloremia alkalosis, hypokalemia , hypotension, blood volume LD50: The oral LD50 exceeded 1000 mg/kg body weight, while the IV LD50 ranged from 300 to 680 mg/kg. Toxicity: The concentration of LASIX in biological fluids associated with toxicity or death is not known. Missed dose: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

29. Management Treatment of overdosage is supportive and consists of replacement of excessive fluid and electrolyte losses. Serum electrolytes, carbon dioxide level and blood pressure should be determined frequently. Adequate drainage must be assured in patients with urinary bladder outlet obstruction Hemodialysis does not accelerate furosemide elimination.

30. Storage Oral Solution or Tablets Parenteral Injection Tight,light resistant containers at 15-30˚C 15–30°C; protect from light. Discard unused portion

31. Patient/Family Teaching Instruct patient to take furosemide as directed. Take missed doses as soon as possible; do not double doses. Caution patient to change positions slowly to minimize orthostatic hypotension. Instruct patient to consult health care professional regarding a diet high in potassium Advise patient to contact health care professional of weight gain more than 3 lbs in 1 day. Instruct patient to notify health care professional of all Rx or OTC medications. Caution patient to use sunscreen and protective clothing to prevent photosensitivity reactions. Advise patient to contact health care professional immediately if rash, muscle weakness, cramps, nausea, dizziness, numbness, or tingling of extremities occurs. Advise diabetic patients to monitor blood glucose closely; may cause increased blood glucose levels. Geri: Caution older patients or their caregivers about increased risk for falls Hypertension: Advise patients on antihypertensive regimen to continue taking medication even if feeling better. Furosemide controls but does not cure hypertension.

32. Instructions for IV Administrations Direct IV: Diluent : Administer undiluted (larger doses may be diluted and administered as intermittent). Concentration: 10 mg/ mL. Rate: Administer at a rate of 20 mg/min. Pedi: Administer at a maximum rate of 0.5–1 mg/kg/min (for doses <120 mg) with infusion not exceeding 10 min. Intermittent Infusion: Diluent : Dilute larger doses in 50 mL of D5W, D10W, D20W, D5/0.9% NaCl , D5/LR, 0.9% NaCl , 3% NaCl , or LR. Infusion stable for 24 hr at room temperature. Do not refrigerate. Protect from light. Concentration: 1 mg/ mL. Rate: Administer at a rate not to exceed 4 mg/min (for doses > 120 mg) in adults to prevent ototoxicity . Pedi: not to exceed 1 mg/kg/min with infusion not exceeding 10 min. Use an infusion pump to ensure accurate dose.

33. Evaluation/Desired Outcomes