complete drug profile of Frusemide

2. Drug Profile Of
FUROSEMIDE
Presented By: JAWERIA AZDEE

3. 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).

4. Brand Manufactu
rer
Dosage
Form
ROA Strength Retail
Price
LASIX Aventis Tabs,inj PO,IV Tabs:20/40
cc
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
FRUSEMID
E
Nawabsons Tablets Orally Frusemide:
40mg
60.00
LAXIDE Munawar
pharma
Tablets Orally Frusemide:
40mg
147.06
Available Brands in Pakistan

5. 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: 206⁰C
Solubility: poorly water soluble, binary mixtures of
ethanol, propylene glycol, and glycerol from 0% to
100% cosolvent concentrations at 25⁰C.
Molecular Weight: 330.7

6. 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).

7. 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

8. 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.

10. Actions
Inhibits renal reabsorption of sodium
and chloride in the renal tubules
Decreases renal vascular resistance
Promotes increased diuresis
Causes vasodilation and reduces
preload and cardiac work load

11. 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.

12. Contraindications
Hypersensitivity
Cross sensitivity with thiazides and
sulfonamides may occur
Hepatic coma and anuria
Some liquid products may contain alcohol,
avoid in patients with alcohol intolerance

13. PRECAUTIONS
Severe liver disease
Electrolyte depletion
Diabetes mellitus
Hypoproteinemia
Severe renal impairment
Lactation
Pedi: Increase risk of renal calculi and patent ductus
arteriosis in premature neonates
Geri: Increase risk of side effects, especially hypotension
and electrolyte imbalance at usual doses

14. Special Considerations
 FDA’s pregnancy category
I. 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)
I. Treatment during pregnancy requires monitoring
of fetal growth because of the potential for higher
birth weights.
Category C

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

16.  Pediatric Use
I. In premature infants furosemide may precipitate
nephrocalcinosis/ nephrolithiasis.
II. 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
I. 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.
II. 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.
III. 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.

17. 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

18. Route/Dosage
Edema
Adults: 20-
80mg/day(single
dose initially)
repeat in 6-8hr
(Children > 1
mo):
2mg/kg(single
dose)increase 1-
2mg/kg q 6-8hr
Neonates: 1-
4mg/kg/dose q 1-
2times
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

19. Route/Dosage
PO: (Adults) 20-
80mg/dose
initially…When added
to regimen, dose of
other antihypertensive
by 50%
C-IV infusion:0.1mg/kg
as an initial bolus dose
followed by
0.1mg/kg/hr doubled q
2hr
Hypertension
Orally: 2-80/dose
IV,IM:10-20mg
once,q 1-2min
C-IV
infusion:0.1mg/kg
initial bolus dose
doubled q 2hr
Ascites

20. Route/Dosage
Orally:20-80/dose
initially-increase
20-40mg q 1-2min
IM,IV:10-20mg
once q 1-2min-
repeat similar to
initial within 2hr
C-IV
infusion:0.1mg/kg-
followed by
0.1mg/kg/dose q
2hr
CHF
Oral:10-40mg 4
times a day
IV:20-100mg
every 1-2hr over
1-2min
Hyperc
alcemi
a

21. 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
Dose adjustment in special population

22. 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
Dose adjustment in special population

23. Drug-Drug Interactions
Amikacin Increase ototoxicity
Cisplatin
Increase ototoxicity,
nephrotoxicity
Digoxin
Possible electrolyte
variations and arrhythmias
Antagonize the effects of
furosemide
NSAIDs
Phenytoin
Decrease effect of
furosemide
Cyclospori
n
Increase risk of gouty
arthritis
Corticosteroids,l
axatives,other
diuretics
Hypokalemia

24. 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).

25. 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

26. 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.

27. 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.

28. 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.
Furosemide -
Midazolam
Leads to a significant reduction in drug
delivered to the patient and result may in
treatment failure.
Furosemide
chemical
incompatibility
Haas been reported in people with chronic
obstructive pulmonary disease, diabeteic
neuropathy, sedation, nausea anti coagulant
therapy.

29. 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

30. 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.

31. 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.

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

33. 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.

34. 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.

35. Evaluation/Desired Outcomes
Decrease in
edema
Decrease in
abdominal
girth and wt
Increase in
urinary
output
Decrease in
BP