COMPOSITION
Plus TM : Each film-coated tablet contains Spironolactone USP 50 mg and Furosemide BP 20 mg.
PHARMACOLOGICAL INFORMATION
Pharmacological Action
Furo-Plus is a combination of diuretic containing a loop diuretic, Furosemide and a potassium sparing diuretic, Spironolactone. Furosemide is a potent loop diuretic which inhibits the Na + /K + /2Cl - co-transport in the ascending limb of loop of henle and blocks the reabsorption of sodium, potassium and chloride ions thereby increasing the quantity of sodium and the volume of water excreted in the urine. Spironolactone inhibits the reabsorption of sodium and excretion of potassium at the distal tubule by blocking the action of aldosterone. So, the excretion of sodium is increased and the excess loss of potassium, induced by furosemide is decreased.
Mechanism of Action
Furosemide is a diuretic which is an anthranilic acid derivative. Furosemide is a loop diuretic acting primarily on the medullary portion of the ascending limb of the loop of henle to inhibit a Na + /K + /2Cl - co-transporter which normally mediates ionic reabsorption. Furosemide inhibits sodium and potassium reabsorption by competing for the chloride binding site on the co-transporter at the luminal face of the epithelial cells. It also inhibits sodium reabsorption in other nephron, but these effects are relatively small. Furosemide causes an increased loss of calcium and magnesium, as well as of sodium, potassium and chloride in the urine. It increases the excretion of ammonia by the kidney. It also decreases left ventricular filling pressure. Spironolactone is a competitive inhibitor of the binding of aldosterone to its receptor. Its most important site of action is the distal portion of renal tubules where it combines with soluble cytoplasmic aldosterone receptor to form complexes which are inactive and which do not bind to nuclear-acceptor sites, thus preventing a chain of biochemical events leading to the synthesis of physiologically active proteins. Thus inhibits the reabsorption of sodium and excretion of potassium at the distal tubule & promotes a diuresis and acts as an antihypertensive agent.
In case of Furo-Plus, sodium excretion is greatly favored and the excess loss of potassium, induced by the furosemide, is reduced.
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PHARMACOKINETICS
Absorption:
After oral administration, Furo-Plus is rapidly absorbed from the GIT. Furosemide is 60-75% absorbed following oral administration.The mean bioavailability of furosemide is approximately 52% but the range is wide 27-80%. The onset of diuresis following oral administration is within 1 hour. The peak plasma concentration occurs 1 to 2 hours after oral dosing. The duration of diuretic effect is 6 to 8 hours. Oral absorption of spironolactone is variable because of its low aqueous solubility. Peak plasma concentration observed at 1 hour. Systemic bioavailability has been estimated at 60-70%.
Distribution:
In plasma, furosemide is extensively bound to plasma protein, mainly albumin. The drug is approximately 98.8% bound to plasma proteins. The volume of distribution (Vd) of furosemide ranges between 170 and 270 ml.kg-1. Plasma half life range from 45-60 min. Spironolactone is 98% protein bound but its volume of distribution is unknown. Although the half-life of spironolactone is 1.4 hours, the half-lives of the metabolites range from 14 to 22 hours.
Metabolism:
Recent evidence suggests that furosemide glucuronide is the only or at least the major biotransformation product of furosemide in man. The major site of biotransformation of spironolactone is thought to be the liver. Many of the metabolites of spironolactone have biological activity with varying affinity for aldosterone receptors.
Elimination:
Total systemic clearance of furosemide is 2 mL/min/kg adults and decreased in uraemia; neonates and heart failure. Sixty six per cent (66%) of the administered dose is excreted unchanged in the urine of a healthy young adult. The percentage excreted in urine of cystic fibrosis patients is reduced. The elimination half-life is 1.42 hours after oral dosing. The metabolites of spironolactone are excreted primarily in the urine and secondarily in bile. With long-term use of spironolactone the elimination half-life is 13-24 hours.
CLINICAL INFORMATION
Therapeutic Indications
" Edema
" Chronic congestive heart failure
" Essential Hypertension
" Liver cirrhosis with ascites.
" Resistant edema associated with secondary hyper-aldosteronism.
Dosage and Administration
1 to 4 tablets daily (50 to 200 mg of spironolactone and 20 to 80 mg of furosemide) according to the patient's response.
Contraindications
Furo-Plus is contraindicated in patients with a history of hypersensitivity to spironolactone or furosemide. The drug should not be prescribed in acute renal insufficiency, rapidly deteriorating or severe impairment of renal function (creatinine clearance: < 30 ml/min), anuria, hyperkalemia, Addison's disease. In addition, the drug should be given with great caution in conjunction with agents lowering plasma aldosterone, such as ACE inhibitors. Severe hypotension and/or renal failure may occur if ACE inhibitors are administered to patients who have been depleted of salt and water with this combination.
Use in patients with impaired renal function
Furo-Plus is contra-indicated in patients with acute renal insufficiency & significant impairment of renal excretory function.
Use in patients with impaired hepatic function
Furo-Plus should be used with caution in patients with impaired hepatic function because minor alterations of fluid and electrolyte balance due to spironolactone may precipitate hepatic coma.
Drug Interactions
The action of other hypotensive drugs (e. g. ACE- inhibitors, beta-blocking agents) may be potentiated by Furo-plus. Non-steroidal anti-inflammatory drugs (e. g. indomethacin, acetylsalicylic acid) may attenuate the action of furosemide. Furosemide may potentiate the nephrotoxic effects of certain antibiotics (e. g. aminoglycosides). Therefore, furosemide should be used with caution in patients with antibiotic-induced renal impairment. It should be borne in mind that the ototoxicity of aminoglycoside antibiotics (e. g. kanamycin, gentamycin, tobramycin) may be potentiated when furosemide is used concurrently. The hearing defects that result may be irreversible. Therefore, this drug combination should be restricted to vital indications. In case of concomitant glucocorticoid medication or abuse of laxatives, Furo-plus may lead to potassium deficiency. In the presence of potassium deficiency the effect of cardiac glycosides may be enhanced.
Use in Pregnancy & Lactation
Pregnancy: Furo-Plus should be used with caution during pregnancy, and only if the expected benefit to the mother is greater than any possible risk to the fetus
Lactation: Furo-Plus passes into breast milk. It is recommended that mothers should avoid using this medicine while breastfeeding.
Overdose
High doses may lead to serious sodium and fluid depletion and to a fall in intravascular volume. Postural hypotension and decrease of glomerular filtration rate may ensue. Overdose may also cause drowsiness, mental confusion, nausea, vomiting, dizziness, and diarrhea.
Treatments include fluid and electrolyte replacement.
Undesirable Effects
Side effects include headache, drowsiness, nausea, gastric discomfort, mental confusion, ataxia and skin rash. Other side effects include a number of endocrine changes including abnormal enlargement of breasts in men (gynaecomastia), menstrual irregularity, impotence, and loss of libido. Transient increase in blood-urea-nitrogen concentrations may occur and mild acidosis has been reported. Spironolactone may cause hyponatraemia and hyperkalemia. The rapid diuresis may cause acute discomfort and incontinence in some elderly patients.
PHARMACEUTICAL INFORMATION
Storage Condition
Store in a cool and dry place away from light. Protect from light and moisture. Keep out of reach of children.
Presentation & Packaging
Furo-Plus TM:: Each commercial box contains 3x10, 5x10, 10x10 tablets in Alu-Alu blister-pack.
LF02401TM-Trade MarkManufactured ByMymensingh, Bangladesh
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