Spironolactone dosage

Adults (CHF, hepatic cirrhosis, nephrotic syndrome) - Initially, 100 mg/day (range, 25 to 200 mg/day). When given as the sole diuretic agent, continue for 5 days at the initial dosage level, then adjust to the optimal level. If after 5 days an adequate diuretic response has not occurred, add a second diuretic, which acts more proximally in the renal tubule. Because of the additive effect of spironolactone with such diuretics, an enhanced diuresis usually begins on the first day of combined treatment combined therapy is indicated when more rapid diuresis is desired. Spironolactone dosage should remain unchanged when other diuretic therapy is added. 

Electrolyte balance When 175 patients with resistant hypertension took spironolactone 25-100 mg/day adverse effects that were attributed to the drug included an acute reduction in renal function in two patients and asymptomatic hyperkalemia (serum potassium concentration over 5.5 mmol/1) in two patients spironolactone was withdrawn in these patients and in one patient, hyperkalemia resolved following a reduction in spironolactone dosage [25 ]. 

Hyperkalemia (increase in potassium in the blood), a serious event, may be seen with the administration of potassium-sparing diuretics. Hyperkalemia is most likely to occur in patients with an inadequate fluid intake and urine output, those with diabetes or renal disease tiie elderly, and those who are severely ill. In patients taking spironolactone, gynecomastia (breast enlargement in tiie male) may occur. This reaction appears to be related to both dosage and duration of therapy. The gynecomastia is usually reversible when therapy is discontinued, but in rare instances, some breast enlargement may remain. 

Spironolactone is also an androgen antagonist and as such is sometimes used in the treatment of hirsutism in women. Dosages of 50-200 mg/d cause a reduction in the density, diameter, and rate of growth of facial hair in patients with idiopathic hirsutism or hirsutism secondary to androgen excess. The effect can usually be seen in 2 months and becomes maximal in about 6 months. 

Eplerenone, another aldosterone antagonist, is approved for the treatment of hypertension (see Chapters 11 and 15). This aldosterone receptor antagonist is somewhat more selective than spironolactone and has no reported effects on androgen receptors. The standard dosage in hypertension is 50-100 mg/d. The most common toxicity is hyperkalemia but this is usually mild. 

Spironolactone, a competitive inhibitor of aldosterone (see Chapter 15), also competes with dihydrotestosterone for the androgen receptors in target tissues. It also reduces 17a-hydroxylase activity, lowering plasma levels of testosterone and androstenedione. It is used in dosages of 50-200 mg/d in the treatment of hirsutism in women and appears to be as effective as finasteride, flutamide, or cyproterone in this condition. 

First-derivative spectroscopy was applied to the analysis of mixture of spironolactone and frusemide in combined dosage forms [19], Calibration curves were linear up to 20 pg/mL. The same mixture has been analyzed by extraction with methanol, and subsequent measurement in either 0.1 N HC1 or in 0.1 N NaOH [20], The relative standard deviation was in the... 

Other spectrophotometric techniques have been reported for the analysis of spironolactone. Near infrared diffuse reflectance first-derivative spectroscopy was used for determination of spironolactone in pharmaceutical dosage forms [30]. Readings were taken at 15 nm intervals, and then 81 absorbance readings were imput into a computer for principal component analysis. 

HPLC is the most frequently used technique for the analysis of spironolactone as the bulk drug, in its dosage forms, or in biological fluids. The reported HPLC methods are summarized in Table 6. 

Because indomethacin may increase serum potassium concentrations, indomethacin and spironolactone should be administered concomitantly with caution. Potassium-sparing diuretics should be used with caution, and serum potassium should be determined frequently in patients receiving an angiotensin-converting enzyme (ACE) inhibitor (e.g., captopril). Concomitant administration with an ACE inhibitor may increase the risk of hyperkalemia. The dosage of spironolactone should be reduced, or the drug discontinued, as necessary. Patients with renal impairment may be at increased risk of hyperkalemia [65]. 

When used in conjunction with other diuretics or hypotensive agents, spironolactone may be additive with, or may potentiate, the action of these drugs. Therefore, dosage of these drugs, particularly ganglionic blocking agents, may need to be reduced by at least 50% when concomitant spironolactone therapy is instituted. 

Spironolactone may increase the half-life of digoxin, so dosage reduction or increased dosing intervals of digoxin may be necessary, and careful monitoring is recommended. 

The dosage of spironolactone is 100 to 400 mg/day in 2-3 single doses. That of potassium canrenoate amounts 100 to 800 mg/day. When therapy commences with potassium canrenoate, spironolactone should be administered orally 1-2 days prior to the intended termination of the i.v. application to ensure a smooth transition, since the onset of its effect is delayed. In 25-30% of male patients, long-term application leads to (generally reversible) potency disorders and gynaecomastia. 

A dosage of 20 to 40 mg xipamide per day is recommended in 1-2 (-3) single doses. For long-term therapy, it is advisable to prescribe 10 mg. Diuresis sets in after about 1 hour with a peak after 2 to 8 hours. There is no rebound effect. The excretion of sodium and chloride is increased to an almost identical degree calciuria, magnesiuresis and kaliuresis occur. For this reason, xipamide should be combined with spironolactone. Biotransformation of xipamide is clearly limited in cirrhotic patients, the half-life (7 hours) is not influenced. Xipamide passes into the ascitic fluid and reaches concentrations of 10-20% of the respective plasma level. It can even be used with restricted renal function, since it has no influence on renal haemodynamics. 

Etacrynic acid, especially in combination with spironolactone and xipamide, markedly enhances natriuresis and diuresis. The dosage is increased as required (e.g. 1 X 25 mg or 50 mg to 2 x 50 mg per day). With a low-dose application in the form of a combined diuretic therapy, there is usually no risk of hepatic encephalopathy developing. The effect of etacrynic acid sets in at the ascending branch of the loop of Henle (active chloride transport). Renovascular resistance is lowered due to enzymatic activity, presumably as a result of a rise in the release of prostaglandin. 

Step 1 (7.) lactulose (2-3 stools/day) and (2.) spironolactone (50 mg per day or every second day). This dosage is practically free of side effects - even during longterm administration, (s. pp 278, 306, 858)... 

Spironolactone inhibits the active tubular secretion of digoxin by about 25% and in some cases digoxin dosages may have to be reduced (295). 

In low dosages (up to 2 g/day), aspirin reduces urate excretion and blocks the effects of probenecid and other uricosuric agents (22,23). However, in 11 patients with gout, aspirin 325 mg/day had no effect on the uricosuric action of probenecid (22). In higher dosages (over 5 g/ day), salicylates increase urate excretion and inhibit the effects of spironolactone, but it is not clear whether these phenomena are of importance. 

Management of these disorders usually consists of treatment of the underlying cause of the mineralocorticoid excess. Patients who are taking corticosteroids may require a dosage reduction or may need to be switched to a corticosteroid with less mineralocorticoid activity. Patients with an endogenous source of excess mineralocorticoid activity may require surgery or the administration of spironolactone, amiloride, or triamterene. " " ... 

Spironolactone, an antiandrogen and inhibitor of 5a-reductase, re-dnees sebum production and improves acne at dosages of 50 to 200 mg twice daily in patients with acne resistant to conventional therapy. Most commonly, it is used in countries where other antiandrogen drugs are not available. 

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