Potasium sparing diuretics include -
Spironolactone, Amiloride, Traimterene
Interacting drugs - summary
hypoprothrombinemic effect decreased
interaction difficult to predict. Spironolactone increases the half-life
of digoxin and can decrease claerance. This may result in increased
serum digoxin levels and subsequent toxicity. Spironolactone both
decreases and increases digitoxins elimination half-life
one patient failed to respond to mitotane while receiving concurrent
spironolactone. Mitotane toxicity developed when the drug was
concurrent administration result in hyperkalemia , possibly with
cardiac arhythmias or cardiac arrest. Avoid concomittant use.
use of ACE inhibitors may elevate serum potassium. Concurrent use with
Spironolactone lead to hyperkalemia
diuretic effect of spironolactone may be decreased by concurrent
salicylate use, due to reduced tubular secretion of canrenone,
this interaction is dose dependent.
observe patients for hypokalemia
Essential hypertension. Hyperkalemia.
FIXED DOSE COMBINATIONS APPROVED BY DCG(I)
FROM JANUARY 1961 TILL NOVEMBER 2014
Name of Drug Indication Date of Approval
1.Spironolactone 25mg + 03-05-2010
Frusemide 20mg tablets
For the teatment of resistent odema associated with
secondary hyperaldoseronism, resistent hypertension
chronic cardiac failure and hepatic cirrhosis
2.Spironolactone IP 25mg + 05-01-2011
Furosemide IP 40mg tablet
for the treatment of resistent oedema associated with
secondary hyperaldosteronism, resistent hypertension
chronic cardiac failure and hepatic cirrhosis
Advese reaction are fully reversible upon discontinuation of the drug
GI- cramping, diarrhea, gastricbleeding, ulceration, gastritis, vomiting
CNS- drowsiness, lethargy, headache, mental confusion, ataxia.
Endocrine- inacbility to acheive or maitain erection, gynaercomatia, irregular menses, or amenorrhea, postmenopausal bleeding, hirustism, deepening of voice
Dermatologic- maculopapular or erythematous cutaneous eruptions, urticara
Miscellaneous- drug fever, hypercholremic mettabolic acidosis, in decompensated hepatic cirrhosis,carcinoma of the breast, agrunolcytosis
Anuria,hyperkalaemia,acute or progressive renal insufficiency. Addisons disease. Lactation.
Hypersens to thiazides.
Monitor serum electrolytes, renal & hepatic impairment. Pregnacy. Gout. Diabetes. Long term use in young patients.
Hyponatremia- may be caused or aggravated by spironolactone especially in combination with other diuretics.
Symptoms include dry mouth, lethargy, drowsiness.
Gynaecomastia- may develop and appears to be related to to both dosage and duration of therapy. It is normally reversible when therapy is disconitnued , however, in rare instances, some breast enlagement may persist
Reversible hyperchloremic metabolic acidosis- usually in association with hyperkalemia, occurs in some patients withdecompensated cirhosis, even in the presence of normal renal function.
Spironolcatone has been shown to be tumerigen in chronic toxicity studies in rats.use only in the conditions that are necessary.Avoid unnecessary use of the drug.
Hyperkalemia- carefully evaluate patients for possible fluid and electrolyte balance disturbances. Hyperkalemia may occur with impaired renal function or excessive potassium. No potassium supplement should ordinarily be given with spironolactone.
Treat Hyperkalemia- promptly by rapid IV glucose (20% to 50% ) and regular insulin 0.25 to 0.5 units of insulin/g of glucose. This temporarymeasure to repeated as required.
Renal function impairment- use of spironolactone may cause a transcient elevation of BUN especially in patients with preexisting renal impairment. The drug may cause mild acidosis.
Carcinogenesis- spironolactone was a tumorigen in chronic toxicity studies in rats. At 25 to 250 times the usual human dose there was a significant dose-related increase in benign adenosine of thyroid and testes, in malignant mammary tumors and in proliferative changes in the liver.
Pregnancy- weigh anticipated benefit against possible hazard to the fetus.
Lactation- The American Academy of Pediatriics considers the drug to be compatible with breast feeding.
Dosages/ Overdosage Etc:
Primary hyperldosteronism, essential hypertension. Hyperkalemia.
Administered single or divided dose. 400 mg/day for 3 to 4 weeks depending on the intensity of requirement.
1. If you miss a dose of this medicine, take it as soon as possible.
2. However, if it is time for your next dose, skip the missed dose and go back to your regular dosing schedule.
3. Do not double doses.
Hyperkalemia ( 442 )
Hyperkalemia is a cardinal feature of adrenal insufficiency ( Addisons disease) and of selective hypoaldosteronism
The causes of haypekalemia are
1. Inadequate excretion
2. Adrenal insufficiency
3. Shift of potassium from tissues
4. Excessive intake
Drugs causing adverse reactions- Hyperkalemia
5. Corticosteroids - withdrawal
7. Digitalis ovedose
8. Potassium salts of drugs
9. Potassium preparations including salt substitutes
1.May produce drowsiness,lack of coordination or mental confusion; observe caution while
driving or performing tasks requiring alertness, coordination or physical dexterity.
2. May cause GI, cramping, diarrhoea, lethargy, thirst, headache, skin rash, menstrual
abnormalities, deepening of voice and breast enlargement in men. Notify physician if these occur.
3. Allergies- Tell your doctor if you have ever had any unusual or allergic reactions to amiloride, spironolactone, or triamterene or other related medicines. Also tell your doctor if your are allergic to any other substances such as foods, preservatives or dyes.
4. Pregnancy- this medicine has not been shown to cause birth defects or other problems in animals
5. Breast feeding- although amiloride, spironolactone and triamterene may pass into breast milk, these medicines has not been reported to cause problems in nursing babies
6. Children- these medicines are not expected to cause differnt side effects in children than they do in adults.
7. Elderly- signs and symptoms of too much potassium are more likely to occur in elderly, who are more sensitive
to the effects of this medicine
8. Other medicines- tell your doctor if you are taking any of the following-
Angiotensin -converting enzyme ACE inhibitors or
Potassium containing medicines or supplements - use with potassium sparing diuretics may cause
high blood levels of potassium which may increase the chance of side effects
Digoxin - use with spironolactone may cause high blood levels of digoxin which may increase the
chance of side effects.
Lithium - use with potassium sparing diuretics may cause high blood levels of lithium which may
increase the chance of side effects
9. Other medical problems- tell your doctor if you have any other medical problems-
Diabetes mellitus or -
Kidney disease or
Liver disease - higher blood levels of potassium may occur which may increase the chance of side
Kidney stones - triamterene may make these conditions worse
Menstrual problems or breast enlargement - spironolactone may make these condition worse
10. Missed dose-
If you miss a dose of this medicine take it as soon as possible. However if it is almost time for your next dose go back to your regular dosing schedule.
Do not double doses.
Ref- Drug Facts And Comparisons (2010)
In the kidney potassium is filtered at the glomerulus and then absorbed parallel to sodium throughout the proximal tubule and thick ascending limb of the loop of Henle so that minor amounts reach the distal convulated tubule.
As a result potassium appearing in the urine is secreted at the distal tubule and collecting duct. The potassium -sparing diuretics interfere with sodium reabsorption at the distal tubule thus decreasing potassium secretion.
Spiranolactone pharmacokinetic Data
Accumulation Mean Peak Mean (SD)
Factor serum post-
AUC (0-24h concentn steady state
day 15) half life
7-a-(thiomethyl 1.25 391ng/mL 13.8h
spirolactone at 3.2h (6.4)
6-b-hydroxy-7- 1.5 125ng/mL 15h
a-(thiomethyl) at 5.1h (4)
Canrenone(C) 1.41 181ng/mL 16.5h
at 4.3h (6.3)
Spironlactone 1.3 80ng/mL approx
at 2.6h 1.4h (0.5)
Interaction with Food:
May increase absorption of the drug.
Pregnancy and lactation:
Spironolactone or its metabolites may cross the placental barrier. Weigh anticipated benefit against possible hazard to the fetus.
Canrenone, a metabolite of spironolactone, appears in breast milk. The American Academy of Pediatrics considers the drug to be compatible with breast feeding