Probon

Uses

Probon is used for Congestive heart failure, Hepatic cirrhosis with ascites and oedema, Nephrotic syndrome, Primary hyperaldosteronism, Essential hypertension, For the treatment of patients with hypokalemia

Probon is a long-acting aldosterone antagonist. Probon is a specific pharmacologic antagonist of aldosterone, acting primarily through competitive binding of receptors at the aldosterone dependent sodium-potassium exchange site in the distal convoluted renal tubule. Probon causes increased amounts of sodium and water to be excreted, while potassium and magnesium is retained.

Probon is also used to associated treatment for these conditions: Acne, Ascites, Congestive Heart Failure (CHF), Edema, High Blood Pressure (Hypertension), Hypokalemia, Idiopathic Hirsutism, Nephrotic Syndrome, Primary Hyperaldosteronism, Secondary hyperaldosteronism, Chronic heart failure with reduced ejection fraction (NYHA Class III), Chronic heart failure with reduced ejection fraction (NYHA Class IV), Idiopathic hyperaldosteronism

How Probon works

Probon competitively inhibits aldosterone dependant sodium potassium exchange channels in the distal convoluted tubule. This action leads to increased sodium and water excretion, but more potassium retention. The increased excretion of water leads to diuretic and also antihypertensive effects.

Dosage

Probon dosage

Edema in adults (congestive heart failure, hepatic cirrhosis, or nephrotic syndrome): An initial daily dosage of 100 mg of Probon administered in either single or divided doses is recommended, but may range from 25 to 200 mg daily. Combined therapy with other diuretics is indicated when more rapid diuresis is desired.

Primary hyperaldosteronism: After the diagnosis of hyperaldosteronism has been established, Probon may be administered in doses of 100 to 400 mg daily in preparation for surgery. For patients who are considered unsuitable for surgery, Probon may be employed for long-term maintenance therapy at the lowest effective dosage determined for the individual patient.

Essential hypertension: For adults, an initial daily dosage of 50 to 100 mg of Probon administered in either single or divided doses is recommended.

Hypokalemia: Probon in a dosage ranging from 25 mg to 100 mg daily is useful in treating a diuretic-induced hypokalemia.

Side Effects

Gynaecomastia may develop in association with the use of Probon. Other adverse reactions are: GI symptoms including cramping and diarrhoea, drowsiness, lethargy, headache, urticaria, mental confusion, impotence, irregular menses or amenorrhoea and post-menopausal bleeding.

Toxicity

Patients experiencing an overdose may present with drowsiness, mental confusion, maculopapular or erythematous rash, nausea, vomiting, dizziness, or diarrhea. Vomiting is generally induced or a gastric lavage is performed. Supportive treatment involves maintining hydration, electrolyte balance, and vital functions.

The oral LD50 in mice, rats, and rabbits is >1g/kg.

Probon should be avoided in pregnancy due to reports of feminization of male fetuses in animal studies. Active metabolites of spironolactone are present in breast milk and levels that are likely inconsequential, though the long term effects have not been studied.

In animal studies, spironolactone slowed follicle development, ovulation, and implantation. Probon increased the incidence of benign adenomas in the testes of male rats, benign uterine endometrial stromal polyps in female rats, and thyroid follicular cell adenomas in both sexes of rats. Probon and canrenone are generally not considered to be mutagenic in tests but canrenone occasionally tests positive for mutagenicity with metabolic activation and spironolactone has occasionally tested inconclusive though slightly positive for mutagenicity.

Precaution

All patients receiving diuretic therapy should be observed for evidence of fluid or electrolyte imbalance. Hyperkalemia may occur in patients with impaired renal function or excessive potassium intake and can cause cardiac irregularities, which may be fatal.

Interaction

ACE inhibitors: Concomitant administration of ACE inhibitors with potassium-sparing diuretics has been associated with severe hyperkalemia.

Alcohol, barbiturates, or narcotics: Potentiation of orthostatic hypotension may occur.

Corticosteroids, ACTH: Intensified electrolyte depletion, particularly hypokalemia, may occur.

Lithium: Lithium generally should not be given with diuretics. Diuretic agents reduce the renal clearance of lithium and add a high risk of lithium toxicity.

Digoxin: Probon has been shown to increase the half-life of digoxin.

Food Interaction

• Avoid alcohol.
• Avoid potassium-containing products. Potassium products increase the risk of hyperkalemia.
• Take with or without food. Food increases the bioavailability of spironolactone by nearly 100%. It should be taken at a consistent time in regards to food.

Probon Alcohol interaction

[Moderate]

Many psychotherapeutic and CNS-active agents (e.g., anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, opioids, alcohol, muscle relaxants) exhibit hypotensive effects, especially during initiation of therapy and dose escalation.

Coadministration with antihypertensives and other hypotensive agents, in particular vasodilators and alpha-blockers, may result in additive effects on blood pressure and orthostasis.

Caution and close monitoring for development of hypotension is advised during coadministration of these agents.

Some authorities recommend avoiding alcohol in patients receiving vasodilating antihypertensive drugs.

Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia.

Probon Drug Interaction

Major: sacubitril / valsartanModerate: duloxetine, apixaban, metoprolol, metoprolol, alprazolamMinor: aspirin, aspirinUnknown: omega-3 polyunsaturated fatty acids, furosemide, atorvastatin, pregabalin, clopidogrel, montelukast, levothyroxine, acetaminophen, cyanocobalamin, ascorbic acid, cholecalciferol, cetirizine

Probon Disease Interaction

Major: acidosis, diabetes, electrolytes/fluid, hyperkalemia, liver disease, renal dysfunctionModerate: hyperuricemia

Volume of Distribution

Volume of distribution data is not readily available.

Elimination Route

Probon reaches a maximum concentration in 2.6 hours and an active metabolite (canrenone) reaches a maximum concentration in 4.3 hours. When taken with food, the bioavailability of spironolactone increases to 95.4%.

Giving spironolactone with food increases the maximum concentration from 209ng/mL to 301ng/mL. The time to maximum concentration also increases from 2.28 hours to 3.05 hours. The area under the curve varies from 2103ng/mL*hr to 4544ng/mL*hr.

Half Life

1.4 hours.

Canrenone has a half life of 16.5 hours, 7-α-thiomethylspirolactone has a half life of 13.8 hours, and 6-ß-hydroxy-7-α-thiomethylspirolactone has a half life of 15 hours.

Clearance

Clearance data is not readily available.

Elimination Route

Metabolites of spironolactone are excreted 42-56% in urine, and 14.2-14.6% in the feces. No unmetabolized spironolactone is present in the urine.

Pregnancy & Breastfeeding use

Pregnancy: Probon should not be used during pregnancy

Lactation: Canrenone, an active metabolite of Probon, appears in breast milk. If use of the drug is deemed essential an alternative method of infant feeding should be instituted.

Contraindication

Probon is contraindicated in patients with acute renal insufficiency, significant impairment of renal function, anuria, hyperkalaemia or sensitivity to Probon.

Acute Overdose

Symptoms of overdosage include drowsiness, mental confusion, dizziness, diarrhea and vomiting etc. Patients should induce vomiting or evacuate the stomach by lavage during Probon overdoasge.

Storage Condition

Store in a cool and dry place protected from light. Keep out of reach of children.

Innovators Monograph

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