UNICORT

Indications

• Adrenal insufficiency
• Addison's disease
• Congenital adrenal hyperplasia
• Orthostatic hypotension

Dosage

Children: Refer to the BNF for Children for specific dosing recommendations.

Adults: The usual dosage for adults is 0.1 mg to 0.2 mg once daily, adjusted based on clinical response and electrolyte levels.

Mechanism of action

Fludrocortisone binds to mineralocorticoid receptors in the renal tubules, increasing the density of sodium channels and Na+-K+-ATPase on renal cell membranes. This enhances sodium reabsorption and potassium excretion, leading to elevated plasma sodium levels and increased blood pressure. Although it also interacts with glucocorticoid receptors, its mineralocorticoid potency is significantly higher, resulting in pronounced effects on fluid and electrolyte balance.

Pharmacodynamics

Fludrocortisone's primary action is to mimic aldosterone, facilitating sodium retention and potassium loss. This mechanism operates through transcriptional changes that alter protein synthesis related to ion transport in the kidneys. Its effects can persist for 1-2 days even with a short half-life, as it influences gene expression and cellular function.

Pharmacokinetics

Fludrocortisone is well absorbed after oral administration, with peak plasma concentrations reached within a few hours. It undergoes hepatic metabolism and has a relatively short half-life, necessitating careful dosing to maintain therapeutic levels. The drug is predominantly excreted via urine, and its pharmacokinetic profile may be affected by interactions with other medications.

Contra-indications

• Systemic fungal infections
• Known hypersensitivity to fludrocortisone or any of its excipients

Adverse effects

• Hypertension
• Hypokalemia
• Fluid retention
• Edema
• Weight gain
• Gastrointestinal disturbances
• Mood changes
• Increased susceptibility to infections

Interactions

• mitotane+fludrocortisone: Moderate (decreases exposure)
• rifampicin+fludrocortisone: Moderate (decreases exposure)
• cobicistat+fludrocortisone: Unknown (increases exposure)
• idelalisib+fludrocortisone: Unknown (increases exposure)
• clarithromycin+fludrocortisone: Unknown (increases exposure)

Precautions

• Monitor blood pressure regularly during treatment
• Assess electrolyte levels, particularly potassium
• Use caution in patients with cardiovascular disease
• Caution in patients with a history of peptic ulcer disease

Pregnancy

Fludrocortisone is classified as category C. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Fludrocortisone is excreted in breast milk. Caution should be exercised when administered to a nursing mother.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Tablets

Indications

• Adrenocortical insufficiency
• Congenital adrenal hyperplasia
• Orthostatic hypotension
• Salt-wasting adrenocortical insufficiency

Dosage

Children: Refer to the BNF for Children for pediatric dosing recommendations, as specific dosages vary significantly by age and clinical condition.

Adults: 100–400 micrograms daily for conditions requiring mineralocorticoid replacement, adjusted based on clinical response.

Mechanism of action

Fludrocortisone acetate exerts its effects primarily by binding to mineralocorticoid receptors in the distal nephron, leading to increased sodium reabsorption and potassium excretion. This action promotes water retention, subsequently increasing blood volume and blood pressure.

Pharmacodynamics

Fludrocortisone has a strong mineralocorticoid effect with minimal glucocorticoid activity, which distinguishes it from other corticosteroids. Its mineralocorticoid activity leads to significant sodium retention, potassium excretion, and increases in blood volume, which are critical in managing conditions like adrenal insufficiency and orthostatic hypotension.

Pharmacokinetics

Fludrocortisone is well absorbed from the gastrointestinal tract, and its effects can last for several days due to its long half-life. It undergoes hepatic metabolism and is excreted primarily in the urine. The onset of action is typically within 1-4 hours after oral administration, with peak effects observed within 8-12 hours.

Adverse effects

• Hypertension
• Hypokalemia
• Edema
• Weight gain
• Hyperglycemia
• Gastrointestinal disturbances
• Mood changes
• Osteoporosis

Interactions

• Potassium-depleting diuretics may enhance the risk of hypokalemia
• Anticoagulants may have altered effects
• Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of gastrointestinal side effects

Precautions

• Monitor blood pressure regularly
• Assess serum electrolytes, particularly potassium
• Use cautiously in patients with heart failure or hypertension
• Taper dosage gradually to avoid adrenal insufficiency upon discontinuation

Pregnancy

Fludrocortisone acetate may cross the placenta. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Fludrocortisone is excreted in breast milk. Caution is advised when administered to nursing mothers.

Storage

Store at room temperature, away from moisture and direct light. Keep out of reach of children.

Formulations

• Tablets: 100 micrograms, 200 micrograms
• Oral solution: concentration not specified in the available data

Mechanism of action

The main endogenous mineralocorticoid, aldosterone, is produced in the zona glomerulosa of the adrenal cortex - it acts on mineralocorticoid receptors in the kidneys to increase sodium reabsorption and potassium excretion, which in turn helps to regulate plasma electrolyte composition and blood pressure. In conditions of adrenal insufficiency, such as Addison’s disease, aldosterone is not produced (or is produced in insufficient quantities) and must be replaced by exogenous mineralocorticoids such as fludrocortisone. Fludrocortisone binding to mineralocorticoid receptors causes alterations to DNA transcription and translation of proteins that result in an increased density of sodium channels on the apical side of renal tubule cells and an increased density of Na⁺-K⁺-ATPase on the basolateral side. These increases in receptor density result in increased plasma sodium concentrations, and thus increased blood pressure, as well as a decreased plasma potassium concentration. Fludrocortisone may also exert a direct effect on plasma sodium levels via action at the Na⁺-H⁺ exchanger found in the apical membrane of renal tubule cells. Fludrocortisone also acts on glucocorticoid receptors, albeit with a much lower affinity - the glucocorticoid potency of fludrocortisone is approximately 5-10 times that of endogenous cortisol, whereas its mineralocorticoid potency is 200-400 times greater. At the cellular level, corticosteroids diffuse across cell membranes and complex with specific cytoplasmic receptors. These complexes then enter the cell nucleus, bind to DNA (chromatin), and stimulate transcription of mRNA (messenger RNA) and subsequent protein synthesis of various enzymes thought to be ultimately responsible for the physiological effects of these hormones. Mineralocorticoids act on the distal tubules to increase potassium excretion, hydrogen ion excretion, and sodium reabsorption and subsequent water retention. Cation transport in other secretory cells is similarly affected; excretion of water and electrolytes by the large intestine and by salivary and sweat glands is also altered, but to a lesser extent.

Pharmacodynamics

Fludrocortisone is a synthetic mineralocorticoid used to replace endogenous [aldosterone] in conditions resulting in missing or inadequate endogenous synthesis. It acts on the kidneys to increase both sodium reabsorption and potassium excretion. As its effects are exerted at the transcriptional level, a single dose of fludrocortisone may work over the course of 1-2 days despite a relatively short plasma half-life. Like other systemic corticosteroids, fludrocortisone may mask signs of infection by depressing the normal immune response - infections occurring during fludrocortisone therapy should be promptly treated with appropriate antimicrobial therapy.