Fludrocortisone

Fludrocortisone is a synthetic steroid hormone belonging to the pharmacological class of mineralocorticoids.

Fludrocortisone, approved by the FDA, aids in managing conditions such as adrenal insufficiency, salt-losing adrenogenital syndrome, and orthostatic hypotension by regulating salt and fluid levels in the body.

Fludrocortisone rapidly absorbs in the GI tract, extensively binds to plasma proteins, and distributes into tissues, including breast milk and the placenta. Liver metabolism enhances its mineralocorticoid potency due to unique 9α-fluorination. Excretion occurs mainly via urine.

The most common side effects of Fludrocortisone include behavioural changes, weight gain, bone disorder, and skin thinning.

Fludrocortisone is available in the form of tablets.

The molecule is available in the United States, Canada, the United Kingdom, Australia, Germany, France, Italy, Japan, India and Brazil.

Fludrocortisone is a synthetic steroid hormone belonging to the pharmacological class of Mineralocorticoids.

The principal endogenous mineralocorticoid, aldosterone, controls potassium excretion and salt reabsorption in the kidneys, preserving blood pressure and electrolyte balance. When aldosterone production is inadequate, as in Addison's illness, Fludrocortisone and other exogenous mineralocorticoids take over. Stimulating DNA transcription caused by Fludrocortisone's binding to mineralocorticoid receptors increases the density of sodium channels on the apical side of renal tubule cells and the density of Na+-K+-ATPase on the basolateral side. As a result, blood pressure rises, and plasma potassium levels fall due to increased plasma sodium. Moreover, Fludrocortisone may directly influence plasma sodium through the Na+-H+ exchanger located in the apical membrane of renal tubule cells. 

Fludrocortisone peaks in plasma within approximately 1.7 hours.

The duration of action of Fludrocortison generally lasts for several hours.

The data onset of Fludrocortisone action typically begins within a few hours after administration

The Cmax (maximum plasma concentration) and Tmax (time to reach maximum concentration) of Fludrocortisone are typically observed at around 1.5 to 2 hours post-administration.

Fludrocortisone is available in the form of tablets.

Tablets: To be swallowed whole with water/liquid. Do not chew, crush or break it.

As the physician recommends, take the medication orally once daily; it can be taken with or without food as directed.

Fludrocortisone can be used for the following health conditions:

Fludrocortisone actively supplements deficient hormones in Addison's disease, a condition of insufficient hormone production by the body. It replaces essential corticosteroids, aiding in retaining sodium and enabling the body to function correctly by maintaining adequate salt levels for optimal bodily functions.

Fludrocortisone actively assists in managing congenital adrenal hyperplasia (CAH), a genetic disorder impacting a child's growth. It regulates electrolyte balance, preventing dehydration and sustaining blood pressure by replacing cortisol, which is significantly reduced in this condition. This hormone replacement supports vital bodily functions, improving individuals' overall quality of life with CAH.

Fludrocortisone is indicated for the treatment of the following conditions:

Orally: Fludrocortisone tablets are typically administered orally and usually taken once daily, often in the morning, with or without food; however, they help with meals to minimize GI upset to ensure optimal efficacy. The medication should be swallowed whole with water.

The dosage and duration of treatment should be as per the treating physician's clinical judgment.

Fludrocortisone is available in the form of tablets.

Dose: 0.1 mg PO three times a week to 0.2 mg PO per day; typical, 0.1 mg PO

In the event of hypertension: 0.05 mg daily PO

0.1–0.2 mg daily PO

0.1 mg/day PO in conjunction with a high-salinity diet and enough fluid consumption; this can be raised to 1 mg/day in weekly increments.

Over 0.3 mg daily doses have not been demonstrated to be helpful and may put a patient at risk for adverse reactions.

When taking Fludrocortisone, it's essential to maintain your diet stable and limit the amount of salt to prevent blood pressure fluctuations. Include foods high in heart-healthy omega-3 fatty acids and low-fat oils such as canola, olive, soybean, and coconut oil. Eat fruits, vegetables, yoghurt, and bananas in addition to Fludrocortisone to protect the lining of your stomach. Choose meals high in omega-3s, such as walnuts, salmon, tuna, flaxseeds, and soybean oil, to reduce discomfort, swelling, and inflammation. To reduce inflammation, choose whole meals, lower carbs, and avoid processed, sugary, and greasy foods. Use natural anti-inflammatory herbs such as turmeric, ginger, and garlic, and cut back on salt. Reduce alcohol intake to improve nutrition absorption and digestive health. Regular check-ups, including blood pressure, electrolytes, and general health, prevent side effects and ensure treatment efficacy.

The dietary restriction should be individualized as per patient requirements.

Fludrocortisone may be contraindicated in the following conditions:-

The adverse reactions related to Fludrocortisone can be categorized as:

The clinically relevant drug interactions of Fludrocortisone are briefly summarized here.

Fludrocortisone may heighten the risk of arrhythmias or toxicity with digitalis glycosides. It can decrease the response of prothrombin time to oral anticoagulants. Additionally, it may diminish the therapeutic effects of antidiabetic drugs and aspirin while reducing the reaction to vaccines. Furthermore, the hypokalemic effect can intensify when used with amphotericin B or potassium-depleting diuretics. Increased metabolic clearance is observed with barbiturates, phenytoin, and rifampicin.

Additionally, it can elevate the risk of oedema with anabolic steroids, especially C-17 alkylated androgens like oxymetholone. Estrogens may elevate corticosteroid-binding globulin levels, increasing the bound (inactive) fraction. Fludrocortisone also counteracts the effect of anticholinesterase agents, enhances the neutropenic effect of immunosuppressants, and exacerbates the adverse effects of NSAIDs.

The common side effects of Fludrocortisone include:-

increased BP;

bloating and stomach ache;

redness on the face;

acne, excessive perspiration;

difficulties with sleep (insomnia);

under-skin pitting, scars, or lumps;

stretch marks.

Pregnancy Category C: Use caution if the benefits outweigh the risks.

There are no human studies on the use of Fludrocortisone during pregnancy. Corticosteroids given during pregnancy have been linked to complications such as preterm abortion, stillbirth, and cleft palate. Pregnant women should only get fludrocortisone acetate if it is necessary. The patient should be informed of the possible dangers if these medications must be taken while pregnant. To guarantee proper replacement during pregnancy, the mother would need extra monitoring; fetal dangers are linked to inadequate treatment of Addison's illness during pregnancy. The standard course of treatment for Addison's disease is typically followed both during and after pregnancy. As the mother's needs recover to pre-pregnancy levels after giving birth, dosage changes may be necessary for appropriate replacement. When a mother uses large amounts of corticosteroids during her pregnancy, her unborn child should be watched for hypoadrenalism symptoms. Furthermore, the infant's medical records should contain thorough documentation of the mother's corticosteroid medication to facilitate follow-up.

Breast milk contains corticosteroids. When using Fludrocortisone during breastfeeding, care should be taken to avoid any potential adverse effects or the possibility of the newborn developing hypoadrenalism.

The safety and efficacy of Fludrocortisone in pediatric use have been established for specific conditions like congenital adrenal hyperplasia and salt-wasting adrenogenital syndrome, following careful consideration of dosage and individual patient requirements.

Not FDA-approved for use in children

0.05 to 0.1 mg per day PO in a single daily dose or divided q12hr in combination with sodium chloride supplementation

0.05 to 0.3 mg per day PO

Renal impairment: No dosage adjustments are needed.

Hepatic impairment: No dosage adjustments are needed.

The physician should be vigilant about the knowledge pertaining to the identification and treatment of overdosage of Fludrocortisone.

Overconsumption of Fludrocortisone could lead to hypertension, oedema, hypokalemia, and heart failure.

There is no specific antidote or treatment for excessive Fludrocortisone. Thus, symptomatic and supportive measures constitute treatment. In recent ingestions, gastric lavage or activated charcoal may limit absorption. Symptomatic management includes addressing nausea, vomiting, and abdominal discomfort.

Vital signs, electrolytes, and cardiovascular function require close monitoring. IV fluids maintain hydration and correct electrolyte imbalances like hypokalemia. Severe overdose cases may necessitate interventions like diuretics or antihypertensive medications for managing hypertension or oedema. Corticosteroid antagonists could potentially counteract excessive corticosteroid effects in specific scenarios. Continuous medical oversight and tailored interventions are vital for managing Fludrocortisone overdose, as no specific antidote exists for its excess.

When there is insufficient or no endogenous aldosterone synthesis, Fludrocortisone, a synthetic mineralocorticoid, is used to replace it. It stimulates the kidneys' ability to excrete potassium and reabsorb sodium. Fludrocortisone has a relatively short plasma half-life, but because it acts at the transcriptional level, a single dose may have effects lasting one to two days. Fludrocortisone depresses the natural immunological response, similar to other systemic corticosteroids, so infections that emerge while on fludrocortisone therapy should be treated immediately with the proper antimicrobial therapy.

Fludrocortisone rapidly and completely absorbs from the GI tract, reaching peak plasma concentrations within 1.5 hours.

It extensively binds to plasma proteins like albumin and transcortin, with only the unbound fraction showing activity.

The drug quickly distributes into various tissues, including kidneys, intestines, skin, liver, and muscles. It crosses into breast milk and the placenta. Plasma protein binding occurs at a rate of 70-80%, predominantly with globulin fractions.

The liver metabolizes Fludrocortisone into inactive forms. Its 9α-fluorination simplifies metabolism compared to other corticosteroids, protecting it from 11β-oxidation, thereby enhancing its mineralocorticoid potency.

A small amount of unchanged drug is excreted in urine. The biological half-life ranges from 18 to 36 hours, with an elimination half-life of at least 3.5 hours in plasma.