What are the primary uses of Fludrocortisone. How should Fludrocortisone be taken. What are the potential side effects of Fludrocortisone. What precautions should be considered when using Fludrocortisone.

Understanding Fludrocortisone: A Synthetic Glucocorticoid

Fludrocortisone is a synthetic glucocorticoid that plays a crucial role in treating various medical conditions. This man-made substance mimics the natural glucocorticoids produced by the body, which are essential for numerous physiological functions. Fludrocortisone is primarily used in conjunction with other medications to address low glucocorticoid levels resulting from adrenal gland disorders.

What is the primary function of Fludrocortisone?

Fludrocortisone serves as a replacement therapy for individuals with insufficient natural glucocorticoid production. It helps maintain proper salt and water balance, regulates blood pressure, and aids in carbohydrate metabolism. This medication is particularly beneficial for patients with Addison’s disease, adrenocortical insufficiency, or salt-losing adrenogenital syndrome.

Proper Administration of Fludrocortisone

Administering Fludrocortisone correctly is crucial for achieving optimal therapeutic results. The medication is typically taken orally, either with or without food, as directed by a healthcare provider. The dosage and frequency may vary depending on the individual’s specific medical condition and response to treatment.

How often should Fludrocortisone be taken?

In most cases, Fludrocortisone is prescribed for once-daily administration. However, some patients may require a different dosing schedule. It is essential to follow the prescribed regimen consistently and take the medication at the same time each day to maintain steady levels in the body.

Can the dosage of Fludrocortisone be adjusted?

Dosage adjustments should only be made under the guidance of a healthcare professional. Patients should not alter their dose or frequency of administration without consulting their doctor. Abrupt changes in dosage, especially sudden discontinuation, may lead to worsening of the underlying condition or withdrawal symptoms.

Potential Side Effects of Fludrocortisone

While Fludrocortisone is generally well-tolerated, it may cause various side effects. Some common adverse reactions include stomach upset, headache, and menstrual irregularities. It is important for patients to be aware of these potential effects and report any persistent or worsening symptoms to their healthcare provider.

What are some serious side effects of Fludrocortisone?

Although rare, Fludrocortisone can cause more severe side effects that require immediate medical attention. These may include:

• Changes in skin appearance (color changes, thinning, fatty deposits)
• Easy bruising or bleeding
• Slow wound healing
• Signs of infection (persistent sore throat, fever, skin sores)
• Bone, joint, or muscle pain
• Swelling of hands or feet
• Unusual weight gain
• Severe fatigue
• Mental or mood changes (agitation, depression, mood swings)
• Vision problems
• Seizures

Patients experiencing any of these symptoms should seek medical help promptly.

Precautions and Considerations for Fludrocortisone Use

Before initiating Fludrocortisone therapy, it is crucial to inform healthcare providers about any existing medical conditions, allergies, or medications. This information helps prevent potential drug interactions and adverse reactions.

Which medical conditions may affect Fludrocortisone use?

Certain pre-existing conditions may require special consideration when using Fludrocortisone. These include:

• Bleeding disorders or history of blood clots
• Osteoporosis
• Diabetes
• Eye problems (cataracts, glaucoma, eye infections)
• Heart conditions (congestive heart failure)
• Hypertension
• Kidney or liver disease
• Mental health disorders
• Thyroid problems

Patients with these conditions may require closer monitoring or dosage adjustments to ensure safe and effective treatment.

Fludrocortisone and Electrolyte Balance

Fludrocortisone significantly impacts the body’s electrolyte balance, particularly sodium retention and potassium excretion. This effect is crucial for maintaining proper fluid balance and blood pressure regulation. However, it also necessitates careful management of dietary salt and mineral intake.

How does Fludrocortisone affect sodium and potassium levels?

Fludrocortisone promotes sodium retention while increasing the excretion of potassium and calcium. This action helps maintain appropriate blood pressure and fluid balance in patients with adrenal insufficiency. However, it also requires careful monitoring of electrolyte levels and potential dietary adjustments.

Should patients on Fludrocortisone modify their diet?

Patients taking Fludrocortisone should follow their healthcare provider’s recommendations regarding dietary salt, potassium, and calcium intake. In some cases, dietary modifications or mineral supplements may be necessary to maintain optimal electrolyte balance. Regular blood tests can help monitor these levels and guide any necessary adjustments.

Fludrocortisone and Infection Risk

One important consideration for patients taking Fludrocortisone is its impact on the immune system. Glucocorticoids, including Fludrocortisone, can suppress immune function, potentially increasing susceptibility to infections or masking signs of existing infections.

How can patients reduce infection risk while on Fludrocortisone?

To minimize infection risk, patients should:

1. Practice good hygiene, including regular handwashing
2. Avoid close contact with individuals who have contagious illnesses
3. Stay up-to-date with recommended vaccinations
4. Promptly report any signs of infection to their healthcare provider
5. Follow any additional precautions recommended by their doctor

It is particularly important for patients to be cautious around highly contagious diseases such as chickenpox, measles, influenza, and COVID-19.

Long-term Considerations for Fludrocortisone Therapy

While Fludrocortisone is essential for managing certain medical conditions, long-term use requires ongoing monitoring and potential adjustments. Patients should be aware of the importance of regular check-ups and open communication with their healthcare providers.

What long-term effects should patients be aware of?

Prolonged use of Fludrocortisone may lead to various effects, including:

• Changes in bone density (osteoporosis)
• Increased risk of cataracts or glaucoma
• Potential weight gain
• Skin changes (thinning, easy bruising)
• Muscle weakness
• Increased susceptibility to infections

Regular monitoring and appropriate preventive measures can help mitigate these risks. Patients should discuss any concerns about long-term use with their healthcare provider.

Can Fludrocortisone be safely discontinued?

Abrupt discontinuation of Fludrocortisone can lead to withdrawal symptoms or a recurrence of the underlying condition. If treatment needs to be stopped, it should be done gradually under medical supervision. The dosage is typically tapered down slowly to allow the body to adjust and resume its natural hormone production.

Fludrocortisone Interactions with Other Medications

Fludrocortisone can interact with various medications, potentially altering its effectiveness or increasing the risk of side effects. It is crucial for patients to inform their healthcare providers about all medications, supplements, and herbal products they are taking.

Which medications may interact with Fludrocortisone?

Some medications that may interact with Fludrocortisone include:

• Anticoagulants (blood thinners)
• Certain antibiotics
• Antifungal medications
• Diabetes medications
• Diuretics
• NSAIDs (nonsteroidal anti-inflammatory drugs)
• Vaccines

This list is not exhaustive, and patients should consult their healthcare provider or pharmacist for a comprehensive review of potential drug interactions.

Special Considerations for Fludrocortisone Use in Specific Populations

Certain groups of patients may require special considerations when using Fludrocortisone. These include pregnant women, breastfeeding mothers, children, and elderly individuals. Each of these populations may have unique risks or dosing requirements.

Is Fludrocortisone safe during pregnancy and breastfeeding?

The use of Fludrocortisone during pregnancy and breastfeeding should be carefully evaluated. While it may be necessary for some women to continue treatment, potential risks to the fetus or infant should be weighed against the benefits. Pregnant or breastfeeding women should consult their healthcare provider to determine the most appropriate course of action.

How is Fludrocortisone use approached in pediatric patients?

Fludrocortisone may be prescribed for children with certain conditions, such as congenital adrenal hyperplasia. However, dosing and monitoring requirements may differ from those of adults. Long-term use in children requires careful consideration of potential effects on growth and development.

What considerations are important for elderly patients taking Fludrocortisone?

Elderly patients may be more susceptible to certain side effects of Fludrocortisone, such as osteoporosis, hypertension, and electrolyte imbalances. Dosing may need to be adjusted, and more frequent monitoring may be necessary to ensure safe and effective treatment in this population.

Managing Fludrocortisone Treatment During Illness or Stress

Patients taking Fludrocortisone for adrenal insufficiency may require dosage adjustments during periods of illness, injury, or significant stress. These situations can increase the body’s demand for glucocorticoids, potentially necessitating temporary increases in medication.

When might a patient need to adjust their Fludrocortisone dose?

Situations that may require dosage adjustments include:

• Acute illnesses, especially those accompanied by fever
• Significant physical injuries
• Major dental or surgical procedures
• Intense physical exertion
• Severe emotional stress

Patients should work with their healthcare provider to develop a plan for managing their medication during these situations. This may include having an emergency supply of medication or knowing when to seek medical attention.

The Importance of Regular Monitoring for Fludrocortisone Users

Ongoing monitoring is crucial for patients taking Fludrocortisone to ensure optimal treatment outcomes and minimize potential risks. Regular check-ups and laboratory tests help healthcare providers assess the medication’s effectiveness and detect any developing side effects or complications.

What types of monitoring are typically recommended for Fludrocortisone users?

Common monitoring practices for patients on Fludrocortisone may include:

• Regular blood pressure checks
• Periodic blood tests to assess electrolyte levels and kidney function
• Bone density scans to monitor for osteoporosis risk
• Eye examinations to check for cataracts or glaucoma
• Assessment of growth and development in pediatric patients
• Monitoring for signs of infection or adrenal crisis

The frequency and specific types of monitoring may vary based on individual patient factors and the underlying condition being treated.

How can patients actively participate in their Fludrocortisone treatment management?

Patients can play an active role in their treatment by:

1. Keeping all scheduled appointments with healthcare providers
2. Promptly reporting any new symptoms or side effects
3. Maintaining accurate records of medication doses and any adjustments
4. Following recommended dietary guidelines
5. Wearing a medical alert bracelet or carrying information about their condition and medication
6. Learning to recognize signs of adrenal insufficiency or crisis
7. Discussing any concerns or questions with their healthcare team

By actively engaging in their care, patients can help ensure the safe and effective use of Fludrocortisone while minimizing potential risks.

Fludrocortisone Oral: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing

Uses

Fludrocortisone is a man-made form of a natural substance (glucocorticoid) made by the body. It is used along with other medications (such as hydrocortisone) to treat low glucocorticoid levels caused by disease of the adrenal gland (such as Addison’s disease, adrenocortical insufficiency, salt-losing adrenogenital syndrome). Glucocorticoids are needed in many ways for the body to function well. They are important for salt and water balance and keeping blood pressure normal. They are also needed to break down carbohydrates in your diet.

How to use Fludrocortisone ACETATE

Take this medication by mouth with or without food as directed by your doctor, usually once daily. Your doctor will adjust your dose to the one that is best for you. The dosage is based on your medical condition and response to treatment.

In order to get the most benefit from this medication, follow the dosing schedule carefully, and take this medication exactly as prescribed. To help you remember, take it at the same time each day. If you are taking this medication on another schedule besides every day (such as only 3 days a week), it may help to mark your calendar with a reminder. Do not increase or decrease your dose, take this drug more often, or stop taking this medication without your doctor’s approval. Some conditions may become worse when the drug is suddenly stopped. Your dose may need to be gradually decreased.

Inform your doctor if your condition lasts or gets worse.

Side Effects

Stomach upset, headache, and menstrual changes (such as delayed/irregular/absent periods) may occur. If any of these effects last or get worse, contact your doctor or pharmacist promptly.

Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor right away if you have any serious side effects, including: change in skin appearance (such as color changes, thinning, fatty areas), easy bleeding/bruising, dizziness, slow wound healing, signs of infection (such as sore throat that doesn’t go away, fever, skin sores), bone/joint/muscle pain, puffy face, swelling of the hands/feet, severe tiredness, increased thirst/urination, unusual weight gain, muscle weakness, eye problems (such as pain, redness, vision changes), severe/continuous headaches, fast/pounding/irregular heartbeat, mental/mood changes (such as agitation, depression, mood swings), seizure, symptoms of stomach/intestinal bleeding (such as stomach/abdominal pain, black/tarry stools, vomit that looks like coffee grounds).

A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US – Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.

In Canada – Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Precautions

Before taking fludrocortisone, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: bleeding problems, blood clots, brittle bones (osteoporosis), diabetes, eye problems (such as cataracts, glaucoma, infection of the eye), heart problems (such as congestive heart failure), high blood pressure, infections (such as candidiasis, valley fever, herpes, tuberculosis), kidney disease, liver disease (such as cirrhosis), mental/mood disorders (such as anxiety, depression, psychosis), low blood minerals (such as calcium, potassium), stomach/intestinal problems (such as diverticulitis, peptic ulcer disease, ulcerative colitis), seizures, thyroid problems.

Fludrocortisone makes your body hold on to salt (sodium) and get rid of other salts (such as calcium, potassium). Follow your doctor’s advice on how much salt, potassium, and calcium should be in your diet.

This medication may mask signs of infection. It can make you more likely to get infections or may make current infections worse. Stay away from anyone who has an infection that may easily spread (such as chickenpox, COVID-19, measles, flu). Talk to your doctor if you have been exposed to an infection or for more details.

Do not have immunizations/vaccinations without the consent of your doctor, and avoid contact with people who have recently received oral polio vaccine or flu vaccine inhaled through the nose.

Using corticosteroid medications for a long time can make it more difficult for your body to respond to physical stress. Before having surgery or emergency treatment, or if you get a serious illness/injury, tell your doctor or dentist that you are using this medication or have used this medication within the past 12 months. Tell your doctor right away if you develop unusual/extreme tiredness or weight loss. If you will be using this medication for a long time, carry a warning card or medical ID bracelet that identifies your use of this medication.

If you have a history of ulcers or take large doses of aspirin or other arthritis medicine, limit alcoholic beverages while taking this medication to lower the risk of stomach/intestinal bleeding.

If you have diabetes, this drug may make it harder to control your blood sugar levels. Monitor your blood sugar levels regularly and inform your doctor of the results. Your diabetic medication or diet may need to be adjusted.

This medication may slow down a child’s growth if used for a long time. Consult the doctor or pharmacist for more details. See the doctor regularly so your child’s height and growth can be checked.

Older adults may be more sensitive to the side effects of this drug, especially water retention, bone loss/pain, stomach/intestinal bleeding, and mental/mood changes (such as confusion).

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor. Infants born to mothers who have been using this medication for an extended time may have low levels of corticosteroid hormone. Tell your doctor right away if you notice symptoms such as nausea/vomiting that doesn’t stop, severe diarrhea, or weakness in your newborn.

This medication passes into breast milk and may have undesirable effects on a nursing infant. Consult your doctor before breast-feeding.

Interactions

Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor’s approval.

Some products that may interact with this drug are: aldesleukin, digoxin, drugs that can cause bleeding/bruising (including antiplatelet drugs such as clopidogrel, “blood thinners” such as dabigatran/warfarin, NSAIDs such as aspirin/celecoxib/ibuprofen), hormones (such as androgens, birth control pills, estrogens), immunosuppressants (such as cyclosporine), mifepristone.

If your doctor has directed you to take low-dose aspirin for heart attack or stroke prevention (usually 81-162 milligrams a day), you should continue taking it unless your doctor instructs you otherwise. Ask your doctor or pharmacist for more details.

This medication may interfere with certain laboratory tests, possibly causing false results. Make sure laboratory personnel and all your doctors know you use this drug.

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Overdose

If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include high blood pressure, water retention, extreme weight gain, and muscle weakness.

Do not share this medication with others.

Lab and/or medical tests (such as blood pressure, eye exams, sodium/potassium levels) should be done while you are taking this medication. Keep all medical and lab appointments. Consult your doctor for more details.

If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.

Different brands of this product have different storage needs. Check the product package for instructions on how to store your brand or ask the pharmacist. Do not store in the bathroom. Keep all medications away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

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CONDITIONS OF USE: The information in this database is intended to supplement, not substitute for, the expertise and judgment of healthcare professionals. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for you or anyone else. A healthcare professional should be consulted before taking any drug, changing any diet or commencing or discontinuing any course of treatment.

Fludrocortisone – StatPearls – NCBI Bookshelf

Continuing Education Activity

Fludrocortisone is a synthetic adrenal steroid with high mineralocorticoid activity that is a commonly used drug to treat adrenocortical insufficiency. This activity will highlight the mechanism of action, adverse event profile, and other key factors (e.g., off-label uses, dosing, pharmacodynamics, pharmacokinetics, monitoring, relevant interactions) pertinent to interprofessional team members to use fludrocortisone appropriately for various indications.

Objectives:

• Identify the mechanism of action of fludrocortisone.

• Describe the potential adverse effects of fludrocortisone.

• Summarize the appropriate monitoring of fludrocortisone use.

• Review some interprofessional strategies that can improve patient outcomes when using fludrocortisone therapy.

Access free multiple choice questions on this topic.

Indications

Given its strong mineralocorticoid effect, fludrocortisone plays an essential role in the treatment of primary and secondary adrenocortical insufficiency.  This drug may also be used to treat congenital adrenal hyperplasia (CAH), which is a congenital enzymatic deficiency disorder that manifests with mineralocorticoid deficiency in up to 75% of cases. Even though this corticosteroid is not approved in the pediatric population by the Food and Drug Administration for uses other than congenital adrenal hyperplasia, it is indicated off-label for adrenocortical insufficiency.[1] It has also been used in the management of septic shock in adults, demonstrating a 90-day all-cause mortality reduction among the group receiving hydrocortisone plus fludrocortisone than among those with placebo[2][3][4][5]

The drug received its patent in 1953 and is on the World Health Organization’s List of Essential Medicines.

Mechanism of Action

Fludrocortisone acetate is an inactive pro-drug requiring hydrolyzation by esterases or pseudo-esterases in the liver and other body fluids.[6] Fludrocortisone is a synthetic adrenal steroid with high mineralocorticoid activity and is practically devoid of glucocorticoid effect. As an analog, its mechanism of action and the permissive effects on α-adrenoreceptors are similar to the endogenous mineralocorticoid. High lipid solubility allows fludrocortisone to easily penetrate the plasma membrane and bind with its cytoplasmic receptor.

Upon binding, receptor complex translocates to the nucleus and initiates the transcription of responsive genes to exert its effects. The primary sites of fludrocortisone’s effect are the distal convoluted tubules and collecting ducts, where it enhances Na+ and water retention as well as increasing K+, H+ excretion. This pharmacologic effect leads to a generalized ECF volume expansion not specifically targeted to the intravascular space. Thus, it is postulated that its efficacy in orthostatic hypotension management is due to potentiating the pressor effects of various endogenous vasoconstrictors such as norepinephrine and angiotensin II.[7]

Administration

Dosage and Form

Fludrocortisone is available in tablet form, and it can be taken orally with or without a meal. It is usually administered in its acetate form.

For primary adrenal cortical insufficiency usual dose is 0.1 mg per day, and it can be increased up to 0.2 mg per day. However, if hypertension develops, the dosage should be reduced to 0.05 mg per day. Dosing should be gradually tapered down to discontinue therapy.

For the salt-losing type of congenital adrenal hyperplasia, the dose is 0.1 mg/day.

When used off-label for orthostatic hypotension, the dose is normally from 0.1 to 0.2 mg orally once daily. Dosing should start at 0.1 mg by mouth each day, then increase the dose by 0.1 mg per day each week until the appearance of trace pedal edema. The maximum dose is 1 mg per day, although doses in excess of 0.5 mg daily are rarely more effective. Dosing should be with food or milk. Discontinuation of therapy requires gradual dose tapering.

Metabolism

The drug is metabolized by the liver. So, if there is any hepatic impairment, the dose should be adjusted accordingly.

Drug Interactions

• Administration with proton pump inhibitors and anemia have shown to decrease its absorption.[6]

• Concurrent use of amphotericin B, diuretics, digoxin with fludrocortisone may cause severe hypokalemia.

• Using NSAIDs can cause peptic ulcer disease.

• It can decrease or increase the efficacy of warfarin.

• It can cause hyperglycemia, so dosages of diabetes drugs (metformin, glipizide, glimepiride, pioglitazone, linagliptin, insulin) must be adjusted.

• Administration of phenobarbital, Phenytoin, Rifampin can lower blood fludrocortisone levels.

• Taking estrogen or male testosterone analog can increase the risk of swelling.

• Fludrocortisone can impair the function of vaccines. Therefore, vaccines should not be given while patients are using fludrocortisone.

Pregnancy Category

Fludrocortisone is a Category C pregnancy drug.

Adverse Effects

Most of the side effect of fludrocortisone is related to mineralocorticoid activity. If this drug is used along with glucocorticoid or other related drugs, the adverse effect increases. Some of the more common or significant side effects appear in the list below:

• Cardiovascular system: Hypertension (dose-dependent iatrogenic has been described as an adverse effect on children using fludrocortisone for CAH, which correlates with plasma renin activity,  Fluid retention, and edema (May cause swelling of lower limbs), congestive heart failure.[8][9]

• Nervous System: Headache, increased intracranial pressure, vertigo, change in behavior, convulsion

• Gastrointestinal: May impair gastric protective barrier and cause stomach ulcer, perforation.

• Endocrine: Menstrual abnormalities, cushingoid features, growth delay in a child, acute adrenal insufficiency in times of stress

• Musculoskeletal: Can cause muscle weakness, can reduce muscle mass, increase risk of osteoporosis and pathological fracture, vertebral compression, necrosis of femoral head.

• Dermatologic: Increased sweating, poor wound healing, hirsutism, thinning of the skin, severe allergic reaction

• Ophthalmic: cataracts, glaucoma

• Metabolic: Elevated blood and urine glucose, weight gain

• Electrolytes Disturbance: Severe hypokalemia, metabolic alkalosis[10]

Contraindications

Fludrocortisone is contraindicated in several conditions. The clinicians should conduct a careful history and examination should be made prior to prescribing this drug. If there is any contraindication to this drug, alternative options should be considered. Contraindications include:

• Known allergy to this drug

• Hypertension

• Hyperaalbuminemia

• Systemic fungal infection

Monitoring

Since this drug can cause a life-threatening hypersensitivity reaction, the patient must be monitored for the development of any allergic sign symptoms such as rash, breathing problem, swelling of the face, or fever. It is recommended to measure blood pressure regularly while using this corticosteroid as it has been associated with iatrogenic hypertension. Serial plasma renin activity should also be checked. If there is weakness, muscle cramps, blood electrolytes should be checked to identify and treat hypokalemia. Whether diabetic or not, serum blood glucose should be monitored, if diabetic glucose should be controlled with appropriate medications. If the drug is being prescribed for a child for a longer duration, the growth and development of the child should be tracked to see if there is any delay in growth.

Toxicity

The toxicity of any drug depends on its pharmacological activity. Since fludrocortisone works at mineralocorticoid receptors, toxicity will present as excess mineralocorticoid activities such as severe hypertension, not pitting edema, congestive heart failure, severe hypokalemia, metabolic alkalosis, rapid weight gain. Unfortunately, there is no antidote for fludrocortisone toxicity. So, conservative management is the mainstay. Reduction of dose, strict blood pressure control, potassium supplementation may be given.

Enhancing Healthcare Team Outcomes

Fludrocortisone is used all around the world and prescribed by clinicians, including NDs, osteopathic clinicians, physician assistants, and nurse practitioners. Since the drug can interact with many other medications and may cause serious adverse effects or toxicity, interprofessional healthcare team members must be aware of these consequences. All team members, whether involved in prescribing, dispensing, administering, or monitoring fludrocortisone, must be well educated about the pharmacology of this drug. A proper history and physical examination must be considered before initiating fludrocortisone. The patient must be educated about the adverse effects, potential toxicity, and appropriate dosing of this drug so they can use the medication properly. They can report to the clinician within a short timeframe if any adverse events occur or are beginning to manifest.

Interprofessional team discussion that includes all clinicians (including specialists such as endocrinologists), nursing staff, and pharmacists is crucial for every patient. The interprofessional team must monitor the patient at a regular interval and be ready for a prompt response if there are any signs or symptoms of adverse events. Besides the health team and patient, other family members should also be educated about proper dosing, adverse effects, and warning signs. This team approach will drive improved patient outcomes and mitigate potential adverse events. [Level 5]

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References

1.

Bonfig W, Schwarz HP. Blood pressure, fludrocortisone dose and plasma renin activity in children with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency followed from birth to 4 years of age. Clin Endocrinol (Oxf). 2014 Dec;81(6):871-5. [PubMed: 24818525]

2.

Benner BJM, Alsma J, Feelders RA. Hyponatraemia and hyperpigmentation in primary adrenal insufficiency. BMJ Case Rep. 2019 Mar 07;12(3) [PMC free article: PMC6424183] [PubMed: 30850564]

3.

Annane D, Renault A, Brun-Buisson C, Megarbane B, Quenot JP, Siami S, Cariou A, Forceville X, Schwebel C, Martin C, Timsit JF, Misset B, Ali Benali M, Colin G, Souweine B, Asehnoune K, Mercier E, Chimot L, Charpentier C, François B, Boulain T, Petitpas F, Constantin JM, Dhonneur G, Baudin F, Combes A, Bohé J, Loriferne JF, Amathieu R, Cook F, Slama M, Leroy O, Capellier G, Dargent A, Hissem T, Maxime V, Bellissant E., CRICS-TRIGGERSEP Network. Hydrocortisone plus Fludrocortisone for Adults with Septic Shock. N Engl J Med. 2018 Mar 01;378(9):809-818. [PubMed: 29490185]

4.

Gomes LG, Madureira G, Mendonca BB, Bachega TA. Mineralocorticoid replacement during infancy for salt wasting congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Clinics (Sao Paulo). 2013;68(2):147-52. [PMC free article: PMC3584273] [PubMed: 23525308]

5.

Hughes IA, Wilton A, Lole CA, Gray OP. Continuing need for mineralocorticoid therapy in salt-losing congenital adrenal hyperplasia. Arch Dis Child. 1979 May;54(5):350-5. [PMC free article: PMC1545561] [PubMed: 475410]

6.

Polito A, Hamitouche N, Ribot M, Polito A, Laviolle B, Bellissant E, Annane D, Alvarez JC. Pharmacokinetics of oral fludrocortisone in septic shock. Br J Clin Pharmacol. 2016 Dec;82(6):1509-1516. [PMC free article: PMC5099539] [PubMed: 27416887]

7.

Bamberg K, William-Olsson L, Johansson U, Jansson-Löfmark R, Hartleib-Geschwindner J. The selective mineralocorticoid receptor modulator AZD9977 reveals differences in mineralocorticoid effects of aldosterone and fludrocortisone. J Renin Angiotensin Aldosterone Syst. 2019 Jan-Mar;20(1):1470320319827449. [PMC free article: PMC6396052] [PubMed: 30813831]

8.

Bhattacharyya A, Tymms DJ. Heart failure with fludrocortisone in Addison’s disease. J R Soc Med. 1998 Aug;91(8):433-4. [PMC free article: PMC1296847] [PubMed: 9816363]

9.

Willis FR, Byrne GC, Jones TW. Fludrocortisone induced heart failure in Addison’s disease. J Paediatr Child Health. 1994 Jun;30(3):280-1. [PubMed: 8074919]

10.

Burns A, Brown TM, Semple P. Extreme metabolic alkalosis with fludrocortisone therapy. Postgrad Med J. 1983 Aug;59(694):506-7. [PMC free article: PMC2417584] [PubMed: 6622340]

Disclosure: Masum Rahman declares no relevant financial relationships with ineligible companies.

Disclosure: Fatima Anjum declares no relevant financial relationships with ineligible companies.

3.2 Replacement therapy MK \ ConsultantPlus

3.2 Replacement therapy MK

– Mineralocorticoid therapy – #fludrocortisone** (starting daily dose of 50-100 mcg) is recommended for all patients with 1-HN (starting daily dose of 50 – 100 mcg), salt intake is not limited [27, 87 – 8 8 , 96 – 105].

Recommendation grade C (level of evidence – 4)

Comments: Synthetic UA #fludrocortisone** is used in substitution therapy, but its use in 1-HN has not been adequately studied. #Fludrocortisone** is usually given once in the morning, as endogenous A levels are normally highest at this time, similar to the circadian rhythm of cortisol [96]. The daily dose of #fludrocortisone** depends on fluid and electrolyte intake/loss and is usually 0.05 – 0.2 mg. In case of excessive sweating, for example, in hot climates, a temporary increase in the dose by 50 – 100% or an increase in the consumption of salty foods may be required. During #prednisolone** therapy, a higher dose of #fludrocortisone** may be required than during treatment with hydrocortisone** and, moreover, against the background of dexamethasone**, which does not have mineralocorticoid activity [26].

Fludrocortisone** therapy for 1-HN may not be prescribed in exceptional cases (with isolated familial HA deficiency and some forms of CHD).

– Compensation of UA insufficiency in patients with 1-HN is recommended to be assessed by clinical signs (craving for salt, orthostatic hypotension, edema, arterial hypertension) and the results of the study of sodium and potassium levels in the blood [26, 98, 99].

Recommendation strength C (level of evidence – 4)

Comments: Patients should be asked about the presence of cravings for salt and pre-syncope, measure blood pressure while sitting and standing, examine for the presence of peripheral edema (has low sensitivity). General well-being, normal levels of electrolytes and blood pressure, the absence of orthostatic hypotension are signs of adequate compensation for mineralocorticoid deficiency. In addition, plasma P activity in the upper reference range is also a useful marker of compensation [26, 98, 99]. It should be taken into account that licorice and grapefruit juice increase the mineralocorticoid effect of hydrocortisone** and should be avoided [100]. Phenytoin** enhances the metabolism of #fludrocortisone**, and therefore, the dose of the drug has to be increased [101].

– It is recommended to reduce the dose of #fludrocortisone** in patients with 1-HH and arterial hypertension, since an increase in blood pressure may indicate an overdose of the drug. If blood pressure remains elevated, it is recommended to prescribe antihypertensive therapy, and continue treatment with #fludrocortisone** [102, 103].

Recommendation grade C (level of evidence – 4)

Comments: 1-HH may be associated with essential arterial hypertension (AH) [102]. In a patient with 1-HH and AH, the adequacy of both mineralocorticoid and glucocorticoid therapy should be assessed, since an overdose of either drug can increase blood pressure. In addition, the patient may be advised to limit excessive consumption of salty foods and liquids [61].

If BP does not normalize after correction of replacement therapy (reducing the dose of #fludrocortisone**), antihypertensive agents should be prescribed, mainly agents acting on the renin-angiotensin system: angiotensin II receptor antagonists or angiotensin-converting enzyme inhibitors [102]. Second-line drugs are selective calcium channel blockers with a predominant effect on the vessels (dihydropyridine derivatives). Diuretics are prescribed in exceptional cases, and aldosterone antagonists are contraindicated in patients with 1-HH [26].

Medications (AZITHROMYCIN, AMOXICILLIN, GENTAMYCIN, DOXYCYCLINE, PENTANEDIC ACID IMIDAZOLYLETHANAMIDE, MEGLUMINE ACRIDONACETATE, OSELTAMIVIR, PREDNISOLONE, FLUDROCORTISON, FOLIC ACID, ETHANOL, DEC STROSA, FAMOTIDINE, METFORMIN, PROCAINE, VINPOCETENE, BROMDIHYDROCHLOROPHENYL BENZODIAZEPINE, NISTATIN, CHLOROHEXIDINE, POVIDONE-IODINE, HYDROGEN PEROXIDE, INDAPAMIDE): procedure 037530003641

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