FLUDROCORTISONE :
Endocrine Hormone :
Special pediatric considerations are noted when applicable, otherwise adult provisions apply.
[1,2] :
Fludrocortisone is classified as a glucocorticoid but it is used for its mineralocorticoid effects. The physiologic effects of fludrocortisone are similar to that of hydrocortisone but it is much more potent.
[1,3,4,5] :
| Oral Absorption | rapid and complete absorption | |
| Distribution | no information found | |
| cross blood brain barrier? | no information found | |
| Vd | no information found | |
| PPB | 42% albumin binding at 12 hours | |
| Metabolism | presumably in liver like other steroids | |
| active metabolite(s) | no information found | |
| inactive metabolite(s) | no information found | |
| Excretion | not elucidated | |
| urine | no information found | |
| t1/2 | 35 minutes (IV administration), biological activity 18-36 hours | |
| Cl | no information found | |
[2] :
Mineralocorticoid replacement for severe orthostatic hypotension with aminoglutethimide and hydrocortisone (breast cancer), or with mitotane (adrenal cortical cancer)
No pediatric indications.
Health Protection Branch approved indication.
[2] :
Corticosteroids have been reported to cause fetal damage when administered to pregnant women. Corticosteroids may be distributed into breast milk and could suppress growth of the infant.
[2] :
| ORGAN SITE | SIDE EFFECT | ONSET | |||
| cardiovascular | fluid retention, hypertension, congestive heart failure | E | |||
| central nervous system | insomnia, headache, mood swings | E | |||
| dermatologic | thin, fragile skin | E | |||
| bruising, petechiae | E | ||||
| hyperpigmentation of skin and nails | D | ||||
| endocrine | Cushingoid state (rare) | D | |||
| adrenal suppression | D | ||||
| amenorrhea, menstrual irregularities | D | ||||
| gastrointestinal | peptic ulcer, esophagitis | D | |||
| hypersensitivity | Type I (anaphylactoid) (rare) | I | |||
| musculoskeletal | protein catabolism (muscle wasting, osteoporosis, fractures) | D | |||
| muscle pain and weakness | E | ||||
| ocular | cataracts, glaucoma (rare) | D | |||
| renal/metabolic | electrolyte disturbances (sodium retention, potassium loss, calcium loss) | E | |||
| calcium loss | D | ||||
| decreased glucose tolerance | D | ||||
Dose-limiting side effects are underlined.
I = immediate (onset in hours to days); E = early (days to weeks); D = delayed (weeks to months); L = late (months to years)
Short-term administration of fludrocortisone, even in high doses, is usually not associated with any severe adverse effects. Prolonged use can result in adrenocortical atrophy and generalized protein depletion. The drug should be withdrawn gradually following long-term therapy. Adrenal suppression may persist up to 12 months following prolonged use.
Protein catabolism
may occur during prolonged therapy, resulting in muscle wasting, muscle weakness and/or osteoporosis. A high protein diet may prevent some of these adverse effects.
Serum electrolytes
should be monitored. Dietary salt restriction and potassium supplementation may be required.
[1,6] :
| AGENT | EFFECT | MECHANISM | MANAGEMENT |
| anticholinesterase agents (eg, neostigmine) | severe muscle weakness in patients with myasthenia gravis | unknown | withdraw anticholinsterase agent 24 hours before giving fludrocortisone |
| anticoagulants (eg, warfarin) | dosing requirements of oral anticoagulants may be increased or decreased (conflicting reports) | unknown | monitor prothrombin time and adjust anticoagulant dose prn when starting or stopping fludrocortisone |
| barbiturates, phenytoin, rifampin | decreased effect of fludrocortisone | increased metabolism of fluldrocortisone due to increased activity of hepatic microsomal enzyme oxidation system | increased dose of fludrocortisone may be required |
| nonsteroidal anti- inflammatory drugs | increased risk of ulcers | additive toxicity | caution |
| potassium-depleting diuretics | enhanced potasium loss | additive | monitor |
| salicylates | decreased salicylate levels | possibly due to increased renal clearance; or to enhanced metabolism of salicylates | salicylate dose may need to be increased if fludrocortisone is given concurrently; and decreased when fludrocortisone is discontinued, observe for salicylate toxicity |
: [2]
Tablets:
0.1 mg (100 mcg); store at room temperature.
[1,2,4,7,8,9,10,11] :
Refer to protocol by which patient is being treated.
Adults:
Oral:
0.05-0.1 mg po every other day or daily
Dosage in myelosuppression:
no adjustment required
Dosage in renal failure:
adjustment required, no details found
Dosage in hepatic failure:
no adjustment required
FLUDROCORTISONE FACT SHEET
FOR THE HEALTH CARE PROFESSIONAL | |
|---|---|
| OTHER NAMES | 9-alpha-fluorohydrocortisone |
| USES | mineralocorticoid replacement for severe orthostatic hypotension with aminoglutethimide and hydrocortisone (breast cancer) or with mitotane (adrenal cortical cancer) |
| DOSAGE FORMS | oral tablet: 0.1 mg (100 mcg) |
| USUAL DOSE RANGE | Adults: 0.05-0.1 mg po every other day or daily |
| DOSE REDUCTIONS | kidney (renal) failure |
| ONSET | SIDE EFFECT * may be life-threatening side effects in bold, italic type are common |
| IMMEDIATE (hours to days) | * anaphylaxis (rare) |
| EARLY (days to weeks) | high blood pressure (hypertension) heart problems (congestive heart failure) electrolyte problems (potassium loss, sodium and water retention) muscle pain and weakness (due to potassium loss) skin problems (thinning, fragility, bruising, petechiae) central nervous system problems (insomnia, headache, mood swings) |
| DELAYED/LATE (weeks to years) | Cushingoid state loss of menstruation (amenorrhea, menstrual irregularities) gastrointestinal problems (esophagitis, peptic ulcer) increased calcium loss (leading to osteoporosis and fractures) eye problems (cataracts, glaucoma) loss of diabetic control (decreased glucose tolerance) muscle wasting (protein catabolism) darkening of skin and nails (hyperpigmentation) |
| CONTRAINDICATIONS | known hypersensitivity to fludrocortisone pregnancy and breast feeding systemic fungal infections |
| SIGNIFICANT INTERACTIONS *increases toxicity | barbiturates, *neostigmine (PROSTIGMIN(r)), *nonsteroidal anti- inflammatory drugs, phenytoin (DILANTIN(r)), *potassium-depleting diuretics, rifampin, salicylates, warfarin (COUMADIN(r)) |
| LABORATORY MONITORING | periodically: electrolytes, blood pressure |
TEACHING AIDS * For the Patient: Fludrocortisone
NOTES:
* Fludrocortisone is often used with aminoglutethimide to prevent low blood pressure (orthostatic hypotension) secondary to hypoaldosteronism. Doses of 0.1 mg po daily or on alternate days are
usually sufficient.
Fluid and electrolyte disturbances are not usually seen with low-dose, short-term treatment. Low salt and sodium intake help prevent fluid retention and hypertension. Potassium supplementation may be required. Patients at risk of developing cardiac problems must be monitored carefully.
Adrenal suppression can occur with chronic, long-term treatment. Supportive steroids may be required for stress due to infection, surgery or injury while on fludrocortisone and for up to 12 months after discontinuation. Upon discontinuation, fludrocortisone doses should be tapered gradually except when used with aminoglutethimide.
FOR THE PATIENT
Fludrocortisone : Other names: FLORINEF(r)
Fludrocortisone (floo-droe-KOR-tis-own) is a drug that is used to replace steroids normally produced by your body. It keeps the balance of fluids and minerals in your body. It is often used with another drug such as hydrocortisone (eg, CORTEF(r)) or cortisone (eg, CORTONE(r)). Fludrocortisone is a tablet that you take by mouth.
It is important to take fludrocortisone exactly as directed by your doctor. Make sure you understand the directions. Fludrocortisone may be taken with food or on an empty stomach with a glass of water or juice.
For once a day dosing: If you miss a dose of fludrocortisone, take it as soon as you can if it is within 12 hours of the missed dose. If it is over 12 hours since your missed dose, skip the missed dose and go back to your usual dosing times.
For every second day dosing: If you miss a dose of fludrocortisone, take it as soon as you can. If it is over 24 hours since your missed dose, take a dose, skip the next day and keep taking it every second day.
Do not stop taking fludrocortisone without telling your doctor. Make sure that you always have a new supply of fludrocortisone on hand before you run out of tablets.
Store fludrocortisone tablets out of the reach of children, at room temperature, away from heat, light and moisture.
Other drugs such as neostigmine (PROSTIGMIN(r)), phenytoin (DILANTIN(r)), rifampin or warfarin (COUMADIN(r)) may interact with fludrocortisone. Tell your doctor if you are taking these or any other drugs as your dose may need to be changed. Check with your doctor or pharmacist before you start taking any new drugs.
The drinking of alcohol (in small amounts) will not affect the safety or usefulness of fludrocortisone. If you are also taking other drugs (like hydrocortisone), ask your doctor about the safety of a drink of alcohol.
For women: Fludrocortisone may harm the baby if used during pregnancy. It is best to use birth control while being treated with fludrocortisone. Tell your doctor right away if you become pregnant. Do not breast feed during treatment.
Tell doctors or dentists that you are being treated with fludrocortisone before you receive any treatment from them.
Wear a medical-alert bracelet to inform doctors in an emergency as you may need extra steroids.
| SIDE EFFECTS | MANAGEMENT |
| Nausea may occur especially when you first start taking fludrocortisone. Most people have little or no nausea. | *Take your fludrocortisone after eating. |
| Your body's ability to handle illness or injury is weakened by fludrocortisone. You may need extra steroids to help you get better. | *Check with your doctor if you have an infection, illness or injury. |
| Sugar control may be affected in diabetics. | *Check your blood sugar regularly if you are diabetic. |
| Swelling of hands, feet or lower legs occur if your body retains extra fluid. | *Check with your doctor as soon as possible. *Your doctor may tell you to reduce the salt in your food. |
SEE YOUR DOCTOR OR GET EMERGENCY HELP IMMEDIATELY IF YOU HAVE:
Signs of an infection such as fever (over 100degF or 38degC); chills; cough; sore throat; pain or burning when you pass urine; redness, pain or swelling of any area of your body; sores forming anywhere on your body.
Signs of an allergic reaction (rare) including dizziness, difficulty breathing, shortness of breath, wheezing; rash over the whole body or swelling of the face.
SEE YOUR DOCTOR AS SOON AS POSSIBLE (DURING OFFICE HOURS) IF YOU HAVE:
Signs of fluid or heart problems such as shortness of breath or difficulty breathing, swelling of feet or lower legs, rapid weight gain. Signs of low potassium such as vomiting, muscle cramps or weakness, numbness or tingling of the lower legs and feet, mental confusion. Severe or constant headache. Changes in eye sight.
CHECK WITH YOUR DOCTOR IF ANY OF THE FOLLOWING CONTINUE OR BOTHER YOU:
Uncontrolled nausea, vomiting, diarrhea or stomach pain. For diabetics: uncontrolled blood sugars. For women: changes in menstrual periods. Easy bruising or bleeding.
REPORT ADDITIONAL PROBLEMS TO YOUR DOCTOR.
Notes:
:
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Kastrup EK, et al, eds. Facts and comparisons: Loose-leaf drug information service. St. Louis: JB Lippincott Co, 1989:121b.
Smith SJ, et al. Evidence that patients with Addison's disease are undertreated with fludrocortisone. Lancet 1984; 1:11-4.
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Benitz WE, Tatro DS. The pediatric drug handbook. Chicago: Year Book Medical Publishers, 1981.
USP DI Volume I: Drug information for the health care professional, 14th ed. Rockville: United States Pharmacopeial Convention Inc, 1994:1390-2.
USP DI Volume II: Advice for the patient: Drug information in lay language, 14th ed. Rockville: United States Pharmacopeial Convention Inc, 1994:643-5.