Fludrocortisone Acetate

Registered South African indications:

• Partial replacement therapy for primary adrenocortical insufficiency in Addison’s disease
• Treatment of salt-losing adrenogenital syndrome

Registered South African contraindications

• Hypersensitivity to the fludrocortisone acetate or to any of the excipients
• Systemic infections unless specific anti-infective therapy is employed
• The treatment of conditions other than those indicated (due to its marked effect on sodium retention)
• Tuberculosis
• Acute psychosis
• Ocular herpes simplex
• Active peptic ulcer
• Acute glomerulonephritis
• Fungal diseases
• Vaccinia
• Varicella
• Patients with uncontrolled congestive heart failure
• Use of live vaccines
• Pregnancy
• Lactation

Contraindications registered in other jurisdictions

• Hypersensitivity to the active substance or to any of the excipients
• Systemic infections unless specific anti-infective therapy is employed
• Because of its marked effect on sodium retention, the use of fludrocortisone acetate in the treatment of conditions other than those indicated, is not advised
• Since fludrocortisone acetate is a potent mineralocorticoid both the dosage and salt intake should be carefully monitored to avoid the development of hypertension, oedema or weight gain. Periodic checking of serum electrolyte levels is advisable during prolonged therapy

• Pregnancy (Recommendations in other jurisdictions)
• Breastfeeding (Recommendations in other jurisdictions)
• Renal impairment
• Hepatic impairment
• Elderly
• Avoid exposure to chickenpox, shingles and measles
• Recent intestinal anastomoses
• Diverticulitis
• Thrombophlebitis
• Existing or previous history of severe affective disorders 
• Exanthematous disease
• Chronic nephritis
• Metastatic carcinoma
• Osteoporosis
• Active peptic ulcer or history thereof
• Myasthenia gravis
• Latent or healed tuberculosis
• In the presence of local or systemic viral infection
• Systemic fungal infections or in active infections not controlled by antibiotics
• Acute psychoses
• Acute glomerulonephritis
• Hypertension
• Congestive cardiac failure
• Glaucoma or a family history thereof
• Previous steroid myopathy
• Epilepsy
• Thyroid disease
• Cirrhosis
• Diabetes mellitus
• History of drug allergies
• Hypoprothrombinaemia
• High doses
• Systemic exposure
• Existing or previous history of severe affective disorders in themselves or in their first degree relatives
• Children
• Galactose intolerance
• Lapp lactase deficiency
• Glucose-galactose malabsorption

Forms avail. in SA and covered in this monograph: tab

South African registered indications and dosages

Partial replacement therapy for primary adrenocortical insufficiency in Addison’s disease (Chronic)

• Oral (tab): Usual dose: 0.1mg; Daily range: 0.1mg three times a week to 0.2mg, daily

In primary adrenal insufficiency, such as Addison’s disease, the combination of fludrocortisone acetate for its mineralocorticoid effect, with a glucocorticoid such as hydrocortisone or cortisone provides substitution therapy approximating normal adrenal activity

If treatment-associated hypertension develops, the dose should be reduced to 0.05mg daily

Fludrocortisone acetate is administered preferably in conjunction with cortisone (10mg to 37.5mg daily in divided doses) or hydrocortisone (10mg to 30mg daily in divided doses)

Treatment of salt-losing adrenogenital syndrome

• Oral (tab): 0.1-0.2mg, daily

Dosage depends on the severity of the disease and the response of the patient. The lowest possible dose should be used to control the condition being treated and a reduction in dosage should be made (gradually) when possible

Paed. forms avail. in SA and covered in this monograph: tab

South African registered indications and dosages

Treatment of salt-losing adrenogenital syndrome

Paediatric and adolescents

• Oral (tab): 0.05-0.1mg, daily

Dosage depends on the severity of the disease and the response of the patient. The lowest possible dose should be used to control the condition being treated and a reduction in dosage should be made (gradually) when possible

The need may decrease with age and therefore the dose should be titrated to the clinical requirements of the child

Pregnancy

South African recommendations

• Contraindicated

Recommendations in other jurisdictions

• Caution
• It may be decided to continue a pregnancy in a woman requiring replacement mineralocorticoid therapy, despite the risk to the foetus. When corticosteroids are essential, however, patients with normal pregnancies may be treated as though they were in the non-gravid state
• There is evidence of harmful effects in pregnancy in animals. There may be a small risk of cleft palate and intra-uterine growth retardation. Hypoadrenalism may occur in the neonate. Patients with pre-eclampsia or fluid retention require close monitoring

Breastfeeding

South African recommendations

• Contraindicated

Recommendations in other jurisdictions

• Caution
• Corticosteroids are found in breast milk
• Infants born of mothers who have received substantial doses of corticosteroids during pregnancy or during breastfeeding should be carefully observed for signs of hypoadrenalism. Maternal treatment should be carefully documented in the infant's medical records to assist in follow up

Fertility

• There are insufficient fertility data available to indicate whether fludrocortisone acetate has any effect on fertility

Renal Impairment

• Caution; no dose adjustment recommended

Hepatic Impairment

• Caution; no dose adjustment recommended

Elderly

• Caution; no dose adjustment recommended

Porphyria

• Probably porphyrinogenic (PRP)

Central Nervous System Disorders

• Euphoria
• Psychological dependence
• Depression
• Insomnia
• Convulsions
• Increased intracranial pressure with papilloedema 
• Vertigo
• Headache
• Neuritis 
• Paraesthesias 
• Agravation of pre-existing psychiatric conditions 
• Epilepsy
• Affective disorders 
• Psychotic reactions
• Behavioural disturbances
• Irritability
• Anxiety
• Sleep disturbances
• Cognitive dysfunction 
• Amnesia 
• Insomnia 
• Syncopal episodes

Cardiovascular Disorders

• Thrombophlebitis
• Thromboembolism
• Hypertension
• Necrotising angiitis

Gastrointestinal Disorders

• Dyspepsia
• Peptic ulcer with possible subsequent perforation and haemorrhage
• Pancreatitis
• Abdominal distension 
• Ulcerative oesophagitis
• Candidiasis

Endocrine and Metabolic Disorders

• Menstrual irregularities 
• Amenorrhoea
• Cushingoid state
• Suppression of growth
• Secondary adrenocortical and pituitary unresponsiveness
• Decreased carbohydrate tolerance
• Latent diabetes mellitus 
• Increased requirements for insulin or oral hypoglycaemic agents in diabetes
• Weight gain
• Negative protein and calcium balance
• Increased appetite
• Sodium retention
• Fluid retention
• Congestive cardiac failure in susceptible patients
• Potassium loss
• Cardiac arrhythmias or ECG changes due to potassium deficiency
• Hypokalaemic alkalosis
• Increased calcium excretion

Musculoskeletal Disorders

• Muscle weakness
• Fatigue
• Steroid myopathy
• Loss of muscle mass
• Osteoporosis
• Avascular osteonecrosis
• Vertebral compression fractures
• Delayed healing of fractures
• Aseptic necrosis of femoral and humeral heads
• Pathological fractures of long bones 
• Spontaneous fractures
• Tendon rupture

Skin and Subcutaneous Tissue Disorders

• Impaired wound healing
• Thin fragile skin
• Petechiae 
• Ecchymoses
• Facial erythema
• Increased sweating
• Purpura
• Striae
• Hirsutism
• Acneiform eruptions
• Lupus erythematosus-like lesions 
• Suppressed reactions to skin tests

Immune, Blood and Lymphatic System Disorders

• Increased susceptibility and severity of infections 
• Opportunistic infections
• Recurrence of dormant tuberculosis
• Anaphylatic reactions
• Angiodema
• Rash
• Pruritus
• Urticaria
• Leucocytosis

Sensory Disorders

• Posterior subcapsular cataracts
• Increased intraocular pressure
• Glaucoma
• Exophthalmos
• Papilloedema
• Corneal or scleral thinning
• Exacerbation of ophthalmic viral or fungal diseases

• Amphotericin B injection 
• Potassium-depleting agents
• Anticholinesterases
• Oral anticoagulants
• Antidiabetics
• Antihypertensives
• Diuretics
• Antitubercular agents
• Cyclosporin
• CYP3A inhibitors
• Digitalis glycosides
• Oral contraceptives
• Oestrogens
• Hepatic enzyme inducers
• Human growth hormone
• Ketoconazole
• Nondepolarising muscle relaxants
• Non-steroidal anti-inflammatory drugs
• Thyroid drugs
• Vaccines

None routine. Specific cases may require

• Electrolytes
• Growth and development (children)
• Blood glucose
• Hypothalamic–pituitary–adrenal axis
• Blood pressure

Fludrocortisone acetate act similarly to hydrocortisone and exerts a profound mineralocorticoid effect, its usefulness is limited to clinical applications which utilise this effect. Small oral doses of fludrocortisone acetate produce marked sodium retention and increased urinary potassium excretion. Fludrocortisone acetate also causes a rise in blood pressure, apparently because of these effects on electrolyte levels. In larger doses, the steroid inhibits endogenous adrenal cortical secretion, thymic activity, and pituitary corticotrophin secretion; promotes the deposition of liver glycogen; and, unless protein intake is adequate, induces negative nitrogen balance.

Tablet 0.1mg

• Florinef (Pharmacare) originator