FLUDROCORTISONE ACETATE

3 mg Fludrocortisone acetate tablets orally. Supplementary parenteral administration of sodium-retaining hormones is not necessary. When an enhanced glucocorticoid effect is desirable, cortisone or hydrocortisone by mouth should be given concomitantly with Fludrocortisone acetate tablets.

4). 1 mg) daily. 3). Method of administration For oral use.

Summary of the safety profile Most adverse reactions to fludrocortisone acetate are caused by the drug’s mineralocorticoid activity and include hypertension, oedema, cardiac enlargement, congestive heart failure, potassium loss, and hypokalemic alkalosis.

Where adverse reactions occur they are usually reversible on cessation of therapy. 4). Tabulated list of adverse reactions The list below is presented by system organ class, MedDRA preferred term, and frequency using the following frequency categories: Very common (≥1/10) Common (≥ 1/100 to < 1/10) Uncommon (≥ 1/1,000 to < 1/100) Rare (≥ 1/10,000 to < 1/1,000) Very rare (< 1/10,000) not known (cannot be estimated from the available data) System Organ Class Frequency MedDRA Terms Metabolism and nutrition Very common Hypokalaemia disorders Uncommon Hypokalaemic alkalosis, Decreased appetite Uncommon Delusional perception, illusion Psychiatric disorders Uncommon Hallucination Common HeadacheNervous System disorders Uncommon Seizure, epilepsy, syncope, loss of consciousness, dysgeusia Very common Cardiac failure congestiveCardiac disorders Uncommon Cardiomegaly Vascular disorders Very common Hypertension Gastrointestinal disorders Uncommon Diarrhoea Common Muscular weaknessMusculoskeletal and connective tissue disorders Uncommon Muscle atrophy General disorders and administration site conditions Common Oedema, swelling Investigations Uncommon Blood potassium decreased Description of selected adverse reactions When fludrocortisone is used at the recommended dosages, the glucocorticoid side effects are not usually present; however, the following adverse events have been spontaneously reported in two or more patients taking Fludrocortisone acetate overdose.

Withdrawal Symptoms and Signs:

On withdrawal, fever, myalgia, arthralgia, rhinitis, conjunctivitis, painful itchy skin nodules and weight loss may occur. 4). 4). Fluid and electrolyte disturbances: sodium retention, fluid retention, cardiac arrhythmias or ECG changes due to potassium deficiency and increased calcium excretion.

Musculoskeletal and connective tissue disorders: 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 and spontaneous fractures, tendon rupture.

Gastrointestinal disorders: dyspepsia, peptic ulcer with possible subsequent perforation and haemorrhage, pancreatitis, abdominal distension and ulcerative oesophagitis, candidiasis.

Hypersensitivity:

Anaphylactic reactions, angioedema, rash, pruritus and urticaria, particularly where there is a history of drug allergies. Skin and subcutaneous tissue disorders: impaired wound healing, thin fragile skin, petechiae and ecchymoses, facial erythema, increased sweating, purpura, striae, hirsutism, acneiform eruptions, lupus erythematosus-like lesions and suppressed reactions to skin tests.

Nervous system disorders: euphoria, psychological dependence, depression, insomnia, increased intracranial pressure with papilloedema (pseudo-tumour cerebri) usually after treatment, vertigo, neuritis or paraesthesias and aggravation of pre- existing psychiatric conditions.

A wide range of psychiatric reactions including affective disorders (such as irritable, euphoric, depressed and labile mood, and suicidal thoughts), psychotic reactions (including mania, delusions, hallucinations, and aggravation of schizophrenia), behavioural disturbances, irritability, anxiety, sleep disturbances, and cognitive dysfunction including confusion and amnesia have been reported.

Reactions are common and may occur in both adults and children. In adults, the frequency of severe reactions has been estimated to be 5-6%. Psychological effects have been reported on withdrawal of corticosteroids; the frequency is unknown.

g. trauma, surgery or illness); decreased carbohydrate tolerance; manifestations of latent diabetes mellitus and increased requirements for insulin or oral hypoglycaemic agents in diabetes, weight gain. Negative protein and calcium balance.

Increased appetite. 4). Others: necrotising angiitis, thrombophlebitis, thromboembolism, leukocytosis, insomnia and syncopal episodes. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Fludrocortisone acetate is a potent mineralocorticoid and is used predominantly for replacement therapy. Although glucocorticoid side effects may occur, these can be reduced by reducing the dosage. Undesirable effects may be minimised using the lowest effective dose for the minimum period.

2). Adrenal cortical atrophy develops during prolonged therapy and may persist for years after stopping treatment. Withdrawal of corticosteroids after prolonged therapy must, therefore, always be gradual to avoid acute adrenal insufficiency and should be tapered off over weeks or months according to the dose and duration of treatment.

Patients on long-term systemic therapy with Fludrocortisone acetate may require supportive corticosteroid therapy in times of stress (such as trauma, surgery or severe illness) both during the treatment period and up to a year afterwards.

If corticosteroids have been stopped following prolonged therapy they may need to be reintroduced temporarily. Patients should carry steroid treatment cards which give clear guidance on the precautions to be taken to minimise risk and which provides details of prescriber, drug, dosage and the duration of treatment.

Anti-inflammatory/immunosuppressive effects:

Suppression of the inflammatory response and immune function increases the susceptibility to infections and their severity. The clinical presentation may often be atypical and serious infections such as septicaemia and tuberculosis may be masked and may reach an advanced stage before being recognised.

Chickenpox, shingles and measles are of particular concern since these illnesses may be fatal in immunosuppressed patients. Patients should be advised to avoid exposure to these diseases, and to seek medical advice without delay if exposure occurs.

Chickenpox:

Unless they have had chickenpox, patients receiving oral corticosteroids for purposes other than replacement should be regarded as being at risk of severe chickenpox. Manifestations of fulminant illness include pneumonia, hepatitis and disseminated intravascular coagulation; rash is not necessarily a prominent feature.

Passive immunisation with varicella zoster immunoglobulin (VZIG) is needed by exposed non-immune patients who are receiving systemic corticosteroids or who have used them within the previous 3 months; this should preferably be given within 3 days of exposure, and not later than 10 days after exposure to chickenpox.

Confirmed chickenpox warrants specialist care and urgent treatment. Corticosteroids should not be stopped and the dose may need to be increased.

Measles:

Prophylaxis with normal immunoglobulin may be needed. During corticosteroid therapy antibody response will be reduced and therefore affect the patient's response to vaccines. Live vaccines should not be administered. Corticosteroids may affect the nitroblue tetrazolium test for bacterial infection, producing false negative results.

Tuberculosis:

Those with a previous history of, or X-ray changes characteristic of, tuberculosis. The emergence of active tuberculosis can, however, be prevented by the prophylactic use of anti-tuberculosis therapy. Chemoprophylaxis should be used in patients with latent tuberculosis or tuberculin reactivity who are taking corticosteroids.

Corticosteroids should be used with caution in patients with the following conditions: nonspecific ulcerative colitis (if there is a probability of perforation, abscess, or other pyogenic infection); recent intestinal anastomoses; diverticulitis; thrombophlebitis; existing or previous history of severe affective disorders (especially previous steroid psychosis); exanthematous disease; chronic nephritis or renal insufficiency; metastatic carcinoma; osteoporosis (post-menopausal females are particularly at risk); in patients with an active or latent peptic ulcer (or a history of peptic ulcer); 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; in acute psychoses, in acute glomerulonephritis; hypertension, congestive heart failure; glaucoma (or a family history of glaucoma), previous steroid myopathy or epilepsy.

Liver failure. Pheochromocytoma crisis Several life-threatening and fatal cases of pheochromocytoma crisis have been reported following administration of systemic corticosteroids to patients with suspected or identified pheochromocytoma.

Use of corticosteroids in these patients should only be considered after an appropriate risk/benefit evaluation. Visual disturbance Visual disturbance may be reported with systemic and topical corticosteroid use. If a patient presents with symptoms such as blurred vision or other visual disturbances, the patient should be considered for referral to an ophthalmologist for evaluation of possible causes which may include cataract, glaucoma or rare diseases such as central serous chorioretinopathy (CSCR) which have been reported after use of systemic and topical corticosteroids.

Corticosteroid effects may be enhanced in patients with hypothyroidism or decreased in hyperthyroid patients. Corticosteroid effects may be enhanced in patients with cirrhosis. Diabetes may be aggravated, necessitating a higher insulin dosage.

Latent diabetes mellitus may be precipitated. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine. Menstrual irregularities may occur, and this possibility should be mentioned to female patients.

Rare instances of anaphylactoid reactions have occurred in patients receiving corticosteroids, especially when a patient has a history of drug allergies. Aspirin should be used cautiously in conjunction with corticosteroids in patients with hypoprothrombinaemia.

Prolonged use of corticosteroids may […]

1. 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.