Bristol-Myers Squibb Pharmaceutical Limited

Florinef 0.1 mg Tablets

Each tablet contains fludrocortisone acetate 0.1 mg.

Also contains lactose, 59.59 mg per tablet

For a full list of excipients, see section 6.1.

Tablet

Round, biconvex, white tablets, scored on one side and engraved on the other side with “SQUIBB” and “429”. The tablets can be divided into equal halves.

For partial replacement therapy for primary adrenocortical insufficiency in Addison's disease and for the treatment of salt-losing adrenogenital syndrome.

Adults

Addison's Disease

A daily dosage range of 0.05 to 0.3 mg Florinef tablets orally. Supplementary parenteral administration of sodium-retaining hormones is not necessary. When an enhanced glucocorticoid effect is necessary, this should be achieved by concurrent administration of cortisone (6.25 to 25 mg) or hydrocortisone (5 to 20 mg) daily.

Adrenal Hyperplasia

The usual daily dosage for control is 1 to 2 mg. Restriction of sodium intake and supplementary potassium administration may be required.

Children

Daily dosage should be adjusted to the age and weight of the child and the severity of the condition. Caution should be used in the event of exposure to chickenpox, measles or other communicable diseases. (See 4.4 Special Warnings and Precautions for Use).

Elderly

No specific dosing recommendations (see Precautions).

Use in patients with peptic ulcer, active tuberculosis, acute psychosis, acute bacterial or viral infection.

Use in patients hypersensitive to the product components.

Since Florinef 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.

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 Florinef 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 normally minor 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.

Particular care is required when considering use of systemic corticosteroids in patients with the following conditions and frequent patient monitoring is necessary.

Diverticulitis, recent intestinal anastomoses, 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 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.

All corticosteroids increase calcium excretion. Corticosteroid effects may be enhanced in patients with hypothyroidism or cirrhosis and decreased in hyperthyroid patients.

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.

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

During corticosteroid therapy antibody response will be reduced and therefore affect the patient's response to vaccines.

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.

There have been a few reports in the literature of the development of cataracts in patients who have been using corticosteroids for prolonged periods of time. Although it is not possible to rule out systemic corticosteroids as a known factor, prescribers should be aware of the possible role of corticosteroids in cataract development.

Patients and/or carers should be warned that potentially severe psychiatric adverse reactions may occur with systemic steroids (see section 4.8). Symptoms typically emerge within a few days or weeks of starting the treatment. Risks may be higher with high doses/systemic exposure (see also section 4.5 pharmacokinetic interactions that can increase the risk of side effects), although dose levels do not allow prediction of the onset, type, severity or duration of reactions. Most reactions recover after either dose reduction or withdrawal, although specific treatment may be necessary. Patients/carers should be encouraged to seek medical advice if worrying psychological symptoms develop, especially if depressed mood or suicidal ideation is suspected. Patients/carers should also be alert to possible psychiatric disturbances that may occur either during or immediately after dose tapering/withdrawal of systemic steroids, although such reactions have been reported infrequently.

Particular care is required when considering the use of systemic corticosteroids in patients with existing or previous history of severe affective disorders in themselves or in their first degree relatives. These would include depressive or manic-depressive illness and previous steroid psychosis.

Children

Growth and development of children on prolonged corticosteroid therapy should be carefully observed. Prolonged use in children may lead to growth retardation. Some recovery may occur on discontinuing the drug.

Elderly

The common adverse effects of systemic corticosteroids may be associated with more serious consequences in old age, especially osteoporosis, hypertension, hypokalaemia, diabetes, susceptibility to infection and thinning of the skin. Close clinical supervision is required to avoid life-threatening reactions.

Amphotericin B injection and potassium-depleting agents: Patients should be observed for hypokalemia.

Anti-cholinesterases: Effects of anticholinesterase agents may be antogonised.

Anti-coagulants, oral: Corticosteroids may potentiate or decrease anticoagulant action. Patients receiving oral anticoagulants and corticosteroids should therefore be closely monitored.

Anti-diabetics: Corticosteroids may increase blood glucose; diabetic control should be monitored, especially when corticosteroids are initiated, discontinued, or changed in dosage.

Anti-hypertensives, including diuretics: corticosteroids antagonise the effects of antihypertensives and diuretics. The hypokalaemic effect of diuretics, including acetazolamide, is enhanced.

Anti-tubercular drugs: Isoniazid serum concentrations may be decreased.

Cyclosporin: Monitor for evidence of increased toxicity of cyclosporin when the two are used concurrently.

Digitalis glycosides: Co-administration may enhance the possibility of digitalis toxicity.

Oestrogens, include oral contraceptives: Corticosteroid half-life and concentration may be increased and clearance decreased.

Hepatic Enzyme Inducers (e.g. aminoglutethemide, barbiturates, carbamazepine, phenytoin, primidone, rifabutin, rifampicin): There may be increased metabolic clearance of Florinef. Patients should be carefully observed for possible diminished effect of steroid, and the dosage should be adjusted accordingly.

Human growth hormone: The growth-promoting effect may be inhibited.

Ketoconazole: Corticosteroid clearance may be decreased, resulting in increased effects.

Non-depolarising muscle relaxants: Corticosteroids may decrease or enhance the neuromuscular blocking action.

Nonsteroidal anti-inflammatory agents (NSAIDs): corticosteroids may increase the incidence and/or severity of GI bleeding and ulceration associated with NSAIDs. Also, corticosteroids can reduce serum salicylate levels and therefore, decrease their effectiveness. Conversely, discontinuing corticosteroids during high-dose salicylate therapy may result in salicylate toxicity. Aspirin should be used cautiously in conjunction with corticosteroids in patients with hypoprothrombinaemia.

Thyroid drugs: Metabolic clearance of adrenocorticoids is decreased in hypothyroid patients and increased in hyperthyroid patients. Changes in thyroid status of the patient may necessitate adjustment in adrenocorticoid dosage.

Vaccines: Neurological complications and lack of antibody response may occur when patients taking corticosteroids are vaccinated. (See 4.4 Special Warnings and Precautions for Use.)

Corticosteroids have been shown to be teratogenic in some animal species; so far there has been no clear evidence of a similar effect in human beings. However, they should not be used in pregnancy unless considered essential by the physician.

None known.

Corticosteroid administration will result in certain effects, the severity, significance and extent of which vary with the dosage and duration of treatment and the particular corticosteroid used.

These include disturbance in electrolyte balance, mineral metabolism, glucose metabolism and gluconeogenesis, nitrogen depletion, diminished lymphoid tissue and immune response, inhibition of pituitary function, Cushingoid Syndrome, increase in blood coagulability, diminished inflammatory response. Cataracts, psychosis, mood changes, avascular osteo necrosis and pancreatitis may occur. Other areas affected include musculoskeletal, gastrointestinal, dermatologic, neurological and endocrine.

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.

A single large dose should be treated with plenty of water by mouth. Careful monitoring of serum electrolytes is essential, with particular consideration being given to the need for administration of potassium chloride and restriction of dietary sodium intake.

Not applicable.

A potent mineralocorticoid with some glucocorticoid properties, well absorbed, metabolised slowly with a T½ of up to 30 hours. It has strong sodium retaining capacity.

Nothing further of relevance to the prescriber.

Dibasic calcium phosphate

Lactose anhydrous

Lactose monohydrate

Talc

Maize starch

Magnesium stearate

Sodium benzoate (E211).

Not applicable.

2 years

Store in a refrigerator (2-8°C). Keep the bottle tightly closed to protect from moisture.

Type III Amber glass bottles of 100 tablets with a cotton plug, induction seal and polypropylene caps.

No special requirements.

Bristol-Myers Squibb Pharmaceuticals Limited

Swords

County Dublin

PA 2/19/1

Date of first authorisation: 1 April 1978

Date of last renewal: 1 April 2008

31 May 2010