Summary of medicine characteristics - DELTALONE TABLETS 1 MG, PREDNISOLONE TABLETS 1 MG
Deltalone Tablets 1mg
Prednisolone Tablets 1mg
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Prednisolone BP 1.00 mg
3 PHARMACEUTICAL FORM
Tablet
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Bronchial asthma, allergic rhinitis, serum sickness, drug sensivity, laryngeal oedema, transfusion reactions.
Allergic dermatoses, angioneurotic odema, pemphigus.
Rheumatoid arthritis, rheumatoid spondylitis, Still’s disease and psoriatic arthritis, acute rheumatic fever disseminated lupus erythematosus, polyarteritis nodosa, scleroderma, dermatomyositis.
Acquired haemolytic anaemia, aplastic anaemia, idiopathic thrombocytopenic purpura, allergic purpura.
Primary or secondary adrenocortical insufficiency.
Lymphocytic leukaemia, pulmonary granulomatosis, lymphomas, Hodgkin’s disease (for short term symptomatic relief).
Iritis, iridocyclitis, chorioretinitis, posterior uveitis, retinitis centralis, herpes zoster opthalmicus (but not herpes simplex) optic neuritis, retrobulbar neuritis, sympathetic opthalmia.
Adrenogenital syndrome, acute gouty artritis, sarcoidosis, idiopathic sprue, ulcerative colitis, ileitis, nephrotic syndrome, non-suppurative thyroiditis, Bell’s palsy, Hunner’s ulcer.
Bursitis, synovitis, tenosynovitis.
4.2 Posology and method of administration
Tablets are best taken dissolved in water. The daily dose should be taken in the morning after breakfast. For further information with refernce to the dosage, see ‘warnings and precautions’ section.
Adults and Elderly: The following regimens are for guidance only.
Short term treatment: 20–30 mg daily for the first few days, subsequently reducing the daily dosage by 2.5 or 5 mg every 2 to 5 days, depending on the response.
Rhematoid Arthritis: 7.5–10 mg daily. For maintenance therapy the lowest effective dosage
is used.
Most other 10–100 mg daily for 1 to 3 weeks, then reducing to the minimum
conditions: effective dosage.
Children: Fractions of the adult dosage may be used (e.g. 75% at 12 years, 50%
at 7 years and 25% at 1 year), but clinical factors must be given due weight.
The lowest dosage that will produce an acceptable result should be used; (see ‘Other special warnings and precautions’) when it is possible to reduce the dosage, this must be accomplished by stages. During prolonged therapy dosage may need to be increased temporarily during periods of stress or in exacerbations of illness. Appropriate conventional therapy should be instituted as indicated. Any decrease in dosage must be gradual. Continued supervision of the patient after cessation of corticosteroid therapy is essential since there may be a sudden reappearance of symptoms.
Where prompt relief is urgent, high dosages are permissible and may be mandatory for a short time. In chronic conditions the lowest dose which provides adequate relief should be used. During periods of spontaneous remission corticosteroiods should be gradually discontinued.
Withdrawal warnings
In patients who have received more than physiological doses of systemic corticosteroids (approximately 7.5 mg prednisolone or equivalent) for greater than 3 weeks, withdrawal should not be abrupt. How dose reduction should be carried out depends largely on whether the disease is likely to relapse as the dose of systemic corticosteroids is reduced. Clinical assessment of disease activity may be needed during withdrawal. If the disease is unlikely to relapse on withdrawal of systemic corticosteroids, but there is uncertainty about HPA suppression, the dose of systemic corticosteroid may be reduced rapidly to physiological doses. Once a daily dose equivalent to 7.5 mg of prednisolone is reached, dose reduction should be slower to allow the HPA-axis to recover.
Abrupt withdrawal of systemic corticosteroid treatment, which has continued up to 3 weeks is appropriate if it is considered that the disease is unlikely to relapse. Abrupt withdrawal of doses of up to 40 mg daily of prednisolone, or equivalent for 3 weeks is unlikely to lead to clinically relevant HPA-axis suppression, in the majority of patients. In the following patient groups, gradual withdrawal of systemic corticosteroid therapy should be considered even after courses lasting 3 weeks or less:
Patients who have had repeated courses of systemic corticosteroids, particularly if taken for greater than 3 weeks,
When a short course has been prescribed within one year of cessation of long-term therapy (months or years),
Patients who may have reasons for adrenocortical insufficiency other than exogenous corticosteroids therapy,
Patients receiving doses of systemic corticosteroid greater than 40 mg daily of prednisolone (or equivalent),
Patients repeatedly taking doses in the evening.
Route of administration: Oral.
4.3 Contraindications
i. Hypersensitivity to Prednisolone.
ii. Systemic infection unless specific anti-infective therapy is employed. (See other Special Warnings and Precautions).
4.4 Special warnings and precautions for use
A patient information leaflet should be supplied with this product.
Undesirable effects may be minimised by using the lowest effective dose for the minimum period, and by administering the daily requirement as a single morning dose or whenever possible as a single morning dose on alternative days. Frequent patient review is required to appropriately titrate the dose against disease activity. (see Dosage section).
Adrenal Suppression: 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, being tapered off over weeks or months according to the dose and duration of treatment. During prolonged therapy any intercurrent illness, trauma or surgical procedure will require a temporary increase in dosage if corticosteroids have been stopped following prolonged therapy they may need to be temporarily reintroduced.
Patients should carry ‘Steroid treatment’ cards which give clear guidance on the precautions to be taken to minimise risk and which provide details of the prescriber, drug, dosage and the duration of treatment.
Anti-inflamatory/Immunosuppressive effects and infection:
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. The emergence of active tuberculosis can, however, be prevented by the prophylactic use of antituberculosis therapy.
Chickenpox is of particular concern since this normally minor illness may be fatal in immunosuppressed patients. Patients (or parents of children) without a definite history of chickenpox should be advised to avoid close personal contact with chickenpox or herpes zoster and if exposed they should seek urgent medical attention. Passive immunisation with varicella/zoster immunoglobin (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 be given within 10 days of exposure to chickenpox. If a diagnosis of chickenpox is confirmed, the illness warrants specialist care and urgent treatment.
Patients should be advised to take particular care to avoid exposure to measles and to seek medical advice without delay if exposure occurs; prophylaxis with intramuscular normal immunoglobulin may be needed.
Corticosteroids should not be stopped and the dose may need to be increased.
Live vaccines should not be given to individuals with impaired immune responsiveness. The antibody response to other vaccines may be diminished.
Particular care is required when considering the use of systemic corticosteroids in patients with the following conditions and frequent patient monitoring is necessary.
a) Osteoporosis (post-menopausal females are particularly at risk)
b) Hypertension or congestive heart failure
c) Existing or previous history of severe affective disorders (especially previous steroid psychosis)
d) Diabetes mellitus (or a family history of diabetes)
e) Previous history of tuberculosis, or characteristic appearance on chest x-ray
f) Glaucoma (or a family history of glaucoma)
g) Previous corticosteroid-induced myopathy
h) Liver failure
i) Renal insufficiency
j) Epilepsy
k) Peptic ulceration
In children corticosteroids cause dose-related growth retardation in infancy, childhood and adolescence, which may be irreversible. In order to minimise suppression of the hypothalamo-pituitary adrenal axis and growth retardation, treatment should be administered where possible as a single dose on alternate days.
In the 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.
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.
4.5 Interaction with other medicinal products and other forms of interaction Rifampicin, rifabutin, carbamazepine, phenobarbitone and other barbiturates, phenytoin, primidone and aminoglutethimide enhance the metabolism of corticosteroids and its therapeutic effects may be reduced.
The desired effects of hypoglycaemic agents (including insulin), antihypertensives and diuretics are antagonised by corticosteroids, and the hypokalaemic effects of acetazolamide, loop diuretics, thiazide diuretics and carbenoxolone are enhanced. Signs of hypokalaemia should be looked for when amphotericin and corticosteroids are used concurrently since both have potassium depleting effects.
The efficacy of coumarin anticoagulants may be enhanced by concurrent corticosteroid therapy and close monitoring of the INR or prothrombin time is required to avoid spontaneous bleeding.
The renal clearance of salicylates is increased by corticosteroids and steroid withdrawal may result in salicylate intoxication. In addition since salicylates and corticosteroids are ulcerogenic, it is possible that there will be an increased rate of gastrointestinal ulceration.
Methotrexate: There is a small amount of evidence that use of corticosteroids and methotrexate simultaneously may cause increased methotrexate toxicity and possibly death, although this combination of drugs has been used very successfully.
4.6 Pregnancy and lactation
The ability of corticosteroids to cross the placenta varies between individual drugs, however, 88% of prednisolone is inactivated as it crosses the placenta.
The administration of corticosteroids to pregnant animals can cause abnormalities of foetal development including cleft palate, intra-uterine growth retardation and affects on brain growth and development. There is no evidence that corticosteroids result in an increased incidence of congenital abnormalities, such as cleft palate/lip in man. However, administered for prolonged periods or repeatedly during pregnancy, corticosteroids may increase the risk of intra-uterine growth retardation. Hypoadrenalism may, in theory, occur in the neonate following parental exposure to corticosteroids but usually revolves spontaneously following birth and is rarely clinically important. As with all drugs, corticosteroids should only be prescribed when the benefits to the mother and child outweigh the risks. When corticosteroids are essential however, patients with normal pregnancies may be treated as though they were in a non-gravid state.
Lactation:
Corticosteroids are excreted in small amounts in breast milk. However, doses of up to 40 mg daily of prednisolone are unlikely to cause systemic effects in the infant. Infants of mothers taking higher doses than this may have a degree of adrenal suppression but the benefits of breast-feeding are likely to outweigh any theoretical risk.
4.7 Effects on ability to drive and use machines
4.7 Effects on ability to drive and use machinesNone stated.
4.8 Undesirable effects
The incidence of predictable undesirable effects, including hypothalamic-pituitaryadrenal suppression correlates with the relative potency and the drug, dosage, timing of administration and duration of treatment (see Other special warnings and precautions).
Gastro-intestinal: Dyspepsia, peptic ulceration with perforation and haemorrhage, abdominal distension, oesophageal ulceration, oesophageal candidiasis, acute pancreatitis.
Musculoskeletal: Proximal myopathy, osteoporosis, vertebral and long bone fractures, avascular osteonecrosis, tendon rupture.
Fluid and electrolyte disturbance: Sodium and water retention, hypertension, potassium loss, hypokalemic alkalosis.
Dermatological: Impaired healing, skin atrophy, bruising, telangiectasia, striae, acne.
Endocrine/metabolic: Suppression of the hypothalamo-pituitary adrenal axis, growth suppression in childhood and adolescence, menstrual irregularity and amenorrhoea. Cushingoid facies, hirsutism, weight gain, impaired carbohydrate tolerance with increased requirement for antidiabetic therapy, negative protein and calcium balance. Increased appetite.
Neuropsychiatric: 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.
Also increased intra-cranial pressure with papilloedema in children (pseudotumour cerebri), usually after treatment withdrawal. Aggravation of epilepsy.
During treatment the patient should be observed for psychotic reactions, muscular weakness, electrocardiographic changes, hypertension and untoward hormonal effects.
Opthalmic: Increased intraocular pressure, glaucoma, papilloedema, cataracts, corneal or scleral thinning, exacerbation of opthalmic viral or fungal diseases.
Anti-inflammatory and immuno-suppressive effects: Increased susceptibility and severity of infections with suppression of clinical symptoms and signs, opportunistic infections, recurrence of dormant tuberculosis. (see Other special warnings and precautions).
General: Opportunistic infection, recurrence of dormant tuberculoses, leucocytosis, hypersensitivity including anaphylaxis has been reported, thromboembolism, nausea, malaise.
Withdrawal symptoms and signs: Too rapid a reduction of corticosteroid dosage following prolonged treatment can lead to acute adrenal insufficiency, hypotension and death. (see Other special warnings and precautions). A ‘withdrawal syndrome’ may also occur including fever, myalgia, arthralgia, rhinitis, conjunctivitis, painful itchy skin nodules and loss of weight.
4.9 Overdose
Treatment is unlikely to be needed in cases of acute overdosage.
5.1 Pharmacodynamic properties
Prednisolone acts through replacing adrenal insufficiency as in Addison’s disease, or after adrenalectomy.
Prednisolone has anti-inflammatory and immuno-suppressant glucocorticoid properties.
5.2 Pharmacokinetic properties
Prednisolone is absorbed from the gastro-intestinal tract and peak plasma concentrations are obtained 1 to 2 hours after administration. The drug has a plasma half-life of 2–3 hours and is extensively bound to plasma protein.
Prednisolone is excreted in the urine as free and conjugated metabolites, together with an appreciable amount of unchanged Prednisolone.
Prenisolone crosses the placenta and small amounts are excreted in breast milk. The biological half-life of Prednisolone lasts for several hours.
5.3 Preclinical safety data
5.3 Preclinical safety dataNot applicable
6.1
Lactose
Maize Starch
Pregelatinated Maize Starch
Sodium Starch Glycollate
Magnesium Stearate
6.2 Incompatibilities
None stated
6.3 Shelf life
36 months all pack sizes
6.4 Special precautions for storage
Store in a dry place below 25°C. Keep container well closed.
6.5 Nature and contents of container
Polypropylene or high density polystyrene containers with polypropylene or polythene lids and/or polyurethane or polythene inserts.
Pack sizes: 100 & 500
6.6 Special precautions for disposal
6.6 Special precautions for disposalNo special instructions