Reports of acute toxicity and/or death following overdosage of glucocorticoids are rare. No specific antidote is available; treatment is supportive and symptomatic. Serum electrolytes should be monitored.
High systemic doses of corticosteroids caused by chronic use have been associated with adverse effects such as neuropsychiatric disorders (psychosis, depression, hallucinations), cardiac dysrhythmias and Cushing's syndrome.
24 months
- Systemic infections unless specific anti-infective therapy is employed.
- Ocular herpes simplex because of possible perforation.
- Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
None known
Lactose monohydrate
Pregelatinised starch
Sodium starch glycolate, type A
Iron oxide yellow (E172)
Iron oxide red (E172)
Glycerol dibehenate
Magnesium stearate
Tablets
10mg tablet
Red, 7mm, round, flat, tablet, with a score line on one side, imprinted with “A630†on one side and “10†on the other.
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.'Special warnings and special precautions for use').
Undesirable effects are listed by MedDRA System Organ Classes.
Assessment of undesirable effects is based on the following frequency groupings:
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 | Undesirable Effect |
| Infections and Infestations | Not known | Increases susceptibility to, and severity of infections1, opportunistic infections, recurrence of dormant tuberculosis2, oesophageal candidiasis. |
| Blood and lymphatic system disorders | Not known | Leucocytosis. |
| Immune system disorders | Not known | Hypersensitivity including anaphylaxis. |
| Endocrine disorders | Not known | Suppression of the hypothalamo-pituitary adrenal axis3, cushingoid facies, impaired carbohydrate tolerance with increased requirement for antidiabetic therapy, manifestation of latent diabetes mellitus. |
| Metabolism and nutrition disorders | Not known | Sodium and water retention, hypokalaemic alkalosis, potassium loss, negative nitrogen and calcium balance, glucose intolerance and protein catabolism. Increase both high and low density lipoprotein cholesterol concentration in the blood. Increased appetite4. Weight gain, obesity, hyperglycaemia, dyslipidaemia. |
| Very rare | Calciphylaxis5 | |
| Psychiatric disorders | Common | Irritability, depressed and labile mood, suicidal thoughts, psychotic reactions, mania, delusions, hallucinations, and aggravation of schizophrenia. behavioural disturbances, irritability, anxiety, sleep disturbances, and cognitive dysfunction including confusion and amnesia. |
| Not known | Euphoria, psychological dependence, depression. | |
| Nervous system disorders | Not known | Depression, insomnia, dizziness, headache, vertigo. Raised intracranial pressure with papilloedema (pseudotumor cerebri)6. Aggravation of epilepsy, epidural lipomatosis. vertebrobasilar stroke7 |
| Eye disorders | Not known Severe exacerbation of bullous exudative retinal detachment; central serous chorioretinopathy or lasting visual loss in some patients with idiopathic central serous chorioretinopathy.8 | |
| Ear and labyrinth disorders | Not known | Vertigo. |
| Cardiac disorders | Not known | Congestive heart failure in susceptible patients, hypertension, increased risk of heart failure. Increased risk of cardiovascular disease, including myocardial infarction.9 |
| Vascular disorders | Not known | Thromboembolism. |
| Gastrointestinal disorders | Not known | Dyspepsia, nausea, peptic ulceration with perforation and haemorrhage, abdominal distension, abdominal pain, diarrhoea, oesophageal ulceration, acute pancreatitis. |
| Skin and subcutaneous tissue disorders | Not known | Hirsutism, skin atrophy, bruising, striae, telangiectasia, acne, increased sweating, pruritis, rash, urticaria. |
| Musculoskeletal and connective tissue disorders | Not known | Proximal myopathy, osteoporosis, vertebral and long bone fractures, avascular osteonecrosis, tendon rupture, tendinopathies (particularly of the Achilles and patellar tendons), myalgia, growth suppression in infancy, childhood and adolescence. |
| Renal and urinary disorders | Not known | Scleroderma renal crisis10 |
| Reproductive system and breast disorders | Not known | Menstrual irregularity, amenorrhoea. |
| General disorders and administration site conditions | Not known | Fatigue, malaise, impaired healing |
| Investigations | Not known | Increased intra-ocular pressure, may suppress reactions to skin tests. 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. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard |
There are no non-clinical data of relevance to the prescriber that are not already covered in other sections of the SmPC.
Allergy and anaphylaxis: bronchial asthma, drug hypersensitivity reactions, serum sickness, angioneurotic oedema, anaphylaxis, incapacitating allergies unresponsive to conventional treatment.
Arteritis/collagenosis: giant cell arteritis/polymyalgia rheumatica, mixed connective tissue disease, polyarteritis nodosa, polymyositis.
Blood disorders: haemolytic anaemia (auto-immune), leukaemia (acute and chronic lymphocytic), lymphoma, multiple myeloma, idiopathic thrombocytopenic purpura.
Cardiovascular disorders: post-myocardial infarction syndrome, rheumatic fever with severe carditis.
Endocrine disorders: primary and secondary adrenal insufficiency, congenital adrenal hyperplasia.
Gastro-intestinal disorders: regional ileitis (Crohn's disease), ulcerative colitis, persistent coeliac syndrome (coeliac disease unresponsive to gluten withdrawal), auto-immune chronic active hepatitis, multisystem disease affecting liver, biliary peritonitis.
Hypercalcaemia: sarcoidosis, vitamin D excess.
Infections (with appropriate chemotherapy): helminthic infestations, Herxheimer reaction, infectious mononucleosis, miliary tuberculosis, mumps orchitis (adult), tuberculous meningitis, rickettsial disease.
Muscular disorders: polymyositis, dermatomyositis.
Neurological disorders: infantile spasms, Shy-Drager syndrome, sub-acute demyelinating polyneuropathy.
Ocular disease: scleritis, posterior uveitis, retinal vasculitis, pseudo-tumours of the orbit, giant cell arteritis, malignant ophthalmic Graves disease.
Renal disorders: lupus nephritis, acute interstitial nephritis, minimal change glomerulonephritis, nephrotic syndrome.
Respiratory disease: allergic pneumonitis, asthma, occupational asthma, pulmonary aspergillosis, pulmonary fibrosis, pulmonary alveolitis, aspiration of foreign body, aspiration of stomach contents, pulmonary sarcoid, drug induced lung disease, adult respiratory distress syndrome, spasmodic croup, fulminating or disseminated pulmonary tuberculosis when used concurrently with appropriate antituberculosis chemotherapy.
Rheumatic disorders: rheumatoid arthritis, polymyalgia rheumatica, juvenile chronic arthritis, psoriatic arthritis, systemic lupus erythematosus, dermatomyositis, mixed connective tissue disease.
Skin disorders: pemphigus vulgaris, exfoliative dermatitis, bullous pemphigoid, systemic lupus erythematosus, pyoderma gangrenosum.
Miscellaneous: sarcoidosis, hyperpyrexia, Behçets disease, immunosuppression in organ transplantation.
Pharmacotherapeutic group: glucocorticoid steroid, ATC code: H02A B06
Naturally occurring glucocorticoids (hydrocortisone and cortisone), which also have salt- retaining properties, are used as replacement therapy in adrenocortical deficiency states. Their synthetic analogs are primarily used for their potent anti-inflammatory effects in disorders of many organ systems.
Glucocorticoids cause profound and varied metabolic effects. In addition, they modify the body's immune responses to diverse stimuli.
Prednisolone is rapidly and apparently almost completely absorbed after oral administration; it reaches peak plasma concentrations after 1-3 hours. There is however wide inter-subject variation suggesting impaired absorption in some individuals. Plasma half-life is about 3 hours in adults and somewhat less in children. Its initial absorption, but not its overall bioavailability, is affected by food. Prednisolone has a biological half-life lasting several hours, making it suitable for alternate-day administration regimens.
Although peak plasma prednisolone levels are somewhat lower after administration of Prednisolone and absorption is delayed, total absorption and bioavailability are the same as after plain prednisolone. Prednisolone shows dose dependent pharmacokinetics, with an increase in dose leading to an increase in volume of distribution and plasma clearance. The degree of plasma protein binding determines the distribution and clearance of free, pharmacologically active drug. Reduced doses are necessary in patients with hypoalbuminaemia.
Prednisolone is metabolised primarily in the liver to a biologically inactive compound. Liver disease prolongs the half-life of prednisolone and, if the patient has hypoalbuminaemia, also increases the proportion of unbound drug and may thereby increase adverse effects.
Prednisolone is excreted in the urine as free and conjugated metabolites, together with small amounts of unchanged prednisolone.
Significant differences in the pharmacokinetics of prednisolone amongst menopausal women have been described. The postmenopausal women had reduced unbound clearance (30%), reduced total clearance and increased half-life of prednisolone.
14/02/2018
Actavis UK Limited
(Trading style: Actavis)
Whiddon Valley
Barnstaple
N. Devon
EX32 8NS
Keep the blister packs in the outer carton in order to protect from light.
Blisters of AL/PVC containing packs of 28 tablets
Not all pack sizes may be marketed.
PL 00142/0843
Pregnancy
The ability of corticosteroids to cross the placenta varies between individual drugs, however 88% of prednisolone is inactivated as it crosses the placenta. Administration of corticosteroids to pregnant animals can cause abnormalities of foetal development including cleft palate, intra-uterine growth retardation and effects 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, when administered for prolonged periods or repeatedly during pregnancy, corticosteroids may increase the risk of intrauterine growth retardation. Hypoadrenalism may occur in the neonate following prenatal exposure to corticosteroids but usually resolves spontaneously following birth and is rarely clinically important. Cataracts have also been rarely reported. 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 abnormal pregnancies may be treated as though they were in the non-gravid state.
Patients with pre-eclampsia or fluid retention require close monitoring.
Breast-feeding
Corticosteroids are excreted in small amounts in breast milk where they may suppress growth and interfere with endogenous glucocorticoid production in nursing infants. Since adequate reproductive studies have not been performed in humans with glucocorticoids, these drugs should be administered to nursing mothers only if the benefits of therapy are judged to outweigh the potential risks to the infant.
The concentration of the steroid in the milk can be between 5 and 25% of those in the serum.
There are no reports found regarding neonatal toxicity following exposure to corticosteroids during lactation, however if maternal doses >40mg/day of prednisolone is prescribed, the infant should be monitored for adrenal suppression.
Fertility
Corticosteroids may alter the motility and number of spermatozoa in certain patients.
Raised intracranial pressure Raised intracranial pressure with papilloedema (pseudotumour cerebri) associated with corticosteroid treatment has been reported in both children and adults.'Undesirable effects').
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.
Use in the elderly
Treatment of elderly patients, particularly if long term, should be undertaken with caution bearing in mind the more serious consequences of the common side-effects of corticosteroids in old age, especially osteoporosis, diabetes, hypertension, hypokalaemia, susceptibility to infection and thinning of the skin. Close clinical supervision is required to avoid life threatening reactions.
Paediatric population
Corticosteroids cause growth retardation in infancy, childhood and adolescence, which may be irreversible, and therefore long-term administration of pharmacological doses should be avoided. If prolonged therapy is necessary, treatment should be limited to the minimum suppression of the hypothalamo-pituitary adrenal axis and growth retardation. The growth and development of infants and children should be closely monitored. Treatment should be administered where possible as a single dose on alternate days.
The effect of Prednisolone on the ability to drive or use machinery has not been evaluated. There is no evidence to suggest that prednisolone may affect these abilities.
Posology
Adults and the elderly
The lowest effective dose should be used for the minimum period.
Children
''Special warnings and special precautions for use')If there is lack of a satisfactory clinical response to Prednisolone Tablets, the drug should be gradually discontinued and the patient transferred to alternative therapy.
Intermittent dosage regimen A single dose of Prednisolone Tablets in the morning on alternate days or at longer intervals is acceptable therapy for some patients. When this regimen is practical, the degree of pituitary-adrenal suppression can be minimised.
Specific dosage guidelines The following recommendations for some corticosteroid-responsive disorders are for guidance only. Acute or severe disease may require initial high dose therapy with reduction to the lowest effective maintenance dose as soon as possible. Dosage reductions should not exceed 5-7.5mg daily during chronic treatment.
Allergic and skin disorders Initial doses of 5-15mg daily are commonly adequate.
Collagenosis Initial doses of 20-30mg daily are frequently effective. Those with more severe symptoms may require higher doses.
Rheumatoid arthritis The usual initial dose is 10-15mg daily. The lowest daily maintenance dose compatible with tolerable symptomatic relief is recommended.
Blood disorders and lymphoma An initial daily dose of 15-60mg is often necessary with reduction after an adequate clinical or haematological response. Higher doses may be necessary to induce remission in acute leukaemia.
Special populations
''Undesirable effects'). Alternate day dosage is preferable where possible.Method of administration
Prednisolone tablets should be taken following a meal to reduce the risk of gastric irritation.
Not available
01/04/2016
| Vaccines | Live vaccines should not be given to individuals with impaired immune responsiveness. The antibody response to other vaccines may be diminished. |
| Antacids | The absorption of prednisolone may be reduced by large doses of some antacids such as magnesium trisilicate or aluminium hydroxide. |
| Antibacterials | Rifamycins accelerate metabolism of corticosteroids and thus may reduce their effect. Erythromycin inhibits metabolism of methylprednisolone and possibly other corticosteroids. Prednisolone can lower plasma levels of isoniazid. Where a reduced response during concurrent use is noted, dosage adjustment of isoniazid may be necessary. |
| Anticoagulants | Response to anticoagulants may be reduced or, less often, enhanced by corticosteroids. Close monitoring of the INR or prothrombin time is required to avoid spontaneous bleeding. |
| Antidiabetic agents | Glucocorticoids may increase blood glucose levels. Patients with diabetes mellitus receiving concurrent insulin and/or oral hypoglycaemic agents (e.g. metformin, sulphonamides) may require dosage adjustments of such therapy. |
| Antiepileptics | Carbamazepine, phenobarbital, phenytoin, and primidone accelerate metabolism of corticosteroids and may reduce their effect. |
| Antifungals | Risk of hypokalaemia may be increased with amphotericin, therefore concomitant use with corticosteroids should be avoided unless corticosteroids are required to control reactions; ketoconazole inhibits metabolism of methylprednisolone and possibly other corticosteroids. |
| Antimuscarinics (Anticholinergics) | Prednisolone has been shown to have antimuscarinic activity. If used in combination with another antimuscarinic drug could cause impairment to memory and attention in the elderly. |
| Antithyroids | Prednisolone clearance increased by the use of carbimazole and thiamazole. |
| Ciclosporin | Concomitant administration of prednisolone and ciclosporin may result in decreased plasma clearance of prednisolone (i.e. increased plasma concentration of prednisolone). The need for appropriate dosage adjustment should be considered when these drugs are administered concomitantly. |
| Cytotoxics | Increased risk of haematological toxicity with methotrexate. |
| Hepatic microsomal enzyme inducers | Drugs that induce hepatic enzyme cytochrome P-450 (CYP) isoenzyme 3A4 such as phenobarbital, phenytoin, rifampicin, rifabutin, carbamazepine, primidone and aminoglutethimide may reduce the therapeutic efficacy of corticosteroids by increasing the rate of metabolism. Lack of expected response may be observed and dosage of prednisolone tablets may need to be increased. |
| Hepatic microsomal enzyme inhibitors | Drugs that inhibit hepatic enzyme cytochrome P-450 (CYP) isoenzyme 3A4 (e.g. ketoconazole, troleandomycin) may decrease glucocorticoid clearance. Dosages of glucocorticoids given in combination with such drugs may need to be decreased to avoid potential adverse effects. |
| Hormonal contraceptives | Oral contraceptives increased prednisolone concentrations by 131%. May increase AUC and reduce clearance in oral contraceptives containing ethinylestradiol, mestranol, desogestrel, levonorgestrel, norgestrel or norethisterone. |
| Immunosupressants | Tumorigenicity: direct tumour-inducing effects of the glucocorticoids are not known, but the particular risk that malignancies in patients undergoing immunosupression with these or other drugs will spread more rapidly is a well-recognised problem. |
| Liquorice | Glycyrrhizin can delay the clearance of prednisolone. |
| Mifepristone | Effect of corticosteroids may be reduced for 3-4 days after mifepristone. |
| Non-steroidal anti-inflammatory drugs | Concomitant administration of ulcerogenic drugs such as indomethacin during corticosteroid therapy may increase the risk of GI ulceration. Aspirin should be used cautiously in conjunction with glucocorticoids in patients with hypoprothrombinaemia. Although concomitant therapy with salicylate and corticosteroids does not appear to increase the incidence or severity of GI ulceration, the possibility of this effect should be considered. Serum salicylate concentrations may decrease when corticosteroids are administered concomitantly. The renal clearance of salicylates is increased by corticosteroids and steroid withdrawal may result in salicylate intoxication. Salicylates and corticosteroids should be used concurrently with caution. Patients receiving both drugs should be observed closely for adverse effects of either drug. |
| Oestrogens | Oestrogens may potentiate the effects of glucocorticoids and dosage adjustments may be required if oestrogens are added to or withdrawn from a stable dosage regimen. |
| Protease Inhibitors | Ritonavir possibly increases plasma concentrations of prednisolone and other corticosteroids by reduction in clearance of prednisolone through the inhibition of P450 isoenzyme CYP3A4. |
| Other | The desired effects of hypoglycaemic agents (including insulin), antihypertensives and diuretics are antagonised by corticosteroids; and the hypokalaemic effect of acetazolamide, amphotericin B (by IV administration), loop diuretics, thiazide diuretics, carbenoxolone and theophylline are enhanced. |
| Somatropin | Growth promoting effect may be inhibited. |
| Sympathomimetics | Increased risk of hypokalaemia if high doses of corticosteroids given with high doses of bambuterol, fenoteral, formoterol, ritodrine, salbutamol, salmeterol and terbutaline. |
