Encortolon®: composition and pharmaceutical form
One tablet contains 5 mg of prednisolone and 82.6 mg of lactose monohydrate, a biologically active excipient. Because of the lactose, the medicine is not used in rare hereditary galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption syndrome.
The tablet is taken during a meal and not divided. Taking it with food is not a formality: it reduces dyspepsia and irritation of the digestive tract.
How Encortolon® works
Prednisolone is a synthetic glucocorticoid with strong anti-inflammatory activity. It suppresses the signs of inflammation without acting on its cause: it inhibits the accumulation of macrophages and leukocytes at the focus, phagocytosis, the release of lysosomal enzymes and the synthesis of inflammatory mediators. It reduces the distensibility and permeability of capillaries and the adhesion of leukocytes to their endothelium, which slows leukocyte migration and the formation of oedema, and it increases the synthesis of lipomodulin, an inhibitor of phospholipase A2, which releases arachidonic acid from the phospholipid membrane.
| Active substance | Dose of equivalent anti-inflammatory effect |
| Prednisolone | 5 mg |
| Methylprednisolone or triamcinolone | 4 mg |
| Dexamethasone | 0.75 mg |
| Betamethasone | 0.6 mg |
| Hydrocortisone | 20 mg |
The mineralocorticoid activity of prednisolone is about 60% of that of hydrocortisone — hence sodium and water retention, potassium loss and rising blood pressure at high doses.
Indications
Prednisolone's list of indications is among the longest in pharmacology: anti-inflammatory and immunosuppressive action is needed across very different fields of medicine. Among endocrine disorders these are primary and secondary adrenal insufficiency including its acute form, adrenogenital syndrome, non-suppurative thyroiditis and tumour-related hypercalcaemia; in Addison's disease hydrocortisone and cortisone remain the drugs of choice.
The remaining groups of indications cover almost every organ system.
- severe allergic diseases resistant to other treatments: serum sickness, hypersensitivity reactions to medicines, allergic rhinitis;
- collagen diseases in flare, systemic lupus erythematosus, acute rheumatic myocarditis, and rheumatic diseases as adjunctive treatment — ankylosing spondylitis, psoriatic, rheumatoid and juvenile arthritis, gouty arthritis, bursitis;
- dermatological diseases: exfoliative and dermatitis herpetiformis, Stevens — Johnson syndrome, contact and atopic dermatitis, pemphigus, severe psoriasis;
- ulcerative colitis and Crohn's disease in flare, haematological diseases — autoimmune haemolytic anaemia, congenital aplastic anaemia, idiopathic thrombocytopenic purpura — leukaemias and lymphomas together with antitumour treatment, nephrotic syndrome, multiple sclerosis in relapse and severe inflammatory eye disease;
- respiratory diseases: berylliosis, Löffler's syndrome, aspiration pneumonia, sarcoidosis, bronchial asthma, and fulminant or disseminated pulmonary tuberculosis, together with antituberculous treatment.
Method of use and dosage
The dose is set individually according to the type of disease and the response to treatment. Once the expected effect is achieved it is reduced gradually to the smallest effective dose, and it is lowered just as gradually before a planned withdrawal. The medicine is given in line with the circadian rhythm, usually once a day in the morning, though more frequent dosing is sometimes needed.
In adults the usual dose is 5–60 mg a day, up to a maximum of 250 mg. In multiple sclerosis relapse 200 mg a day is used for 7 days, then 80 mg a day for a month. In children the usual dose is 0.14–2 mg per kilogram of body weight a day in 3–4 divided doses, and on long treatment they are monitored for the risk of growth disturbance. In hypothyroidism and hepatic cirrhosis prednisolone acts more strongly, and in situations of increased stress — illness, injury, surgery — the dose of a fast-acting glucocorticoid may need to be raised.
Contraindications
Hypersensitivity to prednisolone or to any excipient. Systemic fungal infections. Ocular infections caused by herpes simplex virus, because of the risk of corneal perforation.
The list is short, but it does not cancel the long set of conditions in which the medicine is used with caution: ulcerative colitis with a risk of perforation, abscesses and other purulent infections, diverticulosis, fresh intestinal anastomoses, gastric and duodenal ulcer, renal and hepatic failure, hypertension, osteoporosis, myasthenia, diabetes, glaucoma, fungal and viral infections, hyperlipidaemia.
Special warnings and precautions
The defining feature of steroid therapy is the rule of gradualness. Abrupt discontinuation may cause adrenal insufficiency, so the dose is reduced step by step. After prolonged use, withdrawal may produce a withdrawal syndrome — fever, muscle and joint pain, malaise; these symptoms are possible even when no adrenal insufficiency is found.
- prednisolone may mask the signs of infection, reduce resistance to it and make it harder to localise, and it may also unmask latent amoebiasis: in people arriving from the tropics and in diarrhoea of unknown cause, infection with the dysentery amoeba is ruled out before treatment;
- patients on prednisolone are not given live viral vaccines, and an inactivated vaccine may not produce the expected rise in antibodies, except during replacement therapy;
- in active tuberculosis the medicine is prescribed only in the disseminated or fulminant form and only together with antituberculous treatment, while in latent tuberculosis or with a positive tuberculin test the patient is monitored and, on long treatment, given antituberculous drugs prophylactically;
- prolonged use may cause cataract and glaucoma and increases the risk of secondary fungal and viral infections, while high doses raise blood pressure, retain water and sodium and increase the excretion of potassium and calcium: dietary sodium restriction and potassium supplementation may be needed;
- mental disturbances — euphoria, insomnia, abrupt mood changes, severe depression, symptoms of psychosis — are dose-dependent, and pre-existing emotional instability may worsen during treatment.
In fungal infections treated with amphotericin B, prednisolone is sometimes used to reduce its undesirable effects, but it may then cause congestive heart failure, enlargement of the heart and severe hypokalaemia. CYP3A inhibitors, including products containing cobicistat, raise the risk of systemic adverse effects, so that combination is avoided.
Interaction with other medicines
Prednisolone has many interactions and they fall into several lines. The first is the lining of the digestive tract: taking it with non-steroidal anti-inflammatory drugs or with alcohol raises the risk of ulceration and bleeding, while prednisolone weakens the action of those drugs and speeds up the excretion of salicylates. The second is the water and electrolyte balance: with amphotericin B and carbonic anhydrase inhibitors hypokalaemia and congestive heart failure are possible, and the action of diuretics is weakened while the hypokalaemia they cause is intensified.
- with anticoagulants — coumarins, heparin, streptokinase, urokinase — the risk of ulceration and bleeding rises, and their own effectiveness changes in both directions, so the dose is set by the prothrombin time;
- the antidiabetic action of insulin and oral hypoglycaemic agents is weakened by prednisolone and the dose may need changing; prednisolone itself acts longer alongside oestrogen contraceptives and more weakly alongside inducers of liver enzymes and ephedrine;
- with cardiac glycosides the risk of arrhythmias and toxicity rises, with atropine intraocular pressure increases, and tricyclic antidepressants aggravate the mental disturbances caused by prednisolone, so they are not used to treat them;
- immunosuppressants together with prednisolone raise the risk of infections, lymphomas and other lymphoproliferative diseases, live viral vaccines at immunosuppressive doses may lead to viral replication, and the metabolism of isoniazid and mexiletine is accelerated by prednisolone, lowering their plasma concentrations.
The effect on laboratory results is worth remembering separately: the white cell count rises — above 20 000 per mm³ — while lymphocytes and monocytes fall, blood and urine glucose, serum calcium, cholesterol and triglycerides increase, and reactions in skin allergy tests and the tuberculin test weaken.
Pregnancy and breastfeeding
There are no sufficiently large controlled studies in humans. In animals corticosteroids increased the frequency of cleft palate, miscarriage, placental insufficiency and delayed fetal development. Suspicions of a teratogenic effect in humans have not been confirmed, but there are data indicating an increased risk of placental insufficiency, low birth weight and fetal death in women who received glucocorticoids during pregnancy.
Systemic use of corticosteroids in women of childbearing age and in pregnancy is therefore permissible only where the benefit outweighs the potential threat to the fetus. Treating the mother with doses of up to 5 mg is considered not to produce undesirable effects in the child, but higher doses may suppress growth or the secretion of the child's own adrenal cortex hormones. If prolonged treatment is needed during breastfeeding, feeding should be stopped.
Adverse reactions
Short-term use of prednisolone only occasionally causes undesirable effects. The risk listed below concerns above all patients on long-term treatment, and these effects are far from occurring in everyone.
- musculoskeletal: muscle weakness, steroid myopathy — more often in women, starting in the muscles of the pelvic girdle and moving to the proximal muscles of the shoulder — loss of muscle mass, osteoporosis, compression fractures of the spine, aseptic necrosis of the femoral head;
- gastrointestinal: gastric and intestinal ulceration with perforations and bleeding, especially in inflammatory bowel disease, pancreatitis, ulcerative oesophagitis, digestive disturbances, increased appetite; skin: striae, acne, impaired wound healing, bruising, urticaria, angioedema;
- endocrine and metabolic: secondary insufficiency of the adrenal cortex and pituitary in those on more than 5 mg a day, Cushing's syndrome, growth suppression in children, menstrual disturbances, hyperglycaemia and glycosuria, unmasking of diabetes, weight gain, hirsutism;
- eyes and nervous system: posterior subcapsular cataract — in 2.5 to 60% of patients — glaucoma usually after a year of treatment, raised intracranial pressure with papilloedema, most often in children after too rapid a dose reduction, seizures and headache;
- mental disturbances appear most often in the first weeks of treatment and are dose-dependent, extending to symptoms of schizophrenia, mania or delirium; besides these, thromboembolic syndromes, anaphylactic reactions, sodium and fluid retention, potassium loss, hypertension and congestive heart failure.
Some of these problems can be prevented. The risk of osteoporosis on long treatment is reduced by calcium and vitamin D or by physical exercise, and because protein catabolism increases, a higher protein intake is sometimes indicated. In steroid myopathy, if the glucocorticoid cannot be withdrawn, replacing it with another helps. In psychosis or depression the dose is reduced or the medicine withdrawn, and tricyclic antidepressants are contraindicated here.
Overdose
Even very high doses of corticosteroids usually cause no symptoms of acute overdose. The danger lies elsewhere: prolonged use can produce numerous disturbances typical of excessive adrenal cortex hormone activity — mental disorders, abnormal deposition of fatty tissue, fluid retention, excessive hair growth, acne, striae, rising blood pressure, immune disturbances, osteoporosis and peptic ulcer.
In acute overdose, emptying the stomach by vomiting or lavage is recommended. There is no specific antidote, and treatment comes down to maintaining vital functions.
How to get a prescription for Encortolon® online
The medicine is prescription-only, and the conversation with the doctor begins with what the steroid is being prescribed for: prednisolone has dozens of indications, and the diagnosis determines the dose, which varies fifty-fold, the length of the course and the tapering schedule.
It is worth reporting in advance any infections, including tuberculosis in the history and a positive tuberculin test, ulcer disease and inflammatory bowel disease, diabetes, hypertension, osteoporosis, glaucoma, myasthenia, kidney and liver disease, hypothyroidism, past mental disorders, pregnancy and breastfeeding, and — because of the lactose in the composition — galactose intolerance. It matters to list the medicines being taken — non-steroidal anti-inflammatories, anticoagulants, insulin and hypoglycaemic agents, diuretics — and any planned vaccinations: live vaccines are not given during treatment. The doctor will assess these circumstances during the online consultation and, if there are no contraindications, will issue an electronic prescription.
