Hydrocortisone 10 Mg Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Hydrocortisone 10 mg tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 10 mg hydrocortisone.
Excipient with known effects:
Each tablet contains 64.6 mg of lactose.
For the full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Tablets
White, smooth, scored tablets, flat, bevelled edges, 0 approx. 7 mm, marked ‘ORN35’.
The score line is not intended for breaking the tablet.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
• Replacement therapy in congenital adrenal hyperplasia in children.
• Treatment of adrenal insufficiency in children and adolescents < 18 years of age.
• Emergency treatment of severe bronchial asthma, drug hypersensitivity reactions, serum sickness, angioneurotic oedema and anaphylaxis in adults and children.
Hydrocortisone 10 mg tablets are indicated in adults and children aged from 1 month to 18 years where the dose of 10 mg and tablet formulation is considered appropriate.
4.2 Posology and method of administration
Posology
Dosage must be individualised according to the response of the individual patient. The lowest possible dosage should be used.
In patients requiring replacement therapy, the first dose in the morning should be higher than the other doses, to simulate the normal diurnal rhythm of cortisol secretion.
Patients should be observed closely for signs that might require dosage adjustment, including changes in clinical status resulting from remissions or exacerbations of the disease, individual drug responsiveness, and the effect of stress (e.g. surgery, infection, and trauma). During stress it may be necessary to increase the dosage temporarily.
To avoid hypoadrenalism and/or a relapse of the underlying disease, it may be necessary to withdraw the drug gradually (see section 4.4).
Replacement therapy
Paediatric population
In congenital adrenal hyperplasia, 9-15 mg/m2/day divided in 3 doses, adjusted according to response.
In adrenocortical insufficiency, 8-10 mg/ m2/day divided in 3 doses, adjusted according to response. Higher doses may be needed.
Acute emergencies 60-80 mg every 4-6 hours for 24 hours, then gradually reduce the dose over several days.
Elderly patients
Treatment of elderly patients, particularly if long-term, should be planned bearing in mind the more serious consequences of the common side effects of corticosteroids in old age, especially osteoporosis, diabetes, hypertension, susceptibility to infection and thinning of the skin.
Dosage in special situations
Hydrocortisone replacement therapy
In patients receiving hydrocortisone replacement therapy, the dosage of hydrocortisone should be increased 2 to 4-fold in stressful situations, such as in connection with injuries, infections, or surgical procedures. If necessary, the patient should be switched to parenteral treatment.
Hepatic impairment
The elimination of hydrocortisone may be slower in connection with hepatic diseases, and dose adjustment may be necessary in patients with hepatic impairment.
Method of administration
Oral use.
4.3 Contraindications
High-dose corticosteroid therapy potentially inducing immune deficiency is contraindicated in tuberculosis and other systemic acute and chronic bacterial, fungal, viral and parasitic infections without appropriate antimicrobial drug therapy.
Vaccines containing live, attenuated viruses or bacteria should not be given to patients receiving high-dose corticosteroid therapy during treatment-induced immune deficiency.
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
4.4 Special warnings and precautions for use
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.
In higher doses, hydrocortisone treatment may increase the prevalence of many acute and latent disease complications and lead to the worsening (or development) of some diseases. Therefore, caution should be exercised in patients with diagnosed diabetes,
gastric or duodenal ulcers, osteoporosis or glaucoma; as well as in connection with heart failure, recent myocardial infarction, hypertension, renal insufficiency, liver failure, previous corticosteroid myopathy, epilepsy, hypothyroidism, inflammatory bowel diseases and diverticulitis, and in patients with recent anastomosis surgery. Signs of peritoneal irritation following gastrointestinal perforation in patients receiving high doses of corticosteroids may be minimal or absent.
Particular care is required when considering systemic pharmacological corticosteroid therapy in patients with existing or previous history of severe affective disorders, including depressive or manic-depressive illness, psychosis, and previous steroid psychosis. 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.
Corticosteroid clearance may be decreased in patients with hypothyroidism and increased in patients with hyperthyroidism.
The lowest possible dosage of corticosteroids should be used and when reduction in dosage is possible, the reduction should be gradual. Stopping corticosteroid, after prolonged therapy may cause withdrawal symptoms (see section 4.8).
Drug-induced secondary adrenocortical insufficiency may result from too rapid withdrawal of corticosteroids and may be minimised by gradual reduction of dosage. This type of relative insufficiency may persist for months after discontinuation of therapy; therefore, in any situation of stress occurring during that period, corticosteroid therapy should be reinstated. If the patient is receiving steroids already, the dosage may have to be increased. Since mineralocorticoid secretion may be impaired, salt and/or a mineralocorticoid should be administered concurrently.
Corticosteroids increase the susceptibility to infections and may mask the symptoms of an infection.
As varicella or measles may be particularly dangerous during immune deficiency induced by corticosteroids, special caution is required regarding varicella, measles or herpes zoster infections. Unvaccinated patients and patients without a definite history of chickenpox/measles who receive immunosuppressive doses of corticosteroids should be advised to avoid exposure to chickenpox/measles. If exposed they should seek urgent medical attention.
Due to the risk of latent disease reactivation, caution should also be exercised if the patient has had tuberculosis.
Corticosteroids may activate latent amebiasis or strongyloidiasis, or exacerbate active disease. Therefore, it is recommended that latent or active amebiasis and strongyloidiasis be excluded before initiating corticosteroid therapy in any patient at risk of or with symptoms suggestive of either condition.
Vaccines containing live, attenuated viruses or bacteria should not be given to patients receiving high-dose corticosteroid therapy during treatment-induced immune deficiency. In general, the administration of these vaccines should be avoided during corticosteroid therapy. When using other types of vaccines, vaccine protection may not be as effective as usually, due to immune deficiency.
Prolonged use of corticosteroids may produce cataracts, glaucoma with possible damage to the optic nerve, and may enhance the establishment of secondary ocular infections due to fungi or viruses. Corticosteroids should be used cautiously in patients with ocular herpes simplex because of possible exacerbation of infection and corneal perforation.
Corticosteroid therapy may affect blood coagulation. Caution should be observed in the concomitant use of medicines affecting blood coagulation (such as warfarin or ASA).
Paediatric and elderly population
The adverse effects of systemic corticosteroid therapy may be stronger in elderly patients and in children.
Pharmacological corticosteroid therapy may cause growth retardation in infancy, childhood and adolescence. Treatment should be limited to the minimum effective dosage in order to minimise suppression of the hypothalamic-pituitary-adrenal axis and growth retardation. Growth and development of infants and children on prolonged corticosteroid therapy should be carefully monitored.
Excipients
Hydrocortisone 10 mg tablets contain lactose. Patients with rare problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
4.5 Interaction with other medicinal products and other forms of interaction
Pharmacokinetic interactions
Potent CYP3A4 inducers, such as phenytoin, rifabutin, carbamazepine, barbiturates, rifampicin, St. John’s wort, and less potent inducers, such as the antiretroviral medicinal products efavirenz and nevirapine, can enhance the metabolic clearance of cortisol, decrease the terminal half-life and thus reduce circulating levels. This may require dose adjustment of hydrocortisone.
Potent CYP3A4 inhibitors, such as ketoconazole, itraconazole, posaconazole, voriconazole, erythromycin, telithromycin, clarithromycin, ritonavir and grapefruit juice, can inhibit the metabolism of hydrocortisone, and thus increase blood levels. During long-term prophylactic treatment with any of the antibiotics, adjustment of the hydrocortisone dosage should be considered.
Oestrogen products and oral contraceptives may increase the plasma concentrations of hydrocortisone.
Corticosteroids increase salicylate clearance. Caution should be observed if the corticosteroid dose is lowered after long-term concomitant use.
Pharmacodynamic interactions
Hydrocortisone may increase blood pressure. This should be taken into account in concomitant administration of antihypertensive medication.
Hydrocortisone may decrease, or in some cases increase, the effect of anticoagulants. Caution should be observed in the concomitant use of warfarin and systemic corticosteroids.
The effect of antidiabetics (including insulin) may be weakened in concomitant use with corticosteroids, and a dose increase may be necessary.
When used with anticholinesterases, corticosteroids may cause muscle weakness in patients with myasthenia gravis.
Systemic corticosteroid therapy increases the risk of hypokalaemia in patients receiving diuretics, amphotericin B, cardiac glycosides, theophylline, or beta2 sympathomimetics. If concurrent use is necessary patient should be monitored for signs and symptoms of hypokalemia. The toxicity of cardiac glycosides, e.g. digoxin, is increased if hypokalaemia occurs.
Concomitant use of non-steroidal anti-inflammatory medicines (NSAIDs) or acetylsalicylic acid with corticosteroids increases the risk of ulceration and gastrointestinal bleeding.
Corticosteroids may inhibit the growth-promoting effect of somatropin.
The effect of corticosteroids may be reduced for 3-4 days after treatment with mifepristone.
The concomitant use of fluoroquinolones and corticosteroid may increase the risk of tendon rupture.
Corticosteroids may decrease the efficacy of vaccines and increase the risk of neurological complications in connection with vaccinations. Live virus vaccines may cause an infection in patients receiving hydrocortisone. Vaccines containing live, attenuated viruses or bacteria should not be given to patients receiving high-dose corticosteroid therapy during treatment-induced immune deficiency.
4.6 Fertility, Pregnancy and lactation
Fertility
Corticosteroids may impair semen quality and cause amenorrhoea.
Pregnancy
Hydrocortisone crosses the placenta. Besides replacement therapy, other systemic corticosteroid therapy during pregnancy should be regarded with caution. However, treatment should not be avoided if clearly indicated. If the mother has received hydrocortisone in pharmacological doses during pregnancy, the neonate should be monitored for adrenal insufficiency.
Corticosteroid therapy during pregnancy has been associated with foetal growth reduction, particularly in long-term use, and with insignificant contraction of the ductus arteriosus in isolated cases. During late pregnancy, hydrocortisone may cause adverse effects to the foetus that are similar to those of long-term therapy in general.
In animal tests, corticosteroids have caused cheiloschisis and palatoschisis. An increase in palatoschisis has not been shown in humans.
Lactation
Hydrocortisone is excreted in breast milk. Infants of mothers taking high doses of systemic corticosteroids for prolonged periods may have a degree of adrenal suppression.
4.7 Effects on ability to drive and use machines
Hydrocortisone 10 mg tablets do not usually impair the ability to drive or use machines. In some patients hydrocortisone may cause muscle weakness, muscle atrophy, vertigo, visual field loss, mood changes or psychological instability. If affected, patients should not drive or operate machinery
4.8 Undesirable effects
In replacement therapy in physiological doses, adverse effects are unlikely.
The adverse effects of hydrocortisone are similar to those of other glucocorticoids. The medicinal agent also has a mineralocorticoid effect. Treatment duration and the doses used affect the prevalence of adverse effects. In high-dose long-term therapy, adverse effects regularly develop.
In high-dose long-term therapy, hydrocortisone causes adrenocortical insufficiency; therefore, stress such as surgery or infections may lead to hypotension, hypoglycaemia, and even death, unless the steroid dose is increased to accommodate for the stress.
Sudden discontinuation of long-term steroid treatment leads to corticosteroid withdrawal syndrome. The symptoms may include fever, muscle and joint pain, asthenia, nausea, increased intracranial pressure and hypotension.
Glucocorticoids may cause allergy and anaphylactic reactions.
|
Common (> 1/100 to < 10) |
Uncommon (> 1/1,000 to < 1/100) |
Rare (> 1/10,000 to < 1/1,000) |
Not known (cannot be estimated from the available data) | |
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Blood and lymphatic system disorders |
Leukocytosis | |||
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Immune system disorders |
Increased susceptibility to infections, masked infection symptoms |
Allergic reactions |
Angioneurotic oedema, aggravation of existing infection, activation of latent infection | |
|
Endocrine disorders |
Suppression of endogenous ACTH and cortisol secretion (in |
Secondary adrenocortical and pituitary unresponsiveness (particularly in times of stress, |
|
long-term use), symptoms of Cushing’s syndrome, worsening/ development of diabetes |
as in trauma, surgery, or illness), decreased carbohydrate tolerance | |||
|
Metabolism and nutrition disorders |
Hypokalaemi a, sodium retention |
Increased appetite |
Hypokalaemic alkalosis, increased calcium excretion, fluid retention, negative nitrogen balance due to protein catabolism | |
|
Psychiatric disorders |
Mood changes, depression, mania, psychoses, insomnia |
Affective disorders, behavioural disturbances, irritability, anxiety, sleep disturbances, cognitive dysfunction including confusion and amnesia | ||
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Nervous system disorders |
Increased intracranial pressure (pseudotumor cerebri), convulsions |
Vertigo, headache | ||
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Eye disorders |
Increased eye pressure, glaucoma, cataract |
Papilledema, corneal or scleral thinning, exophthalmos | ||
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Cardiac disorders |
Exacerbation of cardiac insufficiency |
Myocardial rupture following recent myocardial infarction. | ||
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Vascular disorders |
Hypertension |
Thromboses | ||
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Respiratory, thoracic and mediastinal disorders |
Hiccups | |||
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Gastrointestin al disorders |
Pancreatitis |
Gastrointestinal ulcer with |
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possible perforation and haemorrhage, ulcerative oesophagitis, perforation of the small and large bowel, abdominal distension, dyspepsia, oesophageal candidiasis | ||||
|
Skin and subcutaneous tissue disorders |
Skin atrophy (thin, fragile skin), slow healing and scarring of tissue damage, acne, striae, bruising tendency, ecchymosis |
Petechiae, erythema, telangiectasia, increased sweating, allergic dermatitis, urticaria, hirsutism | ||
|
Musculoskele tal and connective tissue disorders |
Muscular atrophy, muscle weakness, osteoporosis |
Aseptic bone necrosis, tendon rupture |
Steroid myopathy, vertebral compression fractures, pathological fracture of long bones | |
|
Reproductive system and breast disorders |
Menstrual irregularities, amenorrhoea | |||
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General disorders and administratio n site conditions |
Growth retardation in children, oedema |
Weight gain, increased appetite, nausea, malaise |
Corticosteroid therapy may also cause increased coagulation tendency, hyperlipidaemia and nephroliths. It may decrease semen quality and cause amenorrhoea.
Paediatric population and elderly
The adverse effects of systemic corticosteroid therapy may be stronger in elderly patients and in children.
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 at: www.mhra.gov.uk/yellowcard.
4.9 Overdose
Acute, massive hydrocortisone overdose is unlikely. Considerably high single doses are tolerated without severe adverse effects. The treatment for oral overdose is supportive; if necessary, activated charcoal may be administered and gastric lavage performed.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Corticosteroids for systemic use, Glucocorticoids,
ATC code: H02AB09
Hydrocortisone, i.e. cortisol, is a natural hormone of the adrenal cortex. Like all glucocorticoids, its effects are mediated by binding to steroid receptors in the cytoplasm. This leads to the formation of a steroid-receptor complex that passes into the nucleus, where it binds to the DNA and thus regulates the transcription of many genes as well as protein synthesis. Its effects are mediated by factors such as increased lipocortin synthesis.
The effect of glucocorticoids is catabolic, especially in muscle tissue. They decrease the production of lymphokines and eicosanoids and the amount of lymphatic tissue, and they weaken the immune response and exert an anti-inflammatory effect regardless of the cause of inflammation. They also reduce fibroblast activity and scarring. Glucocorticoids reduce ACTH secretion and suppress the hypothalamic-pituitary-adrenal axis. Hydrocortisone exerts some mineralocorticoid effect. After a 250 mg single dose of hydrocortisone, ACTH secretion is suppressed for approximately 1 to 1.5 days.
5.2 Pharmacokinetic properties
Hydrocortisone is rapidly and completely absorbed from the gastrointestinal tract. Due to first-pass metabolism, its availability varies between 25 and 90%. The peak plasma concentration of hydrocortisone is reached 1-2 hours after dosing. It binds to transcortin and albumin in plasma. In low concentrations, 10% of the hydrocortisone is in the free form, while in higher concentrations, transcortin binding capacity is saturated, and the proportion of free hydrocortisone may increase to 40-50%. The volume of distribution is 0.4-0.7 L/kg. The mean pharmacological half-life of hydrocortisone is 1.5 h, but the biological effect half-life is considerably longer, approximately 10 hours. Hydrocortisone crosses the placental barrier and is excreted in milk in low quantities.
Hydrocortisone elimination may be slower in hepatic diseases and shorter in thyrotoxicosis.
5.3 Preclinical safety data
In animal tests, corticosteroids have caused cheiloschisis and palatoschisis.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Lactose monohydrate
Maize starch
Talc
Gelatin
Magnesium stearate
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
3 years.
6.4 Special precautions for storage
This medicinal product does not require any special temperature storage conditions.
Keep tablets in the blister in order to protect from light and moisture.
6.5 Nature and contents of container
Blister packs of 30 and 100 tablets.
Blister pack consists of aluminium foil and oriented polyamide film/aluminium foil/polyvinyl chloride (OPA/Al/PVC).
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
No special requirements for disposal.
7 MARKETING AUTHORISATION HOLDER
Alissa Healthcare Research Limited,
Unit 5, Fulcrum 1,
Solent Way, Whiteley,
Fareham, Hampshire,
United Kingdom,
PO15 7FE.
8 MARKETING AUTHORISATION NUMBER(S)
PL 30322/0015
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
25/11/2014
10 DATE OF REVISION OF THE TEXT
16/03/2016