- Approval Id
- 3916ad666e13a2e4
- Drug Approval Emc Name
- Dexamethasone 20mg Soluble Tablets
- Drug Name
- Dexamethasone 20mg Soluble Tablets
- Company Name
- Aspire Pharma Ltd
- Company Address
- 4 Rotherbrook Court, Bedford Road, Petersfield, Hampshire, GU32 3QG, UK
- Company Website
- http://www.aspirepharma.co.uk
- Company Telephone
- +44 (0)1730 231148
- Company Medical Info Direct Line
- +44 (0)1730 231148
- Company Customer Care Direct Line
- +44 (0)1730 231148
- Atc Code
- H02AB02
- Legal Category
- Prescription only medicine
- Authorisation Holder
- Aspire Pharma Limited
Unit 4 Rotherbrook Court
Bedford Road
Petersfield
Hampshire
GU32 3QG
United Kingdom
- Authorisation Number
- PL 35533/0169
- Authorisation Date
- 20/10/2021
- Instruction Authorisation Holder
- Aspire Pharma Limited
Unit 4 Rotherbrook Court
Bedford Road
Petersfield
Hampshire
GU32 3QG
United Kingdom
- Instruction Authorisation Number
- PL 35533/0169
- Instruction Authorisation Date
- 20/10/2021
- Instruction Composition
- Each tablet contains 20 mg dexamethasone (as dexamethasone sodium phosphate).
\*\*Excipient with known effect\*\*
Each tablet contains 18 mg of sodium benzoate, 65.6 mg sodium
For the full list of excipients, see section 6.1.
- Instruction Dosage Form
- Soluble Tablets
Dexamethasone 20 mg Soluble Tablets are pink, round, biconvex tablets (Thickness: 3.5 – 4.1 mm; Diameter: 9.8 – 10.2 mm).
- Instruction Clinical Particulars
- 4.1 Therapeutic indications
\*\*Dermatology\*\*
Pemphigus vulgaris
\*\*Autoimmune disorders/rheumatology\*\*
Myositis
\*\*Haematological disorder\*\*
Idiopathic thrombocytopenic purpura in adults.
\*\*Oncology\*\*
Metastatic spinal cord compression.
Prophylaxis and treatment of emesis induced by cytostatics, emetogenic chemotherapy within antiemetic treatment.
Treatment of symptomatic multiple myeloma, acute lymphocytic leukemia, acute lymphoblastic leukemia, Hodgkin's disease and non-Hodgkin's lymphoma in combination with other medicinal products.4.2 Posology and method of administration
\*\*\*Posology\*\*\*
| |
| --- |
| \*\*\*\*Please be aware that this is a high dose medical product.\*\*\*\* \*\*\*\*Dexamethasone is recommended to be used at the lowest effective dose.\*\*\*\* |
\*\*\*Adults\*\*\*
\*\*\*General considerations:\*\*\*
The initial dosage of Dexamethasone usually varies from 0.5 to 10 mg daily, depending on the disease being treated. In more severe disease conditions, doses above 10 mg per day may be required. The dose should be titrated to the individual patient response and disease severity until satisfactory. In order to minimise side effects, the lowest effective possible dosage should be used (see Side effects). If satisfactory clinical response does not occur after a reasonable period of time, discontinue treatment with Dexamethasone and transfer the patient to another therapy.
\*\*Unless otherwise prescribed, the following dosage recommendations apply:\*\*
\*\*The below mentioned dosing recommendations are given for guidance only. The initial and daily doses should always be determined based on individual patient response and disease severity.\*\*
• \*\*Pemphigus:\*\* initial dose of 300 mg for three days followed by down titration according to clinical need.
• \*\*Myositis:\*\* 40 mg for 4 days in cycles.
• \*\*Idiopathic thrombocytopenic purpura:\*\* 40 mg for 4 days in cycles.
• \*\*Metastatic spinal cord compression:\*\* initial dose and duration of treatment depending on the cause and severity. Very high doses up to 96 mg may be used for palliative treatment. For optimal dosing and reduction of the number or tablets the combination of lower dose strengths (4 and 8 mg) and higher dose strengths (20 mg or 40 mg) can used.
• \*\*Prophylaxis and treatment of emesis induced by cytostatic, emetogenic chemotherapy within antiemetic treatment:\*\* 8-20 mg (one 20 mg tablet or one half of 40 mg tablet) prior to chemotherapy treatment, then 4-16 mg/day on day 2 and 3.
• \*\*Treatment of symptomatic multiple myeloma, acute lymphocytic leukemia, acute lymphoblastic leukemia, Hodgkin's disease and non-Hodgkin's lymphoma in combination with other medicinal products:\*\* the usual posology is 40 mg or 20 mg once per day.
The dose and administration frequency varies with the therapeutic protocol and the associated treatment(s). Dexamethasone administration should follow instructions for dexamethasone administration when described in the Summary of Product Characteristics of the associated treatment(s). If this is not the case, local or international treatment protocols and guidelines should be followed. Prescribing physicians should carefully evaluate which dose of dexamethasone to use, taking into account the condition and disease status of the patient.
\*\*\*Renal impairment\*\*\*
Patients undergoing active hemodialysis may show an increased clearance of drug via the dialysate and thus require an adjustment of steroid dose.
\*\*\*Hepatic impairment\*\*\*
In patients with severe liver disease, dose adjustment may be necessary. In patients with a severe liver impairment, the biological effects of dexamethasone may be potentiated due to its slower metabolism (prolonged plasma half-life) and hypoalbuminaemia (increased plasma levels of free drug), which may also cause more side effects.
\*\*\*Elderly\*\*\*
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 (osteoporosis, diabetes mellitus, hypertension, reduced immunity, psychological changes). In such patients, the plasma concentrations of dexamethasone may be higher and its excretion slower than in younger patients, therefore its dose should be reduced accordingly.
\*\*\*Paediatric population\*\*\*
The excretion of dexamethasone is approximately equal in children and adults if dosage is adjusted to their body area. Dosage should be planned bearing in mind possible effects upon growth and development and for signs of adrenal suppression.
\*\*\*Long-term treatment\*\*\*
For the long-term treatment of several conditions, after initial therapy, glucocorticoid treatment should be switched from dexamethasone to prednisone/prednisolone to reduce suppression on the function of the adrenal cortex.
\*\*\*Discontinuation of treatment\*\*\*
Acute adrenocortical failure may occur after abrupt discontinuation of long-term treatment with large doses of glucocorticoids. Therefore, glucocorticoid doses should be gradually reduced in such cases and treatment should be discontinued gradually. (see section 4.4)
\*\*Method of administration\*\*
Dexamethasone Soluble Tablets should be taken with or after food to minimise irritation to the gastrointestinal tract. Drinks containing alcohol or caffeine should be avoided.
Dexamethasone 20 mg Soluble Tablets should be dissolved in water. The soluble tablets should be dissolved in at least half a small glass of water and the solution drunk immediately after dissolution. A minimum volume of approximately 50 ml of water is sufficient for complete dissolution.
This formulation of Dexamethasone is not suitable for subdivision of dose either as tablet or as solution (after dissolving in glass of water). Other available tablet strength(s) most appropriate for the prescribed dose should therefore be selected. During tapered dose reduction a change to a lower strength tablet or formulation may be needed to ensure optimal dose titration.4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Systemic infection unless specific anti-infective therapy is employed. Stomach ulcer or duodenal ulcer.
Vaccination with live vaccines during treatment with large therapeutic doses of dexamethasone (and other corticosteroids) is contraindicated due to the possibility of viral infection (see sections 4.4 and 4.5).4.4 Special warnings and precautions for use
\*\*\*Adrenocortical insufficiency\*\*\*
An adrenocortical insufficiency, which is caused by glucocorticoid treatment, can, depending on the dose and length of treatment, remain for many months, and in some cases more than a year, after discontinuation of treatment. During treatment with dexamethasone for specific physical stress conditions (trauma, surgery, childbirth, etc.), a temporary increase in dose may be required. Because of the possible risk in stressful conditions, a corticosteroid ID should be made for patients undergoing longterm treatment. Even in cases of prolonged adrenocortical insufficiency after discontinuation of treatment, the administration of glucocorticoids can be necessary in physically stressful situations. An acute therapy-induced adrenocortical insufficiency can be minimised by slow dose reduction until a planned discontinuation time.
There is an enhanced effect of corticosteroids in patients with hypothyroidism or liver cirrhosis.
Treatment with dexamethasone should only be implemented in the event of the strongest indications and, if necessary, additional targeted anti-infective treatment administered for the following illnesses:
• Acute viral infections (Herpes zoster, Herpes simplex, Varicella, herpetic keratitis)
• HBsAG-positive chronic active hepatitis
• Approx. 8 weeks prior through 2 weeks after vaccinations with live vaccines (see section 4.3 and 4.5)
• Systemic mycoses and parasitosis (e.g. Nematodes)
• Poliomyelitis
• Lymphadenitis after BCG vaccination
• Acute and chronic bacterial infections
• With a history of tuberculosis (reactivation risk) use only under tuberculostatic protection
• Known or suspected Strongyloidiasis (threadworm infestation). Treatment with glucocorticoids may lead to lead to Strongyloides hyperinfection and dissemination with widespread larval migration.
In addition, treatment with dexamethasone should only be implemented under strong indications and, if necessary, additional specific treatment must be implemented for:
• Gastrointestinal ulcers
• Severe osteoporosis (as corticosteroids have a negative effect on the calcium balance)
• Difficult to regulate high blood pressure
• Difficult to regulate diabetes mellitus
• Psychiatric disorders (including history)
• Angle closure glaucoma and wide-angle glaucoma
• Corneal ulcerations and corneal injuries
• Severe heart failure. Patients with severe heart failure should be carefully monitored, as there is a risk that their condition may deteriorate.
\*\*\*Anaphylactic reaction\*\*\*
Serious anaphylactic reactions may occur.
\*\*\*Tendinitis\*\*\*
The risk of tendinitis and tendon rupture is increased in patients treated concomitantly with glucocorticoids and fluoroquinolones.
\*\*\*Myasthenia gravis\*\*\*
Pre-existing myasthenia gravis may initially deteriorate in the beginning of dexamethasone treatment.
\*\*\*Ocular disorders\*\*\*
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.
Prolonged use of corticosteroids may cause posterior subcapsular cataracts, glaucoma with possible damage to the optic nerve and can increase the risk of secondary ocular infections due to fungi or viruses.
Corticosteroids should be used cautiously in patients with ocular herpes simplex because of possible corneal perforation.
\*\*\*Intestinal perforation\*\*\*
Because of the risk of an intestinal perforation, dexamethasone must only be used under urgent indication and under appropriate monitoring for:
• Severe ulcerative colitis with threatened perforation
• Diverticulitis
• Entero-anastomosis (immediately postoperative)
Signs of peritoneal irritation after gastrointestinal perforation may be minimal or absent in patients receiving high doses of glucocorticoids.
\*\*\*Diabetes\*\*\*
A higher need for insulin, or oral antidiabetics, must be taken into consideration when administering dexamethasone to diabetics.
\*\*\*Cardiovascular disorders\*\*\*
Regular blood pressure monitoring is necessary during treatment with dexamethasone, particularly during administration of higher doses and with patients with difficult to regulate high blood pressure. Because of the risk of deterioration, patients with severe cardiac insufficiency should be carefully monitored.
Bradycardia may occur in patients treated with high doses of dexamethasone.
Caution should be exercised when using corticosteroids in patients who have recently suffered myocardial infarction as myocardial rupture has been reported.
\*\*\*Infections\*\*\*
Patients who are on immunosuppressive drugs are more susceptible to infections than healthy individuals. Chickenpox and measles, for example, can have a more serious course in nonimmune children or adults on corticosteroids. In such patients who have not had these diseases, particular care should be taken to avoid exposure.
Treatment with dexamethasone can conceal the symptoms of an existing, or developing infection thereby making a diagnosis more difficult. The prolonged use of even small amounts of dexamethasone leads to an increased risk of infection, even by microorganisms which otherwise rarely cause infections (so-called opportunistic infections).
\*\*\*Vaccination\*\*\*
Vaccinations with inactivated vaccine are always possible. However, it should be noted that the immune reaction and thereby the success of inoculation, can be affected by higher doses of corticoids.
Regular check-ups with doctors (including vision check-ups in three-month intervals) are advised during long-term treatment with dexamethasone.
\*\*\*Metabolic disorders\*\*\*
At high doses, sufficient calcium intake and sodium restriction, as well as serum potassium levels should be monitored. Depending on the length and dosage of the treatment, a negative influence on calcium metabolism can be expected, so that an osteoporosis prophylaxis is recommended. This applies, above all, to co-existing risk factors like familial disposition, increased age, after menopause, insufficient protein and calcium intake, heavy smoking, excessive alcohol intake, as well as insufficient exercise. Prevention consists of sufficient calcium and vitamin D intake and physical activity. Additional medical treatment should be considered in the event of pre- existing osteoporosis.
Corticosteroids should be used cautiously in patients with migraine, as corticosteroids may cause fluid retention.
\*\*\*Psychological changes\*\*\*
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.
\*\*\*Cerebral oedema or increased intracranial pressure\*\*\*
Corticosteroids should not be used in conjunction with a head injury since they will probably not be of benefit or may even do harm.
\*\*\*Tumour lysis syndrome\*\*\*
In post marketing experience tumour lysis syndrome (TLS) has been reported in patients with haematological malignancies following the use of dexamethasone alone or in combination with other chemotherapeutic agents. Patients at high risk of TLS, such as patients with high proliferative rate, high tumour burden, and high sensitivity to cytotoxic agents, should be monitored closely and appropriate precaution taken.
\*\*\*Pheochromocytoma crisis\*\*\*
Pheochromocytoma crisis, which can be fatal, has been reported after administration of systemic corticosteroids, Corticosteroids should only be administered to patients with suspected or identified pheochromocytoma after an appropriate risk/benefit evaluation.
\*\*\*Discontinuation of treatment\*\*\*
Glucocorticoid doses should be gradually reduced.
The following risks should be considered upon interruption or discontinuation of long-term glucocorticoid administration:
• Exacerbation or recurrence of the underlying disease, acute adrenal insufficiency, corticosteroid withdrawal syndrome (A 'withdrawal syndrome' may include fever, muscle and joint pain (myalgia and arthralgia), inflammation of the nose lining (rhinitis), weight loss, itchy skin and inflammation of the eye (conjunctivitis)).
• Certain viral diseases (chickenpox, measles) in patients treated with glucocorticoids, may be very severe.
Children and immunocompromised persons without previous chickenpox or measles infection are particularly at risk. If these people have contact with people infected with measles or chickenpox while undergoing treatment with dexamethasone, a preventative treatment should be introduced if necessary.
\*\*\*Other\*\*\*
Pheochromocytoma crisis, which can be fatal, has been reported after administration of systemic corticosteroids. Corticosteroids should only be administered to patients with suspected or identified pheochromocytoma after an appropriate risk/benefit evaluation.
\*\*\*Paediatric population\*\*\*
Corticosteroids cause a dose-dependent inhibition of growth in infancy, childhood, and adolescence since corticosteroids may give rise to early closing of the epiphyses, which may be irreversible. Therefore, during long-term treatment with dexamethasone, the indication should be very strongly presented in children and their growth rate should be checked regularly.
Preterm neonates: Available evidence suggests long-term neurodevelopmental adverse events after early treatment (< 96 hours) of premature infants with chronic lung disease at starting doses of 0.25 mg/hg twice daily.
\*\*\*Elderly\*\*\*
The adverse effects of systemic corticosteroids can have serious consequences especially in old age, mainly osteoporosis, hypertension, hypokalemia, diabetes, susceptibility to infection and skin atrophy. Close clinical monitoring is required to prevent life-threatening reactions.
\*\*\*Influence of diagnostic tests\*\*\*
Glucocorticoids can suppress skin reaction to allergy testing. They can also affect the nitroblue tetrazolium test for bacterial infections and cause false-negative results.
\*\*\*Note on doping\*\*\*
The use of doping tests when taking dexamethasone can lead to positive results.
Patients on long-term dexamethasone treatment should carry a Steroid Treatment Card which gives guidance on minimising risk and provides details of prescriber, drug, dosage and duration of treatment.
\*\*\*Sodium\*\*\*
This medicinal product contains 65.6 mg sodium per 20 mg tablet, equivalent to 3.5% of the WHO recommended maximum daily intake of 2 g sodium for an adult.
\*\*\*Sodium benzoate\*\*\*
Increase in bilirubinaemia following its displacement from albumin may increase neonatal jaundice which may develop into kernicterus (non-conjugated bilirubin deposits in the brain tissue).4.5 Interaction with other medicinal products and other forms of interaction
Prior to the use of Dexamethasone in combination with any other medicinal product, reference should be made to the Summary of Product Characteristics of that product.
\*\*Pharmacodynamic interactions\*\*
Patients taking NSAIDs should be monitored, as NSAIDs may increase the incidence and/or severity of gastric ulcers. Acetylsalicylic acid should be used carefully in combination with corticosteroids in hypoprothrombinaemia.
The renal clearance of salicylates is increased by corticosteroids. Therefore, the dosage of salicylates may be reduced once the steroids are discontinued. Steroid withdrawal may result in salicylate intoxication due to the increase of salicylate concentration in the serum.
Corticosteroids reduce the effect of antidiabetic agents such as insulin, sulfonylurea, and metformin. Hyperglycaemia and diabetic ketoacidosis may occur occasionally.
Therefore, at the beginning of treatment, diabetics should have more frequent blood and urine tests.
The hypokalemic effect of acetazolamide, loop diuretics, thiazide diuretics, kaliuretics, amphotericin B injections (glucomineral)-corticosteroids, tetracosactide and laxatives will increase. Hypokalemia promotes cardiac arrhythmias, especially torsade de pointes, and increases the toxicity of cardiac glycosides. Before the start of corticosteroid treatment, hypokalemia should be corrected and patients should be monitored clinically, for electrolytes and by electrocardiography. Furthermore, there are case reports in which the simultaneous use of amphotericin B and hydrocortisone led to an enlarged heart and heart failure.
Antiulcer drugs: Carbenoxolone increases the risk of hypokalemia.
Chloroquine, hydroxychloroquine and mefloquine: Increased risk of myopathies and cardiomyopathies.
Concomitant administration of ACE inhibitors creates an increased risk of blood disorders.
The blood pressure-lowering effects of antihypertensive drugs may be affected by corticosteroids. The dose of the anti-hypertensive treatment may have to be adjusted during the treatment with dexamethasone.
Thalidomide: Great care should be taken during co-administration with thalidomide, as there have been reported cases of toxic epidermal necrolysis.
The effect of vaccinations may be reduced during treatment with dexamethasone.
Vaccination with live vaccines during treatment with large therapeutic doses of dexamethasone (and other corticosteroids) is contraindicated due to the possibility of viral infection. In this case, vaccination should be postponed for at least 3 months after the completion of treatment with corticosteroids. Other types of immunisation during treatment with large therapeutic doses of corticosteroids are dangerous due to the risk of neurological complications and decreased or absent increase in the antibody titers (in comparison with expected values) and therefore a smaller protective effect. However, patients who have received corticosteroids locally (parenteral) or for a short period of time (less than 2 weeks), in smaller doses may be immunised.
Cholinesterase inhibitors: Concomitant use of cholinesterase inhibitors and corticosteroids may cause serious muscle weakness in patients with myasthenia gravis. If possible, cholinesterase inhibitors should be discontinued at least 24 hours before the start of corticosteroid therapy.
The risk of tendinitis and tendon rupture is increased in patients treated concomitantly with glucocorticoids and fluoroquinolones.
Co-treatment with CYP3A inhibitors, including cobicistat-containing products, is expected to increase the risk of systemic side-effects. The combination should be avoided unless the benefit outweighs the increased risk of systemic corticosteroid side-effects, in which case patients should be monitored for systemic corticosteroid side-effects.
\*\*Pharmacokinetic interactions\*\*
\*\*Effects of other medicinal products on dexamethasone:\*\*
Dexamethasone is metabolized via the cytochrome P450 3A4 (CYP3A4).
The administration of dexamethasone with inducers of CYP3A4, such as ephedrine, barbiturates, rifabutin, rifampicin, phenytoin, and carbamazepine can lead to reduced plasma concentrations of dexamethasone, so the dose must be increased.
Aminoglutethimide can accelerate the reduction of dexamethasone and reduce its efficacy. If necessary, the dexamethasone dosage should be adjusted.
Bile acid resins, such as cholestyramine, may decrease the absorption of dexamethasone.
Topically applied gastrointestinal drugs, antacids, activated charcoal: Decreased glucocorticoid resorption has been described during co-administration of prednisolone and dexamethasone. Therefore, the administration of glucocorticoids and topically applied gastrointestinal drugs, antacids, activated charcoal should be postponed (with an interval of at least two hours).
The administration of dexamethasone with inhibitors of CYP3A4, such as azoleantifungals (e.g. ketoconazole, itraconazole), HIV protease inhibitors (e.g. ritonavir) and macrolide antibiotics (e.g. erythromycin) may lead to increased plasma concentrations and reduced clearance of dexamethasone. If required, the dexamethasone dose should be reduced.
Co-treatment with CYP3A inhibitors, including cobicistat-containing products, is expected to increase the risk of systemic side-effects. The combination should be avoided unless the benefit outweighs the increased risk of systemic corticosteroid side-effects, in which case patients should be monitored for systemic corticosteroid side-effects.
Ketoconazole may not only increase the plasma concentration of dexamethasone by inhibition of CYP3A4, but also suppress adrenal corticosteroid synthesis and cause adrenal insufficiency upon discontinuation of corticosteroid treatment.
Estrogens, including oral contraceptives, may inhibit the metabolism of certain corticosteroids and thus enhance their effect.
\*\*Effects of dexamethasone on other medicinal products\*\*
Dexamethasone is a moderate inducer of CYP3A4. The administration of dexamethasone with substances metabolized by CYP3A4 can lead to increased clearance and decreased plasma concentrations of these substances.
Tuberculostatics: A reduction of isoniazid plasma concentrations was observed during concurrent use of prednisolone. Patients taking isoniazid should be monitored closely.
Cyclosporine: Concomitant administration of cyclosporine and corticosteroids may lead to an increased effect of both substances. There is an increased risk of cerebral seizures.
Praziquantel: Reduced praziquantel plasma concentrations create a risk of treatment failure due to the increased hepatic metabolism of dexamethasone.
Oral anticoagulants (coumarin): Concomitant corticosteroid therapy may either potentiate or lead to a weakening of the effect of oral anticoagulants. In case of high doses or of treatment lasting over 10 days there is a risk of bleeding specific to corticosteroid therapies (gastrointestinal mucosa, vascular fragility). Patients who use corticosteroids combined with oral anticoagulants should be closely monitored (controls on day 8, then every two weeks during and after treatment).
Atropine and other anticholinergics: Intraocular pressure increases may be noted during co-administration with dexamethasone.
Non-depolarizing muscle relaxants: the muscle relaxing effect may last longer. Somatotropin: the effect of the growth hormone can be reduced.
Protirelin: Reduced increase in TSH may be noted during administration of protirelin.4.6 Fertility, pregnancy and lactation
\*\*Pregnancy\*\*
Dexamethasone crosses the placenta. Administration of corticosteroids to pregnant animals can cause abnormalities in foetal development, including cleft palate, intrauterine 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 (see section 5.3). Long-term or repeated corticosteroid therapy in pregnancy increases the risk of intrauterine growth retardation. In newborns exposed to corticosteroids in the prenatal period, there is an increased risk of adrenal insufficiency, which under normal circumstances undergoes spontaneous postnatal regression, and is rarely of clinical significance.
Dexamethasone should be prescribed during pregnancy, and particularly in the first trimester, only if the benefit outweighs the risks for the mother and child.
\*\*Breast-feeding\*\*
Glucocorticoids are excreted in breast milk. There is insufficient information on the excretion of dexamethasone in human milk. A risk to the newborns/infants cannot be excluded. Infants of mothers taking high doses of systemic corticosteroids for prolonged periods may have a degree of adrenal suppression.
A decision on whether to continue/discontinue breast feeding or to continue/discontinue therapy with dexamethasone should be made taking into account the benefit of breast feeding to the child and the benefit of dexamethasone therapy to the woman.
\*\*Fertility\*\*
Dexamethasone decreases testosterone biosynthesis and endogenous ACTH secretion which has an effect on the spermatogenesis and the ovarian cycle.4.7 Effects on ability to drive and use machines
There have been no studies on the effects on the ability to drive and use machines.
Dexamethasone may cause confusional state, hallucinations, dizziness, somnolence, fatigue, syncope and blurred vision (see section 4.8). If affected, patients should be instructed not to drive, use machines or perform hazardous tasks while being treated with dexamethasone.4.8 Undesirable effects
\*\*Summary of the safety profile\*\*
The incidence of anticipated adverse effects correlates with the relative potency of the substance, dose, time of day of administration and duration of treatment. During a short-term therapy, in compliance with the dosage recommendations and close monitoring of patients, the risk of side effects is low.
The usual side effects of short-term dexamethasone treatment (days/weeks) include weight gain, psychological disorders, glucose intolerance and transitory adrenocortical insufficiency. Long-term dexamethasone treatment (months/years) usually causes central obesity, skin fragility, muscle atrophy, osteoporosis, growth retardation and long-term suprarenal insufficiency (see also section 4.4).
\*\*Tabulated list of adverse reactions\*\*
| | |
| --- | --- |
| | \*\*Frequency not known (cannot be estimated from the available data)\*\* |
| Infections and infestations | Increased susceptibility to, or exacerbation of, (latent) infections\\* (including septicaemia, tuberculosis, eye infections, chickenpox, measles, fungal and viral infections) with masking of clinical symptoms, opportunistic infections |
| Blood and lymphatic system disorders | Leukocytosis, lymphopenia, eosinopenia, polycythemia, abnormal coagulation |
| Immune system disorders | Hypersensitivity reactions including anaphylaxis, immunosuppression (see also under “Infections and infestations”) |
| Endocrine disorders | Suppression of the hypothalamic-pituitary- adrenal axis and induction of Cushing's syndrome (typical symptoms: full-moon face, plethora, truncal obesity), secondary adrenal and pituitary insufficiency\\* (especially in stress such as trauma or surgery), growth suppression in infancy, childhood and adolescence, menstrual irregularity and amenorrhoea, hirsutism, |
| Metabolism and nutrition disorders | Weight gain, negative protein and calcium balance\\*, increased appetite, sodium and water retention\\*, potassium loss\\* (caution: rhythm disorders), hypokalemic alkalosis, manifestations of latent diabetes mellitus, impaired carbohydrate tolerance with increased dose requirements of antidiabetic therapy\\*, hypercholesterolemia, hypertriglyceridaemia |
| Psychiatric disorders | Psychological dependence, depression, insomnia, aggravated schizophrenia, mental illness, from euphoria to manifest psychosis |
| Nervous system disorders | Increased intracranial pressure with papilloedema in children (pseudotumor cerebri) usually following discontinuation of treatment; manifestation of latent epilepsy, increased seizures in overt epilepsy, vertigo, headache |
| Eye disorders | Elevated intraocular pressure, glaucoma\\*, papilloedema, cataract\\*, mainly with posterior subcapsular opacity, corneal and scleral atrophy, increased ophthalmic viral, fungal and bacterial infections, worsening of symptoms associated with corneal ulcers, chorioretinopathy, vision blurred\\* |
| Cardiac disorders | Cardiac muscle rupture\\* after recent history of myocardial infarction, congestive heart failure in predisposed patients, cardiac decompensation\\* |
| Vascular disorders | Hypertension, vasculitis, increased atherosclerosis and risk of thrombosis/thromboembolism (increase in coagulability of blood may lead to thromboembolic complications) |
| Respiratory, thoracic and mediastinal disorders | Hiccough |
| Gastrointestinal disorders | Dyspepsia, abdominal distension\\*, gastric ulcers with perforation and bleeding, acute pancreatitis, ulcerative esophagitis, oesophageal candidiasis, flatulence, nausea, vomiting |
| Skin and subcutaneous tissue disorders | Hypertrichosis, skin atrophy, telangiectasia, striea, erythema, steroid acne, petechiae, ecchymosis, hypersensitivity reactions such as allergic dermatitis, urticaria, angioneurotic oedema, thinning hair, pigment disorders, increased capillary fragility, perioral dermatitis, hyperhidrosis, tendency to bruise, , |
| Musculoskeletal and connective tissue disorders | Premature epiphyseal closure, osteoporosis, fractures of the spine and long bones, aseptic necrosis of the femoral and the humeral bones, tendon rupture\\*, proximal myopathy, muscle weakness, loss of muscle mass |
| Reproductive system and breast disorders | Impotence |
| General disorders and administration site conditions | Reduced response to vaccination and skin tests. Delayed wound healing, discomfort, malaise, steroid withdrawal syndrome: a too rapid reduction in corticosteroid dose after prolonged treatment can lead to acute adrenal insufficiency, hypotension, and death. A withdrawal syndrome may present with fever, myalgia, arthralgia, rhinitis, conjunctivitis, painful itchy skin nodules and weight loss. |
\\*see also section 4.4
\*\*Description of selected adverse reactions\*\*
\*\*\*Adrenocortical insufficiency\*\*\*
An adrenocortical insufficiency, which is caused by glucocorticoid treatment, can, depending on the dose and length of treatment, remain for many months and in some cases more than a year, after discontinuation of treatment (see section 4.4).
\*\*\*Psychological changes\*\*\*
Psychological changes are manifested in various forms, the most common being euphoria. Depression, psychotic reactions and suicidal tendencies may also appear.
These illnesses can be serious. Usually they start within a few days or weeks of starting the medicine. They are more likely to happen at high doses. Most of these problems go away if the dose is lowered or the medicine is stopped (see section 4.4).
\*\*\*Infections\*\*\*
Treatment with dexamethasone can conceal the symptoms of an existing, or developing infection thereby making a diagnosis more difficult and can lead to an increased risk of infection (see section 4.4).
\*\*\*Intestinal perforation\*\*\*
Corticosteroids can be associated with an increased risk of colonic perforation in severe ulcerative colitis with threatened perforation, diverticulitis and entero- anastomosis (immediately postoperative).
Signs of peritoneal irritation after gastrointestinal perforation may be absent in patients receiving high doses of glucocorticoids (see section 4.4).
\*\*\*Cardiovascular disorders\*\*\*
Bradycardia, deterioration of severe cardiac insufficiency and difficult to regulate high blood pressure may occur. Caution should be exercised when using corticosteroids in patients who have recently suffered myocardial infarction as myocardial rupture has been reported (see section 4.4).
\*\*\*Paediatric population\*\*\*
Corticosteroids cause a dose-dependent inhibition of growth in infancy, childhood, and adolescence since corticosteroids may give rise to early closing of the epiphyses, which may be irreversible (see section 4.4).
\*\*\*Elderly\*\*\*
The adverse effects of systemic corticosteroids can have serious consequences especially in old age, mainly osteoporosis, hypertension, hypokalemia, diabetes, susceptibility to infection and skin atrophy (see section 4.4).
\*\*\*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 or search for MHRA Yellow Card in the Google Play or Apple App Store.4.9 Overdose
\*\*Symptoms\*\*
Reports of acute toxicity and/or deaths following overdose with glucocorticoids are rare.
Overdose or prolonged use may exaggerate glucocorticoid adverse effects.
\*\*Management\*\*
No antidote is available. Treatment should be symptomatic and supportive with the dosage of dexamethasone being reduced or slowly withdrawn where possible.
Treatment is probably not indicated for reactions due to chronic poisoning unless the patient has a condition that would render him unusually susceptible to ill effects from corticosteroids. In this case, the stomach should be emptied and symptomatic treatment should be instituted as necessary. Anaphylactic and hypersensitivity reactions may be treated with epinephrine (adrenaline), positive-pressure artificial respiration and aminophylline. The patient should be kept warm and quiet. The biological half-life of dexamethasone in plasma is about 190 minutes.
- Instruction Pharmacology
- 5.1 Pharmacodynamic properties
Pharmacotherapeutic group: corticosteroids for systemic use, glucocorticoids
ATC code: H02AB02.
\*\*Mechanism of action\*\*
Dexamethasone is a highly potent and long-acting glucocorticoid with negligible sodium retaining properties and is therefore, particularly suitable for the use in patients with cardiac failure and hypertension.
Its anti-inflammatory potency is 7 times greater than prednisolone and, like other glucocorticoids, dexamethasone also has anti-allergic, antipyretic and immunosuppressive properties.
Dexamethasone has a biological half life of 36 - 54 hours and therefore is suitable in conditions where continuous glucocorticoid action is required.5.2 Pharmacokinetic properties
\*\*Absorption and distribution\*\*
Dexamethasone is well absorbed when given by mouth; peak plasma levels are reached between 1 and 2 hours after ingestion and show wide interindividual variations. The mean plasma half-life is 3.6 ± 0.9 h. Dexamethasone is bound (to about 77%) to plasma proteins, mainly albumins. Percentage protein binding of dexamethasone, unlike that of cortisol, remains practically unchanged with increasing steroid concentrations. Corticosteroids are rapidly distributed to all body tissues. They cross the placenta and may be excreted in small amounts in breast milk.
\*\*Biotransformation\*\*
Dexamethasone is metabolised mainly in the liver but also in the kidney.
\*\*Elimination\*\*
Dexamethasone and its metabolites are excreted in the urine.5.3 Preclinical safety data
Studies in animals have shown that glucocorticoids increase the incidence of cleft palate, spontaneous abortions and intrauterine growth retardation. In some cases these divergences were combined with defects of the central nervous system and of the heart. In non-human primates, minor cranial skeletal abnormalities were observed.
These effects were observed after use of high doses of dexamethasone.
- Instruction Pharmaceutical Particulars
- 6.1 List of excipients
Sodium hydrogen carbonate
Disodium hydrogen citrate
Erythrosine (E 127)
Povidone (K30)
Sodium saccharin
Sodium benzoate (E 211)6.2 Incompatibilities
Not applicable.6.3 Shelf life
Shelf life of medicinal product as packaged for sale
36 months6.4 Special precautions for storage
Do not store above 25° C.
Store in the original blister to protect from moisture6.5 Nature and contents of container
PA/Al/PVC/aluminium blisters.
Pack size: 10, 28, 30, 50, 56, 60 and 100 tablets
Not all pack sizes may be marketed.6.6 Special precautions for disposal and other handling
Any unused medicinal product or waste should be disposed of in accordance with local requirements.
- Instruction Content
- ## Composition
Each tablet contains 20 mg dexamethasone (as dexamethasone sodium phosphate).
\*\*Excipient with known effect\*\*
Each tablet contains 18 mg of sodium benzoate, 65.6 mg sodium
For the full list of excipients, see section 6.1.
## Pharmaceutical Form
Soluble Tablets
Dexamethasone 20 mg Soluble Tablets are pink, round, biconvex tablets (Thickness: 3.5 – 4.1 mm; Diameter: 9.8 – 10.2 mm).
## Clinical Particulars
4.1 Therapeutic indications
\*\*Dermatology\*\*
Pemphigus vulgaris
\*\*Autoimmune disorders/rheumatology\*\*
Myositis
\*\*Haematological disorder\*\*
Idiopathic thrombocytopenic purpura in adults.
\*\*Oncology\*\*
Metastatic spinal cord compression.
Prophylaxis and treatment of emesis induced by cytostatics, emetogenic chemotherapy within antiemetic treatment.
Treatment of symptomatic multiple myeloma, acute lymphocytic leukemia, acute lymphoblastic leukemia, Hodgkin's disease and non-Hodgkin's lymphoma in combination with other medicinal products.4.2 Posology and method of administration
\*\*\*Posology\*\*\*
| |
| --- |
| \*\*\*\*Please be aware that this is a high dose medical product.\*\*\*\* \*\*\*\*Dexamethasone is recommended to be used at the lowest effective dose.\*\*\*\* |
\*\*\*Adults\*\*\*
\*\*\*General considerations:\*\*\*
The initial dosage of Dexamethasone usually varies from 0.5 to 10 mg daily, depending on the disease being treated. In more severe disease conditions, doses above 10 mg per day may be required. The dose should be titrated to the individual patient response and disease severity until satisfactory. In order to minimise side effects, the lowest effective possible dosage should be used (see Side effects). If satisfactory clinical response does not occur after a reasonable period of time, discontinue treatment with Dexamethasone and transfer the patient to another therapy.
\*\*Unless otherwise prescribed, the following dosage recommendations apply:\*\*
\*\*The below mentioned dosing recommendations are given for guidance only. The initial and daily doses should always be determined based on individual patient response and disease severity.\*\*
• \*\*Pemphigus:\*\* initial dose of 300 mg for three days followed by down titration according to clinical need.
• \*\*Myositis:\*\* 40 mg for 4 days in cycles.
• \*\*Idiopathic thrombocytopenic purpura:\*\* 40 mg for 4 days in cycles.
• \*\*Metastatic spinal cord compression:\*\* initial dose and duration of treatment depending on the cause and severity. Very high doses up to 96 mg may be used for palliative treatment. For optimal dosing and reduction of the number or tablets the combination of lower dose strengths (4 and 8 mg) and higher dose strengths (20 mg or 40 mg) can used.
• \*\*Prophylaxis and treatment of emesis induced by cytostatic, emetogenic chemotherapy within antiemetic treatment:\*\* 8-20 mg (one 20 mg tablet or one half of 40 mg tablet) prior to chemotherapy treatment, then 4-16 mg/day on day 2 and 3.
• \*\*Treatment of symptomatic multiple myeloma, acute lymphocytic leukemia, acute lymphoblastic leukemia, Hodgkin's disease and non-Hodgkin's lymphoma in combination with other medicinal products:\*\* the usual posology is 40 mg or 20 mg once per day.
The dose and administration frequency varies with the therapeutic protocol and the associated treatment(s). Dexamethasone administration should follow instructions for dexamethasone administration when described in the Summary of Product Characteristics of the associated treatment(s). If this is not the case, local or international treatment protocols and guidelines should be followed. Prescribing physicians should carefully evaluate which dose of dexamethasone to use, taking into account the condition and disease status of the patient.
\*\*\*Renal impairment\*\*\*
Patients undergoing active hemodialysis may show an increased clearance of drug via the dialysate and thus require an adjustment of steroid dose.
\*\*\*Hepatic impairment\*\*\*
In patients with severe liver disease, dose adjustment may be necessary. In patients with a severe liver impairment, the biological effects of dexamethasone may be potentiated due to its slower metabolism (prolonged plasma half-life) and hypoalbuminaemia (increased plasma levels of free drug), which may also cause more side effects.
\*\*\*Elderly\*\*\*
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 (osteoporosis, diabetes mellitus, hypertension, reduced immunity, psychological changes). In such patients, the plasma concentrations of dexamethasone may be higher and its excretion slower than in younger patients, therefore its dose should be reduced accordingly.
\*\*\*Paediatric population\*\*\*
The excretion of dexamethasone is approximately equal in children and adults if dosage is adjusted to their body area. Dosage should be planned bearing in mind possible effects upon growth and development and for signs of adrenal suppression.
\*\*\*Long-term treatment\*\*\*
For the long-term treatment of several conditions, after initial therapy, glucocorticoid treatment should be switched from dexamethasone to prednisone/prednisolone to reduce suppression on the function of the adrenal cortex.
\*\*\*Discontinuation of treatment\*\*\*
Acute adrenocortical failure may occur after abrupt discontinuation of long-term treatment with large doses of glucocorticoids. Therefore, glucocorticoid doses should be gradually reduced in such cases and treatment should be discontinued gradually. (see section 4.4)
\*\*Method of administration\*\*
Dexamethasone Soluble Tablets should be taken with or after food to minimise irritation to the gastrointestinal tract. Drinks containing alcohol or caffeine should be avoided.
Dexamethasone 20 mg Soluble Tablets should be dissolved in water. The soluble tablets should be dissolved in at least half a small glass of water and the solution drunk immediately after dissolution. A minimum volume of approximately 50 ml of water is sufficient for complete dissolution.
This formulation of Dexamethasone is not suitable for subdivision of dose either as tablet or as solution (after dissolving in glass of water). Other available tablet strength(s) most appropriate for the prescribed dose should therefore be selected. During tapered dose reduction a change to a lower strength tablet or formulation may be needed to ensure optimal dose titration.4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Systemic infection unless specific anti-infective therapy is employed. Stomach ulcer or duodenal ulcer.
Vaccination with live vaccines during treatment with large therapeutic doses of dexamethasone (and other corticosteroids) is contraindicated due to the possibility of viral infection (see sections 4.4 and 4.5).4.4 Special warnings and precautions for use
\*\*\*Adrenocortical insufficiency\*\*\*
An adrenocortical insufficiency, which is caused by glucocorticoid treatment, can, depending on the dose and length of treatment, remain for many months, and in some cases more than a year, after discontinuation of treatment. During treatment with dexamethasone for specific physical stress conditions (trauma, surgery, childbirth, etc.), a temporary increase in dose may be required. Because of the possible risk in stressful conditions, a corticosteroid ID should be made for patients undergoing longterm treatment. Even in cases of prolonged adrenocortical insufficiency after discontinuation of treatment, the administration of glucocorticoids can be necessary in physically stressful situations. An acute therapy-induced adrenocortical insufficiency can be minimised by slow dose reduction until a planned discontinuation time.
There is an enhanced effect of corticosteroids in patients with hypothyroidism or liver cirrhosis.
Treatment with dexamethasone should only be implemented in the event of the strongest indications and, if necessary, additional targeted anti-infective treatment administered for the following illnesses:
• Acute viral infections (Herpes zoster, Herpes simplex, Varicella, herpetic keratitis)
• HBsAG-positive chronic active hepatitis
• Approx. 8 weeks prior through 2 weeks after vaccinations with live vaccines (see section 4.3 and 4.5)
• Systemic mycoses and parasitosis (e.g. Nematodes)
• Poliomyelitis
• Lymphadenitis after BCG vaccination
• Acute and chronic bacterial infections
• With a history of tuberculosis (reactivation risk) use only under tuberculostatic protection
• Known or suspected Strongyloidiasis (threadworm infestation). Treatment with glucocorticoids may lead to lead to Strongyloides hyperinfection and dissemination with widespread larval migration.
In addition, treatment with dexamethasone should only be implemented under strong indications and, if necessary, additional specific treatment must be implemented for:
• Gastrointestinal ulcers
• Severe osteoporosis (as corticosteroids have a negative effect on the calcium balance)
• Difficult to regulate high blood pressure
• Difficult to regulate diabetes mellitus
• Psychiatric disorders (including history)
• Angle closure glaucoma and wide-angle glaucoma
• Corneal ulcerations and corneal injuries
• Severe heart failure. Patients with severe heart failure should be carefully monitored, as there is a risk that their condition may deteriorate.
\*\*\*Anaphylactic reaction\*\*\*
Serious anaphylactic reactions may occur.
\*\*\*Tendinitis\*\*\*
The risk of tendinitis and tendon rupture is increased in patients treated concomitantly with glucocorticoids and fluoroquinolones.
\*\*\*Myasthenia gravis\*\*\*
Pre-existing myasthenia gravis may initially deteriorate in the beginning of dexamethasone treatment.
\*\*\*Ocular disorders\*\*\*
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.
Prolonged use of corticosteroids may cause posterior subcapsular cataracts, glaucoma with possible damage to the optic nerve and can increase the risk of secondary ocular infections due to fungi or viruses.
Corticosteroids should be used cautiously in patients with ocular herpes simplex because of possible corneal perforation.
\*\*\*Intestinal perforation\*\*\*
Because of the risk of an intestinal perforation, dexamethasone must only be used under urgent indication and under appropriate monitoring for:
• Severe ulcerative colitis with threatened perforation
• Diverticulitis
• Entero-anastomosis (immediately postoperative)
Signs of peritoneal irritation after gastrointestinal perforation may be minimal or absent in patients receiving high doses of glucocorticoids.
\*\*\*Diabetes\*\*\*
A higher need for insulin, or oral antidiabetics, must be taken into consideration when administering dexamethasone to diabetics.
\*\*\*Cardiovascular disorders\*\*\*
Regular blood pressure monitoring is necessary during treatment with dexamethasone, particularly during administration of higher doses and with patients with difficult to regulate high blood pressure. Because of the risk of deterioration, patients with severe cardiac insufficiency should be carefully monitored.
Bradycardia may occur in patients treated with high doses of dexamethasone.
Caution should be exercised when using corticosteroids in patients who have recently suffered myocardial infarction as myocardial rupture has been reported.
\*\*\*Infections\*\*\*
Patients who are on immunosuppressive drugs are more susceptible to infections than healthy individuals. Chickenpox and measles, for example, can have a more serious course in nonimmune children or adults on corticosteroids. In such patients who have not had these diseases, particular care should be taken to avoid exposure.
Treatment with dexamethasone can conceal the symptoms of an existing, or developing infection thereby making a diagnosis more difficult. The prolonged use of even small amounts of dexamethasone leads to an increased risk of infection, even by microorganisms which otherwise rarely cause infections (so-called opportunistic infections).
\*\*\*Vaccination\*\*\*
Vaccinations with inactivated vaccine are always possible. However, it should be noted that the immune reaction and thereby the success of inoculation, can be affected by higher doses of corticoids.
Regular check-ups with doctors (including vision check-ups in three-month intervals) are advised during long-term treatment with dexamethasone.
\*\*\*Metabolic disorders\*\*\*
At high doses, sufficient calcium intake and sodium restriction, as well as serum potassium levels should be monitored. Depending on the length and dosage of the treatment, a negative influence on calcium metabolism can be expected, so that an osteoporosis prophylaxis is recommended. This applies, above all, to co-existing risk factors like familial disposition, increased age, after menopause, insufficient protein and calcium intake, heavy smoking, excessive alcohol intake, as well as insufficient exercise. Prevention consists of sufficient calcium and vitamin D intake and physical activity. Additional medical treatment should be considered in the event of pre- existing osteoporosis.
Corticosteroids should be used cautiously in patients with migraine, as corticosteroids may cause fluid retention.
\*\*\*Psychological changes\*\*\*
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.
\*\*\*Cerebral oedema or increased intracranial pressure\*\*\*
Corticosteroids should not be used in conjunction with a head injury since they will probably not be of benefit or may even do harm.
\*\*\*Tumour lysis syndrome\*\*\*
In post marketing experience tumour lysis syndrome (TLS) has been reported in patients with haematological malignancies following the use of dexamethasone alone or in combination with other chemotherapeutic agents. Patients at high risk of TLS, such as patients with high proliferative rate, high tumour burden, and high sensitivity to cytotoxic agents, should be monitored closely and appropriate precaution taken.
\*\*\*Pheochromocytoma crisis\*\*\*
Pheochromocytoma crisis, which can be fatal, has been reported after administration of systemic corticosteroids, Corticosteroids should only be administered to patients with suspected or identified pheochromocytoma after an appropriate risk/benefit evaluation.
\*\*\*Discontinuation of treatment\*\*\*
Glucocorticoid doses should be gradually reduced.
The following risks should be considered upon interruption or discontinuation of long-term glucocorticoid administration:
• Exacerbation or recurrence of the underlying disease, acute adrenal insufficiency, corticosteroid withdrawal syndrome (A 'withdrawal syndrome' may include fever, muscle and joint pain (myalgia and arthralgia), inflammation of the nose lining (rhinitis), weight loss, itchy skin and inflammation of the eye (conjunctivitis)).
• Certain viral diseases (chickenpox, measles) in patients treated with glucocorticoids, may be very severe.
Children and immunocompromised persons without previous chickenpox or measles infection are particularly at risk. If these people have contact with people infected with measles or chickenpox while undergoing treatment with dexamethasone, a preventative treatment should be introduced if necessary.
\*\*\*Other\*\*\*
Pheochromocytoma crisis, which can be fatal, has been reported after administration of systemic corticosteroids. Corticosteroids should only be administered to patients with suspected or identified pheochromocytoma after an appropriate risk/benefit evaluation.
\*\*\*Paediatric population\*\*\*
Corticosteroids cause a dose-dependent inhibition of growth in infancy, childhood, and adolescence since corticosteroids may give rise to early closing of the epiphyses, which may be irreversible. Therefore, during long-term treatment with dexamethasone, the indication should be very strongly presented in children and their growth rate should be checked regularly.
Preterm neonates: Available evidence suggests long-term neurodevelopmental adverse events after early treatment (< 96 hours) of premature infants with chronic lung disease at starting doses of 0.25 mg/hg twice daily.
\*\*\*Elderly\*\*\*
The adverse effects of systemic corticosteroids can have serious consequences especially in old age, mainly osteoporosis, hypertension, hypokalemia, diabetes, susceptibility to infection and skin atrophy. Close clinical monitoring is required to prevent life-threatening reactions.
\*\*\*Influence of diagnostic tests\*\*\*
Glucocorticoids can suppress skin reaction to allergy testing. They can also affect the nitroblue tetrazolium test for bacterial infections and cause false-negative results.
\*\*\*Note on doping\*\*\*
The use of doping tests when taking dexamethasone can lead to positive results.
Patients on long-term dexamethasone treatment should carry a Steroid Treatment Card which gives guidance on minimising risk and provides details of prescriber, drug, dosage and duration of treatment.
\*\*\*Sodium\*\*\*
This medicinal product contains 65.6 mg sodium per 20 mg tablet, equivalent to 3.5% of the WHO recommended maximum daily intake of 2 g sodium for an adult.
\*\*\*Sodium benzoate\*\*\*
Increase in bilirubinaemia following its displacement from albumin may increase neonatal jaundice which may develop into kernicterus (non-conjugated bilirubin deposits in the brain tissue).4.5 Interaction with other medicinal products and other forms of interaction
Prior to the use of Dexamethasone in combination with any other medicinal product, reference should be made to the Summary of Product Characteristics of that product.
\*\*Pharmacodynamic interactions\*\*
Patients taking NSAIDs should be monitored, as NSAIDs may increase the incidence and/or severity of gastric ulcers. Acetylsalicylic acid should be used carefully in combination with corticosteroids in hypoprothrombinaemia.
The renal clearance of salicylates is increased by corticosteroids. Therefore, the dosage of salicylates may be reduced once the steroids are discontinued. Steroid withdrawal may result in salicylate intoxication due to the increase of salicylate concentration in the serum.
Corticosteroids reduce the effect of antidiabetic agents such as insulin, sulfonylurea, and metformin. Hyperglycaemia and diabetic ketoacidosis may occur occasionally.
Therefore, at the beginning of treatment, diabetics should have more frequent blood and urine tests.
The hypokalemic effect of acetazolamide, loop diuretics, thiazide diuretics, kaliuretics, amphotericin B injections (glucomineral)-corticosteroids, tetracosactide and laxatives will increase. Hypokalemia promotes cardiac arrhythmias, especially torsade de pointes, and increases the toxicity of cardiac glycosides. Before the start of corticosteroid treatment, hypokalemia should be corrected and patients should be monitored clinically, for electrolytes and by electrocardiography. Furthermore, there are case reports in which the simultaneous use of amphotericin B and hydrocortisone led to an enlarged heart and heart failure.
Antiulcer drugs: Carbenoxolone increases the risk of hypokalemia.
Chloroquine, hydroxychloroquine and mefloquine: Increased risk of myopathies and cardiomyopathies.
Concomitant administration of ACE inhibitors creates an increased risk of blood disorders.
The blood pressure-lowering effects of antihypertensive drugs may be affected by corticosteroids. The dose of the anti-hypertensive treatment may have to be adjusted during the treatment with dexamethasone.
Thalidomide: Great care should be taken during co-administration with thalidomide, as there have been reported cases of toxic epidermal necrolysis.
The effect of vaccinations may be reduced during treatment with dexamethasone.
Vaccination with live vaccines during treatment with large therapeutic doses of dexamethasone (and other corticosteroids) is contraindicated due to the possibility of viral infection. In this case, vaccination should be postponed for at least 3 months after the completion of treatment with corticosteroids. Other types of immunisation during treatment with large therapeutic doses of corticosteroids are dangerous due to the risk of neurological complications and decreased or absent increase in the antibody titers (in comparison with expected values) and therefore a smaller protective effect. However, patients who have received corticosteroids locally (parenteral) or for a short period of time (less than 2 weeks), in smaller doses may be immunised.
Cholinesterase inhibitors: Concomitant use of cholinesterase inhibitors and corticosteroids may cause serious muscle weakness in patients with myasthenia gravis. If possible, cholinesterase inhibitors should be discontinued at least 24 hours before the start of corticosteroid therapy.
The risk of tendinitis and tendon rupture is increased in patients treated concomitantly with glucocorticoids and fluoroquinolones.
Co-treatment with CYP3A inhibitors, including cobicistat-containing products, is expected to increase the risk of systemic side-effects. The combination should be avoided unless the benefit outweighs the increased risk of systemic corticosteroid side-effects, in which case patients should be monitored for systemic corticosteroid side-effects.
\*\*Pharmacokinetic interactions\*\*
\*\*Effects of other medicinal products on dexamethasone:\*\*
Dexamethasone is metabolized via the cytochrome P450 3A4 (CYP3A4).
The administration of dexamethasone with inducers of CYP3A4, such as ephedrine, barbiturates, rifabutin, rifampicin, phenytoin, and carbamazepine can lead to reduced plasma concentrations of dexamethasone, so the dose must be increased.
Aminoglutethimide can accelerate the reduction of dexamethasone and reduce its efficacy. If necessary, the dexamethasone dosage should be adjusted.
Bile acid resins, such as cholestyramine, may decrease the absorption of dexamethasone.
Topically applied gastrointestinal drugs, antacids, activated charcoal: Decreased glucocorticoid resorption has been described during co-administration of prednisolone and dexamethasone. Therefore, the administration of glucocorticoids and topically applied gastrointestinal drugs, antacids, activated charcoal should be postponed (with an interval of at least two hours).
The administration of dexamethasone with inhibitors of CYP3A4, such as azoleantifungals (e.g. ketoconazole, itraconazole), HIV protease inhibitors (e.g. ritonavir) and macrolide antibiotics (e.g. erythromycin) may lead to increased plasma concentrations and reduced clearance of dexamethasone. If required, the dexamethasone dose should be reduced.
Co-treatment with CYP3A inhibitors, including cobicistat-containing products, is expected to increase the risk of systemic side-effects. The combination should be avoided unless the benefit outweighs the increased risk of systemic corticosteroid side-effects, in which case patients should be monitored for systemic corticosteroid side-effects.
Ketoconazole may not only increase the plasma concentration of dexamethasone by inhibition of CYP3A4, but also suppress adrenal corticosteroid synthesis and cause adrenal insufficiency upon discontinuation of corticosteroid treatment.
Estrogens, including oral contraceptives, may inhibit the metabolism of certain corticosteroids and thus enhance their effect.
\*\*Effects of dexamethasone on other medicinal products\*\*
Dexamethasone is a moderate inducer of CYP3A4. The administration of dexamethasone with substances metabolized by CYP3A4 can lead to increased clearance and decreased plasma concentrations of these substances.
Tuberculostatics: A reduction of isoniazid plasma concentrations was observed during concurrent use of prednisolone. Patients taking isoniazid should be monitored closely.
Cyclosporine: Concomitant administration of cyclosporine and corticosteroids may lead to an increased effect of both substances. There is an increased risk of cerebral seizures.
Praziquantel: Reduced praziquantel plasma concentrations create a risk of treatment failure due to the increased hepatic metabolism of dexamethasone.
Oral anticoagulants (coumarin): Concomitant corticosteroid therapy may either potentiate or lead to a weakening of the effect of oral anticoagulants. In case of high doses or of treatment lasting over 10 days there is a risk of bleeding specific to corticosteroid therapies (gastrointestinal mucosa, vascular fragility). Patients who use corticosteroids combined with oral anticoagulants should be closely monitored (controls on day 8, then every two weeks during and after treatment).
Atropine and other anticholinergics: Intraocular pressure increases may be noted during co-administration with dexamethasone.
Non-depolarizing muscle relaxants: the muscle relaxing effect may last longer. Somatotropin: the effect of the growth hormone can be reduced.
Protirelin: Reduced increase in TSH may be noted during administration of protirelin.4.6 Fertility, pregnancy and lactation
\*\*Pregnancy\*\*
Dexamethasone crosses the placenta. Administration of corticosteroids to pregnant animals can cause abnormalities in foetal development, including cleft palate, intrauterine 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 (see section 5.3). Long-term or repeated corticosteroid therapy in pregnancy increases the risk of intrauterine growth retardation. In newborns exposed to corticosteroids in the prenatal period, there is an increased risk of adrenal insufficiency, which under normal circumstances undergoes spontaneous postnatal regression, and is rarely of clinical significance.
Dexamethasone should be prescribed during pregnancy, and particularly in the first trimester, only if the benefit outweighs the risks for the mother and child.
\*\*Breast-feeding\*\*
Glucocorticoids are excreted in breast milk. There is insufficient information on the excretion of dexamethasone in human milk. A risk to the newborns/infants cannot be excluded. Infants of mothers taking high doses of systemic corticosteroids for prolonged periods may have a degree of adrenal suppression.
A decision on whether to continue/discontinue breast feeding or to continue/discontinue therapy with dexamethasone should be made taking into account the benefit of breast feeding to the child and the benefit of dexamethasone therapy to the woman.
\*\*Fertility\*\*
Dexamethasone decreases testosterone biosynthesis and endogenous ACTH secretion which has an effect on the spermatogenesis and the ovarian cycle.4.7 Effects on ability to drive and use machines
There have been no studies on the effects on the ability to drive and use machines.
Dexamethasone may cause confusional state, hallucinations, dizziness, somnolence, fatigue, syncope and blurred vision (see section 4.8). If affected, patients should be instructed not to drive, use machines or perform hazardous tasks while being treated with dexamethasone.4.8 Undesirable effects
\*\*Summary of the safety profile\*\*
The incidence of anticipated adverse effects correlates with the relative potency of the substance, dose, time of day of administration and duration of treatment. During a short-term therapy, in compliance with the dosage recommendations and close monitoring of patients, the risk of side effects is low.
The usual side effects of short-term dexamethasone treatment (days/weeks) include weight gain, psychological disorders, glucose intolerance and transitory adrenocortical insufficiency. Long-term dexamethasone treatment (months/years) usually causes central obesity, skin fragility, muscle atrophy, osteoporosis, growth retardation and long-term suprarenal insufficiency (see also section 4.4).
\*\*Tabulated list of adverse reactions\*\*
| | |
| --- | --- |
| | \*\*Frequency not known (cannot be estimated from the available data)\*\* |
| Infections and infestations | Increased susceptibility to, or exacerbation of, (latent) infections\\* (including septicaemia, tuberculosis, eye infections, chickenpox, measles, fungal and viral infections) with masking of clinical symptoms, opportunistic infections |
| Blood and lymphatic system disorders | Leukocytosis, lymphopenia, eosinopenia, polycythemia, abnormal coagulation |
| Immune system disorders | Hypersensitivity reactions including anaphylaxis, immunosuppression (see also under “Infections and infestations”) |
| Endocrine disorders | Suppression of the hypothalamic-pituitary- adrenal axis and induction of Cushing's syndrome (typical symptoms: full-moon face, plethora, truncal obesity), secondary adrenal and pituitary insufficiency\\* (especially in stress such as trauma or surgery), growth suppression in infancy, childhood and adolescence, menstrual irregularity and amenorrhoea, hirsutism, |
| Metabolism and nutrition disorders | Weight gain, negative protein and calcium balance\\*, increased appetite, sodium and water retention\\*, potassium loss\\* (caution: rhythm disorders), hypokalemic alkalosis, manifestations of latent diabetes mellitus, impaired carbohydrate tolerance with increased dose requirements of antidiabetic therapy\\*, hypercholesterolemia, hypertriglyceridaemia |
| Psychiatric disorders | Psychological dependence, depression, insomnia, aggravated schizophrenia, mental illness, from euphoria to manifest psychosis |
| Nervous system disorders | Increased intracranial pressure with papilloedema in children (pseudotumor cerebri) usually following discontinuation of treatment; manifestation of latent epilepsy, increased seizures in overt epilepsy, vertigo, headache |
| Eye disorders | Elevated intraocular pressure, glaucoma\\*, papilloedema, cataract\\*, mainly with posterior subcapsular opacity, corneal and scleral atrophy, increased ophthalmic viral, fungal and bacterial infections, worsening of symptoms associated with corneal ulcers, chorioretinopathy, vision blurred\\* |
| Cardiac disorders | Cardiac muscle rupture\\* after recent history of myocardial infarction, congestive heart failure in predisposed patients, cardiac decompensation\\* |
| Vascular disorders | Hypertension, vasculitis, increased atherosclerosis and risk of thrombosis/thromboembolism (increase in coagulability of blood may lead to thromboembolic complications) |
| Respiratory, thoracic and mediastinal disorders | Hiccough |
| Gastrointestinal disorders | Dyspepsia, abdominal distension\\*, gastric ulcers with perforation and bleeding, acute pancreatitis, ulcerative esophagitis, oesophageal candidiasis, flatulence, nausea, vomiting |
| Skin and subcutaneous tissue disorders | Hypertrichosis, skin atrophy, telangiectasia, striea, erythema, steroid acne, petechiae, ecchymosis, hypersensitivity reactions such as allergic dermatitis, urticaria, angioneurotic oedema, thinning hair, pigment disorders, increased capillary fragility, perioral dermatitis, hyperhidrosis, tendency to bruise, , |
| Musculoskeletal and connective tissue disorders | Premature epiphyseal closure, osteoporosis, fractures of the spine and long bones, aseptic necrosis of the femoral and the humeral bones, tendon rupture\\*, proximal myopathy, muscle weakness, loss of muscle mass |
| Reproductive system and breast disorders | Impotence |
| General disorders and administration site conditions | Reduced response to vaccination and skin tests. Delayed wound healing, discomfort, malaise, steroid withdrawal syndrome: a too rapid reduction in corticosteroid dose after prolonged treatment can lead to acute adrenal insufficiency, hypotension, and death. A withdrawal syndrome may present with fever, myalgia, arthralgia, rhinitis, conjunctivitis, painful itchy skin nodules and weight loss. |
\\*see also section 4.4
\*\*Description of selected adverse reactions\*\*
\*\*\*Adrenocortical insufficiency\*\*\*
An adrenocortical insufficiency, which is caused by glucocorticoid treatment, can, depending on the dose and length of treatment, remain for many months and in some cases more than a year, after discontinuation of treatment (see section 4.4).
\*\*\*Psychological changes\*\*\*
Psychological changes are manifested in various forms, the most common being euphoria. Depression, psychotic reactions and suicidal tendencies may also appear.
These illnesses can be serious. Usually they start within a few days or weeks of starting the medicine. They are more likely to happen at high doses. Most of these problems go away if the dose is lowered or the medicine is stopped (see section 4.4).
\*\*\*Infections\*\*\*
Treatment with dexamethasone can conceal the symptoms of an existing, or developing infection thereby making a diagnosis more difficult and can lead to an increased risk of infection (see section 4.4).
\*\*\*Intestinal perforation\*\*\*
Corticosteroids can be associated with an increased risk of colonic perforation in severe ulcerative colitis with threatened perforation, diverticulitis and entero- anastomosis (immediately postoperative).
Signs of peritoneal irritation after gastrointestinal perforation may be absent in patients receiving high doses of glucocorticoids (see section 4.4).
\*\*\*Cardiovascular disorders\*\*\*
Bradycardia, deterioration of severe cardiac insufficiency and difficult to regulate high blood pressure may occur. Caution should be exercised when using corticosteroids in patients who have recently suffered myocardial infarction as myocardial rupture has been reported (see section 4.4).
\*\*\*Paediatric population\*\*\*
Corticosteroids cause a dose-dependent inhibition of growth in infancy, childhood, and adolescence since corticosteroids may give rise to early closing of the epiphyses, which may be irreversible (see section 4.4).
\*\*\*Elderly\*\*\*
The adverse effects of systemic corticosteroids can have serious consequences especially in old age, mainly osteoporosis, hypertension, hypokalemia, diabetes, susceptibility to infection and skin atrophy (see section 4.4).
\*\*\*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 or search for MHRA Yellow Card in the Google Play or Apple App Store.4.9 Overdose
\*\*Symptoms\*\*
Reports of acute toxicity and/or deaths following overdose with glucocorticoids are rare.
Overdose or prolonged use may exaggerate glucocorticoid adverse effects.
\*\*Management\*\*
No antidote is available. Treatment should be symptomatic and supportive with the dosage of dexamethasone being reduced or slowly withdrawn where possible.
Treatment is probably not indicated for reactions due to chronic poisoning unless the patient has a condition that would render him unusually susceptible to ill effects from corticosteroids. In this case, the stomach should be emptied and symptomatic treatment should be instituted as necessary. Anaphylactic and hypersensitivity reactions may be treated with epinephrine (adrenaline), positive-pressure artificial respiration and aminophylline. The patient should be kept warm and quiet. The biological half-life of dexamethasone in plasma is about 190 minutes.
## Pharmacological Properties
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: corticosteroids for systemic use, glucocorticoids
ATC code: H02AB02.
\*\*Mechanism of action\*\*
Dexamethasone is a highly potent and long-acting glucocorticoid with negligible sodium retaining properties and is therefore, particularly suitable for the use in patients with cardiac failure and hypertension.
Its anti-inflammatory potency is 7 times greater than prednisolone and, like other glucocorticoids, dexamethasone also has anti-allergic, antipyretic and immunosuppressive properties.
Dexamethasone has a biological half life of 36 - 54 hours and therefore is suitable in conditions where continuous glucocorticoid action is required.5.2 Pharmacokinetic properties
\*\*Absorption and distribution\*\*
Dexamethasone is well absorbed when given by mouth; peak plasma levels are reached between 1 and 2 hours after ingestion and show wide interindividual variations. The mean plasma half-life is 3.6 ± 0.9 h. Dexamethasone is bound (to about 77%) to plasma proteins, mainly albumins. Percentage protein binding of dexamethasone, unlike that of cortisol, remains practically unchanged with increasing steroid concentrations. Corticosteroids are rapidly distributed to all body tissues. They cross the placenta and may be excreted in small amounts in breast milk.
\*\*Biotransformation\*\*
Dexamethasone is metabolised mainly in the liver but also in the kidney.
\*\*Elimination\*\*
Dexamethasone and its metabolites are excreted in the urine.5.3 Preclinical safety data
Studies in animals have shown that glucocorticoids increase the incidence of cleft palate, spontaneous abortions and intrauterine growth retardation. In some cases these divergences were combined with defects of the central nervous system and of the heart. In non-human primates, minor cranial skeletal abnormalities were observed.
These effects were observed after use of high doses of dexamethasone.
## Pharmaceutical Particulars
6.1 List of excipients
Sodium hydrogen carbonate
Disodium hydrogen citrate
Erythrosine (E 127)
Povidone (K30)
Sodium saccharin
Sodium benzoate (E 211)6.2 Incompatibilities
Not applicable.6.3 Shelf life
Shelf life of medicinal product as packaged for sale
36 months6.4 Special precautions for storage
Do not store above 25° C.
Store in the original blister to protect from moisture6.5 Nature and contents of container
PA/Al/PVC/aluminium blisters.
Pack size: 10, 28, 30, 50, 56, 60 and 100 tablets
Not all pack sizes may be marketed.6.6 Special precautions for disposal and other handling
Any unused medicinal product or waste should be disposed of in accordance with local requirements.
