DEXAMETHASONE 2 MG / 5 ML ORAL SOLUTION - summary of medicine characteristics

1 NAME OF THE MEDICINAL PRODUCT

Dexamethasone 2mg/5ml Oral Solution

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each 5 ml of oral solution contains 2 mg dexamethasone as dexamethasone sodium phosphate.

Excipients with known effect:

Each 5 ml of solution contains:

* 1.75 g maltitol (E965)

* 500 mg sorbitol (E420)

* 470 mg propylene glycol (E1520)

* approximately 7.6 mg ethanol

* 5 mg benzoic acid

* 1.5mg sodium

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Oral solution.

A colourless solution with a mint flavour and odour.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

4.1 Therapeutic indications

Neurology

Cerebral oedema (only with symptoms of intracranial pressure evidenced by computerised tomography) caused by a brain tumour, neuro-surgical intervention, cerebral abscess.

Pulmonary and respiratory diseases:

Acute asthma exacerbations when use of an oral corticosteroid (OCS) is appropriate, croup.

Dermatology

Initial treatment of extensive, severe, acute, skin diseases responding to glucocorticoids, e.g. erythroderma, pemphigus vulgaris.

Autoimmune disorders/rhe­umatology

Initial treatment of autoimmune disorders like systemic lupus erythematodes.

Active phases of systemic vasculitides like panarteritis nodosa (treatment duration should be limited to two weeks in cases of concomitant positive hepatitis B serology).

Severe progressive course of active rheumatoid arthritis, e.g. fast proceeding destructive forms and/or extraarticular manifestations.

Severe systemic course of juvenile idiopathic arthritis (Still's disease).

Haematological disorder

Idiopathic thrombocytopenic purpura in adults.

Infectology

Tuberculous meningitis only in conjunction with anti-infective therapy.

Dexamethasone Oral Solution is indicated in the treatment of coronavirus disease 2019 (COVID-19) in adult and adolescent patients (aged 12 years and older with body weight at least 40kg) who require supplemental oxygen therapy.

Oncology

Palliative treatment of neoplastic diseases.

Prophylaxis and treatment of emesis induced by cytostatics, emetogenic chemotherapy within antiemetic treatment.

Treatment of symptomatic multiple myeloma, acute lymphoblastic leukemia, Hodgkin's disease and non-Hodgkin's lymphoma in combination with other medicinal products.

Various

Prevention and treatment of postoperative vomiting, within antiemetic treatment.

4.2 Posology and method of administration

Adults

General considerations:

The dosage should be titrated to the individual response and the nature of the disease. In order to minimise side effects, the lowest effective possible dosage should be used (see ‚Side effects‘).

The initial dosage varies from 0.5 – 10 mg (equivalent to 1.25 ml – 25ml of product) a day depending on the disease being treated. In more severe diseases, doses higher than 10 mg may be required. The dose should be titrated to the individual patient response and disease severity. In order to minimize side effects, the lowest effective possible dose should be used.

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. If high doses are required other presentations may be more suitable.

– Cerebral oedema: Initial dose and duration of treatment depending on the cause and severity, 6–16 mg (up to 24 mg) / day orally, divided into 3–4 individual doses.

– Acute asthma: Adults: 16 mg / day for two days. Children: 0.6 mg / kg body weight for one or two days.

– Acute skin diseases: Depending on the nature and extent of the disease daily doses of 8–40 mg, in some cases up to 100 mg, which should be followed by down titration according to clinical need.

– Active phase of rheumatic system disorders: Systemic lupus erythematosus 6–16 mg / day.

– Active rheumatoid arthritis with severe progressive course form: running at fast destructive forms 12–16 mg /day, with extra-articular manifestations 6–12 mg / day.

– Idiopathic thrombocytopenic purpura: 40 mg for 4 days in cycles.

– Tuberculous meningitis: Patients with grade II or III disease received intravenous treatment for four weeks (0.4 mg per kilogram per day for week 1, 0.3 mg per kilogram per day for week 2, 0.2 mg per kilogram per day for week 3, and 0.1 mg per kilogram per day for week 4) and then oral treatment for four weeks, starting at a total of 4 mg per day and decreasing by 1 mg each week. Patients with grade I disease received two weeks of intravenous therapy (0.3 mg per kilogram per day for week 1 and 0.2 mg per kilogram per day for week 2) and then four weeks of oral therapy (0.1 mg per kilogram per day for week 3, then a total of 3 mg per day, decreasing by 1 mg each week).

– Palliative treatment of neoplastic diseases: Initial dose and duration of treatment depending on the cause and severity, 3–20 mg / day. Very high doses up to 96 mg may also be used for palliative treatment.

– Prophylaxis and treatment of emesis induced by cytostatics, emetogenic chemotherapy within antiemetic treatment: 8–20 mg dexamethasone prior to chemotherapy treatment, then 4–16 mg/day on day 2 and 3.

– Prevention and treatment of postoperative vomiting, within antiemetic treatment: single dose of 8 mg before the surgery.

– Treatment of symptomatic multiple myeloma, 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.

– Childhood Croup:

Children: 0.15mg/kg-0.6 mg/kg in a single dose.. A second dose may be administered after 12 hours, if considered necessary by the treating physician.

Dexamethasone Oral Solution is not recommended for use in neonates aged < 28 days (see section 4.4).

Doses of up to 0.6mg/kg dexamethasone have been used safely in clinical studies. However, a maximum dose of 10mg (25ml Dexamethasone 2mg/5ml Oral Solution) is recommended.

The following dosage chart should be followed for the treatment of childhood croup at a dose of 0.15mg/kg.

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.

For the treatment of COVID-19

Adult patients 6mg IV or PO, once a day for up to 10 days.

Paediatric population

Paediatric patients (adolescents aged 12 years and older) are recommended to take 6mg/dose IV or PO once a day for up to 10 days.

Duration of treatment should be guided by clinical response and individual patient requirements.

Elderly, renal impairment, hepatic impairment No dose adjustment is needed.

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)

4.3 Contraindications

Hypersensitivity to dexamethasone or 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 section 4.4 and 4.5).

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 provides details of prescriber, drug, dosage and the duration of treatment.

Undesirable effects may be minimised by using the lowest effective dose for the minimum period, and by administering the daily requirement as a single morning dose or whenever possible as a single morning dose on alternative days. Frequent patient review is required to appropriately titrate the dose against disease activity. When reduction in dosage is possible, the reduction should be gradual (Refer to ‚Posology and Administration‘).

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 minimized by slow dose reduction until a planned discontinuati­on time.

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

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.

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 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

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 checkups with doctors (including vision checkups 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 preexisting osteoporosis.

Corticosteroids should be used cautiously in patients with migraine, as corticosteroids may cause fluid retention.

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. However, if problems do happen, they might need treatment. In a few cases, mental health problems have happened when doses are being lowered or stopped.

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.

Visual disturbance

Visual disturbance may be reported with systemic and topical corticosteroid use. If a patient presents with symptoms such as blurred vision or other visual disturbances, the patient should be considered for referral to an ophthalmologist for evaluation of possible causes which may include cataract, glaucoma or rare diseases such as central serous chorioretinopathy (CSCR) which have been reported after use of systemic and topical corticosteroids.

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.

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. Patient 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.

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, 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.

Systemic corticosteroids should not be stopped for patients who are already treated with systemic (oral) corticosteroids for other reasons (e.g. patients with chronic obstructive pulmonary disease) but not requiring supplemental oxygen.

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.

Available evidence suggests long-term neurodevelopmental adverse events after early treatment (<96 hours) of premature infants with chronic lung disease at starting doses of 0.25mg/kg twice daily.

Elderly

The adverse effects of systemic corticosteroids may be associated with more serious consequences in old age, especially osteoporosis, hypertension, hypokalaemia, diabetes, susceptibility to infection and thinning of the skin. Close clinical supervision is required to avoid life-threatening reactions.

Excipient Warnings

Maltitol and sorbitol: Patients with rare hereditary problems of fructose intolerance should not take this medicine.

This medicine contains 94 mg propylene glycol in each ml, which is equivalent to 470 mg/ 5 ml. Co-administration with any substrate for alcohol dehydrogenase such as ethanol may induce serious adverse effects in neonates.

This product contains small amounts of ethanol (alcohol), less than 100mg per dose.

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. Dexamethasone contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

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, a 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 coadministration 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.

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

The following side effects have been reported; their frequency is unknown.

* See also section 4.4 Special warnings and precautions for use

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 Special warnings and precautions for use)

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 Special warnings and precautions for use)

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 Special warnings and precautions for use)

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 Special warnings and precautions for use)

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 Special warnings and precautions for use)

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 Special warnings and precautions for use)

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 Special warnings and precautions for use)

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 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

5   PHARMACOLOGICAL PROPERTIES

5.1   Pharmacodynamic properties

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 inter-individual variations. The mean plasma half-life is 3.6 ± 0.9h. 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.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Benzoic acid (E210)

Propylene glycol (E1520)

Citric acid monohydrate (E330)

Sodium citrate (E331)

Maltitol liquid (E965)

Sorbitol liquid (non-crystallising) (E420)

Garden mint flavour

Ethanol

Hydrochloric acid (for pH adjustment)

Sodium hydroxide (for pH adjustment)

Purified water

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

Unopened: 24 months

After first opening: 3 months

6.4 Special precautions for storage

Do not store above 25°C.

6.5 Nature and contents of container

Bottle: 75ml and 150ml amber soda glass (PhEur, Type III) bottles.

Closure: 28mm white push and turn cap with expanded polyethylene (EPE) liner.

Each pack will contain a 5mL dispensing syringe and bottle adapter.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.