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DEXAMETHASONE 8MG/2ML INJECTION

Active substance(s): DEXAMETHASONE SODIUM PHOSPHATE

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Dexamethasone 8 mg/2ml Injection

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each ml contains 4mg dexamethasone as the sodium phosphate. For excipients
see 6.1.

3.

PHARMACEUTICAL FORM
Solution for injection.

4.

CLINICAL PARTICULARS

4.1.

Therapeutic indications
Dexamethasone can be used for all forms of general and local glucocorticoid
injection therapy and all acute conditions in which intravenous glucocorticoids
may be life-saving.

4.2

Posology and method of administration
Dosage
N.B. For this section of document all doses are expressed as
mg dexamethasone
In general, glucocorticoid dosage depends on the severity of the condition and
response of the patient. Under certain circumstances, for instance in stress,
extra dosage adjustments may be necessary. If no favourable response is
noted within a couple of days, glucocorticoid therapy should be discontinued.
Adults and Elderly

Once the disease is under control the dosage should be reduced or tapered off
to the lowest suitable level under continuous monitoring and observation of
the patient. (See Section 4.4)
For acute life-threatening situations (e.g. anaphylaxis, acute severe asthma)
substantially higher dosages may be needed. Cerebral oedema (adults): initial
dose 8-16 mg iv followed by 5 mg iv or im every 6 hours, until a satisfactory
result has been obtained. In brain surgery these dosages may be necessary
until several days after the operation. Thereafter, the dosage has to be tapered
off gradually. Increase of intracranial pressure associated with brain tumours
can be counteracted by continuous treatment.
For local treatment, the following dosages can be recommended:
• intra-articulary:
1.6 - 3 mg large joints
0.6-0.8 mg small joints
• intrabursally:
1.6- 3 mg
• in tendon sheaths:
0.3 – 0.8 mg
The frequency of these injections may vary from every 3-5 days to every 2 -3
weeks.
For rectal drip in cases of ulcerative colitis: 4 mg diluted in 120 ml saline.
Suggested doses for children
Dosage requirements are variable and may have to be changed according to
individual needs. Usually 0.2-0.4 mg/kg of body weight daily.
Administration
Dexamethasone injections may be administered intravenously,
subcutaneously, intramuscularly, by local injection or as a rectal drip. For
administration by intravenous infusion: see section on compatibility with
infusion fluids. With intravenous administration high plasma levels can be
obtained rapidly.
Rapid intravenous injection of massive doses of glucocorticoids may
sometimes cause cardiovascular collapse; the injection should therefore be
given slowly over a period of several minutes.
Intra-articular injections should be given under strictly aseptic conditions.
4.3

Contraindications
Systemic infection unless specific anti-infective therapy is employed.
Hypersensitivity to any ingredient.
Local injection of a glucocorticoid is contraindicated in bacteraemia and
systemic fungal infections, unstable joints, infection at the injection site e.g.
septic arthritis resulting from gonorrhoea or tuberculosis.

4.4

Special warnings and special precautions for use
A patient information leaflet should be supplied with this product.
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 for 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 infrequentely.
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 pyschosis.
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.
After parenteral administration of glucocorticoids serious anaphylactoid
reactions, such as glottis oedema, urticaria and bronchospasm, have
occasionally occurred, particularly in patients with a history of allergy. If such
an anaphylactoid reaction occurs, the following measures are recommended:
immediate slow intravenous injection of 0.1 - 0.5 ml of adrenaline (solution of
1:1000: 0.1 - 0.5 mg adrenaline dependent on body weight), intravenous
administration of aminophylline and artificial respiration if necessary.
Corticosteroids should not be used for the management of head injury or
stroke because it is unlikely to be of any benefit and may even be harmful.
Dexamethasone withdrawal
Adrenal cortical atrophy develops during prolonged therapy and may persist
for years after stopping treatment. Withdrawal of corticosteroids after
prolonged therapy must therefore always be gradual to avoid acute adrenal
insufficiency, being tapered off over weeks or months according to the dose
and duration of treatment.

In patients who have received more than physiological doses of systemic
corticosteroids (approximately 1 mg dexamethasone) for greater than 3 weeks,
withdrawal should not be abrupt. How dose reduction should be carried out
depends largely on whether the disease is likely to relapse as the dose of
systemic corticosteroids is reduced. Clinical assessment of disease activity
may be needed during withdrawal. If the disease is unlikely to relapse on
withdrawal of systemic corticosteroids but there is uncertainty about HPA
suppression, the dose of systemic corticosteroid may be reduced rapidly to
physiological doses. Once a daily dose of 1mg dexamethasone is reached,
dose reduction should be slower to allow the HPA-axis to recover.
Abrupt withdrawal of systemic corticosteroid treatment, which has continued
up to 3 weeks is appropriate if it is considered that the disease is unlikely to
relapse. Abrupt withdrawal of doses of up to 6mg daily of dexamethasone for
3 weeks is unlikely to lead to clinically relevant HPA-axis suppression in the
majority of patients. In the following patient groups, gradual withdrawal of
systemic corticosteroid therapy should be considered even after courses lasting
3 weeks or less:
• Patients who have had repeated courses of systemic corticosteroids,
particularly if taken for greater than 3 weeks.
• When a short course has been prescribed within one year of cessation of
long-term therapy (months or years).
• Patients who may have reasons for adrenocortical insufficiency other than
exogenous corticosteroid therapy.
• Patients receiving doses of systemic corticosteroid greater than 6mg daily
of dexamethasone.
• Patients repeatedly taking doses in the evening.
During prolonged therapy any intercurrent illness, trauma or surgical
procedure will require a temporary increase in dosage; if corticosteroids have
been stopped following prolonged therapy they may need to be temporarily
re-introduced.
Patients should carry 'Steroid treatment' cards which give clear guidance on
the precautions to be taken to minimise risk and which provide details of
prescriber, drug, dosage and the duration of treatment.
Anti-inflammatory/Immunosuppressive effects and Infection
Suppression of the inflammatory response and immune function increases the
susceptibility to infections and their severity. The clinical presentation may
often be atypical, and serious infections such as septicaemia and tuberculosis
may be masked and may reach an advanced stage before being recognised.
Appropriate antimicrobial therapy should accompany glucocorticoid therapy
when necessary e.g. in tuberculosis and viral and fungal infections of the eye.
Chickenpox is of particular concern since this normally minor illness may be
fatal in immunosuppressed patients. Patients (or parents of children) without a
definite history of chickenpox should be advised to avoid close personal
contact with chickenpox or herpes zoster and if exposed they should seek

urgent medical attention. Passive immunisation with varicella zoster
immunoglobulin (VZIG) is needed by exposed non-immune patients who are
receiving systemic corticosteroids or who have used them within the previous
3 months; this should be given within 10 days of exposure to chickenpox. If a
diagnosis of chickenpox is confirmed, the illness warrants specialist care and
urgent treatment. Corticosteroids should not be stopped and the dose may
need to be increased.
Measles - patients should be advised to take particular care to avoid exposure
to measles and to seek immediate medical advice if exposure occurs;
prophylaxis with intramuscular normal immunoglobin may be needed.
Live vaccines should not be given to individuals with impaired immune
responsiveness. The antibody response to other vaccines may be diminished.
Special precautions
Particular care is required when considering the use of systemic
corticosteroids in patients with the following conditions and frequent patient
monitoring is necessary.
a. Osteoporosis (post-menopausal females are particularly at risk).
b. Hypertension or congestive heart failure.
c. Existing or previous history of severe affective disorders (especially
previous steroid psychosis).
d. Diabetes mellitus (or a family history of diabetes).
e. History of tuberculosis, since glucocorticoids may induce reactivation.
f. Glaucoma (or a family history of glaucoma).
g. Previous corticosteroid-induced myopathy.
h. Liver failure.
i. Renal insufficiency.
j. Epilepsy.
k. Gastro-intestinal ulceration.
l. Migraine
m. Certain parasitic infestations in particular amoebiasis.
n. Incomplete statural growth since glucocorticoids on prolonged
administration may accelerate epiphyseal closure
o. Patients with Cushing’s syndrome
In the treatment of conditions such as tendinitis or tenosynovitis care should
be taken to inject into the space between the tendon sheath and the tendon as
cases of ruptured tendon have been reported.
Use in children
Corticosteroids cause dose-related growth retardation in infancy, childhood
and adolescence, which may be irreversible.
Dexamethasone has been used ‘off label’ to treat and prevent chronic lung
disease in preterm infants. Clinical trials have shown a short term benefit in
reducing ventilator dependence but no long term benefit in reducing time to
discharge, the incidence of chronic lung disease or mortality. Recent trials
have suggested an association between the use of dexamethasone in preterm

infants and the development of cerebral palsy. In view of this possible safety
concern, an assessment of the risk:benefit should be made on an individual
patient basis.
Use in the Elderly
The common 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.
4.5.

Interaction with other medicinal products and other forms of interaction
Rifampicin, rifabutin, ephedrine, carbamazepine, phenylbutazone,
phenobarbital, phenytoin, primidone, and aminoglutethimide enhance the
metabolism of corticosteroids and its therapeutic effects may be reduced.
The desired effects of hypoglycaemic agents (including insulin), antihypertensives, cardiac glycosides and diuretics are antagonised by
corticosteroids, and the hypokalaemic effects of acetazolamide, loop diuretics,
thiazide diuretics and carbenoxolone are enhanced.
The efficacy of coumarin anticoagulants may be enhanced by concurrent
corticosteroid therapy and close monitoring of the INR or prothrombin time is
required to avoid spontaneous bleeding.
The renal clearance of salicylates is increased by corticosteroids and steroid
withdrawal may result in salicylate intoxication. There may be interaction
with salicylates in patients with hypoprothrombinaemia.

4.6.

Pregnancy and lactation
The ability of corticosteroids to cross the placenta varies between individual
drugs, however, dexamethasone readily crosses the placenta.
Administration of corticosteroids to pregnant animals can cause abnormalities
of foetal development including cleft palate, intra-uterine growth retardation
and affects on brain growth and development. There is no evidence that
corticosteroids result in an increased incidence of congenital abnormalities,
such as cleft palate/lip in man. However, when administered for prolonged
periods or repeatedly during pregnancy, corticosteroids may increase the risk
of intra-uterine growth retardation. Hypoadrenalism may, in theory, occur in
the neonate following prenatal exposure to corticosteroids but usually resolves
spontaneously following birth and is rarely clinically important. As with all
drugs, corticosteroids should only be prescribed when the benefits to the
mother and child outweigh the risks. When corticosteroids are essential
however, patients with normal pregnancies may be treated as though they were
in the non-gravid state.

Lactation
Corticosteroids may pass into breast milk, although no data are available for
dexamethasone. Infants of mothers taking high doses of systemic
corticosteroids for prolonged periods may have a degree of adrenal
suppression.

4.7.

Effects on ability to drive and use machines
None known

4.8

Undesirable effects
Side-effects
Local adverse reactions include post-injection flare, and a painless destruction
of the joint reminiscent of Charcots arthropathy especially with repeated intraarticular injection.
The incidence of predictable undesirable effects, including hypothalamicpituitary-adrenal suppression correlates with the relative potency of the drug,
dosage, timing of administration and the duration of treatment. Cases of
ruptured tendon have been reported (see Section 4.4).
Local injection of glucocorticoid may produce systemic effects.
Endocrine/metabolic
Suppression of the hypothalamic-pituitary-adrenal axis, premature epiphyseal
closure, growth suppression in infancy, childhood and adolescence, menstrual
irregularity and amenorrhoea.
Cushingoid faces, hirsutism, weight gain,
impaired carbohydrate tolerance with increased requirement for anti-diabetic
therapy. Negative protein and calcium balance. Increased appetite.
Anti-inflammatory and Immunosuppressive effects
Increased susceptibility and severity of infections with suppression of clinical
symptoms and signs. Diminished lymphoid tissue and immune response.
Opportunistic infections, recurrence of dormant tuberculosis and decreased
responsiveness to vaccination and skin tests. (see Section 4.4).
Musculoskeletal
Osteoporosis, vertebral and long bone fractures, avascular osteonecrosis,
tendon rupture.
Proximal myopathy.
Fluid and electrolyte disturbance
Sodium and water retention, hypertension, potassium loss, hypokalaemic
alkalosis.

Neuropsychiatric
A wide range of psychiatric reactions including affective disorders (such as
irritable, euphoric, depressed and labile mood, and suicidal thoughts),
psychotic reactions (including mania, delusions, hallucinations, and
aggravation of schizophrenia), behavioural disturbances, irritability, anxiety,
sleep disturbances, and cognitive dysfunction including confusion and
amnesia have been reported. Reactions are common and may occur in both
adults and children. In adults, the frequency of severe reactions has been
estimated to be 5-6%. Psychological effects have been reported on
withdrawal of corticosteroids; the frequency is unknown
Increased intra-cranial pressure with papilloedema in children (pseudotumour
cerebri), usually after treatment withdrawal. Aggravation of epilepsy.
Psychological dependence.
Ophthalmic
Increased intra-ocular pressure, glaucoma, papilloedema, posterior
subcapsular cataracts, corneal or scleral thinning, exacerbation of opthalmic
viral or fungal diseases.
Gastrointestinal
Dyspepsia, peptic ulceration with perforation and haemorrhage, acute
pancreatitis, candidiasis.
Dermatological
Impaired healing, skin atrophy, bruising, telangiectasia, striae, increased
sweating and acne.
General
Hypersensitivity including anaphylaxis, has been reported. Leucocytosis.
Thromboembolism.
A transient burning or tingling sensation mainly in the perineal area following
intravenous injection of large doses of corticosteroid phosphates.
Withdrawal symptoms and signs
Too rapid a reduction of corticosteroid dosage following prolonged treatment
can lead to acute adrenal insufficiency, hypotension and death. (see Section
4.4).
A 'withdrawal syndrome' may also occur including, fever, myalgia, arthralgia,
rhinitis, conjunctivitis, painful itchy skin nodules and loss of weight.
4.9.

Overdose
It is difficult to define an excessive dose of a corticosteroid as the therapeutic
dose will vary according to the indication and patient requirements. Massive
i.v. corticosteroid doses given as a pulse in emergencies are relatively free
from hazardous effects.

Exaggeration of corticosteroid related adverse effects may occur. Treatment
should be asymptomatic and supportive as necessary.

5.

PHARMACOLOGICAL PROPERTIES

5.1.

Pharmacodynamic Properties
Dexamethasone is a synthetic adrenocorticoid with approximately a 7 times
higher anti-inflammatory potency than prednisolone and 30 times that of
hydrocortisone. Adrenocorticoids act on the HPA at specific receptors on the
plasma membrane. On other tissues the adrenocorticoids diffuse across cell
membranes and complex with specific cytoplasmic receptors which enter the
cell nucleus and stimulate protein synthesis. Adrenocorticoids have antiallergic, antitoxic, antishock, antipyretic and immunosuppressive properties.
Dexamethasone has only minor mineralocorticoid activities and does
therefore, not induce water and sodium retention.

5.2.

Pharmacokinetic Properties
After administration of Dexamethasone Injection, dexamethasone sodium
phosphate is rapidly hydrolysed to dexamethasone. After an iv dose of 20mg
dexamethasone plasma levels peak within 5 minutes. Dexamethasone is
bound (up to 77%) by plasma proteins, mainly albumin. There is a high
uptake of dexamethasone by the liver, kidney and adrenal glands. Metabolism
in the liver is slow and excretion is mainly in the urine, largely as
unconjugated steroids. The plasma half life is 3.5-4.5 hours but as the effects
outlast the significant plasma concentrations of steroids the plasma half-life is
of little relevance and the use of biological half life is more applicable. The
biological half life of dexamethasone is 36-54 hours, therefore dexamethasone
is especially suitable in conditions where continuous glucocorticoid action is
desirable.

5.3.

Pre-clinical Safety Data
Not applicable.

6.

PHARMACEUTICAL PARTICULARS

6.1.

List of Excipients
Glycerol (E422)
Disodium edetate
Methyl paraben (E218)
Propyl paraben (E216)
Water for injections
Sodium hydroxide (E524) or Phosphoric acid (E338)

6.2.

Incompatibilities
None known.

6.3.

Shelf-Life
2 years.

6.4.

Special Precautions for Storage
Store below 25°C. Protect from light.

6.5.

Nature and Content of Container
2ml glass vials cartons of 1 or 10.

6.6.

Instructions for Use, Handling and Disposal
Use with infusion fluids
Dexamethasone Injection has been shown to retain its potency for at least 24
hours at room temperature, and in daylight conditions, when diluted with one
of the following infusion fluids:
sodium chloride 0.9%
anhydrous glucose 5%
invert sugar 10%
sorbitol 5%
Ringer's solution
Hartmann's solution (ringer-lactate)
Rheomacrodex
Haemaccel

Using these infusion fluids, Dexamethasone Injection can also be injected into
the infusion line without causing precipitation of the ingredients. Direct
injection into the infusion line is also possible with the following infusion
fluids:
mannitol 10%
Vamin N
(see also Section 4.4).

7.

MARKETING AUTHORISATION HOLDER
Organon Laboratories Limited,
Cambridge Science Park,
Milton Road,
Cambridge,
CB4 0FL,
U.K.

8.

MARKETING AUTHORISATION NUMBER(S)
PL 0065/5013R

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
18/06/2010

10

DATE OF REVISION OF THE TEXT
18/06/2010

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Source: Medicines and Healthcare Products Regulatory Agency

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