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BETAMETHASONE 4MG/ML INJECTION

Active substance(s): BETAMETHASONE SODIUM PHOSPHATE

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Betnesol 4mg/ml Solution for Injection
Betamethasone 4mg/ml Solution for Injection

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each ampoule contains 5.3mg of betamethasone sodium phosphate BP equivalent to
4mg betamethasone in 1ml of sterile aqueous solution.
For excipients, see 6.1

3

PHARMACEUTICAL FORM
Solution for Injection
1ml ampoules containing a clear colourless or pale yellow solution.

4
4.1

CLINICAL PARTICULARS
Therapeutic indications
Betamethasone is a glucocorticosteroid which is about eight to ten times as active as
prednisolone on a weight-for-weight basis. It may be indicated in the following
conditions:
Status asthmaticus and acute allergic reactions, including anaphylactic reactions to
drugs. Betnesol Injection/Betamethasone Injection supplements the action of
adrenaline.
Severe shock arising from surgical or accidental trauma or overwhelming infection.
Acute adrenal crisis caused by abnormal stress in Addison’s disease, Simmonds’
disease, hypopituitarism following adrenalectomy, and when adrenocortical function
has been suppressed by prolonged corticosteroid therapy.
Soft tissue lesions such as tennis elbow, tenosynovitis and bursitis.
NB. Betnesol Injection/Betamethasone Injection does not replace other forms of
therapy for the treatment of shock and status asthmaticus.

4.2

Posology and method of administration
Betnesol Injection/Betamethasone Injection may be administered by slow intravenous
injection, deep intramuscular injection or subconjunctival injection. Alternatively,
Betnesol Injection/Betamethasone Injection may be given by intravenous infusion.
Local injections of Betnesol Injection/Betamethasone Injection may be used when
treating soft tissue lesions (see below).
The incidence of predictable undesirable effects, including hypothalamic-pituitaryadrenal (HPA) axis suppression correlates with the relative potency of the drug,
dosage, timing of administration and the duration of treatment (see “Special Warnings
and Precautions for Use”).
Systemic therapy in adults
4 to 20mg betamethasone (1 to 5ml) administered by slow intravenous injection over
half to one minute. This dose can be repeated three or four times in 24 hours, or as
required, depending upon the condition being treated and the patient’s response.
Alternatively, Betnesol Injection/Betamethasone Injection may be given by
intravenous infusion. The same dose can be given by deep intramuscular injection
but the response is likely to be less rapid, especially in shock. This dose can be
repeated three or four times in 24 hours depending upon the condition being treated
and the patient’s response.
Systemic therapy in children
Infants up to 1 year may be given 1mg betamethasone intravenously; children aged 1
to 5 years, 2mg; 6 to 12 years, 4mg (1ml). This dose can be repeated three or four
times in 24 hours, depending upon the condition being treated and the patient’s
response.
Other routes
Local injections of 4 to 8mg Betnesol Injection/Betamethasone Injection may be used
when treating soft tissue lesions in adults; children may require smaller doses. This
dose can be repeated on two or three occasions depending upon the patient’s
response.
Betnesol Injection/Betamethasone Injection has also been administered subconjunctivally as a single injection of 0.5 to 1ml.
Intrathecal use is not recommended.

4.3

Contraindications
Systemic infections, unless specific anti-infective therapy is employed.
Hypersensivity to the active substance or to any of the excipients. Betnesol
Injection/Betamethasone Injection contains sodium metabisulphite (0.1% w/v) as a
preservative and therefore should not be used to treat patients with known
hypersensitivity to bisulphite, metabisulphite.
Betnesol Injection/Betamethasone Injection should not be injected directly into
tendons.

4.4

Special warnings and precautions for use

A patient information leaflet should be supplied with this product.
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 alternate days. Frequent
patient review is required to appropriately titrate the dose against disease activity
(see “Posology and Method of Administration”).
Caution is advised with the use of corticosteroids in patients who have suffered a
recent myocardial infarction because of the risk of myocardial rupture.
Caution is advised on the use of corticosteroids in patients with hypothyroidism or
myasthenia gravis.
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.
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.
Live vaccines should not be given to individuals with impaired immune
responsiveness. The antibody response to other vaccines may be diminished.
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 immunoglobulin may be needed.
Corticosteroids should not be used for management of head injury or stroke because it
is unlikely to be of benefit and may even be harmful.
In the treatment of cerebral oedema due to tumour, gastrointestinal bleeding may
occur and stool examination may be helpful in diagnosis.
Adrenal suppression:
Adrenal cortical atrophy develops during prolonged therapy and may persist for years
after stopping treatment.
In patients who have received more than physiological doses of systemic
corticosteroids (approximately 1mg betamethasone or equivalent) 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 a 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
equivalent to 1mg betamethasone 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 betamethasone, or equivalent 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 have reasons for adrenocortical insufficiency other than exogenous
corticosteroids therapy,
• Patients receiving doses of systemic corticosteroid greater than 6mg daily of
betamethasone (or equivalent),
• 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.
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, or active, tuberculosis.
F. Glaucoma (or a family history of glaucoma).
G. Previous corticosteroid-induced myopathy.
H. Liver failure - blood levels of corticosteroid may be increased, as with other
drugs which are metabolised in the liver.
I.

Renal insufficiency.

J. Epilepsy.
K. History of, or active, peptic ulceration.
L. Herpes simplex keratitis.
M. Diverticulitis.
N. Thromboembolic tendencies.
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.
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 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.
Use in children
Caution is advised in children as they are more susceptible to systemic toxicity from
betamethasone.
Corticosteroids cause dose-related growth retardation in infancy, childhood and
adolescence, which may be irreversible. Treatment should be limited to the minimum
dosage for the shortest possible time. In order to minimise suppression of the HPA
axis and growth retardation, consideration should be given to administration of a
single dose on alternate days.
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
Steroids may reduce the effects of anticholinesterases in myasthenia gravis,
cholecystographic X-ray media and non-steroidal anti-inflammatory agents.
Rifampicin, rifabutin, carbamazepine, phenobarbitone, phenytoin, primidone,
aminoglutethimide and ephedrine enhance the metabolism of corticosteroids; thus the
corticosteroid therapeutic effect may be reduced.
The desired effects of hypoglycaemic agents (including insulin), anti-hypertensives
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.
The risk of hypokalaemia is increased with theophylline, ulcer healing drugs such as
carbenoxolone and antifungals such as amphotericin B.
Increased toxicity may result if hypokalaemia occurs in patients on cardiac
glycosides.
Ritonavir and oral contraceptives may result in increased plasma concentrations or
corticosteroids.

The effect of corticosteroids may be reduced for 3-4 days after mifepristone.
The growth promoting effect of somatropin may be inhibited by corticosteroids.
An increase in the incidence of gastrointestinal bleeding may occur if NSAIDS are
taken concomitantly with corticosteroids.
Corticosteroids may antagonise the effects of neuromuscular blocking drugs such as
vecuronium.
Concurrent use of corticosteroids and fluoroquinolones may result in increased risk of
tendon rupture.
Concomitant use of betamethasone with quetiapine may result in the increased
metabolism of quetiapine and, depending on the clinical response, a higher dose of
quetiapine may need to be considered.
Corticosteroids may enhance the metabolism of tretinoin resulting in decreased levels
of tretinoin.

4.6

Fertility, Pregnancy and lactation
Pregnancy
The ability of corticosteroids to cross the placenta varies between individual drugs,
however, betamethasone readily crosses the placenta.
Administration of
corticosteroids to pregnant animals can cause abnormalities of foetal development
including cleft palate, intra-uterine 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. 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. Myocardial hypertrophy and gastroesophageal reflux have been
reported in association with in-utero exposure to betamethasone.
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 nongravid state. Patients with pre-eclampsia or fluid retention require close monitoring.
Betamethasone, systemically administered to a woman during pregnancy may result
in a transient suppression of the foetal heart rate parameters and biophysical activities
that are widely used for the assessment of foetal well – being. These characteristics
can include a reduction in foetal breathing movements, body movements and heart
rate.
Lactation
Corticosteroids may pass into breast milk, although no data are available for
betamethasone. 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
The incidence of predictable undesirable effects, including hypothalamic-pituitaryadrenal (HPA) axis suppression, correlates with the relative potency of the drug,
dosage, timing of administration and the duration of treatment (see “Special Warnings
and Precautions for Use”).
Endocrine/metabolic
Suppression of the HPA axis, growth suppression in infancy, childhood and
adolescence, menstrual irregularity and amenorrhoea. Cushingoid facies, hirsutism,
weight gain, impaired carbohydrate tolerance with increased requirement for
antidiabetic therapy. Negative protein, nitrogen and calcium balance. Increased
appetite. Hyperhydrosis. Increased high - density lipoprotein and low – density
lipoprotein concentrations in the blood.
Anti-inflammatory and immunosuppressive effects
Increased susceptibility to and severity of infections with suppression of clinical
symptoms and signs, opportunistic infections, recurrence of dormant tuberculosis (see
“Special Warnings and Precautions for Use”).
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 disorder (such a 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 any may occur in both adults and children. In adults, the frequency of
severe reactions has been estimated to the 5-6%. Psychological effects have been
reported on withdrawal of corticosteroids; the frequency is unknown.
Psychological dependence. Increased intra-cranial pressure with papilloedema in
children (pseudotumour cerebri), usually after treatment withdrawal. Aggravation of
epilepsy.
Ophthalmic
Increased intra-ocular pressure, glaucoma, papilloedema, posterior subcapsular
cataracts, corneal or scleral thinning, exacerbation of ophthalmic viral or fungal
diseases
Cardiac
Myocardial rupture following recent myocardial infarction.
Gastrointestinal
Abdominal distension, oesophageal ulceration, nausea, dyspepsia, peptic ulceration
with perforation and haemorrhage, acute pancreatitis, candidiasis.

Dermatological
Impaired healing, skin atrophy, bruising, telangiectasia, striae, acne, Stevens-Johnson
syndrome.
General
Hypersensitivity including anaphylaxis, has been reported. Leucocytosis. Thromboembolism. Malaise. Hiccups.
Withdrawal symptoms and signs
Too rapid a reduction of corticosteroid dosage following prolonged treatment can
lead to acute adrenal insufficiency, hypotension and death (see “Special Warnings
and Precautions for Use”).
A “withdrawal syndrome” may also occur including; fever, myalgia, arthralgia,
rhinitis, conjunctivitis, painful itchy skin nodules and loss of weight.
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions after authorisation of the medicinal product
is important. It allows continued monitoring of the benefit/risk balance of the
medicinal product. Healthcare professionals are asked to report any suspected adverse
reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

4.9

Overdose
Should overdosage occur, the possibility of adrenal suppression should be minimised
by a gradual reduction of dosage over a period of time. The patient may need support
during any further trauma.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

ATC Code: HO2A B01
Betamethasone is a glucocorticoid which is about eight to ten times as active as
prednisolone on a weight-for-weight basis

5.2

Pharmacokinetic properties
Corticosteroids are bound to plasma proteins in varying degrees. Corticosteroids are
metabolised primarily by the liver and then excreted by the kidneys.

5.3

Preclinical safety data
None stated

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Disodium edetate
Sodium metabisulphite
Sodium chloride
Sodium hydroxide
Hydrochloric acid
Water for injection

6.2

Incompatibilities
None known

6.3

Shelf life
15 months

6.4

Special precautions for storage
Do not store above 25°C and protect from light.

6.5

Nature and contents of container
1ml clear, one-point cut (OPC) colourless glass Type 1 Ph Eur ampoules packed in
cartons of 5 ampoules

6.6

Special precautions for disposal

None stated

7

MARKETING AUTHORISATION HOLDER
Focus Pharmaceuticals Ltd
Capital House, 1st Floor,
85 King William Street,
London EC4N 7BL,
United Kingdom.

8

MARKETING AUTHORISATION NUMBER(S)
PL 20046/0281

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
22nd December 1992

10

DATE OF REVISION OF THE TEXT
25/06/2015

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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