Bristol-Myers Squibb Pharmaceutical Limited

Adcortyl^™ Intra-articular / Intradermal Injection 10mg/ml Suspension for Injection, 1ml

Triamcinolone acetonide 10mg per ml (10mg per 1ml ampoule).

Excipients: contains benzyl alcohol 15mg/ml

For a full list of excipients, see section 6.1.

Suspension for Injection (Injection).

White, sterile aqueous suspension with a slight odour.

Intra-articular use: in the local management of inflammation involving joints, bursae or tendon sheaths such as occurs in rheumatoid arthritis, osteoarthritis, bursitis, synovitis, tendinitis, epicondylitis and trauma.

Intradermal use: for inflammatory dermal lesions such as lichen simplex, lichen planus, psoriasis, granuloma annulare, keloids and for alopecia.

Adcortyl Injection is only for intra-articular or intra-dermal use and should not be given by any other route. Strict aseptic precautions should be observed. Since the duration of effect is variable, subsequent doses should be given when symptoms recur and not at set intervals.

Adcortyl Injection should only be given in an appropriate setting where there is access to emergency medical care.

Adults:

The dose of Adcortyl Injection for intra-articular administration, and injection into tendon sheaths and bursae, is dependent on the size of the joint to be treated and on the severity of the condition.

Doses of 2.5 - 5 mg (0.25 - 0.5ml) for smaller joints and 5 - 15 mg (0.5 - 1.5ml) for larger joints usually alleviate the symptoms. Triamcinolone acetonide 40mg/ml (Kenalog) is available to facilitate administration of larger doses. (See Precautions re Achilles tendon.)

Intradermal dosage is usually 2 - 3mg (0.2 - 0.3ml), depending on the size of the lesion. No more than 5mg (0.5ml) should be injected at any one site. If several sites are injected the total dosage administered should not exceed 30mg (3ml). The injection may be repeated if necessary, at one or two week intervals.

Children:

Adcortyl is not recommended in children under 6 years. Adcortyl intra-articular / intradermal may be used in older children in suitably adjusted dosages. Growth and development of children on prolonged corticosteroid therapy should be carefully observed.

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, especially osteoporosis, diabetes, hypertension, hypokalaemia, susceptibility to infection and thinning of the skin. Close supervision is required to avoid life-threatening reactions.

In patients with an active peptic ulcer (or a history of peptic ulcer). Active or latent or healed tuberculosis; in the presence of local or systemic viral infection, systemic fungal infections or in active bacterial infections not controlled by antibiotics. In acute psychoses. In those with allergy or hypersensitivity to the products or its excipients. Administration by intravenous, intrathecal or intraocular injection.

Adcortyl is not suitable for intravenous, intramuscular, intraocular, epidural or intrathecal use.

In common with other steroids, Adcortyl Injection should be used with caution in patients with recent intestinal anastomoses, thrombophlebitis, psychotic tendencies, exanthematous disease, chronic nephritis, metastatic carcinoma, osteoporosis (post-menopausal females are particularly at risk); in acute glomerulonephritis, hypertension, congestive heart failure, glaucoma (or a family history of glaucoma), previous steroid myopathy or epilepsy; liver failure.

Intra-articular injection should not be carried out in the presence of active infection in or near joints. The preparation should not be used to alleviate joint pain arising from infectious states such as gonococcal or tubercular arthritis.

Diabetes may be aggravated, necessitating a higher insulin dosage. Latent diabetes mellitus may be precipitated.

Menstrual irregularities may occur, and this possibility should be mentioned to female patients.

Patients on long-term systemic therapy with Adcortyl may require supportive corticosteroid therapy in times of stress, general anaesthesia or during surgery, both during the treatment period and for a year afterwards. During corticosteroid therapy antibody response will be reduced and therefore affect the patient's response to vaccines.

Cases of serious anaphylactic reactions and anaphylactic shock, including death, have been reported in individuals receiving triamcinolone acetonide injection, regardless of the route of administration.Appropriate precautionary measures should be taken prior to administration, especially when the patient has a history of allergy to any drug (See Posology and Method of Administration).

All corticosteroids increase calcium excretion.

Aspirin should be used cautiously in conjunction with corticosteroids in patients with hypoprothrombinaemia.

Corticosteroid administration will result in certain effects, the severity, significance and extent of which vary with the dosage and duration of treatment and the particular corticosteroid used. These include disturbance in electrolyte balance, mineral metabolism, glucose metabolism and gluconeogenesis, nitrogen depletion, diminished lymphoid tissue and immune response, inhibition of pituitary function, Cushingoid syndrome, increase in blood coagulability, diminished response.

Corticosteroid effects may be enhanced in patients with hypothyroidism or cirrhosis.

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 and measles are of particular concern since these normally minor illnesses may be fatal in immunosuppressed patients.

Unless they have had chickenpox, patients receiving parenteral corticosteroids for purposes other than replacement should be regarded as being at risk of severe chickenpox. Manifestations of fulminant illness include pneumonia, hepatitis and disseminated intravascular coagulation; rash is not necessarily a prominent feature.

Passive immunisation with varicella-zoster immunoglobulin (VZIG) is needed for exposed non-immune patients receiving systemic corticosteroids or for those who have used them within the previous 3 months; varicella-zoster immunoglobulin should preferably be given within 3 days of exposure and not later than 10 days.

Confirmed chickenpox warrants specialist care and urgent treatment. Corticosteroids should not be stopped and dosage may need to be increased.

Patients should be advised to avoid exposure to measles and to seek medical advice without delay if exposure occurs. Prophylaxis with normal immunoglobulin may be needed.

Prolonged use in children may lead to growth retardation. Some recovery may occur on discontinuing therapy.

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 and should be tapered off over weeks or months according to the dose and duration of treatment. 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 reintroduced temporarily. Patients on prolonged therapy should obtain and carry with them a steroid treatment card from their pharmacist which gives clear guidance on the precautions to be taken to minimise risk and which provides 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 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.

Adequate studies to demonstrate the safety of Adcortyl use by intra-turbinal, subconjunctival, sub-tenons, retrobulbar and intraocular (intravitreal) injections have not been performed. Endophthalmitis, eye inflammation, increased intraocular pressure and visual disturbances including vision loss have been reported with intravitreal administration. Several instances of blindness have been reported following injection of corticosteroid suspensions into the nasal turbinates and intralesional injection about the head.

This product contains 15mg/ml benzyl alcohol and must not be given to premature babies or neonates. Benzyl Alcohol may cause toxic reactions and anaphylactoid reactions in infants and children up to 3 years old.

Intra-articular Injection:

Patients should be specifically warned to avoid over-use of joints in which symptomatic benefit has been obtained. Severe joint destruction with necrosis of bone may occur if repeated intra-articular injections are given over a long period of time. Care should be taken if injections are given into tendon sheaths to avoid injection into the tendon itself. Repeated injection into inflamed tendons should be avoided as it has been shown to cause tendon rupture.

Due to the absence of a true tendon sheath, the Achilles tendon should not be injected with depot corticosteroids.

Amphotericin B injection and potassium-depleting agents: Patients should be observed for hypokalemia.

Anticholinesterases: Effects of anticholinesterase agent may be antagonised.

Anticoagulants, oral: Corticosteroids may potentiate or decrease anticoagulant action. Patients receiving oral anticoagulants and corticosteroids should therefore be closely monitored.

Antidiabetics: Corticosteroids may increase blood glucose; diabetic control should be monitored, especially when corticosteroids are initiated, discontinued, or changed in dosage.

Antihypertensives, including diuretics: corticosteroids antagonise the effects of antihypertensives and diuretics. The hypokalaemic effect of diuretics, including acetazolamide, loop diuretics, thiazide diuretics and carbenoxolone, is enhanced.

Anti-tubercular drugs: Isoniazid serum concentrations may be decreased.

Cyclosporin: Monitor for evidence of increased toxicity of cyclosporin when the two are used concurrently.

Digitalis glycosides: Co-administration may enhance the possibility of digitalis toxicity.

Oestrogens, including oral contraceptives: Corticosteroid half-life and concentration may be increased and clearance decreased.

Hepatic Enzyme Inducers (e.g. barbiturates, phenytoin, carbamazepine, rifampicin, primidone, aminoglutethimide): There may be increased metabolic clearance of Adcortyl. Patients should be carefully observed for possible diminished effect of steroid, and the dosage should be adjusted accordingly.

Human growth hormone: The growth-promoting effect may be inhibited.

Ketoconazole: Corticosteroid clearance may be decreased, resulting in increased effects.

Non-depolarising muscle relaxants: Corticosteroids may decrease or enhance the neuromuscular blocking action.

Non-steroidal anti-inflammatory agents (NSAIDS): Corticosteroids may increase the incidence and/or severity of GI bleeding and ulceration associated with NSAIDS. Also, corticosteroids can reduce serum salicylate levels and therefore decrease their effectiveness. Conversely, discontinuing corticosteroids during high-dose salicylate therapy may result in salicylate toxicity. Aspirin should be used cautiously in conjunction with corticosteroids in patients with hypoprothrombinaemia.

Thyroid drugs: Metabolic clearance of adrenocorticoids is decreased in hypothyroid patients and increased in hyperthyroid patients. Changes in thyroid status of the patient may necessitate adjustment in adrenocorticoid dosage.

Vaccines: Neurological complications and lack of antibody response may occur when patients taking corticosteroids are vaccinated. (See 4.4 Special Warnings and Special Precautions for Use.)

Corticosteroids are not recommended for pregnant patients, particularly in the first trimester, or for nursing mothers, except when the disease for which they are indicated warrants their use. When corticosteroids are essential however, patients with normal pregnancies may be treated as though they were in the non-gravid state.

There is evidence of harmful effects in pregnancy in animals. There may be a small risk of cleft palate and intra-uterine growth retardation. Hypoadrenalism may occur in the neonate. Patients with pre-eclampsia or fluid retention require close monitoring.

Corticosteroids are found in breast milk.

None known.

Where adverse reactions occur they are usually reversible on cessation of therapy. The incidence of predictable side-effects, including hypothalamic-pituitary-adrenal suppression correlate with the relative potency of the drug, dosage, timing of administration and duration of treatment (See Warnings and Precautions).

Absorption of triamcinolone following Adcortyl injection, especially when given by the intra-articular route, is rare. However, patients should be watched closely for the following adverse reactions which may be associated with any corticosteroid therapy:

Anti-inflammatory and immunosuppressive effects: Increased susceptibility and severity of infections such as sepsis, necrotising fasciitis, with suppression of clinical symptoms and signs, opportunistic infections, recurrence of dormant tuberculosis (See Warnings and Precautions).

Fluid and electrolyte disturbances: sodium retention, fluid retention, congestive heart failure in susceptible patients, potassium loss, cardiac arrhythmias or ECG changes due to potassium deficiency, hypokalaemic alkalosis, increased calcium excretion and hypertension.

Musculoskeletal: muscle weakness, fatigue, steroid myopathy, loss of muscle mass, osteoporosis, avascular osteonecrosis, vertebral compression fractures, delayed healing of fractures, aseptic necrosis of femoral and humeral heads, pathological fractures of long bones and spontaneous fractures, tendon rupture.

Hypersensitivity: Anaphylactoid reaction, anaphylaxis including anaphylactic reactions and anaphylactic shock, angiodema, rash, pruritus and urticaria, particularly where there is a history of drug allergies.

Gastrointestinal: dyspepsia, peptic ulcer with possible subsequent perforation and haemorrhage, pancreatitis, abdominal distension and ulcerative oesophagitis, candidiasis.

Dermatological: impaired wound healing, thin fragile skin, petechiae and ecchymoses, facial erythema, increased sweating, purpura, striae, hirsutism, acneiform eruptions, lupus erythematous-like lesions and suppressed reactions to skin tests.

Neurological: euphoria, psychological dependence, depression, insomnia, convulsions, increased intracranial pressure with papilloedema (pseudo-tumour cerebri) usually after treatment, vertigo, headache, neuritis or paraesthesias and aggravation of pre-existing psychiatric conditions and epilepsy.

Endocrine: menstrual irregularities and amenorrhoea; development of the Cushingoid state; suppression of growth in childhood and adolescence; secondary adrenocortical and pituitary unresponsiveness, particularly in times of stress (e.g. trauma, surgery or illness); decreased carbohydrate tolerance; manifestations of latent diabetes mellitus and increased requirements for insulin or oral hypoglycaemic agents in diabetes, weight gain. Negative protein and calcium balance. Increased appetite.

Ophthalmic: posterior supcapsular cataracts, increased intraocular pressure, glaucoma, exophthalmos, papilloedema, corneal or scleral thinning, exacerbation of ophthalmic viral or fungal diseases.

Others: necrotising angiitis, thrombophlebitis, thromboembolism, leucocytosis, insomnia and syncopal episodes.

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.

Withdrawal Symptoms and Signs:

On withdrawal, fever, myalgia, arthralgia, rhinitis, conjunctivitis, painful itchy skin nodules and weight loss may occur. Too rapid a reduction in dose following prolonged treatment can lead to acute adrenal insufficiency, hypotension and death (See Warnings and Precautions).

Intra-Articular Injection:

Reactions following intra-articular administration have been rare. In a few instances, transient flushing and dizziness have occurred. Local symptoms such as post-injection flare, transient pain, irritation, sterile abscesses, hyper- or hypo-pigmentation, Charcot-like arthropathy and occasional increase in joint discomfort may occur. Local fat atrophy may occur if the injection is not given into the joint space, but is temporary and disappears within a few weeks to months.

Intradermal Injection:

Local discomfort, sterile abscesses, hyper- and hypo-pigmentation and subcutaneous and cutaneous atrophy (which usually disappears unless the basic disease process is itself atrophic) have occurred.

Not applicable.

Triamcinolone acetonide is a synthetic glucocorticoid, with marked anti-inflammatory and anti-allergic actions. Following local injection of Adcortyl, relief of pain and swelling and greater freedom of movement are usually obtained within a few hours; such administration avoids the more severe side-effects which may accompany parenteral or oral corticosteroid administration.

Triamcinolone acetonide may be absorbed into the systemic circulation from synovial spaces. However clinically significant systemic levels after intra-articular injection are unlikely to occur except perhaps following treatment of large joints with high doses. Systemic effects do not ordinarily occur with intra-articular injections when the proper techniques of administration and the recommended dosage regimens are observed.

The systemic effects of intradermally administered triamcinolone acetonide have not been extensively studied. The risk of systemic absorption, though minimal, should be taken into consideration especially when repeated intralesional administrations may be necessary.

See 4.6 Pregnancy and lactation.

The injection should not be physically mixed with other medicinal products.

Do not store above 25°C.

Do not freeze.

Carton containing 5 x 1ml clear Type I glass ampoules.

Store in an upright position. Shake well before use.

Bristol-Myers Squibb Pharmaceuticals Limited

Swords

County Dublin

Date of first authorisation: 1 April 1978

Date of last renewal: 20 October 2007

August 2011