Adcortyl Intra-Articular / Intradermal Injection 10mg / ml

1. Name Of The Medicinal Product

Adcortyl Intra-articular/Intradermal Injection 10mg/ml

2. Qualitative And Quantitative Composition

Adcortyl Intra-articular/Intradermal Injection contains triamcinolone acetonide 10mg per ml of sterile suspension.

3. Pharmaceutical Form

Sterile aqueous suspension for injection.

4. Clinical Particulars

4.1 Therapeutic Indications

Intra-articular use: for alleviating the joint pain, swelling and stiffness associated with rheumatoid arthritis and osteoarthrosis, with an inflammatory component; also for bursitis, epicondylitis, and tenosynovitis.

Intradermal use: for lichen simplex chronicus (neuro-dermatitis), granuloma annulare, lichen planus, keloids, alopecia areata and hypertrophic scars.

4.2 Posology And Method Of Administration

Adcortyl is for intra-articular or intra-dermal injection. The safety and efficacy of administration by other routes has yet to be established. 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.

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 2.5-5mg (0.25-0.5ml) for smaller joints and 5-15mg (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.

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.

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. Caution should be used in the event of exposure to chickenpox, measles or other communicable diseases. (See 4.4 Special Warnings and Special Precautions for Use.)

4.3 Contraindications

Hypersensitivity to any of the ingredients.

Systemic infections unless specific anti-infective therapy is employed.

Administration by intravenous, intrathecal or intraocular injection.

4.4 Special Warnings And Precautions For Use

Warnings (Intra-Articular Injection):

Corticosteroids should not be injected into unstable joints.

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.

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.

Precautions:

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.

Undesirable effects may be minimised using the lowest effective dose for the minimum period, and by administering the daily requirement, whenever possible, as a single morning dose on alternate days. Frequent patient review is required to titrate the dose appropriately against disease activity (See dosage section).

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 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.

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 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.

During corticosteroid therapy antibody response will be reduced and therefore affect the patient's response to vaccines. Live vaccines should not be administered.

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.

Special Precautions:

Particular care is required when considering use of systemic corticosteroids in patients with the following conditions and frequent patient monitoring is necessary.

Recent intestinal anastomoses, diverticulitis, thrombophlebitis, existing or previous history of severe affective disorders (especially previous steroid psychosis), exanthematous disease, chronic nephritis, or renal insufficiency, metastatic carcinoma, osteoporosis (post-menopausal females are particularly at risk); in patients with an active peptic ulcer (or a history of peptic ulcer). Myasthenia gravis. Latent or healed tuberculosis; in the presence of local or systemic viral infection, systemic fungal infections or in active infections not controlled by antibiotics. In acute psychoses; in acute glomerulonephritis. Hypertension; congestive heart failure; glaucoma (or a family history of glaucoma), previous steroid myopathy or epilepsy. Liver failure.

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

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.

Rare instances of anaphylactoid reactions have occurred in patients receiving corticosteroids, especially when a patient has a history of drug allergies.

All corticosteroids increase calcium excretion.

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

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.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

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

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, 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.

Nondepolarising muscle relaxants: Corticosteroids may decrease or enhance the neuromuscular blocking action.

Nonsteroidal 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.)

4.6 Pregnancy And Lactation

The ability of corticosteroids to cross the placenta varies between individual drugs, however triamcinolone does cross 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.

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 triamcinolone. 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

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 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: Anaphylatic reactions, angiodema, rash, pruritus and urticaria, particularly where there is a history of drug allergies.

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.

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

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.

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.

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 (eg. 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.

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. Very rare instances of blindness associated with intralesional therapy around the face and head have been reported.

4.9 Overdose

Not applicable.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

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

5.2 Pharmacokinetic Properties

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.

In common with other corticosteroids, triamcinolone is metabolised largely hepatically but also by the kidney and is excreted in urine. The main metabolic route is 6-beta-hydroxylation; no significant hydrolytic cleavage of the acetonide occurs. In view of the hepatic metabolism and renal excretion of triamcinolone acetonide, functional impairments of the liver or kidney may affect the pharmacokinetics of the drug. This may become clinically significant if large or frequent doses of intradermal or intra-articular triamcinolone acetonide are given.

5.3 Preclinical Safety Data

See 4.6 Pregnancy and Lactation.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Benzyl alcohol

Polysorbate 80

Sodium carboxymethylcellulose

Sodium chloride

Water.

6.2 Incompatibilities

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

6.3 Shelf Life

36 months

6.4 Special Precautions For Storage

In an upright position. Do not store above 25°C. Avoid freezing.

6.5 Nature And Contents Of Container

Carton containing glass ampoules 5 x 1ml or individually cartoned multidose vials of 5ml.

6.6 Special Precautions For Disposal And Other Handling

No special handling instructions.

7. Marketing Authorisation Holder

E.R. Squibb & Sons Ltd.

Uxbridge Business Park

Sanderson Road

Uxbridge

Middlesex

UB8 1DH

8. Marketing Authorisation Number(S)

PL 0034/5002R

9. Date Of First Authorisation/Renewal Of The Authorisation

25 July 1986 / 8 November 2002

10. Date Of Revision Of The Text

17 July 2008