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 ONLY. The safety and efficacy of administration by other routes has yet to be established (see sections 4.3 and 4.4). 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 2.5-5 mg (0.25-0.5 ml) for smaller joints and 5-15 mg (0.5-1.5 ml) for larger joints usually alleviate the symptoms. Triamcinolone acetonide 40 mg/ml (Kenalog) is available to facilitate administration of larger doses (see section 4.4 re Achilles tendon).

Intradermal dosage is usually 2-3 mg (0.2-0.3 ml), depending on the size of the lesion. No more than 5 mg (0.5 ml) should be injected at any one site. If several sites are injected the total dosage administered should not exceed 30 mg (3 ml). 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 section 4.4).

4.3. Contraindications

Hypersensitivity to any of the ingredients.

Systemic infections unless specific anti-infective therapy is employed.

Administration by intravenous, intrathecal, epidural or intraocular injection.

4.4. Special warnings and precautions for use

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, chorioretinopathy, including crystalline maculopathy and viral retinitis (mainly by cytomegalovirus) 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.

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.

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.

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 section 4.2).

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. In addition, the patient should also carry a 'Steroid Emergency Card' when multiple doses are given in a relatively short period of time.

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 section 4.5), 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.

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. During post marketing use, there have been reports of clinically significant drug interactions in patients receiving triamcinolone acetonide and ritonavir, resulting in systemic corticosteroid effects including Cushing's syndrome and adrenal suppression. Therefore, co-administration of triamcinolone acetonide and ritonavir is not recommended unless the potential benefit of treatment outweighs the risk of systemic corticosteroid effects (see section 4.5).

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 in postmenopausal women vaginal bleeding has been observed. This possibility should be mentioned to female patients but should not deter appropriate investigations as indicated.

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.

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 including triamcinolone acetonide.

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.

CYP 3A4 inhibitors: Triamcinolone acetonide is a substrate of CYP3A4. Co-administration with strong CYP3A4 inhibitors (eg, ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, ketoconazole, telithromycin) with triamcinolone is not recommended because increased systemic corticosteroid adverse effects may occur (see section 4.8). If the potential benefit of co-administration outweighs the increased risk of systemic corticosteroid side-effects, patients should be monitored for these effects. During post marketing use, there have been reports of clinically significant drug interactions in patients receiving triamcinolone acetonide and ritonavir, resulting in systemic corticosteroid effects including Cushing's syndrome and adrenal suppression (see section 4.4).

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 section 4.4).

4.6. Fertility, pregnancy and lactation

Pregnancy:

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.

Breast-feeding:

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

The list of undesirable effects shown below is presented by system organ class, MedDRA preferred term, and frequency. Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1000 to <1/100); rare (≥1/10,000 to <1/1000); very rare (≥1/10,000); Not known (cannot be estimated from the available data).

System Organ Class

Frequency

MedDRA Terms

Infections and infestations

Common

Infection

Uncommon

Injection site abscess sterile, Infection masked, Tuberculosis, Candida infection, Eye infection viral, Eye infection fungal, Rhinitis, Conjunctivitis

Immune system disorders

Uncommon

Anaphylactoid reaction

Anaphylactic reaction

Anaphylactoid shock

Endocrine disorders

Uncommon

Cushingoid, Adrenal suppression, Secondary adrenocortical insufficiency, Hypopituitarism

Metabolism and nutrition disorders

Uncommon

Sodium retention, Fluid retention, Alkalosis hypokalaemic, Hyperglycaemia, Diabetes mellitus inadequate control, Calcium deficiency, Increased appetite

Psychiatric disorders

Uncommon

Psychiatric symptom, Depression, Euphoric mood, Mood swings, Psychotic disorder, Personality change, Insomnia, Drug dependence, Mental disorder, Irritability, Suicidal ideation, Anxiety, Cognitive disorder

Nervous system disorders

Common

Headache

Uncommon

Convulsion, Epilepsy, Syncope, Benign intracranial hypertension, Neuritis, Paraesthesia, Intracranial pressure increased, Dizziness

Eye disorders

Uncommon

Blindness, Cataract, Glaucoma, Exophthalmos, Corneal perforation, Papilloedema

Not known

Vision, blurred (see also section 4.4), central serous chorioretinopathy (see also section 4.4)

Ear and labyrinth disorders

Uncommon

Vertigo

Cardiac disorders

Uncommon

Cardiac failure congestive, Arrhythmia

Vascular disorders

Uncommon

Hypertension, Embolism, Thrombophlebitis, Vasculitis necrotising, Hypotension, Flushing

Gastrointestinal disorders

Uncommon

Peptic ulcer, Peptic ulcer perforation, Peptic ulcer haemorrhage, Pancreatitis, Abdominal distension, Oesophagitis ulcerative, Dyspepsia

Skin and subcutaneous tissue disorders

Uncommon

Urticaria, Rash, Skin hyperpigmentation, Skin hypopigmentation, Skin atrophy, Skin fragility, Petechiae, Ecchymosis, Erythema, Hyperhidrosis, Purpura, Skin striae, Hirsutism, Dermatitis acneiform, Cutaneous lupus erythematosus, Angioedema, Pruritus

Musculoskeletal connective tissue and bone disorders

Common

Arthralgia

Uncommon

Osteoporosis, Osteonecrosis, Pathological fracture, Fracture delayed union, Musculoskeletal discomfort, Muscular weakness, Myopathy, Muscle atrophy, Growth retardation, Neuropathic arthropathy, Myalgia

Renal and urinary disorders

Uncommon

Glycosuria

Reproductive system and breast disorders

Uncommon

Menstrual irregularities, Amenorrhoea and Postmenopausal vaginal bleeding

General disorders and administration site conditions

Common

Injection site reaction

Uncommon

Synovitis, Pain, Injection site irritation, Injection site discomfort, Fatigue, Impaired healing, Hyperthermia

Investigations

Uncommon

Blood potassium decreased, Electrocardiogram change, Carbohydrate tolerance decreased, Nitrogen balance negative, Intraocular pressure increased, Laboratory test interference, Weight decreased, Blood calcium abnormal, Protein total abnormal

Injury and poisoning

Uncommon

Spinal compression fracture

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 the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard

4.9. Overdose

Not applicable.