1. Name Of The Medicinal Product
Kenalog Intra-articular / Intramuscular Injection
2. Qualitative And Quantitative Composition
Kenalog Intra-articular / Intramuscular Injection contains triamcinolone acetonide 40mg 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.
Intramuscular use: Where sustained systemic corticosteroid treatment is required: Allergic states, e.g. bronchial asthma, seasonal or perennial allergic rhinitis. In seasonal allergies, patients who do not respond to conventional therapy may achieve a remission of symptoms over the entire period with a single intramuscular injection (see Dosage); Endocrine disorders, e.g. primary or secondary adrenocortical insufficiency. Collagen disorders, e.g. during an exacerbation of maintenance therapy of selected cases of SLE or acute rheumatic carditis; Dermatological diseases, e.g. pemphigus, severe dermatitis and Stevens Johnson Syndrome; Rheumatic, Gastrointestinal or Respiratory disorders - as an adjunctive, short-term therapy; Haematological disorders, e.g. acquired (autoimmune) haemolytic anaemia; Neoplastic diseases, e.g. palliative management of leukaemia and lymphomas; Renal disease, such as acute interstitial nephritis, minimal change nephrotic syndrome or lupus nephritis.
4.2 Posology And Method Of Administration
Kenalog is for Intra-articular/Intramuscular 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.
Intra-Articular Injection: For intra-articular administration or injection into tendon sheaths and bursae, the dose of Kenalog Injection may vary from 5mg to 10mg (0.125 - 0.25ml) for smaller joints and up to 40mg (1.0ml) for larger joints, depending on the specific disease entity being treated. Single injections into several sites for multiple joint involvement, up to a total of 80mg, have been given without undue reactions.
It is recommended that, when injections are given into the sheaths of short tendons, Adcortyl Injection (triamcinolone acetonide 10mg/ml) should be used. (See under Precautions, re Achilles tendon).
Intramuscular Injection: To avoid the danger of subcutaneous fat atrophy, it is important to ensure that deep intramuscular injection is given into the gluteal site. The deltoid should not be used. Alternate sides should be used for subsequent injections.
Adults and Children over 12 Years: The suggested initial dose is 40mg (1.0ml) injected deeply into the upper, outer quadrant of the gluteal muscle. Subsequent dosage depends on the patient's response and period of relief. Patients with hay fever or pollen asthma who do not respond to conventional therapy may obtain a remission of symptoms lasting throughout the pollen season after a single dose of 40-100mg given when allergic symptoms appear. (See Warnings and Precautions.)
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, susceptibility to infection and thinning of the skin. Close clinical supervision is required to avoid life-threatening reactions.
Children from 6-12 Years of Age: The suggested initial dose of 40mg (1.0ml injected deeply into the gluteal muscle should be scaled according to the severity of symptoms and the age and weight of the child. Kenalog is not recommended for children under six years. Growth and development of children on prolonged corticosteroid therapy should be carefully observed. (See Warnings and Precautions.)
Triamcinolone withdrawal: In patients who have received more than physiological doses of Kenalog (more than one injection during a three week period), withdrawal should not be abrupt. The dose should be reduced and the dosage interval increased until a dose of not more than 40mg and a dosage interval of at least three weeks have been achieved as the dose of systemic corticosteroid is reduced. Clinical assessment of disease activity may be needed.
Abrupt withdrawal of short term systemic corticosteroid treatment is appropriate if it is considered that the disease is unlikely to relapse. A single dose, which is not repeated within a three week period, is unlikely to lead to clinically relevant hpa-axis suppression in the majority of patients. However, in the following patient groups, gradual withdrawal of systemic corticosteroid therapy should always be considered:
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4.3 Contraindications
Hypersensitivity to any of the ingredients.
Systemic infections unless specific anti-infective therapy is employed.
Administration by intravenous or intrathecal injection.
4.4 Special Warnings And Precautions For Use
Warnings
(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.
Due to the absence of a true tendon sheath, the Achilles tendon should not be injected with depot corticosteroids.
(Intramuscular Injection):
During prolonged therapy a liberal protein intake is essential to counteract the tendency to gradual weight loss sometimes associated with negative nitrogen balance and wasting of skeletal muscle.
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 is of particular concern since this normally minor illness may be fatal in immunosuppressed patients. Patients (or parents of children receiving Kenalog Injection) without a definite history of chickenpox should be advised to avoid close personal contact with chickenpox or herpes zoster. 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.
During corticosteroid therapy antibody response will be reduced and therefore affect the patient's response to vaccines. Live vaccines should not be administered.
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.
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.
Use in Children:
Kenalog is not recommended for children under six years. Corticosteroids cause dose-related growth retardation in infancy, childhood and adolescence which may be irreversible, therefore growth and development of children on prolonged corticosteroid therapy should be carefully observed.
Use in 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
Barbiturates, phenytoin, rifampicin, rifabutin, carbamazepine, primidone and aminoglutethimide may enhance the metabolic clearance of corticosteroids, resulting in decreased therapeutic effects.
Corticosteroids antagonise the effects of hypoglycaemic agents (including insulin), anti-hypertensives and diuretics. 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.
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 injection 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.
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
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, syncopal episodes and anaphylactoid reactions, particularly where there is a history of drug allergies.
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. Pain and other local symptoms may continue for a short time before effective relief is obtained, but an increase in joint discomfort has seldom occurred. 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.
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.
Intra-Articular Injection: Following local injection, relief of pain and swelling and greater freedom of movement are usually obtained within a few hours.
Intramuscular Injection: Provides an extended duration of therapeutic effect and fewer side effects of the kind associated with oral corticosteroid therapy, particularly gastro-intestinal reactions such as peptic ulceration. Studies indicate that, following a single intramuscular dose of 80mg triamcinolone acetonide, adrenal suppression occurs within 24 - 48 hours and then gradually returns to normal, usually in approximately three weeks. This finding correlates closely with the extended duration of therapeutic action of triamcinolone acetonide.
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.
Triamcinolone acetonide is absorbed slowly, though almost completely, following depot administration by deep intramuscular injection; biologically active levels are achieved systemically for prolonged periods (weeks to months). 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.
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 below 25°C: avoid freezing.
6.5 Nature And Contents Of Container
Carton containing 5 x 1ml glass vials or individually cartoned 1ml and 2ml syringes.
6.6 Special Precautions For Disposal And Other Handling
No special handling instructions.
7. Marketing Authorisation Holder
E.R. Squibb & Sons Ltd.
BMS House
141-149 Staines Road
Hounslow
Middlesex TW3 3JA
8. Marketing Authorisation Number(S)
PL 0034/5045R
9. Date Of First Authorisation/Renewal Of The Authorisation
July 1986
10. Date Of Revision Of The Text
March 1999
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