Intramuscular administration of KENACORT-A (triamcinolone acetonide suspension for injection) is indicated for systemic corticosteroid therapy in such conditions as allergic syndromes (to control serious or debilitating conditions that cannot be treated conventionally), dermatoses, generalized rheumatoid arthritis and other connective tissue disorders. Intramuscular administration is particularly valuable in such conditions when oral corticosteroid therapy is not feasible.

KENACORT-A may also be administered by intraarticular or intrabursal route. These methods of administration enable effective, local, short-term therapy for joint pain, swelling and stiffness resulting from traumatic or rheumatoid arthritis, osteoarthritis, synovitis and bursitis.

For the treatment of generalized arthritic diseases, intraarticular injection of triamcinolone acetonide should be regarded as an aid to other conventional therapeutic measures. Certain disease processes such as traumatic arthritis or bursitis may represent typical indications for therapy carried out exclusively via the intraarticular route.

General

The initial dose of KENACORT-A may vary from 2.5 to 60 mg per day depending on the specific disease being treated.

In less severe cases, lower dosages may be sufficient while higher initial doses may be needed in other patients. Generally, the quantity of medicinal product administered parenterally ranges from one-third to one-half of the dose given orally every 12 hours. Higher dosages may be warranted in cases where the patient’s life may be at risk. The initial dosage should be maintained or adjusted until a satisfactory clinical response is achieved. If this is not achieved after a reasonable period of time, KENACORT-A should be discontinued gradually, and the patient should be treated with another therapy.

THE DOSAGE REGIMEN IS VARIABLE AND MUST BE INDIVIDUALIZED ACCORDING TO THE DISEASE BEING TREATED AND THE PATIENT’S RESPONSE.

It is recommended to use the lowest effective dose for the disease in question.

Once a positive response to therapy has been achieved, the appropriate maintenance dose should be determined by gradually decreasing the initial dose until the lowest dose effective in maintaining the desired therapeutic response has been reached. If the product is to be discontinued after long-term therapy, gradual rather than sudden discontinuation is recommended.

Posology

Systemic administration

Adults and children over 12 years: the recommended initial dose is 60 mg. Inject deeply into the muscles of the gluteal area.

If the injection is not given correctly, subcutaneous fat atrophy may occur.

The dosage is typically adjusted between 40 and 80 mg, depending on patient response and duration of remission. In some patients, however, symptoms can be well controlled with low dosages of 20 mg or less. Patients with seasonal allergy or pollen asthma who do not respond to desensitization therapy and other conventional therapies may obtain a remission of symptoms lasting the entire pollen season with a single injection of 40 100 mg.

Children aged 6 to 12 years: the recommended initial dosage is 40 mg, although the dosage depends more on the severity of symptoms than on age or body weight.

Neonates or premature babies:

This preparation contains benzyl alcohol. Do not use in neonates or premature babies (see section 4.4 and in particular section “USE IN CHILDREN”).

 

Local administration

Intraarticular or intrabursal administration: A single injection of triamcinolone acetonide is often sufficient, but several injections may be necessary to adequately relieve symptoms.

Initial dose: 2.5 to 5 mg for small joints, 5 to 15 mg for larger joints, depending on the type of disease being treated. In adults, doses of up to 10 mg for smaller areas and up to 40 mg for larger areas are usually sufficient. Doses of up to a total of 80 mg have been given via single injections without incident.

 

Method of administration

 

General

The product must be administered under conditions of absolute sterility. Before use, shake the bottle well to ensure that the preparation is evenly suspended and that no agglomerates have formed. Exposure to low temperatures causes agglomeration and the product should not be used if this occurs. After withdrawal, inject immediately to prevent deposits in the syringe. Take all precautions to avoid the risk of infection or the needle penetrating a blood vessel.

Systemic administration

The injection should be made deeply into the gluteal muscle. For adults, a minimum needle length of 4 cm is recommended. A longer needle may be required in obese individuals. Use alternate sites for subsequent injections.

Local administration

In cases of significant intraarticular effusion, it is advisable to perform preventive aspiration of some of the synovial fluid, without emptying it completely. This measure helps to facilitate the remission of symptoms, while avoiding excessive dilution of the steroid injected in situ. Intraarticular administration should then be performed according to the techniques prescribed for injections into the joint cavity.

A local anesthetic may often be appropriate for intraarticular or intrabursal administration of KENACORT-A.

Extreme care must be taken with this type of injection, especially when performed in the deltoid region, to avoid injecting the suspension into the surrounding tissue, as this may lead to tissue atrophy.

Do not use KENACORT-A for intravenous, intradermal, subtendinous, intranasal (turbinates), subconjunctival, retrobulbar or intravitreal (intraocular), epidural or intrathecal injection. See section 4.4 (Special warnings and precautions for use)

Hypersensitivity to the active substance or to any of the excipients (see section 4.4 “Special warnings and precautions for use”). Corticosteroids are contraindicated in patients with systemic infections and in children under two years of age. Intramuscular administration of corticosteroids is contraindicated in the presence of idiopathic thrombocytopenic purpura.

KENACORT-A contains 9.9 mg/mL benzyl alcohol as a preservative. Benzyl alcohol may cause allergic reactions.

Benzyl alcohol has been associated with serious adverse events and death, especially in neonates. “Gasping syndrome” has been associated with benzyl alcohol. Although normal therapeutic doses of this product deliver amounts of benzyl alcohol that are substantially lower than those reported in association with “gasping syndrome”, the minimum amount of benzyl alcohol that may cause toxicity is not known. Premature babies and low-birth-weight neonates, as well as patients receiving high dosages, may be more likely to develop toxicity.

High volumes should be used with caution and only if necessary, especially in subjects with liver or kidney impairment because of the risk of accumulation and toxicity (metabolic acidosis).

Therefore, the product should not be administered to children under two years of age because it contains benzyl alcohol (see also section “USE IN CHILDREN” below).

This is a suspension; do not inject it intravenously.

No studies have been conducted to demonstrate the safety of therapy with KENACORT-A administered by intranasal (turbinates), subconjunctival, subtendinous, retrobulbar or intraocular (intravitreal) route.

Cases of endophthalmitis, ocular inflammation, increased intraocular pressure, chorioretinopathy, including maculopathy due to deposits of crystals of the active substance and viral retinitis/chorioretinitis (mainly by cytomegalovirus) and vision disorders including loss of vision have been reported following intravitreal administration. Several cases of blindness have been reported following injection of corticosteroid suspensions into the nasal turbinates and injection about the head. Administration of KENACORT-A (Triamcinolone Acetonide Suspension for Injection) by any of these routes is not recommended or indicated.

 

Epidural or intrathecal administration of KENACORT-A should not be used. Cases of serious adverse events have been associated with epidural and intrathecal administration.

Cases of severe anaphylactic reactions and anaphylactic shock, including death, have been reported in individuals receiving triamcinolone acetonide injection, regardless of the route of administration.

KENACORT-A is a long-acting preparation and is not recommended in acute conditions.

To avoid drug-induced adrenal insufficiency, a support dose is indicated in stressful situations (trauma, surgery or serious illness), both during treatment with KENACORT-A and in the following year.

 

Visual disturbances

Visual disturbances may be reported with systemic and topical corticosteroid use. If a patient presents with symptoms such as blurred vision or other visual disturbances, they 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.

 

Prolonged use of corticosteroids may result in posterior subcapsular cataract or glaucoma with possible optic nerve damage and increase the likelihood of secondary ocular infections.

Average and high doses of cortisone or hydrocortisone can cause increased blood pressure, salt and water retention and increased excretion of potassium. These effects are less likely with the synthetic derivatives, except when they are used in high doses. A low-salt diet and simultaneous potassium supplementation may be necessary. All corticosteroids increase calcium excretion, which may then be associated with or exacerbate pre-existing osteoporosis.

Corticosteroids may mask some signs of infection, and intercurrent infections may occur during their use. When receiving corticosteroid therapy, defense capabilities may be diminished and it may be difficult to locate a potential site of infection. In addition, individuals receiving immunosuppressant therapy including corticosteroids are more susceptible to infections than those who do not use these medicinal products. Varicella and measles may be more serious or even fatal in patients receiving corticosteroid therapy. Special care should be taken to avoid infection in children or adults being treated with corticosteroids who have not had these illnesses. If this occurs, therapy with varicella-specific immunoglobulin (VZIG) or intravenous pooled immunoglobulin (IVIG) may be indicated. If varicella or herpes zoster develops, therapy with antiviral agents may be considered.

Similarly, corticosteroids should be used with great caution in individuals with Strongyloides (pinworm) infestation because corticosteroid-induced immunosuppression may lead to Strongyloides superinfection with widespread dissemination and larval migration, often accompanied by severe enterocolitis and potentially fatal gram-negative septicemia.

Patients on corticosteroid therapy, especially at high doses, should not be vaccinated or immunized as they are predisposed to clinical complications, especially neurological because of the loss of antibody response.

The use of triamcinolone acetonide in patients with active tuberculosis should be restricted to those cases of fulminating or disseminated tuberculosis in which the corticosteroid is used to treat the infection in conjunction with an appropriate antitubercular therapy. If corticosteroids are administered in patients with latent tuberculosis or tuberculin-positive response, chemoprophylaxis is necessary.

Since there have been rare cases of anaphylactic reactions in patients undergoing parenteral therapy with corticosteroids, appropriate precautions should be taken before administration, especially when the patient has a history of drug allergies.

It is recommended that intramuscular injection be administered deeply, as local atrophy may occur. The gluteal region is preferred over the deltoid, as a higher incidence of local atrophy occurs in the deltoid region.

 

A state of secondary adrenal insufficiency may occur following corticosteroid treatment and may persist for months after treatment is discontinued. Therefore, in any stressful situation (such as trauma, surgery or serious illness) that occurs during this period, hormone therapy should be resumed. Sodium chloride and/or mineralocorticoids should be administered concomitantly because mineralocorticoid secretion may be impaired.

In patients with hypothyroidism or hepatic cirrhosis, response to corticosteroids may increase. Caution is advised in patients with ocular herpes simplex because corneal perforation is possible.

Various psychiatric disorders may occur with corticosteroid therapy: euphoria, insomnia, mood and personality changes, severe depression or frank psychosis. Pre-existing emotional instability or psychotic tendencies may be aggravated by corticosteroids. The use of antidepressants does not alleviate these disorders and may exacerbate mental disorders induced by corticosteroid therapy.

Corticosteroids should be administered with caution in the following cases: non-specific ulcerative colitis with risk of perforation, pyogenic infections and abscesses in general, diverticulitis, recent intestinal anastomosis, active or latent peptic ulcer, renal failure, acute glomerulonephritis, chronic nephritis, hypertension, congestive cardiac failure, thrombophlebitis, thromboembolic episodes, osteoporosis, exanthem, Cushing’s syndrome, diabetes mellitus, seizure disorders, metastatic carcinoma, myasthenia gravis.

Although KENACORT-A may improve inflammation symptoms, the cause must be investigated and treated.

Intraarticular administration of a corticosteroid may produce systemic and local effects. Accidental injection of the suspension into periarticular soft tissues may also cause systemic effects and is the most frequent cause of local treatment failure. Patients undergoing intraarticular treatment should not exert excessive strain on the joints in which improvement in symptoms has been achieved, otherwise increased deterioration of the joint may occur.

During intraarticular administration, overdistension of the joint capsule and effusion of the steroid along the needle should be avoided, since subcutaneous atrophy may occur.

Avoid injecting the preparation into unstable joints. Repeated intraarticular injections may in some cases result in instability of the joint. In some cases, particularly after repeated administrations, it is advisable to perform an X-ray examination.

Intraarticular injection rarely causes joint discomfort. An increase in pain accompanied by local swelling, further restriction of joint motion, fever and malaise is suggestive of septic arthritis. If confirmed, discontinue corticosteroid administration and immediately start appropriate antibacterial therapy and continue for 7 to 10 days after all signs of infection have disappeared.

Avoid intraarticular injection into joints that have been the site of infectious processes.

Edema may occur in the presence of renal dysfunction with a reduced glomerular filtration rate. During prolonged therapy, good protein intake is essential to counteract the tendency toward the gradual decrease in weight sometimes associated with negative nitrogen balance, weight loss and skeletal muscle weakness.

 

Menstrual irregularities may occur and vaginal bleeding has been observed in postmenopausal women. Female patients should be made aware of the risk but appropriate investigations should still be recommended.

 

In peptic ulcer, recurrence may remain asymptomatic until the moment of perforation or hemorrhage.

Prolonged adrenocortical therapy may cause hyperacidity or peptic ulcer; administration of an antacid is therefore recommended.

It is essential that patients be monitored even after discontinuation of triamcinolone acetonide therapy because there may be a sudden recurrence of the main symptoms of the disease for which the patient was being treated.

 

KENACORT-A contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially “sodium‑free”.

 

Use in Children

Exposure to excessive amounts of benzyl alcohol has been associated with toxicity (hypotension, metabolic acidosis), particularly in neonates, and an increased incidence of nuclear jaundice, particularly in small premature babies. There have been rare reports of deaths, primarily in premature babies, associated with exposure to excessive amounts of benzyl alcohol.

KENACORT-A is not recommended in children under six years old.

The growth and development of children on prolonged corticosteroid therapy should be closely monitored because corticosteroids may suppress growth. Caution should be used in case of exposure to varicella, measles or other infectious diseases.

Children should not be vaccinated or immunized during corticosteroid therapy. Corticosteroids may affect endogenous steroid production.

 

Use in the elderly

Side effects such as osteoporosis or hypertension, which are common in systemic corticosteroid therapy, may have more serious consequences in elderly individuals.

Close clinical monitoring is therefore recommended.

Amphotericin B injection and potassium-depleting agents: Individuals taking these agents should be monitored for possible hypokalemia.

Anticholinesterases: Antagonism reactions may occur with these agents.

Oral anticoagulants: Corticosteroids may increase or decrease anticoagulant action. Therefore, individuals taking oral anticoagulants and corticosteroids should be closely monitored.

Antidiabetics: Corticosteroids may increase blood glucose; diabetic individuals should be closely monitored, especially when corticosteroids are initiated or discontinued or the dosage is modified.

Antitubercular medications: Isoniazid serum concentrations may be decreased.

Cyclosporine: Increased activity of both corticosteroids and cyclosporine has been noted when taken concurrently.

Digitalis glycosides: There may be a possible increase in the toxicity of digitalis when administered concomitantly with corticosteroids.

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

Hepatic enzyme inducers (e.g., barbiturates, phenytoin, carbamazepine, rifampin): Increased metabolic clearance of KENACORT-A has been noted. Individuals taking these therapies should be monitored closely for possible diminished efficacy of the steroid and the dosage of corticosteroids should be adjusted accordingly.

Cytochrome P450 3A4 inhibitors: Triamcinolone acetonide is a substrate of cytochrome P450 3A4. Therefore, caution should be exercised when administering KENACORT-A together with potent cytochrome P450 3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, ketoconazole, telithromycin), because an increase in systemic corticosteroid adverse events may occur (see section 4.8).

During postmarketing use, clinically important interactions were reported in patients taking triamcinolone acetonide and ritonavir, resulting in systemic corticosteroid effects such as Cushing’s Syndrome and adrenal suppression (see sections 4.4, 4.6 and 4.9).

Human growth hormone (e.g. somatrem): The growth-promoting effect may be inhibited.

Nondepolarizing muscle relaxants: Corticosteroids may decrease or increase the neuromuscular blocking action.

Nonsteroidal anti-inflammatory drugs (NSAIDs): Corticosteroids may increase the incidence and/or severity of gastrointestinal bleeding and ulceration caused by NSAIDs. Also, corticosteroids may reduce serum salicylate levels and therefore decrease their efficacy. Conversely, discontinuing corticosteroids during high-dose salicylate therapy may result in salicylate toxicity.

Aspirin should be administered with caution in conjunction with corticosteroids in individuals with hypoprothrombinemia.

Thyroid medications: Metabolic clearance of adrenocorticoids is decreased in hypothyroid individuals and increased in hyperthyroid individuals. Changes in the thyroid status of the patient may require adjustment of adrenocorticoid dosage.

Vaccines: Individuals receiving corticosteroid therapy who are vaccinated may experience neurological complications and loss of antibody response.

Many corticosteroids used at low doses have been shown to have teratogenic effects in laboratory animals. Because adequate reproductive studies in humans have not been conducted, the use of corticosteroids during pregnancy, breast-feeding or in childbearing age should be evaluated in light of the possible benefit versus the potential risk to the mother, embryo, fetus or breast-feeding infant. Newborns born to mothers who received substantial doses of corticosteroids during pregnancy should be closely monitored for any signs of hypoadrenalism.

 

Studies on the ability to drive and use machines have not been performed. However, given the possible occurrence of undesirable effects on the central nervous system (e.g., vertigo), patients should be informed of this possibility.

Table 1 shows the adverse reactions listed by system organ class, according to MedDRA terminology, and by frequency.

The frequencies are defined as: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1 000 to < 1/100); rare (≥ 1/10 000 to < 1/1 000); very rare (< 1/10 000); not known (cannot be estimated from the available data).

Table 1: Adverse reactions during treatment with KENACORT-A, according to MedDRA classification by systems and organs

To reports any side effect(s):

Chronic: The symptoms of glucocorticoid overdose may include confusion, anxiety, depression, gastrointestinal cramping or bleeding, ecchymosis, Cushingoid facies and hypertension. Sudden discontinuation after long-term therapy may result in acute adrenal insufficiency. The latter may also occur in cases of stress. Cushingoid changes can result from continued use of high doses.

Acute: There is no specific treatment for acute corticosteroid overdose; therefore, supportive therapy should be instituted and, if gastrointestinal bleeding occurs, action should be taken as in the case of peptic ulcer.

Pharmacotherapeutic group: corticosteroids for systemic use, ATC code: H02AB08.

KENACORT-A is a synthetic glucocorticoid corticosteroid with marked anti-inflammatory action, in sterile aqueous suspension for intramuscular, intraarticular and intrabursal injection. Do not use this formulation for intravenous, intradermal, subtendinous, intranasal (turbinates), subconjunctival, retrobulbar or intravitreal (intraocular), epidural or intrathecal injection.

KENACORT-A has a long duration of action that can be permanent or extended over a period of several weeks.

Glucocorticoids of natural origin (hydrocortisone), which also cause sodium retention, are used as replacement therapy in states of adrenocortical insufficiency. Synthetic analogs, such as triamcinolone, are used primarily for their potent anti-inflammatory effects in a variety of diseases.

Clinical studies have shown that after a single dose of 60 to 100 mg of triamcinolone acetonide, suppression of adrenal activity occurs between 24 and 48 hours and then returns to normal values, generally in 30 to 40 days. These results are closely related to the prolonged therapeutic action achieved with this product.

Triamcinolone acetonide is absorbed slowly but completely, following administration by deep intramuscular injection. Therapeutic levels of the product are ensured consistently over a long period (weeks to months). As with other corticosteroids, triamcinolone is largely metabolized by the liver as well as the kidneys, and is excreted in urine. The main metabolic pathway is hydroxylation.

Hepatic or renal dysfunction may affect the pharmacokinetics of the drug.

Clinically significant systemic levels of the product following intraarticular administration are unlikely to occur, except for large joints treated with high doses. Systemic effects are not usually observed with the use of appropriate doses and methods of intraarticular administration.

 

The preclinical safety of the product as observed at the time of marketing authorization has been largely surpassed by more than 30 years of clinical use and postmarketing pharmacovigilance.

Sodium carboxymethyl cellulose, sodium chloride, polysorbate 80, benzyl alcohol, water for injections, hydrochloric acid/sodium hydroxide (pH adjusters).

See section 4.4.

3 years.

Store below 30^oC. Do not freeze or refrigerate. Protect from light. Store vials upright.

1 mL suspension for injection in a vial with a cap (chlorobutyl rubber) and a seal (aluminum) in packs containing 3 vials.

See section 4.2.