Triesence

TRIESENCE® (triamcinolone acetonide) Injectable Suspension 40 mg/mL is a synthetic corticosteroid with anti-inflammatory action. Each mL of the sterile, aqueous suspension provides 40 mg of triamcinolone acetonide, with sodium chloride for isotonicity, 0.5% (w/v) carboxymethylcellulose sodium and 0.015% polysorbate 80. It also contains potassium chloride, calcium chloride (dihydrate), magnesium chloride (hexahydrate), sodium acetate (trihydrate), sodium citrate (dihydrate) and water for injection. Sodium hydroxide and hydrochloric acid may be present to adjust pH to a target value 6 - 7.5.

The chemical name for triamcinolone acetonide is 9-Fluro- 11β, 16α, 17,21-tetrahydroxypregna-1,4-diene-3,20-dione cyclic 16,17- acetal with acetone. Its structural formula of C24H31FO6 is:

434.50 MW

Triamcinolone acetonide occurs as a white to cream-colored, crystalline powder having not more than a slight odor and is practically insoluble in water and very soluble in alcohol.

Mechanism of Action

Naturally occurring glucocorticoids (hydrocortisone and cortisone), which also have salt-retaining properties, are used as replacement therapy in adrenocortical deficiency states. Their synthetic analogs such as prednisolone and triamcinolone are primarily used for their anti-inflammatory effects in disorders of many organ systems. Triamcinolone acetonide possesses glucocorticoid activity typical of this class of drug, but with little or no mineralocorticoid activity. For the purposes of comparison, the following is the equivalent milligram dosage of the various glucocorticoids:

Corticosteroids have been demonstrated to depress the production of eosinophils and lymphocytes, but erythropoiesis and production of polymorphonuclear leukocytes are stimulated. Inflammatory processes (edema, fibrin deposition, capillary dilatation, migration of leukocytes and phagocytosis) and the later stages of wound healing (capillary proliferation, deposition of collagen, cicatrization) are inhibited.

Pharmacokinetics

Aqueous humor pharmacokinetics of triamcinolone have been assessed in 5 patients following a single intravitreal administration (4 mg) of triamcinolone acetonide. Aqueous humor samples were obtained from 5 patients (5 eyes) via an anterior chamber paracentesis on Days 1, 3, 10, 17 and 31 post injection. Peak aqueous humor concentrations of triamcinolone ranged from 2151 to 7202 ng/mL, half-life 76 to 635 hours, and the area under the concentration-time curve (AUC0-t) from 231 to 1911 ng.h/mL following the single intravitreal administration. The mean elimination half-life was 18.7 ± 5.7 days in 4 nonvitrectomized eyes (4 patients). In a patient who had undergone vitrectomy (1 eye), the elimination half-life of triamcinolone from the vitreous was much faster (3.2 days) relative to patients that had not undergone vitrectomy.

Animal Toxicology and/or Pharmacology

Studies were conducted with triamcinolone acetonide, including those employing the proposed dosage form, i.e., 4.0% triamcinolone acetonide injectable suspension formulation containing 0.5% carboxymethylcellulose and 0.015% polysorbate-80 in a balanced salt solution.

Triamcinolone acetonide was demonstrated to be non-inflammatory when injected intravitreally in NZW rabbits, non-cytotoxic to mouse L-929 cells in an in-vitro assay and non-sensitizing in a guinea-pig maximization assay. Furthermore, the results of single-dose intravitreal injection studies with triamcinolone acetonide in both rabbits and monkeys demonstrate that the drug is well tolerated for up to one month with only minor findings of slight decrease in body weight gain and slight corneal thinning.

You should not receive this medication if you are allergic to triamcinolone, or if you have a condition called idiopathic thrombocytopenic purpura (ITP).

If you have any of these other conditions, you may need a dose adjustment or special tests:

• any type of bacterial, fungal, or viral infection (including tuberculosis);
• a thyroid disorder;
• a muscle disorder such as myasthenia gravis;
• diverticulitis, stomach or intestinal ulcer, or recent stomach surgery; or
• if you have recently had a heart attack.

FDA pregnancy category C. It is not known whether triamcinolone injection will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication.

Triamcinolone can pass into breast milk and may harm a nursing baby. You should not breast-feed while you are using triamcinolone injection.

This medication can decrease bone formation, which could lead to osteoporosis, especially with long-term use. Talk with your doctor about your specific risk of bone loss while receiving triamcinolone injection.

Steroids can affect growth in children. Talk with your doctor if you think your child is not growing at a normal rate while using this medication.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Adverse event data were collected from 300 published articles containing data from controlled and uncontrolled clinical trials which evaluated over 14,000 eyes treated with different concentrations of triamcinolone acetonide.

The most common dose administered within these trials was triamcinolone acetonide 4 mg administered as primary or adjunctive therapy primarily as a single injection. The most common reported adverse events following administration of triamcinolone acetonide were elevated intraocular pressure and cataract progression. These events have been reported to occur in 20-60% of patients.

Less common reactions occurring in up to 2% include endophthalmitis (infectious and non-infectious), hypopyon, injection site reactions (described as blurring and transient discomfort), glaucoma, vitreous floaters, and detachment of retinal pigment epithelium, optic disc vascular disorder, eye inflammation, conjunctival hemorrhage and visual acuity reduced. Cases of exophthalmos have also been reported.

Common adverse reactions for systemically administered corticosteroids include fluid retention, alteration in glucose tolerance, elevation in blood pressure, behavioral and mood changes, increased appetite and weight gain.

Other reactions reported to have occurred with the administration of corticosteroids include:

Allergic Reactions: Anaphylactoid reaction, anaphylaxis, angioedema

Cardiovascular: Bradycardia, cardiac arrest, cardiac arrhythmias, cardiac enlargement, circulatory collapse, congestive heart failure, fat embolism, hypertrophic cardiomyopathy in premature infants, myocardial rupture following recent myocardial infarction, pulmonary edema, syncope, tachycardia, thromboembolism, thrombophlebitis, vasculitis

Dermatologic: Acne, allergic dermatitis, cutaneous and subcutaneous atrophy, dry scalp, edema, facial erythema, hyper or hypo-pigmentation, impaired wound healing, increased sweating, petechiae and ecchymoses, rash, sterile abscess, striae, suppressed reactions to skin tests, thin fragile skin, thinning scalp hair, urticaria

Endocrine: Abnormal fat deposits, decreased carbohydrate tolerance, development of Cushingoid state, hirsutism, manifestations of latent diabetes mellitus and increased requirements for insulin or oral hypoglycemic agents in diabetics, menstrual irregularities, moon facies, secondary adrenocortical and pituitary unresponsiveness (particularly in times of stress, as in trauma, surgery or illness), suppression of growth in children

Fluid and Electrolyte Disturbances: Potassium loss, hypokalemic alkalosis, sodium retention

Gastrointestinal: Abdominal distention, elevation in serum liver enzymes levels (usually reversible upon discontinuation), hepatomegaly, hiccups, malaise, nausea, pancreatitis, peptic ulcer with possible perforation and hemorrhage, ulcerative esophagitis

Metabolic: Negative nitrogen balance due to protein catabolism

Musculoskeletal: Aseptic necrosis of femoral and humeral heads, charcot-like arthropathy, loss of muscle mass, muscle weakness, osteoporosis, pathologic fracture of long bones, steroid myopathy, tendon rupture, vertebral compression fractures

Neurological: Arachnoiditis, convulsions, depression, emotional instability, euphoria, headache, increased intracranial pressure with papilledema (pseudo-tumor cerebri) usually following discontinuation of treatment, insomnia, meningitis, neuritis, neuropathy, paraparesis/paraplegia, paresthesia, sensory disturbances, vertigo

Reproductive: Alteration in motility and number of spermatozoa.

Read the entire FDA prescribing information for Triesence (Triamcinolone Acetonide Injectable Suspension)

Triesence is part of the drug classes:

• Corticosteroids for local oral treatment

• Corticosteroids, moderately potent group II

• Corticosteroids, moderately potent, other combinations

• Antiinflammatory Corticosteroids

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

• Aminoglutethimide (Cytadren)
• Amphotericin B (Fungizone, Abelcet, AmBisome, Amphotec)
• Antibiotics
• Anticholinesterase agents such as donepezil (Aricept), rivastigmine (Exelon), and galantamine (Ryzadyne)
• Anticoagulants such as warfarin (Coumadin)
• Antidiabetic agents
• Isoniazid
• Cholestyramine
• Cyclosporine (Neoral, Sandimmune)
• Digoxin (Lanoxin)
• Estrogens, including oral contraceptives
• Phenytoin (Dilantin)
• Carbamazepine (Tegretol)
• Rifampin (Rifadin)
• Ketoconazole (Nizoral)
• Non-steroidal anti-inflammatory agents such as aspirin, ibuprofen (Motrin), naproxen (Aleve), and celecoxib (Celebrex)

This is not a complete list of triamcinolone drug interactions. Ask your doctor or pharmacist for more information.

Serious side effects have been reported with topical triamcinolone including the following:

• Burning, drying and itching of the skin
• Convulsions
• Depression
• Increased blood pressure
• Muscle weakness
• Nervousness
• Psychosis
• Sleepiness
• Changes in menstrual cycle
• Swelling in lower extremities
• Water retention
• Worsening of diabetes or ulcers

Serious side effects have been reported with injectable triamcinolone including the following:

• Stomach upset
• Muscle weakness or atrophy
• Adrenal insufficiency
• Increased blood pressure
• Water and salt retention
• Increased susceptibility to infection

Glaucoma, cataracts, optic nerve damage, and ocular infections have been reported with the ophthalmic injections of triamcinolone.

Triamcinolone can cause dizziness. Do not drive or operate heavy machinery until you know how triamcinolone affects you.

Do not take triamcinolone if you are allergic to triamcinolone or to any of its ingredients.

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• Use care when driving or doing other tasks that call for clear eyesight.
• This medicine may affect certain lab tests. Tell all of your health care providers and lab workers that you take Triesence.
• This medicine may raise the chance of cataracts or glaucoma. Talk with the doctor.
• Have your eye pressure checked if you are on this medicine for a long time. Talk with your doctor.
• This medicine may cause weak bones (osteoporosis) with long-term use. Talk with your doctor to see if you have a higher chance of weak bones or if you have any questions.
• Have a bone density test as you have been told by your doctor. Talk with your doctor.
• You may have more chance of getting an infection. Wash hands often. Stay away from people with infections, colds, or flu.
• Chickenpox and measles can be very bad or even deadly in some people taking steroid drugs like Triesence. Avoid being near anyone with chickenpox or measles if you have not had these health problems before. If you have been exposed to chickenpox or measles, talk with your doctor.
• Talk with your doctor before getting any vaccines. Use with this medicine may either raise the chance of an infection or make the vaccine not work as well.
• If you are 65 or older, use Triesence with care. You could have more side effects.
• This medicine may affect growth in children and teens in some cases. They may need regular growth checks. Talk with the doctor.
• This medicine may cause harm to the unborn baby if you take it while you are pregnant. If you are pregnant or you get pregnant while taking this medicine, call your doctor right away.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

• Amphotericin B: There have been cases reported in which concomitant use of Amphotericin B and hydrocortisone was followed by cardiac enlargement and congestive heart failure. See Potassium depleting agents.

• Anticholinesterase agents: Concomitant use of anticholinesterase agents and corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, anticholinesterase agents should be withdrawn at least 24 hours before initiating corticosteroid therapy.

• Anticoagulant agents: Co-administration of corticosteroids and warfarin usually results in inhibition of response to warfarin, although there have been some conflicting reports. Therefore, coagulation indices should be monitored frequently to maintain the desired anticoagulant effect.

• Antidiabetic agents: Because corticosteroids may increase blood glucose concentrations, dosage adjustments of antidiabetic agents may be required.

• Antitubercular drugs: Serum concentrations of isoniazid may be decreased.

• CYP 3A4 inducers (e.g., barbiturates, phenytoin, carbamazepine, and rifampin): Drugs such as barbiturates, phenytoin, ephedrine, and rifampin, which induce hepatic microsomal drug metabolizing enzyme activity may enhance metabolism of corticosteroid and require that the dosage of corticosteroid be increased.

• CYP 3A4 inhibitors (e.g., ketoconazole, macrolide antibiotics): Ketoconazole has been reported to decrease the metabolism of certain corticosteroids by up to 60% leading to an increased risk of corticosteroid side effects.

• Cholestyramine: Cholestyramine may increase the clearance of corticosteroids.

• Cyclosporine: Increased activity of both cyclosporine and corticosteroids may occur when the two are used concurrently. Convulsions have been reported with concurrent use.

• Digitalis: Patients on digitalis glycosides may be at increased risk of arrhythmias due to hypokalemia.

• Estrogens, including oral contraceptives: Estrogens may decrease the hepatic metabolism of certain corticosteroids thereby increasing their effect.

• NSAIDS including aspirin and salicylates: Concomitant use of aspirin or other non-steroidal antiinflammatory agents and corticosteroids increases the risk of gastrointestinal side effects. Aspirin should be used cautiously in conjunction with corticosteroids in hypoprothrombinemia. The clearance of salicylates may be increased with concurrent use of corticosteroids.

• Potassium depleting agents (e.g., diuretics, Amphotericin B): When corticosteroids are administered concomitantly with potassium-depleting agents, patients should be observed closely for development of hypokalemia.

• Skin tests: Corticosteroids may suppress reactions to skin tests.

• Toxoids and live or inactivated vaccines: Due to inhibition of antibody response, patients on prolonged corticosteroid therapy may exhibit a diminished response to toxoids and live or inactivated vaccines. Corticosteroids may also potentiate the replication of some organisms contained in live attenuated vaccines.

Triesence® (triamcinolone acetonide injectable suspension) 40 mg/mL is a synthetic corticosteroid with anti-inflammatory action. Each mL of the sterile, aqueous suspension provides 40 mg of triamcinolone acetonide, with sodium chloride for isotonicity, 0.5% (w/v) carboxymethylcellulose sodium and 0.015% polysorbate 80. It also contains potassium chloride, calcium chloride (dihydrate), magnesium chloride (hexahydrate), sodium acetate (trihydrate), sodium citrate (dihydrate) and water for injection. Sodium hydroxide and hydrochloric acid may be present to adjust pH to a target value 6 - 7.5.

The chemical name for triamcinolone acetonide is 9-Fluro- 11β, 16α, 17,21-tetrahydroxypregna-1,4-diene-3,20-dione cyclic 16,17- acetal with acetone. Its structural formula of C24H31FO6 is:

434.50 MW

Triamcinolone acetonide occurs as a white to cream-colored, crystalline powder having not more than a slight odor and is practically insoluble in water and very soluble in alcohol.