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DRUGS & SUPPLEMENTS
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Ledercort
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Ledercort uses
Ledercort consists of Triamcinolone, Triamcinolone Acetonide.Triamcinolone:
- Indications and usage
- Dosage and administration
- Dosage forms and strengths
- Contraindications
- Warnings and precautions
- Adverse reactions
- Drug interactions
- Use in specific populations
- Description
- Clinical pharmacology
- Nonclinical toxicology
- Clinical studies
- How supplied/storage and handling
- Patient counseling information
1 INDICATIONS AND USAGE
Ledercort (Triamcinolone) (triamcinolone acetonide extended-release injectable suspension) is indicated as an intra-articular injection for the management of osteoarthritis pain of the knee.
Ledercort (Triamcinolone) is an extended-release synthetic corticosteroid indicated as an intra-articular injection for the management of osteoarthritis pain of the knee. ( 1)
Limitation of Use
Ledercort (Triamcinolone) is not intended for repeat administration. ( 1)
Limitation of Use
Ledercort (Triamcinolone) is not intended for repeat administration .
2 DOSAGE AND ADMINISTRATION
- 32 mg administered as a single intra-articular injection in the knee.
- See Instructions for Use (IFU) for instructions on reconstitution of Ledercort (Triamcinolone) with the supplied diluent. ( 2.2)
- It is normal for some residue to be left behind on the vial walls after withdrawing the suspension. ( 2.2)
- Not interchangeable with other formulations of injectable Ledercort (Triamcinolone) acetonide. ( 2.3)
2.1 Important Dosage and Administration Information
- Ledercort (Triamcinolone) is administered as a single intra-articular extended-release injection of Ledercort (Triamcinolone) acetonide, to deliver 32 mg (5 mL).
- Ledercort (Triamcinolone) is for intra-articular use only and should not be administered by the following routes: epidural, intrathecal, intravenous, intraocular, intramuscular, intradermal, subcutaneous.
- Ledercort (Triamcinolone) is not suitable for use in small joints, such as the hand.
- The efficacy and safety of repeat administration of Ledercort (Triamcinolone) for the management of osteoarthritis pain of the knee have not been evaluated.
- The efficacy and safety of Ledercort (Triamcinolone) for management of osteoarthritis pain of shoulder and hip have not been evaluated.
2.2 Preparation and Administration of Intra-Articular Suspension
Refer to the Instructions for Use for directions on the preparation and administration of Ledercort.
Ledercort (Triamcinolone) is supplied as a single-dose kit containing a vial of Ledercort (Triamcinolone) microsphere powder, a vial of sterile diluent, and a sterile vial adapter.
Ledercort (Triamcinolone) must be prepared using the diluent supplied in the kit.
Preparation of Ledercort (Triamcinolone) requires close attention to the Instructions for Use to ensure successful administration.
Use proper aseptic technique throughout the dose preparation and administration procedure.
Ledercort (Triamcinolone) is a suspension product and it is normal for some residue to be left behind on the vial walls after withdrawing the contents.
Promptly inject Ledercort (Triamcinolone) after preparation to avoid settling of the suspension. If needed, the Ledercort (Triamcinolone) suspension can be stored in the vial for up to 4 hours at ambient conditions. Gently swirl the vial to resuspend any of the settled microspheres prior to preparing the syringe for injection.
The usual technique for intra-articular injection should be followed. Aspiration of synovial fluid may be performed based on clinical judgment prior to administration of Ledercort (Triamcinolone).
2.3 Non-Interchangeability with Other Formulations of Ledercort (Triamcinolone) Acetonide for Intra-articular Use
Ledercort (Triamcinolone) is not interchangeable with other formulations of injectable Ledercort (Triamcinolone) acetonide.
3 DOSAGE FORMS AND STRENGTHS
Ledercort (Triamcinolone) is an injectable suspension that delivers 32 mg of Ledercort (Triamcinolone) acetonide. Ledercort (Triamcinolone) is supplied as a single-dose kit, containing:
- One vial of Ledercort (Triamcinolone) white to off-white microsphere powder
- One vial of 5 mL sterile, clear diluent
- One sterile vial adapter
Ledercort (Triamcinolone) is an injectable suspension that delivers 32 mg of Ledercort (Triamcinolone) acetonide. It is supplied as a single-dose kit containing one vial of Ledercort (Triamcinolone) microsphere powder, one vial of 5 mL diluent, and one sterile vial adapter. ( 3)
4 CONTRAINDICATIONS
Ledercort (Triamcinolone) is contraindicated in patients who are hypersensitive to Ledercort (Triamcinolone) acetonide, corticosteroids or any components of the product .
Patients with hypersensitivity to Ledercort (Triamcinolone) acetonide or any component of the product. ( 4)
5 WARNINGS AND PRECAUTIONS
- Intra-articular Use Only: Do not administer Ledercort by epidural, intrathecal, intravenous, intraocular, intramuscular, intradermal, or subcutaneous routes. ( 5.1)
- Serious Neurologic Adverse Reactions with Epidural and Intrathecal Administration: Serious neurologic events have been reported following epidural or intrathecal corticosteroid administration. Corticosteroids are not approved for this use. ( 5.2)
- Hypersensitivity Reactions: Serious reactions have been reported with Ledercort (Triamcinolone) acetonide injection. Institute appropriate care upon occurrence of an anaphylactic reaction. ( 5.3)
- Joint Infection and Damage: May cause joint pain accompanied by joint swelling. If this occurs, conduct appropriate evaluation to exclude septic arthritis and institute appropriate antimicrobial therapy if septic arthritis is confirmed. ( 5.4)
5.1 Warnings and Precautions Specific for Ledercort (Triamcinolone)
Ledercort (Triamcinolone) has not been evaluated and should not be administered by the following routes:
- Epidural
- Intrathecal
- Intravenous
- Intraocular
- Intramuscular
- Intradermal
- Subcutaneous
.
5.2 Serious Neurologic Adverse Reactions with Epidural and Intrathecal Administration
Serious neurologic events, some resulting in death, have been reported with epidural injection of corticosteroids. Specific events reported include, but are not limited to, spinal cord infarction, paraplegia, quadriplegia, cortical blindness, and stroke . These serious neurologic events have been reported with and without use of fluoroscopy.
Reports of serious medical events have been associated with the intrathecal route of corticosteroid administration .
The safety and effectiveness of epidural and intrathecal administration of corticosteroids have not been established, and corticosteroids are not approved for this use. In particular, the formulation of Ledercort (Triamcinolone) should not be considered safe to use for epidural or intrathecal administration.
5.3 Hypersensitivity Reactions
Rare instances of anaphylaxis have occurred in patients with hypersensitivity to corticosteroids. Cases of serious anaphylaxis, including death, have been reported in individuals receiving Ledercort (Triamcinolone) acetonide injection, regardless of the route of administration . Institute appropriate care upon occurrence of an anaphylactic reaction.
5.4 Joint Infection and Damage
Intra-articular injection of corticosteroid may be complicated by joint infection. A marked increase in pain accompanied by local swelling, further restriction of joint motion, fever, and malaise are suggestive of septic arthritis. If this complication occurs and a diagnosis of septic arthritis is confirmed, institute appropriate antimicrobial therapy .
Avoid injection of a corticosteroid into an infected site. Local injection of a corticosteroid into a previously infected joint is not usually recommended. Examine any joint fluid present to exclude a septic process.
Corticosteroid injection into unstable joints is generally not recommended.
Intra-articular injection may result in damage to joint tissues.
5.5 Increased Risk of Infections
Intra-articularly injected corticosteroids are systemically absorbed. Patients who are on corticosteroids are more susceptible to infections than are healthy individuals. There may be decreased resistance and inability to localize infection when corticosteroids are used. Infection with any pathogen (viral, bacterial, fungal, protozoan, or helminthic) in any location of the body may be associated with the use of corticosteroids alone or in combination with other immunosuppressive agents. These infections may be mild to severe. With increasing doses of corticosteroids, the rate of occurrence of infectious complications increases. Corticosteroids may also mask some signs of current infection.
Advise patients to inform their health care provider if they develop fever or other signs or symptoms of infection. Advise patients who have not been vaccinated to avoid exposure to chicken pox or measles. Instruct patients to contact their health care provider immediately if they are exposed .
5.6 Alterations in Endocrine Function
Corticosteroids can produce reversible hypothalamic-pituitary-adrenal axis suppression, with the potential for adrenal insufficiency after withdrawal of treatment, which may persist for months.
In situations of stress during that period, institute corticosteroid replacement therapy.
Metabolic clearance of corticosteroids is decreased in hypothyroid patients and increased in hyperthyroid patients.
5.7 Cardiovascular Effects
Corticosteroids can cause elevations of blood pressure, salt and water retention, and increased excretion of potassium. These effects are less likely to occur with synthetic derivatives.
Monitor patients with congestive heart failure or hypertension for signs of edema, weight gain, and imbalance in serum electrolytes. Dietary salt restriction and potassium supplementation may be necessary.
5.8 Renal Effects
Corticosteroids can cause salt and water retention, and increased excretion of potassium. These effects are less likely to occur with synthetic derivatives. All corticosteroids increase calcium excretion.
Monitor patients with renal insufficiency for signs of edema, weight gain, and imbalance in serum electrolytes. Dietary salt restriction and potassium supplementation may be necessary.
5.9 Increased Intraocular Pressure
Corticosteroid use may be associated with development or exacerbation of increased intraocular pressure.
Monitor patients with elevated intraocular pressure for potential treatment adjustment.
5.10 Gastrointestinal Perforation
Corticosteroid administration is associated with increased risk of gastrointestinal perforation in patients with certain GI disorders such as active or latent peptic ulcers, diverticulosis, diverticulitis, ulcerative colitis and in patients with fresh intestinal anastomoses.
Avoid corticosteroids in these patients because signs of peritoneal irritation following gastrointestinal perforation may be minimal or absent.
5.11 Alterations in Bone Density
Corticosteroids decrease bone formation and increase bone resorption through their effect on calcium regulation and inhibition of osteoblast function.
Special consideration should be given to patients with or at increased risk of osteoporosis before initiating corticosteroid therapy.
5.12 Behavioral and Mood Disturbances
Corticosteroid use may be associated with new or aggravated adverse psychiatric reactions ranging from euphoria, insomnia, mood swings, and personality changes to severe depression and frank psychotic manifestations.
Special consideration should be given to patients with previous or current emotional instability or psychiatric illness before initiating corticosteroid therapy. Advise patients and/or caregivers to immediately report any new or worsening behavior or mood disturbances to their health care provider.
6 ADVERSE REACTIONS
The following serious adverse reactions are described elsewhere in the labeling.
- Serious Neurologic Adverse Reactions with Epidural and Intrathecal Administration [ see Warnings and Precautions ( 5.2) ]
- Hypersensitivity Reactions [ see Warnings and Precautions ( 5.3) ]
- Joint Infection and Damage [ see Warnings and Precautions ( 5.4) ]
- Increased Risk of Infections [ see Warnings and Precautions ( 5.5) ]
- Alterations in Endocrine Function [ see Warnings and Precautions ( 5.6) ]
- Cardiovascular Effects [ see Warnings and Precautions ( 5.7) ]
- Renal Effects [ see Warnings and Precautions ( 5.8) ]
- Increased Intraocular Pressure [ see Warnings and Precautions ( 5.9) ]
- Gastrointestinal Perforation [ see Warnings and Precautions ( 5.10) ]
- Alternations in Bone Density [ see Warnings and Precautions ( 5.11) ]
- Behavioral and Mood Disturbances [ see Warnings and Precautions ( 5.12) ]
Because clinical studies 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.
The data below reflect exposure to a single 32 mg intra-articular injection of Ledercort (Triamcinolone) in clinical studies in patients with moderate to severe pain due to osteoarthritis of the knee. Clinical studies included randomized, double-blind, parallel-group, placebo and/or active-controlled, and pharmacokinetic/pharmacodynamic studies with follow-up ranging from 6-24 weeks. A total of 424 patients received Ledercort (Triamcinolone) and 262 received placebo. Treatment emergent adverse reactions reported by greater than or equal to 1% of patients in the Ledercort (Triamcinolone) arms are summarized below ( Table 1 and 2 ).
Overall, the incidence and nature of adverse reactions was similar to that observed with placebo.
| Preferred Term (MedDRA) | Ledercort (Triamcinolone) (N=424) | Placebo (N=262) |
| Sinusitis | 2% | 1% |
| Cough | 2% | 1% |
| Contusions | 2% | 1% |
| Preferred Term (MedDRA) | Ledercort (Triamcinolone) (N=424) | Placebo (N=262) |
|---|---|---|
| Joint Swelling | 3% | 2% |
| Contusions | 2% | 1% |
Most commonly reported adverse reactions (incidence ≥1%) in clinical studies include sinusitis, cough, and contusions. ( 6)
To report SUSPECTED ADVERSE REACTIONS, contact Flexion Therapeutics, Inc. at 1-844-FLEXION (353-9466) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
Corticosteroid Adverse Reactions
The following adverse reactions, presented alphabetically by body system, are from voluntary reports or clinical studies of corticosteroids. Because some of these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Anaphylactic reactions: Anaphylaxis including death, angioedema .
Cardiovascular: Bradycardia, cardiac arrest, cardiac arrhythmias, cardiac enlargement, circulatory collapse, congestive heart failure, hypertension , 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 scaly skin, ecchymoses and petechiae, edema, erythema, hyperpigmentation, hypopigmentation, impaired wound healing, increased sweating, lupus erythematosus-like lesions, purpura, rash, sterile abscess, striae, suppressed reactions to skin tests, thin fragile skin, thinning scalp hair, urticaria.
Endocrine: Decreased carbohydrate and glucose tolerance, development of Cushingoid state, glycosuria, hirsutism, hypertrichosis, increased requirements for insulin or oral hypoglycemic agents in diabetes, manifestations of latent diabetes mellitus, menstrual irregularities, secondary adrenocortical and pituitary unresponsiveness (particularly in times of stress, as in trauma, surgery, or illness), suppression of growth in pediatric patients.
Fluid and electrolyte disturbances: Congestive heart failure in susceptible patients , fluid retention, sodium retention.
Gastrointestinal: Abdominal distention, bowel/bladder dysfunction (after intrathecal administration) , elevation in serum liver enzyme levels (usually reversible upon discontinuation), hepatomegaly, increased appetite, nausea, pancreatitis, peptic ulcer with possible perforation and hemorrhage, perforation of the small and large intestine (particularly in patients with inflammatory bowel disease) , ulcerative esophagitis.
Metabolic: Negative nitrogen balance due to protein catabolism.
Musculoskeletal: Aseptic necrosis of femoral and humeral heads, calcinosis (following intra-articular or intralesional use), Charcot-like arthropathy, loss of muscle mass, muscle weakness, osteoporosis, pathologic fracture of long bones, post injection flare (following intra-articular use), steroid myopathy, tendon rupture, vertebral compression fractures.
Neurologic/Psychiatric: Convulsions, depression, emotional instability, euphoria, headache, increased intracranial pressure with papilledema (pseudotumor cerebri) usually following discontinuation of treatment, insomnia, mood swings, neuritis, neuropathy, paresthesia, personality changes, psychiatric disorders , vertigo. Arachnoiditis, meningitis, paraparesis/paraplegia, and sensory disturbances have occurred after intrathecal administration. Spinal cord infarction, paraplegia, quadriplegia, cortical blindness, and stroke (including brainstem) have been reported after epidural administration of corticosteroids .
Ophthalmic: Exophthalmos, glaucoma, increased intraocular pressure , posterior subcapsular cataracts, rare instances of blindness associated with periocular injections.
Other: Abnormal fat deposits, decreased resistance to infection, hiccups, increased or decreased motility and number of spermatozoa, malaise, moon face, weight gain.
7 DRUG INTERACTIONS
No drug-drug interaction studies have been conducted with Ledercort (Triamcinolone). Table 3 contains drug interactions associated with systemic corticosteroids.
| Aminoglutethimide | Aminoglutethimide may lead to a loss of corticosteroid-induced adrenal suppression. |
| Amphotericin B injection and potassium-depleting agents | When corticosteroids are administered concomitantly with potassium-depleting agents (i.e., amphotericin B, diuretics), observe patients closely for development of hypokalemia. There have been cases reported in which concomitant use of amphotericin B and hydrocortisone was followed by cardiac enlargement and congestive heart failure. |
| Antibiotics | Macrolide antibiotics have been reported to cause a significant decrease in corticosteroid clearance. |
| Anticholinesterases | Concomitant use of anticholinesterase agents and corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, withdraw anticholinesterase agents at least 24 hours before initiating corticosteroid therapy. |
| Anticoagulants, oral | Coadministration of corticosteroids and warfarin usually results in inhibition of response to warfarin, although there have been some conflicting reports. Therefore, monitor coagulation indices frequently to maintain the desired anticoagulant effect. |
| Antidiabetics | 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 which induce hepatic microsomal drug metabolizing enzyme activity may enhance metabolism of corticosteroids and require that the dosage of corticosteroid be increased. |
| CYP 3A4 inhibitors (e.g., ketoconazole) | Ketoconazole, a strong CYP3A4 inhibitor, 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 this concurrent use. |
| Digitalis glycosides | 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. |
| Nonsteroidal anti-inflammatory drugs (NSAIDs) | Concomitant use of aspirin (or other nonsteroidal anti-inflammatory drugs) 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. |
| Skin tests | Corticosteroids may suppress reactions to allergy related skin tests. |
| Vaccines | Patients on prolonged corticosteroid therapy may exhibit a diminished response to toxoids and live or inactivated vaccines due to inhibition of antibody response. Corticosteroids may also potentiate the replication of some organisms contained in live attenuated vaccines. If possible, defer routine administration of vaccines or toxoids until corticosteroid therapy is discontinued. |
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
There are no data regarding the use of Ledercort in pregnant women to inform a drug associated risk of adverse developmental outcomes. Published studies on the association between corticosteroids and fetal outcomes have reported inconsistent findings and have important methodological limitations. The majority of published literature with corticosteroid exposure during pregnancy includes the oral, topical and inhaled dosage formulations; therefore, the applicability of these findings to a single intra-articular injection of Ledercort (Triamcinolone) acetonide is limited. In animal reproductive studies from the published literature, pregnant mice, rats, rabbits, or primates administered Ledercort (Triamcinolone) acetonide during the period of organogenesis at doses that produced exposures less than the maximum recommended human dose (MRHD) caused resorptions, decreased fetal body weight, craniofacial and/or other abnormalities such as omphalocele .
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Data
Animal Data
The exposure margins listed below are based on body surface area comparisons (mg/m 2) to the highest daily Ledercort (Triamcinolone) acetonide exposure at the MRHD of 32 mg Ledercort (Triamcinolone) acetonide via Ledercort (Triamcinolone).
Pregnant mice dosed with Ledercort (Triamcinolone) acetonide via intramuscular or subcutaneous injection at doses equivalent to 0.8 times the MRHD or higher during organogenesis caused cleft palate and a higher rate of resorption. In pregnant rats dosed with Ledercort (Triamcinolone) acetonide via intramuscular or subcutaneous injection at doses equivalent to 0.3 times the MRHD or higher during organogenesis caused developmental abnormality (cleft palate, omphalocele, late resorption, and growth retardation) and fetal mortality. No notable maternal toxicity was observed in rodents.
Pregnant rabbits dosed with Ledercort (Triamcinolone) acetonide via intramuscular injection for 4 days during organogenesis at doses equivalent to 0.15 times the MRHD or higher caused resorption and cleft palate. No notable maternal toxicity was observed.
Pregnant primates dosed with Ledercort (Triamcinolone) acetonide via intramuscular injection for 4 days during organogenesis at doses equivalent to 3 times the MRHD or higher caused severe craniofacial CNS and skeletal/visceral malformation and higher prenatal death. No notable maternal toxicity was observed.
No peri- and post-natal development studies of Ledercort (Triamcinolone) acetonide in animals have been conducted.
8.2 Lactation
Risk Summary
There are no available data on the presence of Ledercort (Triamcinolone) acetonide in either human or animal milk, the effects on the breastfed infant, or the effects on milk production. However, corticosteroids have been detected in human milk and may suppress milk production. It is not known whether intra-articular administration of Ledercort (Triamcinolone) could result in sufficient systemic absorption to produce detectable quantities in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Ledercort (Triamcinolone) and any potential adverse effects on the breastfed infant from Ledercort (Triamcinolone) or from the underlying maternal condition.
8.3 Females and Males of Reproductive Potential
Corticosteroids may result in menstrual pattern irregularities such as deviations in timing and duration of menses and an increased or decreased loss of blood.
8.4 Pediatric Use
The safety and effectiveness of Ledercort in pediatric patients have not been established.
The adverse effects of corticosteroids in pediatric patients are similar to those in adults. Carefully observe pediatric patients, including weight, height, linear growth, blood pressure, intraocular pressure, and clinical evaluation for the presence of infection, psychosocial disturbances, thromboembolism, peptic ulcers, cataracts, and osteoporosis. Weigh potential growth effects of treatment against clinical benefits obtained and the availability of treatment alternatives.
8.5 Geriatric Use
Of the total number of patients administered 32 mg Ledercort (Triamcinolone) in clinical studies (N=424), 143 patients were 65 years of age or older. No overall differences in safety or effectiveness were observed between elderly and younger subjects, and other reported clinical experience with Ledercort (Triamcinolone) acetonide has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
11 DESCRIPTION
Ledercort (Triamcinolone) (triamcinolone acetonide extended-release injectable suspension) is a microsphere formulation of Ledercort (Triamcinolone) acetonide, a corticosteroid, to be administered by intra-articular injection.
Ledercort (Triamcinolone) is formulated in 75:25 poly(lactic-co-glycolic acid) (PLGA) microspheres with a nominal drug load of 25% (w/w) and is provided as a sterile white to off-white powder. Ledercort (Triamcinolone) is prepared with a supplied diluent containing an isotonic, sterile, aqueous solution of sodium chloride (NaCl; 0.9% w/w), sodium carboxymethylcellulose (CMC; 0.5% w/w) and polysorbate-80 (0.1% w/w) to form a 5 mL sterile suspension intended for intra-articular injection.
Active Ingredient
The chemical name for Ledercort (Triamcinolone) acetonide is 9-fluoro-11β,16α,17,21-tetrahydroxypregna-1,4-diene- 3,20-dione cyclic 16,17-acetal with acetone. Its structural formula is:
| MW 434.50 with a molecular formula of C 24H 31FO 6 |
Ledercort (Triamcinolone) acetonide occurs as a white to almost white, crystalline powder having not more than a slight odor and is practically insoluble in water and very soluble in alcohol. Each vial of Ledercort (Triamcinolone) powder contains 40 mg of Ledercort (Triamcinolone) acetonide in 160 mg of microspheres, resulting in 32 mg of deliverable Ledercort (Triamcinolone) acetonide when prepared according to the Instructions for Use.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Ledercort acetonide is a corticosteroid with anti-inflammatory and immunomodulating properties. It binds to and activates the glucocorticoid receptor, leading to activation of anti-inflammatory transcription factors such as lipocortins and inhibition of inflammatory transduction pathways by blocking the release of arachidonic acid and preventing the synthesis of prostaglandins and leukotrienes.
12.2 Pharmacodynamics
Studies indicate that following a single intramuscular dose of 60 to 100 mg of immediate-release Ledercort (Triamcinolone) acetonide injectable suspension, adrenal suppression occurs within 24 to 48 hours and then gradually returns to normal, usually in 30 to 40 days. To assess potential effects of the systemic levels of Ledercort (Triamcinolone) acetonide associated with a single intra-articular (IA) administration of Ledercort (Triamcinolone) on hypothalamic pituitary adrenal (HPA) axis function, serum and urine cortisol levels were monitored over 6 weeks post injection. Adrenal suppression with Ledercort (Triamcinolone) occurred within 12-24 hours and then gradually returned to normal, within 30-42 days.
Corticosteroids may increase blood glucose concentrations.
In a study where 18 patients with osteoarthritis knee pain and controlled type 2 diabetes mellitus received a single IA injection of Ledercort (Triamcinolone) into the knee, the change from baseline in average blood glucose over the 72 hours after injection as measured by a continuous glucose monitoring device was 8.2 mg/dL (95% confidence interval 0.1, 29.2).
12.3 Pharmacokinetics
Ledercort (Triamcinolone) is an extended-release dosage form consisting of microspheres of poly(lactic-co-glycolic acid) (PLGA) containing Ledercort (Triamcinolone) acetonide. Plasma pharmacokinetic parameters for Ledercort (Triamcinolone) acetonide following IA administration of Ledercort (Triamcinolone) or 40 mg immediate-release Ledercort (Triamcinolone) acetonide into the knee are provided in Table 4.
| * 33 patients contributed to the analyses of these parameters | ||
| † 14 patients contributed to the analyses of these parameters | ||
| 1 Median (min, max) values for t max | ||
| Ledercort (Triamcinolone) Acetonide PK Parameters 1 | Ledercort (Triamcinolone) (N=60) | Ledercort (Triamcinolone) Acetonide (N=18) |
| C max (pg/mL) | 1143.7 (611.06) | 21062.2 (18466.79) |
| AUC 0-24 hour (pg-h/mL) | 21219.2 (11325.62) | 297545.3 (222402.77) |
| AUC 0-inf (pg-h/mL) | 842149.2 (1062004.97)* | 1567565.0 (1246330.95) † |
| t max (h) | 7 (1, 1008) | 6 (2, 24) |
| t 1/2 (h) | 633.9 (893.0)* | 146.9 (213.29) † |
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenesis
Long-term animal studies to evaluate the carcinogenic potential of Ledercort (Triamcinolone) have not been conducted.
Mutagenesis
Adequate mutagenicity studies have not been conducted with Ledercort (Triamcinolone).
Impairment of Fertility
Studies in animals to evaluate the impairment of fertility of Ledercort (Triamcinolone) have not been conducted.
14 CLINICAL STUDIES
The efficacy of Ledercort (Triamcinolone) was demonstrated in a multi-center, international, randomized, double-blind, parallel-arm, placebo- and active-controlled study in patients with osteoarthritis pain of the knee. A total of 484 patients (ZILRETTA 32 mg, N=161; placebo [saline], N=162; active control [a crystalline suspension, immediate-release formulation of Ledercort (Triamcinolone) acetonide 40 mg], N=161) were treated and followed for up to 24 weeks. Patients had a mean age of 62 (range 40 to 85 years); baseline demographics and disease characteristics were balanced across treatment arms. Twenty-five percent (25%) of patients had received at least one prior corticosteroid intra-articular injection more than 3 months prior to treatment. A total of 470 patients (97%) completed follow-up to Week 12, the time point for primary efficacy determination, and 443 (91.5%) completed to Week 24.
The primary efficacy endpoint comparing Ledercort (Triamcinolone) to placebo was change from baseline at Week 12 in the weekly mean of the Average Daily Pain intensity scores (ADP) as assessed by a 0-10 Numeric Rating Scale (NRS). Ledercort (Triamcinolone) demonstrated a statistically significant reduction in pain intensity at the primary endpoint vs placebo. Ledercort (Triamcinolone) also demonstrated a reduction in pain intensity scores each week from Weeks 1 through 12 ( Figure 1 ).
In a secondary exploratory analysis, statistical significance was not demonstrated between the Ledercort (Triamcinolone) and the active control (immediate-release Ledercort (Triamcinolone) acetonide) treatment groups for the change from baseline at Week 12 in weekly mean ADP.
Figure 1: Weekly Change from Baseline to Week 12 in Average Daily Pain
16 HOW SUPPLIED/STORAGE AND HANDLING
| Description | NDC | Presentation/How Supplied |
| Ledercort (Triamcinolone) | NDC 70801-003-01 | Ledercort (Triamcinolone) (triamcinolone acetonide extended-release injectable suspension) single-dose kit. |
| Kit Contents | ||
| Ledercort (Triamcinolone) microsphere powder | NDC 70801-001-01 | 5 mL single-dose vial to deliver 32 mg of Ledercort (Triamcinolone) acetonide supplied as a sterile, white to off-white powder in a cerium glass (clear) vial with a rubber stopper and an aluminum seal with a gray plastic cap. |
| Diluent | NDC 70801-002-01 | 5 mL single-dose vial supplied as a sterile, clear liquid solution of 0.9% w/w sodium chloride (normal saline) containing 0.5% w/w sodium carboxymethylcellulose, and 0.1% w/w polysorbate-80 in a glass vial with a rubber stopper, aluminum seal and white plastic cap. |
| Sterile vial adapter | ||
STORAGE
To maintain expiry period, refrigerate the Ledercort (Triamcinolone) single-dose kit (36°-46°F; 2°-8°C) before use.
If refrigeration is unavailable, store the Ledercort (Triamcinolone) single-dose kit in the sealed, unopened kit at temperatures not exceeding 77°F (25°C) for up to six weeks and then discard. Do not expose the Ledercort (Triamcinolone) single-dose kit to temperatures above 77°F (25°C).
Do not freeze. Store vials in carton.
17 PATIENT COUNSELING INFORMATION
Increased Risk of Infections
Inform patients that they may be more likely to develop infections when taking corticosteroids. Instruct patients to contact their health care provider if they develop fever or other signs or symptoms of infection.
Advise patients who have not been vaccinated to avoid exposure to chicken pox or measles. Instruct patients to contact their health care provider immediately if they are exposed .
Risk of Drug Interactions
There are a number of medicines that can interact with corticosteroids such as Ledercort (Triamcinolone) acetonide. Advise patients to alert their health care provider(s) to assess the need to adjust their medication(s) .
Risk of Adverse Psychiatric Reactions
Inform patients that corticosteroid use may be associated with adverse psychiatric reactions. Advise patients and/or caregivers to immediately report any new or worsening behavioral or mood disturbances to their health care provider .
Manufactured for Flexion Therapeutics, Inc., 10 Mall Rd, Suite 301, Burlington, MA 01803
Ledercort (Triamcinolone) and Flexion are trademarks of Flexion Therapeutics, Inc.
Copyright © 2017 Flexion Therapeutics, Inc. All rights reserved.
For more information, go to Ledercort (Triamcinolone).com or call 1-844-FLEXION (353-9466).
Part Number: 60-004-01
Version: 1, 10/2017
Instructions for Use
Ledercort (Triamcinolone)
(triamcinolone acetonide
extended-release injectable suspension)
For intra-articular injection only
Single-dose device
Do not reuse.
IMPORTANT INFORMATION
- Ledercort (Triamcinolone) must be prepared using only the diluent supplied in the kit.
- To ensure proper dosing, it is important that you follow the preparation and administration steps outlined in these instructions.
- Promptly inject Ledercort (Triamcinolone) after preparation to avoid settling of the suspension.
- Ledercort (Triamcinolone) is supplied as a single-dose kit and administered as a suspension containing microspheres.
- The Ledercort (Triamcinolone) powder vial contains an overfill to allow the appropriate dose to be withdrawn. Ledercort (Triamcinolone) is a suspension product and it is normal for some residue to be left behind on the vial walls after withdrawing the contents.
- Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration.
- Use proper aseptic technique throughout the dose preparation and administration procedure.
- Inspect all kit components to confirm they have not expired and the seals are intact.
- For additional information, visit www.zilretta.com or call Flexion Therapeutics at 1-844-FLEXION (353-9466).
MATERIALS REQUIRED
(Fig.1)
Supplied
- One 32 mg vial of Ledercort (Triamcinolone) microsphere powder
- One 5 mL vial of sterile diluent
- One sterile vial adapter
Not Supplied
- Three sterile needles, 21-gauge, 1½” length
- One sterile Luer Lock compatible syringe, 5 mL
- Sterile alcohol pads
- Paper towels or pad to cushion vial tapping (not shown in Fig. 1)
- Medical-grade gloves (not shown in Fig. 1)
Figure 1
1. Vial Preparation
Loosen Powder.
Place two paper towels or a pad on a properly-cleaned hard surface.
Grip the top of the Ledercort (Triamcinolone) powder vial and tap firmly and repeatedly on the padded surface. Tap the vial until excess powder is dislodged from the vial and stopper ( Fig. 2). Before continuing, ensure that powder moves freely within the vial.
Figure 2
Inspect Ledercort (Triamcinolone) Powder Vial.
As shown in Figure 3, the vial on the left, with the X, requires additional tapping because the powder is not properly dislodged. The vial on the right shows the powder properly dislodged and ready for the next step.
Figure 3
Remove Caps.
Remove the flip-off caps from the Ledercort (Triamcinolone) powder and diluent vials ( Fig. 4).
Figure 4
Clean Vials.
Clean the Ledercort (Triamcinolone) powder and diluent vial tops with an alcohol pad.
Use a separate alcohol pad for each vial.
Peel Off Vial Adapter Cover.
Peel off the paper cover from the vial adapter package ( Fig. 5).
Leave the adapter in the plastic holder.
Figure 5
Attach Vial Adapter to Ledercort (Triamcinolone) Powder Vial.
Grip the plastic holder that contains the vial adapter.
As shown in Figure 6, place the Ledercort (Triamcinolone) powder vial on a flat surface. In a vertical orientation, gently push the adapter down onto the Ledercort (Triamcinolone) powder vial until the spike on the adapter penetrates the rubber stopper on the Ledercort (Triamcinolone) powder vial. The adapter will snap into place.
Figure 6
2. Diluent Preparation
Attach Needle.
Attach a needle to the syringe and remove the needle guard.
Withdraw Diluent.
With a syringe and needle, withdraw 5 mL of diluent.
Replace the needle guard.
3. Dose Preparation
Remove Holder.
Remove the plastic holder from the vial adapter ( Fig. 7).
Figure 7
Remove Needle.
Remove the needle from the syringe containing diluent.
Attach Diluent Syringe.
Attach the syringe onto the vial adapter by pushing down and turning clockwise until you feel resistance ( Fig. 8).
Figure 8
Transfer Diluent.
Slowly and completely push down the syringe plunger to transfer the diluent into the Ledercort (Triamcinolone) powder vial ( Fig. 9).
Note: Equalize the pressure in the syringe by slowly pulling back the plunger to the 5 mL mark. Ensure that no solution is drawn back into the syringe at this stage.
Figure 9
Mix Diluent and Powder ( Fig. 10).
With the syringe still attached to the Ledercort (Triamcinolone) powder vial, hold the syringe and vial at a slight angle. Tap the bottom edge of the vial firmly and repeatedly, in a circular motion, on the padded surface.
Swirl gently every five or six taps.
Tap for at least one minute until all powder is completely dispersed.
Note: Avoid vigorous shaking of the vial to minimize foaming.
Note: At least one minute of tapping and gentle swirling is required to achieve uniform suspension.
Figure 10
Inspect Vial.
Inspect the Ledercort (Triamcinolone) powder vial to ensure no clumped powder is visible and a uniform suspension has been achieved. A properly mixed suspension will be milky white, contain no clumps, and move freely down the vial wall.
As shown in Figure 11, the vial on the left, with the X, requires more tapping and gentle swirling because the powder is not mixed properly with the diluent. The vial on the right shows the powder properly mixed and ready for the next step.
Figure 11
Note: If needed, the Ledercort (Triamcinolone) suspension can be stored in the vial for up to 4 hours at ambient conditions. The syringe must remain on the vial adapter while the suspension remains in the vial.
Withdraw Contents into Syringe.
Swirl the vial gently for at least 10 seconds to ensure the powder is fully suspended. Immediately depress the plunger fully and then invert the syringe so the vial is directly on top of the syringe ( Fig. 12).
Hold the syringe in a completely vertical position, per the illustration on the right, in Figure 12.
Withdraw the full contents from the Ledercort (Triamcinolone) vial into the syringe.
Figure 12
Note: Ledercort (Triamcinolone) is a suspension product and it is normal for some residue to be left behind on the vial walls after withdrawing the contents.
Remove Syringe.
Remove the syringe from the vial adapter by turning counter-clockwise.
Remove Air Bubbles.
Attach a new needle to the syringe and remove the needle guard.
Inspect for bubbles with the syringe held in a completely vertical position (needle upward). If bubbles are observed, gently tap the syringe with your finger until the bubbles rise to the top. Eliminate all bubbles by slowly depressing the plunger to displace the air from the syringe.
Replace the needle guard.
Attach New Needle.
Remove and discard the needle.
Attach a new needle.
4. Administration
Invert Syringe.
To ensure the powder is suspended, gently invert the syringe containing Ledercort (Triamcinolone) several times just prior to administration, as shown in Figure 13.
Grip the syringe firmly and turn it so the syringe plunger is pointing straight down. Then turn the syringe gently, 180 degrees, until the plunger is pointing straight up.
Invert the syringe several times to ensure a properly mixed suspension.
Figure 13
A properly mixed suspension will be uniformly milky white and contain no clumps.
Inspect Syringe.
As shown in Figure 14, the syringe on the left, with the X, requires more inversions (turning) to properly mix the suspension. The syringe on the right shows the suspension properly mixed and ready for the next step.
Figure 14
Administer Ledercort (Triamcinolone).
The usual technique for intra-articular injection should be followed.
Aspiration of synovial fluid may be performed based on clinical judgment prior to administration of Ledercort (Triamcinolone).
Do not reuse excess Ledercort (Triamcinolone). Any excess suspension in the vial should be thrown away immediately after the injection. Leftover Ledercort (Triamcinolone) in the vial must never be reused for another injection.
Note: The entire contents of the syringe must be injected to ensure the intended dose of Ledercort (Triamcinolone) is delivered.
Note: Discard all used components in an appropriate medical waste container according to local regulations.
Note: Ledercort (Triamcinolone) is for intra-articular use only. Ledercort (Triamcinolone) is not intended for epidural, intrathecal, intravenous, intraocular, intramuscular, intradermal, or subcutaneous use.
Part Number: 60-005-01
Rev: 10/2017
Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14
Principal Display Panel - Ledercort (Triamcinolone) Cart 32mg Carton Label
NDC 70801-003-01 Rx Only
Ledercort (Triamcinolone)
(triamcinolone acetonide extended-release
injectable suspension)
32 mg per vial
For intra-articular injection only.
Single-dose kit. Discard unused portion.
Must be reconstituted
with the supplied diluent.
This carton contains:
1 Vial of Ledercort (Triamcinolone)
microsphere powder
1 Vial of diluent (5 mL)
for Ledercort (Triamcinolone)
1 sterile vial adapter
flexion
Principal Display Panel - Ledercort (Triamcinolone) Cart 32mg Professional Carton Label
NDC 70801-003-02 Rx Only
Ledercort (Triamcinolone)
(triamcinolone acetonide extended-release
injectable suspension)
32 mg per vial
For intra-articular injection only.
Single-dose kit. Discard unused portion.
Must be reconstituted
with the supplied diluent.
PROFESSIONAL SAMPLE
NOT FOR SALE
OR REIMBURSEMENT
This carton contains:
1 Vial of Ledercort (Triamcinolone)
microsphere powder
1 Vial of diluent (5 mL)
for Ledercort (Triamcinolone)
1 sterile vial adapter
flexion
Principal Display Panel - Ledercort (Triamcinolone) 32mg Vial Label
NDC 70801-001-01 Rx Only
Ledercort (Triamcinolone)
(triamcinolone acetonide extended-release
injectable suspension)
32 mg per vial
For intra-articular injection only.
Must be reconstituted
with the supplied diluent.
flexion
Principal Display Panel - Ledercort (Triamcinolone) 32mg Professional Vial Label
NDC 70801-001-02 Rx Only
Ledercort (Triamcinolone)
(triamcinolone acetonide extended-release
injectable suspension)
32 mg per vial
For intra-articular injection only.
Must be reconstituted
with the supplied diluent.
flexion
Principal Display Panel - Ledercort (Triamcinolone) Diluent 5mL Vial Label
NDC 70801-002-01 Rx Only
DILUENT
for use with Ledercort (Triamcinolone)
5 mL
Sterile single-use vial
Do not administer directly.
flexion
Principal Display Panel - Ledercort (Triamcinolone) Diluent 5mL Professional Vial Label
NDC 70801-002-02 Rx Only
DILUENT
for use with Ledercort (Triamcinolone)
5 mL
Sterile single-use vial
Do not administer directly.
flexion
Triamcinolone Acetonide:
- Indications and usage
- Dosage and administration
- Dosage forms and strengths
- Contraindications
- Warnings and precautions
- Adverse reactions
- Drug interactions
- Use in specific populations
- Description
- Clinical pharmacology
- Nonclinical toxicology
- Clinical studies
- How supplied/storage and handling
- Patient counseling information
1 INDICATIONS AND USAGE
Ledercort (Triamcinolone Acetonide) (triamcinolone acetonide extended-release injectable suspension) is indicated as an intra-articular injection for the management of osteoarthritis pain of the knee.
Ledercort (Triamcinolone Acetonide) is an extended-release synthetic corticosteroid indicated as an intra-articular injection for the management of osteoarthritis pain of the knee. ( 1)
Limitation of Use
Ledercort (Triamcinolone Acetonide) is not intended for repeat administration. ( 1)
Limitation of Use
Ledercort (Triamcinolone Acetonide) is not intended for repeat administration .
2 DOSAGE AND ADMINISTRATION
- 32 mg administered as a single intra-articular injection in the knee.
- See Instructions for Use (IFU) for instructions on reconstitution of Ledercort (Triamcinolone Acetonide) with the supplied diluent. ( 2.2)
- It is normal for some residue to be left behind on the vial walls after withdrawing the suspension. ( 2.2)
- Not interchangeable with other formulations of injectable Ledercort (Triamcinolone Acetonide). ( 2.3)
2.1 Important Dosage and Administration Information
- Ledercort (Triamcinolone Acetonide) is administered as a single intra-articular extended-release injection of Ledercort (Triamcinolone Acetonide), to deliver 32 mg (5 mL).
- Ledercort (Triamcinolone Acetonide) is for intra-articular use only and should not be administered by the following routes: epidural, intrathecal, intravenous, intraocular, intramuscular, intradermal, subcutaneous.
- Ledercort (Triamcinolone Acetonide) is not suitable for use in small joints, such as the hand.
- The efficacy and safety of repeat administration of Ledercort (Triamcinolone Acetonide) for the management of osteoarthritis pain of the knee have not been evaluated.
- The efficacy and safety of Ledercort (Triamcinolone Acetonide) for management of osteoarthritis pain of shoulder and hip have not been evaluated.
2.2 Preparation and Administration of Intra-Articular Suspension
Refer to the Instructions for Use for directions on the preparation and administration of Ledercort.
Ledercort (Triamcinolone Acetonide) is supplied as a single-dose kit containing a vial of Ledercort (Triamcinolone Acetonide) microsphere powder, a vial of sterile diluent, and a sterile vial adapter.
Ledercort (Triamcinolone Acetonide) must be prepared using the diluent supplied in the kit.
Preparation of Ledercort (Triamcinolone Acetonide) requires close attention to the Instructions for Use to ensure successful administration.
Use proper aseptic technique throughout the dose preparation and administration procedure.
Ledercort (Triamcinolone Acetonide) is a suspension product and it is normal for some residue to be left behind on the vial walls after withdrawing the contents.
Promptly inject Ledercort (Triamcinolone Acetonide) after preparation to avoid settling of the suspension. If needed, the Ledercort (Triamcinolone Acetonide) suspension can be stored in the vial for up to 4 hours at ambient conditions. Gently swirl the vial to resuspend any of the settled microspheres prior to preparing the syringe for injection.
The usual technique for intra-articular injection should be followed. Aspiration of synovial fluid may be performed based on clinical judgment prior to administration of Ledercort (Triamcinolone Acetonide).
2.3 Non-Interchangeability with Other Formulations of Ledercort (Triamcinolone Acetonide) for Intra-articular Use
Ledercort (Triamcinolone Acetonide) is not interchangeable with other formulations of injectable Ledercort (Triamcinolone Acetonide).
3 DOSAGE FORMS AND STRENGTHS
Ledercort (Triamcinolone Acetonide) is an injectable suspension that delivers 32 mg of Ledercort (Triamcinolone Acetonide). Ledercort (Triamcinolone Acetonide) is supplied as a single-dose kit, containing:
- One vial of Ledercort (Triamcinolone Acetonide) white to off-white microsphere powder
- One vial of 5 mL sterile, clear diluent
- One sterile vial adapter
Ledercort (Triamcinolone Acetonide) is an injectable suspension that delivers 32 mg of Ledercort (Triamcinolone Acetonide). It is supplied as a single-dose kit containing one vial of Ledercort (Triamcinolone Acetonide) microsphere powder, one vial of 5 mL diluent, and one sterile vial adapter. ( 3)
4 CONTRAINDICATIONS
Ledercort (Triamcinolone Acetonide) is contraindicated in patients who are hypersensitive to Ledercort (Triamcinolone Acetonide), corticosteroids or any components of the product .
Patients with hypersensitivity to Ledercort (Triamcinolone Acetonide) or any component of the product. ( 4)
5 WARNINGS AND PRECAUTIONS
- Intra-articular Use Only: Do not administer Ledercort by epidural, intrathecal, intravenous, intraocular, intramuscular, intradermal, or subcutaneous routes. ( 5.1)
- Serious Neurologic Adverse Reactions with Epidural and Intrathecal Administration: Serious neurologic events have been reported following epidural or intrathecal corticosteroid administration. Corticosteroids are not approved for this use. ( 5.2)
- Hypersensitivity Reactions: Serious reactions have been reported with Ledercort (Triamcinolone Acetonide) injection. Institute appropriate care upon occurrence of an anaphylactic reaction. ( 5.3)
- Joint Infection and Damage: May cause joint pain accompanied by joint swelling. If this occurs, conduct appropriate evaluation to exclude septic arthritis and institute appropriate antimicrobial therapy if septic arthritis is confirmed. ( 5.4)
5.1 Warnings and Precautions Specific for Ledercort (Triamcinolone Acetonide)
Ledercort (Triamcinolone Acetonide) has not been evaluated and should not be administered by the following routes:
- Epidural
- Intrathecal
- Intravenous
- Intraocular
- Intramuscular
- Intradermal
- Subcutaneous
.
5.2 Serious Neurologic Adverse Reactions with Epidural and Intrathecal Administration
Serious neurologic events, some resulting in death, have been reported with epidural injection of corticosteroids. Specific events reported include, but are not limited to, spinal cord infarction, paraplegia, quadriplegia, cortical blindness, and stroke . These serious neurologic events have been reported with and without use of fluoroscopy.
Reports of serious medical events have been associated with the intrathecal route of corticosteroid administration .
The safety and effectiveness of epidural and intrathecal administration of corticosteroids have not been established, and corticosteroids are not approved for this use. In particular, the formulation of Ledercort (Triamcinolone Acetonide) should not be considered safe to use for epidural or intrathecal administration.
5.3 Hypersensitivity Reactions
Rare instances of anaphylaxis have occurred in patients with hypersensitivity to corticosteroids. Cases of serious anaphylaxis, including death, have been reported in individuals receiving Ledercort (Triamcinolone Acetonide) injection, regardless of the route of administration . Institute appropriate care upon occurrence of an anaphylactic reaction.
5.4 Joint Infection and Damage
Intra-articular injection of corticosteroid may be complicated by joint infection. A marked increase in pain accompanied by local swelling, further restriction of joint motion, fever, and malaise are suggestive of septic arthritis. If this complication occurs and a diagnosis of septic arthritis is confirmed, institute appropriate antimicrobial therapy .
Avoid injection of a corticosteroid into an infected site. Local injection of a corticosteroid into a previously infected joint is not usually recommended. Examine any joint fluid present to exclude a septic process.
Corticosteroid injection into unstable joints is generally not recommended.
Intra-articular injection may result in damage to joint tissues.
5.5 Increased Risk of Infections
Intra-articularly injected corticosteroids are systemically absorbed. Patients who are on corticosteroids are more susceptible to infections than are healthy individuals. There may be decreased resistance and inability to localize infection when corticosteroids are used. Infection with any pathogen (viral, bacterial, fungal, protozoan, or helminthic) in any location of the body may be associated with the use of corticosteroids alone or in combination with other immunosuppressive agents. These infections may be mild to severe. With increasing doses of corticosteroids, the rate of occurrence of infectious complications increases. Corticosteroids may also mask some signs of current infection.
Advise patients to inform their health care provider if they develop fever or other signs or symptoms of infection. Advise patients who have not been vaccinated to avoid exposure to chicken pox or measles. Instruct patients to contact their health care provider immediately if they are exposed .
5.6 Alterations in Endocrine Function
Corticosteroids can produce reversible hypothalamic-pituitary-adrenal axis suppression, with the potential for adrenal insufficiency after withdrawal of treatment, which may persist for months.
In situations of stress during that period, institute corticosteroid replacement therapy.
Metabolic clearance of corticosteroids is decreased in hypothyroid patients and increased in hyperthyroid patients.
5.7 Cardiovascular Effects
Corticosteroids can cause elevations of blood pressure, salt and water retention, and increased excretion of potassium. These effects are less likely to occur with synthetic derivatives.
Monitor patients with congestive heart failure or hypertension for signs of edema, weight gain, and imbalance in serum electrolytes. Dietary salt restriction and potassium supplementation may be necessary.
5.8 Renal Effects
Corticosteroids can cause salt and water retention, and increased excretion of potassium. These effects are less likely to occur with synthetic derivatives. All corticosteroids increase calcium excretion.
Monitor patients with renal insufficiency for signs of edema, weight gain, and imbalance in serum electrolytes. Dietary salt restriction and potassium supplementation may be necessary.
5.9 Increased Intraocular Pressure
Corticosteroid use may be associated with development or exacerbation of increased intraocular pressure.
Monitor patients with elevated intraocular pressure for potential treatment adjustment.
5.10 Gastrointestinal Perforation
Corticosteroid administration is associated with increased risk of gastrointestinal perforation in patients with certain GI disorders such as active or latent peptic ulcers, diverticulosis, diverticulitis, ulcerative colitis and in patients with fresh intestinal anastomoses.
Avoid corticosteroids in these patients because signs of peritoneal irritation following gastrointestinal perforation may be minimal or absent.
5.11 Alterations in Bone Density
Corticosteroids decrease bone formation and increase bone resorption through their effect on calcium regulation and inhibition of osteoblast function.
Special consideration should be given to patients with or at increased risk of osteoporosis before initiating corticosteroid therapy.
5.12 Behavioral and Mood Disturbances
Corticosteroid use may be associated with new or aggravated adverse psychiatric reactions ranging from euphoria, insomnia, mood swings, and personality changes to severe depression and frank psychotic manifestations.
Special consideration should be given to patients with previous or current emotional instability or psychiatric illness before initiating corticosteroid therapy. Advise patients and/or caregivers to immediately report any new or worsening behavior or mood disturbances to their health care provider.
6 ADVERSE REACTIONS
The following serious adverse reactions are described elsewhere in the labeling.
- Serious Neurologic Adverse Reactions with Epidural and Intrathecal Administration [ see Warnings and Precautions ( 5.2) ]
- Hypersensitivity Reactions [ see Warnings and Precautions ( 5.3) ]
- Joint Infection and Damage [ see Warnings and Precautions ( 5.4) ]
- Increased Risk of Infections [ see Warnings and Precautions ( 5.5) ]
- Alterations in Endocrine Function [ see Warnings and Precautions ( 5.6) ]
- Cardiovascular Effects [ see Warnings and Precautions ( 5.7) ]
- Renal Effects [ see Warnings and Precautions ( 5.8) ]
- Increased Intraocular Pressure [ see Warnings and Precautions ( 5.9) ]
- Gastrointestinal Perforation [ see Warnings and Precautions ( 5.10) ]
- Alternations in Bone Density [ see Warnings and Precautions ( 5.11) ]
- Behavioral and Mood Disturbances [ see Warnings and Precautions ( 5.12) ]
Because clinical studies 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.
The data below reflect exposure to a single 32 mg intra-articular injection of Ledercort (Triamcinolone Acetonide) in clinical studies in patients with moderate to severe pain due to osteoarthritis of the knee. Clinical studies included randomized, double-blind, parallel-group, placebo and/or active-controlled, and pharmacokinetic/pharmacodynamic studies with follow-up ranging from 6-24 weeks. A total of 424 patients received Ledercort (Triamcinolone Acetonide) and 262 received placebo. Treatment emergent adverse reactions reported by greater than or equal to 1% of patients in the Ledercort (Triamcinolone Acetonide) arms are summarized below ( Table 1 and 2 ).
Overall, the incidence and nature of adverse reactions was similar to that observed with placebo.
| Preferred Term (MedDRA) | Ledercort (Triamcinolone Acetonide) (N=424) | Placebo (N=262) |
| Sinusitis | 2% | 1% |
| Cough | 2% | 1% |
| Contusions | 2% | 1% |
| Preferred Term (MedDRA) | Ledercort (Triamcinolone Acetonide) (N=424) | Placebo (N=262) |
|---|---|---|
| Joint Swelling | 3% | 2% |
| Contusions | 2% | 1% |
Most commonly reported adverse reactions (incidence ≥1%) in clinical studies include sinusitis, cough, and contusions. ( 6)
To report SUSPECTED ADVERSE REACTIONS, contact Flexion Therapeutics, Inc. at 1-844-FLEXION (353-9466) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
Corticosteroid Adverse Reactions
The following adverse reactions, presented alphabetically by body system, are from voluntary reports or clinical studies of corticosteroids. Because some of these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Anaphylactic reactions: Anaphylaxis including death, angioedema .
Cardiovascular: Bradycardia, cardiac arrest, cardiac arrhythmias, cardiac enlargement, circulatory collapse, congestive heart failure, hypertension , 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 scaly skin, ecchymoses and petechiae, edema, erythema, hyperpigmentation, hypopigmentation, impaired wound healing, increased sweating, lupus erythematosus-like lesions, purpura, rash, sterile abscess, striae, suppressed reactions to skin tests, thin fragile skin, thinning scalp hair, urticaria.
Endocrine: Decreased carbohydrate and glucose tolerance, development of Cushingoid state, glycosuria, hirsutism, hypertrichosis, increased requirements for insulin or oral hypoglycemic agents in diabetes, manifestations of latent diabetes mellitus, menstrual irregularities, secondary adrenocortical and pituitary unresponsiveness (particularly in times of stress, as in trauma, surgery, or illness), suppression of growth in pediatric patients.
Fluid and electrolyte disturbances: Congestive heart failure in susceptible patients , fluid retention, sodium retention.
Gastrointestinal: Abdominal distention, bowel/bladder dysfunction (after intrathecal administration) , elevation in serum liver enzyme levels (usually reversible upon discontinuation), hepatomegaly, increased appetite, nausea, pancreatitis, peptic ulcer with possible perforation and hemorrhage, perforation of the small and large intestine (particularly in patients with inflammatory bowel disease) , ulcerative esophagitis.
Metabolic: Negative nitrogen balance due to protein catabolism.
Musculoskeletal: Aseptic necrosis of femoral and humeral heads, calcinosis (following intra-articular or intralesional use), Charcot-like arthropathy, loss of muscle mass, muscle weakness, osteoporosis, pathologic fracture of long bones, post injection flare (following intra-articular use), steroid myopathy, tendon rupture, vertebral compression fractures.
Neurologic/Psychiatric: Convulsions, depression, emotional instability, euphoria, headache, increased intracranial pressure with papilledema (pseudotumor cerebri) usually following discontinuation of treatment, insomnia, mood swings, neuritis, neuropathy, paresthesia, personality changes, psychiatric disorders , vertigo. Arachnoiditis, meningitis, paraparesis/paraplegia, and sensory disturbances have occurred after intrathecal administration. Spinal cord infarction, paraplegia, quadriplegia, cortical blindness, and stroke (including brainstem) have been reported after epidural administration of corticosteroids .
Ophthalmic: Exophthalmos, glaucoma, increased intraocular pressure , posterior subcapsular cataracts, rare instances of blindness associated with periocular injections.
Other: Abnormal fat deposits, decreased resistance to infection, hiccups, increased or decreased motility and number of spermatozoa, malaise, moon face, weight gain.
7 DRUG INTERACTIONS
No drug-drug interaction studies have been conducted with Ledercort (Triamcinolone Acetonide). Table 3 contains drug interactions associated with systemic corticosteroids.
| Aminoglutethimide | Aminoglutethimide may lead to a loss of corticosteroid-induced adrenal suppression. |
| Amphotericin B injection and potassium-depleting agents | When corticosteroids are administered concomitantly with potassium-depleting agents (i.e., amphotericin B, diuretics), observe patients closely for development of hypokalemia. There have been cases reported in which concomitant use of amphotericin B and hydrocortisone was followed by cardiac enlargement and congestive heart failure. |
| Antibiotics | Macrolide antibiotics have been reported to cause a significant decrease in corticosteroid clearance. |
| Anticholinesterases | Concomitant use of anticholinesterase agents and corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, withdraw anticholinesterase agents at least 24 hours before initiating corticosteroid therapy. |
| Anticoagulants, oral | Coadministration of corticosteroids and warfarin usually results in inhibition of response to warfarin, although there have been some conflicting reports. Therefore, monitor coagulation indices frequently to maintain the desired anticoagulant effect. |
| Antidiabetics | 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 which induce hepatic microsomal drug metabolizing enzyme activity may enhance metabolism of corticosteroids and require that the dosage of corticosteroid be increased. |
| CYP 3A4 inhibitors (e.g., ketoconazole) | Ketoconazole, a strong CYP3A4 inhibitor, 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 this concurrent use. |
| Digitalis glycosides | 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. |
| Nonsteroidal anti-inflammatory drugs (NSAIDs) | Concomitant use of aspirin (or other nonsteroidal anti-inflammatory drugs) 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. |
| Skin tests | Corticosteroids may suppress reactions to allergy related skin tests. |
| Vaccines | Patients on prolonged corticosteroid therapy may exhibit a diminished response to toxoids and live or inactivated vaccines due to inhibition of antibody response. Corticosteroids may also potentiate the replication of some organisms contained in live attenuated vaccines. If possible, defer routine administration of vaccines or toxoids until corticosteroid therapy is discontinued. |
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
There are no data regarding the use of Ledercort in pregnant women to inform a drug associated risk of adverse developmental outcomes. Published studies on the association between corticosteroids and fetal outcomes have reported inconsistent findings and have important methodological limitations. The majority of published literature with corticosteroid exposure during pregnancy includes the oral, topical and inhaled dosage formulations; therefore, the applicability of these findings to a single intra-articular injection of Ledercort (Triamcinolone Acetonide) is limited. In animal reproductive studies from the published literature, pregnant mice, rats, rabbits, or primates administered Ledercort (Triamcinolone Acetonide) during the period of organogenesis at doses that produced exposures less than the maximum recommended human dose (MRHD) caused resorptions, decreased fetal body weight, craniofacial and/or other abnormalities such as omphalocele .
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Data
Animal Data
The exposure margins listed below are based on body surface area comparisons (mg/m 2) to the highest daily Ledercort (Triamcinolone Acetonide) exposure at the MRHD of 32 mg Ledercort (Triamcinolone Acetonide) via Ledercort (Triamcinolone Acetonide).
Pregnant mice dosed with Ledercort (Triamcinolone Acetonide) via intramuscular or subcutaneous injection at doses equivalent to 0.8 times the MRHD or higher during organogenesis caused cleft palate and a higher rate of resorption. In pregnant rats dosed with Ledercort (Triamcinolone Acetonide) via intramuscular or subcutaneous injection at doses equivalent to 0.3 times the MRHD or higher during organogenesis caused developmental abnormality (cleft palate, omphalocele, late resorption, and growth retardation) and fetal mortality. No notable maternal toxicity was observed in rodents.
Pregnant rabbits dosed with Ledercort (Triamcinolone Acetonide) via intramuscular injection for 4 days during organogenesis at doses equivalent to 0.15 times the MRHD or higher caused resorption and cleft palate. No notable maternal toxicity was observed.
Pregnant primates dosed with Ledercort (Triamcinolone Acetonide) via intramuscular injection for 4 days during organogenesis at doses equivalent to 3 times the MRHD or higher caused severe craniofacial CNS and skeletal/visceral malformation and higher prenatal death. No notable maternal toxicity was observed.
No peri- and post-natal development studies of Ledercort (Triamcinolone Acetonide) in animals have been conducted.
8.2 Lactation
Risk Summary
There are no available data on the presence of Ledercort (Triamcinolone Acetonide) in either human or animal milk, the effects on the breastfed infant, or the effects on milk production. However, corticosteroids have been detected in human milk and may suppress milk production. It is not known whether intra-articular administration of Ledercort (Triamcinolone Acetonide) could result in sufficient systemic absorption to produce detectable quantities in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Ledercort (Triamcinolone Acetonide) and any potential adverse effects on the breastfed infant from Ledercort (Triamcinolone Acetonide) or from the underlying maternal condition.
8.3 Females and Males of Reproductive Potential
Corticosteroids may result in menstrual pattern irregularities such as deviations in timing and duration of menses and an increased or decreased loss of blood.
8.4 Pediatric Use
The safety and effectiveness of Ledercort in pediatric patients have not been established.
The adverse effects of corticosteroids in pediatric patients are similar to those in adults. Carefully observe pediatric patients, including weight, height, linear growth, blood pressure, intraocular pressure, and clinical evaluation for the presence of infection, psychosocial disturbances, thromboembolism, peptic ulcers, cataracts, and osteoporosis. Weigh potential growth effects of treatment against clinical benefits obtained and the availability of treatment alternatives.
8.5 Geriatric Use
Of the total number of patients administered 32 mg Ledercort (Triamcinolone Acetonide) in clinical studies (N=424), 143 patients were 65 years of age or older. No overall differences in safety or effectiveness were observed between elderly and younger subjects, and other reported clinical experience with Ledercort (Triamcinolone Acetonide) has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
11 DESCRIPTION
Ledercort (Triamcinolone Acetonide) (triamcinolone acetonide extended-release injectable suspension) is a microsphere formulation of Ledercort (Triamcinolone Acetonide), a corticosteroid, to be administered by intra-articular injection.
Ledercort (Triamcinolone Acetonide) is formulated in 75:25 poly(lactic-co-glycolic acid) (PLGA) microspheres with a nominal drug load of 25% (w/w) and is provided as a sterile white to off-white powder. Ledercort (Triamcinolone Acetonide) is prepared with a supplied diluent containing an isotonic, sterile, aqueous solution of sodium chloride (NaCl; 0.9% w/w), sodium carboxymethylcellulose (CMC; 0.5% w/w) and polysorbate-80 (0.1% w/w) to form a 5 mL sterile suspension intended for intra-articular injection.
Active Ingredient
The chemical name for Ledercort (Triamcinolone Acetonide) is 9-fluoro-11β,16α,17,21-tetrahydroxypregna-1,4-diene- 3,20-dione cyclic 16,17-acetal with acetone. Its structural formula is:
| MW 434.50 with a molecular formula of C 24H 31FO 6 |
Ledercort (Triamcinolone Acetonide) occurs as a white to almost white, crystalline powder having not more than a slight odor and is practically insoluble in water and very soluble in alcohol. Each vial of Ledercort (Triamcinolone Acetonide) powder contains 40 mg of Ledercort (Triamcinolone Acetonide) in 160 mg of microspheres, resulting in 32 mg of deliverable Ledercort (Triamcinolone Acetonide) when prepared according to the Instructions for Use.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Ledercort is a corticosteroid with anti-inflammatory and immunomodulating properties. It binds to and activates the glucocorticoid receptor, leading to activation of anti-inflammatory transcription factors such as lipocortins and inhibition of inflammatory transduction pathways by blocking the release of arachidonic acid and preventing the synthesis of prostaglandins and leukotrienes.
12.2 Pharmacodynamics
Studies indicate that following a single intramuscular dose of 60 to 100 mg of immediate-release Ledercort (Triamcinolone Acetonide) injectable suspension, adrenal suppression occurs within 24 to 48 hours and then gradually returns to normal, usually in 30 to 40 days. To assess potential effects of the systemic levels of Ledercort (Triamcinolone Acetonide) associated with a single intra-articular (IA) administration of Ledercort (Triamcinolone Acetonide) on hypothalamic pituitary adrenal (HPA) axis function, serum and urine cortisol levels were monitored over 6 weeks post injection. Adrenal suppression with Ledercort (Triamcinolone Acetonide) occurred within 12-24 hours and then gradually returned to normal, within 30-42 days.
Corticosteroids may increase blood glucose concentrations.
In a study where 18 patients with osteoarthritis knee pain and controlled type 2 diabetes mellitus received a single IA injection of Ledercort (Triamcinolone Acetonide) into the knee, the change from baseline in average blood glucose over the 72 hours after injection as measured by a continuous glucose monitoring device was 8.2 mg/dL (95% confidence interval 0.1, 29.2).
12.3 Pharmacokinetics
Ledercort (Triamcinolone Acetonide) is an extended-release dosage form consisting of microspheres of poly(lactic-co-glycolic acid) (PLGA) containing Ledercort (Triamcinolone Acetonide). Plasma pharmacokinetic parameters for Ledercort (Triamcinolone Acetonide) following IA administration of Ledercort (Triamcinolone Acetonide) or 40 mg immediate-release Ledercort (Triamcinolone Acetonide) into the knee are provided in Table 4.
| * 33 patients contributed to the analyses of these parameters | ||
| † 14 patients contributed to the analyses of these parameters | ||
| 1 Median (min, max) values for t max | ||
| Ledercort (Triamcinolone Acetonide) PK Parameters 1 | Ledercort (Triamcinolone Acetonide) (N=60) | Ledercort (Triamcinolone Acetonide) (N=18) |
| C max (pg/mL) | 1143.7 (611.06) | 21062.2 (18466.79) |
| AUC 0-24 hour (pg-h/mL) | 21219.2 (11325.62) | 297545.3 (222402.77) |
| AUC 0-inf (pg-h/mL) | 842149.2 (1062004.97)* | 1567565.0 (1246330.95) † |
| t max (h) | 7 (1, 1008) | 6 (2, 24) |
| t 1/2 (h) | 633.9 (893.0)* | 146.9 (213.29) † |
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenesis
Long-term animal studies to evaluate the carcinogenic potential of Ledercort (Triamcinolone Acetonide) have not been conducted.
Mutagenesis
Adequate mutagenicity studies have not been conducted with Ledercort (Triamcinolone Acetonide).
Impairment of Fertility
Studies in animals to evaluate the impairment of fertility of Ledercort (Triamcinolone Acetonide) have not been conducted.
14 CLINICAL STUDIES
The efficacy of Ledercort (Triamcinolone Acetonide) was demonstrated in a multi-center, international, randomized, double-blind, parallel-arm, placebo- and active-controlled study in patients with osteoarthritis pain of the knee. A total of 484 patients (ZILRETTA 32 mg, N=161; placebo [saline], N=162; active control [a crystalline suspension, immediate-release formulation of Ledercort (Triamcinolone Acetonide) 40 mg], N=161) were treated and followed for up to 24 weeks. Patients had a mean age of 62 (range 40 to 85 years); baseline demographics and disease characteristics were balanced across treatment arms. Twenty-five percent (25%) of patients had received at least one prior corticosteroid intra-articular injection more than 3 months prior to treatment. A total of 470 patients (97%) completed follow-up to Week 12, the time point for primary efficacy determination, and 443 (91.5%) completed to Week 24.
The primary efficacy endpoint comparing Ledercort (Triamcinolone Acetonide) to placebo was change from baseline at Week 12 in the weekly mean of the Average Daily Pain intensity scores (ADP) as assessed by a 0-10 Numeric Rating Scale (NRS). Ledercort (Triamcinolone Acetonide) demonstrated a statistically significant reduction in pain intensity at the primary endpoint vs placebo. Ledercort (Triamcinolone Acetonide) also demonstrated a reduction in pain intensity scores each week from Weeks 1 through 12 ( Figure 1 ).
In a secondary exploratory analysis, statistical significance was not demonstrated between the Ledercort (Triamcinolone Acetonide) and the active control (immediate-release Ledercort (Triamcinolone Acetonide)) treatment groups for the change from baseline at Week 12 in weekly mean ADP.
Figure 1: Weekly Change from Baseline to Week 12 in Average Daily Pain
16 HOW SUPPLIED/STORAGE AND HANDLING
| Description | NDC | Presentation/How Supplied |
| Ledercort (Triamcinolone Acetonide) | NDC 70801-003-01 | Ledercort (Triamcinolone Acetonide) (triamcinolone acetonide extended-release injectable suspension) single-dose kit. |
| Kit Contents | ||
| Ledercort (Triamcinolone Acetonide) microsphere powder | NDC 70801-001-01 | 5 mL single-dose vial to deliver 32 mg of Ledercort (Triamcinolone Acetonide) supplied as a sterile, white to off-white powder in a cerium glass (clear) vial with a rubber stopper and an aluminum seal with a gray plastic cap. |
| Diluent | NDC 70801-002-01 | 5 mL single-dose vial supplied as a sterile, clear liquid solution of 0.9% w/w sodium chloride (normal saline) containing 0.5% w/w sodium carboxymethylcellulose, and 0.1% w/w polysorbate-80 in a glass vial with a rubber stopper, aluminum seal and white plastic cap. |
| Sterile vial adapter | ||
STORAGE
To maintain expiry period, refrigerate the Ledercort (Triamcinolone Acetonide) single-dose kit (36°-46°F; 2°-8°C) before use.
If refrigeration is unavailable, store the Ledercort (Triamcinolone Acetonide) single-dose kit in the sealed, unopened kit at temperatures not exceeding 77°F (25°C) for up to six weeks and then discard. Do not expose the Ledercort (Triamcinolone Acetonide) single-dose kit to temperatures above 77°F (25°C).
Do not freeze. Store vials in carton.
17 PATIENT COUNSELING INFORMATION
Increased Risk of Infections
Inform patients that they may be more likely to develop infections when taking corticosteroids. Instruct patients to contact their health care provider if they develop fever or other signs or symptoms of infection.
Advise patients who have not been vaccinated to avoid exposure to chicken pox or measles. Instruct patients to contact their health care provider immediately if they are exposed .
Risk of Drug Interactions
There are a number of medicines that can interact with corticosteroids such as Ledercort (Triamcinolone Acetonide). Advise patients to alert their health care provider(s) to assess the need to adjust their medication(s) .
Risk of Adverse Psychiatric Reactions
Inform patients that corticosteroid use may be associated with adverse psychiatric reactions. Advise patients and/or caregivers to immediately report any new or worsening behavioral or mood disturbances to their health care provider .
Manufactured for Flexion Therapeutics, Inc., 10 Mall Rd, Suite 301, Burlington, MA 01803
Ledercort (Triamcinolone Acetonide) and Flexion are trademarks of Flexion Therapeutics, Inc.
Copyright © 2017 Flexion Therapeutics, Inc. All rights reserved.
For more information, go to Ledercort (Triamcinolone Acetonide).com or call 1-844-FLEXION (353-9466).
Part Number: 60-004-01
Version: 1, 10/2017
Instructions for Use
Ledercort (Triamcinolone Acetonide)
(triamcinolone acetonide
extended-release injectable suspension)
For intra-articular injection only
Single-dose device
Do not reuse.
IMPORTANT INFORMATION
- Ledercort (Triamcinolone Acetonide) must be prepared using only the diluent supplied in the kit.
- To ensure proper dosing, it is important that you follow the preparation and administration steps outlined in these instructions.
- Promptly inject Ledercort (Triamcinolone Acetonide) after preparation to avoid settling of the suspension.
- Ledercort (Triamcinolone Acetonide) is supplied as a single-dose kit and administered as a suspension containing microspheres.
- The Ledercort (Triamcinolone Acetonide) powder vial contains an overfill to allow the appropriate dose to be withdrawn. Ledercort (Triamcinolone Acetonide) is a suspension product and it is normal for some residue to be left behind on the vial walls after withdrawing the contents.
- Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration.
- Use proper aseptic technique throughout the dose preparation and administration procedure.
- Inspect all kit components to confirm they have not expired and the seals are intact.
- For additional information, visit www.zilretta.com or call Flexion Therapeutics at 1-844-FLEXION (353-9466).
MATERIALS REQUIRED
(Fig.1)
Supplied
- One 32 mg vial of Ledercort (Triamcinolone Acetonide) microsphere powder
- One 5 mL vial of sterile diluent
- One sterile vial adapter
Not Supplied
- Three sterile needles, 21-gauge, 1½” length
- One sterile Luer Lock compatible syringe, 5 mL
- Sterile alcohol pads
- Paper towels or pad to cushion vial tapping (not shown in Fig. 1)
- Medical-grade gloves (not shown in Fig. 1)
Figure 1
1. Vial Preparation
Loosen Powder.
Place two paper towels or a pad on a properly-cleaned hard surface.
Grip the top of the Ledercort (Triamcinolone Acetonide) powder vial and tap firmly and repeatedly on the padded surface. Tap the vial until excess powder is dislodged from the vial and stopper ( Fig. 2). Before continuing, ensure that powder moves freely within the vial.
Figure 2
Inspect Ledercort (Triamcinolone Acetonide) Powder Vial.
As shown in Figure 3, the vial on the left, with the X, requires additional tapping because the powder is not properly dislodged. The vial on the right shows the powder properly dislodged and ready for the next step.
Figure 3
Remove Caps.
Remove the flip-off caps from the Ledercort (Triamcinolone Acetonide) powder and diluent vials ( Fig. 4).
Figure 4
Clean Vials.
Clean the Ledercort (Triamcinolone Acetonide) powder and diluent vial tops with an alcohol pad.
Use a separate alcohol pad for each vial.
Peel Off Vial Adapter Cover.
Peel off the paper cover from the vial adapter package ( Fig. 5).
Leave the adapter in the plastic holder.
Figure 5
Attach Vial Adapter to Ledercort (Triamcinolone Acetonide) Powder Vial.
Grip the plastic holder that contains the vial adapter.
As shown in Figure 6, place the Ledercort (Triamcinolone Acetonide) powder vial on a flat surface. In a vertical orientation, gently push the adapter down onto the Ledercort (Triamcinolone Acetonide) powder vial until the spike on the adapter penetrates the rubber stopper on the Ledercort (Triamcinolone Acetonide) powder vial. The adapter will snap into place.
Figure 6
2. Diluent Preparation
Attach Needle.
Attach a needle to the syringe and remove the needle guard.
Withdraw Diluent.
With a syringe and needle, withdraw 5 mL of diluent.
Replace the needle guard.
3. Dose Preparation
Remove Holder.
Remove the plastic holder from the vial adapter ( Fig. 7).
Figure 7
Remove Needle.
Remove the needle from the syringe containing diluent.
Attach Diluent Syringe.
Attach the syringe onto the vial adapter by pushing down and turning clockwise until you feel resistance ( Fig. 8).
Figure 8
Transfer Diluent.
Slowly and completely push down the syringe plunger to transfer the diluent into the Ledercort (Triamcinolone Acetonide) powder vial ( Fig. 9).
Note: Equalize the pressure in the syringe by slowly pulling back the plunger to the 5 mL mark. Ensure that no solution is drawn back into the syringe at this stage.
Figure 9
Mix Diluent and Powder ( Fig. 10).
With the syringe still attached to the Ledercort (Triamcinolone Acetonide) powder vial, hold the syringe and vial at a slight angle. Tap the bottom edge of the vial firmly and repeatedly, in a circular motion, on the padded surface.
Swirl gently every five or six taps.
Tap for at least one minute until all powder is completely dispersed.
Note: Avoid vigorous shaking of the vial to minimize foaming.
Note: At least one minute of tapping and gentle swirling is required to achieve uniform suspension.
Figure 10
Inspect Vial.
Inspect the Ledercort (Triamcinolone Acetonide) powder vial to ensure no clumped powder is visible and a uniform suspension has been achieved. A properly mixed suspension will be milky white, contain no clumps, and move freely down the vial wall.
As shown in Figure 11, the vial on the left, with the X, requires more tapping and gentle swirling because the powder is not mixed properly with the diluent. The vial on the right shows the powder properly mixed and ready for the next step.
Figure 11
Note: If needed, the Ledercort (Triamcinolone Acetonide) suspension can be stored in the vial for up to 4 hours at ambient conditions. The syringe must remain on the vial adapter while the suspension remains in the vial.
Withdraw Contents into Syringe.
Swirl the vial gently for at least 10 seconds to ensure the powder is fully suspended. Immediately depress the plunger fully and then invert the syringe so the vial is directly on top of the syringe ( Fig. 12).
Hold the syringe in a completely vertical position, per the illustration on the right, in Figure 12.
Withdraw the full contents from the Ledercort (Triamcinolone Acetonide) vial into the syringe.
Figure 12
Note: Ledercort (Triamcinolone Acetonide) is a suspension product and it is normal for some residue to be left behind on the vial walls after withdrawing the contents.
Remove Syringe.
Remove the syringe from the vial adapter by turning counter-clockwise.
Remove Air Bubbles.
Attach a new needle to the syringe and remove the needle guard.
Inspect for bubbles with the syringe held in a completely vertical position (needle upward). If bubbles are observed, gently tap the syringe with your finger until the bubbles rise to the top. Eliminate all bubbles by slowly depressing the plunger to displace the air from the syringe.
Replace the needle guard.
Attach New Needle.
Remove and discard the needle.
Attach a new needle.
4. Administration
Invert Syringe.
To ensure the powder is suspended, gently invert the syringe containing Ledercort (Triamcinolone Acetonide) several times just prior to administration, as shown in Figure 13.
Grip the syringe firmly and turn it so the syringe plunger is pointing straight down. Then turn the syringe gently, 180 degrees, until the plunger is pointing straight up.
Invert the syringe several times to ensure a properly mixed suspension.
Figure 13
A properly mixed suspension will be uniformly milky white and contain no clumps.
Inspect Syringe.
As shown in Figure 14, the syringe on the left, with the X, requires more inversions (turning) to properly mix the suspension. The syringe on the right shows the suspension properly mixed and ready for the next step.
Figure 14
Administer Ledercort (Triamcinolone Acetonide).
The usual technique for intra-articular injection should be followed.
Aspiration of synovial fluid may be performed based on clinical judgment prior to administration of Ledercort (Triamcinolone Acetonide).
Do not reuse excess Ledercort (Triamcinolone Acetonide). Any excess suspension in the vial should be thrown away immediately after the injection. Leftover Ledercort (Triamcinolone Acetonide) in the vial must never be reused for another injection.
Note: The entire contents of the syringe must be injected to ensure the intended dose of Ledercort (Triamcinolone Acetonide) is delivered.
Note: Discard all used components in an appropriate medical waste container according to local regulations.
Note: Ledercort (Triamcinolone Acetonide) is for intra-articular use only. Ledercort (Triamcinolone Acetonide) is not intended for epidural, intrathecal, intravenous, intraocular, intramuscular, intradermal, or subcutaneous use.
Part Number: 60-005-01
Rev: 10/2017
Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14
Principal Display Panel - Ledercort (Triamcinolone Acetonide) Cart 32mg Carton Label
NDC 70801-003-01 Rx Only
Ledercort (Triamcinolone Acetonide)
(triamcinolone acetonide extended-release
injectable suspension)
32 mg per vial
For intra-articular injection only.
Single-dose kit. Discard unused portion.
Must be reconstituted
with the supplied diluent.
This carton contains:
1 Vial of Ledercort (Triamcinolone Acetonide)
microsphere powder
1 Vial of diluent (5 mL)
for Ledercort (Triamcinolone Acetonide)
1 sterile vial adapter
flexion
Principal Display Panel - Ledercort (Triamcinolone Acetonide) Cart 32mg Professional Carton Label
NDC 70801-003-02 Rx Only
Ledercort (Triamcinolone Acetonide)
(triamcinolone acetonide extended-release
injectable suspension)
32 mg per vial
For intra-articular injection only.
Single-dose kit. Discard unused portion.
Must be reconstituted
with the supplied diluent.
PROFESSIONAL SAMPLE
NOT FOR SALE
OR REIMBURSEMENT
This carton contains:
1 Vial of Ledercort (Triamcinolone Acetonide)
microsphere powder
1 Vial of diluent (5 mL)
for Ledercort (Triamcinolone Acetonide)
1 sterile vial adapter
flexion
Principal Display Panel - Ledercort (Triamcinolone Acetonide) 32mg Vial Label
NDC 70801-001-01 Rx Only
Ledercort (Triamcinolone Acetonide)
(triamcinolone acetonide extended-release
injectable suspension)
32 mg per vial
For intra-articular injection only.
Must be reconstituted
with the supplied diluent.
flexion
Principal Display Panel - Ledercort (Triamcinolone Acetonide) 32mg Professional Vial Label
NDC 70801-001-02 Rx Only
Ledercort (Triamcinolone Acetonide)
(triamcinolone acetonide extended-release
injectable suspension)
32 mg per vial
For intra-articular injection only.
Must be reconstituted
with the supplied diluent.
flexion
Principal Display Panel - Ledercort (Triamcinolone Acetonide) Diluent 5mL Vial Label
NDC 70801-002-01 Rx Only
DILUENT
for use with Ledercort (Triamcinolone Acetonide)
5 mL
Sterile single-use vial
Do not administer directly.
flexion
Principal Display Panel - Ledercort (Triamcinolone Acetonide) Diluent 5mL Professional Vial Label
NDC 70801-002-02 Rx Only
DILUENT
for use with Ledercort (Triamcinolone Acetonide)
5 mL
Sterile single-use vial
Do not administer directly.
flexion
Ledercort pharmaceutical active ingredients containing related brand and generic drugs:
Ledercort available forms, composition, doses:
Ledercort destination | category:
Ledercort Anatomical Therapeutic Chemical codes:
Ledercort pharmaceutical companies:
References
- Dailymed."VETALOG (TRIAMCINOLONE ACETONIDE) INJECTION, SUSPENSION [BOEHRINGER INGELHEIM VETMEDICA, INC.]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
- Dailymed."TRIAMCINOLONE ACETONIDE: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
- Dailymed."TRIAMCINOLONE: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
Frequently asked Questions
Can i drive or operate heavy machine after consuming Ledercort?Depending on the reaction of the Ledercort after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Ledercort not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.
Is Ledercort addictive or habit forming?Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.
Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.
Review
sdrugs.com conducted a study on Ledercort, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Ledercort consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.Visitor reports
Visitor reported useful
No survey data has been collected yetVisitor reported side effects
No survey data has been collected yetVisitor reported price estimates
No survey data has been collected yetVisitor reported frequency of use
No survey data has been collected yetVisitor reported doses
No survey data has been collected yetOne visitor reported time for results
What is the time duration Ledercort drug must be taken for it to be effective or for it to reduce the symptoms?Most chronic conditions need at least some time so the dose and the drug action gets adjusted to the body to get the desired effect. The stastistics say sdrugs.com website users needed 1 month to notice the result from using Ledercort drug. The time needed to show improvement in health condition after using the medicine Ledercort need not be same for all the users. It varies based on other factors.
| Visitors | % | ||
|---|---|---|---|
| 1 month | 1 | 100.0% | |
Visitor reported administration
No survey data has been collected yetVisitor reported age
No survey data has been collected yetVisitor reviews
There are no reviews yet. Be the first to write one! |
The information was verified by Dr. Rachana Salvi, MD Pharmacology