Zilretta
Generic: TRIAMCINOLONE ACETONIDE EXTENDED-RELEASE INJECTABLE SUSPENSION
Basic Information
Manufacturer
Pacira Pharmaceuticals, Inc.
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
INTRA-ARTICULAR
FDA Set ID
cd5c4673-21f2-4126-9556-da847b3a228b
Indications & Usage
1 INDICATIONS AND USAGE ZILRETTA (triamcinolone acetonide extended-release injectable suspension) is indicated as an intra-articular injection for the management of osteoarthritis pain of the knee.
ZILRETTA 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 The efficacy and safety of repeat administration of ZILRETTA have not been demonstrated.
( 2.1 ) Limitation of Use The efficacy and safety of repeat administration of ZILRETTA have not been demonstrated.
[see Dosage and Administration (2.1) ] .
ZILRETTA 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 The efficacy and safety of repeat administration of ZILRETTA have not been demonstrated.
( 2.1 ) Limitation of Use The efficacy and safety of repeat administration of ZILRETTA have not been demonstrated.
[see Dosage and Administration (2.1) ] .
Adverse Reactions
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) ] Most commonly reported adverse reactions (incidence ≥1%) in clinical studies include sinusitis, cough, and contusions.
( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Pacira Pharmaceuticals, Inc.
at 1-844-353-9466 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1 Clinical Trials 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 ZILRETTA 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 ZILRETTA and 262 received placebo.
Treatment emergent adverse reactions reported by greater than or equal to 1% of patients in the ZILRETTA arms are summarized below ( Table 1 and 2 ).
Overall, the incidence and nature of adverse reactions was similar to that observed with placebo.
Table 1: Most Commonly Reported Treatment-Emergent Adverse Reactions with ZILRETTA (Incidence ≥1%) in Patients with Osteoarthritis of the Knee Preferred Term (MedDRA) ZILRETTA (N=424) Placebo (N=262) Sinusitis 2% 1% Cough 2% 1% Contusions 2% 1% Table 2: Most Commonly Reported Treatment-Emergent Injected Knee Adverse Reactions with ZILRETTA (Incidence ≥1%) in Patients with Osteoarthritis of the Knee Preferred Term (MedDRA) ZILRETTA (N=424) Placebo (N=262) Joint Swelling 3% 2% Contusions 2% 1% The safety of repeat administration of ZILRETTA was evaluated in a multicenter, open-label, single-arm study in patients with osteoarthritis pain of the knee.
A total of 179 patients received a repeat injection on or after Week 12 (median 16.6 weeks) and were followed for 52 weeks from the initial injection.
As assessed by adverse event rates for the periods of baseline to second dose and second dose to the comparable period after the second dose, there were higher rates of reported mild to moderate arthralgia after the second dose (16%) than after the first dose (6%).
The data from this study are insufficient to fully characterize the safety of repeat administration of ZILRETTA.
[See also Nonclinical Toxicology (13.2) ].
6.2 Post-marketing Experience The following adverse reactions, presented alphabetically by body system, have been identified during post-approval use of ZILRETTA.
Because 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.
Endocrine : Increased blood glucose (in diabetic patients).
General and administration site conditions : Pain including injection site pain or discomfort and leg pain.
Immune system : Hypersensitivity reactions including pruritus, rash, angioedema, and anaphylaxis [see Contraindications (4) , Warnings and Precautions (5.3) ] .
Infections and Infestations : Septic arthritis [see Warning and Precautions (5.4) ] .
Musculoskeletal : Arthralgia, joint swelling or effusion, muscle spasms.
Nervous system : Headache.
Reproductive system : Postmenopausal vaginal bleeding (similar to a menstrual period).
Skin and Subcutaneous Tissue : Pruritus.
6.3 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 [see Warnings and Precautions (5.3) ] .
Cardiovascular : Bradycardia, cardiac arrest, cardiac arrhythmias, cardiac enlargement, circulatory collapse, congestive heart failure, hypertension [see Warnings and Precautions (5.7) ] , 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 [see Warnings and Precautions (5.7) ] , fluid retention, sodium retention.
Gastrointestinal : Abdominal distention, bowel/bladder dysfunction (after intrathecal administration) [see Warnings and Precautions (5.2) ] , 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) [see Warnings and Precautions (5.10) ] , 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 [see Warnings and Precautions (5.12) ] , 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 [see Warnings and Precautions (5.2) ] .
Ophthalmic : Exophthalmos, glaucoma, increased intraocular pressure [see Warnings and Precautions (5.9) ] , 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.
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) ] Most commonly reported adverse reactions (incidence ≥1%) in clinical studies include sinusitis, cough, and contusions.
( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Pacira Pharmaceuticals, Inc.
at 1-844-353-9466 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1 Clinical Trials 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 ZILRETTA 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 ZILRETTA and 262 received placebo.
Treatment emergent adverse reactions reported by greater than or equal to 1% of patients in the ZILRETTA arms are summarized below ( Table 1 and 2 ).
Overall, the incidence and nature of adverse reactions was similar to that observed with placebo.
Table 1: Most Commonly Reported Treatment-Emergent Adverse Reactions with ZILRETTA (Incidence ≥1%) in Patients with Osteoarthritis of the Knee Preferred Term (MedDRA) ZILRETTA (N=424) Placebo (N=262) Sinusitis 2% 1% Cough 2% 1% Contusions 2% 1% Table 2: Most Commonly Reported Treatment-Emergent Injected Knee Adverse Reactions with ZILRETTA (Incidence ≥1%) in Patients with Osteoarthritis of the Knee Preferred Term (MedDRA) ZILRETTA (N=424) Placebo (N=262) Joint Swelling 3% 2% Contusions 2% 1% The safety of repeat administration of ZILRETTA was evaluated in a multicenter, open-label, single-arm study in patients with osteoarthritis pain of the knee.
A total of 179 patients received a repeat injection on or after Week 12 (median 16.6 weeks) and were followed for 52 weeks from the initial injection.
As assessed by adverse event rates for the periods of baseline to second dose and second dose to the comparable period after the second dose, there were higher rates of reported mild to moderate arthralgia after the second dose (16%) than after the first dose (6%).
The data from this study are insufficient to fully characterize the safety of repeat administration of ZILRETTA.
[See also Nonclinical Toxicology (13.2) ].
6.2 Post-marketing Experience The following adverse reactions, presented alphabetically by body system, have been identified during post-approval use of ZILRETTA.
Because 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.
Endocrine : Increased blood glucose (in diabetic patients).
General and administration site conditions : Pain including injection site pain or discomfort and leg pain.
Immune system : Hypersensitivity reactions including pruritus, rash, angioedema, and anaphylaxis [see Contraindications (4) , Warnings and Precautions (5.3) ] .
Infections and Infestations : Septic arthritis [see Warning and Precautions (5.4) ] .
Musculoskeletal : Arthralgia, joint swelling or effusion, muscle spasms.
Nervous system : Headache.
Reproductive system : Postmenopausal vaginal bleeding (similar to a menstrual period).
Skin and Subcutaneous Tissue : Pruritus.
6.3 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 [see Warnings and Precautions (5.3) ] .
Cardiovascular : Bradycardia, cardiac arrest, cardiac arrhythmias, cardiac enlargement, circulatory collapse, congestive heart failure, hypertension [see Warnings and Precautions (5.7) ] , 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 [see Warnings and Precautions (5.7) ] , fluid retention, sodium retention.
Gastrointestinal : Abdominal distention, bowel/bladder dysfunction (after intrathecal administration) [see Warnings and Precautions (5.2) ] , 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) [see Warnings and Precautions (5.10) ] , 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 [see Warnings and Precautions (5.12) ] , 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 [see Warnings and Precautions (5.2) ] .
Ophthalmic : Exophthalmos, glaucoma, increased intraocular pressure [see Warnings and Precautions (5.9) ] , 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.