Zilretta
(triamcinolone acetonide)Dosage & Administration
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Zilretta Prescribing Information
ZILRETTA (triamcinolone acetonide extended-release injectable suspension) is indicated as an intra-articular injection for the management of osteoarthritis pain of the knee.
Limitation of Use
The efficacy and safety of repeat administration of ZILRETTA have not been demonstrated. [see Dosage and Administration (2.1)].
Important Dosage and Administration Information
- ZILRETTA is administered as a single intra-articular extended-release injection of triamcinolone acetonide, to deliver 32 mg (5 mL).
- ZILRETTA is for intra-articular use only. Do NOT administer by the following routes: epidural, intrathecal, intravenous, intraocular, intramuscular, intradermal, subcutaneous.
- ZILRETTA is not suitable for use in small joints, such as the hand.
- The efficacy and safety of repeat administration of ZILRETTA have not been demonstrated [see Adverse Reactions (6) and Nonclinical Toxicology (13.2)].
- The efficacy and safety of ZILRETTA for management of osteoarthritis pain of shoulder and hip have not been evaluated.
Preparation and Administration of Intra-Articular Suspension
Refer to the Instructions for Use for directions on the preparation and administration of ZILRETTA.
ZILRETTA is supplied as a single-dose kit containing a vial of ZILRETTA microsphere powder, a vial of sterile diluent, and a sterile vial adapter.
ZILRETTA must be prepared using the diluent supplied in the kit.
Preparation of ZILRETTA requires close attention to the Instructions for Use to ensure successful administration.
Use proper aseptic technique throughout the dose preparation and administration procedure.
ZILRETTA 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 ZILRETTA after preparation to avoid settling of the suspension. If needed, the ZILRETTA 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 ZILRETTA.
Non-Interchangeability with Other Formulations of Triamcinolone Acetonide for Intra-articular Use
ZILRETTA is NOT substitutable with other formulations of injectable triamcinolone acetonide.
ZILRETTA is an injectable suspension that delivers 32 mg of triamcinolone acetonide. ZILRETTA is supplied as a single-dose kit, containing:
- One vial of ZILRETTA white to off-white microsphere powder
- One vial of 5 mL sterile, colorless to pale yellow, clear diluent
- One sterile vial adapter
Pregnancy
Risk Summary
There are no data regarding the use of ZILRETTA 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 triamcinolone acetonide is limited. In animal reproductive studies from the published literature, pregnant mice, rats, rabbits, or primates administered 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 (see Data).
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/m2) to the highest daily triamcinolone acetonide exposure at the MRHD of 32 mg triamcinolone acetonide via ZILRETTA.
Pregnant mice dosed with 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 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 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 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 triamcinolone acetonide in animals have been conducted.
Lactation
Risk Summary
There are no available data on the presence of 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 ZILRETTA 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 ZILRETTA and any potential adverse effects on the breastfed infant from ZILRETTA or from the underlying maternal condition.
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.
Pediatric Use
The safety and effectiveness of ZILRETTA 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.
Geriatric Use
Of the total number of patients administered 32 mg ZILRETTA 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 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.
ZILRETTA is contraindicated in patients who are hypersensitive to triamcinolone acetonide, corticosteroids or any components of the product [see Warnings and Precautions (5.3) and How Supplied/Storage and Handling (16)].
Warnings and Precautions Specific for ZILRETTA
ZILRETTA has not been evaluated and should not be administered by the following routes:
- Epidural
- Intrathecal
- Intravenous
- Intraocular
- Intramuscular
- Intradermal
- Subcutaneous
[see Warnings and Precautions (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 [see Adverse Reactions (6)]. 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 [see Adverse Reactions (6)].
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 ZILRETTA should not be considered safe to use for epidural or intrathecal administration.
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 triamcinolone acetonide injection, regardless of the route of administration [see Adverse Reactions (6)]. Institute appropriate care upon occurrence of an anaphylactic reaction.
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 [see Adverse Reactions (6)].
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.
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 [see Patient Counseling Information (17)].
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 (as in trauma, surgery, or illness), institute corticosteroid replacement therapy.
Metabolic clearance of corticosteroids is decreased in hypothyroid patients and increased in hyperthyroid patients.
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.
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.
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.
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.
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 (e.g., postmenopausal women) before initiating corticosteroid therapy.
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.