GEMS Supplier Focus Guide - Q2 2020 - 50

Pharmaceuticals

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ZILRETTA® (triamcinolone acetonide extended-release injectable suspension) for
intra-articular use
BRIEF SUMMARY OF PRESCRIBING INFORMATION: See package insert for full
Prescribing Information.
1. INDICATIONS AND USAGE
ZILRETTA is indicated as an intra-articular (IA) injection for the management of
osteoarthritis (OA) pain of the knee.
Limitation of Use: The efficacy and safety of repeat administration of ZILRETTA have
not been demonstrated.
4. CONTRAINDICATION
ZILRETTA is contraindicated in patients who are hypersensitive to triamcinolone
acetonide (TA), corticosteroids (CSs), or any components of
the product.
5. WARNINGS AND PRECAUTIONS
5.1 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,
or 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 CSs. 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 CS administration. The safety and effectiveness of epidural
and intrathecal administration of CSs have not been established, and CSs are not
approved for this use. In particular, the formulation of ZILRETTA 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 CSs. Cases of serious anaphylaxis, including death,
have been reported in individuals receiving TA injection, regardless of the route of
administration. Institute appropriate care if an anaphylactic reaction occurs.
5.4 Joint Infection and Damage IA injection of a CS 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 CS into an infected site.
Local injection of a CS into a previously infected joint is not usually recommended.
Examine any joint fluid present to exclude a septic process. CS injection into
unstable joints is generally not recommended. IA injection may result in damage
to joint tissues.
5.5 Increased Risk of Infections Intra-articularly injected CSs are systemically
absorbed. Patients who are on CSs are more susceptible to infections than healthy
individuals. There may be decreased resistance and inability to localize infection
when CSs 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 CSs
alone or in combination with other immunosuppressive agents. These infections
may be mild to severe. With increasing doses of CSs, the rate of occurrence of
infectious complications increases. CSs may also mask some signs of current
infection. Advise patients to inform their health care provider (HCP) 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 HCP immediately if they are exposed.
5.6 Alterations in Endocrine Function CSs can produce reversible hypothalamicpituitary-adrenal axis suppression, with 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 CS replacement therapy.
Metabolic clearance of CSs is decreased in hypothyroid patients and increased in
hyperthyroid patients.
5.7 Cardiovascular Effects CSs 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 (CHF) 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 CSs can cause salt and water retention, and increased excretion
of potassium. These effects are less likely to occur with synthetic derivatives. All
CSs 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 CS 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 (GI) Perforation CS administration is associated with
increased risk of GI 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 CSs in these patients because signs of
peritoneal irritation following GI perforation may be minimal or absent.
5.11 Alterations in Bone Density CSs 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 (eg, postmenopausal women) before initiating CS therapy.
5.12 Behavioral and Mood Disturbances CS 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 CS therapy.
Advise patients and/or caregivers to immediately report any new or worsening
behavior or mood disturbances to their HCP.
6. ADVERSE REACTIONS
6.1 Clinical Trials Experience Because clinical studies are conducted
under widely varying conditions, adverse reaction rates observed in clinical trials
of a drug cannot be directly compared to rates in clinical studies of another drug
and may not reflect rates observed in practice. The data below reflect exposure to
a single 32mg IA injection of ZILRETTA in clinical studies in patients with moderate
to severe pain due to knee OA. Clinical studies included randomized, doubleblind, parallel-group, placebo- and/or active-controlled, and pharmacokinetic/
pharmacodynamic studies with follow-up ranging from 6-24 weeks. 424 patients
received ZILRETTA; 262 received placebo. The most commonly reported treatmentemergent adverse reactions (incidence ≥1% with ZILRETTA) in the ZILRETTA vs
placebo arms were sinusitis, cough, and contusions (2% vs 1% each) and in the
injected knee were joint swelling (3% vs 2%) and contusions (2% vs 1%). Overall,
the incidence and nature of adverse reactions were similar to those observed
with placebo.
The safety of repeat administration of ZILRETTA was evaluated in a multicenter,
open-label, single-arm study in patients with OA knee pain. 179 patients received
a repeat injection on or after Week 12 (median 16.6 weeks) and were followed for
52 weeks from 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%). Data from this study are
insufficient to fully characterize the safety of repeat administration of ZILRETTA.
6.2 Post-marketing Experience The following adverse reactions (alphabetical 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 injectionsite pain or discomfort, and leg pain. Immune system: Hypersensitivity reactions
including pruritis, rash, angioedema, anaphylaxis. Infections and Infestations:
Septic arthritis. 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: Pruritis.
6.3 Corticosteroid Adverse Reactions The following adverse reactions (alphabetical
by body system) are from voluntary reports or clinical studies of CSs. 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, CHF, 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,

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GEMS Supplier Focus Guide - Q2 2020

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