ZILRETTA® (triamcinolone acetonide extended-release injectable suspension)
ZILRETTA is the first and only extended-release, intra-articular therapy for patients confronting osteoarthritis-related knee pain. ZILRETTA employs proprietary microsphere technology combining triamcinolone acetonide — a commonly administered, short-acting corticosteroid — with a poly lactic-co-glycolic acid (PLGA) matrix to provide extended pain relief. The pivotal Phase 3 trial, on which the approval of ZILRETTA was based, showed that ZILRETTA significantly reduced knee pain for 12 weeks, with some people experiencing pain relief through Week 16. ZILRETTA received approval from the U.S. Food and Drug Administration on October 6, 2017 and the company initiated the full commercial launch on November 20, 2017.
Indication and Important Safety Information
What is ZILRETTA?
ZILRETTA is an extended-release corticosteroid approved to manage osteoarthritis knee pain. It is not intended for repeat use.
Who should not receive ZILRETTA?
You should not receive a ZILRETTA injection if you are allergic to corticosteroids, triamcinolone acetonide, or any other component of the product.
What possible side effects of corticosteroids could occur with ZILRETTA?
- Rare serious allergic reactions
- Effects in the injected knee such as infection (with pain, swelling and restricted motion) or joint damage
- Increased chance of getting an infection, and a decreased ability to fight an infection
- Effects on hormone production. These effects can be reversible
- Elevated blood pressure, sodium and water retention, and potassium loss
- Intestinal perforation if you have certain gastrointestinal disorders
- Weakening of bones
- Changes in behavior or mood disturbances
- Increased pressure inside the eye
What are the most common side effects of receiving a ZILRETTA injection?
In multiple clinical trials, the most common side effects seen in people taking ZILRETTA were joint pain, headache, joint swelling, back pain, sore throat and runny nose, upper respiratory tract infection, and bruising.
What should you tell your doctor BEFORE receiving a ZILRETTA injection?
Tell your doctor about all of the medications you are taking (including both prescription and over-the-counter medicines) and about any medical conditions, especially if you have high blood pressure, heart disease, ulcers, diverticulitis or other gastrointestinal disorders, kidney problems, diabetes, glaucoma, behavior or mood disorders, and/or infections.
What should you tell your doctor AFTER receiving a ZILRETTA injection?
Contact your doctor if you develop a fever or other signs of infection, have an increase in pain along with swelling of the injected knee, restriction of joint motion, or a general feeling of discomfort. Contact your doctor immediately if you are exposed to chicken pox or measles, or for any new or worsening changes in behavior or mood.
These are not all of the possible side effects with ZILRETTA or corticosteroid medications. Please see the full Prescribing Information at www.ZILRETTALabel.com/PI.pdf. Always contact your doctor if you have questions or experience any side effects.
You are encouraged to report side effects to the FDA: Call 1-800-FDA-1088 (332-1088), or visit www.fda.gov/medwatch. You may also report side effects to Flexion at 1-844-FLEXION (353-9466).
Microsphere Formulation
ZILRETTA is formulated as a suspension of microspheres measuring approximately 45 microns in diameter. Within each microsphere, small crystals of TA are embedded in a poly lactic-co-glycolic acid (PLGA) co-polymer matrix (Figure 1A).
In vitro, release of TA from the microsphere commences immediately, and scanning electron micrographs reveal the formation of nano-channels, approximately 500 nanometers in diameter, on the microsphere surface (Figure 1B). These nano-channels, limit both egress of TA from the microsphere’s interior and internal hydration of the polymer, prolonging drug release and slowing PLGA erosion. In the final stage of release, the PLGA matrix degrades to oligomeric poly-acid units and then to lactic and glycolic acids, followed by elimination as carbon dioxide and water.
Figure 1. ZILRETTA, an intra-articular, extended-release formulation of TA in a poly lactic-co-glycolic acid (PLGA) co-polymer matrix.
(A) Within each microsphere, small crystals of TA (red) are embedded in a PLGA matrix (green).
(B) In the initial phase of release, small channels (green circles) of approximately 500 nanometers in diameter appear on the surface of the microsphere to slow the release of TA from the microsphere.
