Zilretta

ZILRETTA (triamcinolone acetonide extended-release injectable suspension) is indicated as an intra-articular injection for the management of osteoarthritis pain of the knee.

• 32 mg (5 mL) administered as a single intra-articular injection in the knee. (
  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.
  )
• See
  Instructions for Use

  ZILRETTA^®
  
  (triamcinolone acetonide
  
  extended-release injectable suspension)

  For intra-articular injection only

  Single-dose device
  
  Do not reuse.

  IMPORTANT INFORMATION

  • ZILRETTA 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 ZILRETTA after preparation to avoid settling of the suspension.
  • ZILRETTA is supplied as a single-dose kit and administered as a suspension containing microspheres.
  • The ZILRETTA powder vial contains an overfill to allow the appropriate dose to be withdrawn. ZILRETTA 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 Pacira Pharmaceuticals, Inc. at 1-844-353-9466.

  MATERIALS REQUIRED (Fig. 1)

  Supplied

  • One 32 mg vial of ZILRETTA 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 ZILRETTA 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 ZILRETTA 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 ZILRETTA powder and diluent vials (Fig. 4).

  

  Figure 4

  Clean Vials.

  Clean the ZILRETTA 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 ZILRETTA Powder Vial.

  Grip the plastic holder that contains the vial adapter.

  As shown in Figure 6, place the ZILRETTA powder vial on a flat surface. In a vertical orientation, gently push the adapter down onto the ZILRETTA powder vial until the spike on the adapter penetrates the rubber stopper on the ZILRETTA 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 ZILRETTA 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 ZILRETTA 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 ZILRETTA 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 ZILRETTA 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 ZILRETTA vial into the syringe.

  

  Figure 12

  Note: ZILRETTA 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 ZILRETTA 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 ZILRETTA.

  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.

  Do not reuse excess ZILRETTA. Any excess suspension in the vial should be thrown away immediately after the injection. Leftover ZILRETTA 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 ZILRETTA is delivered.

  Note: Discard all used components in an appropriate medical waste container according to local regulations.

  Note: ZILRETTA is for intra-articular use only. ZILRETTA is not intended for epidural, intrathecal, intravenous, intraocular, intramuscular, intradermal, or subcutaneous use.

  Part Number: 60-005-03
  
  Rev: 03/2022

  Figure 1

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  Figure 8

  Figure 9

  Figure 10

  Figure 11

  Figure 12

  Figure 13

  Figure 14

  for instructions on reconstitution of ZILRETTA with the supplied diluent. (
  2.2 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.
  )
• It is normal for some residue to be left behind on the vial walls after withdrawing the suspension. (
  2.2 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.
  )
• ZILRETTA is NOT substitutable with other formulations of injectable triamcinolone acetonide. (
  2.3 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

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 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.

• Intra-articular Use Only
  : Do not administer ZILRETTA by epidural, intrathecal, intravenous, intraocular, intramuscular, intradermal, or subcutaneous routes. (
  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
  • Subcutaneous

  [see Warnings and Precautions (5.2)].
  )
• 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 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
  : Serious reactions have been reported with triamcinolone acetonide injection. Institute appropriate care upon occurrence of an anaphylactic reaction. (
  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 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
  : 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 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.
  )