Adverse reactions
Information about undesirable effects, reasonably associated with use of the drug, that may occur as part of the pharmacological action of the drug or may be unpredictable in its occurrence. Adverse reactions include those that occur with the drug, and if applicable, with drugs in the same pharmacologically active and chemically related class. There is considerable variation in the listing of adverse reactions. They may be categorized by organ system, by severity of reaction, by frequency, by toxicological mechanism, or by a combination of these.
6 ADVERSE REACTIONS In controlled studies, the most common adverse reactions reported by ≥ 10% of patients and at a rate greater than control included elevated intraocular pressure and eye pain. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Bausch & Lomb Incorporated at 1-800-553-5340 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials 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. XIPERE ® was studied in a multicenter, randomized, sham-controlled, double-masked study in patients with macular edema associated with uveitis. Table 1 summarizes data available from the clinical trial for XIPERE ® treated patients and control patients. The most common ocular (study eye) adverse reactions occurring in ≥ 2% of patients and non-ocular adverse reactions occurring in ≥ 5% of patients are shown in Table 1. Table 1: Ocular Adverse Reactions Reported in ≥ 2% of Patients and Non-ocular Adverse Reactions Reported in ≥ 5% of Patients a Includes intraocular pressure increased and ocular hypertension b Defined as not occurring on the day of the injection procedure, or occurring on the day of the injection procedure and not resolving the same day c Includes cataract, cataract cortical, and cataract subcapsular d Defined as occurring on the day of the injection procedure and resolving the same day Adverse Reaction XIPERE ® (N = 96) n (%) Control (N = 64) n (%) Ocular Increased intraocular pressure, non-acute a, b 13 (14%) 9 (14%) Eye pain, non-acute b 11 (12%) 0 Cataract c 7 (7%) 4 (6%) Increased intraocular pressure, acute a, d 6 (6%) 0 Vitreous detachment 5 (5%) 1 (2%) Injection site pain 4 (4%) 2 (3%) Conjunctival haemorrhage 4 (4%) 2 (3%) Visual acuity reduced 4 (4%) 1 (2%) Dry eye 3 (3%) 1 (2%) Eye pain, acute d 3 (3%) 0 Photophobia 3 (3%) 0 Vitreous floaters 3 (3%) 0 Uveitis 2 (2%) 7 (11%) Conjunctival hyperaemia 2 (2%) 2 (3%) Punctate keratitis 2 (2%) 1 (2%) Conjunctival oedema 2 (2%) 0 Meibomianitis 2 (2%) 0 Anterior capsule contraction 2 (2%) 0 Chalazion 2 (2%) 0 Eye irritation 2 (2%) 0 Eye pruritus 2 (2%) 0 Eyelid ptosis 2 (2%) 0 Photopsia 2 (2%) 0 Vision blurred 2 (2%) 0 Non-ocular Headache 5 (5%) 2 (3%)
Table 1: Ocular Adverse Reactions Reported in ≥ 2% of Patients and Non-ocular Adverse Reactions Reported in ≥ 5% of Patients| a Includes intraocular pressure increased and ocular hypertension |
| b Defined as not occurring on the day of the injection procedure, or occurring on the day of the injection procedure and not resolving the same day |
| c Includes cataract, cataract cortical, and cataract subcapsular |
| d Defined as occurring on the day of the injection procedure and resolving the same day |
| Adverse Reaction | XIPERE® (N = 96) n (%) | Control (N = 64) n (%) |
| Ocular |
| Increased intraocular pressure, non-acute a, b | 13 (14%) | 9 (14%) |
| Eye pain, non-acute b | 11 (12%) | 0 |
| Cataract c | 7 (7%) | 4 (6%) |
| Increased intraocular pressure, acute a, d | 6 (6%) | 0 |
| Vitreous detachment | 5 (5%) | 1 (2%) |
| Injection site pain | 4 (4%) | 2 (3%) |
| Conjunctival haemorrhage | 4 (4%) | 2 (3%) |
| Visual acuity reduced | 4 (4%) | 1 (2%) |
| Dry eye | 3 (3%) | 1 (2%) |
| Eye pain, acute d | 3 (3%) | 0 |
| Photophobia | 3 (3%) | 0 |
| Vitreous floaters | 3 (3%) | 0 |
| Uveitis | 2 (2%) | 7 (11%) |
| Conjunctival hyperaemia | 2 (2%) | 2 (3%) |
| Punctate keratitis | 2 (2%) | 1 (2%) |
| Conjunctival oedema | 2 (2%) | 0 |
| Meibomianitis | 2 (2%) | 0 |
| Anterior capsule contraction | 2 (2%) | 0 |
| Chalazion | 2 (2%) | 0 |
| Eye irritation | 2 (2%) | 0 |
| Eye pruritus | 2 (2%) | 0 |
| Eyelid ptosis | 2 (2%) | 0 |
| Photopsia | 2 (2%) | 0 |
| Vision blurred | 2 (2%) | 0 |
| Non-ocular |
| Headache | 5 (5%) | 2 (3%) |
Clinical pharmacology
Information about the clinical pharmacology and actions of the drug in humans.
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Triamcinolone acetonide is a synthetic glucocorticoid (glucocorticoids are often referred to as corticosteroids) with immunosuppressive and anti-inflammatory activity. The primary mechanism of action for triamcinolone acetonide is as a corticosteroid hormone receptor agonist. 12.3 Pharmacokinetics In animal studies, data demonstrated that suprachoroidal injections resulted in larger amounts in total of triamcinolone acetonide found in the sclera, choroid, retinal pigment epithelial and retina, than with intravitreal injections of triamcinolone acetonide. Lower amounts of triamcinolone acetonide were found in the anterior segment and lens as compared to intravitreal injections of triamcinolone acetonide. Plasma triamcinolone acetonide concentrations were evaluated in 19 patients with dosing of 4 mg XIPERE ® at Day 0 and Week 12. Plasma triamcinolone acetonide concentrations in all 19 patients were below 100 pg/mL at Week 4, 12, and 24 (concentrations ranged from < 10 pg/mL [LLOQ (lower limit of quantitation) of the assay] to 88.9 pg/mL), with the exception of one patient with a value of 243.4 pg/mL prior to the second dose at Week 12.
Mechanism of action
Information about the established mechanism(s) of the drugÕs action in humans at various levels (for example receptor, membrane, tissue, organ, whole body). If the mechanism of action is not known, this field contains a statement about the lack of information.
12.1 Mechanism of Action Triamcinolone acetonide is a synthetic glucocorticoid (glucocorticoids are often referred to as corticosteroids) with immunosuppressive and anti-inflammatory activity. The primary mechanism of action for triamcinolone acetonide is as a corticosteroid hormone receptor agonist.
Pharmacokinetics
Information about the clinically significant pharmacokinetics of a drug or active metabolites, for instance pertinent absorption, distribution, metabolism, and excretion parameters.
12.3 Pharmacokinetics In animal studies, data demonstrated that suprachoroidal injections resulted in larger amounts in total of triamcinolone acetonide found in the sclera, choroid, retinal pigment epithelial and retina, than with intravitreal injections of triamcinolone acetonide. Lower amounts of triamcinolone acetonide were found in the anterior segment and lens as compared to intravitreal injections of triamcinolone acetonide. Plasma triamcinolone acetonide concentrations were evaluated in 19 patients with dosing of 4 mg XIPERE ® at Day 0 and Week 12. Plasma triamcinolone acetonide concentrations in all 19 patients were below 100 pg/mL at Week 4, 12, and 24 (concentrations ranged from < 10 pg/mL [LLOQ (lower limit of quantitation) of the assay] to 88.9 pg/mL), with the exception of one patient with a value of 243.4 pg/mL prior to the second dose at Week 12.
Contraindications
Information about situations in which the drug product is contraindicated or should not be used because the risk of use clearly outweighs any possible benefit, including the type and nature of reactions that have been reported.
4 CONTRAINDICATIONS • Ocular or periocular infections ( 4.1 ) • Hypersensitivity to triamcinolone or any component of this product ( 4.2 ) 4.1 Ocular or Periocular Infections XIPERE ® is contraindicated in patients with active or suspected ocular or periocular infections including most viral diseases of the cornea and conjunctiva, including active epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, varicella, mycobacterial infections, and fungal diseases. 4.2 Hypersensitivity XIPERE ® is contraindicated in patients with known hypersensitivity to triamcinolone acetonide or any other components of this product.
Description
General information about the drug product, including the proprietary and established name of the drug, the type of dosage form and route of administration to which the label applies, qualitative and quantitative ingredient information, the pharmacologic or therapeutic class of the drug, and the chemical name and structural formula of the drug.
11 DESCRIPTION XIPERE ® is a sterile, preservative-free, injectable suspension of triamcinolone acetonide, a synthetic corticosteroid for use with the SCS Microinjector ® . Each mL of the sterile, aqueous suspension contains 40 mg of triamcinolone acetonide with 0.55% (weight/volume [w/v]) sodium chloride for tonicity, 0.5% (w/v) carboxymethylcellulose sodium, and 0.02% (w/v) polysorbate 80. It also contains potassium chloride, calcium chloride (dihydrate), magnesium chloride (hexahydrate), sodium acetate (trihydrate), sodium citrate (dihydrate), and water for injection. Hydrochloric acid may be used to adjust pH to a target value of 6.5. The chemical name for triamcinolone acetonide is 9-fluoro-11β,16ɑ,17,21-tetrahydroxypregna-1,4-diene-3,20-dione cyclic 16,17-acetal with acetone. Its chemical structure is: Molecular weight 434.50; molecular formula C 24 H 31 FO 6 Triamcinolone acetonide occurs as a white to cream-colored, crystalline powder having not more than a slight odor and is practically insoluble in water and very soluble in alcohol. XIPERE ® is provided as an injectable suspension in a single-dose glass vial with a rubber stopper and an aluminum seal. The SCS Microinjector ® is a piston syringe and a needle approximately 1 mm in length (900-µm and 1100-µm needles are included) for conducting the suprachoroidal injection. ChemicalStructure
Dosage and administration
Information about the drug product’s dosage and administration recommendations, including starting dose, dose range, titration regimens, and any other clinically sigificant information that affects dosing recommendations.
2 DOSAGE AND ADMINISTRATION The recommended dosage is 4 mg (0.1 mL) administered as a suprachoroidal injection. ( 2.1 ) 2.1 Dosing Information For suprachoroidal injection using the SCS Microinjector ® . The recommended dose of XIPERE ® is 4 mg (0.1 mL of the 40 mg/mL injectable suspension). 2.2 Preparation for Administration Suprachoroidal injection is performed under aseptic conditions. The components for administration include: A. One single-dose glass vial of triamcinolone acetonide injectable suspension 40 mg/mL B. One SCS Microinjector ® syringe with vial adapter attached C. One 30-G x 900-µm needle D. One 30-G x 1100-µm needle Step 1 Figure A Remove the tray from the carton (see Figure A). The tray consists of two compartments: • An open, non-sterile compartment that holds the vial • A sealed compartment that contains a sterile tray Step 2 Figure B Examine the tray for damage (see Figure B). Ensure that the sealed compartment cover is intact and that there is no evidence of damage. If damage is present, do not use. Step 3 Figure C Remove the vial from the tray (see Figure C). Examine the vial and ensure there is no evidence of damage. Set aside for use in Step 6. Step 4 Figure D Peel off the compartment cover, exposing the sterile tray (see Figure D). Step 5 Figure E Grasp and hold the long sides of the tray and invert the tray. Squeeze gently to release the sterile tray onto the appropriate sterile preparation surface (see Figure E, i – iii ). Step 6 Vigorously shake the vial for 10 seconds. Inspect the vial for clumping or granular appearance of the sterile contents. If clumping or granular appearance is present, do not use. Remove the protective plastic cap from the vial and clean the top of the vial with an alcohol wipe. Place the vial on a flat surface (see Figure F, i – iv ). To avoid settling of the suspension, continue to the next steps without delay. Figure F Step 7 Remove the syringe with attached vial adapter from the tray (see Figure G). Ensure the vial adapter is secured to the syringe by tightening the connection. Figure G Step 8 Holding the clear barrel of the syringe, connect the vial adapter to the vial by firmly pushing the spike of the vial adapter straight through the center of the vial septum until it snaps securely into place (see Figure H). NOTE: Do not introduce additional air into the syringe prior to connecting the vial adapter to the vial. Figure H Step 9 Invert the entire assembly so that the vial is directly above the syringe. Slide the white plunger handle all the way back and forth multiple times to fill the entire syringe with drug and remove any remaining air (see Figure I, i and ii ). NOTE: The syringe should be handled by the clear barrel during filling, connecting and disconnecting procedures. The white plunger handle has a stop to prevent complete removal of the plunger from the syringe. Figure I Step 10 Figure J While holding the vial adapter and vial, disconnect the syringe by twisting it off of the adapter (see Figure J). Retain the vial, with the vial adapter connected, in the event re-access is necessary. Step 11 Figure K Connect the 900-µm needle to the syringe by twisting onto the syringe (see Figure K). At the discretion of the physician, the longer needle may be used. Ensure a secure connection. Step 12 Figure L Hold the syringe barrel with the needle pointing up. Expel air bubbles and excess drug by slowly sliding the white plunger handle so that the plunger tip aligns with the line that marks 0.1 mL on the syringe (see Figure L). NOTE: Perform the suprachoroidal injection without delay to prevent settling of the drug. Components for Administration Step 1 Step 2 Step 3 Step 4 Step 5 Step 6 Step 7 Step 8 Step 9 Step 10 Step 11 Step 12 2.3 Administration The suprachoroidal injection procedure should be carried out under controlled aseptic conditions, which include the use of sterile gloves, a sterile drape, a sterile eyelid speculum (or equivalent), and a sterile cotton swab. Adequate anesthesia and a broad-spectrum microbicide applied to the periocular skin, eyelid, and ocular surface are recommended to be given prior to the suprachoroidal injection. Step 13 Figure M Identify the injection site by measuring 4 – 4.5 mm posterior to the limbus using the tip of the needle cap or ophthalmic calipers (see Figure M). Step 14 Figure N Carefully pull off the needle cap to expose the needle. Holding the syringe perpendicular to the ocular surface, insert the needle through the conjunctiva into the sclera (see Figure N). Step 15 Figure O Once the needle is inserted into the sclera, ensure that the hub of the needle is in firm contact with the conjunctiva, compressing the sclera and creating a dimple on the ocular surface using a light amount of force against the eye. Maintain the dimple and perpendicular positioning throughout the injection procedure (see Figure O). Step 16 Figure P While maintaining the dimple on the ocular surface, gently press the white plunger handle so that the plunger moves forward and drug is slowly injected over 5 – 10 seconds. Movement of the plunger will be felt as a loss of resistance and indicates that the needle is in the correct anatomical location for suprachoroidal injection (see Figure P). If resistance is felt and the plunger does not advance, confirm the hub is in firm contact with the conjunctiva creating a dimple and that the syringe is positioned perpendicular to the ocular surface. Small adjustments in positioning may be necessary. Step 17 Maintain the hub against the eye for 3 – 5 seconds after the drug product has been injected. Step 18 Remove the needle slowly from the eye while holding a sterile cotton swab next to the needle as it is withdrawn. Immediately cover the injection site with a sterile cotton swab. Step 19 Hold the swab over the injection site with light pressure for a few seconds and then remove. If continued resistance is experienced during injection attempts: • Remove the needle from the eye and examine the eye for any issues. If patient safety is not at risk, the physician may use medical judgment to restart the injection procedure at a new site adjacent to the original injection site. • If resistance continues and patient safety is not at risk, the physician may use appropriate medical judgment to change to the additional included needle in the sterile tray. Twist to remove the needle and reconnect the syringe to the vial by twisting the syringe onto the vial adapter. Repeat the preparation and injection process as stated in Steps 9 – 18 with the additional needle (allowing for any partial dose given with the first needle when completing preparation Step 12). Immediately following suprachoroidal injection, patients should be monitored for elevation of intraocular pressure. Appropriate monitoring may consist of a check for perfusion of the optic nerve head or tonometry. Following suprachoroidal injection, patients should be instructed to report any symptoms suggestive of endophthalmitis or retinal detachment (e.g., eye pain, redness of eye, photophobia, blurring of vision) without delay [see Patient Counseling Information (17) ] . Each XIPERE ® package (microinjector syringe with vial adapter, 900-µm needle, 1100-µm needle, and vial of triamcinolone acetonide injectable suspension 40 mg/mL) is single-dose and should only be used for the treatment of one eye. After suprachoroidal injection, all drug product and components (used or unused) must be discarded appropriately. Step 13 Step 14 Step 15 Step 16
- Suprachoroidal injection is performed under aseptic conditions. The components for administration include:
- A.One single-dose glass vial of triamcinolone acetonide injectable suspension 40 mg/mL
- B.One SCS Microinjector® syringe with vial adapter attached
- C.One 30-G x 900-µm needle
- D.One 30-G x 1100-µm needle
| |
| Step 1 Figure A | - Remove the tray from the carton (see Figure A). The tray consists of two compartments:
- • An open, non-sterile compartment that holds the vial
- • A sealed compartment that contains a sterile tray
|
| Step 2 Figure B | - Examine the tray for damage (see Figure B). Ensure that the sealed compartment cover is intact and that there is no evidence of damage. If damage is present, do not use.
|
| Step 3 Figure C | - Remove the vial from the tray (see Figure C). Examine the vial and ensure there is no evidence of damage. Set aside for use in Step 6.
|
| Step 4 Figure D | - Peel off the compartment cover, exposing the sterile tray (see Figure D).
|
| Step 5 | |
| Figure E |
| Grasp and hold the long sides of the tray and invert the tray. Squeeze gently to release the sterile tray onto the appropriate sterile preparation surface (see Figure E, i – iii). |
| Step 6 | - Vigorously shake the vial for 10 seconds. Inspect the vial for clumping or granular appearance of the sterile contents. If clumping or granular appearance is present, do not use. Remove the protective plastic cap from the vial and clean the top of the vial with an alcohol wipe. Place the vial on a flat surface (see Figure F, i – iv). To avoid settling of the suspension, continue to the next steps without delay.
|
| Figure F |
| Step 7 | - Remove the syringe with attached vial adapter from the tray (see Figure G). Ensure the vial adapter is secured to the syringe by tightening the connection.
|
| Figure G |
| Step 8 | - Holding the clear barrel of the syringe, connect the vial adapter to the vial by firmly pushing the spike of the vial adapter straight through the center of the vial septum until it snaps securely into place (see Figure H). NOTE: Do not introduce additional air into the syringe prior to connecting the vial adapter to the vial.
|
| Figure H |
| Step 9 | - Invert the entire assembly so that the vial is directly above the syringe. Slide the white plunger handle all the way back and forth multiple times to fill the entire syringe with drug and remove any remaining air (see Figure I, i and ii). NOTE: The syringe should be handled by the clear barrel during filling, connecting and disconnecting procedures. The white plunger handle has a stop to prevent complete removal of the plunger from the syringe.
|
| Figure I |
| Step 10 Figure J | - While holding the vial adapter and vial, disconnect the syringe by twisting it off of the adapter (see Figure J). Retain the vial, with the vial adapter connected, in the event re-access is necessary.
|
| Step 11 Figure K | - Connect the 900-µm needle to the syringe by twisting onto the syringe (see Figure K). At the discretion of the physician, the longer needle may be used. Ensure a secure connection.
|
| Step 12 Figure L | - Hold the syringe barrel with the needle pointing up. Expel air bubbles and excess drug by slowly sliding the white plunger handle so that the plunger tip aligns with the line that marks 0.1 mL on the syringe (see Figure L). NOTE: Perform the suprachoroidal injection without delay to prevent settling of the drug.
|
| Step 13 Figure M | - Identify the injection site by measuring 4 – 4.5 mm posterior to the limbus using the tip of the needle cap or ophthalmic calipers (see Figure M).
|
| Step 14 Figure N | - Carefully pull off the needle cap to expose the needle. Holding the syringe perpendicular to the ocular surface, insert the needle through the conjunctiva into the sclera (see Figure N).
|
| Step 15 Figure O | - Once the needle is inserted into the sclera, ensure that the hub of the needle is in firm contact with the conjunctiva, compressing the sclera and creating a dimple on the ocular surface using a light amount of force against the eye. Maintain the dimple and perpendicular positioning throughout the injection procedure (see Figure O).
|
| Step 16 Figure P | - While maintaining the dimple on the ocular surface, gently press the white plunger handle so that the plunger moves forward and drug is slowly injected over 5 – 10 seconds. Movement of the plunger will be felt as a loss of resistance and indicates that the needle is in the correct anatomical location for suprachoroidal injection (see Figure P). If resistance is felt and the plunger does not advance, confirm the hub is in firm contact with the conjunctiva creating a dimple and that the syringe is positioned perpendicular to the ocular surface. Small adjustments in positioning may be necessary.
|
- Step 17 Maintain the hub against the eye for 3 – 5 seconds after the drug product has been injected.
|
- Step 18 Remove the needle slowly from the eye while holding a sterile cotton swab next to the needle as it is withdrawn. Immediately cover the injection site with a sterile cotton swab.
|
- Step 19 Hold the swab over the injection site with light pressure for a few seconds and then remove.
|
Information about all available dosage forms and strengths for the drug product to which the labeling applies. This field may contain descriptions of product appearance.
3 DOSAGE FORMS AND STRENGTHS Injectable suspension: triamcinolone acetonide 40 mg/mL suspension in a single-dose glass vial for use with the supplied SCS Microinjector ® . Injectable suspension: triamcinolone acetonide 40 mg/mL in a single-dose vial. ( 3 )
Indications and usage
A statement of each of the drug products indications for use, such as for the treatment, prevention, mitigation, cure, or diagnosis of a disease or condition, or of a manifestation of a recognized disease or condition, or for the relief of symptoms associated with a recognized disease or condition. This field may also describe any relevant limitations of use.
1 INDICATIONS AND USAGE XIPERE ® (triamcinolone acetonide injectable suspension) 40 mg/mL is indicated for the treatment of macular edema associated with uveitis. XIPERE ® is a corticosteroid indicated for the treatment of macular edema associated with uveitis. ( 1 )
Spl product data elements
Usually a list of ingredients in a drug product.
Xipere triamcinolone acetonide TRIAMCINOLONE ACETONIDE TRIAMCINOLONE ACETONIDE CARBOXYMETHYLCELLULOSE SODIUM, UNSPECIFIED FORM POLYSORBATE 80 SODIUM CHLORIDE POTASSIUM CHLORIDE CALCIUM CHLORIDE MAGNESIUM CHLORIDE SODIUM ACETATE TRISODIUM CITRATE DIHYDRATE HYDROCHLORIC ACID WATER clear until shaken then appears white
Carcinogenesis and mutagenesis and impairment of fertility
Information about carcinogenic, mutagenic, or fertility impairment potential revealed by studies in animals. Information from human data about such potential is part of the warnings field.
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis No information is available on the carcinogenic potential of triamcinolone acetonide. Mutagenesis No information is available on the mutagenic potential of triamcinolone acetonide. Fertility No information is available on the effect of triamcinolone acetonide on fertility.
Nonclinical toxicology
Information about toxicology in non-human subjects.
13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis No information is available on the carcinogenic potential of triamcinolone acetonide. Mutagenesis No information is available on the mutagenic potential of triamcinolone acetonide. Fertility No information is available on the effect of triamcinolone acetonide on fertility.
Package label principal display panel
The content of the principal display panel of the product package, usually including the product’s name, dosage forms, and other key information about the drug product.
PACKAGE/LABEL PRINCIPAL DISPLAY PANEL NDC 24208-040-40 XIPERE ® (triamcinolone acetonide Injectable suspension) 40 mg/mL For suprachoroidal use Carton contains: • One single-dose glass vial of triamcinolone acetonide injectable suspension 40 mg/mL • One SCS Microinjector® syringe with vial adapter attached • One 30-G x 900-μm needle • One 30-G x 1100-μm needle • One package insert Rx only Store at 15°C to 25°C (59°F to 77°F). Do not freeze. Protect from light. BAUSCH + LOMB 9771901 Carton
Information necessary for patients to use the drug safely and effectively, such as precautions concerning driving or the concomitant use of other substances that may have harmful additive effects.
17 PATIENT COUNSELING INFORMATION Corticosteroid-Related Effects Advise patients that they may develop elevated intraocular pressure following treatment, which may need to be managed with medication or surgery. When to Seek Physician Advice Advise patients that if the eye becomes red, sensitive to light, painful, or develops a change in vision, they should seek immediate care from an ophthalmologist. Distributed by: Bausch & Lomb Americas Inc. Bridgewater, NJ 08807 USA Patented. See https://patents.bausch.com for US patent information. XIPERE ® , SCS ® , and SCS Microinjector ® are trademarks of Clearside Biomedical, Inc. used under license. © 2022 Bausch & Lomb Incorporated or its affiliates 9772101
Clinical studies
This field may contain references to clinical studies in place of detailed discussion in other sections of the labeling.
14 CLINICAL STUDIES The efficacy of XIPERE ® was assessed in a 6-month, randomized, multicenter, double-masked, sham-controlled study in patients with macular edema associated with anterior-, intermediate-, posterior-, or pan-uveitis. Patients were treated at baseline and Week 12. The primary efficacy endpoint was the proportion of patients in whom best corrected visual acuity (BCVA) had improved by ≥ 15 letters from baseline after 24 weeks of follow-up (Table 2). Table 2: Number of Patients with ≥ 15 Letters Improvement from Baseline at Week 24 * The p-value was based on a Cochran Mantel Haenszel test for general association between treatment and response with stratification by country. Patients Who Gained ≥ 15 Letters from Baseline at Week 24 XIPERE ® (N = 96) Control (N = 64) n (%) 45 (47%) 10 (16%) Estimated Difference (95% CI) 31% (15%, 46%) CMH p-value* < 0.01 A statistically significantly greater proportion of patients treated with XIPERE ® achieved a ≥ 15-letter improvement in BCVA than control patients (p < 0.01) at Week 24. BCVA mean change from baseline at different visits is shown in Figure 1. Central subfield retinal thickness (CST) mean change from baseline at different visits is shown in Figure 2. Figure 1: Mean Change from Baseline in BCVA Figure 2: Mean Change from Baseline in CST Figure1graph Figure2graph
Table 2: Number of Patients with ≥ 15 Letters Improvement from Baseline at Week 24| * The p-value was based on a Cochran Mantel Haenszel test for general association between treatment and response with stratification by country. |
| Patients Who Gained ≥ 15 Letters from Baseline at Week 24 | XIPERE® (N = 96) | Control (N = 64) |
| n (%) | 45 (47%) | 10 (16%) |
| Estimated Difference (95% CI) | 31% (15%, 46%) |
| CMH p-value* | < 0.01 |
Geriatric use
Information about any limitations on any geriatric indications, needs for specific monitoring, hazards associated with use of the drug in the geriatric population.
8.5 Geriatric Use No overall differences in safety or effectiveness have been observed between elderly and younger patients following XIPERE ® administration.
Pediatric use
Information about any limitations on any pediatric indications, needs for specific monitoring, hazards associated with use of the drug in any subsets of the pediatric population (such as neonates, infants, children, or adolescents), differences between pediatric and adult responses to the drug, and other information related to the safe and effective pediatric use of the drug.
8.4 Pediatric Use Safety and effectiveness of XIPERE ® in pediatric patients have not been established.
Pregnancy
Information about effects the drug may have on pregnant women or on a fetus. This field may be ommitted if the drug is not absorbed systemically and the drug is not known to have a potential for indirect harm to the fetus. It may contain information about the established pregnancy category classification for the drug. (That information is nominally listed in the teratogenic_effects field, but may be listed here instead.)
8.1 Pregnancy Risk Summary There are no adequate and well-controlled studies with XIPERE ® in pregnant women to inform drug-associated risks. In animal reproductive studies from the published literature, topical ocular administration of corticosteroids has been shown to produce teratogenicity at clinically relevant doses. There is negligible systemic XIPERE ® exposure following suprachoroidal injection [see Clinical Pharmacology (12.3) ] . Corticosteroids should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. 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. Animal Data Animal reproduction studies using XIPERE ® have not been conducted. In animal reproductive studies from the published literature, topical ocular administration of corticosteroids to pregnant mice and rabbits during organogenesis has been shown to produce cleft palate, embryofetal death, herniated abdominal viscera, hypoplastic kidneys, and craniofacial malformations.
Use in specific populations
Information about use of the drug by patients in specific populations, including pregnant women and nursing mothers, pediatric patients, and geriatric patients.
8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary There are no adequate and well-controlled studies with XIPERE ® in pregnant women to inform drug-associated risks. In animal reproductive studies from the published literature, topical ocular administration of corticosteroids has been shown to produce teratogenicity at clinically relevant doses. There is negligible systemic XIPERE ® exposure following suprachoroidal injection [see Clinical Pharmacology (12.3) ] . Corticosteroids should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. 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. Animal Data Animal reproduction studies using XIPERE ® have not been conducted. In animal reproductive studies from the published literature, topical ocular administration of corticosteroids to pregnant mice and rabbits during organogenesis has been shown to produce cleft palate, embryofetal death, herniated abdominal viscera, hypoplastic kidneys, and craniofacial malformations. 8.2 Lactation Risk Summary It is not known whether ocular administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in human milk. Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for XIPERE ® and any potential adverse effects on the breastfed infant from XIPERE ® . There are no data on the effects of XIPERE ® on milk production. 8.4 Pediatric Use Safety and effectiveness of XIPERE ® in pediatric patients have not been established. 8.5 Geriatric Use No overall differences in safety or effectiveness have been observed between elderly and younger patients following XIPERE ® administration.
How supplied
Information about the available dosage forms to which the labeling applies, and for which the manufacturer or distributor is responsible. This field ordinarily includes the strength of the dosage form (in metric units), the units in which the dosage form is available for prescribing, appropriate information to facilitate identification of the dosage forms (such as shape, color, coating, scoring, and National Drug Code), and special handling and storage condition information.
16 HOW SUPPLIED/STORAGE AND HANDLING XIPERE ® is supplied with the following sterile components for administration, sealed in a Tyvek covered tray, and one single-dose glass vial, in a carton with a package insert (NDC 24208-040-40): • One SCS Microinjector ® syringe with vial adapter attached • One 30-G x 900-µm needle • One 30-G x 1100-µm needle • One single-dose vial of triamcinolone acetonide injectable suspension 40 mg/mL (NDC 24208-040-41) Storage: Store at 15°C to 25°C (59°F to 77°F); do not freeze. The drug vial should be protected from light by storing in the carton. Discard unused portion.
