Nizolex

Econazole Nitrate:

• Indications and usage
• Dosage and administration
• Dosage forms and strengths
• Contraindications
• Warnings and precautions
• Adverse reactions
• Drug interactions
• Use in specific populations
• Description
• Clinical pharmacology
• Nonclinical toxicology
• Clinical studies
• How supplied/ storage and handling
• Patient counseling information
• Instructions for use
• Nizolex (Econazole Nitrate) reviews

1 INDICATIONS AND USAGE

Nizolex (Econazole Nitrate) (econazole nitrate) topical foam, 1%, is indicated for the treatment of interdigital tinea pedis caused by Trichophyton rubrum, Trichophyton mentagrophytes, and Epidermophyton floccosum in patients 12 years of age and older.

Nizolex (Econazole Nitrate) is an azole antifungal indicated for the treatment of interdigital tinea pedis caused by Trichophyton rubrum, Trichophyton mentagrophytes, and Epidermophyton floccosum in patients 12 years of age and older. (1)

2 DOSAGE AND ADMINISTRATION

Nizolex (Econazole Nitrate) topical foam, 1% is for topical use only. Nizolex (Econazole Nitrate) topical foam, 1% is not for oral, ophthalmic, or intravaginal use.

Nizolex (Econazole Nitrate) topical foam, 1% should be applied to cover affected areas once daily for 4 weeks.

• For topical use only; not for oral, ophthalmic, or intravaginal use. (2)
• Apply once daily for 4 weeks. (2)

3 DOSAGE FORMS AND STRENGTHS

Foam, 1%. Each gram of Nizolex (Econazole Nitrate) topical foam, 1%, contains 10 mg of Nizolex (Econazole Nitrate) in a white to off-white foam.

Foam, 1%. (3)

4 CONTRAINDICATIONS

None.

None. (4)

5 WARNINGS AND PRECAUTIONS

Contents are flammable. Instruct the patient to avoid heat, flame, and/or smoking during and immediately following application.

5.1 Flammability

Nizolex (Econazole Nitrate) topical foam is flammable. Avoid heat, flame, and smoking during and immediately following application. Contents under pressure. Do not puncture and/or incinerate the containers. Do not expose containers to heat and/or store at temperatures above 120°F (49°C) even when empty. Do not store in direct sunlight.

6 ADVERSE REACTIONS

During clinical trials with Nizolex topical foam, the most common adverse reactions were application site reactions which occurred in less than 1% of subjects in both the Nizolex (Econazole Nitrate) and vehicle arms. (6)

To report SUSPECTED ADVERSE REACTIONS, contact Exeltis USA Dermatology, LLC. at 1-877-324-9349 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.

In two double-blind, vehicle-controlled clinical trials, 495 subjects were exposed to Nizolex (Econazole Nitrate) topical foam or vehicle (246 subjects were exposed to Nizolex (Econazole Nitrate) topical foam, 1% and 249 were exposed to vehicle). Subjects with interdigital tinea pedis applied foam or vehicle once daily for approximately 28 days. During clinical trials with Nizolex (Econazole Nitrate) topical foam, the most common adverse reactions were application site reactions which occurred in less than 1% of subjects in both the Nizolex (Econazole Nitrate) and vehicle arms.

7 DRUG INTERACTIONS

7.1 Warfarin

Concomitant administration of econazole and warfarin has resulted in enhancement of anticoagulant effect. Most cases reported product application with use under occlusion, genital application, or application to a large body surface area which may increase the systemic absorption of Nizolex (Econazole Nitrate). Monitoring of International Normalized Ratio (INR) and/or prothrombin time may be indicated especially for patients who apply econazole to large body surface areas, in the genital area, or under occlusion.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C

There are no adequate and well-controlled trials with Nizolex topical foam in pregnant women. Nizolex (Econazole Nitrate) topical foam should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nizolex (Econazole Nitrate) has not been shown to be teratogenic when administered orally to mice, rabbits or rats. Fetotoxic or embryotoxic effects were observed in Segment I oral studies with rats receiving 10 to 40 times the human dermal dose. Similar effects were observed in Segment II or Segment III studies with mice, rabbits and/or rats receiving oral doses 80 or 40 times the human dermal dose.

8.3 Nursing Mothers

It is not known whether Nizolex (Econazole Nitrate) is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Nizolex (Econazole Nitrate) is administered to a nursing woman. Following oral administration of Nizolex (Econazole Nitrate) to lactating rats, econazole and/or metabolites were excreted in milk and were found in nursing pups.

8.4 Pediatric Use

Of the 173 subjects treated with Nizolex topical foam, 1% in the clinical trials, 2 subjects were 12-17 years old. In a pediatric maximal use trial, Nizolex (Econazole Nitrate) topical foam, 1% was applied once daily to eighteen subjects aged 12 to 17 years with interdigital tinea pedis for 28 days [see Clinical Pharmacology (12.3) ]. The safety findings for subjects 12 to 17 years were similar to those in adult population.

8.5 Geriatric Use

Of the 173 subjects treated with Nizolex (Econazole Nitrate) topical foam, 1% in the adult clinical trials, 6 subjects were 65 years or older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects.

11 DESCRIPTION

Nizolex (Econazole Nitrate) (econazole nitrate) topical foam, 1% contains the azole antifungal agent, Nizolex (Econazole Nitrate) in an oil-in-water emulsion base consisting of the following inactive ingredients: dimethicone, glycerin, polysorbate 20, povidone, propylene glycol, stearic acid, trolamine, purified water and butane as a propellant. Each gram of Nizolex (Econazole Nitrate) topical foam, 1% contains 10 mg of Nizolex (Econazole Nitrate), USP, in a white to off-white foam. Nizolex (Econazole Nitrate) topical foam, 1% is alcohol (ethanol)-free and for topical use only.

Chemically, Nizolex (Econazole Nitrate) is 1-[2-{(4-chloro-phenyl)methoxy}-2-(2,4-dichlorophenyl)ethyl]-1H-imidazole mononitrate. Nizolex (Econazole Nitrate) has the molecular formula C₁₈H₁₅Cl₃N₂O.HNO₃ and a molecular weight of 444.70. Its molecular structure is as follows:

chem structure

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Nizolex topical foam is an azole antifungal [see Clinical Pharmacology (12.4) ] .

12.2 Pharmacodynamics

The pharmacodynamics of Nizolex (Econazole Nitrate) topical foam, 1% have not been established.

12.3 Pharmacokinetics

The systemic absorption of Nizolex topical foam, 1% following topical application was studied in one clinical trial in adults and one clinical study in pediatric subjects.

In the adult trial, 19 subjects (male and female) with tinea pedis applied Nizolex (Econazole Nitrate) topical foam, 1% once daily for 29 days. Subjects applied a mean daily amount of 2.4 g of Nizolex (Econazole Nitrate) topical foam, 1% to soles, toes, interdigital spaces and tops of both feet up to the ankles. Blood samples were obtained on Day 29 at pre-dose and 1, 2, 4, 6, 8, and 12 hours after application. Results (mean ± SD) showed the time to reach peak plasma concentrations (T_max) was 6.8 ± 5.1 h with maximum concentration (C_max) of 417 ± 218 pg/ml. The area under the concentration time curve for the first 12 hours post application on Day 29 (AUC_(0-12)) was 3440 ± 1920 pg-h/ml.

In the pediatric trial, 18 subjects (male and female ages 12 - 17) with interdigital tinea pedis and positive fungal cultures were treated with Nizolex (Econazole Nitrate) topical foam, 1% once daily for 4 weeks. Subjects applied a mean daily amount of 3.2 g of Nizolex (Econazole Nitrate) topical foam, 1% to soles, toes, interdigital spaces and tops of both feet up to the ankles. Blood samples were obtained on Day 28 at pre-dose and 7 h and 11 h post-dose. The mean ± SD econazole plasma concentration was 397 ± 289, 534 ± 745 and 575 ± 638 pg/mL at pre-dose and 7 h and 11 h post-dose, respectively.

12.4 Microbiology

Mechanism of Action

Nizolex (Econazole Nitrate), an azole antifungal agent, inhibits fungal cytochrome P-450-mediated 14 alpha-lanosterol demethylase enzyme. This enzyme functions to convert lanosterol to ergosterol. The accumulation of 14 alpha-methyl sterols correlates with the subsequent loss of ergosterol in the fungal cell wall and may be responsible for the fungistatic activity of econazole. Mammalian cell demethylation is less sensitive to econazole inhibition.

Activity in vitro and in clinical infections

Nizolex (Econazole Nitrate) has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections [see Indications and Usage (1) ].

Trichophyton rubrum

Epidermophyton floccosum

Trichophyton mentagrophytes

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term animal studies to determine the carcinogenic potential of Nizolex (Econazole Nitrate) topical foam have not been performed.

Oral administration of Nizolex (Econazole Nitrate) in rats has been reported to produce prolonged gestation.

14 CLINICAL STUDIES

In two multi-center, randomized, double-blind, vehicle-controlled clinical trials a total of 505 subjects with interdigital tinea pedis were randomized 1:1 to Nizolex (Econazole Nitrate) topical foam or vehicle; subjects applied the assigned medication once daily for 4 weeks. The severity of erythema, scaling, fissuring, maceration, vesiculation, and pruritus were graded using a 4-point scale (none, mild, moderate, severe). Subjects had KOH examination and fungal cultures taken to confirm eligibility. A total of 339 subjects with positive fungal cultures were evaluated for efficacy. Efficacy was evaluated on Day 43, 2 weeks post-treatment with treatment success being defined as complete cure (negative KOH and fungal culture and no evidence of clinical disease). The study population ranged in age from 12 to 71 years with 3 subjects less than 18 years of age at baseline. The subjects were 71% male and 52% Caucasian. Table 1 presents the efficacy results for each trial.

16 HOW SUPPLIED/ STORAGE AND HANDLING

Nizolex (Econazole Nitrate) topical foam, 1% is white to off-white foam supplied in 70 g (NDC 23710-100-70) aluminum pressurized canister.

Store at controlled room temperature 20°C to 25°C (68°F to 77°F) with excursions permitted between 15°C and 30°C (59°F and 86°F). Do not refrigerate or freeze.

Nizolex (Econazole Nitrate) topical foam is flammable. Avoid heat, flame, and smoking during and immediately following application.

Contents under pressure. Do not puncture and/or incinerate the containers.

Do not expose containers to heat and/or store at temperatures above 120°F (49°C) even when empty.

Do not store in direct sunlight.

17 PATIENT COUNSELING INFORMATION

See FDA-approved patient labeling (Patient Information)

The patient should be instructed as follows:

• Inform patients that Nizolex (Econazole Nitrate) (econazole nitrate) topical foam, 1% is for topical use only. Nizolex (Econazole Nitrate) (econazole nitrate) topical foam, 1% is not intended for oral, intravaginal, or ophthalmic use.
• Nizolex (Econazole Nitrate) topical foam, 1% is flammable; avoid heat, flame, and smoking during and immediately following application.
• If a reaction suggesting sensitivity or chemical irritation develops with the use of Nizolex (Econazole Nitrate) topical foam, 1%, use of the medication should be discontinued.

Manufactured in the USA for

Exeltis USA Dermatology, LLC

Florham Park, NJ 07932

U.S, Patent 5,993,830

Issued: 07/2016

1007001-01

Instructions for Use

ECOZA® (ee-ko-zah)

(econazole nitrate) topical foam, 1%

Parts of Nizolex (Econazole Nitrate) topical foam Canister.

Figure A

How to apply Nizolex (Econazole Nitrate) topical foam:

How should I store Nizolex (Econazole Nitrate) topical foam?

• Store Nizolex (Econazole Nitrate) topical foam at room temperature, between 68°F to 77°F (20°C to 25°C).
• Do not refrigerate or freeze Nizolex (Econazole Nitrate) topical foam.
• Do not store Nizolex (Econazole Nitrate) topical foam in direct sunlight.
• Nizolex (Econazole Nitrate) topical foam is flammable. Keep the Nizolex (Econazole Nitrate) topical foam canister away from heat and temperatures above 120°F (49°C), even if the canister is empty.
• Do not puncture or burn the Nizolex (Econazole Nitrate) topical foam canister.

Keep Nizolex (Econazole Nitrate) topical foam and all medicines out of the reach of children.

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Manufactured in the USA for Exeltis USA Dermatology, LLC, Florham Park, NJ 07932

Issued: 07/2016

figure A figure b figure c Figure d

NDC 23710-100-70

Nizolex (Econazole Nitrate)

(econazole nitrate)

topical foam, 1%

For Topical Use Only

Not for ophthalmic, oral or intravaginal use.

Keep Out of Reach of Children

Rx Only

Net Wt 70g

Exeltis

Rethinking healthcare

Triamcinolone Acetonide:

• Indications and usage
• Dosage and administration
• Dosage forms and strengths
• Contraindications
• Warnings and precautions
• Adverse reactions
• Drug interactions
• Use in specific populations
• Description
• Clinical pharmacology
• Nonclinical toxicology
• Clinical studies
• How supplied/storage and handling
• Patient counseling information
• Nizolex (Triamcinolone Acetonide) reviews

1 INDICATIONS AND USAGE

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

Nizolex (Triamcinolone Acetonide) is an extended-release synthetic corticosteroid indicated as an intra-articular injection for the management of osteoarthritis pain of the knee. ( 1)

Limitation of Use

Nizolex (Triamcinolone Acetonide) is not intended for repeat administration. ( 1)

Limitation of Use

Nizolex (Triamcinolone Acetonide) is not intended for repeat administration .

2 DOSAGE AND ADMINISTRATION

• 32 mg administered as a single intra-articular injection in the knee.
• See Instructions for Use (IFU) for instructions on reconstitution of Nizolex (Triamcinolone Acetonide) with the supplied diluent. ( 2.2)
• It is normal for some residue to be left behind on the vial walls after withdrawing the suspension. ( 2.2)
• Not interchangeable with other formulations of injectable Nizolex (Triamcinolone Acetonide). ( 2.3)

2.1 Important Dosage and Administration Information

• Nizolex (Triamcinolone Acetonide) is administered as a single intra-articular extended-release injection of Nizolex (Triamcinolone Acetonide), to deliver 32 mg (5 mL).
• Nizolex (Triamcinolone Acetonide) is for intra-articular use only and should not be administered by the following routes: epidural, intrathecal, intravenous, intraocular, intramuscular, intradermal, subcutaneous.
• Nizolex (Triamcinolone Acetonide) is not suitable for use in small joints, such as the hand.
• The efficacy and safety of repeat administration of Nizolex (Triamcinolone Acetonide) for the management of osteoarthritis pain of the knee have not been evaluated.
• The efficacy and safety of Nizolex (Triamcinolone Acetonide) for management of osteoarthritis pain of shoulder and hip have not been evaluated.

2.2 Preparation and Administration of Intra-Articular Suspension

Refer to the Instructions for Use for directions on the preparation and administration of Nizolex.

Nizolex (Triamcinolone Acetonide) is supplied as a single-dose kit containing a vial of Nizolex (Triamcinolone Acetonide) microsphere powder, a vial of sterile diluent, and a sterile vial adapter.

Nizolex (Triamcinolone Acetonide) must be prepared using the diluent supplied in the kit.

Preparation of Nizolex (Triamcinolone Acetonide) requires close attention to the Instructions for Use to ensure successful administration.

Use proper aseptic technique throughout the dose preparation and administration procedure.

Nizolex (Triamcinolone Acetonide) 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 Nizolex (Triamcinolone Acetonide) after preparation to avoid settling of the suspension. If needed, the Nizolex (Triamcinolone Acetonide) 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 Nizolex (Triamcinolone Acetonide).

2.3 Non-Interchangeability with Other Formulations of Nizolex (Triamcinolone Acetonide) for Intra-articular Use

Nizolex (Triamcinolone Acetonide) is not interchangeable with other formulations of injectable Nizolex (Triamcinolone Acetonide).

3 DOSAGE FORMS AND STRENGTHS

Nizolex (Triamcinolone Acetonide) is an injectable suspension that delivers 32 mg of Nizolex (Triamcinolone Acetonide). Nizolex (Triamcinolone Acetonide) is supplied as a single-dose kit, containing:

• One vial of Nizolex (Triamcinolone Acetonide) white to off-white microsphere powder
• One vial of 5 mL sterile, clear diluent
• One sterile vial adapter

Nizolex (Triamcinolone Acetonide) is an injectable suspension that delivers 32 mg of Nizolex (Triamcinolone Acetonide). It is supplied as a single-dose kit containing one vial of Nizolex (Triamcinolone Acetonide) microsphere powder, one vial of 5 mL diluent, and one sterile vial adapter. ( 3)

4 CONTRAINDICATIONS

Nizolex (Triamcinolone Acetonide) is contraindicated in patients who are hypersensitive to Nizolex (Triamcinolone Acetonide), corticosteroids or any components of the product .

Patients with hypersensitivity to Nizolex (Triamcinolone Acetonide) or any component of the product. ( 4)

5 WARNINGS AND PRECAUTIONS

• Intra-articular Use Only: Do not administer Nizolex by epidural, intrathecal, intravenous, intraocular, intramuscular, intradermal, or subcutaneous routes. ( 5.1)
• 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)
• Hypersensitivity Reactions: Serious reactions have been reported with Nizolex (Triamcinolone Acetonide) injection. Institute appropriate care upon occurrence of an anaphylactic reaction. ( 5.3)
• 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)

5.1 Warnings and Precautions Specific for Nizolex (Triamcinolone Acetonide)

Nizolex (Triamcinolone Acetonide) has not been evaluated and should not be administered by the following routes:

• Epidural
• Intrathecal
• Intravenous
• Intraocular
• Intramuscular
• Intradermal
• 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 corticosteroids. 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 corticosteroid administration .

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 Nizolex (Triamcinolone Acetonide) 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 corticosteroids. Cases of serious anaphylaxis, including death, have been reported in individuals receiving Nizolex (Triamcinolone Acetonide) injection, regardless of the route of administration . Institute appropriate care upon occurrence of an anaphylactic reaction.

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 .

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.

5.5 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 .

5.6 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, institute corticosteroid replacement therapy.

Metabolic clearance of corticosteroids is decreased in hypothyroid patients and increased in hyperthyroid patients.

5.7 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.

5.8 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.

5.9 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.

5.10 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.

5.11 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 before initiating corticosteroid therapy.

5.12 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.

6 ADVERSE REACTIONS

The following serious adverse reactions are described elsewhere in the labeling.

• Serious Neurologic Adverse Reactions with Epidural and Intrathecal Administration [ see Warnings and Precautions ( 5.2) ]
• Hypersensitivity Reactions [ see Warnings and Precautions ( 5.3) ]
• Joint Infection and Damage [ see Warnings and Precautions ( 5.4) ]
• Increased Risk of Infections [ see Warnings and Precautions ( 5.5) ]
• Alterations in Endocrine Function [ see Warnings and Precautions ( 5.6) ]
• Cardiovascular Effects [ see Warnings and Precautions ( 5.7) ]
• Renal Effects [ see Warnings and Precautions ( 5.8) ]
• Increased Intraocular Pressure [ see Warnings and Precautions ( 5.9) ]
• Gastrointestinal Perforation [ see Warnings and Precautions ( 5.10) ]
• Alternations in Bone Density [ see Warnings and Precautions ( 5.11) ]
• Behavioral and Mood Disturbances [ see Warnings and Precautions ( 5.12) ]

Because clinical studies 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.

The data below reflect exposure to a single 32 mg intra-articular injection of Nizolex (Triamcinolone Acetonide) in clinical studies in patients with moderate to severe pain due to osteoarthritis of the knee. Clinical studies included randomized, double-blind, parallel-group, placebo and/or active-controlled, and pharmacokinetic/pharmacodynamic studies with follow-up ranging from 6-24 weeks. A total of 424 patients received Nizolex (Triamcinolone Acetonide) and 262 received placebo. Treatment emergent adverse reactions reported by greater than or equal to 1% of patients in the Nizolex (Triamcinolone Acetonide) arms are summarized below ( Table 1 and 2 ).

Overall, the incidence and nature of adverse reactions was similar to that observed with placebo.

Most commonly reported adverse reactions (incidence ≥1%) in clinical studies include sinusitis, cough, and contusions. ( 6)

To report SUSPECTED ADVERSE REACTIONS, contact Flexion Therapeutics, Inc. at 1-844-FLEXION (353-9466) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

Corticosteroid Adverse Reactions

The following adverse reactions, presented alphabetically by body system, are from voluntary reports or clinical studies of corticosteroids. 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, congestive heart failure, 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, increased requirements for insulin or oral hypoglycemic agents in diabetes, manifestations of latent diabetes mellitus, menstrual irregularities, secondary adrenocortical and pituitary unresponsiveness (particularly in times of stress, as in trauma, surgery, or illness), suppression of growth in pediatric patients.

Fluid and electrolyte disturbances: Congestive heart failure in susceptible patients , fluid retention, sodium retention.

Gastrointestinal: Abdominal distention, bowel/bladder dysfunction (after intrathecal administration) , elevation in serum liver enzyme levels (usually reversible upon discontinuation), hepatomegaly, increased appetite, nausea, pancreatitis, peptic ulcer with possible perforation and hemorrhage, perforation of the small and large intestine (particularly in patients with inflammatory bowel disease) , ulcerative esophagitis.

Metabolic: Negative nitrogen balance due to protein catabolism.

Musculoskeletal: Aseptic necrosis of femoral and humeral heads, calcinosis (following intra-articular or intralesional use), Charcot-like arthropathy, loss of muscle mass, muscle weakness, osteoporosis, pathologic fracture of long bones, post injection flare (following intra-articular use), steroid myopathy, tendon rupture, vertebral compression fractures.

Neurologic/Psychiatric: Convulsions, depression, emotional instability, euphoria, headache, increased intracranial pressure with papilledema (pseudotumor cerebri) usually following discontinuation of treatment, insomnia, mood swings, neuritis, neuropathy, paresthesia, personality changes, psychiatric disorders , vertigo. Arachnoiditis, meningitis, paraparesis/paraplegia, and sensory disturbances have occurred after intrathecal administration. Spinal cord infarction, paraplegia, quadriplegia, cortical blindness, and stroke (including brainstem) have been reported after epidural administration of corticosteroids .

Ophthalmic: Exophthalmos, glaucoma, increased intraocular pressure , posterior subcapsular cataracts, rare instances of blindness associated with periocular injections.

Other: Abnormal fat deposits, decreased resistance to infection, hiccups, increased or decreased motility and number of spermatozoa, malaise, moon face, weight gain.

7 DRUG INTERACTIONS

No drug-drug interaction studies have been conducted with Nizolex (Triamcinolone Acetonide). Table 3 contains drug interactions associated with systemic corticosteroids.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

There are no data regarding the use of Nizolex 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 Nizolex (Triamcinolone Acetonide) is limited. In animal reproductive studies from the published literature, pregnant mice, rats, rabbits, or primates administered Nizolex (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 .

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/m ²) to the highest daily Nizolex (Triamcinolone Acetonide) exposure at the MRHD of 32 mg Nizolex (Triamcinolone Acetonide) via Nizolex (Triamcinolone Acetonide).

Pregnant mice dosed with Nizolex (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 Nizolex (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 Nizolex (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 Nizolex (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 Nizolex (Triamcinolone Acetonide) in animals have been conducted.

8.2 Lactation

Risk Summary

There are no available data on the presence of Nizolex (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 Nizolex (Triamcinolone Acetonide) 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 Nizolex (Triamcinolone Acetonide) and any potential adverse effects on the breastfed infant from Nizolex (Triamcinolone Acetonide) or from the underlying maternal condition.

8.3 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.

8.4 Pediatric Use

The safety and effectiveness of Nizolex 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.

8.5 Geriatric Use

Of the total number of patients administered 32 mg Nizolex (Triamcinolone Acetonide) 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 Nizolex (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.

11 DESCRIPTION

Nizolex (Triamcinolone Acetonide) (triamcinolone acetonide extended-release injectable suspension) is a microsphere formulation of Nizolex (Triamcinolone Acetonide), a corticosteroid, to be administered by intra-articular injection.

Nizolex (Triamcinolone Acetonide) is formulated in 75:25 poly(lactic-co-glycolic acid) (PLGA) microspheres with a nominal drug load of 25% (w/w) and is provided as a sterile white to off-white powder. Nizolex (Triamcinolone Acetonide) is prepared with a supplied diluent containing an isotonic, sterile, aqueous solution of sodium chloride (NaCl; 0.9% w/w), sodium carboxymethylcellulose (CMC; 0.5% w/w) and polysorbate-80 (0.1% w/w) to form a 5 mL sterile suspension intended for intra-articular injection.

Active Ingredient

The chemical name for Nizolex (Triamcinolone Acetonide) is 9-fluoro-11β,16α,17,21-tetrahydroxypregna-1,4-diene- 3,20-dione cyclic 16,17-acetal with acetone. Its structural formula is:

Nizolex (Triamcinolone Acetonide) occurs as a white to almost white, crystalline powder having not more than a slight odor and is practically insoluble in water and very soluble in alcohol. Each vial of Nizolex (Triamcinolone Acetonide) powder contains 40 mg of Nizolex (Triamcinolone Acetonide) in 160 mg of microspheres, resulting in 32 mg of deliverable Nizolex (Triamcinolone Acetonide) when prepared according to the Instructions for Use.

Structural Formula

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Nizolex is a corticosteroid with anti-inflammatory and immunomodulating properties. It binds to and activates the glucocorticoid receptor, leading to activation of anti-inflammatory transcription factors such as lipocortins and inhibition of inflammatory transduction pathways by blocking the release of arachidonic acid and preventing the synthesis of prostaglandins and leukotrienes.

12.2 Pharmacodynamics

Studies indicate that following a single intramuscular dose of 60 to 100 mg of immediate-release Nizolex (Triamcinolone Acetonide) injectable suspension, adrenal suppression occurs within 24 to 48 hours and then gradually returns to normal, usually in 30 to 40 days. To assess potential effects of the systemic levels of Nizolex (Triamcinolone Acetonide) associated with a single intra-articular (IA) administration of Nizolex (Triamcinolone Acetonide) on hypothalamic pituitary adrenal (HPA) axis function, serum and urine cortisol levels were monitored over 6 weeks post injection. Adrenal suppression with Nizolex (Triamcinolone Acetonide) occurred within 12-24 hours and then gradually returned to normal, within 30-42 days.

Corticosteroids may increase blood glucose concentrations.

In a study where 18 patients with osteoarthritis knee pain and controlled type 2 diabetes mellitus received a single IA injection of Nizolex (Triamcinolone Acetonide) into the knee, the change from baseline in average blood glucose over the 72 hours after injection as measured by a continuous glucose monitoring device was 8.2 mg/dL (95% confidence interval 0.1, 29.2).

12.3 Pharmacokinetics

Nizolex (Triamcinolone Acetonide) is an extended-release dosage form consisting of microspheres of poly(lactic-co-glycolic acid) (PLGA) containing Nizolex (Triamcinolone Acetonide). Plasma pharmacokinetic parameters for Nizolex (Triamcinolone Acetonide) following IA administration of Nizolex (Triamcinolone Acetonide) or 40 mg immediate-release Nizolex (Triamcinolone Acetonide) into the knee are provided in Table 4.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Long-term animal studies to evaluate the carcinogenic potential of Nizolex (Triamcinolone Acetonide) have not been conducted.

Mutagenesis

Adequate mutagenicity studies have not been conducted with Nizolex (Triamcinolone Acetonide).

Impairment of Fertility

Studies in animals to evaluate the impairment of fertility of Nizolex (Triamcinolone Acetonide) have not been conducted.

14 CLINICAL STUDIES

The efficacy of Nizolex (Triamcinolone Acetonide) was demonstrated in a multi-center, international, randomized, double-blind, parallel-arm, placebo- and active-controlled study in patients with osteoarthritis pain of the knee. A total of 484 patients (ZILRETTA 32 mg, N=161; placebo [saline], N=162; active control [a crystalline suspension, immediate-release formulation of Nizolex (Triamcinolone Acetonide) 40 mg], N=161) were treated and followed for up to 24 weeks. Patients had a mean age of 62 (range 40 to 85 years); baseline demographics and disease characteristics were balanced across treatment arms. Twenty-five percent (25%) of patients had received at least one prior corticosteroid intra-articular injection more than 3 months prior to treatment. A total of 470 patients (97%) completed follow-up to Week 12, the time point for primary efficacy determination, and 443 (91.5%) completed to Week 24.

The primary efficacy endpoint comparing Nizolex (Triamcinolone Acetonide) to placebo was change from baseline at Week 12 in the weekly mean of the Average Daily Pain intensity scores (ADP) as assessed by a 0-10 Numeric Rating Scale (NRS). Nizolex (Triamcinolone Acetonide) demonstrated a statistically significant reduction in pain intensity at the primary endpoint vs placebo. Nizolex (Triamcinolone Acetonide) also demonstrated a reduction in pain intensity scores each week from Weeks 1 through 12 ( Figure 1 ).

In a secondary exploratory analysis, statistical significance was not demonstrated between the Nizolex (Triamcinolone Acetonide) and the active control (immediate-release Nizolex (Triamcinolone Acetonide)) treatment groups for the change from baseline at Week 12 in weekly mean ADP.

Figure 1: Weekly Change from Baseline to Week 12 in Average Daily Pain

Figure 1

16 HOW SUPPLIED/STORAGE AND HANDLING

STORAGE

To maintain expiry period, refrigerate the Nizolex (Triamcinolone Acetonide) single-dose kit (36°-46°F; 2°-8°C) before use.

If refrigeration is unavailable, store the Nizolex (Triamcinolone Acetonide) single-dose kit in the sealed, unopened kit at temperatures not exceeding 77°F (25°C) for up to six weeks and then discard. Do not expose the Nizolex (Triamcinolone Acetonide) single-dose kit to temperatures above 77°F (25°C).

Do not freeze. Store vials in carton.

17 PATIENT COUNSELING INFORMATION

Increased Risk of Infections

Inform patients that they may be more likely to develop infections when taking corticosteroids. Instruct patients to contact 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 .

Risk of Drug Interactions

There are a number of medicines that can interact with corticosteroids such as Nizolex (Triamcinolone Acetonide). Advise patients to alert their health care provider(s) to assess the need to adjust their medication(s) .

Risk of Adverse Psychiatric Reactions

Inform patients that corticosteroid use may be associated with adverse psychiatric reactions. Advise patients and/or caregivers to immediately report any new or worsening behavioral or mood disturbances to their health care provider .

Manufactured for Flexion Therapeutics, Inc., 10 Mall Rd, Suite 301, Burlington, MA 01803

Nizolex (Triamcinolone Acetonide) and Flexion are trademarks of Flexion Therapeutics, Inc.

Copyright © 2017 Flexion Therapeutics, Inc. All rights reserved.

For more information, go to Nizolex (Triamcinolone Acetonide).com or call 1-844-FLEXION (353-9466).

Part Number: 60-004-01

Version: 1, 10/2017

Instructions for Use

Nizolex (Triamcinolone Acetonide)

(triamcinolone acetonide

extended-release injectable suspension)

For intra-articular injection only

Single-dose device

Do not reuse.

IMPORTANT INFORMATION

• Nizolex (Triamcinolone Acetonide) 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 Nizolex (Triamcinolone Acetonide) after preparation to avoid settling of the suspension.
• Nizolex (Triamcinolone Acetonide) is supplied as a single-dose kit and administered as a suspension containing microspheres.
• The Nizolex (Triamcinolone Acetonide) powder vial contains an overfill to allow the appropriate dose to be withdrawn. Nizolex (Triamcinolone Acetonide) 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 Flexion Therapeutics at 1-844-FLEXION (353-9466).

MATERIALS REQUIRED

(Fig.1)

Supplied

• One 32 mg vial of Nizolex (Triamcinolone Acetonide) 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 Nizolex (Triamcinolone Acetonide) 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 Nizolex (Triamcinolone Acetonide) 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 Nizolex (Triamcinolone Acetonide) powder and diluent vials ( Fig. 4).

Figure 4

Clean Vials.

Clean the Nizolex (Triamcinolone Acetonide) 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 Nizolex (Triamcinolone Acetonide) Powder Vial.

Grip the plastic holder that contains the vial adapter.

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

Figure 12

Note: Nizolex (Triamcinolone Acetonide) 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 Nizolex (Triamcinolone Acetonide) 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 Nizolex (Triamcinolone Acetonide).

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 Nizolex (Triamcinolone Acetonide).

Do not reuse excess Nizolex (Triamcinolone Acetonide). Any excess suspension in the vial should be thrown away immediately after the injection. Leftover Nizolex (Triamcinolone Acetonide) 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 Nizolex (Triamcinolone Acetonide) is delivered.

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

Note: Nizolex (Triamcinolone Acetonide) is for intra-articular use only. Nizolex (Triamcinolone Acetonide) is not intended for epidural, intrathecal, intravenous, intraocular, intramuscular, intradermal, or subcutaneous use.

Part Number: 60-005-01

Rev: 10/2017

Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14

Principal Display Panel - Nizolex (Triamcinolone Acetonide) Cart 32mg Carton Label

NDC 70801-003-01 Rx Only

Nizolex (Triamcinolone Acetonide)

(triamcinolone acetonide extended-release

injectable suspension)

32 mg per vial

For intra-articular injection only.

Single-dose kit. Discard unused portion.

Must be reconstituted

with the supplied diluent.

This carton contains:

1 Vial of Nizolex (Triamcinolone Acetonide)

microsphere powder

1 Vial of diluent (5 mL)

for Nizolex (Triamcinolone Acetonide)

1 sterile vial adapter

flexion

Principal Display Panel - Nizolex (Triamcinolone Acetonide) Cart 32mg Professional Carton Label

NDC 70801-003-02 Rx Only

Nizolex (Triamcinolone Acetonide)

(triamcinolone acetonide extended-release

injectable suspension)

32 mg per vial

For intra-articular injection only.

Single-dose kit. Discard unused portion.

Must be reconstituted

with the supplied diluent.

PROFESSIONAL SAMPLE

NOT FOR SALE

OR REIMBURSEMENT

This carton contains:

1 Vial of Nizolex (Triamcinolone Acetonide)

microsphere powder

1 Vial of diluent (5 mL)

for Nizolex (Triamcinolone Acetonide)

1 sterile vial adapter

flexion

Principal Display Panel - Nizolex (Triamcinolone Acetonide) 32mg Vial Label

NDC 70801-001-01 Rx Only

Nizolex (Triamcinolone Acetonide)

(triamcinolone acetonide extended-release

injectable suspension)

32 mg per vial

For intra-articular injection only.

Must be reconstituted

with the supplied diluent.

flexion

Principal Display Panel - Nizolex (Triamcinolone Acetonide) 32mg Professional Vial Label

NDC 70801-001-02 Rx Only

Nizolex (Triamcinolone Acetonide)

(triamcinolone acetonide extended-release

injectable suspension)

32 mg per vial

For intra-articular injection only.

Must be reconstituted

with the supplied diluent.

flexion

Principal Display Panel - Nizolex (Triamcinolone Acetonide) Diluent 5mL Vial Label

NDC 70801-002-01 Rx Only

DILUENT

for use with Nizolex (Triamcinolone Acetonide)

5 mL

Sterile single-use vial

Do not administer directly.

flexion

Principal Display Panel - Nizolex (Triamcinolone Acetonide) Diluent 5mL Professional Vial Label

NDC 70801-002-02 Rx Only

DILUENT

for use with Nizolex (Triamcinolone Acetonide)

5 mL

Sterile single-use vial

Do not administer directly.

flexion