Daktarin-T

Miconazole 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
• Daktarin-T (Miconazole Nitrate) reviews

1 INDICATIONS AND USAGE

• Daktarin-T Ointment is indicated for adjunctive treatment of diaper dermatitis when complicated by documented candidiasis (microscopic evidence of pseudohyphae and /or budding yeast) in immunocompetent pediatric patients 4 weeks and older. (1)
• Daktarin-T (Miconazole Nitrate) Ointment should not be used as a substitute for frequent diaper changes. (1)
• Daktarin-T (Miconazole Nitrate) Ointment should not be used to prevent the occurrence of diaper dermatitis, since preventative use may result in the development of drug resistance. (1)

1.1 Indication

Daktarin-T (Miconazole Nitrate) Ointment is indicated for the adjunctive treatment of diaper dermatitis only when complicated by documented candidiasis (microscopic evidence of pseudohyphae and/or budding yeast), in immunocompetent pediatric patients 4 weeks and older. A positive fungal culture for Candida albicansis not adequate evidence of candidal infection since colonization with C. albicans can result in a positive culture. The presence of candidal infection should be established by microscopic evaluation prior to initiating treatment.

Daktarin-T (Miconazole Nitrate) should be used as part of a treatment regimen that includes measures directed at the underlying diaper dermatitis, including gentle cleansing of the diaper area and frequent diaper changes.

Daktarin-T (Miconazole Nitrate) should not be used as a substitute for frequent diaper changes. Daktarin-T (Miconazole Nitrate) should not be used to prevent the occurrence of diaper dermatitis, since preventative use may result in the development of drug resistance.

1.2 Limitations of Use

The safety and efficacy of Daktarin-T (Miconazole Nitrate) have not been demonstrated in immunocompromised patients, or in infants less than 4 weeks of age (premature or term).

The safety and efficacy of Daktarin-T (Miconazole Nitrate) have not been evaluated in incontinent adult patients. Daktarin-T (Miconazole Nitrate) should not be used to prevent the occurrence of diaper dermatitis, such as in an adult institutional setting, since preventative use may result in the development of drug resistance.

2 DOSAGE AND ADMINISTRATION

Daktarin-T (Miconazole Nitrate) is not for oral, ophthalmic, or intravaginal use.

Before applying Daktarin-T (Miconazole Nitrate), gently cleanse the skin with lukewarm water and pat dry with a soft towel. Avoid using any scented soaps, shampoos, or lotions on the diaper area.

Apply Daktarin-T (Miconazole Nitrate) to the affected area at each diaper change for 7 days. Continue treatment for the full 7 days, even if there is improvement. The safety of Daktarin-T (Miconazole Nitrate) when used for longer than 7 days is not known. Do not use Daktarin-T (Miconazole Nitrate) for longer than 7 days. If symptoms have not improved by day 7, see your health care provider.

Gently apply a thin layer of Daktarin-T (Miconazole Nitrate) to the diaper area with the fingertips. Do not rub Daktarin-T (Miconazole Nitrate) into the skin as this may cause additional irritation. Thoroughly wash hands after applying Daktarin-T (Miconazole Nitrate).

• Daktarin-T (Miconazole Nitrate) Ointment is for topical use only. Daktarin-T (Miconazole Nitrate) Ointment is not for oral, ophthalmic, or intravaginal use. (2)
• Daktarin-T (Miconazole Nitrate) Ointment should be applied as a thin layer to the affected area at each diaper change for 7 days. (2)
• Daktarin-T (Miconazole Nitrate) Ointment should be used as part of a treatment regimen that includes gentle cleansing of the diaper area and frequent diaper changes. (2)

3 DOSAGE FORMS AND STRENGTHS

White ointment containing 0.25% Daktarin-T (Miconazole Nitrate) nitrate, 15% zinc oxide, and 81.35% white petrolatum.

• Ointment with 0.25% Daktarin-T (Miconazole Nitrate) nitrate, 15% zinc oxide, and 81.35% white petrolatum. (3)

4 CONTRAINDICATIONS

None

• None

5 WARNINGS AND PRECAUTIONS

If irritation occurs or if the disease worsens, discontinue use of the medication, and contact the health care provider.

The safety and efficacy of Daktarin-T (Miconazole Nitrate) have not been evaluated in incontinent adult patients. Daktarin-T (Miconazole Nitrate) should not be used to prevent the occurrence of diaper dermatitis, such as in an adult institutional setting, since preventative use may result in the development of drug resistance.

• If irritation occurs or if the disease worsens, discontinue use of the medication, and contact the health care provider. (5)

6 ADVERSE REACTIONS

To report SUSPECTED ADVERSE REACTIONS, contact Prestium Pharma, Inc. at 1-866-897-5002 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 rate 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 clinical practice.

A total of 835 infants and young children were evaluated in the clinical development program. Of 418 subjects in the Daktarin-T group, 58 (14%) reported one or more adverse events. Of 417 subjects in the zinc oxide/white petrolatum control group, 85 (20%) reported one or more adverse events. Adverse events that occurred at a rate of ≥ 1% for subjects who were treated with Daktarin-T (Miconazole Nitrate) were approximately the same in type and frequency as for subjects who were treated with zinc oxide/white petrolatum ointment.

6.2 Post-marketing Experience

The following adverse reactions have been identified during post approval use of Daktarin-T (Miconazole Nitrate).

GASTROINTESTINAL DISORDERS: vomiting

GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS: burning sensation, condition aggravated, inflammation, pain

INJURY, POISONING AND PROCEDURAL COMPLICATIONS: accidental exposure

SKIN AND SUBCUTANEOUS TISSUE DISORDERS: blister, dermatitis contact, diaper dermatitis, dry skin, erythema, pruritus, rash, skin exfoliation

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

7 DRUG INTERACTIONS

Drug-drug interaction studies were not conducted. Women who take a warfarin anticoagulant and use a Daktarin-T (Miconazole Nitrate) intravaginal cream or suppository may be at risk for developing an increased prothrombin time, international normalized ratio (INR), and bleeding. The potential for this interaction between warfarin and Daktarin-T (Miconazole Nitrate) is unknown.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C

There are no adequate and well-controlled studies of Daktarin-T in pregnant women. Therefore, Daktarin-T (Miconazole Nitrate) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Daktarin-T (Miconazole Nitrate) nitrate administration has been shown to result in prolonged gestation and decreased numbers of live young in rats and in increased number of resorptions and decreased number of live young in rabbits at oral doses of 100 mg/kg/day and 80 mg/kg/day, which are 28 and 45 times the maximum possible topical exposure of caregivers, respectively, assuming 100% absorption.

8.3 Nursing Mothers

Safety and efficacy of Daktarin-T (Miconazole Nitrate) have not been established in nursing mothers. It is not known if the active components of Daktarin-T (Miconazole Nitrate) may be present in milk.

8.4 Pediatric Use

Efficacy was not demonstrated in infants less than 4 weeks of age. Safety and efficacy have not been established in very-low-birth-weight infants.

Daktarin-T should not be used to prevent diaper dermatitis.

The safety of Daktarin-T (Miconazole Nitrate) when used for longer than 7 days is not known. Do not use more than 7 days.

8.5 Geriatric Use

Safety and efficacy in a geriatric population have not been evaluated.

11 DESCRIPTION

Daktarin-T (Miconazole Nitrate) contains the synthetic antifungal agent, Daktarin-T (Miconazole Nitrate) nitrate (0.25%) USP, zinc oxide (15%) USP, and white petrolatum (81.35%) USP.

The chemical name of Daktarin-T (Miconazole Nitrate) nitrate is 1-[2, 4-dichloro-ß-{(2,4-dichlorobenzyl)oxy} phenethyl] imidazole mononitrate with empirical formula C₁₈H₁₄Cl₄N₂O-HNO₃ and molecular weight of 479.15. The structural formula of Daktarin-T (Miconazole Nitrate) nitrate is as follows:

The zinc oxide has an empirical formula of ZnO and a molecular weight of 81.39.

The white petrolatum, which is obtained from petroleum and is wholly or nearly decolorized, is a purified mixture of semisolid saturated hydrocarbons having the general chemical formula C_nH_2n+2. The hydrocarbons consist mainly of branched and unbranched chains. White petrolatum contains butylated hydroxytoluene (BHT) as stabilizer.

Each gram of Daktarin-T (Miconazole Nitrate) contains 2.5 mg of Daktarin-T (Miconazole Nitrate) nitrate USP, 150 mg of zinc oxide USP, and 813.5 mg of white petrolatum USP containing butylated hydroxytoluene, trihydroxystearin, and Chemoderm^® 1001/B fragrance.¹

Daktarin-T (Miconazole Nitrate) is a smooth, uniform, white ointment.

Structural formula of Daktarin-T (Miconazole Nitrate) nitrate

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

The Daktarin-T component of Daktarin-T (Miconazole Nitrate) is an antifungal agent. The mechanism of action of white petrolatum and zinc oxide for the adjunctive treatment of diaper dermatitis is unknown.

12.2 Pharmacodynamics

The human pharmacodynamics of Daktarin-T (Miconazole Nitrate) is unknown.

12.3 Pharmacokinetics

The topical absorption of Daktarin-T from Daktarin-T (Miconazole Nitrate) was studied in immunocompetent male and female infants and children (n=17) with diaper dermatitis complicated by documented candidiasis (microscopic evidence of pseudohyphae and/or budding yeast) ranging in age from 1 month to 21 months. After multiple daily applications to the affected area at every diaper change (approximately 5-12 times per day) for 7 days, the plasma concentrations of Daktarin-T (Miconazole Nitrate) were below the lower limit of quantitation (LOQ) of 0.5 ng/mL in 15 out of 17 (88%) subjects. In the other 2 remaining subjects, the plasma concentrations of Daktarin-T (Miconazole Nitrate) were 0.57 and 0.58 ng/mL, respectively at a single timepoint (4 hours after the last application) on Day 7.

12.4 Microbiology

The Daktarin-T (Miconazole Nitrate) nitrate component in this product has been shown to have in vitro activity against Candida albicans, an organism that is associated with diaper dermatitis. The activity of Daktarin-T (Miconazole Nitrate) nitrate against C. albicans is based on the inhibition of the ergosterol biosynthesis in the cell membrane. The accumulation of ergosterol precursors and toxic peroxides results in cytolysis of the cell. In vitro minimal inhibitory concentration (MIC) test results for C. albicans isolates obtained from treatment failures in Clinical Study 1 (see Clinical Studies (14)) does not appear to indicate that resistance to Daktarin-T (Miconazole Nitrate) nitrate was the reason for treatment failure. The clinical significance of the in vitro activity of Daktarin-T (Miconazole Nitrate) nitrate against C. albicans in the setting of diaper dermatitis is unclear.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

The carcinogenic potential of Daktarin-T (Miconazole Nitrate) in animals has not been evaluated.

Daktarin-T (Miconazole Nitrate) nitrate was negative in a bacterial reverse mutation test, a chromosome aberration test in mice, and micronucleus assays in mice and rats.

Daktarin-T (Miconazole Nitrate) nitrate had no adverse effect on fertility in a study in rats at oral doses of up to 320 mg/kg/day, which is 89 times the maximum possible topical exposure of caregivers, assuming 100% absorption.

14 CLINICAL STUDIES

Study 1 was a double-blind, multicenter study in which Daktarin-T (Miconazole Nitrate) was compared to the zinc oxide and white petrolatum combination treatment and included 236 infants and toddlers with diaper dermatitis, complicated by candidiasis as documented by KOH tests that demonstrated psuedohyphae and/or budding yeasts. Study medication was applied at every diaper change for 7 days.

The primary endpoint was “Overall Cure” and required that subjects be both clinically cured (total resolution of all signs and symptoms of infection) and microbiologically cured (eradication of candidiasis). Primary efficacy was assessed 1 week following the end of treatment, at Day 14.

Study results are shown in the following table.

Two additional studies provided supportive evidence of the clinical efficacy of Daktarin-T (Miconazole Nitrate) in infants and toddlers with diaper dermatitis, some of whom cultured positive for C. albicans. However, candidal infection was not documented in the culture-positive subjects, as microscopic testing (e.g. KOH) was not done. Therefore, the positive culture results may have reflected colonization rather than infection.

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

Daktarin-T is a smooth, uniform, white ointment supplied in an aluminum tube, as follows:

50g (NDC 40076-002-50)

16.2 Storage Conditions

Store at controlled room temperature between 20°C and 25°C (68°F and 77°F); with excursions permitted between 15°C and 30°C (59°F and 86°F).

Keep out of reach of children.

17 PATIENT COUNSELING INFORMATION

See FDA-Approved Patient Labeling

Patients using Daktarin-T (Miconazole Nitrate) should be informed about the following information:

• Daktarin-T (Miconazole Nitrate) is to be used only for diaper dermatitis that is complicated by documented candidiasis (i.e. documented by microscopic testing).
• Daktarin-T (Miconazole Nitrate) should not be used as a substitute for frequent diaper changes.
• Daktarin-T (Miconazole Nitrate) should not be used to prevent diaper dermatitis.
• Daktarin-T (Miconazole Nitrate) should not be used long term.
• Daktarin-T (Miconazole Nitrate) should be used only as directed by the health care provider.
• Daktarin-T (Miconazole Nitrate) is for external use only. It is not for oral, ophthalmic, or intravaginal use.
• Gently cleanse the diaper area with lukewarm water or a very mild soap and pat the area dry with a soft towel before applying Daktarin-T (Miconazole Nitrate).
• Gently apply Daktarin-T (Miconazole Nitrate) to the diaper area with the fingertips after each diaper change. Do not rub Daktarin-T (Miconazole Nitrate) into the skin as this may cause additional irritation.
• Thoroughly wash hands after applying Daktarin-T (Miconazole Nitrate).
• Treatment should be continued for 7 days, even if there is improvement. Do not use Daktarin-T (Miconazole Nitrate) for longer than 7 days. If symptoms have not improved by day 7, see your health care provider.
• Daktarin-T (Miconazole Nitrate) should not be used on children for whom it is not prescribed.

Manufactured for:

Prestium Pharma, Inc.

Newtown, PA 18940

Manufactured by:

GlaxoSmithKline

Mississauga, ON, Canada

Made in Canada

© 2013 Delcor Asset Corporation, an affiliate of Prestium Pharma, Inc.

Revised Oct 2013 VSN:3PI

FDA-Approved Patient Labeling

Daktarin-T (Miconazole Nitrate)^® (Vu-sion) Ointment

(0.25% Daktarin-T (Miconazole Nitrate) nitrate, 15% zinc oxide and 81.35% white petrolatum)

IMPORTANT: For Skin Use Only. Do not use in the mouth, eyes, or vagina.

Read the Patient Information that comes with Daktarin-T (Miconazole Nitrate) before you use it on your child. This leaflet does not take the place of talking to your health care provider about your child’s medical condition or treatment. If you have any questions or if you are not sure about any of the information on Daktarin-T (Miconazole Nitrate), ask your health care provider, or pharmacist.

What is Daktarin-T (Miconazole Nitrate)?

Daktarin-T (Miconazole Nitrate) is a prescription skin medicine used to treat diaper rash that also has a yeast infection in children who are at least 4 weeks old and who have a normal immune system. Daktarin-T (Miconazole Nitrate) contains medicines that will help treat the yeast infection and the diaper rash, but you must also change your child’s diapers very often so that your child is not wearing a wet or soiled diaper. Even if you use Daktarin-T (Miconazole Nitrate), diaper rash will not go away if you do not keep your child’s diaper area clean and dry. You should use water or a very mild cleanser to clean your child’s diaper area. Daktarin-T (Miconazole Nitrate) is not to be used to prevent diaper rash or to be used for more than 7 days.

Your health care provider will need to do a special test to tell if your child’s diaper rash also has a yeast infection. Do not use Daktarin-T (Miconazole Nitrate) on your child’s diaper rash unless your health care provider tells you that there is also a yeast infection.

Who should not use Daktarin-T (Miconazole Nitrate)?

Daktarin-T (Miconazole Nitrate) is not for treatment of all cases of diaper rash. Daktarin-T (Miconazole Nitrate) is only for diaper rash that also has a yeast infection. Most cases of diaper rash do not need the yeast medicine that is in Daktarin-T (Miconazole Nitrate) because most cases of diaper rash do not also have a yeast infection.

Do not use Daktarin-T (Miconazole Nitrate) on any other children or other family member.

Do not use Daktarin-T (Miconazole Nitrate) on your child’s diaper rash if they are allergic to anything in it. See the end of this leaflet for a list of ingredients in Daktarin-T (Miconazole Nitrate).

Do not use on infants less than 4 weeks of age.

Do not use in infants or children who do not have a normal immune system.

How should I use Daktarin-T (Miconazole Nitrate) on my child?

Daktarin-T (Miconazole Nitrate) is applied to the skin on your child’s diaper area at each diaper change for 7 days.

Apply Daktarin-T (Miconazole Nitrate) for the full 7 days even if the diaper rash starts to go away. Call your child’s health care provider if the diaper rash gets worse or does not go away with 7 days of treatment with Daktarin-T (Miconazole Nitrate). Daktarin-T (Miconazole Nitrate) should not be used for more than 7 days.

To apply Daktarin-T (Miconazole Nitrate):

• Gently, clean the skin on your child’s diaper area with warm ( not hot ) water. You may also use a very mild soap. Pat the area dry with a soft towel.
• Use your fingertips and gently apply a thin layer of Daktarin-T (Miconazole Nitrate) to your child’s diaper area at each diaper change. Do not rub Daktarin-T (Miconazole Nitrate) into your child’s skin. Rubbing the skin can cause more irritation.
• Wash your hands after applying Daktarin-T (Miconazole Nitrate) on your child.

Daktarin-T (Miconazole Nitrate) is for skin use only.

Call your child’s health care provider or poison control center right away if any Daktarin-T (Miconazole Nitrate) is swallowed. Call your child’s health care provider if Daktarin-T (Miconazole Nitrate) gets in the eye.

Keep out of reach of children.

What other steps will help diaper rash go away?

• Check your child’s diaper often. Change the diaper at the first sign of wetness.
• Clean your child’s diaper area after each diaper change. Gently wipe the diaper area from the front to back using warm ( not hot )water. You may also use a mild soap. Rinse the diaper area well. Pat dry with a soft towel.
• Keep the diaper area open to air when possible.
• Even if you use Daktarin-T (Miconazole Nitrate), diaper rash will not go away if you do not keep your child’s diaper area clean and dry.

What are the possible side effects of Daktarin-T (Miconazole Nitrate)?

Daktarin-T (Miconazole Nitrate) may cause irritation. You should call your child’s health care provider if irritation appears or if the diaper rash gets worse.

How should I store Daktarin-T (Miconazole Nitrate)?

• Keep Daktarin-T (Miconazole Nitrate) out of the reach of children to avoid the risk of accidental ingestion.
• Store Daktarin-T (Miconazole Nitrate) at room temperature between 68°F to 77°F (20°C to 25°C).

General information about Daktarin-T (Miconazole Nitrate)

Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets.

Do not use Daktarin-T (Miconazole Nitrate) for a condition for which it was not prescribed. Do not give Daktarin-T (Miconazole Nitrate) to other children or family members, even if they have the same symptoms your child has. It may harm them.

This leaflet summarizes the most important information about Daktarin-T (Miconazole Nitrate). If you would like more information, talk to your child’s health care provider. You can ask your child’s health care provider or pharmacist for information about Daktarin-T (Miconazole Nitrate) that is written for healthcare professionals.

Side effects may be reported to Prestium Pharma, Inc. at 1-866-897-5002 or the FDA at 1-800-FDA-1088.

What are the ingredients in Daktarin-T (Miconazole Nitrate)?

Active Ingredients: Daktarin-T (Miconazole Nitrate) nitrate, zinc oxide, and white petrolatum

Inactive Ingredients: trihydroxystearin, butylated hydroxyltoluene (BHT), and Chemoderm^® 1001/B fragrance

This Patient Information leaflet has been approved by the U.S. Food and Drug Administration.

The Patient Information leaflet was last revised: October 2013

Manufactured for:

Prestium Pharma, Inc.

Newtown, PA 18940

Manufactured by:

GlaxoSmithKline

Mississauga, ON, Canada

Made in Canada

© 2013 Delcor Asset Corporation, an affiliate of

Prestium Pharma, Inc.

Revised Oct 2013

VSN:3PIL

Principal Display Panel

NDC 40076-002-50

Daktarin-T (Miconazole Nitrate)^®

(miconazole nitrate 0.25% USP, zinc oxide 15% USP, white petrolatum 81.35% USP)

Ointment

50 grams

R_x only

Principal Display Panel NDC 40076-002-50 Vusion® (miconazole nitrate 0.25% USP, zinc oxide 15% USP, white petrolatum 81.35% USP) Ointment 50 grams Rx only

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
• Daktarin-T (Triamcinolone Acetonide) reviews

1 INDICATIONS AND USAGE

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

Daktarin-T (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

Daktarin-T (Triamcinolone Acetonide) is not intended for repeat administration. ( 1)

Limitation of Use

Daktarin-T (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 Daktarin-T (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 Daktarin-T (Triamcinolone Acetonide). ( 2.3)

2.1 Important Dosage and Administration Information

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

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

Daktarin-T (Triamcinolone Acetonide) must be prepared using the diluent supplied in the kit.

Preparation of Daktarin-T (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.

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

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

Daktarin-T (Triamcinolone Acetonide) is not interchangeable with other formulations of injectable Daktarin-T (Triamcinolone Acetonide).

3 DOSAGE FORMS AND STRENGTHS

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

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

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

4 CONTRAINDICATIONS

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

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

5 WARNINGS AND PRECAUTIONS

• Intra-articular Use Only: Do not administer Daktarin-T 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 Daktarin-T (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 Daktarin-T (Triamcinolone Acetonide)

Daktarin-T (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 Daktarin-T (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 Daktarin-T (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 Daktarin-T (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 Daktarin-T (Triamcinolone Acetonide) and 262 received placebo. Treatment emergent adverse reactions reported by greater than or equal to 1% of patients in the Daktarin-T (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 Daktarin-T (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 Daktarin-T 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 Daktarin-T (Triamcinolone Acetonide) is limited. In animal reproductive studies from the published literature, pregnant mice, rats, rabbits, or primates administered Daktarin-T (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 Daktarin-T (Triamcinolone Acetonide) exposure at the MRHD of 32 mg Daktarin-T (Triamcinolone Acetonide) via Daktarin-T (Triamcinolone Acetonide).

Pregnant mice dosed with Daktarin-T (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 Daktarin-T (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 Daktarin-T (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 Daktarin-T (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 Daktarin-T (Triamcinolone Acetonide) in animals have been conducted.

8.2 Lactation

Risk Summary

There are no available data on the presence of Daktarin-T (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 Daktarin-T (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 Daktarin-T (Triamcinolone Acetonide) and any potential adverse effects on the breastfed infant from Daktarin-T (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 Daktarin-T 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 Daktarin-T (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 Daktarin-T (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

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

Daktarin-T (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. Daktarin-T (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 Daktarin-T (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:

Daktarin-T (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 Daktarin-T (Triamcinolone Acetonide) powder contains 40 mg of Daktarin-T (Triamcinolone Acetonide) in 160 mg of microspheres, resulting in 32 mg of deliverable Daktarin-T (Triamcinolone Acetonide) when prepared according to the Instructions for Use.

Structural Formula

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Daktarin-T 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 Daktarin-T (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 Daktarin-T (Triamcinolone Acetonide) associated with a single intra-articular (IA) administration of Daktarin-T (Triamcinolone Acetonide) on hypothalamic pituitary adrenal (HPA) axis function, serum and urine cortisol levels were monitored over 6 weeks post injection. Adrenal suppression with Daktarin-T (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 Daktarin-T (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

Daktarin-T (Triamcinolone Acetonide) is an extended-release dosage form consisting of microspheres of poly(lactic-co-glycolic acid) (PLGA) containing Daktarin-T (Triamcinolone Acetonide). Plasma pharmacokinetic parameters for Daktarin-T (Triamcinolone Acetonide) following IA administration of Daktarin-T (Triamcinolone Acetonide) or 40 mg immediate-release Daktarin-T (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 Daktarin-T (Triamcinolone Acetonide) have not been conducted.

Mutagenesis

Adequate mutagenicity studies have not been conducted with Daktarin-T (Triamcinolone Acetonide).

Impairment of Fertility

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

14 CLINICAL STUDIES

The efficacy of Daktarin-T (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 Daktarin-T (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 Daktarin-T (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). Daktarin-T (Triamcinolone Acetonide) demonstrated a statistically significant reduction in pain intensity at the primary endpoint vs placebo. Daktarin-T (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 Daktarin-T (Triamcinolone Acetonide) and the active control (immediate-release Daktarin-T (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 Daktarin-T (Triamcinolone Acetonide) single-dose kit (36°-46°F; 2°-8°C) before use.

If refrigeration is unavailable, store the Daktarin-T (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 Daktarin-T (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 Daktarin-T (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

Daktarin-T (Triamcinolone Acetonide) and Flexion are trademarks of Flexion Therapeutics, Inc.

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

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

Part Number: 60-004-01

Version: 1, 10/2017

Instructions for Use

Daktarin-T (Triamcinolone Acetonide)

(triamcinolone acetonide

extended-release injectable suspension)

For intra-articular injection only

Single-dose device

Do not reuse.

IMPORTANT INFORMATION

• Daktarin-T (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 Daktarin-T (Triamcinolone Acetonide) after preparation to avoid settling of the suspension.
• Daktarin-T (Triamcinolone Acetonide) is supplied as a single-dose kit and administered as a suspension containing microspheres.
• The Daktarin-T (Triamcinolone Acetonide) powder vial contains an overfill to allow the appropriate dose to be withdrawn. Daktarin-T (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 Daktarin-T (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 Daktarin-T (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 Daktarin-T (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 Daktarin-T (Triamcinolone Acetonide) powder and diluent vials ( Fig. 4).

Figure 4

Clean Vials.

Clean the Daktarin-T (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 Daktarin-T (Triamcinolone Acetonide) Powder Vial.

Grip the plastic holder that contains the vial adapter.

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

Figure 12

Note: Daktarin-T (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 Daktarin-T (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 Daktarin-T (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 Daktarin-T (Triamcinolone Acetonide).

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

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

Note: Daktarin-T (Triamcinolone Acetonide) is for intra-articular use only. Daktarin-T (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 - Daktarin-T (Triamcinolone Acetonide) Cart 32mg Carton Label

NDC 70801-003-01 Rx Only

Daktarin-T (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 Daktarin-T (Triamcinolone Acetonide)

microsphere powder

1 Vial of diluent (5 mL)

for Daktarin-T (Triamcinolone Acetonide)

1 sterile vial adapter

flexion

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

NDC 70801-003-02 Rx Only

Daktarin-T (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 Daktarin-T (Triamcinolone Acetonide)

microsphere powder

1 Vial of diluent (5 mL)

for Daktarin-T (Triamcinolone Acetonide)

1 sterile vial adapter

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

NDC 70801-001-01 Rx Only

Daktarin-T (Triamcinolone Acetonide)

(triamcinolone acetonide extended-release

injectable suspension)

32 mg per vial

For intra-articular injection only.

Must be reconstituted

with the supplied diluent.

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

NDC 70801-001-02 Rx Only

Daktarin-T (Triamcinolone Acetonide)

(triamcinolone acetonide extended-release

injectable suspension)

32 mg per vial

For intra-articular injection only.

Must be reconstituted

with the supplied diluent.

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

NDC 70801-002-01 Rx Only

DILUENT

for use with Daktarin-T (Triamcinolone Acetonide)

5 mL

Sterile single-use vial

Do not administer directly.

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

NDC 70801-002-02 Rx Only

DILUENT

for use with Daktarin-T (Triamcinolone Acetonide)

5 mL

Sterile single-use vial

Do not administer directly.

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