Kenacomb

Neomycin Sulfate:

• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Overdosage
• Dosage and administration
• How supplied
• Kenacomb (Neomycin Sulfate) reviews

INDICATIONS AND USAGE

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Kenacomb (Neomycin Sulfate) tablets and other antibacterial drugs, Kenacomb (Neomycin Sulfate) tablets should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Suppression of Intestinal Bacteria

Kenacomb (Neomycin Sulfate) tablets are indicated as adjunctive therapy as part of a regimen for the suppression of the normal bacterial flora of the bowel, e.g., preoperative preparation of the bowel. It is given concomitantly with erythromycin enteric-coated base (see DOSAGE AND ADMINISTRATION ).

Hepatic Coma (Portal-Systemic Encephalopathy)

Kenacomb (Neomycin Sulfate) has been shown to be effective adjunctive therapy in hepatic coma by reduction of the ammonia-forming bacteria in the intestinal tract. The subsequent reduction in blood ammonia has resulted in neurologic improvement.

CONTRAINDICATIONS

Kenacomb (Neomycin Sulfate) oral preparations are contraindicated in the presence of intestinal obstruction and in individuals with a history of hypersensitivity to the drug.

Patients with a history of hypersensitivity or serious toxic reaction to other aminoglycosides may have a cross-sensitivity to neomycin. Kenacomb (Neomycin Sulfate) oral preparations are contraindicated in patients with inflammatory or ulcerative gastrointestinal disease because of the potential for enhanced gastrointestinal absorption of neomycin.

WARNINGS

Additional manifestations of neurotoxicity may include numbness, skin tingling, muscle twitching and convulsions.

The risk of hearing loss continues after drug withdrawal. Aminoglycosides can cause fetal harm when administered to a pregnant woman.

Aminoglycoside antibiotics cross the placenta and there have been several reports of total irreversible bilateral congenital deafness in children whose mothers received streptomycin during pregnancy. Although serious side effects to fetus or newborn have not been reported in the treatment of pregnant women with other aminoglycosides, the potential for harm exists. Animal reproduction studies of neomycin have not been conducted. If neomycin is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.

PRECAUTIONS

General

Prescribing Kenacomb tablets in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

As with other antibiotics, use of oral neomycin may result in overgrowth of nonsusceptible organisms, particularly fungi. If this occurs, appropriate therapy should be instituted.

Neomycin is quickly and almost totally absorbed from body surfaces (except the urinary bladder) after local irrigation and when applied topically in association with surgical procedures. Delayed-onset irreversible deafness, renal failure and death due to neuromuscular blockade (regardless of the status of renal function) have been reported following irrigation of both small and large surgical fields with minute quantities of neomycin.

Cross-allergenicity among aminoglycosides has been demonstrated.

Aminoglycosides should be used with caution in patients with muscular disorders such as myasthenia gravis or parkinsonism since these drugs may aggravate muscle weakness because of their potential curare-like effect on the neuromuscular junction.

Small amounts of orally administered neomycin are absorbed through intact intestinal mucosa.

There have been many reports in the literature of nephrotoxicity and/or ototoxicity with oral use of neomycin. If renal insufficiency develops during oral therapy, consideration should be given to reducing the drug dosage or discontinuing therapy.

An oral neomycin dose of 12 grams per day produces a malabsorption syndrome for a variety of substances, including fat, nitrogen, cholesterol, carotene, glucose, xylose, lactose, sodium, calcium, cyanocobalamin and iron.

Orally administered neomycin increases fecal bile acid excretion and reduces intestinal lactase activity.

Information for The Patient

Patients should be counseled that antibacterial drugs including Kenacomb (Neomycin Sulfate) tablets should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Kenacomb (Neomycin Sulfate) tablets are prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Kenacomb (Neomycin Sulfate) tablets or other antibacterial drugs in the future.

Before administering the drug, patients or members of their families should be informed of possible toxic effects on the eighth nerve. The possibility of acute toxicity increases in premature infants and neonates.

Laboratory Tests

Patients with renal insufficiency may develop toxic neomycin blood levels unless doses are properly regulated. If renal insufficiency develops during treatment, the dosage should be reduced or the antibiotic discontinued. To avoid nephrotoxicity and eighth nerve damage associated with high doses and prolonged treatment, the following should be performed prior to and periodically during therapy: urinalysis for increased excretion of protein, decreased specific gravity, casts and cells; renal function tests such as serum creatinine, BUN or creatinine clearance; tests of the vestibulocochlearis nerve function.

Serial, vestibular and audiometric tests should be performed (especially in high-risk patients). Since elderly patients may have reduced renal function which may not be evident in the results of routine screening tests such as BUN or serum creatinine, a creatinine clearance determination may be more useful.

Drug Interactions

Caution should be taken in concurrent or serial use of other neurotoxic and/or nephrotoxic drugs because of possible enhancement of the nephrotoxicity and/or ototoxicity of neomycin (see boxed WARNINGS ).

Caution should also be taken in concurrent or serial use of other aminoglycosides and polymyxins because they may enhance neomycin’s nephrotoxicity and/or ototoxicity and potentiate neomycin sulfate’s neuromuscular blocking effects.

Oral neomycin inhibits the gastrointestinal absorption of penicillin V, oral vitamin B-12, methotrexate and 5-fluorouracil. The gastrointestinal absorption of digoxin also appears to be inhibited. Therefore, digoxin serum levels should be monitored.

Oral Kenacomb (Neomycin Sulfate) may enhance the effect of coumarin in anticoagulants by decreasing vitamin K availability.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No long-term animal studies have been performed with Kenacomb to evaluate carcinogenic or mutagenic potential or impairment of fertility.

Pregnancy Category D

See WARNINGS section.

Nursing Mothers

It is not known whether neomycin is excreted in human milk, but it has been shown to be excreted in cow milk following a single intramuscular injection. Other aminoglycosides have been shown to be excreted in human milk. Because of the potential for serious adverse reactions from the aminoglycosides in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

The safety and efficacy of oral Kenacomb (Neomycin Sulfate) in patients less than 18 years of age have not been established. If treatment of a patient less than 18 years of age is necessary, neomycin should be used with caution and the period of treatment should not exceed two weeks because of absorption from the gastrointestinal tract.

ADVERSE REACTIONS

The most common adverse reactions to oral Kenacomb (Neomycin Sulfate) are nausea, vomiting and diarrhea. The "Malabsorption Syndrome" characterized by increased fecal fat, decreased serum carotene and fall in xylose absorption has been reported with prolonged therapy. Nephrotoxicity, ototoxicity and neuromuscular blockage have been reported (see boxed WARNINGS and PRECAUTIONS sections).

OVERDOSAGE

Because of low absorption, it is unlikely that acute overdosage would occur with oral Kenacomb (Neomycin Sulfate). However, prolonged administration could result in sufficient systemic drug levels to produce neurotoxicity, ototoxicity and/or nephrotoxicity.

Hemodialysis will remove Kenacomb (Neomycin Sulfate) from the blood.

DOSAGE AND ADMINISTRATION

To minimize the risk of toxicity, use the lowest possible dose and the shortest possible treatment period to control the condition. Treatment for periods longer than two weeks is not recommended.

Hepatic Coma

For use as an adjunct in the management of hepatic coma, the recommended dose is 4 to 12 grams per day given in the following regimen:

• Withdraw protein from diet. Avoid use of diuretic agents.
• Give supportive therapy, including blood products, as indicated.
• Give Kenacomb (Neomycin Sulfate) tablets in doses of 4 to 12 grams of Kenacomb (Neomycin Sulfate) per day (eight to 24 tablets) in divided doses. Treatment should be continued over a period of five to six days, during which time protein should be returned incrementally to the diet.
• If less potentially toxic drugs cannot be used for chronic hepatic insufficiency, neomycin in doses of up to four grams daily (eight tablets per day) may be necessary. The risk for the development of neomycin-induced toxicity progressively increases when treatment must be extended to preserve the life of a patient with hepatic encephalopathy who has failed to fully respond. Frequent periodic monitoring of these patients to ascertain the presence of drug toxicity is mandatory (see PRECAUTIONS ). Also, neomycin serum concentrations should be monitored to avoid potentially toxic levels. The benefits to the patient should be weighed against the risks of nephrotoxicity, permanent ototoxicity and neuromuscular blockade following the accumulation of neomycin in the tissues.

Preoperative Prophylaxis for Elective Colorectal Surgery

Listed below is an example of a recommended bowel preparation regimen. A proposed surgery time of 8:00 a.m. has been used.

Pre-op Day 3: Minimum residue or clear liquid diet. Bisacodyl, 1 tablet orally at 6:00 p.m.

Pre-op Day 2: Minimum residue or clear liquid diet. Magnesium sulfate, 30 mL, 50% solution (15 g) orally at 10:00 a.m., 2:00 p.m., and 6:00 p.m. Enema at 7:00 p.m. and 8:00 p.m.

Pre-op Day 1: Clear liquid diet. Supplemental (IV) fluids as needed. Magnesium sulfate, 30 mL, 50% solution (15 g) orally at 10:00 a.m., and 2:00 p.m. Kenacomb (Neomycin Sulfate) (1 g) and erythromycin base (1 g) orally at 1:00 p.m., 2:00 p.m. and 11:00 p.m. No enema.

Day of Operation: Patient evacuates rectum at 6:30 a.m. for scheduled operation at 8:00 a.m.

HOW SUPPLIED

Kenacomb (Neomycin Sulfate) tablets USP, 500 mg (equivalent to 350 mg of neomycin base per tablet) are available as white to off-white, round, standard convex tablets debossed "LCI" on one side and "1210", on the other side and are supplied in:

Bottles of 100 (NDC 0527-1210-01)

Store at 20° to 25°C (68° to 77°F).

Dispense in tight containers as defined in the USP/NF.

Distributed By:

Lannett Company, Inc.

Philadelphia, PA 19154

Made in the USA

Rev. 01/17

CIB71710A

Nystatin:

• Description
• Clinical pharmacology
• Indications and usage
• Contraindications
• Precautions
• Adverse reactions
• Overdosage
• Dosage and administration
• How supplied
• Kenacomb (Nystatin) reviews

DESCRIPTION

Kenacomb (Nystatin), USP is an antimycotic polyene antibiotic obtained from Streptomyces noursei. Its structural formula:

• C₄₇H₇₅NO₁₇ M.W. 926.13

Kenacomb (Nystatin) Tablets USP contain the inactive ingredients: Corn Starch, Povidone, Compressible Sugar, Microcrystalline Cellulose, Sodium Starch Glycolate, Talc, Magnesium Stearate, Purified Water, and Coloring.

Structural formula for Kenacomb (Nystatin)

CLINICAL PHARMACOLOGY

Pharmacokinetics

Gastrointestinal absorption of Kenacomb is insignificant. Most orally administered Kenacomb (Nystatin) is passed unchanged in the stool. In patients with renal insufficiency receiving oral therapy with conventional dosage forms, significant plasma concentrations of Kenacomb (Nystatin) may occasionally occur.

Microbiology

Kenacomb (Nystatin) is both fungistatic and fungicidal in vitro against a wide variety of yeasts and yeast like fungi. Candida albicans demonstrates no significant resistance to Kenacomb (Nystatin) in vitro on repeated subculture in increasing levels of Kenacomb (Nystatin); other Candida species become quite resistant. Generally, resistance does not develop in vivo. Kenacomb (Nystatin) acts by binding to sterols in the cell membrane of susceptible Candida species with a resultant change in membrane permeability allowing leakage of intracellular components. Kenacomb (Nystatin) exhibits no appreciable activity against bacteria, protozoa, or viruses.

INDICATIONS AND USAGE

Kenacomb (Nystatin) tablets are intended for the treatment of non-esophageal mucus membrane gastrointestinal candidiasis.

CONTRAINDICATIONS

Kenacomb (Nystatin) tablets are contraindicated in patients with a history of hypersensitivity to any of their components.

PRECAUTIONS

General

This medication is not to be used for the treatment of systemic mycoses. Discontinue treatment if sensitization or irritation is reported during use.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No long-term animal studies have been performed to evaluate carcinogenic potential. There also have been no studies to determine mutagenicity or whether this medication affects fertility in males or females.

Pregnancy

Teratogenic Effects

Pregnancy Category C

Animal reproduction studies have not been conducted with Kenacomb. It is also not known whether Kenacomb (Nystatin) can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Kenacomb (Nystatin) should be given to a pregnant woman only if clearly needed.

Nursing Mothers

It is not known whether Kenacomb (Nystatin) is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Kenacomb (Nystatin) is administered to a nursing woman.

ADVERSE REACTIONS

Kenacomb is well tolerated even with prolonged therapy. Oral irritation and sensitization have been reported (see PRECAUTIONS, General).

Gastrointestinal

Diarrhea (including one case of bloody diarrhea), nausea, vomiting, gastrointestinal upset/disturbances.

Dermatologic

Rash, including urticaria has been reported rarely. Stevens-Johnson syndrome has been reported very rarely.

Other

Tachycardia, bronchospasm, facial swelling, and nonspecific myalgia have also been rarely reported.

OVERDOSAGE

Oral doses of Kenacomb (Nystatin) in excess of five million units daily have caused nausea and gastrointestinal upset. There have been no reports of serious toxic effects of superinfections (see CLINICAL PHARMACOLOGY, Pharmacokinetics).

DOSAGE AND ADMINISTRATION

The usual therapeutic dosage is one to two tablets (500,000 to 1,000,000 units Kenacomb (Nystatin)) three times daily. Treatment should generally be continued for at least 48 hours after clinical cure to prevent relapse.

HOW SUPPLIED

Kenacomb (Nystatin) Tablets USP, 500,000 Units are round, convex, brown, film-coated tablet debossed with 93 on one side and 983 on the reverse and are packaged in bottles of 100 tablets (NDC 0093-0983-01).

Store at 20° to 25°C (68° to 77°F).

Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).

Keep tightly closed.

KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.

Manufactured By:

TEVA CANADA LIMITED

Toronto, Canada M1B 2K9

Manufactured For:

TEVA PHARMACEUTICALS USA, INC.

North Wales, PA 19454

Rev. N 2/2016

NDC 0093-0983-01

Kenacomb (Nystatin)

Tablets USP

500,000 units (oral)

Rx only

100 TABLETS

TEVA

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
• Kenacomb (Triamcinolone Acetonide) reviews

1 INDICATIONS AND USAGE

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

Kenacomb (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

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

Limitation of Use

Kenacomb (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 Kenacomb (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 Kenacomb (Triamcinolone Acetonide). ( 2.3)

2.1 Important Dosage and Administration Information

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

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

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

Preparation of Kenacomb (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.

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

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

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

3 DOSAGE FORMS AND STRENGTHS

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

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

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

4 CONTRAINDICATIONS

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

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

5 WARNINGS AND PRECAUTIONS

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

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

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

8.2 Lactation

Risk Summary

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

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

Kenacomb (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. Kenacomb (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 Kenacomb (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:

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

Structural Formula

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

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

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

Mutagenesis

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

Impairment of Fertility

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

14 CLINICAL STUDIES

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

If refrigeration is unavailable, store the Kenacomb (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 Kenacomb (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 Kenacomb (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

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

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

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

Part Number: 60-004-01

Version: 1, 10/2017

Instructions for Use

Kenacomb (Triamcinolone Acetonide)

(triamcinolone acetonide

extended-release injectable suspension)

For intra-articular injection only

Single-dose device

Do not reuse.

IMPORTANT INFORMATION

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

Figure 4

Clean Vials.

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

Grip the plastic holder that contains the vial adapter.

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

Figure 12

Note: Kenacomb (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 Kenacomb (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 Kenacomb (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 Kenacomb (Triamcinolone Acetonide).

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

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

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

NDC 70801-003-01 Rx Only

Kenacomb (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 Kenacomb (Triamcinolone Acetonide)

microsphere powder

1 Vial of diluent (5 mL)

for Kenacomb (Triamcinolone Acetonide)

1 sterile vial adapter

flexion

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

NDC 70801-003-02 Rx Only

Kenacomb (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 Kenacomb (Triamcinolone Acetonide)

microsphere powder

1 Vial of diluent (5 mL)

for Kenacomb (Triamcinolone Acetonide)

1 sterile vial adapter

flexion

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

NDC 70801-001-01 Rx Only

Kenacomb (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 - Kenacomb (Triamcinolone Acetonide) 32mg Professional Vial Label

NDC 70801-001-02 Rx Only

Kenacomb (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 - Kenacomb (Triamcinolone Acetonide) Diluent 5mL Vial Label

NDC 70801-002-01 Rx Only

DILUENT

for use with Kenacomb (Triamcinolone Acetonide)

5 mL

Sterile single-use vial

Do not administer directly.

flexion

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

NDC 70801-002-02 Rx Only

DILUENT

for use with Kenacomb (Triamcinolone Acetonide)

5 mL

Sterile single-use vial

Do not administer directly.

flexion