Get your patient on Kirsty - Insulin Aspart - Xjhz injection, Solution (Water)

• Always check insulin labels before administration [see Warnings and Precautions (5.4)].

• Inspect KIRSTY visually before use. It should appear clear and colorless. Do not use KIRSTY if particulate matter or coloration is seen.

• In patients with visual impairment who rely on audible clicks to dial their dose, use KIRSTY prefilled pen with caution.

• Do not mix KIRSTY with other insulins when administering using a continuous subcutaneous infusion pump.

Subcutaneous Injection

• Inject KIRSTY subcutaneously within 5-10 minutes before a meal into the abdominal area, thigh, buttocks or upper arm.
• Rotate injection sites within the same region from one injection to the next to reduce the risk of lipodystrophy and localized cutaneous amyloidosis. Do not inject into areas of lipodystrophy or localized cutaneous amyloidosis [see Warnings and Precautions (5.2) and Adverse Reactions (6.1 , 6.3) ] .
• Dial the KIRSTY prefilled pen in 1-unit increments.
• Generally use KIRSTY (administered by subcutaneous injection) in regimens with an intermediate-or long-acting insulin.
• May dilute KIRSTY with Insulin Diluting Medium for KIRSTY for subcutaneous injection. Diluting one part KIRSTY to:
  • Nine parts diluent will yield a concentration one-tenth that of KIRSTY (equivalent to U-10).
  • One part diluent will yield a concentration one-half that of KIRSTY (equivalent to U-50). Discard any unused diluent after opening the vial of Insulin Diluting Medium for KIRSTY.
  

Continuous Subcutaneous Infusion (Insulin Pump)

• Can use this KIRSTY product with the continuous subcutaneous insulin infusion pumps labeled for use with KIRSTY or NOVOLOG. Refer to the insulin pump user manual to see if KIRSTY or NOVOLOG can be used with the insulin pump, in which case KIRSTY can be used with the pump. Use KIRSTY in accordance with the insulin pump system’s instructions for use.

• Train patients using continuous subcutaneous insulin fusion pump therapy to administer insulin by injection and have alternate insulin therapy available in case of pump failure.
• Administer KIRSTY by continuous subcutaneous infusion in a region recommended in the instructions from the pump manufacturer. Rotate infusion sites within the same region to reduce the risk of lipodystrophy or localized cutaneous amyloidosis [see Warnings and Precautions (5.2) and Adverse Reactions (6.1, 6.3)].

• Instruct patients to follow healthcare provider recommendations when setting basal and meal time infusion rate.

• Change the KIRSTY in the reservoir at least every 7 days or according to the pump user manual, whichever is shorter. Follow the KIRSTY-specific information for in-use time because KIRSTY-specific information may differ from general pump manual instructions.

• Change the infusion set and the infusion set insertion site according to the manufacturer’s user manual.

• Do not dilute or mix KIRSTY when administering by continuous subcutaneous infusion.

• Do not expose KIRSTY in the pump reservoir to temperatures greater than 98.6°F (37°C).

Intravenous Administration

• Administer KIRSTY intravenously only under medical supervision with close monitoring of blood glucose and potassium levels to avoid hypoglycemia and hypokalemia [see Warnings and Precautions (5.3, 5.6) and How Supplied/Storage and Handling (16.2)] .

• Dilute KIRSTY to concentrations from 0.05 unit/mL to 1 unit/mL insulin aspart-xjhz in infusion systems using polypropylene infusion bags. KIRSTY is stable in infusion fluids such as 0.9% Sodium Chloride Injection, USP.

• Individualize the dosage of KIRSTY based on the route of administration, the patient's metabolic needs, blood glucose monitoring results and glycemic control goal.

• Dosage adjustments may be needed with changes in physical activity, changes in meal patterns (i.e., macronutrient content or timing of food intake), changes in renal or hepatic function or during acute illness [see Warnings and Precautions (5.2 , 5.3) and Use in Specific Populations (8.6 , 8.7) ] .

• When switching from another insulin to KIRSTY, a different dosage of KIRSTY may be needed [see Warnings and Precautions (5.2) ] .

• During changes to a patient’s insulin regimen, increase the frequency of blood glucose monitoring [see Warnings and Precautions (5.2 )].

Dosage modification may be needed when KIRSTY is used concomitantly with certain drugs [see Drug Interactions (7) ].

The safety and effectiveness of KIRSTY to improve glycemic control have been established in pediatric patients with diabetes mellitus. Use of KIRSTY for this indication is supported by evidence from an adequate and well-controlled study of insulin aspart in 283 pediatric patients with type 1 diabetes mellitus aged 6 to 18 years and from studies in adults with diabetes mellitus [see Adverse Reactions (6.1) , Clinical Pharmacology (12.3) , and Clinical Studies (14.1) ] .

Of the total number of patients (n=1,375) treated with insulin aspart in 3 controlled clinical studies, 2.6% (n=36) were 65 years of age or over. One-half of these patients had type 1 diabetes (18/1285) and the other half had type 2 diabetes (18/90). The HbA _1c response to insulin aspart, as compared to regular human insulin, did not differ by age.

Patients with renal impairment may be at increased risk of hypoglycemia and may require more frequent KIRSTY dose adjustment and more frequent blood glucose monitoring [see Warnings and Precautions (5.3) and Clinical Pharmacology (12.3) ].

Patients with hepatic impairment may be at increased risk of hypoglycemia and may require more frequent KIRSTY dose adjustment and more frequent blood glucose monitoring [see Warnings and Precautions (5.3) and Clinical Pharmacology (12.3) ].

KIRSTY prefilled pens should never be shared between patients, even if the needle is changed. Patients using KIRSTY vials must never share needles or syringes with another person. Sharing poses a risk for transmission of blood-borne pathogens.

Changes in an insulin regimen (e.g., insulin strength, manufacturer, type, injection site or method of administration) may affect glycemic control and predispose to hypoglycemia [see Warnings and Precautions (5.3) ] or hyperglycemia. Repeated insulin injections into areas of lipodystrophy or localized cutaneous amyloidosis have been reported to result in hyperglycemia; and a sudden change in the injection site (to an unaffected area) has been reported to result in hypoglycemia [see Adverse Reactions (6.1 , 6.3) ].

Make any changes to a patient’s insulin regimen under close medical supervision with increased frequency of blood glucose monitoring. Advise patients who have repeatedly injected into areas of lipodystrophy or localized cutaneous amyloidosis to change the injection site to unaffected areas and closely monitor for hypoglycemia. For patients with type 2 diabetes, dosage adjustments of concomitant anti-diabetic products may be needed.

Hypoglycemia is the most common adverse reaction of all insulins, including insulin aspart products. Severe hypoglycemia can cause seizures, may lead to unconsciousness, may be life threatening or cause death. Hypoglycemia can impair concentration ability and reaction time; this may place an individual and others at risk in situations where these abilities are important (e.g., driving or operating other machinery).

Hypoglycemia can happen suddenly and symptoms may differ in each individual and change over time in the same individual. Symptomatic awareness of hypoglycemia may be less pronounced in patients with longstanding diabetes in patients with diabetic nerve disease, in patients using medications that block the sympathetic nervous system (e.g., beta-blockers) [see Drug Interactions (7) ] , or in patients who experience recurrent hypoglycemia.

Accidental mix-ups between insulin products have been reported. To avoid medication errors between KIRSTY and other insulins, instruct patients to always check the insulin label before each injection.

Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with insulins, including insulin aspart products. If hypersensitivity reactions occur, discontinue KIRSTY; treat per standard of care and monitor until symptoms and signs resolve [see Adverse Reactions (6) ]. KIRSTY is contraindicated in patients who have had hypersensitivity reactions to insulin aspart products or any of the excipients in KIRSTY [see Contraindications (4) ].

All insulins, including insulin aspart products, can cause a shift in potassium from the extracellular to intracellular space, possibly leading to hypokalemia. Untreated hypokalemia may cause respiratory paralysis, ventricular arrhythmia, and death. Monitor potassium levels in patients at risk for hypokalemia if indicated (e.g., patients using potassium-lowering medications, patients taking medications sensitive to serum potassium concentration).

Thiazolidinediones (TZDs), which are peroxisome proliferator-activated receptor (PPAR)-gamma agonists, can cause dose-related fluid retention, particularly when used in combination with insulin. Fluid retention may lead to or exacerbate heart failure. Patients treated with insulin, including KIRSTY, and a PPAR-gamma agonist should be observed for signs and symptoms of heart failure. If heart failure develops, it should be managed according to current standards of care, and discontinuation or dose reduction of the PPAR-gamma agonist must be considered.

Malfunction of the insulin pump or insulin infusion set or insulin degradation can rapidly lead to hyperglycemia and ketoacidosis. Prompt identification and correction of the cause of hyperglycemia or ketosis is necessary. Interim subcutaneous injections with KIRSTY may be required. Patients using continuous subcutaneous insulin infusion pump therapy must be trained to administer insulin by injection and have alternate insulin therapy available in case of pump failure [see How Supplied/Storage and Handling (16.2) and Patient Counseling Information (17) ] .

Because clinical trials are conducted under widely varying designs, the adverse reaction rates reported in one clinical trial may not be easily compared to those rates reported in another clinical trial, and may not reflect the rates actually observed in clinical practice. The safety of insulin aspart was evaluated in two treat-to-target trials of 6 months duration, conducted in patients with type 1 diabetes or type 2 diabetes [see Clinical Studies (14) ].

The data in Table 1 reflect the exposure of 596 patients with type 1 diabetes to insulin aspart in one clinical trial with a mean exposure duration to insulin aspart of 24 weeks. The mean age was 39 years. Fifty-one percent were male, 94% were Caucasian, 2% were Black and 4% were other races. The mean body mass index (BMI) was 25.6 kg/m ² . The mean duration of diabetes was 15.7 years and the mean HbA _1c at baseline was 7.9%.

The data in Table 2 reflect the exposure of 91 patients with type 2 diabetes to insulin aspart in one clinical trial with a mean exposure duration to insulin aspart of 24 weeks. The mean age was 57 years. Sixty-three percent were male, 76% were Caucasian, 9% were Black and 15% were other races. The mean BMI was 29.7 kg/m ² . The mean duration of diabetes was 12.7 years and the mean HbA _1c at baseline was 8.1%.

Common adverse reactions were defined as events that occurred in ≥5%, excluding hypoglycemia, of the population studied. Common adverse events that occurred at the same rate or greater for insulin aspart-treated patients than in comparator-treated patients during clinical trials in patients with type 1 diabetes mellitus and type 2 diabetes mellitus (other than hypoglycemia) are listed in Table 1 and Table 2, respectively.

As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies in the studies described below with the incidence of antibodies in other studies or to other insulin aspart products may be misleading.

In a 6-month study with a 6-month extension in adult subjects with type 1 diabetes, 99.8% of patients who received insulin aspart were positive for anti-insulin antibodies (AIA) at least once during the study, including 97.2% that were positive at baseline. A total of 92.1% of patients who received insulin aspart were positive for anti-drug antibodies (ADA) at least once during the study, including 64.6% that were positive at baseline.

In a phase 3 type 1 diabetes clinical trial of insulin aspart, initial increase in titers of antibodies to insulin, followed by a decrease to baseline values, was observed in regular human insulin and insulin aspart treatment groups with similar incidences. These antibodies did not cause deterioration in glycemic control or necessitate increases in insulin dose.

The following adverse reactions have been identified during post-approval use of insulin aspart products. Because these adverse reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Medication errors have been reported in which other insulins have been accidentally substituted for insulin aspart products.

Localized cutaneous amyloidosis at the injection site has occurred with insulin aspart products. Hyperglycemia has been reported with repeated insulin injections into areas of localized cutaneous amyloidosis; hypoglycemia has been reported with a sudden change to an unaffected injection site.

The primary activity of insulin, including insulin aspart products, is the regulation of glucose metabolism. Insulin and its analogs lower blood glucose by stimulating peripheral glucose uptake, especially by skeletal muscle and fat, and by inhibiting hepatic glucose production. Insulin inhibits lipolysis and proteolysis, and enhances protein synthesis.

Standard 2-year carcinogenicity studies in animals have not been performed to evaluate the carcinogenic potential of insulin aspart products. In 52-week studies, Sprague-Dawley rats were dosed subcutaneously with insulin aspart at 10, 50, and 200 units/kg/day (approximately 2, 8, and 32 times the human subcutaneous dose of 1.0 units/kg/day, based on units/body surface area, respectively). At a dose of 200 units/kg/day, insulin aspart increased the incidence of mammary gland tumors in females when compared to untreated controls. The relevance of these findings to humans is unknown.

Insulin aspart was not genotoxic in the following tests: Ames test, mouse lymphoma cell forward gene mutation test, human peripheral blood lymphocyte chromosome aberration test, in vivo micronucleus test in mice, and in ex vivo UDS test in rat liver hepatocytes.

In fertility studies in male and female rats, at subcutaneous doses up to 200 units/kg/day (approximately 32 times the human subcutaneous dose, based on units/body surface area), no direct adverse effects on male and female fertility, or general reproductive performance of animals was observed.

In standard biological assays in mice and rabbits, one unit of insulin aspart has the same glucose-lowering effect as one unit of regular human insulin.

The safety and effectiveness of subcutaneous insulin aspart were compared to regular human insulin in 596 type 1 diabetes adult, 187 pediatric type 1 diabetes, and 91 adult type 2 diabetes patients using NPH as basal insulin (see Tables 3, 4, 5). The reduction in glycated hemoglobin (HbA _1c ) was similar to regular human insulin.

The safety and effectiveness of insulin aspart administered by continuous subcutaneous insulin infusion (CSII) by external pump were compared to buffered regular human insulin (administered by CSII), to lispro (administered by CSII) and compared to insulin aspart injections and NPH injection. Overall, the reduction in HbA _1c was similar to the comparator.

KIRSTY (insulin aspart-xjhz) injection 100 units/mL (U-100) is available as a clear and colorless solution in:

The KIRSTY prefilled pen dials in 1-unit increments.

Dispense in the original sealed carton with the enclosed Instructions for Use. Store unused KIRSTY in a refrigerator between 2°C to 8°C (36°F to 46°F). Do not freeze KIRSTY and do not use KIRSTY if it has been frozen. Do not expose KIRSTY to excessive heat or light. Do not withdraw KIRSTY into a syringe and store for later use.

Always remove and discard the needle after each injection from the KIRSTY prefilled pen and store without a needle attached.

The storage conditions are summarized in the following table:

Table 9. Storage conditions for vial and KIRSTY prefilled pen

• For insulin pump use, the total in-use time is 19 days, including 7 days pump in-use time.

Storage in External Insulin Pump:

Change the KIRSTY in the pump reservoir at least every 7 days or according to the pump user manual instructions for KIRSTY or NOVOLOG, whichever is shorter, or after exposure to temperatures that exceed 37°C (98.6°F).

Storage of Diluted KIRSTY

KIRSTY diluted with Insulin Diluting Medium for KIRSTY to a concentration equivalent to U-10 or equivalent to U-50 prepared as indicated under Dosage and Administration (2.2) may remain in patient use at temperatures up to 30°C (86°F) for 28 days. Discard any unused diluent after opening the vial of Insulin Diluting Medium for KIRSTY.

Storage of KIRSTY in Intravenous Infusion Fluids

Infusion bags prepared as indicated under Dosage and Administration (2.2) are stable at room temperature for 12 hours. Some insulin will be initially adsorbed to the material of the infusion.