Fiasp

FIASP is indicated to improve glycemic control in adult and pediatric patients with diabetes mellitus.

• •Individualize and adjust the dosage of FIASP based on route of administration, individual’s metabolic needs, blood glucose monitoring results and glycemic control goal (
  2.3 Dosage Recommendations

  • •Individualize the dosage of FIASP based on the route of administration, patient’s metabolic needs, blood glucose monitoring results, and glycemic control goal.
  • •If converting from another mealtime insulin to FIASP, the initial change can be done on a unit-to-unit basis.
  • •Dose adjustments may be needed when switching from another insulin, with changes in physical activity, changes in concomitant medications, changes in meal patterns (i.e., macronutrient content or timing of food intake), changes in renal or hepatic function or during acute illness to minimize the risk of hypoglycemia or hyperglycemia
    [see Warnings and Precautions and Drug Interactions , and Use in Specific Populations ]
    .
  • •Closely monitor blood glucose when converting insulins used in insulin pumps as individualization of insulin pump parameters may be necessary to minimize the risk of hypoglycemia and hyperglycemia
    [see Warnings and Precautions and Adverse Reactions ]
  • •During changes to a patient’s insulin regimen, increase the frequency of blood glucose monitoring
    [see Warnings and Precautions ].
  • •Dosage adjustment may be needed when FIASP is co-administered with certain drugs
    [see Drug Interactions ].
  ).
• •Dosage adjustments may be needed when switching from another insulin, with changes in physical activity, changes in concomitant medications, changes in meal patterns, changes in renal or hepatic function or during acute illness (
  2.3 Dosage Recommendations

  • •Individualize the dosage of FIASP based on the route of administration, patient’s metabolic needs, blood glucose monitoring results, and glycemic control goal.
  • •If converting from another mealtime insulin to FIASP, the initial change can be done on a unit-to-unit basis.
  • •Dose adjustments may be needed when switching from another insulin, with changes in physical activity, changes in concomitant medications, changes in meal patterns (i.e., macronutrient content or timing of food intake), changes in renal or hepatic function or during acute illness to minimize the risk of hypoglycemia or hyperglycemia
    [see Warnings and Precautions and Drug Interactions , and Use in Specific Populations ]
    .
  • •Closely monitor blood glucose when converting insulins used in insulin pumps as individualization of insulin pump parameters may be necessary to minimize the risk of hypoglycemia and hyperglycemia
    [see Warnings and Precautions and Adverse Reactions ]
  • •During changes to a patient’s insulin regimen, increase the frequency of blood glucose monitoring
    [see Warnings and Precautions ].
  • •Dosage adjustment may be needed when FIASP is co-administered with certain drugs
    [see Drug Interactions ].
  ).
• •
  Subcutaneous injection (
  2.2 Route of Administration Instructions

  Subcutaneous Injection:

  • •Inject FIASP at the start of a meal or within 20 minutes after starting a meal subcutaneously into the abdomen, upper arm, or thigh.
  • •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 Adverse Reactions Adverse Reactions ].
  • •Train patients using continuous subcutaneous insulin infusion therapy to administer insulin by injection and have alternate insulin therapy available in case of insulin pump failure
    [see Warnings and Precautions ].
  • •Change FIASP in the pump reservoir at least every 6 days or replace the PumpCart cartridge at least every 4 days, or according to the pump user manual, whichever is shorter. Follow the FIASP-specific information for in-use time because FIASP-specific information may differ from general insulin pump user manual instructions.
  • •Change the infusion sets and the infusion set insertion site according to the manufacturers user manual.
  • •Do not mix with other insulins or diluents in the insulin pump.
  • •Do not expose FIASP in the pump reservoir to temperatures greater than 37°C (98.6°F).

  Intravenous Administration:

  • •Administer FIASP intravenously
    only
    under medical supervision with close monitoring of blood glucose and potassium levels to avoid hypoglycemia and hypokalemia
    [see Warnings and Precautions]
    .
  • •Dilute FIASP to concentrations from 0.5 unit/mL to 1 unit/mL insulin aspart in infusion systems using polypropylene infusion bags.
  • •FIASP is stable at room temperature at 20°C to 25°C (68°F to 77°F) for 24 hours in 0.9% sodium chloride or 5% dextrose infusion fluids.
  ):
  • oInject at the start of a meal or within 20 minutes after starting a meal into the abdomen, upper arm, or thigh.
  • oRotate injection sites within the same region to reduce the risk of lipodystrophy and localized cutaneous amyloidosis.
  • oShould generally be used in regimens with an intermediate- or long-acting insulin.
• •
  Continuous Subcutaneous Infusion (Insulin Pump)
  (
  2.2 Route of Administration Instructions

  Subcutaneous Injection:

  • •Inject FIASP at the start of a meal or within 20 minutes after starting a meal subcutaneously into the abdomen, upper arm, or thigh.
  • •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 Adverse Reactions Adverse Reactions ].
  • •Train patients using continuous subcutaneous insulin infusion therapy to administer insulin by injection and have alternate insulin therapy available in case of insulin pump failure
    [see Warnings and Precautions ].
  • •Change FIASP in the pump reservoir at least every 6 days or replace the PumpCart cartridge at least every 4 days, or according to the pump user manual, whichever is shorter. Follow the FIASP-specific information for in-use time because FIASP-specific information may differ from general insulin pump user manual instructions.
  • •Change the infusion sets and the infusion set insertion site according to the manufacturers user manual.
  • •Do not mix with other insulins or diluents in the insulin pump.
  • •Do not expose FIASP in the pump reservoir to temperatures greater than 37°C (98.6°F).

  Intravenous Administration:

  • •Administer FIASP intravenously
    only
    under medical supervision with close monitoring of blood glucose and potassium levels to avoid hypoglycemia and hypokalemia
    [see Warnings and Precautions]
    .
  • •Dilute FIASP to concentrations from 0.5 unit/mL to 1 unit/mL insulin aspart in infusion systems using polypropylene infusion bags.
  • •FIASP is stable at room temperature at 20°C to 25°C (68°F to 77°F) for 24 hours in 0.9% sodium chloride or 5% dextrose infusion fluids.
  ):
  • oRefer to the insulin infusion pump user manual to see if FIASP can be used. Use in accordance with the insulin pumps’ instructions for use.
  • oAdminister by continuous subcutaneous infusion using an insulin pump in a region recommended in the instructions from the pump manufacturer. Rotate infusion sites within the same region to reduce the risk of lipodystrophy and localized cutaneous amyloidosis.
• •
  Intravenous Infusion:
  Administer only under medical supervision after diluting to concentrations from 0.5 to 1 unit/mL insulin aspart in infusion systems using polypropylene infusion bags (
  2.2 Route of Administration Instructions

  Subcutaneous Injection:

  • •Inject FIASP at the start of a meal or within 20 minutes after starting a meal subcutaneously into the abdomen, upper arm, or thigh.
  • •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 Adverse Reactions Adverse Reactions ].
  • •Train patients using continuous subcutaneous insulin infusion therapy to administer insulin by injection and have alternate insulin therapy available in case of insulin pump failure
    [see Warnings and Precautions ].
  • •Change FIASP in the pump reservoir at least every 6 days or replace the PumpCart cartridge at least every 4 days, or according to the pump user manual, whichever is shorter. Follow the FIASP-specific information for in-use time because FIASP-specific information may differ from general insulin pump user manual instructions.
  • •Change the infusion sets and the infusion set insertion site according to the manufacturers user manual.
  • •Do not mix with other insulins or diluents in the insulin pump.
  • •Do not expose FIASP in the pump reservoir to temperatures greater than 37°C (98.6°F).

  Intravenous Administration:

  • •Administer FIASP intravenously
    only
    under medical supervision with close monitoring of blood glucose and potassium levels to avoid hypoglycemia and hypokalemia
    [see Warnings and Precautions]
    .
  • •Dilute FIASP to concentrations from 0.5 unit/mL to 1 unit/mL insulin aspart in infusion systems using polypropylene infusion bags.
  • •FIASP is stable at room temperature at 20°C to 25°C (68°F to 77°F) for 24 hours in 0.9% sodium chloride or 5% dextrose infusion fluids.
  ).

Injection: 100 units of insulin aspart per mL (U-100) is available as a clear and colorless solution in:

• •10 mL multiple-dose vial
• •3 mL single-patient-use FIASP FlexTouch pen
• •3 mL single-patient-use PenFill cartridges for use in a PenFill cartridge delivery device
• •1.6 mL single-patient-use PumpCart cartridges for use in a compatible insulin pump.

There are no available data with FIASP in pregnant women to inform a drug-associated risk for major birth defects and miscarriage. Available information from published randomized controlled trials with insulin aspart use during the second trimester of pregnancy have not reported an association with insulin aspart and major birth defects or adverse maternal or fetal outcomes

In animal reproduction studies, administration of subcutaneous insulin aspart to pregnant rats and rabbits during the period of organogenesis did not cause adverse developmental effects at exposures 8- times and equal to the human subcutaneous dose of 1.0 unit/kg/day, respectively. Pre- and post-implantation losses and visceral/skeletal abnormalities were seen at higher exposures, which are considered secondary to maternal hypoglycemia. These effects were similar to those observed in rats administered regular human insulin

The estimated background risk of major birth defects is 6-10% in women with pre-gestational diabetes with a HbA_1c >7% and has been reported to be as high as 20-25% in women with a HbA_1c >10%. The estimated background risk of miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity.

Published data from 5 randomized controlled trials of 441 pregnant women with diabetes mellitus treated with insulin aspart starting during the late 2^nd trimester of pregnancy did not identify an association of insulin aspart with major birth defects or adverse maternal or fetal outcomes. However, these studies cannot definitely establish the absence of any risk because of methodological limitations, including a variable duration of treatment and small size of the majority of the trials.

Fertility, embryo-fetal and pre-and postnatal development studies have been performed with insulin aspart and regular human insulin in rats and rabbits. In a combined fertility and embryo-fetal development study in rats, insulin aspart was administered before mating, during mating, and throughout pregnancy. Further, in a pre- and postnatal development study insulin aspart was given throughout pregnancy and during lactation to rats. In an embryo-fetal development study insulin aspart was given to female rabbits during organogenesis. The effects of insulin aspart did not differ from those observed with subcutaneous regular human insulin. Insulin aspart, like human insulin, caused pre- and post-implantation losses and visceral/skeletal abnormalities in rats at a dose of 200 units/kg/day (approximately 32 times the human subcutaneous dose of 1.0 unit/kg/day, based on human exposure equivalents) and in rabbits at a dose of 10 units/kg/day (approximately three times the human subcutaneous dose of 1.0 unit/kg/day, based on human exposure equivalents). No significant effects were observed in rats at a dose of 50 units/kg/day and in rabbits at a dose of 3 units/kg/day. These doses are approximately 8 times the human subcutaneous dose of 1.0 unit/kg/day for rats and equal to the human subcutaneous dose of 1.0 unit/kg/day for rabbits, based on human exposure equivalents. The effects are considered secondary to maternal hypoglycemia.

• •
  Never share
  a FIASP FlexTouch pen, PenFill cartridge or PenFill cartridge device between patients, even if the needle is changed (
  5.1 Never Share a FIASP FlexTouch Pen, PenFill Cartridge or PenFill Cartridge Device Between Patients

  FIASP FlexTouch disposable pen, PenFill cartridge and PenFill cartridge devices should never be shared between patients, even if the needle is changed. Patients using FIASP vials should never share needles or syringes with another person. Sharing poses a risk for transmission of blood-borne pathogens.
  ).
• •
  Hyperglycemia or hypoglycemia with changes in insulin regimen
  : Make changes to a patient’s insulin regimen (e.g., insulin strength, manufacturer, type, injection site or method of administration) under close medical supervision with increased frequency of blood glucose monitoring (
  5.2 Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen

  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 ]

  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 ]

  . 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). FIASP, or any insulin, should not be used during episodes of hypoglycemia

  [see Contraindications].

  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]

  , or in patients who experience recurrent hypoglycemia.

  Risk Factors for Hypoglycemia

  The risk of hypoglycemia after an injection is related to the duration of action of the insulin and, in general, is highest when the glucose lowering effect of the insulin is maximal. The timing of hypoglycemia usually reflects the time-action profile of the administered insulin formulation. As with all insulin preparations, the glucose lowering effect time course of FIASP may vary in different individuals or at different times in the same individual and depends on many conditions, including the area of injection as well as the injection site blood supply and temperature

  [see Use in Specific Populations, Clinical Pharmacology].

  Other factors which may increase the risk of hypoglycemia include changes in meal pattern (e.g., macronutrient content or timing of meals), changes in level of physical activity, or changes to co-administered medication

  [see

  Drug Interactions].

  Patients with renal or hepatic impairment may be at higher risk of hypoglycemia

  [see

  Use in Specific Populations].

  Risk Mitigation Strategies for Hypoglycemia

  Patients and caregivers must be educated to recognize and manage hypoglycemia. Self-monitoring of blood glucose plays an essential role in the prevention and management of hypoglycemia. In patients at higher risk for hypoglycemia and patients who have reduced symptomatic awareness of hypoglycemia, increased frequency of blood glucose monitoring is recommended.
  ).
• •
  Hypoglycemia due to medication errors
  : Accidental mix-ups between insulin products can occur. Instruct patients to check insulin labels before injection (
  5.4 Hypoglycemia Due to Medication Errors

  Accidental mix-ups between insulin products have been reported. To avoid medication errors between FIASP and other insulins, instruct patients to always check the insulin label before each injection.
  ).
• •
  Hypokalemia
  : May be life-threatening. Monitor potassium levels in patients at risk for hypokalemia and treat if indicated (
  5.5 Hypokalemia

  All insulin products, including FIASP, 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 potassium concentrations).
  ).
• •
  Hypersensitivity reactions:
  Severe, life-threatening, generalized allergy, including anaphylaxis, can occur. Discontinue FIASP, monitor and treat if indicated (
  5.6 Hypersensitivity and Allergic Reactions

  Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with insulin products, including FIASP

  [see Adverse Reactions]

  . If hypersensitivity reactions occur, discontinue FIASP; treat per standard of care and monitor until symptoms and signs resolve. FIASP is contraindicated in patients who have had hypersensitivity reactions to insulin aspart, or any of the excipients in FIASP

  [see Contraindications]

  .
  ).
• •
  Fluid retention and heart failure with concomitant use of thiazolidinediones (TZDs):
  Observe for signs and symptoms of heart failure; consider dosage reduction or discontinuation if heart failure occurs (
  5.7 Fluid Retention and Heart Failure with Concomitant Use of PPAR-Gamma Agonists

  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 FIASP, 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.
  7).
• •
  Hyperglycemia and Ketoacidosis Due to Insulin Pump Device Malfunction:
  Monitor glucose and administer FIASP by subcutaneous injection if pump malfunction occurs (
  5.8 Hyperglycemia and Ketoacidosis Due to Insulin Pump Device Malfunction

  Pump or infusion set malfunctions can lead to a rapid onset of hyperglycemia and ketoacidosis. Prompt identification and correction of the cause of hyperglycemia or ketosis is necessary. Interim therapy with subcutaneous injection of FIASP 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 Dosage and Administration, How Supplied/Storage and Handling, and Patient Counseling Information].
  ).