Fiasp

Important Preparation and Administration Instructions

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Always check insulin label before administration [see Warnings and Precautions Adverse Reactions ].

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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 ].

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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.

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Change the infusion sets and the infusion set insertion site according to the manufacturers user manual.

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Do not mix with other insulins or diluents in the insulin pump.

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

Intravenous Administration:

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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 ].

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Dilute FIASP to concentrations from 0.5 unit/mL to 1 unit/mL insulin aspart in infusion systems using polypropylene infusion bags.

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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.

Dosage Recommendations

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

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If converting from another mealtime insulin to FIASP, the initial change can be done on a unit-to-unit basis.

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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 ].

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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 ]

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

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Dosage adjustment may be needed when FIASP is co-administered with certain drugs [see Drug Interactions ].

Pregnancy

Risk Summary

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 [see Data]. There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy [see Clinical Considerations].

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 [see Data].

The estimated background risk of major birth defects is 6-10% in women with pre-gestational diabetes with a HbA1c >7% and has been reported to be as high as 20-25% in women with a HbA1c >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.

Clinical Considerations

Disease-Associated Maternal and/or Embryo-Fetal Risk

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.

Data

Human Data

Published data from 5 randomized controlled trials of 441 pregnant women with diabetes mellitus treated with insulin aspart starting during the late 2nd 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.

Animal Data

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.

Lactation

Risk Summary

There are no data on the presence of FIASP in human milk, the effects on the breastfed infant, or the effect on milk production. One small published study reported that exogenous insulin, including insulin aspart, was present in human milk. However, there is insufficient information to determine the effects of insulin aspart on the breastfed infant and no available information on the effects of insulin aspart on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for insulin, any potential adverse effects on the breastfed child from FIASP or insulin aspart or from the underlying maternal condition.

Pediatric Use

The safety and effectiveness of FIASP have been established to improve glycemic control in pediatric patients with diabetes mellitus. Use of FIASP for this indication is supported by evidence from an adequate and well-controlled study in 777 pediatric patients with type 1 diabetes mellitus aged 2 to 17 years, and from studies in adults with diabetes mellitus [see Clinical Pharmacology and Clinical Studies ].

Pediatric patients with type 1 diabetes mellitus treated with mealtime and postmeal FIASP reported a higher rate of blood glucose confirmed hypoglycemic episodes compared to patients treated with NovoLog; the imbalance was greater during the nocturnal period. Monitor blood glucose levels closely in pediatric patients [see Warnings and Precautions , Clinical Trial Experience ].

Geriatric Use

In the three controlled clinical studies, 192 of 1219 (16%) FIASP treated patients with type 1 or type 2 diabetes mellitus were ≥ 65 years of age and 24 of 1219 (2%) were ≥ 75 years of age. No overall differences in safety or effectiveness were observed between these elderly patients and younger adult patients.

Nevertheless, caution should be exercised when FIASP is administered to geriatric patients. In elderly patients with diabetes, the initial dosing, dose increments, and maintenance dosage should be conservative to avoid hypoglycemia [see Warnings and Precautions , Adverse Reactions and Clinical Studies ].

Pharmacokinetic/pharmacodynamic study to assess the effect of age on the onset of FIASP action has been performed [see Clinical Pharmacology ].

Renal Impairment

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

Hepatic Impairment

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

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

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 have been reported. To avoid medication errors between FIASP and other insulins, instruct patients to always check the insulin label before each injection.

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 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 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.

 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 ].