Dosing and uses of Afrezza (insulin inhaled)
Adult dosage forms and strengths
orally inhaled powder
- Available as single-use cartridges
- 4 units/cartridge
- 8 units/cartridge
- 12 units/cartridge
Diabetes Mellitus (Types 1 and 2)
Orally inhaled rapid-acting insulin indicated to improve glycemic control in adults with diabetes mellitus
Dosing must be individualized
Administer via oral inhalation only at the beginning of a meaL
Administer using a single inhalation per cartridge
Mealtime dose conversion
- Dosage adjustment may be needed when switching from insulin to inhaled insulin
- NOTE: Also see starting mealtime conversion instructions below
- Up to 4 units SC = 4 units inhaled
- 5-8 units SC = 8 units inhaled
- 9-12 units SC = 12 units inhaled
- 13-16 units SC = 16 units inhaled
- 17-20 units SC = 20 units inhaled
- 21-24 units SC = 24 units inhaled
Starting mealtime dose
- Insulin naïve: 4 units at each meal initially
- Converting from SC mealtime (prandial) insulin: Determine the appropriate inhaled insulin dose for each meal by converting from the injected dose using conversion table (above)
- Using SC premixed insulin: Estimate the mealtime injected dose by dividing half of the total daily injected premixed insulin dose equally among the 3 meals of the day; convert each estimated injected mealtime dose to an appropriate inhaled insulin dose (use conversion table above); administer half of the total daily injected premixed dose as an injected basal insulin dose
Dose adjustment
- Adjust the inhaled insulin dosage based on the individual'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 (ie, macronutrient content or timing of food intake), and changes in renal or hepatic function or during acute illness
- Carefully monitor blood glucose control in patients requiring high doses; if blood glucose control is not achieved with increased inhaled insulin doses, consider use of SC mealtime insulin
Dosing Considerations
Before initiating, perform a detailed medical history, physical examination, and spirometry (FEV1) in all patients to identify potential lung disease
Limitations of use
- Not a substitute for long-acting insulin; must be used in combination with long-acting insulin in patients with type 1 diabetes mellitus
- Not recommended for treatment of diabetic ketoacidosis
- Safety and efficacy not established in patients who smoke and is not recommended in patients who smoke or who have recently stopped smoking
Administration
Keep inhaler level and white mouthpiece on top and purple base on the bottom after a cartridge has been inserted into the inhaler
Loss of drug effect can occur if the inhaler is turned upside down, held with the mouthpiece pointing down, or shaken (or dropped) after the cartridge has been inserted but before the dose has been administered
If any of the above occurs, the cartridge should be replaced before use
The inhaler can be used for up to 15 days from the date of first use; after 15 days of use, the inhaler must be discarded and replaced with a new inhaler
See complete illustrated administration instructions provided in packaging
Inhaled insulin doses >12 units
- Doses >12 units require inhalations from multiple cartridges
- To achieve the required total mealtime dose, patients should use a combination of 4-unit, 8-unit, and 12-unit cartridges
- For doses >24 units, combinations of different multiple cartridges can be used
Storage
Before use, cartridges and inhaler should be at room temperature for 10 minutes
Cartridges not in use
- Sealed [unopened] cartridges in foil package
- Refrigerate at 2-8ºC (36-46ºF)
- If foil package is not refrigerated, must use within 10 days
Cartridges in use
- Store at room temperature (25ºC [77ºF]), excursions permitted 15-30ºC (59-86ºF)
- Sealed [unopened] blister cards and strips: Must be used within 10 days
- Opened strips: Must be used within 3 days
Inhaler
- May be refrigerated, but should be at room temperature before use
- Store between 2-25ºC (36-77ºF); excursions permitted
Pediatric dosage forms and strengths
<18 years: Safety and efficacy not established
Geriatric dosage forms and strengths
See adult dosing
Afrezza (insulin inhaled) adverse (side) effects
>10%
Nonsevere hypoglycemia (67%)
Cough (25.6-29.4%)
1-10%
Throat pain or irritation (4.4-5.5%)
Severe hypoglycemia (5.1%)
Headache (3.1-4.7%)
Pulmonary function test decreased (2.8%)
Diarrhea (2.7%)
Bronchitis (2.5%)
Urinary tract infection (2.3%)
Productive cough (2.2%)
Fatigue (2%)
Nausea (2%)
Warnings
Black box warnings
Acute bronchospasm reported in patients with asthma and COPD using inhaled insulin
Contraindicated in patients with chronic lung disease
Before initiating, perform a detailed medical history, physical examination, and spirometry (FEV1) to identify potential lung disease in all patients
Contraindications
During episodes of hypoglycemia
Chronic lung disease (eg, asthma, COPD), because of the risk of acute bronchospasm
Hypersensitivity to regular human insulin or any inhaled insulin excipients
Cautions
Acute bronchospasm observed in patients with asthma and COPD; before initiating, perform spirometry (FEV1) in all patients; do not use in patients with chronic lung disease
Change insulin regimen under close medical supervision and increase frequency of blood glucose monitoring
Hypoglycemia reported and may be life-threatening; increase frequency of glucose monitoring with changes to insulin dosage, coadministered glucose-lowering medications, meal pattern, and physical activity; and in patients with renal or hepatic impairment and hypoglycemia unawareness
Assess pulmonary function (eg, spirometry) before initiating, after 6 months of therapy, and annually, even in the absence of pulmonary symptoms
Do not use in patients with history of, at risk for, or active lung cancer
More patients using inhaled insulin (0.43%) experienced diabetic ketoacidosis in clinical trials compared with comparators (0.14%); monitor and change to alternate route of insulin delivery, if indicated
Hypersensitivity reactions, including severe, life-threatening, generalized allergy, and anaphylaxis can occur with insulin products
Hypokalemia may occur, including life-threatening low serum levels; monitor potassium levels in patients at risk
Monitor for fluid retention and heart failure with concomitant use of thiazolidinediones; consider dosage reduction or discontinuation if heart failure occurs
Pregnancy and lactation
Pregnancy category: C
Lactation: Unknown if distributed in human breast milk
A study in rats indicated that the carrier is excreted in milk at ~10% of maternal exposure levels
It is therefore highly likely that the insulin and carrier in inhaled insulin is excreted in human milk; a decision should be made whether to discontinue nursing or suspend use of the drug
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Afrezza (insulin inhaled)
Mechanism of action
Recombinant regular human insulin administered as a powder for oral inhalation
Lowers blood glucose levels by stimulating peripheral glucose uptake by skeletal muscle and fat and by inhibiting hepatic glucose production
Inhibits lipolysis in adipocytes, inhibits proteolysis, and enhances protein synthesis
Pharmacokinetics
Peak plasma time: 12-15 minutes
Median time to maximum effect: ~53 minutes (SD: 74 minutes)
Return to baseline levels: 160 minutes
39% of dose distributed to the lungs
7% of dose swallowed
Half-life: 28-39 minutes
