AFREZZA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for AFREZZA (AFREZZA).
Inhaled human insulin that lowers blood glucose by stimulating peripheral glucose uptake, especially by skeletal muscle and fat, and by inhibiting hepatic glucose production. Insulin binds to the insulin receptor, activating tyrosine kinase activity leading to downstream metabolic effects.
| Metabolism | Degraded by insulin-degrading enzyme (IDE) and other proteolytic enzymes; no significant hepatic or renal metabolism. |
| Excretion | Renal: approximately 60-80% as unchanged drug and metabolites (insulin degradation products). Biliary/fecal: minor, <20%. |
| Half-life | Terminal elimination half-life: 1.5-2 hours for insulin component; clinical context: duration of glucose-lowering effect may extend beyond due to receptor binding. |
| Protein binding | <5% (insulin is minimally bound); primary binding proteins: none significant. |
| Volume of Distribution | 0.3-0.4 L/kg (approximates extracellular fluid volume; smaller than subcutaneous regular insulin due to inhalation route). |
| Bioavailability | Inhalation: approximately 30-40% (relative to subcutaneous regular insulin). |
| Onset of Action | Inhalation: 12-15 minutes (peak serum concentration at 12-15 min). |
| Duration of Action | 2-3 hours (short-acting, typically used for prandial glucose control). |
Inhaled powder; initial dose: 4 units per inhalation at each meal, titrated based on blood glucose; maximum 48 units per meal. Administer via Afrezza Inhaler.
| Dosage form | POWDER |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (eGFR >=30 mL/min/1.73m2). Not recommended in severe renal impairment (eGFR <30 mL/min/1.73m2) or end-stage renal disease due to lack of data. |
| Liver impairment | No formal studies; use with caution in Child-Pugh Class C (severe hepatic impairment) as metabolism may be altered; monitor glucose closely. |
| Pediatric use | Not approved for pediatric patients; safety and efficacy have not been established. |
| Geriatric use | Initiate at low end of dosing range; consider age-related decline in renal function; monitor for hypoglycemia. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for AFREZZA (AFREZZA).
| Breastfeeding | Insulin is excreted in human milk in low amounts; however, AFREZZA (insulin human) is administered via inhalation, and its systemic absorption is similar to subcutaneous insulin. The M/P ratio for insulin is not specifically determined for AFREZZA. Due to low oral bioavailability of insulin in infants, risk to the breastfed infant is low. Caution should be exercised, and hypoglycemia in the infant is unlikely. |
| Teratogenic Risk | Insufficient human data; animal studies show no evidence of fetal harm at doses up to 3.5 times the human exposure based on AUC. Insulin does not cross the placenta in significant amounts. Risk of hypoglycemia in the mother may pose fetal risk, especially in the first trimester. There is no known teratogenic risk associated with insulin use, including AFREZZA, across all trimesters. |
■ FDA Black Box Warning
Acute bronchospasm has been observed in patients with asthma and COPD. Afrezza is contraindicated in patients with chronic lung disease such as asthma or COPD. Before initiating therapy, perform spirometry (FEV1) to exclude lung disease in all patients.
| Serious Effects |
["Chronic lung disease (asthma, COPD)","During episodes of hypoglycemia","Hypersensitivity to regular insulin or any component of Afrezza"]
| Precautions | ["Risk of acute bronchospasm in patients with underlying lung disease","Decline in pulmonary function (FEV1) over time","Diabetic ketoacidosis (DKA) in patients with rapid-acting insulin use","Hypoglycemia, including severe hypoglycemia","Lung cancer risk observed in clinical trials; avoid in patients with active lung cancer"] |
| Food/Dietary | No known direct food interactions. Meals affect timing: administer immediately before or within 20 minutes of starting a meal. Avoid alcohol as it can increase hypoglycemia risk. |
Loading safety data…
| Fetal Monitoring | Monitor maternal blood glucose levels frequently to maintain normoglycemia and avoid hypoglycemia, which can be accentuated in pregnancy. Fetal monitoring includes ultrasound for growth assessment and biophysical profile as indicated. Monitor for signs of maternal hypoglycemia, especially during labor and delivery. |
| Fertility Effects | No adverse effects on fertility have been reported with insulin therapy. In animal studies, no impairment of fertility was observed with inhaled insulin. Human data are lacking, but insulin is not expected to negatively impact fertility. |
| Clinical Pearls | AFREZZA is an inhaled insulin product for prandial glucose control. Administer at the start of a meal. Must perform spirometry before initiation to exclude lung disease (FEV1 <70% predicted is a contraindication). Bronchospasm risk; contraindicated in asthma, COPD, and smokers. Monitor pulmonary function annually. Dose adjustment needed for switching from subcutaneous insulin. Use with caution in patients with active lung cancer or history of lung cancer. |
| Patient Advice | Inhale one cartridge at the start of each meal. Do not use for meals you skip. · Do not smoke or use if you have lung problems like asthma or COPD. · Perform a deep inhale from the inhaler; do not exhale into the device. · Rotate injection site if also using injectable insulin not required for Afrezza. · Monitor blood glucose regularly; carry fast-acting glucose for hypoglycemia. · Store cartridges at room temperature; do not freeze or expose to heat. |