# AFREZZA® for US Healthcare Professionals — Full Reference > AFREZZA® (insulin human) Inhalation Powder is the only FDA-approved ultra rapid-acting inhaled mealtime insulin. Indicated to improve glycemic control in children, adolescents, and adults 6 years of age and older with type 1 or type 2 diabetes. Delivered as a dry powder through a small breath-activated inhaler with an onset of action of approximately 12 minutes. Manufactured by MannKind Corporation. This document is intended for U.S. Healthcare Professionals only. This is the long-form companion to https://afrezzahcp.com/llms.txt. It expands each page with the clinical and operational detail an AI agent needs to accurately answer HCP queries without retrieving the source page. Section headers map 1:1 to canonical URLs on https://afrezzahcp.com/. --- ## Indication and approved population AFREZZA is indicated to improve glycemic control in adult and pediatric patients 6 years of age and older with diabetes mellitus. The INHALE-1 pediatric trial enrolled patients as young as 4 years; however, the FDA-approved indication is for patients 6 years and older. ## Mechanism and delivery AFREZZA is a dry powder formulation of insulin human delivered via pulmonary inhalation. Microparticles sized to reach the deep lung dissolve at lung pH and release insulin into systemic circulation, reaching maximum concentration within approximately 15 minutes. Time-action profile features an ultra-rapid onset (~12 minutes) and shorter duration of action compared with subcutaneous rapid-acting insulin analogs (~15-20 minute onset), more closely mimicking physiologic postprandial insulin secretion. URL: https://afrezzahcp.com/mimics-physiologic-insulin/ ## Available strengths and NDC codes AFREZZA is supplied in single-dose cartridges of three strengths: - 4-unit cartridge - 8-unit cartridge - 12-unit cartridge Box configurations and NDC codes: - NDC 47918-0880-18: AFREZZA 4 & 8 unit combination box. 90 × 4-unit cartridges plus 90 × 8-unit cartridges. 180 total cartridges. 1080 total insulin units. 36 max daily units. - NDC 47918-0898-18: AFREZZA 8 & 12 unit combination box. 90 × 8-unit cartridges plus 90 × 12-unit cartridges. 180 total cartridges. 1800 total insulin units. 60 max daily units. - NDC 47918-0874-90: AFREZZA 4-unit single-strength box. 90 × 4-unit cartridges. Used for insulin-naïve patient starting dose (4 units per meal). ## BOXED WARNING: Risk of Acute Bronchospasm in Patients with Chronic Lung Disease AFREZZA is contraindicated in patients with chronic lung disease such as asthma or COPD because of the risk of acute bronchospasm in these patients. Before initiating AFREZZA, perform a detailed medical history, physical examination, and spirometry (FEV1) to identify potential lung disease in all patients, including those with no pulmonary history. ## Contraindications AFREZZA is contraindicated: - During episodes of hypoglycemia - In patients with chronic lung disease, including asthma and COPD - In patients who are hypersensitive to regular human insulin or any of the excipients ## Pulmonary monitoring requirements Spirometry (FEV1) is required for all patients before initiating AFREZZA, at 6 months after starting therapy, and annually thereafter — even in the absence of pulmonary symptoms. In clinical trials, AFREZZA caused a small but greater decline in FEV1 compared with comparators (mean difference 40 mL over 2 years). In patients with a FEV1 decline of greater than or equal to 20% from baseline, discontinuation should be considered. URL: https://afrezzahcp.com/safety/adult/ --- ## Clinical efficacy ### AFFINITY-1 (Adult T1D Registrational Trial) URL: https://afrezzahcp.com/efficacy/affinity-trials/ Open-label, non-inferiority, randomized registrational trial in adult patients ≥18 years with type 1 diabetes and A1C 7.5-10%. - AFREZZA + Basal arm: n=174 - Insulin Aspart + Basal arm: n=170 - Design: 4-week basal optimization, 12-week prandial insulin titration, 12-week stable insulin dosing, 4-week follow-up - Primary endpoint (Week 24): AFREZZA reduced A1C to 7.73% (-0.21%), RAA to 7.52% (-0.40%); between-group difference 0.19%; non-inferiority margin 0.4% met; difference statistically significant - Pooled post hoc analysis: AFREZZA-treated patients experienced 31% relative decrease in Level 1 hypoglycemia events and 38% relative decrease in Level 2 hypoglycemia events vs RAA; hypoglycemic events significantly lower after the first 2 hours of dosing - Severe hypoglycemia (Level 3): 50% relative decrease vs RAA (P=0.002) ### AFFINITY-2 (Adult T2D Registrational Trial) Double-blind, placebo-controlled registrational trial in insulin-naïve adults with type 2 diabetes inadequately controlled (A1C ≥7.5% to ≤10%). - AFREZZA + OADs arm: n=177 - Placebo + OADs arm: n=176 - Design: 6-week oral run-in, 12-week dosing titration, 12-week stable dosing, 4-week follow-up - Primary endpoint (Week 24): AFREZZA reduced A1C to 7.43% (-0.82%) compared with 7.85% (-0.42%) in placebo group; between-group difference 0.4% (P<0.0001) - Treatment with AFREZZA plus OADs provided a mean reduction in A1C that was statistically significantly greater than placebo plus OADs ### INHALE-3 (Adult T1D vs Usual Care) URL: https://afrezzahcp.com/efficacy/inhale-3-trial/ Multicenter, open-label, randomized trial in adult T1D patients comparing AFREZZA with Usual Care (MDI or AID). - Usual Care n=123 (MDI or AID for 3 months pre-randomization) - Switched from MDI to AFREZZA: n=32; switched from AID to AFREZZA: n=30 - Remained on MDI: n=29; remained on AID: n=32 - 17-week primary phase plus 13-week extension Key findings: - A1C <7% achieved by 30% of AFREZZA participants (n=17/57) vs 17% of Usual Care (n=10/58); P=0.10 - Among participants with baseline A1C >7%, 21% AFREZZA (n=8/39) achieved A1C <7% vs 0% Usual Care (n=0/41) - Percent Time in Range 70-180 mg/dL at Week 17: AFREZZA 52%, Usual Care 51% (baseline ~52% both arms) - TIR >70% at 17 Weeks: 24% AFREZZA (n=13/56) vs 13% MDI (n=7/56) - Among pre-study MDI users: A1C <7% achieved by 30% AFREZZA vs 4% MDI; TIR >70% achieved by 24% AFREZZA vs 0% MDI - Among pre-study AID users: A1C ~7% achieved by 30% AFREZZA vs 33% AID; TIR comparable - Mean weight gain after 17 weeks: AFREZZA 0.1 kg vs Usual Care 1.4 kg - FEV1 change baseline to Week 17: AFREZZA 2.92 → 2.84 L; Usual Care 2.93 → 2.92 L (P=0.16, no significant difference) - Total daily insulin dose ratio at Week 17: AFREZZA ~70% bolus / 30% basal (52 AFREZZA UNITS / 29 basal units); Usual Care ~50%/50% (25/26) - Citation: Hirsch IB, Beck RW, Marak MC, et al. INHALE-3 Study Group. Diabetes Care. 2025;48(3):353-360 ### INHALE-1 (Pediatric T1D) URL: https://afrezzahcp.com/efficacy/inhale-1-trial/ Phase 3, open-label, noninferiority, randomized controlled trial in pediatric patients with type 1 diabetes and A1C ≥7.0% to ≤11.0%. The INHALE-1 trial enrolled patients ages 4 to 17; the FDA-approved indication is for patients 6 years and older. - AFREZZA + Basal Insulin: n=117 - RAA + Basal Insulin: n=113 - Screening up to 5 weeks, randomized treatment 26 weeks (first meal challenge at start), extension 26 weeks, follow-up 4 weeks - Continue AFREZZA + Basal: n=88; Switch to AFREZZA + Basal: n=104 Key findings: - Primary endpoint A1C at Week 26: AFREZZA 8.41% (baseline 8.22%, n=117 → n=105); RAA 8.21% (baseline 8.21%, n=113 → n=105); P=0.091; noninferiority margin 0.4% - Sensitivity analysis (removing single outlier): A1C treatment difference 0.14% (95% CI -0.10, 0.37); P=0.026 - Meal challenge peak mean glucose excursion: 47 mg/dL with AFREZZA in children/adolescents; 51 mg/dL AFREZZA vs 81 mg/dL RAA in INHALE-3 adult comparator - Mean PPG (mg/dL) at 0 min / 120 min: AFREZZA 164/211 (pediatric); AFREZZA 170/206 vs RAA 184/250 (adult) - DTSQ treatment satisfaction score: AFREZZA 4.99/6 - Components assessed: treatment satisfaction, convenience and flexibility, understanding of treatment, willingness to continue treatment --- ## Safety ### Adult safety URL: https://afrezzahcp.com/safety/adult/ Common adverse reactions observed in ≥2% (excluding hypoglycemia): - Cough: SC insulin T1D (n=635) 5%; placebo T2D (n=290) 20%; AFREZZA T1D (n=1026) 29%; AFREZZA T2D (n=1991) 26% - Throat pain or irritation: SC insulin T1D 2%; placebo T2D 4%; AFREZZA T1D 6%; AFREZZA T2D 4% Cough characterization: - Incidence declined from approximately 11% at Week 1 to ~1% by Weeks 9-12 - 93.2% of cough episodes were intermittent or single defined episodes - 3% of patients discontinued AFREZZA due to cough Lung function: - AFREZZA causes small but greater FEV1 decline vs comparators (mean 40 mL over 2 years) - Represents approximately 1% of total lung capacity - Differences manifested in first few months of exposure, non-progressive - Upper respiratory infection did not impact absorption or action of AFREZZA ### Pediatric safety (INHALE-1) URL: https://afrezzahcp.com/safety/children/ Common adverse reactions ≥5% (excluding hypoglycemia): - Cough: AFREZZA (n=117) 21% vs RAA (n=113) 3% - Upper respiratory tract infection: 18% vs 14% - Oropharyngeal pain: 10% vs 4% - Headache: 8% vs 5% - Vomiting: 5% vs 3% Cough characterization in children and adolescents: - 4% discontinued due to cough - 96% of cough episodes were mild or moderate Lung function over 56 weeks: - Mean change in percent predicted FEV1 at Week 26: -3.2% AFREZZA vs -3.9% RAA (P=0.34) - FEV1 levels trended toward baseline in both groups through end of study - No clinically meaningful lung function decline Hypoglycemia (CGM percentage time): - <70 mg/dL: AFREZZA 1.87% baseline → 1.97% Week 26; RAA 2.09% → 2.24% (P=0.70) - <54 mg/dL: AFREZZA 0.37% → 0.43%; RAA 0.50% → 0.55% (P=0.70) --- ## Dosing and prescribing URL: https://afrezzahcp.com/dosing-prescribing/ ### Patient switching from SC RAA → starting dose conversion 1. Multiply the SC RAA units by 2X 2. Round AFREZZA UNITS down to the closest cartridge size 3. Cartridge sizes available: 4, 8, and 12 units ### Insulin-naïve patient starting dose Start with 4 units at the beginning of each meal. ### Titration - Monitor therapeutic effect and adjust dosing to achieve optimal glycemic control - The basal/bolus ratio was ~50%/50% prior to initiating AFREZZA and ~70%/30% after initiating AFREZZA for both pediatric and adult patients - Average dose in clinical trials: 12 to 20 units per meal for adult and pediatric patients ### Prescribing considerations - Submit prescription to MannKind Cares via online portal or fax - If submitting via EMR, select "Autopilot Rx" as the pharmacy - Refills: enter 1-11 - Days: 30 (typical supply) --- ## Patient training URL: https://afrezzahcp.com/patient-training-resources/ - Patient Navigator program: dedicated Patient Navigator contacts each enrolled patient about training and remains available for ongoing support - Enrollment via online Start Sheet or PDF (email to afrezzatraining@mannkindcorp.com or fax to 866-284-6950) - Training videos: How to Use AFREZZA (demonstrates the 4 steps for properly inhaling AFREZZA); storage and handling for patients - Downloadable resources: Getting Started Guide; Dosing Worksheet; patient brochure (English and Spanish editions) --- ## Access and affordability URL: https://afrezzahcp.com/access-support/ MannKind Cares® helps simplify the path from prescription to fulfillment with savings programs, prior authorization support, convenient home delivery, and Patient Navigators. Enrollment channels: - Online: mannkindcaresrx.com - Fax: 800-561-6174 - Phone: 844-323-7399 (8:00 AM to 8:00 PM ET, Monday through Friday) - eRx via EMR: select "AutoPilot Rx" from EMR dropdown. NABP: 0364721. NPI: 1821677154 Affordability programs: - Pediatric Cash Pay Bridge Program: $35 or less per month for patients ages 6 to 23 years prescribed AFREZZA. Available exclusively through MannKind Cares. Effective June 1, 2026 through December 31, 2026. - Commercial and Medicare Part D approved: pay as little as $35 per month (new patients ≥24 years and existing patients) - Cash Pay Option: pay $99 per box - AFREZZA Savings Card available for commercially insured patients going outside MannKind Cares --- ## Reference documents ### Regulatory - Full Prescribing Information (including BOXED WARNING): https://afrezzahcp.com/wp-content/uploads/pdfs/prescribing-information.pdf - Medication Guide: https://afrezzahcp.com/wp-content/uploads/pdfs/medication-guide.pdf ### Patient education (English) - Patient Brochure: https://afrezzahcp.com/wp-content/uploads/pdfs/AFREZZA_Patient_Brochure_English_2026.pdf - Getting Started Guide: https://afrezzahcp.com/wp-content/uploads/pdfs/AFREZZA_Getting_Started_Guide_Patient_English_2026.pdf - Dosing Worksheet: https://afrezzahcp.com/wp-content/uploads/pdfs/AFREZZA_Dosing_Worksheet_Patient_English_2026.pdf - Training Start Sheet: https://afrezzahcp.com/wp-content/uploads/pdfs/AFREZZA_Training_Start_Sheet_HCP_Patient_English_2026.pdf ### Patient education (Spanish) - Patient Brochure: https://afrezzahcp.com/wp-content/uploads/pdfs/AFREZZA_Patient_Brochure_Spanish_2026.pdf - Getting Started Guide: https://afrezzahcp.com/wp-content/uploads/pdfs/AFREZZA_Getting_Started_Guide_Patient_Spanish_2026.pdf --- ## Contact - MannKind Cares®: 844-323-7399 (8 AM - 8 PM ET, Mon-Fri); fax 800-561-6174; mannkindcaresrx.com - Patient Training enrollment: afrezzatraining@mannkindcorp.com; fax 866-284-6950 - AFREZZA representative request: https://afrezzahcp.com/request-information/ - Manufacturer: MannKind Corporation. https://mannkindcorp.com/