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Exubera

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Exubera

Exubera

SIDE EFFECTS

The safety of EXUBERA (insulin human [rdna origin]) alone, or in combination with subcutaneous insulin or oral agents, has been evaluated in approximately 2500 adult patients with type 1 or type 2 diabetes who were exposed to EXUBERA (insulin human [rdna origin]) . Approximately 2000 patients were exposed to EXUBERA (insulin human [rdna origin]) for greater than 6 months and more than 800 patients were exposed for more than 2 years.

Non-Respiratory Adverse Events

Non-respiratory adverse events reported in ≥ 1% of 1977 EXUBERA (insulin human [rdna origin]) -treated patients in controlled Phase 2/3 clinical studies, regardless of causality, include (but are not limited to) the following:

Metabolic and Nutritional: hypoglycemia (see WARNINGS and PRECAUTIONS)

Body as a whole: chest pain

Digestive: dry mouth

Special senses: otitis media (type 1 pediatric diabetics)

Hypoglycemia

The rates and incidence of hypoglycemia were comparable between EXUBERA (insulin human [rdna origin]) and subcutaneous regular human insulin in patients with type 1 and type 2 diabetes. In type 2 patients who were not adequately controlled with single oral agent therapy, the addition of EXUBERA (insulin human [rdna origin]) was associated with a higher rate of hypoglycemia than was the addition of a second oral agent.

Chest pain

A range of different chest symptoms were reported as adverse reactions and were grouped under the non-specific term chest pain. These events occurred in 4.7% of EXUBERA (insulin human [rdna origin]) -treated patients and 3.2% of patients in comparator groups. The majority ( > 90%) of these events were reported as mild or moderate. Two patients in the EXUBERA (insulin human [rdna origin]) and one in the comparator group discontinued treatment due to chest pain. The incidence of all-causality adverse events related to coronary artery disease, such as angina pectoris or myocardial infarction was comparable in the EXUBERA (insulin human [rdna origin]) (0.7% angina pectoris; 0.7% myocardial infarction) and comparator (1.3% angina pectoris; 0.7% myocardial infarction) treatment groups.

Dry Mouth

Dry mouth was reported in 2.4% of EXUBERA (insulin human [rdna origin]) -treated patients and 0.8% of patients in comparator groups. Nearly all ( > 98%) of dry mouth reported was mild or moderate. No patients discontinued treatment due to dry mouth.

Ear Events in Pediatric Diabetics

Pediatric type 1 diabetics in EXUBERA (insulin human [rdna origin]) groups experienced adverse events related to the ear more frequently than did pediatric type 1 diabetics in treatment groups receiving only subcutaneous insulin. These events included otitis media (EXUBERA (insulin human [rdna origin]) 6.5%; SC 3.4%), ear pain (EXUBERA (insulin human [rdna origin]) 3.9%; SC 1.4%), and ear disorder (EXUBERA (insulin human [rdna origin]) 1.3%; SC 0%).

Respiratory Adverse Events

Table 6 shows the incidence of respiratory adverse events for each treatment group that were reported in ≥ 1% of any treatment group in controlled Phase 2 and 3 clinical studies, regardless of causality.

Table 6: Respiratory Adverse Events Reported in ≥ 1% of Any Treatment Group in Controlled Phase 2 and 3 Clinical Studies, Regardless of Causality

  Percent of Patients Reporting Event
Type 1 Diabetes Type 2 Diabetes
Adverse Event EXUBERA
N = 698
SC
N= 705
EXUBERA
N = 1279
SC
N = 488
OAs
N = 644
Respiratory Tract Infection 43.3 42.0 29.2 38.1 19.7
Cough Increased 29.5 8.8 21.9 10.2 3.7
Pharyngitis 18.2 16.6 9.5 9.6 5.9
Rhinitis 14.5 10.9 8.8 10.5 3.0
Sinusitis 10.3 7.4 5.4 10.0 2.3
Respiratory Disorder 7.4 4.1 6.1 10.2 1.7
Dyspnea 4.4 0.9 3.6 2.5 1.4
Sputum Increased 3.9 1.3 2.8 1.0 0.5
Bronchitis 3.2 4.1 5.4 3.9 4.0
Asthma 1.3 1.3 2.0 2.3 0.5
Epistaxis 1.3 0.4 1.2 0.4 0.8
Laryngitis 1.1 0.4 0.5 0.4 0.3
Pneumonia 0.9 1.1 0.9 1.6 0.6
Voice Alteration 0.1 0.1 1.3 0.0 0.3
SC = subcutaneous insulin comparator; OA = oral agent comparators

Cough

In 3 clinical studies, patients who completed a cough questionnaire reported that the cough tended to occur within seconds to minutes after EXUBERA (insulin human [rdna origin]) inhalation, was predominantly mild in severity and was rarely productive in nature. The incidence of this cough decreased with continued EXUBERA (insulin human [rdna origin]) use. In controlled clinical studies, 1.2% of patients discontinued EXUBERA (insulin human [rdna origin]) treatment due to cough.

Dyspnea

Nearly all ( > 97%) of dyspnea was reported as mild or moderate. A small number of EXUBERA (insulin human [rdna origin]) -treated patients (0.4%) discontinued treatment due to dyspnea compared to 0.1% of comparator-treated patients.

Other Respiratory Adverse Events - Pharyngitis, Sputum Increased and Epistaxis

The majority of these events were reported as mild or moderate. A small number of EXUBERA (insulin human [rdna origin]) -treated patients discontinued treatment due to pharyngitis (0.2%) and sputum increased (0.1%); no patients discontinued treatment due to epistaxis.

Pulmonary Function

The effect of EXUBERA (insulin human [rdna origin]) on the respiratory system has been evaluated in over 3800 patients in controlled phase 2 and 3 clinical studies (in which 1977 patients were treated with EXUBERA (insulin human [rdna origin]) ). In randomized, open-label clinical trials up to two years duration, patients treated with EXUBERA (insulin human [rdna origin]) demonstrated a greater decline in pulmonary function, specifically the forced expiratory volume in one second (FEV1) and the carbon monoxide diffusing capacity (DLCO), than comparator treated patients. The mean treatment group differences in FEV1 and DLCO , were noted within the first several weeks of treatment with EXUBERA (insulin human [rdna origin]) , and did not progress over the two year treatment period. In one completed controlled clinical trial in patients with type 2 diabetes following two years of treatment with EXUBERA (insulin human [rdna origin]) , patients showed resolution of the treatment group difference in FEV1 six weeks after discontinuation of therapy. Resolution of the effect of EXUBERA (insulin human [rdna origin]) on pulmonary function in patients with type 1 diabetes has not been studied after long-term treatment.

Figures 3 through 6 display the mean FEV 1 and DLCO change from baseline versus time from two ongoing randomized, open-label, two year studies in 580 patients with type 1 and 620 patients with type 2 diabetes.

Figure 3: Change from Baseline FEV1 (L) in Patients with Type 1 Diabetes (Mean +/-Standard Deviation)

Change from Baseline FEV1 (L) in Patients with Type 1 Diabetes (Mean +/-Standard Deviation) - Illustration

Figure 4: Change from Baseline FEV1 (L) in Patients with Type 2 Diabetes (Mean +/- Standard Deviation)

Change from Baseline FEV1 (L) in Patients with Type 2 Diabetes (Mean +/- Standard Deviation) - Illustration

Following 2 years of EXUBERA (insulin human [rdna origin]) treatment in patients with type 1 and type 2 diabetes, the difference between treatment groups for the mean change from baseline FEV1 was approximately 40 mL, favoring the comparator.

Figure 5: Change from Baseline DLco (mL/min/mmHg) in Patients with Type 1 Diabetes (Mean +/- Standard Deviation)

Change from Baseline DLco (mL/min/mmHg) in Patients with Type 1 Diabetes (Mean +/- Standard Deviation) - Illustration

Figure 6: Change from Baseline DLco (mL/min/mmHg) in Patients with Type 2 Diabetes (Mean +/- Standard Deviation)

Change from Baseline DLco (mL/min/mmHg) in Patients with Type 2 Diabetes (Mean +/- Standard Deviation) - Illustration

Following 2 years of EXUBERA (insulin human [rdna origin]) treatment, the difference between treatment groups for themean change from baseline DLCO was approximately 0.5mL/min/mmHg (type 1 diabetes), favoring the comparator, and approximately 0.1mL/min/mmHg (type 2 diabetes), favoring EXUBERA (insulin human [rdna origin]) .

During the two-year clinical trials, individual patients experienced notable declines in pulmonary function in both treatment groups. A decline from baseline FEV1 of ≥ 20% at last observation occurred in 1.5% of EXUBERA (insulin human [rdna origin]) -treated and 1.3% of comparator-treated patients. A decline from baseline DLCO of ≥ 20% at last observation occurred in 5.1% of EXUBERA (insulin human [rdna origin]) - treated and 3.6% of comparator treated patients.

Read the Exubera (insulin human [rdna origin]) Side Effects Center for a complete guide to possible side effects

DRUG INTERACTIONS

A number of substances affect glucose metabolism and may require insulin dose adjustment and particularly close monitoring.

The following are examples of substances that may reduce the blood glucose-lowering effect of insulin that may result in hyperglycemia: corticosteroids, danazol, diazoxide, diuretics, sympathomimetic agents (e.g., epinephrine, albuterol, terbutaline), glucagon, isoniazid, phenothiazine derivatives, somatropin, thyroid hormones, estrogens, progestogens (e.g., in oral contraceptives), protease inhibitors, and atypical antipsychotic medications (e.g., olanzapine and clozapine).

The following are examples of substances that may increase the blood glucose-lowering effect of insulin and susceptibility to hypoglycemia: oral antidiabetic products, ACE inhibitors, disopyramide, fibrates, fluoxetine, MAO inhibitors, pentoxifylline, propoxyphene, salicylates, and sulfonamide antibiotics.

Beta-blockers, clonidine, lithium salts, and alcohol may either increase or reduce the blood glucose-lowering effect of insulin. Pentamidine may cause hypoglycemia, which may sometimes be followed by hyperglycemia.

In addition, under the influence of sympatholytic medicinal products such as beta-blockers, clonidine, guanethidine, and reserpine, the signs and symptoms of hypoglycemia may be reduced or absent.

Bronchodilators and other inhaled products may alter the absorption of inhaled human insulin (see CLINICAL PHARMACOLOGY, Special Populations). Consistent timing of dosing of bronchodilators relative to EXUBERA (insulin human [rdna origin]) administration, close monitoring of blood glucose concentrations and dose titration as appropriate are recommended.

Last reviewed on RxList: 12/11/2008
This monograph has been modified to include the generic and brand name in many instances.

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