Recommended Topic Related To:

Exubera

"Nov. 21, 2012 -- The number of children and teens with type 1 and type 2 diabetes is expected to spike dramatically in the next 40 years, creating what one expert calls a potential catastrophe for the nation's health care system.

Rat"...

Exubera

Exubera

WARNINGS

EXUBERA (insulin human [rdna origin]) differs from regular human insulin by its rapid onset of action. When used as mealtime insulin, the dose of EXUBERA (insulin human [rdna origin]) should be given within 10 minutes before a meal.

Hypoglycemia is the most commonly reported adverse event of insulin therapy, including EXUBERA (insulin human [rdna origin]) . The timing of hypoglycemia may differ among various insulin formulations.

Patients with type 1 diabetes also require a longer-acting insulin to maintain adequate glucose control.

Any change of insulin should be made cautiously and only under medical supervision. Changes in insulin strength, manufacturer, type (e.g., regular, NPH, analogs), or species (animal, human) may result in the need for a change in dosage. Concomitant oral antidiabetic treatment may need to be adjusted.

Glucose monitoring is recommended for all patients with diabetes.

Because of the effect of EXUBERA (insulin human [rdna origin]) on pulmonary function, all patients should have pulmonaryfunction assessed prior to initiating therapy with EXUBERA (insulin human [rdna origin]) (see PRECAUTIONS: Pulmonary Function).

The use of EXUBERA (insulin human [rdna origin]) in patients with underlying lung disease, such as asthma or COPD, is not recommended because the safety and efficacy of EXUBERA (insulin human [rdna origin]) in this population have not been established (see PRECAUTIONS: Underlying Lung Disease).

In clinical trials of Exubera (insulin human [rdna origin]) , there have been 6 newly diagnosed cases of primary lung malignancies among Exubera (insulin human [rdna origin]) -treated patients, and 1 newly diagnosed case among comparator-treated patients. There has also been 1 postmarketing report of a primary lung malignancy in an Exubera (insulin human [rdna origin]) -treated patient. In controlled clinical trials of Exubera (insulin human [rdna origin]) , the incidence of new primary lung cancer per 100 patient-years of study drug exposure was 0.13 (5 cases over 3800 patient-years) for Exubera (insulin human [rdna origin]) -treated patients and 0.03 (1 case over 3800 patient-years) for comparator-treated patients. There were too few cases to determine whether the emergence of these events is related to Exubera (insulin human [rdna origin]) . All patients who were diagnosed with lung cancer had a prior history of cigarette smoking.

PRECAUTIONS

General

As with all insulin preparations, the time course of EXUBERA (insulin human [rdna origin]) action may vary in different individuals or at different times in the same individual. Adjustment of dosage of any insulin may be necessary if patients change their physical activity or their usual meal plan. Insulin requirements may be altered during intercurrent conditions such as illness, emotional disturbances, or stress.

Hypoglycemia

As with all insulin preparations, hypoglycemic reactions may be associated with theadministration of EXUBERA (insulin human [rdna origin]) . Rapid changes in serum glucose concentrations may induce symptoms similar to hypoglycemia in persons with diabetes, regardless of the glucose value. Early warning symptoms of hypoglycemia may be different or less pronounced under certain conditions, such as long duration of diabetes, diabetic nerve disease, use of medications such as beta-blockers, or intensified diabetes control (see PRECAUTIONS: DRUG INTERACTIONS). Such situations may result in severe hypoglycemia (and, possibly, loss of consciousness) prior to patients' awareness of hypoglycemia.

Renal Impairment

Studies have not been performed in patients with renal impairment. As with other insulin preparations, the dose requirements for EXUBERA (insulin human [rdna origin]) may be reduced in patients with renal impairment (see CLINICAL PHARMACOLOGY, Special Populations).

Hepatic Impairment

Studies have not been performed in patients with hepatic impairment. As with other insulin preparations, the dose requirements for EXUBERA (insulin human [rdna origin]) may be reduced in patients with hepatic impairment (see CLINICAL PHARMACOLOGY, Special Populations).

Allergy

Systemic Allergy

In clinical studies, the overall incidence of allergic reactions in patients treated with EXUBERA (insulin human [rdna origin]) was similar to that in patients using subcutaneous regimens with regular human insulin.

As with other insulin preparations, rare, but potentially serious, generalized allergy to insulin may occur, which may cause rash (including pruritus) over the whole body, shortness of breath, wheezing, reduction in blood pressure, rapid pulse, or sweating. Severe cases of generalized allergy, including anaphylactic reactions, may be life threatening. If such reactions occur from EXUBERA (insulin human [rdna origin]) , EXUBERA (insulin human [rdna origin]) should be stopped and alternative therapies considered.

Antibody Production

Insulin antibodies may develop during treatment with all insulin preparations including EXUBERA (insulin human [rdna origin]) . In clinical studies of EXUBERA (insulin human [rdna origin]) where the comparator was subcutaneous insulin, increases in insulin antibody levels (as reflected by assays of insulin binding activity) were significantly greater for patients who received EXUBERA (insulin human [rdna origin]) than for patients who received subcutaneous insulin only. No clinical consequences of these antibodies were identified over the time period of clinical studies of EXUBERA (insulin human [rdna origin]) ; however, the long-term clinical significance of this increase in antibody formation is unknown.

Respiratory

Pulmonary Function

In 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 difference in pulmonary function favoring the comparator group, was noted within the first several weeks of treatment with EXUBERA (insulin human [rdna origin]) , and did not change over the two year treatment period (See ADVERSE REACTIONS: Pulmonary Function).

During the controlled 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.

Because of the effect of EXUBERA (insulin human [rdna origin]) on pulmonary function, all patients should have spirometry (FEV1) assessed prior to initiating therapy with EXUBERA (insulin human [rdna origin]) . Assessment of DLCO should be considered. The efficacy and safety of EXUBERA (insulin human [rdna origin]) in patients with baseline FEV1 or DLCO < 70% predicted have not been established and the use of EXUBERA (insulin human [rdna origin]) in this population is not recommended.

Assessment of pulmonary function (e.g., spirometry) is recommended after the first 6 months of therapy, and annually thereafter, even in the absence of pulmonary symptoms. In patients who have a decline of ≥ 20% in FEV1 from baseline, pulmonary function tests should be repeated. If the ≥ 20% decline from baseline FEV1 is confirmed, EXUBERA (insulin human [rdna origin]) should be discontinued. The presence of pulmonary symptoms and lesser declines in pulmonary function may require more frequent monitoring of pulmonary function and consideration of discontinuation of EXUBERA (insulin human [rdna origin]) .

Underlying Lung Disease

The use of EXUBERA (insulin human [rdna origin]) in patients with underlying lung disease, such as asthma or COPD, is not recommended because the efficacy and safety of EXUBERA (insulin human [rdna origin]) in this population have not been established.

Bronchospasm

Bronchospasm has been rarely reported in patients taking EXUBERA (insulin human [rdna origin]) . Patients experiencing such a reaction should discontinue EXUBERA (insulin human [rdna origin]) and seek medical evaluation immediately. Re- administration of EXUBERA (insulin human [rdna origin]) requires a careful risk evaluation, and should only be done under close medical monitoring with appropriate clinical facilities available.

Intercurrent Respiratory Illness

EXUBERA (insulin human [rdna origin]) has been administered to patients with intercurrent respiratory illness (e.g. bronchitis, upper respiratory tract infections, rhinitis) during clinical studies. In patients experiencing these conditions, 3-4% temporarily discontinued EXUBERA (insulin human [rdna origin]) therapy. There was no increased risk of hypoglycemia or worsened glycemic control observed in EXUBERA (insulin human [rdna origin]) -treated patients compared to patients treated with subcutaneous insulin. During intercurrent respiratory illness, close monitoring of blood glucose concentrations, and dose adjustment, may be required.

Information for Patients

Patients should be instructed on self-management procedures including glucose monitoring;proper EXUBERA (insulin human [rdna origin]) inhalation technique; and hypoglycemia and hyperglycemia management. Patients must be instructed on handling of special situations such as intercurrent conditions (illness, stress, or emotional disturbances), an inadequate or skipped insulin dose, inadvertent administration of an increased insulin dose, inadequate food intake, or skipped meals. Refer patients to the EXUBERA Patient Medication Guide for additional information.

Patients should be informed that in clinical studies, treatment with EXUBERA (insulin human [rdna origin]) was associated with small, non-progressive mean declines in pulmonary function relative to comparator treatments. Because of the effect of EXUBERA (insulin human [rdna origin]) on pulmonary function, pulmonary functiontests are recommended prior to initiating treatment with EXUBERA (insulin human [rdna origin]) . Following initiation of therapy, periodic pulmonary function tests are recommended (see PRECAUTIONS, Respiratory, Pulmonary Function).

Patients should inform their physician if they have a history of lung disease, because the use of EXUBERA (insulin human [rdna origin]) is not recommended in patients with underlying lung disease (e.g., asthma or COPD), and is contraindicated in patients with poorly controlled lung disease.

Women with diabetes should be advised to inform their doctor if they are pregnant or are contemplating pregnancy.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Two-year carcinogenicity studies in animals have not been performed. Insulin was not mutagenic in the Ames bacterial reverse mutation test in the presence and absence of metabolic activation.

In Sprague-Dawley rats, a 6-month repeat-dose toxicity study was conducted with insulin inhalation powder at doses up to 5.8 mg/kg/day (compared to the clinical starting dose of 0.15 mg/kg/day, the rat high dose was 39 times or 8.3 times the clinical dose, based on either a mg/kg or a mg/m2 body surface area comparison). In Cynomolgus monkeys, a 6-month repeat-dose toxicity study was conducted with inhaled insulin at doses up to 0.64 mg/kg/day. Compared to the clinical starting dose of 0.15 mg/kg/day, the monkey high dose was 4.3 times or 1.4 times the clinical dose, based on either a mg/kg or a mg/m2 body surface area comparison. These were maximum tolerated doses based on hypoglycemia.

Compared to control animals, there were no treatment-related adverse effects in either specieson pulmonary function, gross or microscopic morphology of the respiratory tract or bronchial lymph nodes. Similarly, there was no effect on cell proliferation indices in alveolar orbronchiolar area of the lung in either species.

Because recombinant human insulin is identical to the endogenous hormone, reproductive/fertility studies were not performed in animals.

Pregnancy

Teratogenic Effects

Pregnancy Category C

Animal reproduction studies have not been conducted with EXUBERA (insulin human [rdna origin]) . It is also not known whether EXUBERA (insulin human [rdna origin]) can cause fetal harm when administered to a pregnant woman or whether EXUBERA (insulin human [rdna origin]) can affect reproductive capacity. EXUBERA (insulin human [rdna origin]) should be given to a pregnant woman only if clearly needed.

Nursing Mothers

Many drugs, including human insulin, are excreted in human milk. For this reason, caution should be exercised when EXUBERA (insulin human [rdna origin]) is administered to a nursing woman. Patients with diabetes who are lactating may require adjustments in EXUBERA (insulin human [rdna origin]) dose, meal plan, or both.

Pediatric Use

Long-term safety and effectiveness of EXUBERA (insulin human [rdna origin]) in pediatric patients have not been established (see CLINICAL PHARMACOLOGY, Special Populations).

Geriatric Use

In controlled Phase 2/3 clinical studies (n=1975), EXUBERA (insulin human [rdna origin]) was administered to 266 patients ≥ 65 years of age and 30 patients ≥ 75 years of age. The majority of these patients had type 2 diabetes. The change in HbA 1C and rate of hypoglycemia did not differ by age.

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

A A A

Report Problems to the Food and Drug Administration

 

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.


Diabetes

Find tips and advances in treatment.

Related Drugs
Health Resources
advertisement
advertisement
Use Pill Finder Find it Now See Interactions

Pill Identifier on RxList

  • quick, easy,
    pill identification

Find a Local Pharmacy

  • including 24 hour, pharmacies

Interaction Checker

  • Check potential drug interactions
Search the Medical Dictionary for Health Definitions & Medical Abbreviations