ptor Blocking Agents
Beta-blockers not only block the pulmonary effect of beta-agonists, such as salmeterol, acomponent of AirDuo Digihaler, but may also produce severe bronchospasm in patients withasthma. Therefore, patients with asthma should not normally be treated with beta-blockers.
However, under certain circumstances, there may be no acceptable alternatives to the use ofbeta-adrenergic blocking agents for these patients; cardioselective beta-blockers could beconsidered, although they should be administered with caution.
7.4 Non-Potassium-Sparing Diuretics
The ECG changes and/or hypokalemia that may result from the administration of non–potassium-sparing diuretics (such as loop or thiazide diuretics) can be acutely worsened bybeta-agonists, such as salmeterol, a component of AirDuo Digihaler, especially when therecommended dose of the beta-agonist is exceeded. Although the clinical significance of theseeffects is not known, caution is advised in the coadministration of AirDuo Digihaler with non–potassium-sparing diuretics.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
There are no randomized clinical studies of AirDuo Digihaler or individual monoproducts,fluticasone propionate and salmeterol, in pregnant women. There are clinical considerations withthe use of AirDuo Digihaler in pregnant women [see Clinical Considerations]. Animalreproduction studies are available with the combination of fluticasone propionate and salmeterolas well as individual components. In animals, teratogenicity characteristic of corticosteroids,decreased fetal body weight and/or skeletal variations, in rats, mice, and rabbits were observedwith subcutaneously administered maternal toxic doses of fluticasone propionate less than the
maximum recommended human daily inhaled dose (MRHDID) on a mcg/m2basis [see Data].
However, fluticasone propionate administered via inhalation to rats decreased fetal body weight,but did not induce teratogenicity at a maternal toxic dose less than the MRHDID on a mcg/m2basis [see Data]. Experience with oral corticosteroids suggests that rodents are more prone toteratogenic effects from corticosteroids than humans. Oral administration of salmeterol topregnant rabbits caused teratogenicity characteristic of beta-adrenoceptor stimulation at maternaldoses approximately 700 times the MRHDID on a mcg/m2basis. These adverse effects generallyoccurred at large multiples of the MRHDID when salmeterol was administered by the oral route
to achieve high systemic exposures. No such effects occurred at an oral salmeterol doseapproximately 420 times the MRHDID [see Data].
The estimated risk of major birth defects and miscarriage for the indicated population isunknown. In the U.S. general population, the estimated risk of major birth defects andmiscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Clinical Considerations
Disease-Associated Maternal and/or Embryo/Fetal RiskIn women with poorly or moderately controlled asthma, there is an increased risk of severalperinatal adverse outcomes such as preeclampsia in the mother and prematurity, low birthweight, and small for gestational age in the neonate. Pregnant women with asthma should be
closely monitored and medication adjusted as necessary to maintain optimal asthma control.
Data
Animal Data
Fluticasone Propionate and Salmeterol: In a |
