ale rats and rabbits have revealed no evidence of harm to the fetus due to ORALAIR. In these studies, the effect of ORALAIR on embryo-fetal development was eva luated. Animals were administered 1000 IR/kg/day of ORALAIR by oral gavage on days 6-17 of gestation for rats, and days 6-18 of gestation for rabbits. A dose of 1000 IR/kg/day of ORALAIR corresponds to approximately 200 fold a human dose on an IR/kg/day basis. No adverse effects on embryo-fetal development were observed. There are, however, no adequate and well controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, ORALAIR should be used during pregnancy only if clearly needed.
Because systemic and local adverse reactions with immunotherapy may be poorly tolerated during pregnancy, ORALAIR should be used during pregnancy only if clearly needed.
8.2 Labor and Delivery
Safety and effectiveness of ORALAIR in labor and delivery have not been established.
8.3 Nursing Mothers
It is not known if ORALAIR is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when ORALAIR is administered to a nursing woman.
8.4 Pediatric Use
Efficacy and safety of ORALAIR have been established in children and adolescents 10 through 17 years of age. ORALAIR is not approved for use in children younger than 10 years of age because safety has not been established.
8.5 Geriatric Use
11 DESCRIPTION
ORALAIR (Sweet Vernal, Orchard, Perennial Rye, Timothy, and Kentucky Blue Grass Mixed Pollens Allergen Extract) is a mixed allergen extract of the following five pollens: Sweet Vernal (Anthoxanthum odoratum L), Orchard (Dactylis glomerata L), Perennial Rye (Lolium perenne L), Timothy (Phleum pratense L), and Kentucky Blue Grass (Poa pratensis L).
ORALAIR is available as a sublingual tablet in the following strengths:
100 IR (equivalent to approximately 3000 BAU (bioequivalent allergy units)
300 IR (equivalent to approximately 9000 BAU
Inactive ingredients: mannitol, microcrystalline cellulose, croscarmellose sodium, colloidal anhydrous silica, magnesium stearate and lactose monohydrate.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
The mechanisms of action of allergen immunotherapy are not known.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
No carcinogenicity studies were conducted in animals. There was no evidence of mutagenic or clastogenic activity in response to ORALAIR in the in vitro bacterial mutagenesis assay and mouse lymphoma thymidine kinase cell assay or the in vivo bone marrow micronucleus and unscheduled DNA synthesis tests in rats.
No fertility study was conducted with ORALAIR.
14 CLINICAL STUDIES
The efficacy of ORALAIR for the treatment of grass pollen-induced allergic rhinoconjunctivitis was investigated in five double-blind, placebo-controlled clinical trials: four natural field studies and an environmental exposure chamber study.
The natural field studies included three trials, each conducted over a single season (two in adults and one in adolescents and children) and one five-year study (adults). Participants received ORALAIR or placebo daily for four months prior to grass pollen season and throughout grass pollen season.
Study participants reported at least a two grass pollen season history of rhinoconjunctivitis symptoms. For the European studies, subjects had a positive skin pri |
