Oralair

Immunotherapy for Allergic Rhinitis

For sublingual use only.
Administer the first dose of allergen extract in a healthcare setting where acute allergic reactions can be recognized and treated by an experienced clinician.
Observe the patient for at least 30 minutes after the initial dose; monitor for signs and symptoms of a severe systemic or local allergic reaction.
If the patient tolerates the initial dose, subsequent doses may be taken at home.
Pediatric doses should be administered under adult supervision.
Auto-injectable epinephrine should be available to all patients receiving sublingual allergen extract outside the healthcare setting; educate on proper use.
Remove the tablet from the blister packaging immediately prior to dosing.
Place the tablet under the tongue. Wait until the tablet is completely dissolved (at least 1 minute) and then swallow.
Do not take with food or drink. To avoid swallowing the allergen extract, do not eat or drink for at least 5 minutes after tablet dissolution.
Wash hands after handling the tablet.

anaphylactic shock / Rapid / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
serious hypersensitivity reactions or anaphylaxis / Rapid / Incidence not known
angioedema / Rapid / Incidence not known
laryngeal edema / Rapid / Incidence not known
myocarditis / Delayed / Incidence not known

edema / Delayed / 2.3-8.2
atopic dermatitis / Delayed / 3.2-3.2
dysphonia / Delayed / 2.6-2.6
stomatitis / Delayed / 2.1-2.1
dysphagia / Delayed / 0-2.0
gastritis / Delayed / 0-2.0
hyperemia / Delayed / 2.0-2.0
wheezing / Rapid / Incidence not known
dyspnea / Early / Incidence not known
esophagitis / Delayed / Incidence not known
eosinophilia / Delayed / Incidence not known
lymphadenopathy / Delayed / Incidence not known
chest pain (unspecified) / Early / Incidence not known
hypotension / Rapid / Incidence not known
palpitations / Early / Incidence not known
sinus tachycardia / Rapid / Incidence not known

pruritus / Rapid / 3.2-25.1
throat irritation / Early / 22.0-22.0
paresthesias / Delayed / 4.3-11.1
cough / Delayed / 6.2-7.3
abdominal pain / Early / 2.3-4.2
infection / Delayed / 3.9-3.9
dyspepsia / Early / 3.9-3.9
vomiting / Early / 0-2.6
urticaria / Rapid / 2.3-2.3
hypoesthesia / Delayed / 2.2-2.2
gastroesophageal reflux / Delayed / 0-2.0
nausea / Early / 0-2.0
rash / Early / Incidence not known
flushing / Rapid / Incidence not known
weight loss / Delayed / Incidence not known
diarrhea / Early / Incidence not known
xerostomia / Early / Incidence not known
hypersalivation / Early / Incidence not known
anxiety / Delayed / Incidence not known
dizziness / Early / Incidence not known
headache / Early / Incidence not known
drowsiness / Early / Incidence not known
tinnitus / Delayed / Incidence not known
pallor / Early / Incidence not known
asthenia / Delayed / Incidence not known
malaise / Early / Incidence not known
xerophthalmia / Early / Incidence not known

Oralair

Rx

Sublingual immunotherapy; mixed grass allergen extract of Sweet Vernal, Orchard, Perennial Rye, Timothy, and Kentucky Blue Grass
Used for treatment of allergic rhinitis +/- conjunctivitis due to grass pollen
Give first dose in doctor's office due to risk of anaphylaxis; auto-injectable epinephrine must be available for home use

300 IR (index of reactivity) SL once daily. Give the first dose in a health care setting where acute allergic reactions can be recognized and treated by an experienced clinician; observe the patient for at least 30 minutes after administration. If the patient tolerates the first dose, subsequent doses can be taken at home. Auto-injectable epinephrine should be available; instruct patients who are prescribed epinephrine in proper technique for emergency self-injection.[56951]

100 IR (index of reactivity) SL on day 1 followed by 200 IR SL on day 2 and 300 IR SL once daily on day 3 and thereafter. Give the first dose in a health care setting where acute allergic reactions can be recognized and treated by an experienced clinician; observe the patient for at least 30 minutes after administration. If the patient tolerates the first dose, subsequent doses can be taken at home. Auto-injectable epinephrine should be available; instruct patients who are prescribed epinephrine in proper technique for emergency self-injection.[56951]

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

There are no drug interactions associated with Mixed Grass Pollens Allergen Extract products.

Oralair Oral Tablet, SL

300 IR/day SL.

65 years: 300 IR/day SL.
66 years and older: Safety and efficacy have not been established.

300 IR/day SL.

5 to 12 years: 300 IR/day SL.
1 to 4 years: Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

When mixed grass pollens allergen extract is allowed to dissolve sublingually, allergens bind to epithelial cells and cross the oral mucosa, where they are taken up by tolerogenic antigen-presenting cells (i.e., Langerhans cells and myeloid dendritic cells). The allergens are then processed into small immunogenic peptides, and the antigen-presenting cells migrate into local regional lymph nodes (submaxillary, cervical, internal jugular). There, allergen peptide fragments are presented to naive CD4+ T cells. This interaction stimulates suppressive T helper (Th) 1 and regulatory T cells and inhibits the activation and proliferation of Th2 cells. Subsequently, T cells encourage B cells to produce protective antibody responses, including secretion of allergen-specific IgG4 and IgA and, later, inhibition of IgE. Regulatory T cells may also suppress other inflammatory cells (e.g., eosinophils, mast cells, basophils) either by cytokine secretion or direct cell-to-cell contact. CD4+ T cells eventually migrate into the blood and tissues, resulting in allergen tolerance.

Mixed grass pollens allergen extract is administered sublingually. The pharmacokinetics of the extract are not well defined and in vivo human research is lacking. Limited pharmacokinetic data are available for sublingual immunotherapy in general. However, direct contact with the oral mucosa has been determined to be the critical step in ensuring adequate exposure.
 
Parietaria judaica is a perennial plant with highly allergenic pollen. Human pharmacodynamic studies of radiolabeled Parietaria judaica allergen have shown little systemic absorption into the bloodstream through the sublingual mucosa, despite its highly vascular nature. In one study, radioactivity was not detectable in the plasma until swallowing occurred, at which point the plasma radioactivity slowly rose and peaked at approximately 2 hours. In another study using Parietaria judaica, a small amount of the allergen (about 2% of the administered dose) was detected within the oral mucosa 20 hours after dosing. It has been suggested allergens bind to epithelial cells within a few minutes. In a biodistribution study of sublingual radiolabeled ovalbumin in mice, allergen crossed the oral mucosa within 15—30 minutes and was captured by antigen-presenting cells within 30—60 minutes. At 60 minutes, allergen began to disappear from the submucosa, perhaps coinciding with uptake and processing by the antigen-presenting cells. Within 12—24 hours after administration, the antigen-presenting cells migrate to the lymph nodes where they interact with CD4+ cells and further promote the desensitization process.
 
Affected cytochrome P450 isoenzymes: none

Adequate and well-controlled studies with mixed grass pollens allergen extract have not been conducted in pregnant women. Reproductive and developmental toxicity studies in animals revealed no evidence of fetal harm. Mixed grass pollens allergen extract should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus, as systemic and local adverse reactions to immunotherapy may be poorly tolerated during pregnancy.[56951]

It is not known if mixed grass pollens allergen extract is excreted into human breast milk.[56951] Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.