ODACTRA 12

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.
Auto-injectable epinephrine should be available to all patients receiving sublingual allergen extract outside the healthcare setting; educate on proper use.
With dry hands, remove the tablet from the blister packaging immediately prior to dosing.
Place the tablet under the tongue where it will dissolve within 10 seconds. Do not swallow for at least 1 minute.
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.

anaphylactoid reactions / Rapid / Incidence not known
anaphylactic shock / Rapid / Incidence not known
serious hypersensitivity reactions or anaphylaxis / Rapid / Incidence not known
angioedema / Rapid / Incidence not known

oral ulceration / Delayed / 10.3-24.5
stomatitis / Delayed / 2.1-2.5
dysphagia / Delayed / 1.1-1.4
chest pain (unspecified) / Early / 1.1-1.3
esophagitis / Delayed / 0-1.1
erythema / Early / Incidence not known

throat irritation / Early / 67.0-73.4
pruritus / Rapid / 1.1-73.4
abdominal pain / Early / 11.3-23.4
nausea / Early / 14.2-17.0
dysgeusia / Early / 4.3-10.0
paresthesias / Delayed / 5.3-9.2
diarrhea / Early / 6.9-7.7
vomiting / Early / 2.5-4.3
dyspepsia / Early / 2.2-2.7
ocular pruritus / Rapid / 1.1-1.7
gastroesophageal reflux / Delayed / 1.6-1.6
infection / Delayed / 1.6-1.6
sneezing / Early / 1.6-1.6
hypoesthesia / Delayed / 1.3-1.3
fatigue / Early / 1.3-1.3
urticaria / Rapid / 1.1-1.1
arthralgia / Delayed / 1.1-1.1
flushing / Rapid / 1.1-1.1
rhinorrhea / Early / 1.1-1.1
cough / Delayed / Incidence not known

ODACTRA 12

Rx

Oral, sublingual immunotherapy
For allergic rhinitis with or without conjunctivitis that is induced by Dermatophagoides farinae or Dermatophagoides pteronyssinus house dust mites (HDM)
First dose given in health care provider's office to allow for patient observation for potential adverse reactions

1 tablet sublingually once daily. Do not swallow the tablet. Administer the first dose 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 administration. If the patient tolerates the initial dose, subsequent doses can be taken at home; auto-injectable epinephrine should be available. Patients who are prescribed epinephrine should be instructed in proper technique for emergency self-injection. Each tablet contains 12 SQ-HDM [6 SQ-HDM Dermatophagoides farinae and 6 SQ-HDM Dermatophagoides pteronyssinus], in a 1:1:1:1 potency ratio of D. farinae group 1 allergen, D. farinae group 2 allergen, D. pteronyssinus group 1 allergen, and D. pteronyssinus group 2 allergen.

1 tablet sublingually once daily. Do not swallow the tablet. Administer the first dose 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 administration. If the patient tolerates the initial dose, subsequent doses can be taken at home; auto-injectable epinephrine should be available. Patients who are prescribed epinephrine should be instructed in proper technique for emergency self-injection. Each tablet contains 12 SQ-HDM [6 SQ-HDM Dermatophagoides farinae and 6 SQ-HDM Dermatophagoides pteronyssinus], in a 1:1:1:1 potency ratio of D. farinae group 1 allergen, D. farinae group 2 allergen, D. pteronyssinus group 1 allergen, and D. pteronyssinus group 2 allergen.

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 House Dust Mite Allergen Extract products.

ODACTRA 12 Sublingual Tablet, SL: 6-6U

1 tablet (12 SQ-HDM)/day sublingually.

65 years: 1 tablet (12 SQ-HDM)/day sublingually.
Older than 65 years: Safety and efficacy have not been established.

1 tablet (12 SQ-HDM)/day sublingually.

12 years: 1 tablet (12 SQ-HDM)/day sublingually.
1 to 11 years: Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

The precise mechanisms of action of house dust mite (HDM) allergen immunotherapy have not been fully established. When house dust mite (HDM) 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.

House dust mite (HDM) allergen extract is administered sublingually. The pharmacokinetics of the extract are not well defined. Limited pharmacokinetic data are available for sublingual immunotherapy in general because allergen extracts do not act on a single receptor or mediator, but rather induce a complex immunological response. However, direct contact with the oral mucosa has been determined to be the critical step in ensuring adequate exposure.
 
Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: None

Pharmacokinetic studies of subjects treated with radiolabeled allergens have demonstrated that the pharmacokinetic values of the sublingual route of administration are independent of the allergen involved. 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 1 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 to 30 minutes and was captured by antigen-presenting cells within 30 to 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 to 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. Trials have showed a relevant dose-dependent increase of allergen-specific IgE levels in all subjects receiving HDM sublingual immunotherapy (SLIT) tablets when compared to subjects receiving placebo. These trials have also found increased levels of IgE-blocking factor (IgE-BF), which has inhibitory activity against circulating IgEs, after 28 days of treatment with more than 4 HDM SLIT tablets.

Available data on house dust mite (HDM) allergen extract administered to pregnant women are insufficient to inform associated risks in pregnancy. In a fetal/embryo developmental toxicity study performed in mice, administration of HDM allergen extract during gestation did not reveal adverse developmental outcomes in fetuses.

Data are not available to assess the effects of house dust mite (HDM) allergen extract on the breast-fed infant or on milk production and excretion in the nursing woman. 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.