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  • CLASSES

    Allergen Specific Immunotherapies

    DEA CLASS

    Rx

    DESCRIPTION

    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

    COMMON BRAND NAMES

    ODACTRA 12

    HOW SUPPLIED

    ODACTRA 12 Sublingual Tablet, SL: 6-6U

    DOSAGE & INDICATIONS

    For the treatment of allergic rhinitis (with or without allergic conjunctivitis) induced by house dust mite (HDM) allergen.
    Sublingual dosage
    Adults 65 years and younger

    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.

    MAXIMUM DOSAGE

    Adults

    1 tablet (12 SQ-HDM)/day SL

    Geriatric

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

    Adolescents

    Safety and efficacy have not been established.

    Children

    Safety and efficacy have not been established.

    Infants

    Safety and efficacy have not been established.

    Neonates

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

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

    Renal Impairment

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

    ADMINISTRATION

    Oral Administration
    Oral Solid Formulations

    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.

    STORAGE

    ODACTRA 12:
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    - Store in original package until time of use

    CONTRAINDICATIONS / PRECAUTIONS

    Angina, atopy, cardiac arrhythmias, fish hypersensitivity, gelatin hypersensitivity, hypertension, mannitol hypersensitivity, myocardial infarction, requires a specialized care setting, serious hypersensitivity reactions or anaphylaxis, sublingual allergen immunotherapy hypersensitivity

    House dust mite (HDM) allergen extract can cause life-threatening allergic reactions, including a risk of serious hypersensitivity reactions or anaphylaxis. Use with great caution in patients with a history of atopy or sublingual allergen immunotherapy hypersensitivity; these patients may be predisposed to severe allergic reactions. HDM allergen extract is contraindicated in patients with a history of severe local reaction to sublingual allergen immunotherapy and/or severe systemic allergic reactions of any type. Additionally, do not use the extract in patients with a hypersensitivity to any of the inactive ingredients present in the product, including those with mannitol hypersensitivity, gelatin hypersensitivity, or fish hypersensitivity (the gelatin is fish-sourced). The use of more than 1 type of immunotherapy (i.e. allergy shots, sublingual immunotherapy) may increase the likelihood of a severe allergic reaction. Concomitant use of HDM allergen extract with other allergen immunotherapy has not been studied; concurrent use may increase the risk of local or systemic reactions to either subcutaneous or sublingual immunotherapy. Systemic allergic reactions including life-threatening anaphylaxis and severe local reactions (e.g., laryngopharyngeal swelling) that may compromise breathing may occur; treatment with epinephrine may be required. Patients who experience a systemic reaction to HDM allergen extract should stop taking the extract immediately. Those who have persistent or escalating local reactions in the mouth or throat should be reevaluated, and discontinuation of the extract should be considered to avoid potential airway compromise. Administration of the first dose requires a specialized care setting due to the risk of severe allergic reactions; give 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 post-dose for signs or symptoms of a severe systemic or local reaction. If the patient tolerates the first dose, subsequent doses may be administered outside of the healthcare setting. Auto-injectable epinephrine should be made available to patients; instruct patients to recognize symptoms of a severe allergic reaction, about the proper use of epinephrine, and to seek immediate medical care upon use. HDM allergen extract may not be suitable for patients with medical conditions that may decrease the patient's ability to survive a serious allergic reaction or increase the risk of adverse reactions after epinephrine administration. These conditions may include, but are not limited to, unstable angina, recent myocardial infarction, significant cardiac arrhythmias, and uncontrolled hypertension. Further, the extract may not be suitable for patients taking medications that can potentiate or inhibit the effects of epinephrine or decrease the effectiveness of inhaled bronchodilators; these medications include beta-adrenergic blockers, alpha-adrenergic blockers, ergot alkaloids, tricyclic antidepressants, levothyroxine, monoamine oxidase inhibitors, chlorpheniramine, diphenhydramine, cardiac glycosides, and diuretics.

    Acute bronchospasm, asthma, chronic lung disease (CLD), chronic obstructive pulmonary disease (COPD), emphysema, pulmonary disease, status asthmaticus

    House dust mite (HDM) allergen extract is contraindicated in patients with severe, unstable, or uncontrolled asthma (e.g., status asthmaticus or acute bronchospasm). Withhold immunotherapy with HDM allergen extract if the patient is experiencing an acute asthma exacerbation. Patients with recurrent asthma exacerbations should be reevaluated for appropriateness of therapy and discontinuation should be considered. The extract may not be suitable for patients who have acute or chronic compromised lung function (e.g., asthma, chronic lung disease (CLD), chronic obstructive pulmonary disease (COPD) such as emphysema, or other serious pulmonary disease) that may reduce the patient's ability to survive a serious allergic reaction or increase the risk of adverse reactions after epinephrine administration. The extract has not been studied in patients with moderate or severe asthma.

    Eosinophilic esophagitis

    House dust mite (HDM) allergen extract is contraindicated in patients with a history of eosinophilic esophagitis. Discontinue the extract in patients who experience severe or persistent gastro-esophageal symptoms (e.g., dysphagia, chest pain) and consider a diagnosis of eosinophilic esophagitis.

    Dental work, inflammation, stomatitis

    Patients with any type of oral inflammation (e.g., oral lichen planus, mouth ulcers or stomatitis, or thrush) or oral wounds, such as those after dental work such as dental extraction or oral surgery, should not receive house dust mite (HDM) allergen extract until complete healing of the oral cavity occurs.

    Pregnancy

    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.

    Breast-feeding

    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.

    Geriatric

    Safety and efficacy have not been established for the use of House Dust Mite (HDM) Allergen Extract in geriatric patients. Some clinical studies allowed for enrollment of patients up to 85 years of age.

    Children, infants

    The safety and efficacy of House Dust Mite (HDM) Allergen Extract have not been established in children or infants less than 18 years of age.

    ADVERSE REACTIONS

    Severe

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

    Moderate

    oral ulceration / Delayed / 10.3-10.3
    stomatitis / Delayed / 2.5-2.5
    dysphagia / Delayed / 1.4-1.4
    chest pain (unspecified) / Early / 1.3-1.3
    esophagitis / Delayed / 0-1.0
    erythema / Early / Incidence not known

    Mild

    throat irritation / Early / 67.0-67.0
    pruritus / Rapid / 1.1-61.0
    nausea / Early / 14.2-14.2
    abdominal pain / Early / 11.3-11.3
    dysgeusia / Early / 10.0-10.0
    paresthesias / Delayed / 9.2-9.2
    diarrhea / Early / 6.9-6.9
    dyspepsia / Early / 2.2-2.7
    vomiting / Early / 2.5-2.5
    ocular pruritus / Rapid / 1.7-1.7
    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

    DRUG INTERACTIONS

    There are no drug interactions associated with House Dust Mite Allergen Extract products.

    PREGNANCY AND LACTATION

    Pregnancy

    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.

    MECHANISM OF ACTION

    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.

    PHARMACOKINETICS

    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

    Oral Route

    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.