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    All Other Respiratory System Products

    BOXED WARNING

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

    Short ragweed pollen allergen extract is contraindicated in patients with severe, unstable, or uncontrolled asthma (e.g., status asthmaticus or acute bronchospasm). 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), or emphysema) 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.

    DEA CLASS

    Rx

    DESCRIPTION

    Oral, sublingual immunotherapy
    For allergic rhinitis with or without conjunctivitis that is induced by short ragweed pollens
    First dose given in health care provider's office to allow for patient observation for potential adverse reactions

    COMMON BRAND NAMES

    RAGWITEK

    HOW SUPPLIED

    RAGWITEK Oral Tablet, SL

    DOSAGE & INDICATIONS

    For the treatment of allergic rhinitis (with or without allergic conjunctivitis) induced by short ragweed pollen.
    Sublingual dosage
    Adults <= 65 years

    1 tablet (12 Amb a 1-Unit [arbitrary measurement of major allergen]) SL once daily. 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.

    MAXIMUM DOSAGE

    Adults

    1 tablet (12 Amb a 1-Unit)/day SL

    Geriatric

    65 years: 1 tablet (12 Amb a 1-Unit)/day SL
    > 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. Wait until the tablet is completely dissolved (at least 1 minute) before swallowing.
    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

    RAGWITEK:
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    - Store in original package until time of use

    CONTRAINDICATIONS / PRECAUTIONS

    Angina, atopy, cardiac arrhythmias, gelatin hypersensitivity, hypertension, mannitol hypersensitivity, myocardial infarction, requires a specialized care setting, sublingual allergen immunotherapy hypersensitivity

    Short ragweed pollen allergen extract can cause life-threatening allergic reactions. 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. The use of more than one type of immunotherapy (i.e. allergy shots, sublingual immunotherapy) may increase the likelihood of a severe allergic reaction. Short ragweed pollen 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 sodium hydroxide hypersensitivity. 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 short ragweed pollen 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. Short ragweed pollen 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. Concomitant use of short ragweed pollen 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.

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

    Short ragweed pollen allergen extract is contraindicated in patients with severe, unstable, or uncontrolled asthma (e.g., status asthmaticus or acute bronchospasm). 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), or emphysema) 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

    Short ragweed pollen 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

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

    Pregnancy

    Adequate and well-controlled studies with the short ragweed pollen allergen extract have not been conducted in pregnant women, and animal reproduction studies have not been performed. The short ragweed pollen 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.

    Breast-feeding

    According to the manufacturer, short ragweed pollen allergen extract should be used with caution in breast-feeding women. It is not known if the extract is excreted into human breast milk. 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.

    ADVERSE REACTIONS

    Severe

    anaphylactoid reactions / Rapid / Incidence not known
    anaphylactic shock / Rapid / Incidence not known
    angioedema / Rapid / Incidence not known

    Moderate

    edema / Delayed / 1.1-6.1
    dysphagia / Delayed / 1.0-1.0
    chest pain (unspecified) / Early / 1.0-1.0
    esophagitis / Delayed / Incidence not known

    Mild

    throat irritation / Early / 16.6-16.6
    pruritus / Rapid / 1.5-10.9
    paresthesias / Delayed / 10.0-10.0
    xerostomia / Early / 1.4-1.4
    nausea / Early / 1.1-1.1

    DRUG INTERACTIONS

    There are no drug interactions associated with Short Ragweed Pollen Allergen Extract products.

    PREGNANCY AND LACTATION

    Pregnancy

    Adequate and well-controlled studies with the short ragweed pollen allergen extract have not been conducted in pregnant women, and animal reproduction studies have not been performed. The short ragweed pollen 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.

    According to the manufacturer, short ragweed pollen allergen extract should be used with caution in breast-feeding women. It is not known if the extract is excreted into human breast milk. 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

    When short ragweed pollen 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

    Short ragweed pollen allergen extract is administered sublingually. The pharmacokinetics of the extract are not well defined. 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