Short ragweed pollen allergen extract is a sublingual immunotherapy (SLIT) approved for the treatment of allergic rhinitis with or without conjunctivitis that is induced by short ragweed pollen in pediatric and adult patients aged 5 to 65 years. Short ragweed is a prevalent seasonal allergen in much of North America and a major cause of seasonal allergies during the autumn months. Standard therapy for allergic rhinitis consists of allergen avoidance as well as pharmacotherapy (e.g., antihistamines, leukotriene antagonists, intranasal corticosteroids) for symptom management. Allergen immunotherapy modifies the disease process and is used in patients who are not adequately controlled with environmental or medication changes. In general, SLIT is associated with fewer serious adverse reactions than subcutaneous immunotherapy; however, experience with SLIT in patients with severe asthma, a population that may be more likely to experience serious reactions, is limited. Most adverse reactions to SLIT are local and transient and do not require treatment discontinuation. However, as with any immunotherapy, severe systemic and local allergic reactions (e.g., anaphylaxis, laryngopharyngeal swelling) are possible. After administration of the first dose at the health care provider's office, where the patient can be observed for potential adverse reactions, short ragweed pollen allergen extract can be taken at home. Short ragweed pollen allergen extract was approved by the FDA in April 2014.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific 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.
Short ragweed pollen extract may cause gastrointestinal adverse reactions. Abdominal pain (10.1% pediatric patients), nausea (1.6% to 11.5% pediatric patients; 1.1% adults), diarrhea (2.7% pediatric patients), and vomiting (1.2% pediatric patients) were reported during clinical trials.
As with all immunotherapy, short ragweed pollen allergen extract can cause life-threatening serious hypersensitivity reactions or anaphylaxis, including anaphylactoid reactions, severe angioedema (e.g., laryngopharyngeal edema), and anaphylactic shock. In general, severe allergic reactions appear to be less common with sublingual immunotherapy (SLIT) than with subcutaneous immunotherapy; however, it should be noted that SLIT has not been studied in as many high-risk patients. During trials, oral pruritus (7.8% to 47.8% pediatric patients; 10.9% adults), tongue pruritus (4.5% pediatric patients; 5.1% adults), lip pruritus (1.5% adults), and ear pruritus (4.5% to 33.9% pediatric patients; 10.4% adults) were reported. Throat irritation and/or tickle (7.6% to 48.3% pediatric patients; 16.6% adults) was another common adverse reaction. During clinical trials, 3.9% of pediatric patients discontinued therapy due to an adverse reaction compared to 1% placebo with throat irritation being the most common reaction that lead to study discontinuation. Mouth edema (6.1% adults), lip swelling (1.9% to 13.8% pediatric patients; 3% adults), swollen tongue (1.4% to 11.3% pediatric patients; 2.9% adults), throat swelling (10.7% pediatric patients), mouth swelling (1.8% pediatric patients), tongue edema (1.3% adults), palatal edema (1.1% adults), pharyngeal edema (1.2% pediatric patients), dysphagia (1.6% pediatric patients; 1% adults), throat tightness (1.3% adults), pruritus (type unspecified, 1.2% pediatric patients; 1.8% adults), and chest pain (unspecified) or chest discomfort (1% adults) were reported during clinical trials. One pediatric patient (0.2%) reported severe intensity of swelling of the tongue. Swelling of the uvula/back of the mouth, which included patients with an enlarged uvula, palatal swelling/edema, and/or mouth swelling/edema (which was not limited to the back of the mouth, but could be anywhere in the mouth) was reported in 9.9% of pediatric patients. Sudden onset of symptoms such as these are characteristic of anaphylaxis; monitor patients closely. In clinical trials, 1 adult patient (0.1%) experienced a severe systemic allergic reaction that led to treatment discontinuation. On day 1 of treatment, the patient developed local reactions which progressed to throat swelling, dyspnea, nausea, and lightheadedness on day 6. Epinephrine, antihistamines, and oral corticosteroids were given with subsequent full recovery. Oral pruritus is common with oral immunotherapy and not necessarily a symptom of anaphylaxis. In pediatric clinical trials, 3 patients (0.6%) treated with short ragweed pollen allergen extract and 1 (0.2%) receiving placebo experienced treatment-related systemic allergic reactions. The first patient reported hypersensitivity events (skin/face/neck itching, eye itching/swelling, sneezing, runny/itching nose, neck/abdomen redness) beginning on day 6 that resolved by day 26. The events resolved within minutes to less than an hour and on 2 occasions the patient was treated with an antihistamine. Treatment was subsequently discontinued on day 34 due to persistent local allergic symptoms (swollen tongue). The second patient reported hypersensitivity (generalized rash on body and face) on day 26 and was treated with an antihistamine and systemic corticosteroids. The reaction resolved in 1 week, but the patient discontinued treatment. The third patient reported pruritus (on cheeks, arms, and legs) and dyspnea on day 1 after administration of the first dose. Both adverse events resolved within 2 hours without treatment, did not reoccur upon restarting the trial 1 week later, and the patient completed the trial. Another patient experienced severe laryngitis on day 126 and was hospitalized and treated with inhaled racemic epinephrine; the laryngitis resolved in 2 days. Urticaria and dry throat have been reported during postmarketing use. Advise patients who experience a systemic allergic reaction to stop taking the extract immediately. Reevaluate those who have persistent or escalating local reactions for appropriateness of therapy and consider extract discontinuation. 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 patients for at least 30 minutes after sublingual administration to monitor for signs and symptoms of a severe allergic reaction. If the first dose is tolerated, subsequent doses may be administered at home. Auto-injectable epinephrine should be available to all patients. Educate patients and their caregivers about the signs and symptoms of severe allergic reactions, the proper use of auto-injectable epinephrine, and the need to seek immediate medical attention upon epinephrine use.
Oropharyngeal pain (1.8% pediatric patients; 1.5% adults), oral pain (1.6% pediatric patients), mouth pain (18.9% pediatric patients), oral paresthesias (1.9% pediatric patients; 10% adults), oral ulceration including mouth ulcer/sore (8.4% pediatric patients) and tongue ulcer/sore (6.8% pediatric patients), xerostomia (1.4% adults), and taste alterations/dysgeusia (3.9% pediatric patients) occurred during clinical trials of short ragweed pollen allergen extract. Eosinophilic esophagitis has been reported with sublingual tablet immunotherapy. Glossodynia, gastroesophageal reflux disease, dyspepsia, oral hypoesthesia, paresthesia, ear discomfort, and ear pain have been reported during postmarketing use. Discontinue extract therapy in patients who experience severe or persistent gastroesophageal symptoms (e.g., dysphagia, chest pain).
Dysphonia and sensation of foreign body have been reported during postmarketing use of short ragweed pollen allergen extract.
Sneezing (1.6%) and rhinorrhea (1.2%) have been reported in pediatric patients receiving short ragweed pollen allergen extract in clinical trials. Asthma exacerbation, cough, and pharyngeal erythema have been reported during postmarketing use of short ragweed pollen allergen extract.
Short ragweed pollen 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. 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.
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.
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.
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.
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.
-Hypersensitivity to short ragweed pollen should be confirmed by positive skin test or in vitro testing for pollen-specific IgE antibodies before administering.
-Initiate treatment at least 12 weeks prior to the expected onset of each ragweed pollen season and continue throughout the season.
-Safety and efficacy data regarding starting treatment during the ragweed pollen season are not available. Safety data regarding restarting treatment after missing a dose are limited; during clinical trials, treatment interruptions for up to 7 days were allowed.
For the treatment of allergic rhinitis (with or without allergic conjunctivitis) induced by short ragweed pollen:
Sublingual dosage:
Adults 18 to 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.
Children and Adolescents 5 to 17 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 Limits:
-Adults
1 tablet (12 Amb a 1-Unit)/day SL
-Geriatric
65 years: 1 tablet (12 Amb a 1-Unit)/day SL
older than 65 years: Safety and efficacy have not been established.
-Adolescents
1 tablet (12 Amb a 1-Unit)/day SL
-Children
5 to 12 years: 1 tablet (12 Amb a 1-Unit)/day SL
1 to 4 years: Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
There are no drug interactions associated with Short Ragweed Pollen Allergen Extract products.
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.
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