RAGWITEK

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. 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.

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

oral ulceration / Delayed / 6.8-8.4
edema / Delayed / 1.1-6.1
dysphagia / Delayed / 1.0-1.6
chest pain (unspecified) / Early / 1.0-1.0
esophagitis / Delayed / Incidence not known
dysphonia / Delayed / Incidence not known
erythema / Early / Incidence not known

throat irritation / Early / 7.6-48.3
pruritus / Rapid / 1.2-47.8
nausea / Early / 1.1-11.5
abdominal pain / Early / 10.1-10.1
paresthesias / Delayed / 1.9-10.0
dysgeusia / Early / 3.9-3.9
diarrhea / Early / 2.7-2.7
sneezing / Early / 1.6-1.6
xerostomia / Early / 1.4-1.4
vomiting / Early / 1.2-1.2
rhinorrhea / Early / 1.2-1.2
urticaria / Rapid / Incidence not known
gastroesophageal reflux / Delayed / Incidence not known
dyspepsia / Early / Incidence not known
hypoesthesia / Delayed / Incidence not known
cough / Delayed / Incidence not known

RAGWITEK

Rx

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

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.

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.

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 Short Ragweed Pollen Allergen Extract products.

RAGWITEK Oral Tablet, SL

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

65 years: 1 tablet (12 Amb a 1-Unit)/day SL
older than 65 years: Safety and efficacy have not been established.

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

5 to 12 years: 1 tablet (12 Amb a 1-Unit)/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 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

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.