Source: FDA, National Drug Code (US) Revision Year: 2021
ORALAIR is contraindicated in patients with:
ORALAIR can cause systemic allergic reactions including anaphylaxis which may be life-threatening. In addition, ORALAIR can cause severe local reactions, including laryngopharyngeal swelling, which can compromise breathing and be life-threatening.
Patients who have a systemic allergic reaction to ORALAIR should stop taking ORALAIR.
Patients who have either escalating or persistent local reactions to ORALAIR should be reevaluated and considered for discontinuation of ORALAIR.
Administer the initial dose of ORALAIR in a healthcare setting under the supervision of a physician prepared to manage a severe
systemic or a severe local allergic reaction. Observe patients in the office for at least 30 minutes following the initial dose of ORALAIR.
Severe and serious allergic reactions may require treatment with epinephrine [See Warnings and Precautions (5.2)].
Prescribe auto-injectable epinephrine to patients receiving ORALAIR. Instruct patients to recognize the signs and symptoms of a severe allergic reaction and in the proper use of emergency self-injection of epinephrine, and instruct patients to seek immediate medical care upon its use [See Patient Counseling Information (17)].
ORALAIR may not be suitable for patients with certain medical conditions that may reduce the ability to survive a serious allergic reaction or increase the risk of adverse reactions after epinephrine administration. Examples of these medical conditions include but are not limited to: markedly compromised lung function (either chronic or acute), unstable angina, recent myocardial infarction, significant arrhythmia, and uncontrolled hypertension.
ORALAIR may not be suitable for patients who are taking medications that can potentiate or inhibit the effect of epinephrine.
These medications include:
Βeta-adrenergic blockers: Patients taking beta-adrenergic blockers may be unresponsive to the usual doses of epinephrine used to treat serious systemic reactions, including anaphylaxis. Specifically, beta-adrenergic blockers antagonize the cardiostimulating and bronchodilating effects of epinephrine.
Alpha-adrenergic blockers, ergot alkaloids: Patients taking alpha-adrenergic blockers may be unresponsive to the usual doses of epinephrine used to treat serious systemic reactions, including anaphylaxis. Specifically, alpha-adrenergic blockers antagonize the vasoconstricting and hypertensive effects of epinephrine. Similarly, ergot alkaloids may reverse the pressor effects of epinephrine.
Tricyclic antidepressants, levothyroxine sodium, monoamine oxidase inhibitors and certain antihistamines: The adverse effects of epinephrine may be potentiated in patients taking tricyclic antidepressants, levothyroxine sodium, monoamine oxidase inhibitors, and the antihistamines chlorpheniramine, and diphenhydramine.
Cardiac glycosides, diuretics: Patients who receive epinephrine while taking cardiac glycosides or diuretics should be observed carefully for the development of cardiac arrhythmias.
Eosinophilic esophagitis has been reported in association with sublingual tablet immunotherapy [See Contraindications (4) and Adverse Reactions (6.2)]. Discontinue ORALAIR and consider a diagnosis of eosinophilic esophagitis in patients who experience severe or persistent gastro-esophageal symptoms including dysphagia or chest pain.
ORALAIR has not been studied in subjects with moderate or severe asthma or any subjects who required daily medication.
Immunotherapy with ORALAIR should be withheld if the patient is experiencing an acute asthma exacerbation. Reevaluate patients who have recurrent asthma exacerbations and consider discontinuation of ORALAIR.
ORALAIR has not been studied in subjects receiving concomitant allergen immunotherapy. Concomitant dosing with other allergen immunotherapy may increase the likelihood of local or systemic adverse reactions to either subcutaneous or sublingual allergen immunotherapy.
Stop treatment with ORALAIR to allow complete healing of the oral cavity in patients with oral inflammation (e.g., oral lichen planus, mouth ulcers or thrush) or oral wounds, such as those following oral surgery or dental extraction.
The risk of ORALAIR may be increased when treatment is initiated during the grass pollen season.
Adverse reactions reported in ≥5% of patients were: oral pruritus, throat irritation, ear pruritus, mouth edema, tongue pruritus, cough, oropharyngeal pain.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rate observed in practice.
Overall, in 6 placebo-controlled clinical trials, 1,038 adults 18 through 65 years of age received at least one dose of ORALAIR 300IR, of whom 611 (59%) completed at least four months of therapy. Of study participants, 56% were male, 17% had a history of mild intermittent asthma at study entry, and 64% were polysensitized. Data on race and ethnicity were not systematically captured in the five European studies (N=805). In the US study (N=233), a limited number of patients reported their race as other than White/Caucasian (Black/African American: 5.6%, Asian: 2.6%, Other: 2.1%) or their ethnicity as Hispanic or Latino (3.0%). Adverse events were captured on a daily diary card that did not solicit for specific adverse events.
Across the six clinical studies, adverse reactions reported at an incidence of ≥2% of ORALAIR recipients and at a greater incidence than that in participants treated with placebo are listed in Table 2.
Table 2. Adverse Reactions Reported by ≥2% of Adults Receiving ORALAIR 300 IR and at a Greater Incidence than that in Participants Treated with Placebo:
| Adverse Reactions | ORALAIR 300 IR (N=1,038) | PLACEBO (N=840) |
|---|---|---|
| Ear and labyrinth disorders | ||
| Ear pruritus | 8.4% | 0.6% |
| Respiratory, thoracic and mediastinal disorders | ||
| Throat irritation | 22.0% | 3.7% |
| Cough | 7.3% | 5.9% |
| Oropharyngeal pain | 5.1% | 3.7% |
| Pharyngeal edema | 3.8% | 0.1% |
| Gastrointestinal disorders | ||
| Oral pruritus | 25.1% | 5.0% |
| Edema mouth | 8.2% | 0.6% |
| Tongue pruritus | 7.9% | 0.7% |
| Lip edema | 4.4% | 0.4% |
| Paraesthesia oral | 4.3% | 1.0% |
| Abdominal pain | 4.2% | 1.3% |
| Dyspepsia | 3.9% | 0.4% |
| Tongue edema | 2.7% | 0.1% |
| Hypoaesthesia oral | 2.2% | 0.1% |
| Stomatitis | 2.1% | 0.7% |
| Skin and subcutaneous tissue disorders | ||
| Urticaria | 2.3% | 1.5% |
Additional adverse reactions of interest that occurred in <2% of ORALAIR recipients include dysphagia, nausea, vomiting, esophageal pain, gastritis, and gastroesophageal reflux.
Overall, in placebo-controlled clinical trials, 154 children and adolescents 5 through 17 years of age received ORALAIR 300 IR, of whom 147 were exposed for more than 3 months. Of study participants, 66% were male, and 21% had a history of mild intermittent asthma at study entry. Data on race and ethnicity were not systematically captured.
The safety profile in the pediatric population, was generally similar to that of adults. In pediatric patients receiving ORALAIR, additional adverse reactions reported at an incidence of ≥2% and at a greater incidence than that in participants treated with placebo are listed in Table 3.
Table 3. Additional Adverse Reactions Reported by ≥2% of Children and Adolescents Receiving ORALAIR 300 IR and at a Greater Incidence than that in Participants Treated with Placebo:
| Adverse Rections | ORALAIR 300 IR (N=154) | PLACEBO (N=158) |
|---|---|---|
| Infections and infestations | ||
| Tonsillitis | 5.8% | 3.2% |
| Upper respiratory tract infection | 3.9% | 1.9% |
| Respiratory, thoracic and mediastinal disorders | ||
| Asthma | 7.1% | 3.8% |
| Dysphonia | 2.6% | 1.3% |
| Gastrointestinal disorders | ||
| Lip pruritus | 3.2% | 0.0% |
| Skin and subcutaneous tissue disorders | ||
| Atopic dermatitis | 3.2% | 0.6% |
An open-label study was conducted to evaluate the 30-day safety profile of ORLAIR in 307 children 5 through 9 years of age. Of study participants, 71% were male and 36% had a history of mild intermittent asthma at study entry. Data on race and ethnicity were not systematically captured. Adverse reactions reported at an incidence of ≥2% were: throat irritation (22.1%), oral pruritus (11.7%), oral paresthesia (11.1%), tongue pruritus (8.1%), mouth edema (6.2%), cough (6.2%), oropharyngeal pain (4.2%), ear pruritus (5.2%), eye pruritus (4.6%), lip edema (3.3%), vomiting (2.6%), tongue edema (2.3%), abdominal pain (2.3%), oral discomfort (2.3%), and ocular hyperemia (2.0%).
At least 1 serious adverse event was reported in 22 of 1514 (1.5%) pediatric and adult subjects from randomized clinical trials who received ORALAIR at any dose, and 11 of 840 (1.1%) of placebo recipients. Of the 22 serious adverse events in the ORALAIR recipients, 2 were considered “definitely related” to ORALAIR.
The first subject was an adult who experienced a severe hypersensitivity reaction which began 5 minutes after administration of ORALAIR. The symptoms were violent coughing and marked dyspnea. The subject was treated with antihistamines, salbutamol and prednisolone and the reaction resolved without sequelae.
The second subject was an adult who experienced severe laryngeal edema. The subject was treated with prednisolone and event resolved without sequelae.
There was also one case of gastroenteritis with an onset on Day 93 of therapy that was possibly related to ORALAIR.
In the open-label study conducted in 307 children 5 through 9 years of age, 2 serious adverse events were considered “likely” related to ORALAIR.
The first subject was an 8-year-old subject with a history of allergic bronchial asthma who developed oral pruritus, conjunctivitis, urticaria and asthma exacerbation 15 minutes after administration of ORALAIR on Day 5. The subject was treated with antihistamines and inhaled salbutamol and the reactions fully resolved in 30 minutes. The subject continued ORALAIR.
The second subject was a 6-year-old subject who developed severe lip, eye and eyelid swelling after administration of ORALAIR on Day 26 of therapy. The subject was treated with intravenous antihistamines and prednisolone. Reaction fully resolved within 6 hours. Treatment with ORALAIR was discontinued.
A total of 1728 individuals (808 adults; 920 children 5 through 17 years of age) received ORALAIR in post marketing safety studies. Reported adverse reactions included: anaphylactic reaction, oral allergy syndrome, flushing, dyspnea, laryngeal edema, and diarrhea.
In addition to adverse reactions reported in clinical and post marketing safety studies, the following adverse reactions have been identified during post approval use of ORALAIR. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: autoimmune thyroiditis, eosinophilic myocarditis, eosinophilic esophagitis, palpitations, tachycardia, hypotension, loss of consciousness, circulatory collapse, malaise, pallor, peripheral vascular disorder, stridor, angioedema, face edema, weight decreased, wheezing, exacerbation of asthma, chest discomfort, oropharyngeal paresthesia, oropharyngeal blistering, headache, dizziness, tinnitus, asthenia, somnolence, anxiety, rash, pruritus, salivary gland enlargement and/or hypersecretion, dry mouth, dry eye, influenza-like syndrome, lymphadenopathy, eosinophil count increased.
All pregnancies have a risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
Available human data do not establish the presence or absence of ORALAIR-associated risks during pregnancy, labor and delivery.
Two developmental toxicity studies were performed in female rats and female rabbits given doses up to 250 IR/day and 3500 IR/day of ORALAIR, respectively, during gestation.
In developmental toxicity studies, the effect of ORALAIR on embryo/fetal development was evaluated in female rats and female rabbits administered with doses up to 250 IR/day and 3500 IR/day of ORALAIR, respectively, by oral gavage on days 6-17 of gestation for rats, and days 6-18 of gestation for rabbits. The human dose is 300 IR/day. There were no ORALAIR-related fetal malformations or other evidence of teratogenesis noted in these studies.
Data are not available to assess the effects of ORALAIR on the breastfed child or on milk production/excretion. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ORALAIR and any potential adverse effects on the breastfed child from ORALAIR or from the underlying maternal condition.
The safety and effectiveness of ORALAIR have not been established in children below 5 years of age.
ORALAIR has not been studied in patients over 65 years of age.
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