Grastek

SIDE EFFECTS

Adverse reactions reported in ≥5% of patients were: ear pruritus, oral pruritus, tongue pruritus, mouth edema, and throat irritation.

Clinical Trials Experience

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 rates observed in clinical practice.

Adults

The safety data described below are based on 6 clinical trials which randomized 3589 subjects 18 through 65 years of age with Timothy grass pollen induced rhinitis with or without conjunctivitis, including 1669 subjects who were exposed to at least one dose of GRASTEK. Of the subjects treated with GRASTEK, 25% had mild asthma and 80% were sensitized to other allergens in addition to grass. The subject population was 88% White, 7% African American, and 3% Asian. Subjects were 52% male, and 88% of subjects were between 18 and 50 years of age. Subject demographics in placebo-treated subjects were similar to the active group.

The most common adverse reactions reported in subjects treated with GRASTEK were oral pruritus (26.7% vs 3.5% placebo), throat irritation (22.6% vs 2.8%), ear pruritus (12.5% vs 1.1%) and mouth edema (11.1% vs 0.8%). The percentage of subjects who discontinued from the clinical trials because of an adverse reaction while exposed to GRASTEK or placebo was 4.9% and 0.9%, respectively. The most common adverse reactions that led to study discontinuation in subjects who were exposed to GRASTEK were pharyngeal edema and oral pruritus.

Seven adult subjects (7/1669; 0.4%) who received GRASTEK experienced treatment-related systemic allergic reactions that led to discontinuation of GRASTEK in four out of the seven subjects.

• Five of the seven subjects had reactions on Day 1 of treatment with GRASTEK. Symptoms included swelling of lips/mouth; oral/pharyngeal itching; ear itching, sneezing, rhinorrhea, throat irritation, dysphonia, dysphagia, chest discomfort, and rash. Three of the five subjects received treatment with epinephrine and antihistamines, and one of the three also received oral corticosteroids. One of the five subjects who had a reaction on Day 1 of treatment with GRASTEK also had a reaction on Day 2 of treatment with GRASTEK. Symptoms on Day 2 included oral burning sensation; rhinorrhea; and throat irritation.
• One of the seven subjects had a reaction on Day 2 after tolerating treatment with GRASTEK on Day 1. Symptoms included edema of the lower lip, epigastric discomfort and dizziness.
• One of the seven subjects developed chest tightness and shortness of breath on Day 42 of treatment with GRASTEK.

Adverse reactions reported in ≥1% of subjects treated with GRASTEK are shown in Table 1.

Table 1: Adverse Reactions Reported in ≥1% of Adults Treated with GRASTEK

Adverse reactions of interest that occurred in ≤1% of GRASTEK recipients include abdominal pain and gastroesophageal reflux.

Pediatrics

Safety data are based on 3 clinical trials which randomized 881 subjects between 5 and 17 years of age with grass pollen induced rhinitis with or without conjunctivitis. Overall, 445 subjects received at least one dose of GRASTEK. Of the subjects treated with GRASTEK, 31% had mild asthma and 86% were sensitized to other allergens in addition to grass. The subject population was 86% White, 7% African American and 3% multi-racial. The majority (66%) of subjects were male. The mean age of subjects was 11.7 years. Subject demographics in placebo-treated subjects were similar to the active group.

The most common adverse reactions in pediatric subjects treated with GRASTEK were oral pruritus (24.4% vs 2.1% placebo), throat irritation (21.3% vs 2.5%) and mouth edema (9.8% vs 0.2%). The percentage of subjects who discontinued from the clinical trials because of an adverse reaction while exposed to GRASTEK or placebo was 6.3% and 0.7%, respectively.

One pediatric subject (1/447; 0.2%) who received GRASTEK experienced a treatment-related systemic allergic reaction consisting of lip angioedema, slight dysphagia due to the sensation of a lump in the throat, and intermittent cough which was of moderate intensity on Day 1. The subject was treated with epinephrine, recovered, and was discontinued from the trial.

Adverse reactions reported in ≥1% of subjects treated with GRASTEK are shown in Table 2.

Table 2: Adverse Reactions Reported in ≥1% of Pediatric Subjects Treated with GRASTEK

Postmarketing Experience

Postmarketing Safety Studies

In European post-approval studies which included 1,666 patients treated with GRASTEK (marketed under the name GRAZAX), reported serious adverse reactions assessed as related to GRASTEK use included anaphylactic reaction, asthma exacerbation, hoarseness, laryngitis, oral ulceration, and ulcerative colitis exacerbation.

Spontaneous Postmarketing Reports

The following adverse reactions have been identified during post-approval use of GRASTEK (marketed under the name GRAZAX in Europe). 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. These include: altered state of consciousness, anaphylactic shock, angioedema, asthma exercise induced, chest pressure, diarrhea, difficulty speaking, dizziness, drowsiness, enlarged uvula, eosinophilic esophagitis, erythema facial, face edema, forced expiratory volume decreased, heart rate increased, heart rate irregular, hyperventilation, hypotension, laryngeal discomfort, oral pain, oxygen saturation decreased, peak expiratory flow rate decreased, pneumonia, rash, respiratory distress, sensation of foreign body, status asthmaticus, swelling of neck, throat pruritus, tremor, vital capacity decreased, vomiting, and wheezing. Included in these reports was an adult male with asthma who experienced anaphylactic shock within two minutes of administration of GRASTEK. The patient experienced depressed level of consciousness, hypotension, increased heart rate, wheezing, urticaria, and face edema.

Eosinophilic esophagitis has been reported following treatment with GRASTEK (marketed under the name GRAZAX). The clinical details of some postmarketing reports are consistent with a drug-induced effect, including at least one case with resolution of symptoms upon discontinuation of GRASTEK, relapse after resuming GRASTEK and resolution again after discontinuation of GRASTEK.

Read the entire FDA prescribing information for Grastek (Timothy Grass Pollen Allergen Extract Tablets)