Allergen extracts, Grass pollen

Lyophilisate

Standardised allergen extract of grass pollen from Timothy (Phleum pratense) 75,000 SQ-T* per oral lyophilisate. * [Standardised Quality units Tablet (SQ-T)]

Oral lyophilisate White to off-white circular oral lyophilisate marked with a debossed image on one side.

Treatment of grass pollen induced rhinitis and conjunctivitis in adults and children (5 years or older) with clinically relevant symptoms and diagnosed with a positive skin prick test and/or specific IgE test to grass pollen. Children should be carefully selected for treatment

The recommended dose for adults and children (5 years or older) is one oral lyophilisate (75,000 SQ-T) daily. Clinical experience on immunotherapy with Grazax in children (younger than 5 years) and the elderly (65 years or older) is lacking.

Grazax treatment should only be initiated by physicians with experience in treatment of allergic diseases and the capability to treat allergic reactions.

For treatment of children physicians should be experienced in treating allergic diseases in children and the patients should be carefully selected considering the expected level of efficacy in this age group.

In order to enable patient and physician to discuss any side effects and possible actions it is recommended that the first oral lyophilisate is taken under medical supervision (20-30 minutes).

Efficacy data on treatment with Grazax for two years of continuous treatment is available in adult patients. If no relevant improvement of symptoms is observed during the first pollen season, there is no indication for continuing the treatment.

No data on treatment with Grazax in children beyond one grass pollen season is available.

Clinical effect in the first grass pollen season is expected when treatment is initiated at least 4 months prior to the expected start of the grass pollen season. If treatment is initiated 2-3 months before the season some efficacy may also be obtained. Continuous daily treatment with Grazax in adult patients for, at least 2 years resulted in a progressive immunomodulatory effect. It is recommended to continue treatment with Grazax for a period of 3 years.

Grazax is an oral lyophilisate. The oral lyophilisate should be taken from the blister unit with dry fingers, and placed under the tongue, where it will disperse.

Swallowing should be avoided for about 1 minute. Food and beverage should not be taken for the following 5 minutes.

The oral lyophilisate should be taken immediately after opening the blister.

Hypersensitivity to any of the excipients.

Malignancy or systemic diseases affecting the immune system e.g. autoimmune diseases, immune complex diseases or immune deficiency diseases.

Inflammatory conditions in the oral cavity with severe symptoms such as oral lichen planus with ulcerations or severe oral mycosis.

Patients with uncontrolled or severe asthma (in adults: FEV₁ < 70% of predicted value after adequate pharmacologic treatment; in children: FEV₁ <80% of predicted value after adequate pharmacologic treatment) should not be treated with Grazax immunotherapy.

In case of oral surgery, including dental extraction and shedding of a deciduous tooth in children, treatment with Grazax should be stopped for 7 days to allow healing of the oral cavity.

In children with concomitant asthma and experiencing an acute upper respiratory tract infection, Grazax treatment should be temporarily discontinued until the infection has resolved.

When treated with Grazax the patient is exposed to the allergen that causes the allergic symptoms. Therefore, primarily mild or moderate local allergic reactions are to be expected during the treatment period. If the patient experiences significant local adverse reactions from the treatment, anti-allergic medication (e.g. antihistamines) should be considered.

In post marketing experience, rare cases of severe systemic allergic reactions have been reported and therefore the medical supervision at start of treatment is an important precaution.

The onset of systemic symptoms may include flushing, intensive itching in palms of hand and soles of the feet, and other areas of the body (like a nettle rash). Sense of heat, general discomfort and agitation/anxiety may also occur. In case of severe systemic reactions, angioedema, difficulty in swallowing, difficulty in breathing, changes in voice, hypotension or feeling of fullness in the throat a physician should be contacted immediately. In such cases treatment should be discontinued permanently or until otherwise advised by the physician.If patients with concomitant asthma experience symptoms and signs indicating asthma deterioration, treatment should be discontinued and a physician consulted immediately in order to evaluate the continuation of treatment.

In patients who have previously had a systemic reaction to grass pollen subcutaneous immunotherapy, the risk of experiencing a severe reaction with Grazax may be increased. Initiation of Grazax should be carefully considered and measures to treat reactions should be available.

Severe allergic reactions may be treated with adrenaline. The effects of adrenaline may be potentiated in patients treated with tricyclic antidepressants and monoamine oxidase inhibitors (MAOIs) with possible fatal consequences; this should be taken into consideration prior to initiating specific immunotherapy.

Clinical experience in relation to simultaneous vaccination and treatment with Grazax is missing. Vaccination may be given without interrupting treatment with Grazax after medical evaluation of the general condition of the patient.

Grazax contains fish-derived gelatine. The available data have not indicated an increased risk of allergic reactions in severe fish allergic patients. However, awareness is suggested when initiating treatment with Grazax in these patients

Concomitant therapy with symptomatic anti-allergic agents (e.g. antihistamines, corticosteroids and mast cell stabilisers) may increase the tolerance level of the patient to immunotherapy.

There are no data available on possible risks of simultaneous immunotherapy with other allergens during treatment with Grazax.

In studies investigating treatment with Grazax 75,000 SQ-T daily in adult patients, 70% of the patients receiving Grazax reported side effects during the first treatment year. This number decreased markedly in the second year of continuous treatment.

Very commonly reported adverse reactions in adult patients, with seasonal grass pollen induced allergic rhinoconjunctivitis, treated with Grazax were local allergic reactions in the mouth which mostly were mild to moderate. In the majority of patients these reactions started early in therapy, lasted from minutes to hours after each intake of Grazax and tended to subside spontaneously within 1 to 7 days.

The following Table of undesirable effects is based on data from controlled clinical trials investigating Grazax in adult patients with seasonal grass-pollen induced rhinoconjunctivitis including patients with mild to moderate co-existing grass-pollen induced asthma, during the first treatment year.

Adverse reactions are divided into groups according to the MedDRA- Convention frequencies: Very common (>1/10), Common (>1/100, <1/10), Uncommon (>1/1,000, <1/100), and Rare (>1/10,000, <1/1,000).

If the patient experiences significant adverse events from the treatment, anti-allergic medication should be considered.

In post marketing experience, rare cases of severe systemic allergic reactions have been reported and therefore the medical supervision at start of treatment is an important precaution.

In case of severe systemic reactions, angioedema, difficulty in swallowing, difficulty in breathing, changes in voice, hypotension or feeling of fullness in the throat a physician should be contacted immediately. In such cases treatment should be discontinued permanently or until otherwise advised by the physician.

Experience in children

Overall, the adverse events profile in children and adolescents treated with Grazax was similar to that observed in adults. Upper respiratory tract infections, abdominal pain, vomiting and swollen lips were reported more frequently in the paediatric population than in the adult population (all common).

ALK-Abello Ltd

(POM)

01 July 2009