Consumer medicine information

Actair

American house dust mite extract; European house dust mite extract

BRAND INFORMATION

Brand name

Actair

Active ingredient

American house dust mite extract; European house dust mite extract

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Actair.

What is in this leaflet

This leaflet answers some common questions about Actair Initiation Treatment and Actair Continuation Treatment sublingual tablets.

It does not contain all the available information.

It does not take the place of talking to your doctor.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking Actair against the expected benefits it will have for you.

If you have any concerns about taking this medicine, ask your doctor.

What is Actair used for

Actair contains a 50% mixture of allergen extracts from 2 species of house dust mite. The treatment with Actair is intended to increase the immunological tolerance towards house dust mites, and thereby reducing the allergic symptoms.

Actair is used for the treatment of house dust mite allergies that are characterised by rhinitis (sneezing, runny or itchy nose, nasal congestion) with or without conjunctivitis (itchy and watery eyes) in adults and adolescents over 12 years.

Before treatment, the allergy is confirmed by a doctor with adequate training and experience in allergic diseases, who will perform the appropriate skin and/or blood tests.

The house dust mites that Actair is used for are: European house dust mite (Dermatophagoides pteronyssinus) and American house dust mite (Dermatophagoides farinae).

How it works:

Treatment with Actair is intended to increase the immunological tolerance towards house dust mites, thereby building immunity to the specific allergens in house dust mites, thus helping to reduce the allergic symptoms.

Ask your doctor if you have any questions why Actair has been prescribed for you.

Actair is not addictive.

This medicine is available only with a doctor’s prescription.

Before you are given Actair

Do not take Actair:

  • if you are hypersensitive (allergic) to any of the other ingredients of Actair;
  • if you suffer from severe and/or unstable asthma;
  • if your immune system is very weakened or if you suffer from a disease that attacks your own immune system;
  • if you suffer from a malignant disease (for example cancer);
  • if you have any inflammation in your mouth (for example mouth ulcers, bleeding gums).

If you are not sure if you should be taking Actair, talk to your doctor.

Before you start your treatment with Actair:

Take special care with Actair:

If you have to undergo surgery in the mouth or if you are having a tooth pulled, you should stop the treatment with Actair for 7 days to allow your oral cavity to heal. Thereafter, restart the treatment with the previous dosage. If you stopped the treatment for more than 7 days, please ask your doctor how you should restart the treatment.

Talk to your doctor if:

  • you have any history of allergic inflammation of the oesophagus (eosinophilic oesophagitis). During treatment with Actair, if you have severe or persistent upper abdominal pain, swallowing difficulties or chest pain, please contact your doctor who may reconsider your treatment.
  • you are taking a beta blocker (i.e., a class of drugs often prescribed for heart conditions and high blood pressure but also present in some eye drops and ointments), as this drug may decrease the effectiveness of adrenaline, a medicine used to treat serious allergic reactions.

Taking other medicines

Tell your doctor if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

Pregnancy and breast-feeding

Ask your doctor for advice before taking any medicine.

At present there is no experience for the use of Actair during pregnancy. Therefore, you should not start immunotherapy if you are pregnant. If you become pregnant, speak to your doctor about whether it is appropriate for you to continue treatment.

There is no experience for the use of Actair during breast-feeding as well. No effects on infants who are breast-fed during treatment are anticipated. However, you should not start immunotherapy if you are breast-feeding. If you wish to breastfeed while on treatment, speak to your doctor about whether it is appropriate for you to continue treatment.

Driving and using machines

No effect on the capacity to drive or use machines has been observed with Actair.

Important information about some of the ingredients of Actair

This medicine contains lactose. If you have been told by your doctor that you have intolerance to some sugars, contact your doctor before taking this medicinal product.

Your doctor will advise you.

Your doctor has more information on medicines to be careful with or avoid while taking Actair.

If necessary, your doctor may at the same time prescribe medications to treat the possible allergic reactions.

How Actair is given

Always take Actair exactly as your doctor has told you. Check with your doctor if you are not sure.

Actair is prescribed by doctors with adequate training and experience in treatment of allergy. With prescriptions for adolescents over 12 years, the doctor will have the relevant experience in the treatment of patients in this age group.

You are advised to take the first tablet under medical supervision and be monitored for 30 minutes. This gives you the possibility of discussing possible side effects with your doctor.

Dosage

Adults and adolescents over 12 years
The therapy is composed of an initiation treatment (including a 3-day dose escalation) and a continuation treatment.

Initiation Treatment:

The pack corresponding to the initiation treatment contains two or four blisters:

  • One small blister with 3 tablets of 100 IR
  • One large blister with 28 tablets of 300 IR or three large blisters with respectively 28, 30 and 30 tablets of 300 IR

Method of administration

Take one 100 IR tablet on day one. Keep the tablet under your tongue until it is completely disintegrated before you swallow. On the second day of treatment, two 100 IR tablets must be placed under the tongue simultaneously and then swallowed.

It is recommended that the tablets be taken during the day. You should have no food or drink in your mouth at the same time you are taking the medicine.

Use the following dosing scheme:

Always start with the small blister:

Continuation Treatment:

The pack corresponding to the continuation treatment contains large blister strip with 30 or 90 tablets of 300IR sublingual tablets

The treatment must be continued with 1 tablet of 300 IR once a day from the Actair continuation treatment which contains 300 IR sublingual tablets only.

Do not halve the tablet. Tablet is to be taken whole.

Duration of treatment

Start your Actair treatment on the day determined by your doctor.

Take these tablets as prescribed by your doctor until the end of the treatment course.

After one year of treatment, efficacy has been shown to be maintained in the following year without treatment.

There is no experience with Actair in children younger than 5 years and in patients over 65 years of age.

How long should Actair be taken for?

Actair is started on the day determined by your doctor. It is recommended to maintain the treatment all year round.

Each year your doctor will assess if it is suitable for you to continue Actair treatment.

If you take more Actair than you should

Higher doses may be associated with reduced tolerability and may potentially increase the risk of serious allergic reactions.

In the event of overdose you may need medical treatment.

Contact the Poisons Information Centre on (13 11 26 in Australia and 0800 POISON (0800 764 766) in New Zealand) for advice on the management of overdose.

If you forget to take Actair

Do not take a double dose to make up for forgotten dose.

If you interrupted the treatment with Actair for less than one week, you can take up treatment where you left off.

If you stop taking Actair

If you stop taking Actair, you may not have an effect of the treatment.

If you interrupt treatment for longer than 7 days, you should ask your doctor before restarting treatment

If you have any further questions on the use of this product, ask your doctor.

While you are receiving Actair

Things you must do

Tell all doctors, dentists and pharmacists who are treating you, that you are receiving Actair.

Tell your doctor if you feel the treatment is not helping your condition.

If you experience any infection or inflammation in the mouth or if you experience an increase in asthma or allergy symptoms, ask your doctor for advice before continuing treatment with Actair.

Side effects

Actair helps people with allergies to the house dust mites allergen extracts of the product but they may have unwanted side effects in a few people.

All medicines can have side effects. Sometimes they may be serious, most of the time they are not. You may need medical treatment if you get some of these side effects.

Contact your doctor or nurse immediately if symptoms of an allergic reaction occur.

During treatment with Actair, you will be exposed to substances that may cause application site reactions and/or symptoms, which affect the whole body. You may experience application site reactions (such as itching of the mouth and throat irritation).

Stop taking ACTAIR and contact your doctor immediately if you develop or notice:

Allergic symptoms that affect the whole body (i.e. rapid onset of an illness associated with involvement of the skin and/or mucosa, breathing difficulty, abdominal pain or symptoms related to a drop in blood pressure).

Other possible side effects include the following:

Very common (affects more than 1 in 10 people)

  • Throat irritation, itchy mouth, swelling mouth, itchy ears

Common (affects less than 1 in 10 people):

  • Inflammation in the eyes, itchy eyes, watery eyes
  • Swelling tongue, itchy tongue, inflammation of the tongue
  • Swelling or itching or blistering of lips,
  • Formation of blisters in the mouth, uncomfortable feeling in the mouth or throat, tingling or numbness in the mouth, Decreased sensitivity in the mouth, Inflammation in the mouth with or without ulcers, pain in the mouth,
  • Pain in the throat, swelling in the throat, sensation of dryness in throat.
  • Difficulty in swallowing
  • Ear pain
  • Sinus congestion
  • Cough
  • Breathing difficulty, chest discomfort, asthma, bronchospasm
  • Nausea, abdominal pain, diarrhoea
  • Itching, dry skin, abnormal skin sensations

Uncommon (affects less than 1 in 100 people):

  • Eyelid spasm
  • Rhinitis (stuffy nose, runny nose, sneezing, , nasal discomfort ),
  • Dry mouth
  • Inflammation of the nose and throat, Throat tightness
  • Gum swelling, gum pain, swelling of palate
  • Salivary gland enlargement, increased production of saliva
  • Wheezing
  • Chest pain,
  • Serious allergic reaction with swelling of the face and throat (angioedema)
  • Headache
  • Tiredness, malaise
  • Bad breath, heartburn, vomiting, bowel disorders
  • Increased heartbeat rhythm
  • Anxiety, Sleepiness
  • Muscle spasms
  • Rash, urticaria, blisters
  • Abnormalities in morphology or count of blood cells or in biological parameters

Side effects in children and adolescents
In children and adolescents, malaise was reported at a higher incidence than in adults. In patients of this age group, oral disorder, bronchitis, enterocolitis, candida infection, seborrhoea and ear disorder were also reported as uncommon (affects less than 1 in 100 people).

Additional side effects experienced with similar products

Cases of oesophageal inflammation have been reported with other sublingual immunotherapy products.

These do not represent all possible adverse drug reactions. For a full list of all reported adverse drug reactions refer to the Australian Product Information, New Zealand Data Sheet or Doctor.

After using Actair

Storage

  • Keep it where children cannot reach it
  • Keep it in the original pack in order to protect from moisture
  • Keep it below 30ºC.
  • Do not use if past the expiry date which is stamped on the carton side panel

Product Description

Actair Initiation Treatment sublingual tablets 100 IR and 300 IR contain a small blister with 3 tablets of 100 IR concentration and a large blister with 28 tablets of 300 IR concentration

OR

Actair Initiation Treatment sublingual tablets 100 IR and 300 IR contain a small blister with 3 tablets of 100 IR concentration and a three large blisters with respectively 28, 30 and 30 tablets of 300 IR concentration

OR

Actair Initiation Treatment sublingual tablets 100 IR and 300 IR contain a small blister with 3 tablets of 100 IR concentration and a large blister with 7 tablets of 300 IR concentration

Actair Continuation Treatment sublingual tablets 300 IR contain blisters with 30 tablets of 300 IR concentration. The continuation treatment is available in packs of 30 or 90 tablets.

The tablets are round, biconvex, white to beige, brown speckled. The 100 IR tablets are engraved “SAC” on one side and “100” on the other and the 300 IR tablets are engraved SAC” on one side and “300” on the other.

Presentation

The following pack sizes are available:

Actair Initiation Treatment sublingual tablets 100 IR and 300 IR (AUST R 233470)

  • Pack with 3 tablets 100 IR and 28 tablets 300 IR
  • Pack with 3 tablets 100 IR and 88 tablets 300 IR
  • Pack with 3 tablets 100 IR and 7 tablets 300 IR

Actair Continuation Treatment sublingual tablets 300 IR (AUST R 233471)

  • Pack with 30 tablets
  • Pack with 90 tablets

NAME AND ADDRESS OF THE SPONSOR IN AUSTRALIA:

Stallergenes Australia Pty Ltd
Suite 2408,
4 Daydream St.,
Warriewood, NSW 2102
Ph: 1800 824 166
Fax: 1800 824 199

NAME AND ADDRESS OF THE SPONSOR IN NEW ZEALAND:

Stallergenes Greer New Zealand Limited
Level 1, 24 Manukau Road,
Epsom, Auckland 1023
New Zealand
Ph: 0800 824 166

Date Prepared: 30 May 2019

Published by MIMS August 2019

BRAND INFORMATION

Brand name

Actair

Active ingredient

American house dust mite extract; European house dust mite extract

Schedule

S4

 

1 Name of Medicine

Actair initiation treatment sublingual tablets 100 IR and 300 IR.

Mixture of American (D. farinae) and European (D. pteronyssinus) house dust mite allergen extracts.

Actair continuation treatment sublingual tablets 300 IR.

Mixture of American (D. farinae) and European (D. pteronyssinus) house dust mite allergen extracts.

6.7 Physicochemical Properties

Not applicable.

2 Qualitative and Quantitative Composition

A 50% mixture of house dust mite allergen extracts from: European house dust mites (Dermatophagoides pteronyssinus) and American house dust mites (Dermatophagoides farinae), 100 IR* or 300 IR* per sublingual tablet.
*IR (index of reactivity): the IR unit has been defined to measure the allergenicity of an allergen extract. The allergen extract contains 100 IR/mL when, on a skin prick test using a Stallerpoint, it induces a wheal diameter of 7 mm in 30 patients sensitized to this allergen, (geometric mean). The cutaneous reactivity of these patients is simultaneously demonstrated by a positive skin prick test to either 9% codeine phosphate or 10 mg/mL histamine. The IR unit of Stallergenes is not comparable to the units used by other allergen manufacturers.

Excipients with known effects.

Lactose monohydrate.
One sublingual tablet of 100 IR contains 82.8 - 83.3 mg lactose monohydrate.
One sublingual tablet of 300 IR contains 80.8 - 82.3 mg lactose monohydrate.
For full list of excipients, see Section 6.1.

3 Pharmaceutical Form

Actair is presented as white to beige, brown speckled tablet. The 100 IR tablets are engraved "SAC" on one side and "100" on the other and the 300 IR tablets are engraved "SAC" on one side and "300" on the other.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Treatment with Actair has been shown to induce a systemic antibody response towards house dust mite allergens, with an increase in specific IgG4 antibodies in some patients. These immunoglobulins may compete with IgE for allergen binding, thereby decreasing allergen capture and presentation.

Mechanism of action.

Immunologic changes associated with immunotherapy are complex, and the exact mechanism(s) responsible for its clinical efficacy are unknown.
The allergic reaction is dependent on the presence of allergen specific immunoglobulin E (IgE) antibodies bound to specific receptors on mast cells and basophils. Upon interaction of allergens with such cell bound IgE antibodies, histamine and other mediators are released and produce local or systemic responses in atopic individuals.
The immunologic response to allergen immunotherapy is characterized by changes in allergen specific antibody responses (with a decrease in IgE and the induction of IgG4 antibodies) as well as in the polarization of CD4+ T cell responses (from a Th2 to a regulatory T cell pattern).

Clinical trials.

Clinical experience in adults: study 1.

During a European, multicenter, multinational, randomized, double blind, placebo controlled study conducted over 2 years, 509 patients received either the 300 IR dose (n = 170) or the 500 IR dose (n = 169) sublingual tablet of house dust mites allergen extract or placebo (n = 170) daily for 12 months and were followed up during the subsequent treatment free year.
Study patients had allergic rhinitis caused by house dust mites, confirmed by positive skin tests and in vitro testing for dust mites specific IgE antibodies. Patients with intermittent asthma were included. Approximately 30% had asthma at baseline and 52% were polysensitized (i.e. sensitized to house dust mites allergens and at least one of the other allergens tested).
Efficacy was assessed via daily recording of rhinitis symptoms and rescue medication use by patients.
Patients receiving the 300 IR dose had a lower average adjusted symptom score over the last 3 months of treatment by 17.9% than those receiving placebo.
The results of the primary efficacy analysis are presented in Table 2.
Patients receiving the 300 IR dose had a lower average rhinitis total symptom score by 18.5% than those receiving placebo. There was no difference in the average rescue medication score between the active and placebo treatment groups.
The individual symptom scores for sneezing, nasal pruritus and nasal congestion were significantly reduced in the 300 IR group by 19.0%, 21.2%, and 20.7%, respectively, compared to the placebo group. The reductions observed for rhinorrhoea (12.2%) and ocular itching (20.5%) were not statistically significant.
A significant overall improvement of 23.0% was demonstrated in the rhinoconjunctivitis quality of life questionnaire score in the 300 IR group versus the placebo group in the first year. The improvement was also observed for each of the 7 domains: activities, sleep, non-nose/ eye symptoms, practical problems, nasal symptoms, eye symptoms, and emotional.
At the end of treatment, the proportion of patients reporting marked improvement was higher in the 300 IR group (36.9%) than in the placebo group (18.0%) with significantly higher treatment success (80.5% for 300 IR and 59.6% for placebo).

Clinical experience in adults and adolescents (12-17): study 2.

During a multicenter, randomized, double blind, placebo controlled study conducted in Japan over one treatment year, 968 adults and adolescents aged 12 to 64 years received either a 300 IR dose (n = 322) or a 500 IR dose (n = 324) of sublingual tablet of house dust mites allergen extract or placebo (n = 322) daily for 12 months.
Study patients had allergic rhinitis caused by house dust mites, confirmed by positive nasal provocation test and in vitro testing for dust mites specific IgE antibodies. Patients with intermittent or mild asthma were included.
Patients receiving the 300 IR dose had a lower average adjusted symptom score over the last 2 months of treatment by 18.2% than those receiving placebo.
The results of the primary efficacy analysis are presented in Table 3.
In the subset of adolescents (aged 12 to 17 years), patients receiving the 300 IR dose had a lower average adjusted symptom score by 26.9% than those receiving placebo.
Patients receiving the 300 IR dose had a lower average rhinitis total symptom score by 17.7% and a lower average rescue medication score by 41.6% than those receiving placebo.
The individual symptoms scores for sneezing, rhinorrhoea, nasal pruritus, nasal congestion and eye tearing were significantly reduced in the 300 IR group by 11.4%, 17.8%, 17.7%, 22.8% and 18.1%, respectively, compared to the placebo group.
For each of the domains of the Japanese rhinoconjunctivitis quality of life questionnaire score (i.e. 'nasal and eye symptoms', 'QOL related questionnaire' and 'general state'), a significant improvement was demonstrated at the end of the treatment in patients receiving 300 IR compared to those receiving placebo.
At the end of treatment, the proportion of patients reporting marked improvement was higher in the 300 IR group (22.2%) than in the placebo group (9.7%).

Clinical experience in children: study 3.

During a European, multinational, randomized, double blind, placebo controlled study, 471 patients from 5 to 17 years old received either the 300 IR dose (n = 241) of sublingual tablet of house dust mites allergen extract or placebo (n = 230) daily for 12 months. The patients were not sufficiently symptomatic to enable assessment of the efficacy of Actair.

5.2 Pharmacokinetic Properties

Allergens in Actair consist mainly of proteins and glycoproteins. There is no direct bioavailability of intact allergens in the blood. Therefore, no pharmacokinetic studies in animals or in humans have been carried out to investigate the pharmacokinetic profile and metabolism of Actair.

5.3 Preclinical Safety Data

Genotoxicity.

Actair active substances revealed no evidence of mutagenic or clastogenic potential based on the results of in vitro genotoxicity tests (bacterial reverse mutation, mouse lymphoma thymidine kinase and micronucleus assays).

Carcinogenicity.

Carcinogenicity studies have not been conducted with Actair.

4 Clinical Particulars

4.1 Therapeutic Indications

Treatment of house dust mite allergic rhinitis with or without conjunctivitis in adults and adolescents over 12 years diagnosed with house dust mite allergy.

4.3 Contraindications

Hypersensitivity to any of the excipients.
Severe, uncontrolled or unstable asthma.
Immune deficiency diseases or active forms of autoimmune disorder.
Malignant diseases (e.g. cancer).
Oral inflammations (such as oral lichen planus, oral ulcerations or oral mycosis).

4.4 Special Warnings and Precautions for Use

Identified precautions.

In case of oral surgery, including dental extraction, treatment with Actair should be stopped until complete healing.
In general, if treatment is interrupted for less than 7 days, it is to be continued. Should the interruption period be longer than 7 days, it is recommended to continue treatment only after seeking medical advice.
For the treatment of allergic rhinitis, Actair has been evaluated in patients with or without asthma requiring therapies consistent with GINA treatment step 1. In ongoing clinical studies conducted to evaluate the efficacy and safety of the treatment for asthma, no safety findings have been detected with doses up to 1500 IR in patients with asthma controlled or partly controlled by therapies consistent with GINA treatment step 2, 3 or 4.
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 Actair is missing. Vaccination may be given without interrupting treatment with Actair after medical evaluation of the general condition of the patient.
Due to the presence of lactose, patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Eosinophilic esophagitis has been reported in association with sublingual immunotherapy. During treatment with Actair, if severe or persistent gastrointestinal symptoms including dysphagia or chest pain occur, Actair should be interrupted and the patient evaluated by their physician. Treatment should only be resumed upon instruction of the physician. Patients with a history of eosinophilic esophagitis should be warned of the association of sublingual immunotherapy and eosinophilic esophagitis.
Patients taking beta-adrenergic blockers may be unresponsive to the usual doses of adrenaline used to treat serious systemic reactions, including anaphylaxis. Specifically, beta-adrenergic blockers antagonize the cardiostimulating and bronchodilating effects of adrenaline.

Use in the elderly.

Clinical experience on immunotherapy with Actair in patients older than 65 years is lacking.

Paediatric use.

The safety and efficacy of Actair in children below the age of 5 years is lacking.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

No interactions were reported in clinical trials with Actair, during which patients were able to take medications to treat allergic symptoms (antihistamines, corticosteroids).
There are no data on possible risks of simultaneous immunotherapy with other allergens during treatment with Actair.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

There are no fertility data available in humans.
Animal fertility studies have not been conducted with Actair active substances. However, histopathological examination of the male and female reproductive organs revealed no adverse effects in the repeat dose toxicity studies with mite allergen extracts.
There are no adequate and well controlled studies of Actair in pregnant women.
There was no evidence of maternal and embryofetal development toxicity following oral administration of Actair active substances to pregnant rats and rabbits, commencing on gestation day 6, at doses at least 76 times the 300 IR Actair dose, based on body surface area.
No peripostnatal toxicity study has been conducted.
As a precautionary measure, it is preferable to avoid initiating treatment during pregnancy. If pregnancy occurs during treatment, the treatment may be continued with close medical supervision.
No clinical data are available for the use of Actair during lactation. Studies in animals to investigate excretion of Actair into milk were not conducted.
No effects on the breastfed infants are anticipated. It is not recommended to initiate immunotherapy during breastfeeding. However, if a patient is under treatment at delivery, she can breastfeed with close supervision.

4.8 Adverse Effects (Undesirable Effects)

During treatment with Actair, patients are exposed to allergens that may cause application site reactions and/or systemic allergic symptoms. Application site reactions (e.g. oral pruritus and mouth oedema) of mild or moderate severity may therefore be expected during the period of therapy.
As with any allergen immunotherapy, severe allergic reactions including severe laryngopharyngeal disorder or systemic allergic reactions (i.e. acute onset of an illness with involvement of the skin, mucosal tissue, or both, respiratory compromise, persistent gastrointestinal symptoms, or reduced blood pressure and/or associated symptoms) can rarely occur. Patients should be informed of the associated signs and symptoms. Should these occur, patients should discontinue therapy and seek immediate medical care and treatment should only be resumed at the instruction of a physician.
Because clinical trials are conducted under widely varying conditions, adverse reactions 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.

Adults and adolescents.

In study 1, 339 adults with house dust mites associated allergic rhinitis with or without intermittent asthma were treated daily with the 300 IR dose (n = 170) or the 500 IR dose (n = 169). A total of 221 patients (65.2%) receiving the active treatment (111 in the 300 IR group and 110 in the 500 IR group) reported adverse reactions as did 38 (22.4%) of those receiving placebo.
In study 2, 646 adults and adolescents (aged 12 to 64 years) with house dust mites associated allergic rhinitis with or without intermittent or mild asthma were treated with the 300 IR dose (n = 322) or the 500 IR dose (n = 324).
A total of 452 patients (70.0%) receiving the active treatment (215 in the 300 IR group and 237 in the 500 IR group) reported adverse reactions as did 60 (18.6%) of those receiving placebo.
In both studies, most adverse reactions leading to premature study withdrawal were application site reactions, were of mild or moderate severity and were nonserious.
Adverse events reported at an incidence of ≥ 2% of patients receiving Actair 300 IR in study 1 and study 2 pooled data are listed in Table 1.
Adverse events with an incidence < 2% and with causality assigned to Actair are listed below according to the MedDRA convention by system organ class and by frequency into common: ≥ 1/100, < 1/10, uncommon: ≥ 1/1,000, < 1/100, rare: ≥ 1/10,000, < 1/1,000.

Ear and labyrinth disorders.

Common: ear pain.

Gastrointestinal disorders.

Common: glossitis, oral mucosal blistering, hypoaesthesia oral, gastritis, cheilitis.
Uncommon: oral pain, tongue pruritus, dysphagia, glossodynia, vomiting, gingivitis, gastrointestinal disorder, palatal oedema, dry mouth, lip pruritus, breath odour, chapped lips, frequent bowel movements, irritable bowel syndrome, gingival pain, mouth ulceration, odynophagia, oesophageal discomfort, salivary gland enlargement, salivary hypersecretion.

Respiratory, thoracic and mediastinal disorders.

Common: dry throat.
Uncommon: laryngeal oedema, wheezing, asthma, oropharyngeal pain, pharyngolaryngeal pain, sneezing, rhinorrhoea, nasal discomfort, nasal congestion, throat tightness.

Cardiac disorders.

Uncommon: tachycardia.

Eye disorders.

Common: conjunctivitis.
Uncommon: eye oedema, blepharospasm, lacrimation increased.

General disorders and administration site conditions.

Uncommon: chest discomfort, lump feeling in throat, chest pain, asthenia, malaise.

Infections and infestations.

Uncommon: periodontitis.

Musculoskeletal and connective tissue disorders.

Uncommon: muscle spasms.

Nervous system disorders.

Uncommon: somnolence.

Psychiatric disorders.

Uncommon: anxiety.

Skin and subcutaneous tissue disorders.

Common: pruritus, urticaria.
Uncommon: rash, angioedema, blister.

Investigations.

Common: gamma glutamyltransferase increased.
Uncommon: alanine aminotransferase increased, lymphocyte morphology abnormal, aspartate aminotransferase increased, basophil count increased, blood bilirubin increased, blood uric acid increased.
In addition to the reactions listed in the tabulated summary, in a double blind, placebo controlled study conducted in an environmental exposure chamber over 6 months, 59 patients with or without intermittent asthma who received Actair 300 IR have reported at least one of the following reactions:
Lip blister, bronchospasm, sinus congestion, rhinitis allergic, ear discomfort, eye pruritus, ocular hyperaemia, paraesthesia, pharyngitis (all reported as common).

Paediatric population (age 5 to 17).

In a multicenter, multinational, randomized, double blind, placebo controlled paediatric clinical trial, 239 children and adolescents with house dust mites associated allergic rhinitis were treated with Actair 300 IR once daily over 12 months.
Overall, the safety profile in the paediatric population was similar to that of adults. In addition to the reactions listed in the tabulated summary, the following reactions were reported:
Enterocolitis, oral disorder, seborrhoea, bronchitis, candida infections, and ear disorder (all reported as uncommon) and malaise (reported at a higher frequency than in adults, i.e. common).

Potential adverse effects experienced with the same class of product.

Cases of eosinophilic esophagitis have been reported with other sublingual immunotherapy products.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.2 Dose and Method of Administration

Treatment with Actair should only be prescribed and initiated by physicians with adequate training and experience in the treatment of allergic diseases. In the case of treatment of adolescent patients over 12 years, the physicians should have the corresponding training and experience in patients in this age group. It is recommended that the first tablet of Actair is taken under medical supervision and that the patient is monitored for 30 minutes.

Method of administration.

On the first day, one 100 IR tablet should be taken. Tablets must be placed under the tongue until complete disintegration and then swallowed. On the second day of treatment, two 100 IR tablets must be placed under the tongue simultaneously and then swallowed. It is recommended that the tablets be taken during the day in an empty mouth.

Dose regimen in adults and adolescents over 12 years.

The therapy is composed of an initiation treatment (including a 3 day dose escalation) and a continuation treatment.
The initiation treatment pack corresponds to the first month of treatment with Actair 100 IR and 300 IR sublingual tablets.

Small blister.

Day 1: 1 x 100 IR tablet.
Day 2: 2 x 100 IR tablets.

Large blister.

Day 3: 1 x 300 IR tablet.
Day 4: 1 x 300 IR tablet.
Day 5-30: 1 x 300 IR tablet.
From the 2nd month onwards, treatment must be continued with the continuation treatment packs, with one Actair 300 IR sublingual tablet per day until the end of treatment.
Study 1 has shown that, after one year of treatment in adults, efficacy is demonstrated during the subsequent treatment free year.

Duration of treatment.

Efficacy has been demonstrated for one year of treatment with additional clinical data available for one year post-treatment.

4.7 Effects on Ability to Drive and Use Machines

Actair has no known influence on the ability to drive and use machines.

4.9 Overdose

Overdoses of up to 1000 IR for up to 28 days were reported in patients receiving Actair. Higher doses may be associated with reduced tolerability and may potentially increase the risk of serious allergic reactions.
In the event of an overdose, the adverse effects should be treated symptomatically.
Contact the Poisons Information Centre on 13 11 26 for advice on the management of an overdose.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

7 Medicine Schedule (Poisons Standard)

S4.

6 Pharmaceutical Particulars

6.1 List of Excipients

Mannitol, microcrystalline cellulose, croscarmellose sodium, colloidal anhydrous silica, magnesium stearate and lactose monohydrate.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 30°C.
Store in the original package in order to protect from moisture.

6.5 Nature and Contents of Container

Initiation treatment.

Pack of 1 x 3 sublingual tablets of 100 IR in a small blister + 1 x 28 sublingual tablets of 300 IR in a blister, pack of 1 x 3 sublingual tablets of 100 IR in a small blister + 88 sublingual tablets of 300 IR in 3 blisters (1 x 28, 1 x 30 and 1 x 30 sublingual tablets) and pack of 1 x 3 sublingual tablets of 100 IR in a small blister + 1 x 7 sublingual tablets of 300 IR in a blister.

Continuation treatment.

1 x 30 sublingual tablets of 300 IR in a blister. Pack of 30 or 90 tablets.
Actair Initiation Treatment Sublingual Tablets 100 IR and 300 IR (A 50% mixture of Allergen house dust mite extracts of European house dust mite (D. pteronyssinus) and American house dust mite (D. farinae) - (AUST R233470).
Actair Continuation Treatment Sublingual Tablets 300 IR (A 50% mixture of Allergen house dust mite extracts of European house dust mite (D. pteronyssinus) and American house dust mite (D. farinae) - (AUST R 233471).
Not all pack sizes may be marketed.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

Summary Table of Changes