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.

SUMMARY CMI

ACTAIR®

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using ACTAIR?

ACTAIR contains active ingredients which are a 50% mixture of allergen extracts from 2 species of house dust mite - American House Dust Mite and European House Dust Mite. 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, adolescents and children 5 years and over

For more information, see Section 1. Why am I using ACTAIR? in the full CMI.

2. What should I know before I use ACTAIR?

Do not use if you have ever had an allergic reaction to any of the ingredients listed at the end of the CMI or if you suffer from severe and/or unstable asthma; your immune system is very weakened; if you suffer from a cancer; if you have any inflammation in your mouth

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding. For more information, see Section 2. What should I know before I use ACTAIR? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with ACTAIR and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use ACTAIR?

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

The tablets are taken by keeping the tablet under your tongue until it is completely disintegrated (at least 2 minutes) before you swallow. More instructions can be found in Section 4. How do I use ACTAIR? in the full CMI.

5. What should I know while using ACTAIR?

Things you should doRemind any doctor, dentist or pharmacist you visit that you are using ACTAIR.
You are advised to take the first tablet under medical supervision and be monitored for 30 minutes. Take these tablets as prescribed until the end of the treatment course.
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 and ask your doctor how you should restart the treatment.
Things you should not doDo not take food or beverage at the same time you are taking the medicine and for at least 5 minutes afterwards.
Do not halve the tablet. Tablet is to be taken whole.
If you forget to take ACTAIR, do not take a double dose to make up for forgotten dose.
Do not start taking ACTAIR if you are pregnant.
Driving or using machinesNo effect on the capacity to drive or use machines has been observed
Looking after your medicineStore below 30°C. Store in the original package in order to protect from moisture

For more information, see Section 5. What should I know while using ACTAIR? in the full CMI.

6. Are there any side effects?

Common side effects: Swelling or itching of the mouth, throat irritation and itchy ear.

Serious side effects: Allergic symptoms that affect the whole body, (i.e., rapid onset of an illness associated with involvement of the skin and/or mucosa, difficulties in swallowing, breathing difficulty, voices change, abdominal pain or symptoms related to drop in blood pressure). Serious allergic reaction with swelling of the face and/or mouth or tongue and throat. For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

ACTAIR® Pronounced (Act-air)

Active ingredient(s): Extracts of American House Dust Mite and European House Dust Mite


Consumer Medicine Information (CMI)

This leaflet provides important information about using ACTAIR. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using ACTAIR.

Where to find information in this leaflet:

1. Why am I using ACTAIR?
2. What should I know before I use ACTAIR?
3. What if I am taking other medicines?
4. How do I use ACTAIR?
5. What should I know while using ACTAIR?
6. Are there any side effects?
7. Product details

1. Why am I using ACTAIR?

ACTAIR contains a 50% mixture of allergen extracts from 2 species of house dust mite. The house dust mites that ACTAIR is used for are: European house dust mite (Dermatophagoides pteronyssinus) and American house dust mite (Dermatophagoides farinae).

ACTAIR is an allergen extract from house dust mites. 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, adolescents and children 5 years and over.

2. What should I know before I use ACTAIR?

Warnings

Do not use ACTAIR if:

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

Check with 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 experience severe allergic symptoms, such as difficulty in swallowing or breathing, changes in your voice, hypotension (low blood pressure) or a feeling of a lump in the throat. Stop the treatment and contact your doctor immediately or go to the Emergency Department at your nearest hospital
  • You have previously had a severe allergic reaction to a drug with allergen extracts.
  • Your asthma symptoms get noticeably worse than normal. Stop treatment and contact your doctor immediately.
  • You have a cardiovascular disease.
  • 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 (epinephrine), a medicine used to treat serious allergic reactions.
  • You are taking MAOIs, tricyclic antidepressants and COMT inhibitors. Allergen immunotherapy in patients treated with mono amine oxidase inhibitors (MAOIs) or tricyclic antidepressants or for Parkinson's disease with COMT inhibitors should be considered carefully as these treatments could potentiate the effect of adrenaline (epinephrine).
  • You need mouth surgery or a tooth extraction, you should temporarily stop treatment with ACTAIR until completely healed.
  • You experience persistent heartburn or difficulty swallowing. You should contact your doctor.
  • You have an autoimmune disease in remission.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them especially if you have cardiac diseases. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

Do not start taking ACTAIR if you are pregnant.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

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.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines may interfere with ACTAIR and affect how it works.

If you are taking other allergy medicines such as antihistamines, asthma relief medication or steroids or a medication that blocks a substance called immunoglobulin E (IgE) e.g. omalizumab, discuss with your doctor whether to continue taking them. Do not stop taking these medicines before talking to your doctor. If you stop taking those allergy medicines you may experience more side effects during ACTAIR treatment.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect ACTAIR.

4. How do I use ACTAIR?

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 and children 5 years and above, 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.

How much to take / use

Adults, adolescents and children 5 years and over

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

It is recommended to take the tablets during the day in an empty mouth. Tablets should be placed under the tongue until complete disintegration (at least 2 minutes) and then swallowed. Food or beverage should not be taken for the following 5 minutes. On the first day, one 100 IR tablet should be taken. On the second day of treatment, two 100 IR tablets should be placed under the tongue simultaneously

Continuation Treatment:

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

When to take / use ACTAIR

ACTAIR should be used according to the following dosing scheme:

Always start with the small blister:

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

How long ACTAIR should be taken for?

ACTAIR is started on the day determined by your doctor. Take these tablets as prescribed by your doctor until the end of the treatment course.

It is recommended to maintain the treatment all year round.

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

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

If you forget to use ACTAIR

ACTAIR should be used regularly every day as per above dosing scheme.

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to.

Do not take a double dose to make up for the dose you missed.

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

If you use too much ACTAIR

If you think that you have used too much ACTAIR, you may need urgent medical attention.

You should immediately:

phone the Poisons Information Centre
(by calling 13 11 26), or

contact your doctor, or
go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while using ACTAIR?

Things you should do

Call your doctor straight away if you:

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
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.

If you become pregnant, speak to your doctor about whether it is appropriate for you to continue treatment.

Remind any doctor, dentist or pharmacist you visit that you are using ACTAIR.

Things you should not do

Do not take food or beverage at the same time you are taking the medicine and for at least 5 minutes afterwards.
Do not halve the tablet. Tablet is to be taken whole.
If you forget to take ACTAIR, do not take a double dose to make up for forgotten dose.

Driving or using machines

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

Looking after your medicine

Keep it in the original pack in order to protect from moisture.

Keep it below 30°C.

Store it in a cool dry place away from moisture, heat or sunlight; for example, do not store it:
in the bathroom or near a sink, or
in the car or on window sills.

Keep it where young children cannot reach it.

When to discard your medicine (as relevant)

Do not use if past the expiry date which is stamped on the carton side panel.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Do not be alarmed by the following list of side effects. You may not experience any of them.

During treatment with ACTAIR, you will be exposed to substances that may cause 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, difficulties in swallowing, breathing difficulty, voices changes, abdominal pain or symptoms related to a drop in blood pressure).
  • Serious allergic reaction with swelling of the face and/or mouth or tongue and throat.

Other possible serious side effects include the following:

Serious side effects in adults and adolescents

Serious side effectsWhat to do
[Nose/mouth/throat]
  • swelling of lips, swelling of the palate, mouth and throat swelling due to eating fruits or vegetables,
  • swelling in the back of the throat
  • swelling of the tongue
[Respiratory]
  • asthma, shortness of breath, wheezing
[Gastrointestinal]
  • oesophagus swelling
[Skin]
  • acute skin reaction
Stop taking ACTAIR and Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Less serious side effects in adults and adolescents

Less serious side effectsWhat to do
[Eye/ear]
  • Itchy eyes, eye redness and inflammation, eye swelling, tearing, eyelid inflammation, abnormal eyelid contraction, eye irritation
  • Itchy ear, vertigo, ear pain or tingling, blocked ear, ringing in the ears
[Nose/mouth/throat]
  • Rhinitis (sneezing, runny or itchy nose, blocked nose), nose discomfort, blocked sinuses, common cold, nose bleeds
  • Itching in the mouth or of lips or tongue, burning or tingling mouth, mouth ulcer, inflamed and sore mouth, inflammation of lips or tongue, altered taste, oral disorder such as burning mouth, mouth numbness, oral thrush, salivary problems, gum inflammation, bleeding in the mouth, breath odour, burping
  • Discomfort or pain in the mouth and/or throat, dry mouth or throat, thirst, mouth and/or throat blisters
  • Throat irritation, throat disorder such as burning/tingling or tightness in throat, hoarseness, feeling of a lump in the throat, discomfort in the back of the throat, throat numbness
  • Seasonal allergy
[Respiratory]
  • Voice box irritation, cough, rapid breathing
  • Bronchitis
[Gastrointestinal]
  • Painful swallowing, pain in the oesophagus, inflammation of oesophagus or stomach, heartburn, stomach pain, indigestion, vomiting, nausea, diarrhoea, gastroenteritis, frequent bowel movements, irritable bowel, having gas
[Nervous system]
  • Headache, dizziness
  • Malaise or fatigue
  • Anxiety, irritability, disturbance in attention, somnolence, speech disorder, tremor
  • Tingling or prickling sensation, numbness
[Cardiovascular]
  • Palpitations, rapid heartbeat
[Skin]
  • Itchiness, rash, skin irritation, hives, redness of the skin, scratching lesions, blisters, localised swelling, swelling beneath the skin
[Other organs]
  • Chest pain, chest discomfort, breast pain
  • Muscle discomfort or contractions
  • Urgent urination
[Laboratory tests]
  • Abnormal blood results
Speak to your doctor if you have any of these less serious side effects and they worry you.

Additional less serious side effects in children

Less serious side effects in childrenWhat to do
[Eye]
  • Eye pain
[Gastrointestinal]
  • Bowel inflammation, decreased appetite
[Skin]
  • Oily skin
[Other organs]
  • Fever
Speak to your doctor if you have any of these less serious side effects and they worry you.

In children, the following side effects were reported at a higher frequency than in adults and adolescents: discomfort in the back of the throat, vomiting, hives and abnormal blood results were reported as common (affecting less than 10 in 100 people and more than 1 in 100 people), eye redness and voice box irritation were reported as uncommon (affecting less than 1 in 100 people).

Additional side effects experienced with similar products

As with any sublingual allergen immunotherapy, cases of oesophageal inflammation have been reported with ACTAIR.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side affects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

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

What ACTAIR contains

Active ingredient
(main ingredient)
Extract of European house dust mite
Extract of American house dust mite
Other ingredients
(inactive ingredients)
Mannitol, Microcrystalline cellulose, Croscarmellose sodium, Colloidal anhydrous silica, Magnesium stearate and Lactose monohydrate.

Do not take this medicine if you are allergic to any of these ingredients.

What ACTAIR looks like

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.

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

Who distributes ACTAIR

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

This leaflet was prepared in
10 Jan 2022

Published by MIMS April 2022

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.

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 dihydrochloride. 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 List of Excipients.

3 Pharmaceutical Form

Sublingual tablet.
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.

4 Clinical Particulars

4.1 Therapeutic Indications

Treatment of house dust mite allergic rhinitis with or without conjunctivitis in adults, adolescents and children 5 years and over diagnosed with house dust mite allergy.

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 and paediatric patients 5 years and over, 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.

It is recommended to take the tablets during the day in an empty mouth. Tablets should be placed under the tongue until complete disintegration (at least 2 minutes) and then swallowed. Food or beverage should not be taken for the following 5 minutes. On the first day, one 100 IR tablet should be taken. On the second day of treatment, two 100 IR tablets should be placed under the tongue simultaneously.

Dose regimen in adults, adolescents and children 5 years and over.

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.
The dose-escalation period could be prolonged, when considered necessary by the physician according to the patient's condition.
Study 1 (VO57.07) has shown that, after one year of Actair treatment in adults, efficacy is demonstrated during the subsequent treatment free year.

Duration of treatment.

Post treatment efficacy data after 12 months of treatment with Actair are available (see Section 5.1 Pharmacodynamic Properties, Clinical trials). Discontinuation should be considered if no improvement is observed during the first year of treatment with Actair.

Paediatric population.

The posology is the same for adults, adolescents and children (5 years and over).
The efficacy of Actair in children below the age of 5 years has not been established.

Discontinuation of therapy.

In general, if treatment is interrupted for less than 7 days, treatment can be resumed by the patient. Should the interruption period be longer than 7 days, it is recommended to contact a physician before resuming the treatment.

4.3 Contraindications

Hypersensitivity to any of the excipients (see Section 6.1 List of Excipients).
Severe, uncontrolled or unstable asthma; (FEV1 < 80% of predicted value) or severe exacerbation of asthma within the previous 3 months.
Initiation of allergen immunotherapy treatment during pregnancy is contraindicated (see Section 4.6 Fertility, Pregnancy and Lactation).
Patients with active or poorly controlled autoimmune disease, immune defects, immunodeficiencies or immunosuppression or malignant neoplasia with current disease relevance.
Severe oral inflammations (such as oral lichen planus, oral ulcerations or oral mycosis).

4.4 Special Warnings and Precautions for Use

Identified precautions.

Severe allergic reactions.

As with any sublingual allergen immunotherapy, severe allergic reactions including severe laryngopharyngeal disorders, or systemic allergic reactions may occur. Patients should be made aware of the signs and symptoms of severe allergic reactions. Severe allergic reactions may be treated with adrenaline (epinephrine). In case of severe allergic reactions, patients should discontinue the treatment and seek immediate medical care. The treatment should only be resumed upon instruction of a physician.

Previous systemic allergic reaction to allergen immunotherapy.

Initiation of Actair in patients who have had a systemic allergic reaction to previous allergen immunotherapy should be carefully considered, and measures to treat potential reactions should be available.

Mild to moderate local allergic reactions.

The treatment consists of exposure to allergens to which the patient is allergic. Therefore, mild or moderate local allergic reactions in the oropharyngeal area (e.g. oral pruritus, throat irritation, ear pruritus) may be expected. If the patient experiences significant application site reactions, symptomatic treatment (e.g. antihistamines) may be considered.

Autoimmune diseases in remission.

Limited data are available on treatment with allergen immunotherapy in patients with autoimmune diseases in remission. Actair should therefore be prescribed with caution in these patients.

Cardiovascular diseases.

Patients with cardiac disease may be at increased risk in case of systemic allergic reactions to allergen immunotherapy. This should be taken into consideration prior to initiating Actair.

Oral lesions.

In case of oral surgery, including dental extraction, treatment with Actair should be stopped until complete healing.

Eosinophilic oesophagitis.

Cases of eosinophilic oesophagitis have been reported in association with Actair treatment and other sublingual immunotherapies. If severe or persistent gastroesophageal symptoms including dysphagia or chest pain occur, Actair should be interrupted and the patients evaluated by their physician. Treatment should only be resumed upon instruction of the physician.

Asthma.

The asthma status should be carefully evaluated before starting therapy (see Section 4.3 Contraindications).
Asthma is a known risk factor for severe systemic allergic reactions. Patients with associated asthma should be controlled at the initiation and during all the duration of Actair treatment. Abrupt discontinuation of asthma controller medication after initiation of Actair treatment is not recommended.
Patients with concomitant asthma should be informed of the need to seek medical attention immediately if their asthma deteriorates suddenly.

Beta-adrenergic blockers.

Patients taking beta-adrenergic blockers may be unresponsive to the usual doses of adrenaline (epinephrine) used to treat serious systemic reactions, including anaphylaxis. Specifically, beta-adrenergic blockers antagonise the cardiostimulating and bronchodilating effects of adrenaline (epinephrine).

MAOIs, tricyclic antidepressants and COMT inhibitors.

Allergen immunotherapy in patients treated with mono amine oxidase inhibitors (MAOIs) or tricyclic antidepressants or COMT inhibitors should be considered carefully as these treatments could potentiate the effect of adrenaline (epinephrine).

Lactose.

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.

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 have not been demonstrated.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

No interaction studies have been performed.
No interactions were reported in clinical trials with Actair, during which patients were able to take medications to treat allergic symptoms (antihistamines, corticosteroids).
Concomitant therapy with symptomatic anti-allergic medications or anti-IgE medications e.g. omalizumab may increase the tolerance level of the patient to immunotherapy. This should be considered at discontinuation of such medications.
There are no data on possible risks of simultaneous immunotherapy with other allergens during treatment with Actair.
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.

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.
(Category B2)
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.
Treatment with Actair should not be initiated during pregnancy (see Section 4.3 Contraindications). If pregnancy occurs during treatment, the treatment may continue after evaluation of the general condition of the patient and reactions to previous administration of Actair.
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.

4.7 Effects on Ability to Drive and Use Machines

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

4.8 Adverse Effects (Undesirable Effects)

Assessment of adverse reactions from clinical study data is based on trials in which 3007 patients received at least one dose of house dust mite sublingual tablet. The most frequent adverse reactions were application site reactions: oral pruritus, mouth oedema, throat irritation and ear pruritus. Adverse reactions were generally mild or moderate. They mostly occurred within the first days of treatment and decreased over the next 3 months.
Severe allergic reactions including severe laryngopharyngeal disorder or systemic allergic reactions such as serious anaphylactic 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 occur (see Section 4.4 Special Warnings and Precautions for Use).

Adults and adolescents.

In adults and adolescents with house dust mite-induced allergic rhinitis receiving Actair (N=1583) or placebo (N=1588) once daily for up to 12 months, 1238 patients (78.2%) in the 300 IR treatment group reported adverse events as did 1036 (65.2%) in the placebo group.
Adverse events reported at an incidence of ≥ 5% of patients receiving Actair 300 IR compared to placebo in pooled study data are listed in Table 1.
Adverse events with an incidence < 5% and with causality assigned to Actair are listed below according to the MedDRA convention by system organ class and by frequency common: ≥ 1/100, < 1/10, uncommon: ≥ 1/1,000, < 1/100, rare: ≥ 1/10,000, < 1/1,000.

Infections and infestations.

Uncommon: Gastroenteritis, oral candidiasis.
Rare: Bronchitis, periodontitis.

Immune system disorders.

Uncommon: Oral allergy syndrome.
Rare: Seasonal allergy.

Psychiatric disorders.

Uncommon: Anxiety.
Rare: Irritability.

Nervous system disorders.

Common: Dysgeusia.
Uncommon: Dizziness, paraesthesia.
Rare: Disturbance in attention, hypoaesthesia, somnolence, speech disorder, tremor.

Eye disorders.

Common: Eye pruritus.
Uncommon: Conjunctivitis, eye oedema, lacrimation increased.
Rare: Ocular hyperaemia, blepharitis, blepharospasm, eye irritation.

Ear and labyrinth disorders.

Uncommon: Vertigo, ear pain, paraesthesia ear.
Rare: Ear congestion, tinnitus.

Cardiac disorders.

Rare: Tachycardia, palpitations.

Respiratory, thoracic and mediastinal disorders.

Common: Pharyngeal oedema, dyspnoea, cough.
Uncommon: Laryngeal oedema, pharyngeal disorder, asthma, bronchospasm, wheezing, throat tightness, dysphonia, epistaxis, laryngeal discomfort, pharyngeal paraesthesia, rhinitis (nasal congestion, nasal pruritus, rhinorrhoea, sneezing).
Rare: Hyperventilation, larynx irritation, nasal discomfort, pharyngeal hypoaesthesia, sinus congestion.

Gastrointestinal disorders.

Common: Mouth ulceration, stomatitis, diarrhoea, dyspepsia, dysphagia, oropharyngeal discomfort, paraesthesia oral, tongue pruritus, lip pruritus.
Uncommon: Eosinophilic oesophagitis, palatal oedema, gastritis, gastrooesophageal reflux disease, oropharyngeal blistering, oesophageal pain, cheilitis, dry mouth, dry throat, glossitis, glossodynia, hypoaesthesia oral, oral disorder, salivary gland disorder, vomiting.
Rare: Oesophageal oedema, mouth haemorrhage, irritable bowel syndrome, frequent bowel movements, breath odour, eructation, flatulence, odynophagia.

Skin and subcutaneous tissue disorders.

Common: Pruritus.
Uncommon: Angioedema, dermatitis, rash, urticaria.
Rare: Erythema multiforme, blister, erythema, prurigo.

Musculoskeletal and connective tissue disorders.

Rare: Muscle spasms, musculoskeletal discomfort.

Renal and urinary disorders.

Rare: Micturition urgency.

Reproductive system and breast disorders.

Rare: Breast pain.

General disorders and administration site conditions.

Common: Chest pain.
Uncommon: Face oedema, localised oedema, chest discomfort, lump feeling in throat, asthenia, malaise, thirst.

Investigations.

Uncommon: Laboratory test abnormal (haematologic, hepatic, uric acid).

Paediatric population (5-11 years).

The safety experience in the paediatric population is based on clinical trials enrolling 270 children from 5 to 11 years old with house dust mite-induced allergic rhinitis and who received Actair at the 300 IR dose. Overall, the safety profile of Actair in the paediatric population was similar to that in adults and adolescents.
In addition to the reactions listed in the Tabulated Summary, the following reactions were reported:
Uncommon: enterocolitis, eye pain, decrease appetite, pyrexia and seborrhoea.
Moreover, the following reactions were reported at a higher incidence than in adults and adolescents: Common: laryngeal discomfort, vomiting, urticaria and laboratory test abnormal (haematologic, hepatic, uric acid).
Uncommon: ocular hyperhaemia and larynx irritation.

Patients enrolled in studies of allergic asthma.

The safety experience in patients with allergic asthma is based on clinical trials enrolling 589 patients from 6 to 50 years old with a medical history of house dust mite-induced allergic asthma controlled with asthma therapies consistent with GINA treatment Step 2, 3 or 4 with or without perennial rhinitis and who received Actair at doses up to 2000 IR. Overall, the safety profile of Actair in patients with house dust mite-induced allergic asthma was similar to that in patients with house dust mite-induced allergic rhinitis.
In addition to the reactions listed in the Tabulated Summary, the following reaction was reported with Actair 300 IR: Common: intranasal paraesthesia.

Post-marketing.

Cases of systemic allergic reactions, including serious anaphylactic reactions have been reported in post marketing and are considered a class effect.

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.

4.9 Overdose

Overdoses of up to 1000 IR for up to 28 days and overdosing of at least 600 IR for up to 324 days were reported in patients receiving Actair. No unexpected safety risk emerged in those patients. Doses up to 2000 IR for 10 days in asthmatic patients have been investigated without any new safety concerns. 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.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

Pharmacotherapeutic group: Allergen extract, house dust mites. ATC code: V01AA03.

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.
Several studies have shown that the immunological response to allergen immunotherapy is characterized by an induction of allergen specific IgG4 that competes with IgE for the binding to allergens, and thereby reduces activation of immune cells. Treatment with Actair has been shown to induce a systemic antibody response towards house dust mite allergens, with an early and transient increase in specific IgE antibodies followed by a gradual decrease and an increase in specific IgG4.

Clinical trials.

Clinical experience in adults: study 1-VO57.07.

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, nasal congestion, rhinorrhoea and ocular itching were reduced in the 300 IR group by 19.0%, 21.2%, 20.7%, 12.2% and 20.5%, respectively, compared to the placebo group.
An 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%). A higher proportion of patients in the 300 IR group reported treatment success (80.5% versus 59.6% for placebo).

Clinical experience in adults and adolescents (12-17): study 2-1207D1731.

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 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 numerically superior 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 paediatric population (5-16): study 3-1501D1732.

During a multicenter, randomized, double-blind, placebo-controlled study conducted in Japan over one treatment year, 438 children and adolescents aged 5 to 16 years received either a 300 IR dose (n=219) of sublingual tablet of house dust mites allergen extract or placebo (n=219) 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 4 weeks of treatment by 13.1% than those receiving placebo.
The results of the primary efficacy analysis are presented in Table 4.
Patients receiving the 300 IR dose had a lower Average Rhinitis Total Symptom Score by 12.7% and a lower Average Rescue Medication Score by 8.5% than those receiving placebo.
The individual symptoms scores for sneezing, rhinorrhoea, nasal pruritus and nasal congestion were reduced in the 300 IR group by 14.4%, 9.9%, 12.1% and 15.0%, respectively, compared to the placebo group.
At the end of treatment, the proportion of patients reporting marked improvement was higher in the 300 IR group (19.7%) than in the placebo group (8.8%).
Study 3 included 282 children aged 5 to 11 years and 156 adolescents aged 12 to 17 years. Of these, 268 children (300 IR: 130, Placebo: 138) and 154 adolescents (300 IR: 75, Placebo: 79) were evaluable for efficacy. Although this study was not designed for efficacy analysis in the age subgroups, the treatment effect in children and in adolescents was consistently in favour of 300 IR as observed in the overall population. Children and adolescents receiving the 300 IR dose had a lower Average Adjusted Symptom Score by 12.4% and 13.6%, respectively, than those receiving placebo.
In another double-blind, placebo-controlled paediatric study (VO64.08), 471 children and adolescents (5-17 years old) received Actair at a dose up to 300 IR (n=241) or placebo (n=230). Patients were not sufficiently symptomatic to enable assessment of the efficacy of Actair.

5.2 Pharmacokinetic Properties

The pharmacological effect of the active substances of house dust mite tablet is not related to blood allergen levels. Allergens are large molecules; after swallowing, allergens that have not been captured within the sublingual mucosa are broken down into smaller polypeptides and amino acids in the lumen of the gastrointestinal tract and in tissues. The extent of systemic absorption of the house dust mite extracts is assumed to be very low or negligible.
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.

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.

6.7 Physicochemical Properties

Not applicable.

7 Medicine Schedule (Poisons Standard)

Prescription Only Medicine - S4.

Summary Table of Changes