Consumer medicine information

Brimica Genuair 340/12

Aclidinium; Formoterol (eformoterol) fumarate dihydrate

BRAND INFORMATION

Brand name

Brimica Genuair 340/12

Active ingredient

Aclidinium; Formoterol (eformoterol) fumarate dihydrate

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Brimica Genuair 340/12.

What is in this leaflet

This leaflet answers some common questions about BRIMICA GENUAIR 340/12.

It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your pharmacist or doctor will be able to advise you about the risks and benefits of using BRIMICA GENUAIR 340/12.

If you have any concerns about using this medicine, ask your pharmacist or doctor.

Keep this leaflet with the medicine. You may need to read it again.

What BRIMICA GENUAIR 340/12 is used for

BRIMICA GENUAIR 340/12 contains two different medicines called aclidinium bromide and formoterol fumarate dihydrate.

Both belong to a group of medicines known as bronchodilators. Bronchodilators relax airways and help keep bronchioles open.

BRIMICA GENUAIR 340/12 is a dry powder inhaler that uses your breath to deliver the medicine directly into your lungs. This makes it easier for chronic obstructive pulmonary disease (COPD) patients to breathe.

BRIMICA GENUAIR 340/12 is used to help open the airways and relieve symptoms of COPD, a serious long-term lung disease characterised by breathing difficulties. Regular use of BRIMICA GENUAIR 340/12 can help you when you have ongoing shortness of breath related to your disease and will help you to minimise the effects of the disease on your everyday life.

BRIMICA GENUAIR 340/12 is indicated for maintenance treatment of your COPD; it should not be used to treat a sudden attack of breathlessness or wheezing. If your COPD symptoms (breathlessness, wheezing, cough) do not improve or get worse you should contact your doctor for advice as soon as possible.

Ask your doctor if you have any questions about why BRIMICA GENUAIR 340/12 has been prescribed for you.

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

It is not addictive.

Before you use BRIMICA GENUAIR 340/12

When you must not use it

Do not use BRIMICA GENUAIR 340/12 if you have an allergy to:

  • aclidinium bromide, formoterol fumarate dihydrate or any of the other ingredient of this medicine listed at the end of this leaflet.

Some of the symptoms of an allergic reaction may include:

  • shortness of breath
  • wheezing or difficulty breathing
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching or hives on the skin.

Do not use this medicine after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering. In that case, return it to your pharmacist.

Before you start to use it

Tell your doctor if you have any of the following medical conditions:

  • if you have asthma
  • if you have had heart problems recently
  • if you have epilepsy
  • if you have thyroid gland problems (thyrotoxicosis)
  • if you have a tumour in one of your adrenal glands (phaeochromocytoma)
  • if you have difficulty passing urine
  • if you see halos around lights and coloured images, have eye pain or discomfort or temporary blurring of vision (narrow angle glaucoma)
  • if you have rare hereditary galactose intolerance, total lactase deficiency or glucose-galactose malabsorption.

Your doctor may want to take special precautions if you have any of the above conditions.

BRIMICA GENUAIR 340/12 may cause dryness in the mouth, which may cause tooth decay after using your medicine for a long time. Therefore, please remember to pay attention to oral hygiene.

Tell your doctor if you are pregnant, intend to become pregnant or are breastfeeding. BRIMICA GENUAIR 340/12 is not recommended for use during pregnancy or while breastfeeding. If it is necessary for you to use this medicine during pregnancy or while breastfeeding, your doctor will discuss with you the benefits and risks involved.

Children and adolescents

BRIMICA GENUAIR 340/12 is not for use in children or adolescents below 18 years of age.

Taking other medicines

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

Some medicines and BRIMICA GENUAIR 340/12 may interfere with each other. These include:

  • other medicines used to treat breathing difficulties
  • medicines that lower the amount of potassium in your blood. These include:
    - steroids that you take by mouth (such as prednisolone)
    - diuretics (such as furosemide or hydrochlorothiazide)
    - certain medicines used to treat breathing conditions (such as theophylline).
  • medicines called beta blockers that may be used to treat high blood pressure or other heart problems (such as atenolol or propranolol) or to treat glaucoma (such as timolol)
  • medicines which can cause a change in your heart trace (electrocardiogram) known as QT interval prolongation. These include medicines for the treatment of:
    - depression, such as monoamine oxidase inhibitors or tricyclic antidepressants
    - bacterial infections (such as erythromycin, clarithromycin, telithromycin)
    - allergic reaction (such as anti-histamines).

You may need to take different amounts of your medicines or you may need to take different medicines. Your doctor and pharmacist will advise you.

If you have not told your doctor about any of these things, tell him/ her before you start using BRIMICA GENUAIR 340/12.

How to use BRIMICA GENUAIR 340/12

Follow all directions given to you by your doctor and pharmacist carefully. These directions may differ from the information contained in the leaflet.

If you do not understand the instructions, ask your doctor or pharmacist for help.

How much to use

The recommended dose is one inhalation twice a day in the morning and night, 12 hours apart.

The effects of BRIMICA GENUAIR 340/12 last for 12 hours; therefore, you should try to use your BRIMICA GENUAIR 340/12 inhaler at the same time every morning and at night. This ensures that there is always enough medicine in your body to help you breathe more easily throughout the day and night. It will also help you to remember to use it.

How to use

See instructions at the end of this leaflet or refer to the booklet contained within the carton for instructions on how to use the BRIMICA GENUAIR 340/12 inhaler.

If you are not sure of how to use BRIMICA GENUAIR 340/12, ask your doctor or pharmacist.

How long to use

Continue to use this medicine for as long as your doctor tells you to.

If it helps your breathing problems, your doctor may want you to keep using it for a long time.

This medicine helps to control your condition but it does not cure it.

If you want to stop treatment, first talk to your doctor, as your symptoms may worsen.

If you forget to use it

If you forget to have a dose of BRIMICA 340/12, inhale the dose as soon as you remember. However, if it is nearly time for your next dose, skip the missed dose.

Do not take a double dose to make up for the one that you missed. This may increase the chance of you getting an unwanted side effect.

If you have trouble remembering when to use your medicine, ask your pharmacist for some hints.

If you use too much (overdose)

Immediately telephone your doctor or the Poisons Information Centre (telephone 13 11 26) for advice, or go to Accident and Emergency at the nearest hospital, if you think that you or anyone else may have used too much BRIMICA GENUAIR 340/12. Do this even if there are no signs of discomfort or poisoning.

While you are using BRIMICA GENUAIR 340/12

Things you must do

Use this medicine exactly as your doctor has prescribed. Try not to miss any doses and use it even if you feel well. If you do not follow your doctor’s instructions, you may not get relief from your breathing problems or you may have unwanted side effects.

If you find that the usual dose of BRIMICA 340/12 is not giving as much relief as before, or does not last as long as usual, contact your doctor so that your condition can be checked. This is important to ensure your COPD is controlled properly.

If you become pregnant while using this medicine, tell your doctor. Your doctor can discuss with you the risks of using it while you are pregnant.

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are using BRIMICA GENUAIR 340/12.

Tell any other doctors, dentists, and pharmacists who treat you that you are using this medicine.

Things you must not do

Do not exceed the recommended daily dose – it will not help you to do this.

Do not take any other medicines for your breathing problems without checking with your doctor.

Do not give this medicine to anyone else, even if their condition seems similar to yours.

Do not use it to treat any other complaints unless your doctor tells you to.

Things to be careful of

Be careful driving, operating machinery or doing jobs that require you to be alert until you know how BRIMICA GENUAIR 340/12 affects you. This medicine may cause headache, dizziness or blurred vision. If you are affected by either of these side effects do not drive or use machinery until the headache has cleared and your vision has returned to normal.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are using BRIMICA GENUAIR 340/12.

All medicines may have some unwanted side effects. Sometimes they are serious, but most of the time they are not. You may need medical attention if you get some of the side effects.

Do not be alarmed by these lists of possible side effects. You may not experience any of them. Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor or pharmacist if you notice any of the following and they worry you:

  • headache
  • inflammation of the sinuses (sinusitis)
  • runny nose or sneezing (rhinitis)
  • common cold or flu symptoms
  • cough
  • increased mucous (sputum)
  • diarrhoea, vomiting or nausea
  • dry mouth
  • changes in voice
  • changes in sense of taste
  • sore mouth or throat from inhaling the powder or irritation in the throat
  • painful swelling and sores inside the mouth
  • cellulitis
  • itchy rash
  • being unable to sleep
  • fatigue
  • dizziness
  • muscle aching, cramps or spasms
  • chest pain
  • trembling, shakiness or agitation
  • nervousness or anxiety
  • infection in the tissues at the base of a tooth (tooth abscess)
  • blurred vision

Tell your doctor as soon as possible if you notice any of the following:

  • palpitations (feeling that your heartbeat is unusually fast or irregular)
  • painful and/or frequent urination – these may be signs of a urinary tract infection
  • difficulty passing urine (urinary retention)
  • difficulty in breathing.

The above list includes side effects that may require medical attention.

Tell your doctor immediately or go to Accident and Emergency at your nearest hospital if any of the following happen:

  • you develop signs of an allergic reaction such as swelling of the face, lips, tongue, throat, eyes or other part of the body; difficulty in breathing, palpitations, severe dizziness or fainting; redness, itching or rash on the skin
  • if you get tightness of the chest, coughing, wheezing or breathlessness immediately after using the medicine. These may be signs of a condition called paradoxical bronchospasm. Your doctor may consider other treatment for your COPD.

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

After using BRIMICA GENUAIR 340/12

Storage

Keep the BRIMICA GENUAIR 340/12 inhaler protected in the sealed pouch until you need to start using it. The inhaler must be used within 60 days of opening the pouch.

Keep your inhaler in a cool dry place where the temperature stays below 30°C.

Do not store BRIMICA GENUAIR 340/12 or any other medicine in the bathroom or near a sink. Do not leave it on a window sill or in the car. Heat and dampness can destroy some medicines.

Keep it where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

If your doctor tells you to stop using the inhaler or the expiry date has passed, ask your pharmacist how to dispose of it properly.

Product description

What it looks like

BRIMICA 340/12 is a white or almost white powder.

The BRIMICA GENUAIR 340/12 inhaler device is white coloured with an integral dose indicator and an orange dosage button. The mouthpiece is covered with an orange removable protective cap. It is supplied in a sealed pouch.

Ingredients

Active Ingredients

Each delivered dose contains 396 micrograms aclidinium bromide (equivalent to 340 micrograms aclidinium) and 12 micrograms of formoterol fumarate dihydrate.

Inactive Ingredient

BRIMICA GENUAIR 340/12 also contains lactose monohydrate.

Supplier

BRIMICA GENUAIR 340/12 is supplied in Australia by:

A. Menarini Australia Pty Ltd
Level 8, 67 Albert Avenue
Chatswood NSW 2067

Medical Information: 1800 644 542

BRIMICA® is a registered trademark of Almirall, S.A.

GENUAIR® is a registered trademark of AstraZeneca AB

Australian Registration Number(s):
AUST R 224899

This leaflet was revised in January 2023

For the most up to date version of this document, please go to www.menarini.com.au/cmi

[vA07-0]

Instructions for Use

Getting Started

Before using the BRIMICA GENUAIR 340/12 inhaler, please read the full instructions.

You should become familiar with the parts of your inhaler (see image 1).

Before Use

  • Before first use, tear the sealed pouch along the notch and remove the inhaler.
  • Do not press the orange button until you are ready to take a dose.
  • When you are about to take your dose of medicine, remove the protective cap by LIGHTLY SQUEEZING THE ARROWS marked on each side and pulling outwards (see image 2).

Step 1: Activate your inhaler

1.1 Look to see that nothing is blocking the mouthpiece (see image 3).

1.2 Look at the coloured control window and it should be red (see image 3).

1.3 Hold the inhaler horizontally with the mouthpiece towards you and the orange button facing straight up (see image 4).

Make sure the orange button is on top. DO NOT TILT.

1.4 Press the orange button all the way down to load your dose (see image 5). When you press the button all the way down, the control window changes from red to green.

1.5 Release the orange button (see image 6).

Make sure you release the orange button so the inhaler can work correctly.

Stop and Check: Make sure your dose is ready for inhalation

1.6 Make sure the coloured control window has changed to GREEN (see image 7).

  • The green control window confirms that your medicine is ready for inhalation.

IF THE COLOURED CONTROL WINDOW STAYS RED AFTER PRESSING THE ORANGE BUTTON ALL THE WAY DOWN, GO BACK TO 'STEP 1 ACTIVATE YOUR INHALER' AND REPEAT STEPS 1.1 TO 1.6.

Step 2: Inhale your dose

Read steps 2.1 to 2.7 fully before use. DO NOT HOLD THE ORANGE BUTTON DOWN WHILE INHALING. Do not tilt.

2.1 Before bringing the inhaler to your mouth, breathe out completely away from the mouthpiece. Do not breathe out into the mouthpiece of the inhaler.

2.2 Hold your head upright and close your lips tightly around the mouthpiece of the inhaler.

2.3 Breathe in STRONGLY and DEEPLY through your mouth (see image 8). This strong, deep breath pulls the medicine through the inhaler into your lungs.

While you breathe in you will hear a “CLICK” which signals that you are inhaling correctly. Keep breathing in for as long as possible even after you have heard the “CLICK” to be sure you get the full dose.

ATTENTION: DO NOT HOLD THE ORANGE BUTTON DOWN WHILE YOU ARE INHALING. DO NOT TILT.

2.4 Remove the inhaler from your mouth.

2.5 Hold your breath for as long as is comfortable.

2.6 Breathe out slowly through your nose, away from the mouthpiece.

Some patients may experience a grainy sensation in their mouth, or a slightly sweet or bitter taste when inhaling the medicine. Do not take an extra dose if you do not taste or feel anything after inhaling.

Stop and Check: Make sure you have inhaled correctly

2.7 Make sure the control window is now RED (see image 9). This confirms that you have inhaled your full dose correctly.

IF THE COLOURED CONTROL WINDOW IS STILL GREEN, THIS MEANS YOU HAVE NOT INHALED YOUR FULL DOSE CORRECTLY. GO BACK TO 'STEP 2 INHALE YOUR DOSE' AND REPEAT STEPS 2.1 TO 2.7.

  • If the control window still does not change to RED, you may have forgotten to release the orange button before inhaling or may not have inhaled correctly. If that happens, try again.

Make sure you have RELEASED the orange button and take a STRONG DEEP breath in through the mouthpiece.

Note: If you are unable to inhale correctly after several attempts, consult your doctor.

  • Once the control window has turned red, replace the protective cap by pressing it back onto the mouthpiece (see image 10). This will prevent moisture from getting inside the mouthpiece of your inhaler.

Additional Information

What should you do if you accidentally prepared a dose? Store your inhaler with the protective cap in place until it is time to inhale your dose, then remove the cap and start at Step 1.6.

How should you clean the inhaler? You DO NOT NEED to clean your inhaler. However, if you wish to clean it you should do so by wiping the outside of the mouthpiece with a dry tissue or paper towel.

NEVER use water to clean the inhaler, as this may damage your medicine.

How does the dose indicator work?

  • The inhaler is equipped with a dose indicator to show you approximately how many doses are left in the inhaler.
  • On first use, every inhaler contains at least 60 doses, or at least 30 doses, depending on the pack size.
  • Each time you load a dose by pressing the orange button all the way down, the dose indicator moves down slowly displaying intervals of 10 (60, 50, 40, 30, 20, 10, 0) (see image 11).

When should you get a new inhaler?

You should get a new inhaler:

  • When a RED STRIPED BAND appears in the dose indicator (see image 11); this means you are nearing your last dose, or
  • If your inhaler appears to be damaged or if you lose the cap, or
  • If your inhaler is empty (see 'How do you know that your inhaler is empty?').

How do you know that your inhaler is empty?

  • When 0 (zero) appears in the middle of the dose indicator, you should continue using any doses remaining in the inhaler.
  • When the last dose has been prepared for inhalation, the orange button will not return to its full upper position, but will be locked in a middle position (see image 12). Even though the orange button is locked, your last dose may still be inhaled. After that, the inhaler cannot be used again and you should start using a new BRIMICA GENUAIR 340/12 inhaler.

Published by MIMS October 2023

BRAND INFORMATION

Brand name

Brimica Genuair 340/12

Active ingredient

Aclidinium; Formoterol (eformoterol) fumarate dihydrate

Schedule

S4

 

1 Name of Medicine

Aclidinium bromide and formoterol fumarate dihydrate.

2 Qualitative and Quantitative Composition

Brimica Genuair 340/12 contains an adhesive mixture of micronised aclidinium bromide, formoterol fumarate dihydrate (hereafter referred to as formoterol) and α-lactose monohydrate, contained in a metered device, dry powder inhaler.
Each metered dose is equal to 400 micrograms aclidinium bromide (equivalent to 343 micrograms aclidinium) and 12 micrograms formoterol fumarate dihydrate.
Each delivered dose (the dose leaving the mouthpiece) contains 396 micrograms aclidinium bromide (equivalent to 340 micrograms aclidinium) and 11.8 micrograms formoterol fumarate dihydrate.

List of excipients with known effect.

Contains lactose.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

The inhalation powder is white or almost white, and is delivered from a white inhaler with an integral dose indicator and an orange dosage button.

4 Clinical Particulars

4.1 Therapeutic Indications

Brimica Genuair 340/12 is indicated as a long-term twice daily maintenance bronchodilator treatment to relieve symptoms in adult patients with chronic obstructive pulmonary disease (COPD).

4.2 Dose and Method of Administration

Use in adults.

The recommended dose is one inhalation of Brimica Genuair 340/12 twice daily, once in the morning and once at night.

Method of administration.

Brimica Genuair 340/12 must be administered only by the oral inhalation route. Brimica Genuair 340/12 should be administered in the morning and at night and should be taken 12 hours apart. If a dose is missed the next dose should be taken as soon as possible. However, if it is nearly time for the next dose, the missed dose should be skipped.

Use in children.

Brimica Genuair 340/12 should not be used in patients under 18 years of age.

Use in the elderly.

No dose adjustments are required for elderly patients (see Section 5.2 Pharmacokinetic Properties).

Use in patients with impaired renal function.

No dose adjustments are required for patients with renal impairment (see Section 5.2 Pharmacokinetic Properties).

Use in patients with impaired hepatic function.

No dose adjustments are required for patients with hepatic impairment (see Section 5.2 Pharmacokinetic Properties).

4.3 Contraindications

Patients with hypersensitivity to aclidinium bromide, formoterol fumarate dihydrate or to any other component of Brimica Genuair 340/12.

4.4 Special Warnings and Precautions for Use

Asthma.

Brimica Genuair 340/12 should not be used for the treatment of asthma; clinical studies of Brimica Genuair 340/12 in the treatment of asthma have not been conducted.

Paradoxical bronchospasm.

In clinical studies, paradoxical bronchospasm was not observed in patients using Brimica Genuair 340/12. However, paradoxical bronchospasm has been observed with other inhalation therapies. If this occurs, medication should be stopped and other treatment considered.

Deterioration of disease.

Brimica Genuair 340/12 is intended for the maintenance treatment of COPD. Brimica Genuair 340/12 should not be used for the relief of acute episodes of bronchospasm, i.e. as a rescue therapy. In the event of a change in COPD intensity while the patient is being treated with Brimica Genuair 340/12 so that the patient considers additional rescue medication is required, medical advice and a re-evaluation of the patient and the patient's treatment regimen should be conducted. An increase in the daily dose of Brimica Genuair 340/12 beyond the maximum dose is not appropriate.

Sympathomimetic amines.

In patients with increased susceptibility to sympathomimetic amines (e.g. inadequately controlled hyperthyroidism), Brimica Genuair 340/12 should be used with caution.

Cardiovascular effects.

Patients with a myocardial infarction during the previous 6 months, unstable angina, newly diagnosed arrhythmia within the previous 3 months, QTc (Bazett's method) above 470 msec, or hospitalisation within the previous 12 months for heart failure functional classes III and IV as per the "New York Heart Association" were excluded from the clinical studies, therefore Brimica Genuair 340/12 should be used with caution in these patients groups.
β2-adrenergic agonists may produce increases in pulse rate and blood pressure, electrocardiogram (ECG) changes such as T-wave flattening, ST segment depression and prolongation of the QTc-interval in some patients. In case such effects occur, treatment may need to be discontinued.

Systemic effects.

Brimica Genuair 340/12 should be used with caution in patients with severe cardiovascular disorders, convulsive disorders, thyrotoxicosis and phaeochromocytoma.
Metabolic effects of hyperglycaemia and hypokalaemia may be observed with high doses of β2-adrenergic agonists. In phase III clinical studies, the frequency of notable increases in blood glucose with Brimica Genuair 340/12 was low (0.1%) and similar to placebo. Hypokalaemia is usually transient, not requiring supplementation. In patients with severe COPD, hypokalaemia may be potentiated by hypoxia and concomitant treatment. Hypokalaemia increases susceptibility to cardiac arrhythmias.
Due to its anticholinergic activity, Brimica Genuair 340/12 should be used with caution in patients with symptomatic prostatic hyperplasia, urinary retention or narrow angle glaucoma (even though direct contact of the product with the eyes is very unlikely). Dry mouth, which has been observed with anticholinergic treatment, may in the long term be associated with dental caries.

Excipients.

Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Use in the elderly.

No pharmacokinetic studies have been performed with aclidinium/formoterol in elderly subjects.

Paediatric use.

Brimica Genuair 340/12 should not be used in patients under 18 years of age.

Effects on laboratory tests.

No available data.

4.5 Interactions with Other Medicines and Other Forms of Interactions

COPD medicinal products.

Co-administration of Brimica Genuair 340/12 with other inhaled anticholinergic (e.g. tiotropium bromide, glycopyrronium, aclidinium) and/or long-acting β2-adrenergic agonist (e.g. indacaterol, salmeterol, formoterol) containing medicinal products has not been studied, therefore caution should be taken when co-administering Brimica Genuair 340/12 with these drugs.
Although no formal in vivo drug interaction studies have been performed with Brimica Genuair 340/12, it has been used concomitantly with other COPD medicinal products including short-acting β2-adrenergic bronchodilators, methylxanthines, and oral and inhaled steroids without clinical evidence of drug interactions.

Metabolic interactions.

In vitro studies have shown that aclidinium or its metabolites at the therapeutic dose are not expected to cause interactions with P-glycoprotein (P-gp) substrate drugs or drugs metabolised by cytochrome P450 (CYP450) enzymes and esterases. Formoterol does not inhibit the CYP450 enzymes at therapeutically relevant concentrations.

Hypokalaemic treatment.

Concomitant treatment with methylxanthine derivatives, steroids, or non-potassium-sparing diuretics may potentiate the possible hypokalaemic effect of β2-adrenergic agonists, therefore caution is advised in their concomitant use.

β-adrenergic blockers.

β-adrenergic blockers may weaken or antagonise the effect of β2-adrenergic agonists. If β-adrenergic blockers are required (including eye drops), cardioselective β-adrenergic blockers are preferred, although they should be administered with caution.

Other pharmacodynamic interactions.

Brimica Genuair 340/12 should be administered with caution to patients being treated with medicines known to prolong the QTc interval such as monoamine oxidase inhibitors, tricyclic antidepressants, antihistamines or macrolides because the action of formoterol, a component of Brimica Genuair 340/12, on the cardiovascular system may be potentiated by these medicinal products. Medicinal products that are known to prolong the QTc interval are associated with an increased risk of ventricular arrhythmias.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No animal studies have been conducted with aclidinium and formoterol in combination to evaluate effects on fertility. In studies with the individual active components, fertility was unaffected in rats with inhalational administration of aclidinium bromide at doses up to 0.86 mg/kg/day (females) or 1.84 mg/kg/day (males), yielding plasma AUC values for aclidinium bromide > 78 times higher than in patients at the recommended human dose. No effect on male or female fertility was observed with formoterol in rats dosed orally at 60 mg/kg/day. It is considered unlikely that Brimica Genuair 340/12 administered at the recommended dose will affect fertility in humans.
(Category B3)
There are no data available on the use of Brimica Genuair 340/12 in pregnant women. No animal embryofetal development studies have been conducted with aclidinium and formoterol in combination.
Aclidinium bromide and/or its metabolites were shown to cross the placenta in rats. Developmental toxicity studies in animals revealed delayed ossification of fetuses in rats treated at ≥ 0.78 mg/kg/day by inhalation (yielding 29 times the plasma AUC for aclidinium bromide in patients at the recommended dose) and decreased fetal weight in rabbits with oral administration at ≥ 300 mg/kg/day; these doses were maternotoxic. Embryofetal development was unaffected in the rabbit at inhalational doses ≤ 3.58 mg/kg/day (yielding 13 times the plasma AUC in patients). Aclidinium bromide was not teratogenic in either animal species.
In studies completed by other companies, no teratogenic effects have been observed in rats receiving formoterol fumarate at doses up to 1.2 mg/kg/day by inhalation or oral doses of up to 60 mg/kg/day or in rabbits given formoterol fumarate at oral doses of up to 500 mg/kg/day over the period of organogenesis. Decreases in birth weight and increases in perinatal mortality have been observed when formoterol fumarate was given to rats at oral doses greater than 0.2 mg/kg/day during late gestation.
β2-adrenoceptor agonists including formoterol may inhibit labour due to a relaxant effect on uterine smooth muscle.
Because there are no adequate and well controlled studies in pregnant women, Brimica Genuair 340/12 should only be used during pregnancy if the expected benefits justify the potential risks to the fetus.
 It is unknown whether aclidinium (and/or its metabolites) are excreted in human milk.
Studies in rats have shown excretion of small amounts of aclidinium (and/or its metabolites) and formoterol into milk. Postnatal body weight gain was suppressed in the offspring of animals given aclidinium bromide during pregnancy and lactation at ≥ 0.20 mg/kg/day by inhalation (there was no effect at 0.018 mg/kg/day, estimated to yield around 8 times the clinical plasma AUC), and increased postnatal mortality was observed with formoterol at maternal oral doses of 0.2 mg/kg/day, with retardation of pup growth at 15 mg/kg/day.
A decision must be made whether to discontinue breast-feeding or to discontinue therapy with Brimica Genuair 340/12 taking into account the benefit of breast-feeding for the child and the benefit of long-term Brimica Genuair 340/12 therapy to the woman.

4.7 Effects on Ability to Drive and Use Machines

Brimica Genuair 340/12 has no or negligible influence on the ability to drive and use machines. The occurrence of blurred vision or dizziness may influence the ability to drive or to use machinery.

4.8 Adverse Effects (Undesirable Effects)

The safety profile of Brimica Genuair 340/12 is based on the experience with Brimica Genuair 340/12 and the individual components which comprised exposure in clinical trials at the recommended therapeutic dose for up to 12 months and in post-marketing experience. Adverse events associated with Brimica Genuair 340/12 were similar to those of the individual components. As Brimica Genuair 340/12 contains aclidinium bromide and formoterol fumarate dihydrate, the type and severity of adverse events associated with each of the components may be expected with Brimica Genuair 340/12.
A total of 1222 patients (527 females and 695 males) with moderate to severe COPD were treated with Brimica Genuair 340/12 at the recommended therapeutic dose. The incidence of adverse events associated with Brimica Genuair 340/12 is based on a pooled analysis of three placebo controlled trials in patients with COPD of at least 6 months duration or on experience with individual components. In these trials, 720 COPD patients were treated with Brimica Genuair 340/12 at the recommended dose of twice daily. Of these, 557 patients were treated with Brimica Genuair 340/12 for at least 6 months and 127 patients were treated with Brimica Genuair 340/12 for at least 12 months.
Across these studies, 8.4% of patients who received placebo and 7.2% of patients who received Brimica Genuair 340/12 twice daily discontinued prematurely due to adverse events. Pooled data from these placebo controlled clinical trials in COPD patients showed that the most frequently reported adverse reactions with Brimica Genuair 340/12 were nasopharyngitis (7.9%) and headache (6.8%).

Clinical trial adverse drug reactions.

Table 1 summarises the common adverse reactions that occurred with a frequency of ≥ 1.0% in the Brimica Genuair 340/12 group in the three placebo controlled clinical trials from 6 to 12 months duration, where the rates in the Brimica Genuair 340/12 group exceeded placebo by 0.5%.
Other adverse reactions that occurred in the Brimica Genuair 340/12 group at a frequency of < 1.0% and at a higher frequency than placebo include:

Cardiac disorders.

Tachycardia.

Eye disorders.

Blurred vision.

Ear and labyrinth disorders.

Cerumen impaction.

Gastrointestinal disorders.

Diverticulum.

General disorders and administration site conditions.

Product taste abnormal.

Infections and infestations.

Cellulitis, fungal infection.

Investigations.

Gamma-glutamyltransferase increased, prostatic specific antigen increased.

Metabolism and nutrition disorders.

Hypercholesterolemia.

Psychiatric disorders.

Anxiety.

Respiratory, thoracic and mediastinal disorders.

Dysphonia, pulmonary congestion, pulmonary mass.
The following adverse reactions, not already listed above, were reported in clinical trials of the individual components of Brimica Genuair 340/12 and are listed in each component PI (see Tables 2 and 3):
The following post-marketing events have been reported in patients treated with Foradile. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency which is therefore categorized as not known. Adverse drug reactions are listed according to system organ classes in MedDRA. Within each system organ class, ADRs are presented in order of decreasing seriousness.

Metabolism and nutrition disorders.

Hypokalaemia, hyperglycaemia.

Investigations.

Electrocardiogram QT prolonged, blood pressure increased (including hypertension).

Skin and subcutaneous tissue disorders.

Rash.

Cardiac disorders.

Angina pectoris, cardiac arrhythmias, e.g. atrial fibrillation, ventricular extrasystoles, tachyarrhythmia.

Respiratory, thoracic and mediastinal disorders.

Cough.

Aclidinium.

The following post-marketing events have been reported in patients treated with aclidinium bromide. Adverse drug reactions are listed according to system organ classes in MedDRA and the frequency established in the EU SmPC. See Table 4.

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

For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).
There is limited evidence on the management of overdose with Brimica Genuair 340/12. High doses of Brimica Genuair 340/12 may lead to signs and symptoms that are typical of anticholinergic (e.g. dry mouth, blurred vision, nausea and tachycardia) and/or β2-adrenergic agents (e.g. hypertension, tremor, headache, tachycardia, palpitations, dizziness and muscle spasms).
Brimica Genuair 340/12 should be discontinued in case of overdose. Supportive and symptomatic treatment is indicated.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Drugs for obstructive airway diseases, adrenergics in combination with anticholinergics. ATC code: R03AL05.

Mechanism of action.

Brimica Genuair 340/12 contains two bronchodilators: aclidinium is a long acting muscarinic antagonist (also known as an anticholinergic) and formoterol is a long-acting β2-adrenergic agonist. The combination of these substances with different mechanisms of action results in additive efficacy compared to that achieved with either component alone. As a consequence of the differential density of muscarinic receptors and β2-adrenoceptors in the central and peripheral airways of the lung, muscarinic antagonists should be more effective in relaxing central airways and β2-adrenergic agonists should be more effective in relaxing peripheral airways; relaxation of both central and peripheral airways with combination treatment may contribute to its beneficial effects on lung function. Further information regarding these two substances is provided below.
Aclidinium is a competitive muscarinic receptor antagonist, with subnanomolar affinity for all five human muscarinic receptor subtypes (M1-M5) and a longer residence time at the M3 receptors than the M2 receptors. M3 receptors mediate contraction of airway smooth muscle. Inhaled aclidinium bromide acts locally in the lungs to antagonise M3 receptors of airway smooth muscle and induce bronchodilation. Aclidinium has also been shown to provide benefits to patients with COPD in terms of symptom reduction, improvement in disease specific health status, reduction in exacerbation rates and improvements in exercise tolerance. Since aclidinium bromide is quickly broken down in plasma, the level of systemic anticholinergic side effects is therefore low.
Formoterol is a potent selective β2-adrenoceptor agonist. Bronchodilation is induced by causing direct relaxation of airway smooth muscle as a consequence of the increase in cyclic AMP through activation of adenylate cyclase. In addition to improving pulmonary function, formoterol has been shown to improve symptoms and quality of life in patients with COPD.

Pharmacodynamic effects.

Clinical efficacy studies showed that Brimica Genuair 340/12 provides clinically meaningful improvements in lung function (as measured by the forced expiratory volume in 1 second [FEV1]) over 12 hours following administration.
Brimica Genuair 340/12 demonstrated a rapid onset of action within 5 minutes of the first inhalation relative to placebo (p < 0.0001). The onset of action of Brimica Genuair 340/12 was comparable to the effect of the fast-acting β2-agonist formoterol 12 micrograms. Maximal bronchodilator effects (peak FEV1) relative to baseline were evident from day one (304 mL) and were maintained over the 6 month treatment period (326 mL).

Cardiac electrophysiology.

No clinically relevant effects of Brimica Genuair 340/12 on ECG parameters (including QT-interval) compared with aclidinium, formoterol and placebo were seen in phase III studies of 6 to 12 months duration conducted in approximately 4,000 patients with COPD. No clinically significant effects of Brimica Genuair 340/12 on cardiac rhythm were observed on 24 hour Holter monitoring in a subset of 551 patients, of whom 114 received Brimica Genuair 340/12 twice daily.

Duration and persistence of effects on lung function.

A 12-hour serial spirometry substudy, which evaluated the bronchodilation time-profile over 12 hrs post-dose, was performed in both the ACLIFORM-COPD (n = 366) and AUGMENT (n = 270) clinical studies. Statistically significant and clinically relevant adjusted mean increases from baseline in FEV1 were observed with Brimica Genuair 340/12 compared to placebo at all post-dose time points from 5 min post-dose to 12 hrs post-dose on day 1 and from 0.5 hrs to 12 hrs post-dose at week 24 (see Figure 1 and Figure 2).

Clinical trials.

Study demographics and trial design.

The efficacy of Brimica Genuair 340/12 was established in two 6-month randomised, double-blind, placebo and active-controlled pivotal clinical trials (ACLIFORM-COPD and AUGMENT). The persistence of efficacy was assessed in a 6-month extension of the AUGMENT study and in a further 12-month randomised controlled study, where the long-term safety was also evaluated. These studies enrolled 3986 patients aged ≥ 40 years who had a clinical diagnosis of stable moderate to severe COPD (with post-bronchodilator FEV1 of ≥ 30% to < 80% of predicted normal value) and a history of smoking of at least 10 pack-years. During these studies, patients were permitted to continue their stable treatment with inhaled corticosteroids, low doses of oral corticosteroids, oxygen therapy (if less than 15 hrs/day) or methylxanthines and to use salbutamol as rescue medication. The study design and patient demographics for these studies is described in Table 5.
In the pooled pivotal 6-month studies ACLIFORM-COPD and AUGMENT, the mean post-bronchodilator percent predicted FEV1 at screening was 53.9% (range: 28.0-85.8%).
The co-primary endpoints in both pivotal studies (ACLIFORM-COPD and AUGMENT) where the changes from baseline in FEV1 at 1 hour post-dose and in trough FEV1 at week 24 (compared to aclidinium bromide 400 micrograms and formoterol fumarate dihydrate 12 micrograms, respectively) to demonstrate the bronchodilator contributions of aclidinium and formoterol in Brimica Genuair 340/12, respectively. Secondary endpoints were improvement from baseline to week 24 in the Transition Dyspnoea Index (TDI) focal score and the change from baseline to week 24 in the St. George's Respiratory Questionnaire (SGRQ) total score. Other efficacy variables included: rescue medication usage, COPD exacerbations, COPD symptoms (recorded using an electronic patient diary) and other measures of lung function (FEV1 at various time points, forced vital capacity and inspiratory capacity).

Effects on lung function.

Inhalation of Brimica Genuair 340/12 twice daily by patients with moderate to severe COPD resulted in statistically and clinically meaningful improvements in lung function (as measured by FEV1) relative to placebo in both ACLIFORM-COPD and AUGMENT.
In ACLIFORM-COPD, Brimica Genuair 340/12 showed statistically significant improvements in FEV1 at 1 hour post-dose relative to placebo and aclidinium bromide of 299 mL and 125 mL, respectively (both p < 0.0001) and statistically significant improvements in trough FEV1 relative to placebo and formoterol fumarate of 143 mL and 85 mL, respectively (both p < 0.0001) at week 24. In AUGMENT, Brimica Genuair 340/12 showed statistically significant improvements in FEV1 at 1 hour post-dose relative to placebo and aclidinium bromide of 284 mL and 108 mL (both p < 0.0001), respectively, and improvements in trough FEV1 relative to placebo and formoterol fumarate of 130 mL (p < 0.0001) and 45 mL (p = 0.01), respectively.
The lung function effects of Brimica Genuair 340/12 were observed within 5 minutes of the first dose and were maintained over the dosing interval. There was a sustained effect over time in the 6 months (see Figure 3 and Figure 4 for representative data from ACLIFORM-COPD) and one year phase III studies.

Symptom relief and disease specific health status.

The effects of Brimica Genuair 340/12 on dyspnoea and disease specific health status were evaluated using the Transition Dyspnoea Index (TDI), and the St. George's Respiratory Questionnaire (SGRQ), respectively.
Following 24 weeks of treatment, Brimica Genuair 340/12 provided statistically significant (p < 0.0001) and clinically meaningful improvements in breathlessness (assessed by the TDI) with a mean difference compared to placebo of 1.29 units and 1.44 units in ACLIFORM-COPD and AUGMENT, respectively. Significantly more patients treated with Brimica Genuair 340/12 had an increase in TDI focal score greater than the minimal clinically important difference (MCID) of 1 unit compared to placebo in both studies (Table 6). Improvements were observed in each of the individual TDI domains (functional impairment, magnitude of effort and magnitude of task) at all time points in both ACLIFORM-COPD and AUGMENT when compared to placebo (p < 0.05 for each measure).
Following 24 weeks of treatment, Brimica Genuair 340/12 provided improvements in disease specific health status (assessed by the St. George's Respiratory Questionnaire [SGRQ] total score) relative to placebo (-4.35 units, p < 0.0001) as well as improvements in all 3 SGRQ domains (symptoms, activities and impact; p < 0.02 for each domain) in AUGMENT, while only a small decrease in SGRQ total score compared to placebo was observed in ACLIFORM-COPD (-0.65 units, p = 0.598) due to an unexpectedly large placebo response (see Table 6).
In the pooled analysis of the two 6-month phase III studies (ACLIFORM-COPD and AUGMENT) Brimica Genuair 340/12 showed statistically significant greater improvements in TDI focal score compared to aclidinium (0.4 units, p = 0.016) or formoterol (0.5 units, p = 0.009). In addition, a higher percentage of patients receiving Brimica Genuair 340/12 responded with a clinically meaningful improvement in TDI focal score (defined as an increase of at least 1 unit) compared to either aclidinium or formoterol (61.9% compared to 55.7% and 57.0%, respectively; p = 0.056 and p = 0.100, respectively). Brimica Genuair 340/12 also showed statistically significant improvements in SGRQ when compared to formoterol (-1.7 units; 95% CI: -3.2 to -0.3; p = 0.018).
Brimica Genuair 340/12 improved daily symptoms of COPD (assessed by E-RS total score) as well as overall night-time symptoms, overall early morning symptoms and symptoms limiting early morning activities compared to placebo, aclidinium bromide and formoterol fumarate (all p < 0.05).

COPD exacerbations.

Pooled efficacy analysis of the two 6-month phase III studies demonstrated a statistically significant reduction of 29% in the rate of moderate or severe exacerbations (requiring treatment with antibiotics or corticosteroids or resulting in hospitalisations) with Brimica Genuair 340/12 compared to placebo (rates per patient per year: 0.29 vs. 0.42, respectively; p = 0.036).
In addition, Brimica Genuair 340/12 statistically significantly delayed the time to first moderate or severe exacerbation compared to placebo (hazard ratio = 0.70; p = 0.027).

Use of rescue medication.

Brimica Genuair 340/12 reduced the use of rescue medication over 6 months compared to placebo (by 0.9 puffs per day [p < 0.0001]), aclidinium (by 0.4 puffs/day [p < 0.001]) and formoterol (by 0.2 puffs/day [p = 0.062]).

5.2 Pharmacokinetic Properties

When aclidinium and formoterol were administered in combination by the inhaled route, the pharmacokinetics of each component showed no relevant differences from those observed when the medicinal products were administered separately.

Absorption.

Following inhalation of a single dose of Brimica Genuair 340/12, aclidinium and formoterol were rapidly absorbed into plasma, reaching peak plasma concentrations within 5 minutes of inhalation in healthy subjects and within 24 minutes of inhalation in patients with COPD. The peak plasma concentrations at steady state of aclidinium and formoterol observed in patients with COPD treated with Brimica Genuair 340/12 twice daily for 5 days were reached within 5 minutes post-inhalation and were 128 picogram/mL and 17 picogram/mL, respectively.

Distribution.

Whole lung deposition of inhaled aclidinium via Genuair averaged approximately 30% of the metered dose. The plasma protein binding of aclidinium determined in vitro most likely corresponded to the protein binding of the metabolites due to the rapid hydrolysis of aclidinium in plasma; human plasma protein binding was 87% for the carboxylic acid metabolite and 15% for the alcohol metabolite. The main plasma protein that binds aclidinium is albumin.
The plasma protein binding of formoterol is 61% to 64% (34% primarily to albumin). There is no saturation of binding sites in the concentration range reached with therapeutic doses.

Metabolism.

Aclidinium is rapidly and extensively hydrolysed to its pharmacologically inactive alcohol- and carboxylic acid-derivatives. Plasma levels of the acid metabolite are approximately 100-fold greater than those of the alcohol metabolite and the unchanged active substance following inhalation. The hydrolysis occurs both chemically (non-enzymatically) and enzymatically by esterases (principally in plasma), with butyrylcholinesterase being the main human esterase involved in the hydrolysis. The low absolute bioavailability of inhaled aclidinium (< 5%) is because aclidinium undergoes extensive systemic and pre-systemic hydrolysis whether deposited in the lung or swallowed. Biotransformation via CYP450 enzymes plays a minor role in the total metabolic clearance of aclidinium. In vitro studies have shown that aclidinium bromide and its major metabolites do not inhibit human CYPs 1A2, 2A6, 2B6, 2B8, 2C9, 2C19, 2D6, 2E1, 3A4/5 or 4A9/11, do not induce CYPs 1A2, 2B6, 2C8, 2C9, 2C19 or 3A4/5, and do not inhibit esterases (carboxylesterase, acetylcholinesterase and butyrylcholinesterase) at therapeutic concentrations. In vitro studies have shown that neither aclidinium bromide nor the main metabolites of aclidinium bromide are inhibitors of P-glycoprotein. The same studies have also demonstrated that aclidinium bromide and its acid metabolite are not substrates of P-glycoprotein however its alcohol metabolite is a potentially weak substrate.
Formoterol is eliminated primarily by metabolism. The prominent pathway involves direct glucuronidation, with O-demethylation followed by glucuronide conjugation being a further metabolic pathway. Cytochrome P450 isoenzymes CYP2D6, CYP2C19, CYP2C9 and CYP2A6 are involved in the O-demethylation of formoterol. Formoterol does not inhibit CYP450 enzymes at therapeutically relevant concentrations.

Excretion.

Following inhalation of Brimica Genuair 340/12 micrograms, with plasma sampling up to 24 hours post-dose, the terminal elimination half-life observed for aclidinium bromide ranged from 11-33 hours and for formoterol from 12-18 hours.
Mean effective half-lives* observed for both aclidinium and formoterol (based on the accumulation ratio) are approximately 10 hours.
*Half-life consistent with product accumulation based on a known dose regimen.
Following intravenous administration of radiolabelled aclidinium 400 micrograms to healthy subjects, approximately 1% of the dose was excreted as unchanged aclidinium bromide in the urine. Up to 65% of the dose was eliminated as metabolites in the urine and up to 33% as metabolites in the faeces. Following inhalation of aclidinium 200 micrograms and 400 micrograms by healthy subjects or patients with COPD, the urinary excretion of unchanged aclidinium was very low at about 0.1% of the administered dose, indicating that renal clearance plays a minor role in the total aclidinium clearance from plasma.
The major part of a dose of formoterol is transformed by liver metabolism followed by renal elimination. After inhalation, 6% to 9% of the delivered dose of formoterol is excreted in the urine unchanged or as direct conjugates of formoterol.

Special populations.

Elderly patients.

No pharmacokinetics studies have been performed with aclidinium/formoterol in elderly subjects. Since no dosage adjustments are needed for either aclidinium or formoterol medicinal products in elderly patients, no dosage adjustment is warranted for aclidinium/formoterol in geriatric patients.

Renally and hepatically impaired patients.

There are no data regarding the specific use of aclidinium/formoterol in patients with renal or hepatic impairment. Since no dosage adjustments are needed for either aclidinium or formoterol medicinal products in patients with renal or hepatic impairment, no dosage adjustment is warranted for aclidinium/formoterol.

Race.

Following repeated inhalations of Brimica Genuair 340/12, the systemic exposure of aclidinium and formoterol, as measured by AUC, is similar in Japanese and Caucasian patients.

5.3 Preclinical Safety Data

Genotoxicity.

Aclidinium bromide.

Aclidinium bromide returned equivocal results in assays for bacterial mutagenicity and in the mouse lymphoma-TK assay in vitro. Aclidinium bromide, at high levels of systemic exposure, was devoid of genotoxicity in vivo in the mouse bone marrow micronucleus test and in the unscheduled DNA synthesis (UDS) assay in rat liver. Aclidinium bromide is not considered to pose a genotoxic hazard to patients.

Formoterol fumarate.

Mutagenicity tests covering a broad range of experimental endpoints have been conducted. No genotoxic effects were found in any of the in vitro or in vivo tests performed.

Carcinogenicity.

Aclidinium bromide.

No treatment-related neoplastic lesions were noted in the carcinogenicity studies of 2 years duration in mice and rats, involving inhalational administration. The highest dose levels employed in the respective species (2.45 mg/kg/day in mice and 0.20 mg/kg/day in rats) yield approximately 63 and 26 times the plasma AUC in patients at the recommended dose and approximately 120 and 11 times the local dose in the lung.

Formoterol fumarate.

In studies performed by other companies over 2 years in rats and mice, formoterol fumarate, given via the diet or drinking water at very high doses, was associated with increases in a variety of tumour types. In rats, treatment was associated with benign granulosa/ theca cell tumours in the ovaries (≥ 0.5 mg/kg/day), mesovarian leiomyomas (≥ 18 mg/kg/day), mammary adenocarcinomas (≥ 36 mg/kg/day) and thyroid C-cell neoplasms (46 mg/kg/day). A mesovarian leiomyoma was also seen in a female rat dosed by inhalation at 130 micrograms/kg/day for two years (approximately 49 times the MRHD (maximum recommended human dose) in adults and children on a micrograms/m2 basis). In mice, these included hepatocellular adenoma and carcinomas (≥ 2 mg/kg/day), leiomyomas and leiomyosarcomas in the female reproductive tract (≥ 2 mg/kg/day) and adrenal subcapsular cell tumours (≥ 66 mg/kg/day). Mammary adenocarcinomas, smooth muscle tumours in the female reproductive tract and effects on the ovary have been reported in rats and mice treated with other β2-adrenoreceptor agonists and are likely to be secondary to prolonged stimulation of β2-adrenoreceptors in these tissues.

6 Pharmaceutical Particulars

6.1 List of Excipients

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.

In-use shelf life.

Keep the Genuair inhaler inside the sealed pouch until the administration period starts.
To be used within 60 days of opening the pouch.

6.4 Special Precautions for Storage

Store below 30°C.

6.5 Nature and Contents of Container

The inhaler device is a multicomponent device. It is white-coloured with an integral dose indicator and a orange dosage button. The mouthpiece is covered with a removable orange protective cap.
The inhaler is supplied in an aluminium laminated pouch, placed in a cardboard carton.
Carton containing 1 inhaler with 30 unit doses.
Carton containing 1 inhaler with 60 unit doses.
Carton containing 3 inhalers each with 60 unit doses.
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

Chemical structure.

Aclidinium bromide.


Stereochemistry: The product has one optically active centre. Aclidinium bromide is a single stereoisomer with the (3R) configuration.
Chemical name: (3R)-3-[(hydroxy)di(thiophen-2-yl)acetyloxy]-1-(3-phenoxypropyl)-1 lambda5-azabicyclo[2.2.2] octan-1-ylium bromide.
Molecular formula: C26H30NO4S2Br.
Molecular mass: 564.56.
AAN: aclidinium bromide.

Formoterol fumarate dihydrate.


Stereochemistry: The product has two optically active centres. Formoterol fumarate dihydrate is a racemate consisting of the (R,R) and (S,S) enantiomers.
Chemical name: (±)-N-[2-Hydroxy-5- [(1RS)-1-hydroxy-2- [[(1RS)-2-(4-methoxyphenyl)-1-methylethyl]amino]ethyl]phenyl] formamide, E-butenedioate (2:1 salt) dihydrate.
Molecular formula: C42H52N4O12.2H2O.
Molecular mass: 840.9.
AAN: formoterol fumarate dihydrate.

CAS number.

Aclidinium bromide.

320345-99-1.

Formoterol fumarate dihydrate.

183814-30-4.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription only medicine.

Summary Table of Changes