Consumer medicine information

Aridol

Mannitol

BRAND INFORMATION

Brand name

Aridol

Active ingredient

Mannitol

Schedule

Unscheduled

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Aridol.

What is in this leaflet

This leaflet answers some common questions about Aridol. 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 doctor has weighed the risks of you taking Aridol against the benefits they expect it will have for you.

If you have any concerns about taking an Aridol test, ask your doctor or pharmacist.

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

What Aridol is used for

Aridol is a test to see if you have asthma or not.

Aridol contains the active ingredient mannitol.

Asthma is a condition causing inflammation of the airways, making it difficult to breathe sometimes. People with asthma are often very susceptible to factors in the environment such as exercise, dust, smoke and other irritants.

Your doctor or another specifically trained healthcare professional will ask you to breathe in Aridol, using a small inhaler.

  • For people who do have asthma, their airways will become narrower and so they may find it harder to breathe.
  • People who do not have asthma will not experience their airways becoming narrower when breathing in Aridol. They will still be able to breathe normally.

As part of the test, you will be asked to blow into a tube that will measure the effect of Aridol on your lungs.

This medicine is only used to see whether you have asthma.

Ask your doctor if you have any questions about why an Aridol test has been ordered for you.

Before you start to use it

When you must not use it

Do not take an Aridol test if you have an allergy to:

  • mannitol
  • any of the ingredients listed at the end of this leaflet

Some of the symptoms of an allergic reaction to a medicine 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 take an Aridol test:

  • if you now have or used to have a swollen or weakened blood vessel around the heart or brain (aneurysm);
  • if you have high blood pressure which is not controlled by medicine;
  • if you have had a heart attack in the last 6 months;
  • if you have had a stroke in the last 6 months.

Do not take an Aridol test after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering.

If you are not sure whether you should do the Aridol test, talk to your doctor.

Before you start to take the test

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor:

  • if your lung capacity is reduced (this will be measured prior to the test);
  • if you have previously experienced difficulty in breathing, or have wheezed or coughed during a spirometry test (blowing into a measuring instrument);
  • if you are coughing up blood;
  • if you have air in the pleural space between the chest wall and the lungs, causing chest pain and shortness of breath (pneumothorax);
  • if you have recently had stomach, chest or eye surgery;
  • if you experience chest pain (angina pectoris);
  • if you have problems performing the spirometry test (the person doing the test will tell you);
  • if you have had an infection of the airways in the last 2 weeks.

Your doctor may want to take special precautions or delay the test if you have any of these conditions.

If you experience an asthma attack (breathlessness, wheezing and/or cough) during the spirometry test, you may be given a medicine to keep your air passages open and the test will be stopped.

Do not take Aridol on your own. Aridol is only to be given by trained professionals familiar with the use of similar tests and their possible effects.

Children under the age of 6 should not be given Aridol or perform the test.

Tell your doctor if you are pregnant or plan to become pregnant. Aridol is not recommended during pregnancy.

Tell your doctor if you are breast-feeding or plan to breast-feed. It is not known if Aridol passes into the breast milk.

If you have not told your doctor about any of the above, tell him/her before you do the Aridol test.

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.

If you are taking medicines to treat asthma or allergies, you may need to stop taking these before the test. These medicines may affect your body’s response to Aridol. Your doctor will tell you which medicine(s) to stop and for how long (usually between 6 hours and 4 days before the test).

Do not drink coffee, tea or cola, eat chocolate or any other foods containing caffeine on the day of the test, especially before the test is done.

Do not take vigorous exercise on the day of the test, especially before the test is done.

Do not smoke for at least 6 hours before the test.

How to take Aridol

You will be given Aridol via an inhaler (Osmohaler™) by a doctor or another specially trained healthcare professional who will be with you throughout the test. You will not be left on your own.

You must not put Aridol capsules in your mouth or swallow them.

Performing the test

  1. You will be asked to sit comfortably on a chair.
  2. Initially you will be asked to blow forcefully into a tube (spirometry test).
  3. A nose clip will then be put on your nose so you will only be able to breathe in and out of your mouth.
  4. After breathing out fully, you will be asked to deeply breathe in the Aridol medicine using a special inhaler (Osmohaler™).
  5. You will then hold your breath for five seconds before breathing out.
  6. The nose clip will be removed and you will be asked to breathe normally.
  7. Next you will be asked to blow forcefully into the tube again. This test measures the effect of Aridol on your lungs.
  8. Steps 3-7 may be repeated up to 9 times with more and more Aridol depending on the effect on your lungs (as measured in step 7), until the test is finished.
  9. Once the test has finished you may be given a medicine to help you breathe.

If you are unsure about any part of the test, or have questions about the medicine, please talk to the doctor or another specially trained healthcare professional performing the test.

If you take too much (overdose)

If you think you may have been given too much Aridol, tell the doctor or healthcare professional performing the test straight away. You may feel that you cannot breathe, become wheezy or cough if you have taken too much Aridol. The doctor may give you oxygen and medicines to help you breathe.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well during or after an Aridol test. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

Very common (likely to affect more than 1 in 10 people):

  • Headache

Common (likely to affect less than 1 in 10 but more than 1 in 100 people):

  • Nausea (feeling sick)
  • upper stomach pains
  • diarrhoea
  • vomiting
  • dizziness
  • tiredness
  • itchy eyes
  • runny nose
  • cold or flu
  • sore or irritated throat
  • discomfort when swallowing
  • chest tightness
  • back pain
  • breathlessness
  • cough or wheezing

Tell your doctor if you notice anything else that is making you feel unwell. Other side effects not listed above may also occur in some people.

After using Aridol

Storage

Aridol must be kept in a cool, dry place where the temperature stays below 25 degrees Celsius. Protect from sunlight.

Do not store medicines in the bathroom or near a sink. Do not leave any medicine on a window sill or in the car. Heat and dampness can destroy some medicines.

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

Product Description

What it looks like

Aridol comes as a powder contained within capsules which are utilised for inhalation.

The capsules are supplied in blister packs. One diagnostic kit, packed in a box, consists of:

  • 1 empty capsule
  • 1 x 5 mg capsule
  • 1 x 10 mg capsule
  • 1 x 20 mg capsule
  • 15 x 40 mg capsules
  • 1 Osmohaler™

The powder is white to off-white.

The empty capsule is clear printed with two white bands.

The 5 mg capsule is half white, half clear with “5 mg” printed on body.

The 10 mg capsule is half yellow, half clear with “10 mg” printed on body.

The 20 mg capsule is half pink, half clear with “20 mg” printed on body.

The 40 mg capsules are half red, half clear with “40 mg” printed on body.

Ingredients

Active Ingredients

Aridol capsules contain 0mg, 5mg, 10mg, 20mg or 40mg of the active ingredient mannitol.

Inactive Ingredients

The other ingredients of Aridol are gelatin, titanium dioxide, yellow iron oxide and red iron oxide (contained in the capsule shells).

Supplier

Aridol is supplied in Australia by:

BTC Speciality Health
Level 1, 10 Oxley Road
Hawthorn Vic 3122
Australia
www.btchealth.com.au
Tel: 1800 100 282

Australian Registration Number

AUST R 116832

This leaflet was revised on 06 Jan 2022.© Pharmaxis Ltd (2006)

All rights reserved

® Registered Trademark

Published by MIMS March 2022

BRAND INFORMATION

Brand name

Aridol

Active ingredient

Mannitol

Schedule

Unscheduled

 

1 Name of Medicine

Mannitol.

2 Qualitative and Quantitative Composition

Each capsule contains 0 mg, 5 mg, 10 mg, 20 mg or 40 mg mannitol. The delivered dose from each of the 5, 10, 20 and 40 mg capsules is approximately 3, 8, 16 and 31 mg, respectively.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Powder for inhalation in hard capsules.
Hard gelatin capsule-size 3:
Empty capsule: Clear body and cap printed with two white bands.
5 mg capsule: Clear body/white cap with "5 mg" printed on body.
10 mg capsule: Clear body/yellow cap with "10 mg" printed on body.
20 mg capsule: Clear body/pink cap with "20 mg" printed on body.
40 mg capsule: Clear body/red cap with "40 mg" printed on body.

4 Clinical Particulars

4.1 Therapeutic Indications

Aridol is indicated for identifying bronchial hyperresponsiveness to assist in the diagnosis of asthma.

4.2 Dose and Method of Administration

Aridol is supplied in kit form containing sufficient capsules to complete one complete challenge, and the inhalation device (Osmohaler).
Prior to the challenge, spirometry should be performed and the reproducibility of the resting FEV1 established.
The patient should be seated comfortably and encouraged to maintain good posture to assist the effective delivery of Aridol to the lungs. The test should proceed as follows:
1. Apply nose clip and subject should be directed to breathe through the mouth.
2. Insert 0 mg capsule into inhalation device. Puncture capsule by depressing buttons on side of device slowly and once only (a second puncture may fragment the capsules).
3. The patient should exhale completely before inhaling from device in a controlled rapid deep inspiration.
4. At the end of deep inspiration start 60 second timer; subject should hold breath for 5 seconds and exhale through mouth before removal of nose clip.
5. At the end of 60 seconds, measure the FEV1 in duplicate (this becomes baseline FEV1).
6. Insert 5 mg capsule into inhalation device and proceed as above.
7. Repeat steps 1 to 4 following the dose steps in Table 1 until the patient has a positive response or 635 mg has been administered.
A positive response is achieved when the patient experiences either of the following:
≥ 15% fall in FEV1 from baseline (0 mg dose); or
≥ 10% incremental fall in FEV1 between doses.

Examples of positive tests.

1. FEV1 fall following dose step 2: 3%;
FEV1 fall following dose step 3: 8%;
FEV1 fall following dose step 4: 16%; as the total fall is 16% (≥ 15%), the test is positive.
2. FEV1 fall following dose step 2: 3%;
FEV1 fall following dose step 3: 14%; although the total fall is < 15%, the incremental fall is 11% (≥ 10%) and the test is positive.

Points to remember.

1. There should be minimal delay between FEV1 measurement and the next dose so that the osmotic effect in the airway is cumulative.
2. At least 2 repeatable FEV1 measures should be obtained after each dose.
3. The 80 and 160 mg doses are administered in multiples of 40 mg capsules (i.e. 2 x 40 mg and 4 x 40 mg, respectively). There is no interval between administering multiple capsules for these doses. One capsule should be followed immediately by the next until that total dose has been inhaled.
4. After inhalation of each dose, the capsule should be checked to ensure it is empty. A second inhalation from the same capsule may be required if the dose has not been entirely dispersed from the capsule.
5. The gelatin capsules may fragment when punctured. To minimise the possibility of this occurring, each capsule should not be punctured more than once.
6. A new inhalation device is to be used for each test which should not be cleaned during the test.
As with all challenge tests, most patients recover spontaneously. However, those with a positive challenge result or who experience aggravation of asthma or significant respiratory symptoms should receive a standard dose of a beta2 agonist to expedite recovery. Those with a negative challenge may also receive a standard dose of a beta2-agonist to expedite recovery. Following administration of a beta2-agonist FEV1 usually recovers within 10-20 minutes. Patients should be monitored until their FEV1 is to within 5% of baseline levels.

4.3 Contraindications

Known hypersensitivity to mannitol or any of the excipients.
Aridol should not be given to patients with conditions that may be compromised by induced bronchospasm or repeated blowing manoeuvres. These include aortic or cerebral aneurysm, uncontrolled hypertension, myocardial infarction or a cerebral vascular accident in the previous six months.

4.4 Special Warnings and Precautions for Use

Aridol is to be administered by inhalation only. The Aridol inhalation test should be conducted only under the supervision of a physician or other appropriately trained personnel thoroughly familiar with all aspects of bronchial provocation tests and the management of acute bronchospasm. Patients should not be left unattended during the procedure once the administration of Aridol has begun.
Mannitol, the active ingredient in Aridol, acts as a bronchoconstrictor and may cause bronchospasm/bronchoconstriction in susceptible patients. Medications to treat severe bronchospasm must be present in the testing area including bronchodilators and oxygen.
General precautions when conducting spirometry and bronchial provocation testing should be observed, including using caution in patients with the following: ventilatory impairment (resting FEV1 of less than 70% of normal predicted values or an absolute value of 1.5 L in adults); spirometry induced bronchoconstriction, haemoptysis of unknown origin, pneumothorax, recent abdominal or thoracic surgery, recent eye surgery, unstable angina, inability to perform spirometry of acceptable quality or upper or lower respiratory tract infection in the previous 2 weeks.
If a patient has spirometry induced asthma or the FEV1 fall following the 0 mg capsule is greater than 10%, a standard dose of bronchodilator should be given and the Aridol challenge discontinued.

Exercise.

Vigorous exercise should not be performed prior to testing on the day of the test.

Smoking.

Patients should refrain from smoking for at least 6 hours prior to testing.

Use in hepatic impairment.

Formal pharmacokinetic studies with mannitol, the active ingredient, have not been conducted in patients with hepatic impairment.

Use in renal impairment.

Formal pharmacokinetic studies with mannitol, the active ingredient, have not been conducted in patients with renal impairment.
However, an increase in systemic exposure of mannitol can be expected in patients with renal impairment based on the kidney being its primary route of elimination.

Use in the elderly.

Aridol has been given to a limited number of elderly patients.

Paediatric use.

The Aridol test should not be used in patients below 6 years of age due to their inability to produce acceptable quality spirometric measurements.
The pivotal trial enrolled 138 children (125 asthmatic and 13 nonasthmatic subjects). Also there have been a small number of other studies investigating the safety and efficacy of Aridol in children. It appears the sensitivity and specificity as well as adverse event profile is comparable with adults. The mean maximum fall in FEV1 was approx. 21% in children which was the same as in adults.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Regular use of inhaled corticosteroids reduces the airway sensitivity to Aridol and, in many individuals, complete inhibition of the airway response occurs.
The following should be withheld before conducting an Aridol test as they may affect the results.

Medicines.

Recommended periods for withholding medicines before the Aridol test are listed in Table 2.

Foods.

Ingestion of significant quantities of coffee, tea, cola drinks, chocolate or other food containing caffeine may decrease bronchial responsiveness. These substances should be withheld on the day of the test.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

The effect of inhaled mannitol on fertility has not been investigated.
(Category B2)
Animal reproduction studies have not been carried out with inhaled mannitol. However, studies with orally administered mannitol indicate no teratogenic effects in mice or rats, at doses of up to 1.6 g/kg, or in hamsters at 1.2 g/kg. The effects of a possible hyperresponsiveness reaction on the mother and/or the foetus are unknown and therefore Aridol should not be given to pregnant women.
 It is not known whether this drug is excreted in human milk. Many compounds are excreted in human milk and therefore caution should be exercised when mannitol is administered to breastfeeding women.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

A positive result with Aridol may produce symptoms of bronchospasm such as chest tightness, cough or wheezing.
Most patients experience cough during the challenge; however, it is only occasional in the vast majority of patients (83%) experiencing cough. In the remainder, it is frequent enough to cause some delay in continuation of the challenge (16%) or discontinuation (1%). Oropharyngeal pain, a commonly reported adverse event, may be reduced if the mouth is rinsed after the test.
Adverse events were monitored in the pivotal clinical trial from the beginning of the challenge to a week following the challenge day. Due to the short half-life of mannitol, the causal link would be expected to diminish over that time. Most adverse events were reported to be mild and transient. Table 3 is a table of adverse events reported in the trial (compared to hypertonic saline) at an incidence of 1% or more.
Adverse events reported in this study in the mannitol group at an incidence of < 1% include chest pain, oxygen saturation decreased, retching and migraine.
Adverse events reported in other clinical trials include chest discomfort, rhinitis, hyperhidrosis and feeling jittery.

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

Susceptible persons may suffer a hyperresponsiveness reaction from an overdose. The reaction can be treated with a bronchodilator. There is some experience with Aridol in clinical studies where patients experienced a 15% fall and inhaled a further dose. These studies used 20-25% as the target FEV1 fall. The maximum fall measured was 50.2%. If excessive bronchoconstriction occurs, a beta2-agonist should be given, and oxygen if necessary.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

When inhaled, mannitol induces an increase in osmolarity in the airways similar to other bronchial provocation tests such as hypertonic saline, exercise and the hyperpnea of dry air. The increase in osmolarity is associated with the release of a wide variety of mediators of bronchoconstriction from inflammatory cells within the airways. These mediators then act via specific receptors on bronchial smooth muscle to cause contraction and the airways to narrow. The airway response is most pronounced (hyperresponsiveness) in patients with asthma and exercise induced asthma. The airway response to Aridol is measured using the forced expiratory volume in one second (FEV1). The sensitivity to mannitol is reported as the delivered dose of mannitol to cause a 15% reduction in FEV1.
The involvement of airway inflammation has been demonstrated by a reduction in the sensitivity to inhaled mannitol following treatment with inhaled corticosteroids. The involvement of mediators has been demonstrated by the reduction in response to mannitol after specific antagonists. The histamine antagonist, fexofenadine, has been shown to reduce the airway sensitivity to mannitol. The time to recover to baseline FEV1 is reduced after treatment with the cysteinyl leukotriene receptor antagonist, montelukast although there was no effect observed on the sensitivity to mannitol. Nedocromil sodium, a drug that inhibits mast cell mediator release as well as reducing sensory nerve activation, has been shown to reduce sensitivity to mannitol and in some cases the airway response to mannitol was inhibited.

Clinical trials.

The pivotal trial in the clinical development program was a controlled, randomised, crossover study which compared Aridol with hypertonic (4.5%) saline in identifying bronchial hyperresponsiveness. The study enrolled 646 subjects of whom 592 completed both arms of the trial. The study enrolled both asthmatic (n = 551) and nonasthmatic (n = 95) subjects aged 6 to 83 years.
The mannitol challenge test was positive (15% fall in FEV1) in 296 subjects at a mean dose of 186 mg. In nonasthmatic subjects the mean maximum fall in FEV1 was 4.95% ± 4.7%. Compared to the hypertonic saline challenge, the mannitol challenge had a sensitivity of 81% and a specificity of 87%. The mean maximum FEV1 fall (± SD) for the two challenges was comparable: 21.02% (± 5.7) for mannitol and 21.34% (± 5.9) for hypertonic saline.
Following completion of the two challenge tests, a respiratory physician assessed the data and categorised the subjects as being asthmatic or non asthmatic on the basis of their medical history, history of respiratory symptoms and the results of the hypertonic saline challenge. Compared to this clinical diagnosis, the mannitol challenge had a sensitivity of 60% and a specificity of 95%. The hypertonic saline challenge had a sensitivity of 65% and a specificity of 95%. The positive and negative predictive values for the mannitol challenge were 98.3% and 33.9% respectively, resulting in positive and negative likelihood ratios of 12.55 and 0.42, respectively.
Of the 196 subjects classified as asthmatic by the respiratory physician, but having a negative mannitol challenge, 159 (81%) were taking glucocorticosteroids, 72.7% had no wheezing in the week prior to the challenge and 65.6% had not used a reliever puffer more than once in the previous week. It is important to consider current glucocorticosteroid therapy when interpreting indirect challenge test results.

5.2 Pharmacokinetic Properties

There are no pharmacokinetic data available for mannitol following inhalation using a dry powder inhaler although limited animal data on mannitol solution indicates an absorption half-life of approximately 0.2-1 hours. Following absorption, the pharmacokinetic profile of inhaled mannitol can be expected to follow that of intravenous administered mannitol.
When administered intravenously, mannitol is eliminated largely unchanged by glomerular filtration and 80% of the dose is excreted in the urine within 3 hours. The elimination half-life in adults is approximately 1-2 hours. In the presence of renal failure, the half-life is extended.

5.3 Preclinical Safety Data

Genotoxicity.

Mannitol was not genotoxic in Salmonella typhimurium and E. coli strain WP2. Negative results were also recorded in Saccharomyces cerevisiae, rat bone marrow cells and human WI-38 cells. Doses of up to 5 g/kg by gavage were also negative in a dominant lethal assay in rats.

Carcinogenicity.

Dietary mannitol (≤ 5%) given for 2 years had no significant effect on tumour incidence in B6C3F1 mice and F344 rats. Animal carcinogenicity studies have not been carried out with inhaled mannitol.

6 Pharmaceutical Particulars

6.1 List of Excipients

Capsule shell: gelatin.

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 25°C. Protect from sunlight.

6.5 Nature and Contents of Container

The capsules are available in Al/Al blister packs.
Aridol is provided as a complete diagnostic kit. Each kit contains:
1 x empty clear/clear capsule;
1 x 5 mg white/clear capsule;
1 x 10 mg yellow/clear capsule;
1 x 20 mg pink/clear capsule;
15 x 40 mg red/clear capsule;
1 x Inhalation device (Osmohaler).

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.


Also known as D-mannitol.
Mannitol is a hexahydric alcohol. The powder is a white or almost white, crystalline powder of free flowing granules. Mannitol is freely soluble in water and very slightly soluble in alcohol. Mannitol shows polymorphism.
The empirical formula is C6H14O6. Molecular weight is 182.2.

CAS number.

69-65-8.

7 Medicine Schedule (Poisons Standard)

Unscheduled.

Summary Table of Changes