OSMOHALE Inhalation powder, hard capsule Ref.[27640] Active ingredients: Mannitol

Osmohale is to be administered by inhalation only. Inhaled mannitol causes bronchoconstriction. The Osmohale inhalation test should only be conducted in suitable laboratories/clinics under the supervision of an experienced physician and by a physician or another health professional appropriately trained to perform bronchial provocation tests and to manage acute bronchospasm. The responsible physician, appropriately trained to treat acute bronchospasm, including appropriate use of resuscitation equipment, must be close enough to respond quickly to an emergency. A stethoscope, sphygmomanometer, and pulse oximeter should be available.

Patients should not be left unattended during the procedure once the administration of Osmohale has begun.

Medications to treat severe bronchospasm must be present in the testing area. They include adrenaline for subcutaneous injection, and salbutamol or other beta agonists in metered-dose inhalers. Oxygen must be available. A small-volume nebuliser should be readily available for the administration of bronchodilators.

General precautions when conducting spirometry and bronchial provocation testing should be observed, including using caution in patients with the following: ventilatory impairment (baseline FEV1 of less than 70% of predicted normal values or an absolute value of 1.5 l or less in adults), spirometry induced bronchoconstriction, haemoptysis of unknown origin, pneumothorax, recent abdominal or thoracic surgery, recent intraocular 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 is greater than 10% at continued administration after the 0 mg capsule, a standard dose of bronchodilator should be given and the Osmohale challenge discontinued.

Exercise: Vigorous exercise should be fully avoided on the day of the test, as this may affect test results.

Smoking: Since smoking may affect test results it is recommended that patients refrain from smoking for at least 6 hours prior to testing.

The effects of repeat Osmohale testing within a short period of time have not been investigated therefore careful consideration should be given to repeat use of Osmohale.

Paediatric population

The Osmohale test should not be used in patients below 6 years of age due to their inability to provide reproducible spirometric measurements.

There is limited information on the use of Osmohale in patients 6-18 years of age therefore Osmohale is not recommended in this population.

Regular use of inhaled corticosteroids reduces the airway sensitivity to Osmohale and in many individuals, complete inhibition of the airway response occurs.

The following medicines should be withheld before conducting an Osmohale test as they may affect the results:

Recommended periods for withholding medicines before the Osmohale test are listed below.

Food

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

Pregnancy

There are no data or limited amount of data (less than 300 pregnancy outcomes) from the use of D-mannitol in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3).

The effects of a possible hyperresponsiveness reaction on the mother and/or the foetus is unknown and therefore Osmohale should not be given to pregnant women.

Breastfeeding

No effects on the breast-fed newborn/infant are anticipated since the systemic exposure of the breast-feeding woman to inhaled D-mannitol is negligible. Osmohale may be used during breast-feeding.

Fertility

For mannitol no clinical data on fertility are available. Animal reproduction studies have not been carried out with inhaled mannitol. However, studies with orally administered mannitol indicate no fertility effects (see section 5.3).

No studies on the effects on the ability to drive and use machines have been performed. Osmohale has no or negligible influence on the ability to drive and use machines.

Summary of the safety profile

A positive result with Osmohale may produce symptoms of bronchospasm such as chest tightness, cough or wheezing.

The safety population consisted of 1,046 subjects including patients with asthma, symptoms suggestive of asthma, and healthy individuals from 6 to 83 years of age who participated in the two clinical trials. The racial distribution of subjects was 84% Caucasian, 5% Asian, 4% Black, and 7% Other. In study DPM-A-301, adverse events were monitored from the beginning of the challenge to a week following the challenge day. In study DPM-A-305, adverse reactions were reported at the time of the testing procedure and for one day thereafter. No serious adverse reactions were reported following bronchial challenge testing with Osmohale in either trial. Due to the short half-life of mannitol, the causal link would be expected to diminish over this period of time. No serious adverse events were reported during the study. Most adverse events were reported to be mild and transient.

Most patients experienced cough during the challenge; however, it was only occasional in the majority of these patients (87%). In the remainder, it was frequent enough to cause some delay in continuation of the challenge (13%) or discontinuation (1%). Pharyngolaryngeal pain was also a commonly reported adverse event; its occurrence may be reduced if the mouth is rinsed after the test. Five adult subjects (0.6%) discontinued from the studies within a day following administration of Osmohale because of cough, decreased lung function, feeling jittery, sore throat, and throat irritation. One subject (0.4%) discontinued from the studies within a day following administration of Osmohale because of retching.

Tabulated list of adverse reactions

The adverse reactions reported in the two studies are listed below by organ class and absolute frequency: Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000).

Infections and infestations

Common: Nasopharyngitis

Nervous system disorders

Common: Headache

Uncommon: Dizziness

Eye disorders

Uncommon: Eye irritation

Vascular disorders

Uncommon: Flushing, Peripheral coldness

Respiratory, thoracic and mediastinal disorders

Common: Cough*, Dyspnoea, Pharyngolaryngeal pain, Rhinorrhoea, Throat irritation, Aggravated Asthma

Uncommon: Hoarseness, Epistaxis, Oxygen saturation decreased

Gastrointestinal disorders

Common: Nausea, Vomiting

Uncommon: Upper abdominal pain, Diarrhoea, Mouth ulceration

Skin and subcutaneous tissue disorders

Uncommon: Pruritus, Hyperhidrosis

Musculoskeletal and connective tissue disorders

Uncommon: Musculoskeletal pain

General disorders

Common: Chest tightness

Uncommon: Fatigue, Feeling jittery, Thirst

^* Cough was only defined as an adverse event during the challenge test if it led to discontinuation of the challenge.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation 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 via the Yellow Card Scheme in the UK, Website: www.mhra.gov.uk/yellowcard or in Ireland to HPRA Pharmacovigilance, Earlsfort Terrace, IRL – Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517; Website: www.hpra.ie; e-mail: medsafety@hpra.ie.

Not applicable.