VENTAVIS

Drug product Suitable inhalation device (nebuliser) to be used Ventavis 10 microgram/ml Breelib I-Neb AAD Venta-Neb Ventavis should only be initiated and monitored by a physician experienced in the treatment of pulmonary hypertension.

5 microgram iloprost as delivered at the mouthpiece of the nebuliser. If this dose is well tolerated, dosing should be increased to 5 microgram iloprost and maintained at that dose. 5 microgram iloprost. Daily dose The dose per inhalation session should be administered 6 to 9 times per day according to the individual need and tolerability.

Duration of treatment The duration of treatment depends on clinical status and is left to the physician’s discretion. Should patients deteriorate on this treatment intravenous prostacyclin treatment should be considered. 2). To avoid undesired accumulation over the day, special caution has to be exercised with these patients during initial dose titration.

5 microgram iloprost should be administered using Ventavis 10 microgram/ml with dosing intervals of 3-4 hours (corresponds to administration of max. 6 times per day). Thereafter, dosing intervals may be shortened cautiously based on individual tolerability.

If a dose up to 5 microgram iloprost is indicated, again dosing intervals of 3-4 hours should be chosen initially and shortened according to individual tolerability. An accumulation of iloprost following treatment over several days is not likely due to the overnight break in administration of the medicinal product.

Renal impairment There is no need for dose adaptation in patients with a creatinine clearance >30 ml/min (as determined from serum creatinine using the Cockroft and Gault formula). Patients with a creatinine clearance of ≤30 ml/min were not investigated in the clinical trials.

Data with intravenously administered iloprost indicated that the elimination is reduced in patients with renal failure requiring dialysis. Therefore, the same dosing recommendations as in patients with hepatic impairment (see above) are to be applied.

Paediatric population The safety and efficacy of Ventavis in children aged up to 18 years have not been established. No data from controlled clinical trials are available. Method of administration Ventavis is intended for inhalation use by nebulisation.

Summary of the safety profile In addition to local effects resulting from administration of iloprost by inhalation such as cough, adverse reactions with iloprost are related to the pharmacological properties of prostacyclins. The most frequently observed adverse reactions (≥ 20 %) in clinical trials include vasodilatation (including hypotension), headache and cough.

The most serious adverse reactions were hypotension, bleeding events, and bronchospasm. Tabulated list of adverse reactions The adverse reactions reported below are based on pooled clinical trial data from phase II and III clinical trials involving 131 patients taking the medicinal product and on data from post-marketing surveillance.

The frequencies of adverse reactions are defined as very common (≥1/10) and common (≥1/100 to <1/10). The adverse reactions identified only during post-marketing surveillance, and for which a frequency could not be estimated from clinical trial data, are listed under "Frequency not known".

Within each frequency grouping, adverse reaction are presented in order of decreasing seriousness. 4) / Wheezing Gastrointestinal disorders Nausea Diarrhoea Vomiting Mouth and tongue irritation including pain Dysgeusia Skin and subcutaneous tissue disorders Rash Musculoskeletal and connective tissue disorders Pain in jaw/trismus General disorders and administration site condition Peripheral oedema§ * Life-threatening and/or fatal cases have been reported.

§ see section “Description of selected adverse reactions” Description of selected adverse reactions Bleeding events (mostly epistaxis and haemoptysis) were very common as expected in this patient population with a high proportion of patients taking anticoagulant co-medication.

5). Fatal cases included cerebral and intracranial haemorrhage. Syncope is a common symptom of the disease itself, but can also occur under therapy. 4). 2% of patients on placebo. Peripheral oedema is a very common symptom of the disease itself, but can also occur under therapy.

The use of Ventavis is not recommended in patients with unstable pulmonary hypertension, with advanced right heart failure. In case of deterioration or worsening of right heart failure transfer to other medicinal products should be considered.

Hypotension Blood pressure should be checked while initiating Ventavis. In patients with low systemic blood pressure and in patients with postural hypotension or receiving medicinal products known to reduce blood pressure levels, care should be taken to avoid further hypotension.

Ventavis should not be initiated in patients with systolic blood pressure less than 85 mmHg. 5). Syncope The pulmonary vasodilatory effect of inhaled iloprost is of short duration (one to two hours). Syncope is a common symptom of the disease itself and can also occur under therapy.

Patients who experience syncope in association with pulmonary hypertension should avoid any exceptional straining, for example during physical exertion. Before physical exertion it might be useful to inhale. The increased occurrence of syncope can reflect therapeutic gaps, insufficient effectiveness and/or deterioration of the disease.

8). 8). Moreover, the benefit of Ventavis has not been established in patients with concomitant Chronic Obstructive Pulmonary Disease (COPD) and severe asthma. Patients with concomitant acute pulmonary infections, COPD and severe asthma should be carefully monitored.

Pulmonary veno-occlusive disease Pulmonary vasodilators may significantly worsen the cardiovascular status of patients with pulmonary veno-occlusive disease. Should signs of pulmonary oedema occur, the possibility of associated pulmonary veno-occlusive disease should be considered and treatment with Ventavis should be discontinued.

Interruption of therapy In case of interruption of Ventavis therapy, the risk of rebound effect is not formally excluded. Careful monitoring of the patient should be performed, when inhaled iloprost therapy is stopped and an alternative treatment should be considered in critically ill patients.

1. g. active peptic ulcers, trauma, intracranial haemorrhage). − Severe coronary heart disease or unstable angina. − Myocardial infarction within the last six months. − Decompensated cardiac failure if not under close medical supervision.

− Severe arrhythmias. g. transient ischaemic attack, stroke) within the last 3 months. − Pulmonary hypertension due to venous occlusive disease. − Congenital or acquired valvular defects with clinically relevant myocardial function disorders not related to pulmonary hypertension.