VENTAVIS Nebuliser solution Ref.[9385] Active ingredients: Iloprost

Ventavis should only be initiated and monitored by a physician experienced in the treatment of pulmonary hypertension.

Posology

Dose per inhalation session

At initiation of Ventavis treatment the first inhaled dose should be 2.5 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. In case of poor tolerability of the 5 microgram dose, the dose should be reduced to 2.5 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.

Special populations

Hepatic impairment

Iloprost elimination is reduced in patients with hepatic dysfunction (see section 5.2).

To avoid undesired accumulation over the day, special caution has to be exercised with these patients during initial dose titration. Initially, doses of 2.5 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.

To minimize accidental exposure it is recommended to keep the room well ventilated.

The ready-to-use Ventavis nebuliser solution is administered with a suitable inhalation device (nebuliser) (see below and section 6.6). Patients stabilised on one nebuliser should not switch to another nebuliser without supervision by the treating physician as different nebulisers have been shown to produce aerosols with slightly different physical characteristics and delivery of the solution that may be faster (see section 5.2).

Breelib

Breelib is a small handheld, battery-powered, breath activated, vibrating mesh technology system.

Ventavis 10 microgram/ml (1 ml ampoule) and Ventavis 20 microgram/ml nebuliser solution

Ventavis 10 microgram/ml nebuliser solution (1 ml ampoule) delivers 2.5 microgram and Ventavis 20 microgram/ml nebuliser solution delivers 5 microgram at the mouthpiece of the Breelib nebuliser.

At initiation of Ventavis treatment or if the patient is switched from an alternative device, the first inhalation should be made with 1 ml ampoule of Ventavis 10 microgram/ml (see section 4.4). If inhalation with Ventavis 10 microgram/ml is well tolerated, the dose should be increased by using Ventavis 20 microgram/ml. This dose should be maintained. In case of poor tolerability of Ventavis 20 microgram/ml, the dose should be reduced by using 1 ml ampoule of Ventavis 10 microgram/ml (see section 4.4).

The duration of an inhalation session with Breelib nebuliser is approximately 3 minutes, which reflects the higher delivery rate of the Breelib compared to other nebulisers.

Patients initiating Ventavis treatment or switching from an alternative device to Breelib should be closely supervised by the treating physician to ensure that dose and speed of inhalation are well tolerated.

When using the Breelib nebuliser please follow the instructions for use provided with the device. Fill the medication chamber with Ventavis immediately before use.

I-Neb AAD

The I-Neb AAD system is a portable, hand-held, vibrating mesh technology nebuliser system. This system generates droplets by ultrasound, which forces the solution through a mesh. The I-Neb AAD nebuliser has been shown to be suitable for the administration of Ventavis 10 microgram/ml (1 ml ampoule) and 20 microgram/ml nebuliser solution. The Mass Median Aerodynamic Diameter (MMAD) of the aerosol measured using I-Neb nebulising systems equipped with power level 10 disc was similar between Ventavis 20 microgram/ml (golden programme) and Ventavis 10 microgram/ml (purple programme) nebuliser solutions (i.e.: around 2 micrometres) but with faster delivery when using Ventavis 20 microgram/ml.

The dose delivered by the I-Neb AAD system is controlled by the medication chamber in combination with a control disc. Each medication chamber is colour coded and has a corresponding colour coded control disc.

Ventavis 10 microgram/ml nebuliser solution (1 ml ampoule)

At initiation of Ventavis treatment with I-Neb system the first inhaled dose should be 2.5 microgram iloprost as delivered at the mouthpiece of the nebuliser using 1 ml ampoule of Ventavis 10 microgram/ml. If this dose is well tolerated, dosing should be increased to 5 microgram iloprost using 1 ml ampoule of Ventavis 10 microgram/ml and maintained at that dose. In case of poor tolerability of the 5 microgram dose, the dose should be reduced to 2.5 microgram iloprost.

This nebuliser monitors the breathing pattern to determine the aerosol pulse time required to deliver the pre-set dose of 2.5 or 5 microgram iloprost.

For the 2.5 microgram dose of Ventavis 10 microgram/ml the medication chamber with the red coloured latch is used together with the red control disc.

For the 5 microgram dose of Ventavis 10 microgram/ml the medication chamber with the purple coloured latch is used together with the purple control disc.

For each inhalation session with the I-Neb AAD, the content of one 1 ml ampoule of Ventavis 10 microgram/ml, with two coloured rings (white – yellow), is transferred into the medication chamber immediately before use.

Ventavis 20 microgram/ml nebuliser solution

Only patients who are maintained at the 5 microgram dose and who have repeatedly experienced extended inhalation times with Ventavis 10 microgram/ml, which could result in incomplete inhalation, may be considered suitable for switching to Ventavis 20 microgram/ml.

Close supervision by the treating physician is necessary if switching from Ventavis 10 microgram/ml to Ventavis 20 microgram/ml to control the acute tolerance relating to faster delivery rate of iloprost with the double concentration.

This nebuliser monitors the breathing pattern to determine the aerosol pulse time required to deliver the pre-set dose of 5 microgram iloprost. For the 5 microgram dose of Ventavis 20 microgram/ml the medication chamber with the gold coloured latch is used together with the gold control disc.

For each inhalation session with the I-Neb AAD, the content of one 1 ml ampoule of Ventavis 20 microgram/ml with two coloured rings (yellow – red), is transferred into the medication chamber immediately before use.

Venta-Neb

Venta-Neb, a portable ultrasonic battery-powered nebuliser, has been shown to be suitable for the administration of Ventavis 10 microgram/ml nebuliser solution (2 ml ampoule). The measured MMAD of the aerosol droplets was 2.6 micrometres.

At initiation of Ventavis treatment with Venta-Neb the first inhaled dose should be 2.5 microgram iloprost as delivered at the mouthpiece of the nebuliser using 2 ml ampoule of Ventavis 10 microgram/ml. If this dose is well tolerated, dosing should be increased to 5 microgram iloprost using 2 ml ampoule of Ventavis 10 microgram/ml and maintained at that dose. In case of poor tolerability of the 5 microgram dose, the dose should be reduced to 2.5 microgram iloprost.

For each inhalation session with the Venta-Neb, the content of one 2 ml ampoule of Ventavis 10 microgram/ml with two coloured rings (white – pink) is transferred into the nebuliser medication chamber immediately before use.

Two programmes can be operated:

P1 Programme 1: 5 microgram active substance on the mouth piece 25 inhalation cycles.

P2 Programme 2: 2.5 microgram active substance on the mouth piece 10 inhalation cycles. The selection of the pre-set programme is made by the physician.

Venta-Neb prompts the patient to inhale by an optical and an acoustic signal. It stops after the pre-set dose has been administered.

To obtain the optimal droplet size for the administration of Ventavis 10 microgram/ml nebuliser solution the green baffle plate should be used. For details refer to the instruction manual of the Venta-Neb nebuliser.

Other nebulising systems

The efficacy and tolerability of inhaled iloprost when administered with other nebulising systems, which provide different nebulisation characteristics of iloprost solution, have not been established.

Symptoms

Cases of overdose were reported. Symptoms of overdoses are mainly related to the vasodilatory effect of iloprost. Frequently observed symptoms following overdose are dizziness, headache, flushing, nausea, jaw pain or back pain. Hypotension, an increase of blood pressure, bradycardia or tachycardia, vomiting, diarrhoea and limb pain might also be possible.

Management

A specific antidote is not known. Interruption of the inhalation session, monitoring and symptomatic measures are recommended.

Ventavis 10 microgram/ml nebuliser solution: 4 years.

Ventavis 20 microgram/ml nebuliser solution: 5 years.

This medicinal product does not require any special storage conditions.

Ventavis 10 microgram/ml nebuliser solution

1 ml ampoules, colourless, glass type I, containing 1 ml nebuliser solution, ring coded with two coloured rings (white – yellow).

3 ml ampoules, colourless, glass type I, containing 2 ml nebuliser solution, ring coded with two coloured rings (white – pink).

Ampoules with 1 ml nebuliser solution (for the use of Breelib or I-Neb AAD)

Packages containing:

• 30 ampoules
• 42 ampoules.

Multipacks containing:

• 168 (4x42) ampoules
• 168 (4x42) ampoules co-packed with Breelib consumables set (containing 1 mouthpiece and 1 medication chamber).

Ampoules with 2 ml nebuliser solution (for the use of Venta-Neb)

Packages containing:

• 30 ampoules
• 90 ampoules
• 100 ampoules
• 300 ampoules.

Multipacks containing:

• 90 (3x30) ampoules
• 300 (10x30) ampoules.

Ventavis 20 microgram/ml nebuliser solution

1 ml ampoules, colourless, glass type I, containing 1 ml nebuliser solution, ring coded with two coloured rings (yellow – red).

Ampoules with 1 ml nebuliser solution (for the use of Breelib or I-Neb AAD)

Packages containing:

• 30 ampoules
• 42 ampoules.

Multipacks containing:

• 168 (4x42) ampoules
• 168 (4x42) ampoules co-packed with Breelib consumables set (containing 1 mouthpiece and 1 medication chamber).

Not all pack sizes may be marketed.

For each inhalation session the content of one opened ampoule of Ventavis has to be transferred completely into the medication chamber immediately before use.

After each inhalation session, any solution remaining in the nebuliser should be discarded. In addition, instructions for hygiene and cleaning of the nebulisers provided by the device manufacturers should be followed carefully. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.