Posology : מינונים

4.2     Posology and method of administration

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 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).

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 nebuliser solution.
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

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. 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.

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 ampoule of Ventavis 10 microgram/ml, with two coloured rings (white - pink), is transferred into the medication chamber immediately before use.


Drug       Ampoule             Dosage          I-Neb AAD                       Estimated product    coloured ring                                                       inhalation Medication       Control        time chamber          disc latch
Ventavis         2 ml ampoule       2.5 mcg       red              red            3.2 min 10 mcg/ml        white – pink       5 mcg         purple           purple         6.5 min ring


Other nebulising systems
The efficacy and tolerability of inhaled iloprost when administered with other nebulising systems (Venta-Neb and Breelib) were established by these systems, but are not currently available for use in the country.

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.