Aiolos Nebuliser Instructions for Use Ver 3 Jan 2012

Aiolos Nebuliser for Virazole® (ribavirin) Aerosol

Instructions for use Version 3, 2012-01-12 Art no 10040

CAUTION: Do not assemble or use this device without reading the instructions for use. This device is not for use at home. Incorrect use of this device can result in failure to deliver the correct dose of medication or damage to equipment.

CONTENTS Chapter Page 1. Introduction ... 2 2. The device ... 2 3. Assembly ... 3 4. General operation ... 6 5. Assembly instructions and spare part list for Aiolos nebuliser for Virazole® ... 7 6. Cleaning the Aiolos nebuliser for Virazole® ... 8 7. Trouble shooting and maintenance... 8 8. Technical information ... 9

Page 1 of 9

Aiolos Nebuliser for Virazole® (ribavirin) Aerosol

1. Introduction The Aiolos nebuliser for Virazole® (ribavirin) is indicated for administration of Virazole® (ribavirin) aerosol only. Virazole® aerosol is indicated in the treatment of infants and children with severe Respiratory Syncytial Virus (RSV) bronchiolitis. Full details of the indications can be seen in the relevant approved Virazole Summary of Product Characteristics (SPC) for each Marketing Authorisation.

2. The device The Aiolos nebuliser for Virazole® consists of:      

Nebuliser for Virazole® (article no 10420) Nebuliser parts for Aiolos Nebuliser (article no 10421) Sparepart kit (article no 10422) Holder nebuliser (article no 10423) Tubing 60 cm (article no 10531) Instructions for use (article no 10040)

The operation of the Aiolos nebuliser for Virazole® is dependent upon the following equipment and items being provided by the hospital or clinic: 

Aerosol delivery tubing, 60 cm (with plain inside walls) (22 mm diameter) for connecting the upper nebuliser part to a delivery mask, hood or tent. A starter tube will be supplied with the Aiolos nebuliser, however, additional tubes required are to be supplied by the hospital.



Nebuliser hose (6 mm outer diameter, 4 mm inner diameter) for connecting the nebuliser to the flow meter. In some countries, graduated oxygen tubing may be used instead.



Compressed air / oxygen source (9–10 L/min). Use air or oxygen that meets specifications for medical breathing use.



Infusion pump, syringe pump or equivalent device that can be regulated to 17.5 mL/h.



Infusion bag, syringe or equivalent container containing a solution of ribavirin prepared as per the instructions in the SPC for Virazole® Aerosol.

Further equipment required will depend on the particular chosen mode of aerosol administration. Virazole® aerosol may be delivered to a mask (any mask that allows elephant tubing to be fitted), hood, tent, or mechanical ventilator.

Page 2 of 9

Aiolos Nebuliser for Virazole® (ribavirin) Aerosol

3. Assembly 1. Assemble the nebuliser according to the instructions (see page 6) and connect the nebuliser hose between the nebuliser and the flow meter. 2. Connect the flow meter to the air or oxygen supply. 3. Prepare the Virazole® solution and transfer the solution to the infusion bag. Connect the infusion bag through an infusion pump to the Luer-lock connection on the medicine reservoir (see picture below). 4. Connect the aerosol delivery tubing to the upper nebuliser part. NOTE: The length of the aerosol delivery tubing between the Aiolos nebuliser and the hood or tent should be kept as short as conveniently possible to minimise collection of aerosol during operation. The starter delivery tube supplied is 60 cm long. Tubes longer than 90 cm should not be used. The tubing should be replaced at the same frequency as the wetted parts of the nebuliser. The wet parts of the nebuliser should be cleaned between patients. They should also be cleaned during administration to a patient if crystallisation is observed (see Sections 4.1 and 6). Aerosol delivery Tubing

Note: Medicine usage rate: 17.5 mL/hour with the Aiolos Nebuliser for Virazole® and 3 bar driving pressure with a regulator and approx 10 L/min for a flow meter. The medicine usage rate may vary somewhat with different nebulisers and the rate (mL/hour) may need to be adjusted during treatment.

Nebuliser Luer-lock connection Nebuliser hose (driving pressure)

Syringe, infusion pump or equivalent

Page 3 of 9

Aiolos Nebuliser for Virazole® (ribavirin) Aerosol 5. For use with mask: The aerosol delivery tubing from the Aiolos nebuliser should be connected to the mask. 6. For use with a hood: The aerosol delivery tubing from the Aiolos nebuliser should be placed into the inlet port of the hood. 7. For use with a tent: The tent must be set up with the customary air flow and cooling systems. The aerosol delivery tubing from the Aiolos nebuliser should be connected to the inlet port of the tent. CAUTION: The Aiolos nebuliser for Virazole® may not cover the patient’s total need of air or oxygen delivery. CAUTION: The air/gas source must be connected to the flow meter and turned on whenever the Aiolos nebuliser is in use. The source must have a flow of 9-10 L/min. Use air or oxygen which meets specifications for medical breathing use. CAUTION: During operation, water/drug collection may form in the medical reservoir cap and in the 22 mm aerosol delivery tubing. Monitor these components hourly. Collection may increase after 4 hours of operation. If excessive collection is seen, these components should be cleaned or replaced. Before de-activating the Aiolos nebuliser, confirm that the nebuliser has been removed from the patient and the patient has an alternative source of oxygen or air. To de-activate the Aiolos nebuliser, turn off the infusion pump and the flow meter. 8. For use with ventilators: read the instructions for use (below) very carefully. Connect the Aiolos nebuliser delivery tube into the inspiratory line of the patient breathing circuit immediately downstream from the heated humidifier. Place a one-way valve in the Aiolos nebuliser tubing at the junction with the ventilator circuit (See Figure below). Check the operation of the one-way valve before installing it into the circuit. Aiolos nebuliser delivery

One way valve Ventilator

Heated Humidifier

T-adapter

Bacteria filter Patient

CAUTION: Failure to place a one-way valve at the junction of the Aiolos nebuliser tubing line and the inspiratory limb of the ventilator will result in reducing the tidal volume delivery by diverting the ventilator’s output through the pressure relief valve.

Page 4 of 9

Aiolos Nebuliser for Virazole® (ribavirin) Aerosol CAUTION: Virazole® Aerosol may be used for infants requiring assisted ventilation, but requires regular monitoring by experienced hospital personnel. Drug precipitation in the system can be a serious problem. Mechanical ventilators used in conjunction with an Aiolos nebuliser should utilise an internal wire heated ventilator circuit to minimise accumulation of drug precipitate. In addition, bacteria filters in the expiratory limb of the circuit and a high PEEP alarm should be used. A water column relief valve must be employed in circuits with volume-cycled ventilators and may be used as well as in circuits with pressure cycled ventilators. CAUTION: Water/drug precipitate may form in the one way valve, the ventilation tubing and/or the endotracheal tube; frequent (hourly) monitoring of these components for precipitate is required. If the valve and/or tubing collect precipitate, they must be cleaned or replaced (see Sections 4.1 and 6.). CAUTION: If airway pressure increases, the endotracheal tube should be checked, and the patient suctioned, to minimise precipitate build-up. Airway pressure increases can also be caused by clogged bacteria filters. CAUTION: Filters should be changed if an increase in peak inspiratory pressure (PIP) or positive end expiratory pressure (PEEP) of 1-2 cm of water is observed. Because these pressure increases may occur, airway and ventilator circuits should include CONTINUOUS MONITORING. Use of a pressure monitor with both high and low PEEP alarms is essential to assist the user in detecting changes in the PEEP level. Water condensation (rainout) associated with the use of conventional tubing may require frequent (hourly) removal of the condensate. To minimise rainout, internal wire-heated tubing must be used. Maintain the temperature in the circuit at 33-37°C. It may be necessary to set the heated humidifier at a higher temperature. BEFORE DlSCONNECTlNG the Aiolos nebuliser FROM THE VENTILATOR CIRCUIT, THE TEMPERATURE AT THE HEATED HUMIDIFIER MUST BE ADJUSTED APPROPRIATELY. CAUTION: Both the heater/humidifier and the internal wire heater sensors must be checked hourly for evidence of water/drug precipitate which can decrease the accuracy of the sensor. When internal wire heated circuits are used, precipitate may also form at the loop of the wire.

Page 5 of 9

Aiolos Nebuliser for Virazole® (ribavirin) Aerosol

4. General operation 1. Connect the flow meter to the gas source. 2. Fill the medicine reservoir with 2-5 mL of the Virazole® solution. 3. Start the flow meter and adjust to give an air flow of 9-10 L/min. 4. Set the infusion pump to give a flow of 17.5 mL/hour (according to the instructions for use for the infusion pump). 5. Start the infusion pump. The nebuliser will now give a flow rate of 9-10 L per minute. 4.1 Functional checks during use During treatment with Virazole®, the following must be checked: 1. Crystal formation during treatment During treatment, the medicine solution may form crystal deposits on the inner surfaces of the nebuliser, hoses and connectors and these can affect the flow. It is therefore very important to check the system at regular intervals. Check the system components every hour. In any event it is recommended that the nebuliser is rinsed and the tubing is changed daily. Procedure for checking crystal formation:  Turn off the nebuliser and the infusion pump.  Check for the formation of medicine solution crystals in the nebuliser, all tubing and connectors.  If the crystal deposit exceeds 1 mm, rinse using sterile water or fit new tubing if necessary. NB: Local hospital guidelines should be checked for the disposal of residual medicinal product in the Aiolos nebuliser or tubing. 2. Fluid levels during treatment Check that the fluid level in the medicine reservoir is correct (2-5 mL). The medicine usage rate may vary somewhat with different nebulisers and the rate (mL/hour) may need to be adjusted during treatment. Other checks Other monitoring should include normal patient check routines depending on the devices being used. NB: There should be no tension in the tubing. This may occur in the tube to the gas/air supply if this tube is unplugged after the gas/air supply has been started and then the tube is plugged in again without stopping the air supply. There should be no kinks or twists in the tubing.

Page 6 of 9

Aiolos Nebuliser for Virazole ® (ribavirin) Aerosol

5 . As s embly ins tructions a nd s pa re pa r t lis t for Aiolos nebulis er for Vira zole® Plug 10 725 1. Press insert tube down into nebuliser upper part. 2. Press baffle cap firmly into nebuliser upper part. 3. Screw medicine reservoir into nebuliser upper part. 4. Assemble nozzle. The two parts snap together. 5. Check that the bl ack O-ring is properly located. 6. Press the nozzle assembly into the medicine reservoir. 7. Check that the black O -ring is correctly located in the groove of the nebuliser lower part. 8. Screw the nebuliser lower part into the medicine reservoir. Attachment of hose between nebuliser and driving pressure source : 1. Screw in the hose connector nut on the nebuliser as far as possible 2. Attach the hose. 3. Unscrew the nut so that it locks the hose. 4. Connect the hose to the pressure source in a similar way.

Page 7 of 9

Insert tube 10 330

Nebuliser upper part 10 329

Baffle cap 11 075 Medicine reservoir with plastic fitting 11 078 Nozzle assembly, exploded view 10 320 O-ring, nozzle assembly/nebuliser lower part 10 323 Nebuliser lower part 10 347-4

Aiolos Nebuliser for Virazole® (ribavirin) Aerosol

6. Cleaning the Aiolos nebuliser for Virazole® The nebuliser must be cleaned prior to treatment of each new patient. 6.1 Cleaning the treatment system Use a heat disinfector to sterilise ventilator hoses. Dry the components in a drying cabinet. The nebuliser hose must be changed prior to the treatment of each new patient. 6.2 Cleaning the nebuliser Dismantle the nebuliser into its component parts, i.e. nebuliser upper part, insert tube, baffle cap, medicine reservoir, nozzle assembly and nebuliser lower part. Separate the two parts of the nozzle assembly. Alternative 1. Disinfection solution according to hospital or clinic procedures Immerse all nebuliser components, apart from hose and nebuliser lower part, in disinfection solution for 30 minutes. The components must be completely immersed in the solution. Then rinse under running cold water. Place all components in a bowl of clean tap water and leave for about 10 minutes. Clean components using a detergent if necessary and rinse again. Allow to dry in air. Wipe over hose and nebuliser lower part with isopropyl alcohol. Alternative 2. Autoclaving. The nebuliser upper part, lower part, nozzle assembly, inset tube, medicine reservoir and baffle cap can be autoclaved (standard autoclave cycles with a maximum temperature of 137 C). Disinfect all components before autoclaving. Alternative 3. Washing disinfector The nebuliser upper part, lower part, nozzle assembly, inset tube, medicine reservoir and baffle cap can be processed through a washer disinfector. Place all parts in a net basket with lid. Make sure that all parts stay in the basket. NB: Local hospital guidelines should be checked for the disposal of residual medicinal product in the Aiolos nebuliser or tubing. CAUTION: To reduce the risk of bacterial contamination, the nebuliser components should not be stored while still damp. Shake off as much water as possible before the components are air dried.

7. Trouble shooting and maintenance 7.1. Trouble shooting There is little or no aerosol  The nebuliser is not correctly assembled.  The flow meter is turned off, or is not fully adjusted to give a flow rate of 9- 10 L/min.  The nozzle is dirty or clogged.  The O-ring on the lower nebuliser part is missing or broken.

Page 8 of 9

Aiolos Nebuliser for Virazole® (ribavirin) Aerosol The nebuliser is leaking  Check that the baffle is inserted correctly into the upper nebuliser part  Check all O-rings, they may be defective or missing.  Replace O-rings if necessary. 7.2. Maintenance O-rings should be replaced if necessary as they might dry up after repeated disinfections. The nozzle should be replaced at least every other year.

8. Technical information Article No. 10040 (Instructions for use) Class IIa according to MDD (93/42/EEC) Item Description Nebuliser: Aiolos nebuliser for Virazole®, Art no 10420 Output flow: 9-10 liters/min NOTE: Medicine usage rate: 17.5 mL/hour with the Aiolos nebuliser (with baffle cap), Art. No. 10420, and 3.0 bar driving pressure (9-10 L/min). The medicine usage rate may vary somewhat between batches of Aiolos nebulisers and the rate (mL/hour) may need to be adjusted during treatment. It is recommended that the device is replaced after 2 years of continuous use. Technical data: Nebulising pressure: 3.0 bar (9-10 L/min) Medication output: 0.27 mL/min (3 bar Virazole®) Mass Median Diameter: 1.7 μm (3 bar Virazole®) Aiolos Medical AB makes no warranty or representation, either express or implied, with respect to any other manufacturer’s items or equipment, their quality, performance, or fitness for a particular purpose. In no event will Aiolos Medical AB be liable for direct, indirect, special, incidental or consequential damages resulting from any defect in construction of performance of other manufacturer’s equipment.

Contact information: Aiolos Medical AB Fjärrviksvägen 4 653 50 Karlstad Sweden

Page 9 of 9

Phone: +46 54 53 48 05 Fax: +46 54 53 87 47 E-mail: [email protected] www.aiolos.se