Improved Aerosol Therapy FAVORITE Inhalation · 2012. 6. 8. · FAVORITE Inhalation Flow And Volume...
Transcript of Improved Aerosol Therapy FAVORITE Inhalation · 2012. 6. 8. · FAVORITE Inhalation Flow And Volume...
Improved Aerosol Therapy
FAVORITE Inhalation
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FAVORITE Inhalation
Flow And Volume Regulated Inhalation Technology
Content
Short Product Description 4Inspiration and Volume Regulation 6Lung Dosage Control and Reproducibility 8Inhalation for COPD patients 10Alveolar Therapy 12”Drug Targeting“ 14Antibiotic Inhalation 16Efficient Use of Drugs 18Shorter Therapeutic Treatment 20Increasing Lung Capacity 22Asthma Therapy 24Drug and Patient-Specific Therapy Control 26Equivalent or Maximal Lung Dosing 28Compliance Analysis 30Technical Data 32Appendix 34
Innovative Technology
AKITA® JET’s FAVORITE Technology actively regulates inspiration flow as well as inhalation volume. Optimal inhalation patterns can thus be guided and controlled according to therapeutic requirements and the patient’s individual condition. The drug can thus be delivered to the patient’s lungs in an optimal manner and unwanted deposition in the throat is minimized.
FAVORITE offers clear advantages in comparison to conventional inhalation systems – significantly improved utilization of the drug, better reprodu-cibility of lung dosage and targeted deposition of the drug into even the smallest respiratory areas.
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AKITA® JET with FAVORITE
Technology Platform for Optimal Inhalation
Additional tube for air flowTo assist inspiration and volume control.
FAVORITEInhalation technology with optimized inspiration flow and volume control using controlledpressure ventilation and drug aerosol.
Drug TargetingElectronically controlled inhalation patterns for selective drug deposition into predefined areas of the lung.
DrugsΩ Fluticasone, Budesonide, etc.Ω Tobramycin, Colistin, etc.Ω DNAseΩ Ipratropium BromideΩ Salbutamol, Formetorol, etc.Ω Sodium Chloride solutionsΩ Other active ingredients
IndicationsΩ Severe AsthmaΩ Cystic Fibrosis Ω Chronic Obstructive Pulmonary Disease (COPD) Ω BronchiectasisΩ α1-antitrypsin deficiencyΩ Pulmonary HypertensionΩ Ciliary Dyskinesia
Compressor tube For generation of drug aerosol.
SMART CARDDrug-specific cards for recording therapy-related data; contains drug data and information on dosage.
Navigation and DisplayΩ Patient friendly therapy supportΩ Adjustable settings for patient-specific
inhalation time (flexible volume regulation)Ω Instructions for therapy Ω Feedback on inhalation Ω Information on unit progress
AKITA® JET Nebulizer Set Robust, continuous nebulizer with valve system based on Basis PARI LC Sprint®.High aerosol output of 0,23 ml/min and optimal particle size ø 3,8 μm.
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The key to successful inhalation therapy
Slow Inspiration and High Inhalation Volume
The AKITA® concept: High deposition through the electronic control of inspiration flow and volume
Ω Inhaling a drug with an optimal particle size does not guarantee sufficient deposition within the lungs. In addition, a patient’s breathing pattern is crucial – the full potency of an inhaled drug can only be reached with slow inspiration flow and a high inhalation volume.
Ω With FAVORITE, the AKITA® JET can electronically regulate both inspiration flow and inhalation volume. This guarantees that these parameters will always be maintained within an optimal range and also ensures a higher drug deposition in the lungs.
ICRP 1994; Human Respiratory Tract Model for Radiological Protection. A Report of a Task Group of the International Commission on Radiological Protection. Ann. ICRP 24, 1-482 (1994).
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Alveolar lung deposition [%
]
Particle size [µm]21 3 4 5
Flow[ml/s]
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1000
1000
Volume[ml]
1800
1800
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Alveolar lung deposition of 1 to 5 µm particles following inhalation using different inspiration patterns and inhalation volumes.
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Everything that conventional inhalation systems can’t deliver
Reproducibility and Higher Lung Deposition
AKITA® JET guarantees optimal inhalation
Ω Patients with lung disease generally have variable and sub-optimal breathing patterns, which can negatively affect lung deposition. Conventional inhalation devices are unable to compensate for such complications, as inhalation can occur too quickly (increased inspiration flow) and for an insufficient length
of time (reduced inhalation volume).
Ω FAVORITE resolves this problem – the administration of drug aerosol ensures controlled breathing and optimized inhalation maneuvers. In addition to a higher deposition, FAVORITE maintains low dosage variability and exact reproducibility of the patient’s daily required dose of drugs.
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1.0
Lung and throat deposition, relative
Inhalation flow
Inhalation volume 1000 ml
Uncontrolled 100 ml/s 250 ml/s 500 ml/s
Conventional Inhalation
FAVORITE Inhalation
Brand et al. 2000; Total Deposition of Therapeutic Particles During Spontaneous and Controlled Breathing. Journal of Pharmaceutical Science, 2000. 89: p. 724-731.
Variability of lung
deposition in 18 patients
with severe lung disease
after inhalation of 3µm
particles.
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Effective strategies for patients with pulmonary obstructions
Controlled Respiration with Over Pressure
Ω Even inhalation with optimized inspiration and volume can be limited when specific areas of the lung are inaccessible due to obstruction. Special physiotherapeutic procedures, such as pausing during respiration, may help to improve respiration.
Scintigraphic depiction of
lung deposition in a healthy
subject and in a patient with
pulmonary obstructions
following drug inhalation
(Black area shows a large
amount of swallowed drug
in the stomach due to high
deposition in the throat).
Ω AKITA® JET’s FAVORITE concept offers patients with COPD the advantage of flow and volume-controlled respiration using over pressure. The slight increase in pressure is required in order to efficiently deliver the drug to less ventilated areas in the lungs.
Conventional Inhalation
Healthy Subject Patient
FAVORITE Inhalation Conventional Inhalation FAVORITE Inhalation
AKITA® JET effectively delivers the drug into all areas of the lung
Meyer et al. 2001; Deposition von therapeutischen Aerosolen in der Lungenperipherie. Aerosole in der Inhalationstherapie, ed. G. Scheuch. Vol. 5. 2001, Dustri-Verlag Dr Karl Feistle: München. 93-100
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FAVORITE Inhalation
Delivering Drugs to the Lower Airways
Ω For certain lung diseases, such as cystic fibrosis or α1-antitrypsin deficiency, the alveoli must be targeted in order to ensure adequate inhalation therapy. Drug deposition in the alveoli not only depends on a patient’s laryngeal or upper airway morphology, but also on the drug’s particle size as well as inspiration flow and volume.
Scintigraphic depiction of
lung deposition in the alveoli
of 10 COPD patients after
inhalation of radioactive
marked, mono-dispersed
Fe3O4 particles with a flow
rate of 200 cm3/s.
Ω The AKITA® JET inhalation system fulfills the exact requirements needed in order to deliver the maximum amount of drug aerosol to the alveoli. Flow and volume-controlled inhalation shows a clear superiority in peripheral alveolar deposition compared to conventional nebulizers.
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Lung deposition in the alveoli [%], relative
FAVORITE Inhalation
Particle size2 µm 3 µm 4 µm
Conventional Inhalation FAVORITE Inhalation
Sommerer et al. 2002; A Strategy to Optimize Peripheral Lung Deposition in Patients with Emphysema. Abstracts of the RDD Conference, Respiratory Drug Delivery, Arizona, USA 2002.
AKITA® JET significantly improves drug deposition in the alveoli
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“Drug Targeting”
Therapy for Predefined Areas of the Lung
Ω FAVORITE allows continuous control of both aerosolized drugs and air during the inhalation process. Pre-defined variation of the pattern of the drug and air bolus means that the drug deposition can be navigated into either the smaller air ways or into the central air ways. Depending on the treatment requirements, this location of drug deposition control helps to use drugs more specifically – they can be deposited directly at the place of action, a process called “Drug Targeting”.
“Drug Targeting” via
continuous control of
aerosolized drugs and air.
Ω For the very first time, precise pulmonary “Drug Targeting” is now possible for inhalation therapy in combination with AKITA® JET – depending on the drug and therapeutic goal, drug deposition can easily be adjusted.
Ω The central air ways are targets for bronchiodilating drugs – the systemic entry of the drug and subsequent side effects can be avoided by introducing an air bolus into the alveoli beforehand.
Ω The peripheral airways are targets for the inhalation of substances such as antibiotics or anti-inflammatory drugs. Following inhalation of the aerosolized drug, a small air bolus pushes the aerosol into the obstructed airways.
Peripheral Airway depositione.g. α1-antitrypsin and antibiotics
aerosolJust air
Central Airway Depositione.g. bronchiodilator applications
aerosol Just airJust air
For the very first time in inhaled treatment, AKITA® JET allows for precise “Drug Targeting”
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Exact drug dosage
Safer Inhalation of Antibiotics
Inhalation of Tobramycin (TOBI®) in a homogeneous collective of 12 healthy volunteers, detected scinitigraphic means
and cross-over investigation.
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Lung deposition to
bram
ycin [m
g]
dose variability32 % 11 %
ø Lung dose40,8 mg 42,8 mg
Conventional Inhalationwith 300 mg Tobramycin
FAVORITE Inhalationwith 160 mg Tobramycin
ø Serum level1 h after inhalation
0,39 mg/L 0,56 mg/L
Conventional inhalationwith 300 mg Tobramycin
FAVORITE Inhalationwith 160 mg Tobramycin
Ω AKITA® JET has several advantages, particularly for drugs with a narrow therapeutic window and high risk of side effects, e.g. antibiotics.
Ω The inhaled lung dosage can be easily reproduced with low variability.
Ω Slow regulated inhalation of the aerosolized drug helps significantly reduce throat deposition and avoid potential side effects, such as bronchospasms.
Brandt et al. 2006; Reduction of Drug-Dose and Therapy-Costs in High-Dose Tobramycin-Inhalation, Journal of Cystic Fibrosis; 2006; 5: Suppl 1: 86 June 2006.
AKITA® JET guarantees low variability of lung dosage and reduction of drug deposition in the throat
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Reducing wastage of expensive drugs
Equivalent Lung Deposition with 50% Less Input Dose
Lung deposition and serum level in 12 healthy volunteers after inhalation of Tobramycin. Cross-over inhalation test.
Szintigraphic depiction of lung deposition; Measurement of serum level 1 hour after inhalation.
Input dose [mg] Lung deposition [mg] Serum level [mg x 10/L]
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150
100
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Conventional inhalation
FAVORITE Inhalation
160 300 42,8 40,7 5,6 3,9
Ω With FAVORITE, nebulization occurs only during inspiration – when combined with AKITA® JET and controlled breathing techniques, FAVORITE inhalation allows for expensive drugs to be used fully and efficiently.
AKITA® JET – an investment that quickly pays off by saving expensive drugs
Ω In comparison to conventional nebulizers, AKITA® JET can provide equivalent lung dosing with a significantly reduced input dose, allowing for a 50% reduction in drug investment depending on the drug. Using AKITA® JET for the inhalation of high-dose Tobramycin could save patients more than €1.000 per month (based on average market prices in Europe).
Brandt et al. 2006; Reduction of Drug-Dose and Therapy-Costs in High-Dose Tobramycin-Inhalation, Journal of Cystic Fibrosis 2006; 5: Suppl 1: 86 June 2006.
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Increasing therapeutic quality
Effective Inhalation and Shorter Treatment Time
Inhalation time for Tobramycin 300 mg/4 ml, AKITA® JET vs. mesh nebulizer and conventional jet nebulizer.
AKITA® JET provides high quality therapy within a short treatment period
eFlow® rapid Optineb®
Therapy time [min]
Mesh nebulizers1 Jet nebulizers2
AKITA® JET with LC Sprint®
PARI Boy SX with LC Sprint®
12 min
10 min
8 min
6 min
4 min
0 min
2 min5,45 5,5 7,8 12,2
Ω Mesh nebulizers create large amounts of drug aerosol, which allows for a shorter treatment period. However, the quality of this kind of inhalation is questionable. When continuous aerosol nebulization is combined with sub- optimal and variable inspiration, a large amount of the drug is often wasted and the inhaled drug deposition can vary widely.
Ω The AKITA® JET inhalation system uses a reliable and robust jet nebulizer technology for aerosol generation. In comparison with a jet nebulizer using a normal compressor, a jet ne-bulizer combined with AKITA® JET significantly decreases inhalation time. Each inspiration with AKITA® JET is highly efficient with regard to the amount of drug deposited in the lungs per breath, meaning that fewer breaths are needed in order to reach the required dosage. AKITA® JET also decreases the inhaled treat-ment time typically required for high volume drug formulations to just under 10 minutes.
1.) Schneiders et al 2008; In-vitro Characterization of Bramitob® with Next Generation Nebulisers, Journal of Cystic Fibrosis 2006 CF - Volume 7, Supplement 3, Page S26, July 2008.
2.) Kroneberg et al 2009; The Choice of Nebulizers Effects Treatment Time and the Delivered Dose of Tobramycin. Abstract of DDL, Drug Delivery to the Lungs Conference; Dec. 2009, Edinburgh; UK.
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New treatment options
Greater Lung Dosing with FAVORITE
In vitro study with Fluticasone: Drug concentration at the mouthpiece and lung deposition measured using different
inhalation systems.
Compared to conventional inhalation systems, AKITA® JET allows for a significantly higher drug deposition in the lungs even with average dosing
DPI
Input dose 2 mg/2 ml Fluticasone, 250 µg with DPI
4,1o µm 4,26 µm 3,76 µmParticle size [MMAD]
PARI Turbo Boy N AKITA® JET
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Dose at the mouthpiece [µg]
Lung dose [µg]
210 55 367 142 668 497
Ω AKITA® JET’s outstanding efficacy ensures that a higher drug dose can be deposited into the lungs. A drug deposition of 75% not only shows efficient use of the drug, but it also shows that only a minimal amount is deposited in the throat – thus, a higher lung dose is possible without raising the risk of possible negative side effects.
Ω With a normal 2 mg/2ml dose of Fluticasone, AKITA® JET can achieve a lung dose four times higher than normal as compared to conventio-nal nebulizers and nine times more than with a Dry Powder Inhaler (DPI). AKITA® JET deposits 75% of the dose measured at the mouthpiece into the lungs, whereas conventional nebulizers only reach a deposition rate of 39% and DPI’s only 26%.
Müllinger et al. 2008; Drug Output of Inhalers is not a Predictor of Lung Dose. Abstracts of the RDD Conference, Respiratory Drug Delivery 2008; Arizona, USA.
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Therapeutic outlook for severe asthma
High Dose Inhalation of Steroids
Add-on Therapy with AKITA® JET: 2 mg/2 ml Fluticasone per day; 112 patients with severe asthma treated with oral
Corticosteroids, no placebo group has been tested.
Possible benefit from high dose inhalation with AKITA® JET – first clinical data
Change of therapy parameters after three weeks of AKITA® Inhalation [%]
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– 44,5 % NO-Exalat
+ 17,2 % FEV1
– 33,2 % Dose reduction of oral steroids
Ω 112 severe asthma patients with a need for permanent treatment with oral corticosteroids received a high dose of inhaled Fluticasone as an add-on therapy using AKITA® JET. The retrospective data analysis showed significant improvements after three weeks. Lung function improved on average by 17%, the need for oral corticosteroids could be reduced by 30% and NO-measurements showed that pulmonary inflammation wasreduced by 40%.
Ω Because of this promising data, ACTIVAERO has initiated a clinical program to validate this therapeutic approach. A first ramdomized, double blind, placebo-controlled multi-centre study is underway.
Ω The first clinical data with Fluticasone give an outlook how the high dose inhalation with AKITA JET could be used to develop new treatment regimes in the future. ACTIVAERO’S intends to achieve an improved clinical response and a reduction in systemic treatment and prevention of related side effects. In Asthma, for example, the long-term use of systemic
corticosteroids carries safety risks such as osteoporosis and diabetes.
Jung et al. 2008; Treatment of Patients with uncontrolled Asthma using high dose inhaled Corticosteroids administered by controlled Inhalation – A retrospective Analysis. ERJ Volume 34 Supplement 53 Sept 2009.
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Two fundamental options for therapy
Better Equivalent or Higher Maximum Dosing
Ω With AKITA® JET, equivalent drug doses (like those shown in scientific study results with conventional nebulizers) can by achieved, but with additional advantages:
Ω Better reproducibility of dosingΩ More precise drug targetingΩ Less drug consumptionΩ Less throat depositionΩ Better drug deposition in obstructive patientsΩ Reproducible therapy time
Ω Based on different therapeutic indications, AKITA® JET also offers the option to maximize drug dosage in the lungs – possible advantages for new treatment regimes in the future are:
Ω Higher local effectΩ Reduction or avoidance of a systemic therapy
PARI boy N; LC Plus AKITA®; LC Star
Starting dose 300 mg 150 mg
Nebulized dose 240 mg 60 mg
Therapy time 20 min 7–8 min
Serum level after 1 hour 1,2 ± 0,78 mg/L 1,1 ± 0,46 mg/L
After 3 Weeks add-on inhalation; Maximum dose of Fluticasone with AKITA®
Improvement of FEV1 + 17,2 %
Reduction of systemic steroid dose – 33,2 %
Additional side effects None
Equivalent inhalation of
Tobramycin with AKITA®: 16
patients with cystic fibrosis,
measured by serum levels–
in comparison with conven-
tional nebulizers, inhalation
time and drug consumption
were reduced by 50%.
Equivalent dosing with AKITA® JET: Shorter inhalation time and reduced drug consumption
Maximum dosing with AKITA® JET:An ongoing clinical program is checkingpossible benefits for the treatment of Asthma
First clinical data from a non con-
trolled pilot study on the high dose
inhalation of Fluticasone in severe
asthma: 122 patients needing sys-
temic steroids received high doses
of Fluticasone; inhalation of 2 mg
daily with AKITA®.
1.) Dopfer et al. 2007; Inhalation of Tobramycin in Patients with Cystic Fibrosis: Comparison of two Different Methods; Journal of Physiology and Pharmacology, 2007, 58, Suppl 5, 141-154.
2.) Jung et al. 2008; Treatment of Patients with uncontrolled Asthma using high dose inhaled Corticosteroids administered by controlled Inhalation – A retrospective Analysis. ERJ Volume 34 Supplement 53 Sept 2009.
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Smart Card ID 000991Language EnglishInhalation units 600Drug ColistinDosage 1 Mio IE Colistin/ 3,0 mlDeposition Peripheral-alveolar
Inhalation time Total numberper breath of breaths1,5 sec (0,3 l) 842,0 sec (0,4 l) 562,5 sec (0,5 l) 463,0 sec (0,6 l) 363,5 sec (0,7 l) 334,0 sec (0,8 l) 285,0 sec (1,0 l) 216,0 sec (1,2 l) 177,0 sec (1,4 l) 148,0 sec (1,6 l) 12
The SMART CARD
Specific Therapy Control
Ω The SMART CARD is an electronic chip card that provides and controls all relevant therapy parameters, such as the drug and dosage-specific inhalation information for AKITA® JET. Furthermore, all treatment data can be stored on the SMART CARD. This allows physicians, physiotherapists and patients to optimize the therapy using a computer-based compliance analysis.
Drug-specificOne SMART CARD per drug and dosage e.g. Colistin antibiotic– starting dose 1 Mio. IE Colistin in 3 ml solvent.
The improved SMART CARD CONCEPT – simple, flexible, drug-specific and patient-focused
Adapted to the patientThe AKITA® Display allows the patient to quickly and effectively adapt inhalation time per breath to his or her own inhalation capabilities – the chosen inhalation time determines the inhalation volume per breath.
Ω There is one SMART CARD for each drug and dosage and this determines the exact drug dose and deposition area in the lung. A patient can control the SMART CARD via the AKITA® JET display. The patient can select their breathing capacity by selecting their personal inspiration time or volume – a measurement of lung function can provide a recommendation for this setting. Based on this patient-specific information, the AKITA® JET calculates the number of breaths necessary to inhale the required lung dose. The treatment automatically finishes when the complete lung dose has been inhaled – in this way, under and over dosing can be prevented.
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Analyzing and optimizing patient compliance
Therapeutic Success is Measurable
Date Time Number of breaths
Therapy time [min]
Target breaths
Inhaled dose [%] Status
01-04-09 08:32 21 3:40 21 100 % HIT
01-04-09 18:34 21 3:55 21 100 % HIT
02-04-09 08:16 21 4:01 21 100 % HIT
02-04-09 19:02 28 4.25 28 100 % HIT
03-04-09 09:01 -- -- 21 0 % MISS
03-04-09 20:10 21 3:39 21 100 % HIT
04-04-09 08:32 -- -- 28 0 % MISS
04-04-09 18:34 21 3:55 21 100 % HIT
05-04-09 08:16 21 4:01 21 100 % HIT
05-04-09 19:02 28 4.25 28 100 % HIT
06-04-09 09:01 -- -- 21 0 % MISS
06-04-09 20:10 21 3:39 21 100 % HIT
…
…
…
22-04-09 09:01 -- -- 21 0 % MISS
22-04-09 20:10 21 3:46 21 100 % HIT
23-04-09 08:32 -- -- 28 0 % MISS
23-04-09 18:34 -- -- 28 0 % MISS
24-04-09 08:32 21 3:40 21 100 % HIT
24-04-09 18:34 21 3:32 21 100 % HIT
25-04-09 08:16 -- -- 21 0 % MISS
25-04-09 19:02 28 4.33 28 100 % HIT
26-04-09 09:01 -- -- 21 0 % MISS
26-04-09 20:10 21 3:29 21 100 % HIT
27-04-09 08:32 21 3:46 21 100 % HIT
27-04-09 18:34 21 3:56 21 100 % HIT
28-04-09 08:16 12 2:01 28 50 % incomplete
28-04-09 19:02 14 2:15 28 50 % incomplete
Therapeutic data
Treatment period 28 days
Inhalation time per breath 4,0 – 5,0 sec
Inhalation volume 0,8 – 1,0 l
Necessary treatments 56
Completed treatments 46
Skipped treatments 8
Partial treatments 2
Average treatment time 4:09 min
Example of therapeutic
data recorded on the
SMART CARD for the
inhalation of Colistin.
1 Mio. IE over 28 days.
Treatment record and evaluation using the SMART CARD
Ω The SMART CARD saves all therapeutic data:Data can be read and analyzed using a PC. This data is not only interesting in a clinical study setting, but also during outpatient procedures. This enables both doctor and patient to easily analyze and optimize compliance.
Ω Compliance analysis via SMART CARD provi-des information on:
Ω Number of breaths per treatmentΩ Treatment timeΩ Timing of treatment, e.g. morning vs. eveningΩ Inhaled drug dosage, e.g. over all dose and
seven-day doseCompliance analysis [%]
1008060400 20
Last 7 days
Evening
Morning
In total
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Technical details
Overview of AKITA® JET
AKITA® JET Control unit
Inhalation flow 12 l/min
Weight 2,85 kg
Size (L x H x B) 206 x 180 x 130 mm (including nebulizer)
Electric protection category II Typ B
AKITA® JET Power supply
Manufacturer FRIWO
Model DT50 Medical
Type FW7405M/24
Input voltage 100 – 240 V / 50 – 60 Hz / 1,1 A
Output voltage 24 VDC 2,2 A
AKITA® JET Nebulizer Set
Manufacturer PARI
Model LC Sprint®
min. Input volume 2 ml
max. Input volume 8 ml
Flow rate 12 l/min
Aerosol release 0,23 ml/min
MMAD Mass Median Aerodynamic Diameter 3,8 μm (sodium fluoride solution 1,0 %)
Additional Information
Germany HMZ 14.24.01.3002
Europe in accordance with 93/43/EWG
USA cleared in the USA (K090730)
Commercial launch 2008
Manufactured in Germany
Producer ACTIVAERO
Distribution, technical service, reimbursement National medical technology partner
1275
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Notes
Notes and Personal Information
Activaero GmbHHeadquarters & Logistics
Wohraer Straße 3735285 Gemünden/WohraGermanyTel. +49 (0)6453 64818-0Fax +49 (0)6453 64818-22
Activaero GmbHResearch & Development
Robert-Koch-Allee 2982131 GautingGermany
Activaero America, Inc.Subsidiary in America
P.O. Box 351 Dublin, OH 43017-9684USA
Service Hotline+49 (0)6453 64818-0
Internetwww.activaero.com
This project (HA-Projekt-Nr.: 144/08-06) has been supported by the state of Hess and their innovation promotion program, financed by LOEWE - Landes-Offensive zur Entwicklung Wissenschaftlich-ökonomischer Exzellenz, Förderlinie 3: KMU-Verbundvorhaben.
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