La lecture en ligne est gratuite
Le téléchargement nécessite un accès à la bibliothèque YouScribe
Tout savoir sur nos offres
Télécharger Lire

VECTARION - VECTARION - CT 12442 - Version anglaise

De
17 pages
Présentation VECTARION, lyophilisat et solution pour préparation injectable (code CIS : 60047143) Boîte de 12 flacons de lyophilisat et 12 ampoules de solvant - Code CIP : 3400932142798 Mis en ligne le 21 mai 2013 Substance active (DCI) almitrine (mésilate d') Le service médical rendu par VECTARION, lyophilisat et solution pour préparation injectable, dans l’hypoxémie et l’hypercapnie liées à une hypoventilation alvéolaire est faible lors du sevrage de l’assistance respiratoire artificielle. Le service médical rendu par VECTARION, lyophilisat et solution pour préparation injectable, dans l’hypoxémie et hypercapnie liées à une hypoventilation alvéolaire est insuffisant :- dans les épisodes de décompensation respiratoire aiguë compliquant les bronchopneumopathies chroniques obstructives ;- dans la dépression respiratoire momentanée induite par les analgésiques centraux, les neuroleptiques, le fluothane. Code ATC R07AB07 Laboratoire / fabricant SERVIER VECTARION, lyophilisat et solution pour préparation injectable (code CIS : 60047143) Boîte de 12 flacons de lyophilisat et 12 ampoules de solvant - Code CIP : 3400932142798 Mis en ligne le 21 mai 2013
Voir plus Voir moins

Vous aimerez aussi

 
The legally binding text is the original French version 
  TRANSPARENCYCOMMITTEE Opinion 20 March 2013    VECTARION, lyophilisate and solution for preparation for injection B/12 vials of lyophilisate and 12 ampoules of solvent (CIP code: 34009 321 4279 8)  
Applicant: SERVIER
INN
ATC Code (2012):
Reason for the review
List(s) concerned
Indication(s) concerned
     
almitrine bismesylate 
R07AB07 (respiratory stimulant) Re-assessment of Actual Benefit in response to a request by the Directorate-General for Health and the Social Security Directorate, pursuant to Article R-163-19 of the Social Security Code 
Hospital use(French Public Health Code L.5123-2) 
“Hypoxaemia and hypercapnia associated with alveolar hypoventilation in the following situations: · episodes of acute respiratory decompensation as a complication of chronic obstructive pulmonary disease, · weaning off artificial ventilatory support, · temporary respiratory depression induced by central analgesics, neuroleptics and fluothane.”  
HAS - Medical, Economic and Public Health Assessment Division 
1/17
 
Actual benefit
Improvement Actual Benefit
Therapeutic use
 
in
In view of its place in the therapeutic strate , endorsed b uidelines and b experts, in particular in hospitals that do not have appropriate ventilator support equipment, althou h its efficac is b no means proven in such cases, the actual benefit of VECTARION, l ophilisate and solution for preparation for in ection, in h poxaemia and h percapnia associated with alveolar h poventilation is low when weanin patients off artificial ventilator support.  In the absence of an uidelines, and accordin to expert opinion, the actual benefit of VECTARION, l ophilisate and solution for preparation for in ection, in h poxaemia and h percapnia associated with alveolar h poventilation is insufficient: -  as a complication ofin episodes of acute respirator decompensation chronic obstructive pulmonar disease; - in temporary respiratory depression induced by central analgesics, neuroleptics and fluothane.  
Not applicable
According to guidelines (SFAR (French Society of Anaesthesia and Intensive Care and SRLF (French Language Intensive Care Society) and expert opinion, injectable VECTARION still has a place in the management of acute respiratory syndromes as an adjuvant therapy alongside mechanical ventilation, especially when patients are being weaned off ventilation in the most serious cases and in the absence of appropriate ventilatory support equipment. In the absence of guidelines and according to expert opinion, injectable VECTARION no longer has any place in the management of: ·  ensation as a com lication ofe isodes of acute res irator decom chronic obstructive pulmonar disease, · temporary respiratory depression induced by central analgesics, neuroleptics and fluothane.  
HAS - Medical, Economic and Public Health Assessment Division 
2/17
01ADMINISTRATIVE AND REGULATORY INFORMATION 
 Marketing Authorisation (procedure) Prescribing and dispensing conditions / special status   
ATC Classification
 
Initial Marketing Authorisation: 25 July 1977 (national procedure) 7 October 2003: changed indication (present wording) and prescribing conditions (list II, reserved for hospital use). List II Medicinal product for hospital use only.
2012 R R07 R07A R07AB  R07AB07
02BACKGROUND 
Respiratory system Other respiratory system products Other respiratory system products Respiratory stimulants almitrine
VECTARION, lyophilisate and solution for preparation for injection, has only been on the list of medicinal products approved for use by hospitals and by various public services since 1978. At the request of the Directorate-General for Health and the Social Security Directorate, pursuant to Article R-163-19 of the Social Security Code dated 12 May 2012, the Transparency Committee is re-assessing the actual benefit of this proprietary medicinal product in a presentation for injection for hospital use only, as an addition to VECTARION tablets, which were re-assessed in 2011.  
03THERAPEUTIC INDICATIONS 
“Hypoxaemia and hypercapnia associated with alveolar hypoventilation in the following situations: · episodesof acute respiratory decompensation as a complication of chronic obstructive pulmonary disease, · off artificial ventilatory support, weaning · respiratory depression induced by central analgesics, neuroleptics and fluothane.” temporary  
04DOSAGE 
“Slow intravenous infusion: - preparing the solution,  Afterdilute in a bottle of isotonic glucose solution. Do not put any other products in this bottle as there is a possible risk of precipitation or denaturing. Infuse using an access cannula affording an adequate flow rate (greater than 18-gauge). - The direct intravenous (I.V.) route is not recommended; it does, however, remain an option; if it is used, administer the injection very slowly into a sufficiently large vein (maximum recommended flow-rate: 15 mg/minute, i.e. 1 bottle/minute). - Administration of injectable VECTARION is compatible with concomitant oxygen therapy.     
HAS - Medical, Economic and Public Health Assessment Division 
3/17
The posology is variable, depending on the patient’s clinical condition: -3 mg/kg/24 h, by slow intravenous infusion (2 the treatment of alveolar hypoventilation: 1 to  in to 3 infusions per 24 h) at a rate of 2 to 4 bottles per 2 h infusion, without exceeding 12 bottles per 24 h; - anaesthesiology (recovery room): 0.5 to 1 mg/kg/24 h, i.e. 2 to 4 bottles of 15 mg. As an in induction treatment: slow direct intravenous injection: 2 bottles, to be repeated if needed.  Treatment by intravenous infusion should be restricted to the shortest possible time and should be replaced by the oral form as soon as possible.”  
05THERAPEUTIC STRATEGY 
Acute respiratory failure is an immediately life-threatening syndrome associated with an inability of the ventilatory system to maintain gas exchanges at a level compatible with survival  Acute respiratory failure is a medical emergency. It can have very different causes and occur during an episode of chronic respiratory decompensation in COPD, or acute asthma, or be triggered by the presence of a foreign body in the upper respiratory tract, trauma, state of shock, coma, postoperative effects, lung disease – whether infectious (pneumonia, lymphangitis, septicaemia) or non-infectious (interstitial disease, tumor) – neuromuscular disease, anaphylactic reaction, heart disease (congestive heart failure), pleural effusion and other causes.  Treatment includes: - correction of hypoxaemia with oxygen therapy -the aid of bronchodilators or physiotherapy reducing ventilatory effort with - reducing respiratory muscle fatigue through assisted ventilation (invasive or non-invasive) - aetiological treatment.  In the management of acute respiratory failure during exacerbations of COPD requiring hospitalisation, respiratory stimulants no longer have a place in the therapeutic strategy.1 The recommended drug treatments in this clinical situation are short-acting bronchodilators, systemic corticosteroids, and antibiotics.  In the management of acute respiratory distress syndromes (ARDS), almitrine is an adjuvant treatment in mechanical ventilation, in particular when weaning patients off ventilation; however, it is not recommended for routine use.2,3Almitrine is reserved for use in the most severe cases, and should not be administered in cases of right ventricular failure or dysfunction, liver failure or lactic acidosis.  There is no recommendation for using injectable almitrine in temporary respiratory depression induced by central analgesics, neuroleptics or fluothane.       
                                               1GOLD (2013) 2Richard JC et al.Prise en charge ventilatoire du syndrome de détresse respiratoire aiguë de l’adulte et de l’enfant (nouveau-né exclu) - Recommandations d’Experts de la Société de Réanimation de Langue Françai 3 aux questions fréquemment posées. SFAR (2010). http://www.sfar.org/ar Réponsesstei c(l2e0/4051)5 /prise-en-charge-du-sdra-en-dehors-de-la-ventilation
HAS - Medical, Economic and Public Health Assessment Division 
4/17
06CLINICALLY RELEVANT COMPARATORS 
 06.1Medicinal products
There is one other respiratory stimulant with Marketing Authorisation for use in Intensive Care Units: DOPRAM 2%, solution for injection (doxapram). In practice, this proprietary medicinal product is not used in cases of profound acute respiratory failure. This proprietary medicinal product was included in the list approved for use by hospitals in 1982 and has not undergone an assessment by the Transparency Committee since that date.  06.2Other health technologies
Oxygen therapy, assisted ventilation.  
07INTERNATIONAL INFORMATION ON THE MEDICINAL PRODUCT 
VECTARION, lyophilisate and solution for preparation for injection, is marketed only in France.  
08SUMMARY OF PREVIOUS ASSESSMENTS 
Given that VECTARION, lyophilisate and solution for preparation for injection, is only included in the list of medicinal products approved for use by hospitals and other public services, and in the absence of any particular flag against it, this proprietary medicinal product has not been re-assessed since it was first listed in 1978.  
09ANALYSIS OF AVAILABLE DATA 
 09.1Efficacy
The Applicant has provided 32 studies in which the efficacy of injectable almitrine was assessed in patients with acute respiratory failure (see the table and references in the Appendix): -  11studies in patients with acute exacerbation of chronic respiratory failure; - 4 studies in patients recovering from general anaesthesia; - studies in toxic coma patients with respiratory depression; 2 - 11 studies in patients with acute respiratory distress syndrome;  4 studies in patients with acute respiratory failure due to various pulmonary causes. - These studies showed a decrease in hypoxaemia and hypercapnia with almitrine in various different clinical situations of acute respiratory failure; however, their level of evidence is poor (old studies, for the most part non-comparative and in small patient populations).  
HAS - Medical, Economic and Public Health Assessment Division 
5/17
09.2Safety/Adverse effects
The adverse effects observed during clinical studies and mentioned in the SPC are: - breathing difficulties; paradoxical - digestive disturbances such as nausea, heartburn and bloating. possible These effects do not routinely entail the discontinuation of treatment. Injectable VECTARION should be administered for a limited time.  The Applicant forwarded the latest periodic pharmacovigilance update report covering the period from 26/11/2006 to 25/11/2009 and from 26/11/2009 to 25/11/2011 relating to almitrine for injection. Over the period from 26/11/2006 to 25/11/2009, the number of treatment days was estimated at 44,079, and there were no pharmacovigilance reports submitted. Over the period from 26/11/2009 to 25/11/2011, exposure from the time the product came onto the market was estimated at 9453 patient-months. Two cases of adverse events were reported: one case of a non-serious increase in lactic acidaemia with a plausible causal link to VECTARION for injection, and one case of Stevens-Johnson syndrome in a polymedicated female patient under treatment with injectable VECTARION. No changes were made in the SPC based on the pharmacovigilance data.  09.3Usage/prescription data
Injectable VECTARION is only prescribed in hospitals. During the period from June 2011 to May 2012, 12,057 boxes (B/12 ampoules) were sold. Sales data for the past 3 years show steady sales.  09.4Summary & discussion
There have been many studies assessing the efficacy of almitrine in patients with acute respiratory failure. The results have shown a decrease in hypoxaemia and hypercapnia with almitrine in different clinical situations of acute respiratory failure; however, their level of evidence is poor (old studies, for the most part non-comparative, and in small patient populations).  The adverse effects observed with injectable almitrine are paradoxical breathing difficulties and possible digestive disturbances such as nausea, heartburn and bloating. Updated pharmacovigilance data for the injectable form do not reveal any new flags.  
HAS - Medical, Economic and Public Health Assessment Division 
6/17
010
THERAPEUTIC USE 
Despite a low level of evidence owing to the age of the studies, according to the guidelines of the 4 SRLF and SFAR5 societies of anaesthetists, and the opinion of experts, injectable VECTARION still has a place in the treatment of hypoxic and hypercapnic patients in the context of acute respiratory distress syndrome, and as an adjuvant treatment to mechanical ventilation, notably when patients are being weaned off ventilation in the most severe cases, especially in hospitals that do not have appropriate ventilatory support equipment.  In the absence of guidelines in these indications, injectable VECTARION no longer has any place in the management of: · episodes of acute respiratory decompensation as a complication of chronic obstructive pulmonary disease, · temporary respiratory depression induced by central analgesics, neuroleptics and fluothane.  
011
TRANSPARENCYCOMMITTEE CONCLUSIONS 
 In view of all the above information, and followin the debate and vote, the Committee’s opinion is as follows:  011.1Actual benefit
respiratory failure is a life-threatening medical emergency.Acute This proprietary medicinal product is intended for symptomatic treatment. The efficacy/adverse effects ratio is low. There are alternative treatments. Therapeutic use of this medicinal product: According to the guidelines (SFAR and SRLF) and expert opinion, injectable VECTARION still has a place in the management of acute respiratory syndromes as an adjuvant therapy to mechanical ventilation, especially when weaning patients off ventilation in the most serious cases and in the absence of appropriate ventilatory support equipment. In the absence of guidelines, and according to expert opinion, VECTARION for injection no longer has any place in the management of: · episodes of acute respiratory decompensation as a complication in chronic obstructive pulmonary disease, · temporary respiratory depression induced by central analgesics, neuroleptics and fluothane.   
                                               4Richard JC et al.respiratoire aiguë de l’adulte et de l’enfantPrise en charge ventilatoire du syndrome de détresse 5(nouveoaun-sneésexacluux) -qRueecsotimonmsa nfdraétiqounesmd’mExepnetrtsp odseélae sS.ocSFA Rd e(R2é0a1n0i)m.atihottnp :d//ewLwanwg.usef aFrr.aorngç/aaisrtei c(l2e0/0451)5 /prise-en- Rép charge-du-sdra-en-dehors-de-la-ventilation
HAS - Medical, Economic and Public Health Assessment Division 
7/17
Public health benefit: VECTARION for injection is unlikely to provide any public health benefit given the existence of alternative treatments, and the fact that it has not been shown to have any impact on morbidity or mortality or on quality of life compared to existing treatments.  Taking account of these points, the Committee considers that:   In view of its therapeutic usefulness, as endorsed by guidelines and by experts, in particular in the case of hospitals that do not have appropriate ventilatory support equipment, and even though its efficacy is by no means proven in this situation, the actual benefit of VECTARION, lyophilisate and solution for preparation for injection, in hypoxaemia and hypercapnia associated with alveolar hypoventilation is low when patients are being weaned off artificial ventilatory support.   the absence of any guideline and according to expert opinion, the actual benefit of In VECTARION, lyophilisate and solution for preparation for injection, in hypoxaemia and hypercapnia associated with alveolar hypoventilation is insufficient: - episodes of acute respiratory decompensation as a complication of chronicin obstructive pulmonary disease; - in temporary respiratory depression induced by central analgesics, neuroleptics and fluothane.  The Committee recommends the continued inclusion of VECTARION, lyophilisate and solution for preparation for injection, in the list of medicines approved for hospital use in hypoxaemia and hypercapnia associated with alveolar hypoventilation when weaning patients off artificial ventilatory support and at the dosages indicated in the Marketing Authorisation.  The Committee does not recommend the continued inclusion of VECTARION, lyophilisate and solution for preparation for injection, on the list of medicines approved for hospital use in: - episodes of acute respiratory decompensation as a complication of chronic obstructive pulmonary disease; - temporary respiratory depression induced by central analgesics, neuroleptics and fluothane.  
012
TRANSPARENCYCOMMITTEE RECOMMENDATIONS 
Packaging Appropriate for the prescription conditions.  
HAS - Medical, Economic and Public Health Assessment Division 
8/17
  
 
Study
APPENDIX: Tabulated summary of the studies on VECTARION, lyophilisate and solution for preparation for injection
SADOUL 19731 
MORERE 19731 
BERTRAND 19731 
MAIRESSE 2 1978
Design
Studies in acute respiratory decompensation in patients with chronic respiratory failure
Treatment
Open-label, 0.85-3 mg/kg/day  ncoonnt-rolled  (mean: 2 mg) 
  Assoecinaatteiod n N* Duration oxyg   
By mask or nasal prongs
Open-label, non- 60 mg/day -controlled Bird ncOoopnnet-rno-lllaebde l, 0.5-1.50 mg/kg/day r(e2s7)p igroars t n(o3ra )s al (mean: 1 mg) pron
abel, / or nOopnet-n-llled 03.05  mminguktge sf con ro
GERMOUTY Open-label, 19793ello d non-contr TENAILLON Open-label, 19804rolled  on-noctn SERGYSELS Open-label,  (NAEIJE) 19815octnon -ned roll
- 
rtificial ntilation
1 mg/kg for 1 hour -0.5 mg/kg for A 1 hour ve 0.25-0.5 mg/kg for -30 minutes
HAS - Medical, Economic and Public Health Assessment Division 
33
53
30
6
10
13
12
9 days
5-6 days
4 days
1 day
1 day
1 day
1 day
Population
Acute exacerbation of chronic respiratory failure
Acute exacerbation of chronic respiratory failure
Acute exacerbation of chronic respiratory failure
Acute exacerbation of chronic respiratory failure
Acute exacerbation of chronic respiratory failure
Acute exacerbation of chronic respiratory failure
Acute exacerbation of chronic respiratory failure
9/17
Blood gas parameters
PaO2: +18% (p<0.001) SaO2: +16% (p<0.001) PaCO2: -13% (p<0.001) Blood pH: +1.05% (p<0.001) PaO2: +17% (p<0.001) SaO2: +10% (p<0.001) PaCO2: -15% (p<0.001) Blood pH: +0.4% (p<0.001) PaO2: from +55 to +66 mmHg aO2: fro S m +82 to +90% PaCO2: from -62.2 to -54 mmHg Blood pH: from +7.34 to +7.37 PaO2: from 41.3 to 48.8 mmHg, +7.5% (p<0.05) SaO2: from 71.8 to 82.7%; +10.8% (p<0.05) PaCO2: from 56.6 to 49.3 mmHg; -7.3% (p<0.01) Blood pH: from 7.36 to 7.40; +0.04% (p<0.02) PaO2: from 52.2 to 56.9 mmHg (p<0.05) SaO2: from 84.7 to 88.4% (p<0.05) PaCO2: from 57.0 à 48.9 mmHg (p<0.001) Blood pH: from 7.39 to 7.45 (p<0.001) aO2: from 105 to 133 mmHg (p<0.001) P PaCO2: from 42 to 41 mmHg (NS) PaO2: from +43.7 to +53.9 mmHg (p<0.001) SaO2: from +78.5 to +86.9% (p<0.001) PaCO2: from -55.0 to -50.0 mmHg (p<0.001) Blood pH: from 7.39 to 7.43 (p<0.001)
  ciated N Duration * Study Design Treatment oAxsysgoenation     Comparative, WEITZENBLUM open-label, our  for -  14 6v s 1 day 19826h 1el lgrka/lgamh t5.0  wi p groups vs placebo Single-blind, randomised, Infusion for 30 comparative minutes: /kg 8 vs MARCQ 19797 - 0.5 mg Almitrine study with parallel or doxapram 8 groups vs 1 mg/kg doxapram Double-blind, randomised, comparative 2 mg/kg/day By nasal TOUATY 19808 with study parallel or placebo prongs groups vs placebo Double-blind, randomised, Infusion for 30 RAVEZ comparative, minutes: 19829 - 0.5 mg/kg Almitrine crossover study vs or placebo placebo * N: number of subjects treated with almitrine I.V. versus (vs) the control group
12 vs 3 days 12
HAS - Medical, Economic and Public Health Assessment Division 
14
1 day
Population
Chronic bronchitis with respiratory decompensation (PaO2<65 mmHg PaCO245 mmHg)
Acute exacerbation of chronic respiratory failure
Acute exacerbation of chronic respiratory failure
Acute exacerbation of chronic respiratory failure
10/17
Blood gas parameters
PaO2: from +51.9 to +61.9 mmHg, p<0.001 vs placebo PaCO2: from -52.8 to -45.7 mmHg, p<0.001 vs placebo Blood pH: from +7.39 to +7.43, p<0.001 vs placebo
PaO2: from 51.8 to 67.4 mmHg SaO2: from 86.0 to 92.7% PaCO2: from 53.2 to 46.9 mmHg Almitrine better than doxapram (p<0.05)
PaO2: +9.8 ± 4.1 mmHg SaO2: +5.6 ± 3.8% PaCO2: -6.45 ± 4.1 mmHg pH: +0.03 ± 0.04 Almitrine better than placebo (p<0.02)
PaO2: from 50.0 to 58.4 mmHg, p<0.001 vs placebo PaCO2: from -52.5 to -42.3 mmHg, p<0.001 vs placebo Blood pH: from 7.39 à 7.45, p<0.001 vs placebo
 Study
BIMAR 1 1976
SABATHIE 197810  
PAROTTE 198011 
LAXENAIRE 198012 
Design
Open-label, non-controlled  
Open-label, non-controlled
Open-label, comparative study with parallel groups vs absence of treatment
Comparative, randomised, double-blind study with parallel groups vs placebo
Studies in hypoventilation after anaesthesia, surgery and extubation
Treatment
0.5-1 mg/kg in 1 or 2 slow intravenous injections
0.5 mg/kg
1.5 mg/kg for 1 hour
Almitrine 0.5 mg/kg for 1 minute then almitrine 2.0 mg/kg for 2 hours Or placebo in the same infusion line
N*
140
16
10 vs 10
14 vs 14
Duration Population
1 day
1 day
1 day
1 day
Patients recovering from general anaesthesia
Patients recovering from general anaesthesia
Patients recovering from general anaesthesia (extubation)
Patients recovering from general anaesthesia (extubation)
* N: number of subjects treated with almitrine I.V. versus (vs) the control group
HAS - Medical, Economic and Public Health Assessment Division 
11/17
Main results Significant increase in minute ventilation (>100%), tidal volume and respiratory rate Significant changes in PaCO2and blood pH; 10 minutes after the injection: regression of the acidosis and hypercapnia Significant increase in minute ventilation Significant fall in PaCO2from 43.87 to 30.65 mmHg (p<0.001) Significant rise in the pH of arterial blood from 7.38 to 7.42 (p<0.001)  Significant fall in PaCO2in the almitrine group from 46.1 to 38.4 mmHg, p<0.005. In contrast, no significant fall in PaCO2in the control group (from 48.7 to 45.2 mmHg) Significant rise in PaO2from 85.2 to 108.1 mmHg in the almitrine group Small and non-significant increase in the respiratory rate for the first 15 minutes Significant increase in the tidal volume throughout the entire study, p<0.01 versus placebo Significant increase in minute ventilation, from 8.7 to 12.2 l/min, p<0.001 versus placebo Significant fall in PaCO2, p<0.001 versus placebo  
Un pour Un
Permettre à tous d'accéder à la lecture
Pour chaque accès à la bibliothèque, YouScribe donne un accès à une personne dans le besoin