Int J Clin Pharm (2015) 37:296–299 DOI 10.1007/s11096-015-0074-7
SHORT RESEARCH REPORT
Attitudes of community pharmacists to off-label prescribing of baclofen in Northern France Marine Auffret • Benjamin Rolland • Anne-Sylvie Caous Sylvie Deheul • Johana Be´ne´ • Olivier Cottencin • Re´gis Bordet • Sophie Gautier
•
Received: 13 October 2014 / Accepted: 27 January 2015 / Published online: 10 February 2015 Koninklijke Nederlandse Maatschappij ter bevordering der Pharmacie 2015
Abstract Background Community pharmacists’ liability is involved when they dispense off-label prescriptions (OLPs). However, their attitudes to off-label prescribing are little known, while in France off-label baclofen use for alcohol dependence is increasing. Objective To determine community pharmacists’ attitudes to off-label prescribing of baclofen. Method A postal questionnaire was sent to 219 community pharmacies in the Nord-Pas-de-Calais region, France, previously identified as delivering at least five boxes of oral baclofen monthly. The questionnaire
Electronic supplementary material The online version of this article (doi:10.1007/s11096-015-0074-7) contains supplementary material, which is available to authorized users. M. Auffret (&) Centre Re´gional de Pharmacovigilance, CHRU de Lille, 59037 Lille Cedex, France e-mail: [email protected] B. Rolland O. Cottencin Service d’Addictologie, CHRU Lille, Lille Cedex, France B. Rolland R. Bordet S. Gautier EA 1046, Laboratoire de Pharmacologie, Universite´ de Lille 2, Lille Cedex, France A.-S. Caous S. Deheul R. Bordet Centre d’Evaluation et d’Information sur la Pharmacode´pendance du Nord-Pas de Calais, CHRU Lille, Lille Cedex, France
examined whether pharmacists delivered baclofen for alcohol dependence, how pharmacists detected off-label prescribing of baclofen, who were the most frequent prescribers (general practitioners or specialists), and pharmacists’ attitudes to OLPs. Results Eighty pharmacies responded (36.5 %). Detection criteria for OLPs were supra-threshold dose (77.3 %) and ‘‘off-label’’ written on prescription (52.5 %). General practitioners were the most frequent prescribers of off-label baclofen. Pharmacists were more likely to refuse to fill prescriptions not marked ‘‘off-label’’ (6.0 %) than correctly marked prescriptions (1.5 %). 85 % of respondents considered they lacked information on off-label use. Conclusion Although community pharmacists felt they were poorly informed on offlabel baclofen, the majority nevertheless delivered the drug. Since our survey, off-label baclofen prescribing has been strictly controlled in France. Pharmacists’ current attitudes will need further evaluation. Keywords Alcohol dependence Baclofen Community pharmacists Drug dispensing France Off-label
Impact of findings on practice •
J. Be´ne´ S. Gautier Centre Re´gional de Pharmacovigilance du Nord-Pas de Calais, CHRU Lille, Lille Cedex, France
•
O. Cottencin LNFP, EA 4559, Universite´ Lille Nord de France, 59045 Lille Cedex, France
•
123
Off-label prescription of baclofen in alcohol dependence has become ‘‘empirically accepted’’ in France, since pharmacists frequently receive OLPs for baclofen in alcohol dependence and very rarely refuse to deliver the drug. For pharmacists, the main criterion for detecting OLPs was a supra-threshold dose, which may raise concerns with regard to dose-dependent adverse drug reactions. The main prescribers of off-label baclofen are general practitioners.
Int J Clin Pharm (2015) 37:296–299
297
Background
Methods
Off-label prescribing is widespread around the world, and may account for approximately 20 % of prescriptions made out by general practitioners (GPs) [1]. In France, off-label prescribing is permitted, but prescribers have to comply with several rules: (1) off-label treatments may be used only when approved medications have failed; (2) the patient must be fully informed that he/she is receiving an off-label treatment, which carries possible benefits but also possible risks; (3) the prescriber has to write ‘‘off-label’’ on his prescription [2]. Theoretically, off-label prescriptions (OLPs) should not be reimbursed by health insurance. Since 2011 when a new law controlling prescribing was passed in France, community pharmacists have been more deeply involved in supervising OLPs [3]. They have to report any off-label use of medicines or any resulting adverse event to the French Health Agency (Agence Nationale de Se´curite´ du Me´dicament et des Produits de Sante´, ANSM). Notwithstanding, it remains largely unknown to what extent this new law has affected how pharmacists actually deal with OLPs. In France, the gamma-aminobutyric acid type B (GABA-B) receptor agonist baclofen is now commonly prescribed offlabel for alcohol dependence by a large number of both GPs and specialists. These OLPs often exceed the maximum authorized dose of 80 mg/day and may be as high as 400 mg/day or more. However, there has been no strong evidence that this treatment is effective, and the possible interactions between baclofen and alcohol are unknown. Numerous adverse drug reactions have been reported with the off-label use of high-dose baclofen [4–6], and several safety concerns have been raised by the French Health Agency [7, 8]. Since March 2014, a special regulatory procedure, called temporary recommendation for use (TRU), controls the off-label prescribing of high-dose baclofen for alcohol dependence [9].
Selection of relevant community pharmacies
Objective We aimed to examine the attitudes of community pharmacists to off-label prescribing of baclofen before the TRU came into force.
We contacted the community pharmacies of the Nord-Pasde-Calais region, France, that dispensed more than five boxes of baclofen per month. These pharmacies were identified from the regional data of a large wholesaler and distributor. Two hundred and nineteen pharmacies fulfilled the selection criteria for our survey and were contacted as detailed below. Survey characteristics A questionnaire was initially sent by postal mail to the 219 community pharmacies on July 15, 2013. The questionnaire was again sent with a reminder letter on November 15, 2013, to the pharmacies which had not responded at this date. The survey was closed on December 15, 2013. Pharmacists could send the completed questionnaire by postal mail, fax, or email. The questions put to the pharmacists are listed in the supplement Table.
Results Eighty pharmacies responded to the survey (response rate 36.5 %). Table 1 summarized pharmacy characteristics of respondents. The responses to each survey question are detailed in the Table 2. Sixty two pharmacies, or 77.5 % of responders and 28.3 % of all pharmacies contacted, reported that they fulfilled off-label baclofen prescriptions. On average, pharmacists reported 5.25 ± 3.56 deliveries per month of baclofen for all indications and 2.14 ± 1.46 deliveries per month for alcohol dependence. Pharmacists estimated that 58.1 % of off-label baclofen prescriptions were issued by GPs and 48.8 % by specialists. The criteria used to identify off-label prescribing were suprathreshold dose (77.3 %, 51/66 respondents), patients’ medical history (53.0 %, 35/66), ‘‘off-label’’ on the prescription (52.5 %, 34/66), and prescriber identity (34.8 %, 23/66). Eighty-five percent of pharmacists (51/60) considered they had insufficient information about the off-label use of baclofen in alcohol dependence and 88.3 % (53/60) wanted more information.
Ethical approval
Discussion
Ethical approval was not required. In France, only data concerning patients require ethical approval.
Individual attitudes to off-label prescribing have already been investigated among prescribers, but the attitude of
123
298
Int J Clin Pharm (2015) 37:296–299
Table 1 Pharmacy Characteristics
For all respondent pharmacies % (n/n of responders)
For pharmacies that fulfilled off-label baclofen prescriptions % (n/n of responders)
Total number of pharmacists working in respondent pharmacies Mean
2.5
B2
60.0 (48/80)
2.6 56.5 (35/62)
[3–5]
35.0 (28/80)
37.1 (23/62)
C5
5.0 (4/80)
6.5 (4/62)
Location of respondent pharmacies Urban area Suburban or rural area
Table 2 Pharmacists’ attitude in two situations: prescription marked or not marked ‘‘offlabel’’
Pharmacist’s attitude
67.7 (42/62) 32.3 (20/62)
‘‘Off-label’’ written on prescription % (n/n of responders)
No ‘‘off-label’’ written on prescription % (n/n of responders)
Deliver without calling the prescriber
77.3 (50/66)
70.1 (47/67)
Call the prescriber
22.8 (15/66)
23.9 (16/67)
whatever the dose
12.1 (8/66)
–
if dose [110 mg/day on average
10.7 (7/66)
–
Request reimbursement from health insurance
–
80.6 (54/67)
Refuse to deliver
1.5 (1/66)
6.0 (4/67)
Ensure that the patient clearly understands the meaning of off-label use
59.1 (39/66)
–
pharmacists to delivery of these prescriptions has been little studied. Nevertheless, they are both legally and ethically concerned by the impact such prescribing may have on patients. In France, off-label prescribing of baclofen for alcohol dependence is particularly illustrative of the public health issues that may be raised by such practices. We therefore thought it would be interesting to investigate the attitudes of community pharmacists to offlabel delivery of baclofen. The main objective of our survey was to determine the proportion of community pharmacies that had identified baclofen OLPs for alcohol dependence among all baclofen prescriptions they received. Although a large majority of responders reported that they identified such OLPs in their practice, this result needs to be considered in relation to the overall response rate, as discussed below. However, our findings were in agreement with previous reports that offlabel prescribing of baclofen has become widespread in France [7]. Furthermore, through direct investigation among dispensing pharmacies we were able to compare the relative proportion of off-label and authorized prescriptions. This comparison revealed that alcohol dependence is becoming the main indication for baclofen prescription in this country, even though there had been no officially management of off-label baclofen prescription until 2014. Our survey also confirmed the results of a previous study that GPs were the main prescribers of baclofen in alcohol
123
62.5 (50/80) 37.5 (30/80)
dependence [10]. Lastly, it confirmed that most OLPs involve high doses of baclofen. Moreover, for pharmacists, the main criterion for detecting OLPs was a supra-threshold dose. Our survey revealed that community pharmacists only exceptionally refused to deliver baclofen to patients, despite the fact that they felt insufficiently informed about its off-label use. Even when the prescriber did not write ‘‘offlabel’’ on his prescription, pharmacists usually delivered the drug. Nevertheless, refusals to dispense were more frequent when off-label use was not specified. This may suggest that French pharmacists, similarly to many French physicians, considered that because of the volume and frequency of off-label prescription of baclofen, it had become ‘‘empirically accepted’’ and that questioning the prescription was justified only in exceptional circumstances. In support of this hypothesis, it should be noted that in July 2013 the ANSM had already announced the forthcoming publication of a TRU measure for off-label baclofen [9]. This measure was widely publicized in both the specialized and the general press. Consequently, although off-label prescribing was not officially controlled at this time, it is likely that many health professionals considered that it would soon be regularized and so was already more or less legitimate. Our survey has several limitations, principally the low response rate (36.5 %). It is possible that the pharmacists
Int J Clin Pharm (2015) 37:296–299
who responded were those who were more likely to deliver off-label baclofen, and so in our study the proportion of pharmacists who fulfilled such prescriptions could be overestimated. Moreover, the criteria used to select pharmacies for the survey can be debated. Pharmacies that delivered prescriptions for low-dose baclofen, i.e. \50 mg/day per patient, were not all included in the study. This may explain why high baclofen dose was the main criterion for detection of off-label prescribing in alcohol dependence. Our study is original because it was conducted among community pharmacists, who delivered prescriptions issued by GPs and by specialist physicians (psychiatrists or addiction specialists), and so it provides a global view of both medical and pharmaceutical practice with regard to off-label baclofen prescribing.
Conclusion Community pharmacists regularly received off-label prescriptions for baclofen in alcohol dependence. Like other studies conducted in France, we found that the main prescribers were GPs. In spite of the fact that prescriber did write ‘‘off-label’’ on prescription and that pharmacists feel they are insufficiently informed on off-label use of baclofen, they very rarely refused to deliver the drug. Our survey shows that off-label prescribing of baclofen has become empirically accepted. Since the survey, strict regulatory measures have been introduced in France to control off-label prescribing of baclofen, and it will be important to re-evaluate pharmacists’ attitudes since these measures have come into force. Acknowledgments The research team would like to thank pharmacists who agreed to complete the questionnaire. Funding
No special funding was received.
Conflicts of interest B.R. and O.C. are associate investigators in the ALPADIR clinical trial, a placebo-controlled study of the efficacy of baclofen in maintaining abstinence in alcohol dependence funded by the pharmaceutical company Ethypharm S.A. B.R. participated as an unpaid speaker at a conference organised by the Institut de Recherche Scientifique sur les Boissons Alcoolise´es (IREB), an organisation funded by companies in the alcohol industry. O.C. participated in
299 symposia organised by Lundbeck, Pfizer, Servier, Reckit Benckiser, Bouchara Recordati and Janssen Cilag. S.G., T.D., R.B., M.A. and S.D. have no conflict of interest.
References 1. Radley DC, Finkelstein SN, Stafford RS. Off-label prescribing among office-based physicians. Arch Intern Med. 2006;166: 1021–6. 2. Loi no. 2011—2012 du 29 de´cembre 2011 relative au renforcement de la se´curite´ sanitaire du me´dicament et des produits de sante´. Journal Officiel de la Re´publique Franc¸aise. 2011. 3. Auffret M, Rolland B, Deheul S, Lecomte L, Cottencin O, Bordet R, et al. Le dispositif CAMTEA. Involvement of pharmacists in systems for supervising off-label medications: example of the CAMTEA system for the prescription of baclofen in alcohol use disorder in Northern France. Ann Pharm Fr. 2014;72:28–32. 4. Geoffroy PA, Auffret M, Deheul S, Bordet R, Cottencin O, Rolland B. Baclofen-induced manic symptoms: case report and systematic review. Psychosomatics. 2014;55:326–32. 5. Auffret M, Rolland B, Deheul S, Loche V, Hennaux C, Cottencin O, et al. Severe tinnitus induced by off-label baclofen. Ann Pharmacother. 2014;48:656–9. 6. Rolland B, Deheul S, Danel T, Bordet R, Cottencin O. A case of de novo seizures following a probable interaction of high-dose baclofen with alcohol. Alcohol Alcohol. 2012;47:577–80. 7. Agence Nationale de Se´curite´ du Me´dicament et des Produits de Sante´ (ANSM). Point d’information—Utilisation du baclofe`ne dans l’alcoolode´pendance: actualisation juin. 2012. http://ansm. sante.fr/S-informer/Points-d-information-Points-d-information/ Utilisation-du-baclofene-dans-le-traitement-de-l-alcoolo-depen dance-Point-d-information-actualisation-juin-2012/%28language% 29/fre-FR. Accessed 26 Sept 2014. 8. Agence Nationale de Se´curite´ du Me´dicament et des Produits de Sante´ (ANSM). Commission e´valuation initiale du rapport entre les be´ne´fices et les risques des produits de sante´. Compte-rendu de la re´union du 4 juillet 2013. http://ansm.sante.fr/var/ansm_site/ storage/original/application/693a562657d53e271bf6836f9ce03f57. pdf. Accessed 29 Sept 2014. 9. Agence Nationale de Se´curite´ du Me´dicament et des Produits de Sante´ (ANSM). Une recommandation temporaire d’utilisation (RTU) est accorde´e pour le baclofe`ne—Point d’information. 14 mars 2014. http://ansm.sante.fr/S-informer/Points-d-informationPoints-d-information/Une-recommandation-temporaire-d-utilisa tion-RTU-est-accordee-pour-le-baclofene-Point-d-information Accessed September 296 2014. 10. Dupouy J, Fournier JP, Jouanjus E´, Palmaro A, Poutrain JC, Oustric S, et al. Baclofen for alcohol dependence in France: incidence of treated patients and prescription patterns–a cohort study. Eur Neuropsychopharmacol. 2014;24:192–9.
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SHORT RESEARCH REPORT
Attitudes of community pharmacists to off-label prescribing of baclofen in Northern France Marine Auffret • Benjamin Rolland • Anne-Sylvie Caous Sylvie Deheul • Johana Be´ne´ • Olivier Cottencin • Re´gis Bordet • Sophie Gautier
•
Received: 13 October 2014 / Accepted: 27 January 2015 / Published online: 10 February 2015 Koninklijke Nederlandse Maatschappij ter bevordering der Pharmacie 2015
Abstract Background Community pharmacists’ liability is involved when they dispense off-label prescriptions (OLPs). However, their attitudes to off-label prescribing are little known, while in France off-label baclofen use for alcohol dependence is increasing. Objective To determine community pharmacists’ attitudes to off-label prescribing of baclofen. Method A postal questionnaire was sent to 219 community pharmacies in the Nord-Pas-de-Calais region, France, previously identified as delivering at least five boxes of oral baclofen monthly. The questionnaire
Electronic supplementary material The online version of this article (doi:10.1007/s11096-015-0074-7) contains supplementary material, which is available to authorized users. M. Auffret (&) Centre Re´gional de Pharmacovigilance, CHRU de Lille, 59037 Lille Cedex, France e-mail: [email protected] B. Rolland O. Cottencin Service d’Addictologie, CHRU Lille, Lille Cedex, France B. Rolland R. Bordet S. Gautier EA 1046, Laboratoire de Pharmacologie, Universite´ de Lille 2, Lille Cedex, France A.-S. Caous S. Deheul R. Bordet Centre d’Evaluation et d’Information sur la Pharmacode´pendance du Nord-Pas de Calais, CHRU Lille, Lille Cedex, France
examined whether pharmacists delivered baclofen for alcohol dependence, how pharmacists detected off-label prescribing of baclofen, who were the most frequent prescribers (general practitioners or specialists), and pharmacists’ attitudes to OLPs. Results Eighty pharmacies responded (36.5 %). Detection criteria for OLPs were supra-threshold dose (77.3 %) and ‘‘off-label’’ written on prescription (52.5 %). General practitioners were the most frequent prescribers of off-label baclofen. Pharmacists were more likely to refuse to fill prescriptions not marked ‘‘off-label’’ (6.0 %) than correctly marked prescriptions (1.5 %). 85 % of respondents considered they lacked information on off-label use. Conclusion Although community pharmacists felt they were poorly informed on offlabel baclofen, the majority nevertheless delivered the drug. Since our survey, off-label baclofen prescribing has been strictly controlled in France. Pharmacists’ current attitudes will need further evaluation. Keywords Alcohol dependence Baclofen Community pharmacists Drug dispensing France Off-label
Impact of findings on practice •
J. Be´ne´ S. Gautier Centre Re´gional de Pharmacovigilance du Nord-Pas de Calais, CHRU Lille, Lille Cedex, France
•
O. Cottencin LNFP, EA 4559, Universite´ Lille Nord de France, 59045 Lille Cedex, France
•
123
Off-label prescription of baclofen in alcohol dependence has become ‘‘empirically accepted’’ in France, since pharmacists frequently receive OLPs for baclofen in alcohol dependence and very rarely refuse to deliver the drug. For pharmacists, the main criterion for detecting OLPs was a supra-threshold dose, which may raise concerns with regard to dose-dependent adverse drug reactions. The main prescribers of off-label baclofen are general practitioners.
Int J Clin Pharm (2015) 37:296–299
297
Background
Methods
Off-label prescribing is widespread around the world, and may account for approximately 20 % of prescriptions made out by general practitioners (GPs) [1]. In France, off-label prescribing is permitted, but prescribers have to comply with several rules: (1) off-label treatments may be used only when approved medications have failed; (2) the patient must be fully informed that he/she is receiving an off-label treatment, which carries possible benefits but also possible risks; (3) the prescriber has to write ‘‘off-label’’ on his prescription [2]. Theoretically, off-label prescriptions (OLPs) should not be reimbursed by health insurance. Since 2011 when a new law controlling prescribing was passed in France, community pharmacists have been more deeply involved in supervising OLPs [3]. They have to report any off-label use of medicines or any resulting adverse event to the French Health Agency (Agence Nationale de Se´curite´ du Me´dicament et des Produits de Sante´, ANSM). Notwithstanding, it remains largely unknown to what extent this new law has affected how pharmacists actually deal with OLPs. In France, the gamma-aminobutyric acid type B (GABA-B) receptor agonist baclofen is now commonly prescribed offlabel for alcohol dependence by a large number of both GPs and specialists. These OLPs often exceed the maximum authorized dose of 80 mg/day and may be as high as 400 mg/day or more. However, there has been no strong evidence that this treatment is effective, and the possible interactions between baclofen and alcohol are unknown. Numerous adverse drug reactions have been reported with the off-label use of high-dose baclofen [4–6], and several safety concerns have been raised by the French Health Agency [7, 8]. Since March 2014, a special regulatory procedure, called temporary recommendation for use (TRU), controls the off-label prescribing of high-dose baclofen for alcohol dependence [9].
Selection of relevant community pharmacies
Objective We aimed to examine the attitudes of community pharmacists to off-label prescribing of baclofen before the TRU came into force.
We contacted the community pharmacies of the Nord-Pasde-Calais region, France, that dispensed more than five boxes of baclofen per month. These pharmacies were identified from the regional data of a large wholesaler and distributor. Two hundred and nineteen pharmacies fulfilled the selection criteria for our survey and were contacted as detailed below. Survey characteristics A questionnaire was initially sent by postal mail to the 219 community pharmacies on July 15, 2013. The questionnaire was again sent with a reminder letter on November 15, 2013, to the pharmacies which had not responded at this date. The survey was closed on December 15, 2013. Pharmacists could send the completed questionnaire by postal mail, fax, or email. The questions put to the pharmacists are listed in the supplement Table.
Results Eighty pharmacies responded to the survey (response rate 36.5 %). Table 1 summarized pharmacy characteristics of respondents. The responses to each survey question are detailed in the Table 2. Sixty two pharmacies, or 77.5 % of responders and 28.3 % of all pharmacies contacted, reported that they fulfilled off-label baclofen prescriptions. On average, pharmacists reported 5.25 ± 3.56 deliveries per month of baclofen for all indications and 2.14 ± 1.46 deliveries per month for alcohol dependence. Pharmacists estimated that 58.1 % of off-label baclofen prescriptions were issued by GPs and 48.8 % by specialists. The criteria used to identify off-label prescribing were suprathreshold dose (77.3 %, 51/66 respondents), patients’ medical history (53.0 %, 35/66), ‘‘off-label’’ on the prescription (52.5 %, 34/66), and prescriber identity (34.8 %, 23/66). Eighty-five percent of pharmacists (51/60) considered they had insufficient information about the off-label use of baclofen in alcohol dependence and 88.3 % (53/60) wanted more information.
Ethical approval
Discussion
Ethical approval was not required. In France, only data concerning patients require ethical approval.
Individual attitudes to off-label prescribing have already been investigated among prescribers, but the attitude of
123
298
Int J Clin Pharm (2015) 37:296–299
Table 1 Pharmacy Characteristics
For all respondent pharmacies % (n/n of responders)
For pharmacies that fulfilled off-label baclofen prescriptions % (n/n of responders)
Total number of pharmacists working in respondent pharmacies Mean
2.5
B2
60.0 (48/80)
2.6 56.5 (35/62)
[3–5]
35.0 (28/80)
37.1 (23/62)
C5
5.0 (4/80)
6.5 (4/62)
Location of respondent pharmacies Urban area Suburban or rural area
Table 2 Pharmacists’ attitude in two situations: prescription marked or not marked ‘‘offlabel’’
Pharmacist’s attitude
67.7 (42/62) 32.3 (20/62)
‘‘Off-label’’ written on prescription % (n/n of responders)
No ‘‘off-label’’ written on prescription % (n/n of responders)
Deliver without calling the prescriber
77.3 (50/66)
70.1 (47/67)
Call the prescriber
22.8 (15/66)
23.9 (16/67)
whatever the dose
12.1 (8/66)
–
if dose [110 mg/day on average
10.7 (7/66)
–
Request reimbursement from health insurance
–
80.6 (54/67)
Refuse to deliver
1.5 (1/66)
6.0 (4/67)
Ensure that the patient clearly understands the meaning of off-label use
59.1 (39/66)
–
pharmacists to delivery of these prescriptions has been little studied. Nevertheless, they are both legally and ethically concerned by the impact such prescribing may have on patients. In France, off-label prescribing of baclofen for alcohol dependence is particularly illustrative of the public health issues that may be raised by such practices. We therefore thought it would be interesting to investigate the attitudes of community pharmacists to offlabel delivery of baclofen. The main objective of our survey was to determine the proportion of community pharmacies that had identified baclofen OLPs for alcohol dependence among all baclofen prescriptions they received. Although a large majority of responders reported that they identified such OLPs in their practice, this result needs to be considered in relation to the overall response rate, as discussed below. However, our findings were in agreement with previous reports that offlabel prescribing of baclofen has become widespread in France [7]. Furthermore, through direct investigation among dispensing pharmacies we were able to compare the relative proportion of off-label and authorized prescriptions. This comparison revealed that alcohol dependence is becoming the main indication for baclofen prescription in this country, even though there had been no officially management of off-label baclofen prescription until 2014. Our survey also confirmed the results of a previous study that GPs were the main prescribers of baclofen in alcohol
123
62.5 (50/80) 37.5 (30/80)
dependence [10]. Lastly, it confirmed that most OLPs involve high doses of baclofen. Moreover, for pharmacists, the main criterion for detecting OLPs was a supra-threshold dose. Our survey revealed that community pharmacists only exceptionally refused to deliver baclofen to patients, despite the fact that they felt insufficiently informed about its off-label use. Even when the prescriber did not write ‘‘offlabel’’ on his prescription, pharmacists usually delivered the drug. Nevertheless, refusals to dispense were more frequent when off-label use was not specified. This may suggest that French pharmacists, similarly to many French physicians, considered that because of the volume and frequency of off-label prescription of baclofen, it had become ‘‘empirically accepted’’ and that questioning the prescription was justified only in exceptional circumstances. In support of this hypothesis, it should be noted that in July 2013 the ANSM had already announced the forthcoming publication of a TRU measure for off-label baclofen [9]. This measure was widely publicized in both the specialized and the general press. Consequently, although off-label prescribing was not officially controlled at this time, it is likely that many health professionals considered that it would soon be regularized and so was already more or less legitimate. Our survey has several limitations, principally the low response rate (36.5 %). It is possible that the pharmacists
Int J Clin Pharm (2015) 37:296–299
who responded were those who were more likely to deliver off-label baclofen, and so in our study the proportion of pharmacists who fulfilled such prescriptions could be overestimated. Moreover, the criteria used to select pharmacies for the survey can be debated. Pharmacies that delivered prescriptions for low-dose baclofen, i.e. \50 mg/day per patient, were not all included in the study. This may explain why high baclofen dose was the main criterion for detection of off-label prescribing in alcohol dependence. Our study is original because it was conducted among community pharmacists, who delivered prescriptions issued by GPs and by specialist physicians (psychiatrists or addiction specialists), and so it provides a global view of both medical and pharmaceutical practice with regard to off-label baclofen prescribing.
Conclusion Community pharmacists regularly received off-label prescriptions for baclofen in alcohol dependence. Like other studies conducted in France, we found that the main prescribers were GPs. In spite of the fact that prescriber did write ‘‘off-label’’ on prescription and that pharmacists feel they are insufficiently informed on off-label use of baclofen, they very rarely refused to deliver the drug. Our survey shows that off-label prescribing of baclofen has become empirically accepted. Since the survey, strict regulatory measures have been introduced in France to control off-label prescribing of baclofen, and it will be important to re-evaluate pharmacists’ attitudes since these measures have come into force. Acknowledgments The research team would like to thank pharmacists who agreed to complete the questionnaire. Funding
No special funding was received.
Conflicts of interest B.R. and O.C. are associate investigators in the ALPADIR clinical trial, a placebo-controlled study of the efficacy of baclofen in maintaining abstinence in alcohol dependence funded by the pharmaceutical company Ethypharm S.A. B.R. participated as an unpaid speaker at a conference organised by the Institut de Recherche Scientifique sur les Boissons Alcoolise´es (IREB), an organisation funded by companies in the alcohol industry. O.C. participated in
299 symposia organised by Lundbeck, Pfizer, Servier, Reckit Benckiser, Bouchara Recordati and Janssen Cilag. S.G., T.D., R.B., M.A. and S.D. have no conflict of interest.
References 1. Radley DC, Finkelstein SN, Stafford RS. Off-label prescribing among office-based physicians. Arch Intern Med. 2006;166: 1021–6. 2. Loi no. 2011—2012 du 29 de´cembre 2011 relative au renforcement de la se´curite´ sanitaire du me´dicament et des produits de sante´. Journal Officiel de la Re´publique Franc¸aise. 2011. 3. Auffret M, Rolland B, Deheul S, Lecomte L, Cottencin O, Bordet R, et al. Le dispositif CAMTEA. Involvement of pharmacists in systems for supervising off-label medications: example of the CAMTEA system for the prescription of baclofen in alcohol use disorder in Northern France. Ann Pharm Fr. 2014;72:28–32. 4. Geoffroy PA, Auffret M, Deheul S, Bordet R, Cottencin O, Rolland B. Baclofen-induced manic symptoms: case report and systematic review. Psychosomatics. 2014;55:326–32. 5. Auffret M, Rolland B, Deheul S, Loche V, Hennaux C, Cottencin O, et al. Severe tinnitus induced by off-label baclofen. Ann Pharmacother. 2014;48:656–9. 6. Rolland B, Deheul S, Danel T, Bordet R, Cottencin O. A case of de novo seizures following a probable interaction of high-dose baclofen with alcohol. Alcohol Alcohol. 2012;47:577–80. 7. Agence Nationale de Se´curite´ du Me´dicament et des Produits de Sante´ (ANSM). Point d’information—Utilisation du baclofe`ne dans l’alcoolode´pendance: actualisation juin. 2012. http://ansm. sante.fr/S-informer/Points-d-information-Points-d-information/ Utilisation-du-baclofene-dans-le-traitement-de-l-alcoolo-depen dance-Point-d-information-actualisation-juin-2012/%28language% 29/fre-FR. Accessed 26 Sept 2014. 8. Agence Nationale de Se´curite´ du Me´dicament et des Produits de Sante´ (ANSM). Commission e´valuation initiale du rapport entre les be´ne´fices et les risques des produits de sante´. Compte-rendu de la re´union du 4 juillet 2013. http://ansm.sante.fr/var/ansm_site/ storage/original/application/693a562657d53e271bf6836f9ce03f57. pdf. Accessed 29 Sept 2014. 9. Agence Nationale de Se´curite´ du Me´dicament et des Produits de Sante´ (ANSM). Une recommandation temporaire d’utilisation (RTU) est accorde´e pour le baclofe`ne—Point d’information. 14 mars 2014. http://ansm.sante.fr/S-informer/Points-d-informationPoints-d-information/Une-recommandation-temporaire-d-utilisa tion-RTU-est-accordee-pour-le-baclofene-Point-d-information Accessed September 296 2014. 10. Dupouy J, Fournier JP, Jouanjus E´, Palmaro A, Poutrain JC, Oustric S, et al. Baclofen for alcohol dependence in France: incidence of treated patients and prescription patterns–a cohort study. Eur Neuropsychopharmacol. 2014;24:192–9.
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