“Off-label use” is defined as the use of medicine for indications other than recommended or registered for, e.g. the prescribing of a particular active substance for a patient younger than the substance is recommended or indicated for, or different formulations or dosages of a substance (Ekins-Daukes et al., 2004:349; Stedman’s medical dictionary, 2006). Off-label prescribing is common, and fluctuates by physician, patient and drug (Eguale et al., 2012:781). Drug classes most commonly prescribed off-label include anti-asthmatic, cardiovascular drugs and antidepressants. Lee et al. (2012:140) found that 9 out of 10 antidepressants prescribed were associated with unapproved usage of antidepressants. An antidepressant can be defined as a substance that prevents or relieves depression or depressive episodes (Mosby, 2009:115). There is paucity of information on the off-label prescribing practices of antidepressants in the South African private health sector. According to Eguale et al. (2012:781), the paucity of information on off-label prescribing practices may be, in part, ascribed to the difficulty in the establishment of reasons for treatment. The objective of this study was to determine the prescribing patterns of antidepressants as well as to identify off-label prescribing of antidepressants among adults in a section of the private health sector of South Africa by using a medicine claims database. A quantitative and observational, descriptive cross-sectional design was followed in this study. Data for a period of a year, from January to December 2010 were obtained for analysis. The data set consisted of medicine claims for a total number of 1 220 289 patients, containing a total of 8 515 428 prescriptions and 20 527 777 medicine items. The study population (patients receiving antidepressants 18 years and older) accounted for 14.8% (n = 1 220 289) of the total data set. The average age of patients receiving antidepressants was 56.1 ± 16.6 (median = 56.2) (Inter quartile range = 43.3–68.1). Results of the study showed that antidepressant prescriptions accounted for 8.3% (n = 8 515 428) of all prescriptions claimed during 2010. A total 3.5 % (n = 20 527 777) of antidepressants were claimed during the study period. Using the DU90% method it was established that the majority of antidepressant medicine items were prescribed by general practitioners (i.e. 75.7%, n = 702 285) and psychiatrists (14.9%, n = 702 285). Almost 72% (n = 702 885) of antidepressant medicine items claimed for the study population were for women. The most prescribed antidepressants (based on the DU90%) were amitriptyline (20.6%, n = 702 885), citalopram (19.2%), escitalopram (14.6%), fluoxetine (11.7%), venlafaxine (5.7%), paroxetine (5.2%), duloxetine (4.4%), sertraline (3.8%), bupropion (3.1%) and mirtazapine (2.6%). Amitriptyline accounted for 82.4% of off-label prescriptions (n = 2 635), whereas escitalopram and fluoxetine accounted for 4.2% and 3.8%, respectively. The tricyclic antidepressants (TCAs) were mostly prescribed off-label for migraine, headache and sleep disorders. The off-label prescribing of selective serotonin re-uptake inhibitors (SSRIs) included menopause, schizophrenia and headache. The off-label indicated prescriptions of the serotonin and noradrenaline re-uptake inhibitors (SNRIs) were mostly for schizophrenia and other anxiety disorders. Mirtazapine, a serotonin modulator/tetracyclic antidepressant, was mostly prescribed off-label for anxiety disorders. Off-label prescriptions for bupropion, a noradrenaline and dopamine re-uptake inhibitor mainly included other anxiety disorders and attention deficit hyperactivity disorder (ADHD). Furthermore, the prescribed daily dose (PDD) of each active antidepressant for all off-label indications was determined. In conclusion: This study investigated the off-label prescribing patterns of antidepressants among adults a section of the private health sector of a South Africa, using a large medicine claims database. Recommendations for future research were made. / MPham (Pharmacy Practice), North-West University, Potchefstroom Campus, 2014

“Off-label use” is defined as the use of medicine for indications other than recommended or registered for, e.g. the prescribing of a particular active substance for a patient younger than the substance is recommended or indicated for, or different formulations or dosages of a substance (Ekins-Daukes et al., 2004:349; Stedman’s medical dictionary, 2006). Off-label prescribing is common, and fluctuates by physician, patient and drug (Eguale et al., 2012:781). Drug classes most commonly prescribed off-label include anti-asthmatic, cardiovascular drugs and antidepressants. Lee et al. (2012:140) found that 9 out of 10 antidepressants prescribed were associated with unapproved usage of antidepressants. An antidepressant can be defined as a substance that prevents or relieves depression or depressive episodes (Mosby, 2009:115). There is paucity of information on the off-label prescribing practices of antidepressants in the South African private health sector. According to Eguale et al. (2012:781), the paucity of information on off-label prescribing practices may be, in part, ascribed to the difficulty in the establishment of reasons for treatment. The objective of this study was to determine the prescribing patterns of antidepressants as well as to identify off-label prescribing of antidepressants among adults in a section of the private health sector of South Africa by using a medicine claims database. A quantitative and observational, descriptive cross-sectional design was followed in this study. Data for a period of a year, from January to December 2010 were obtained for analysis. The data set consisted of medicine claims for a total number of 1 220 289 patients, containing a total of 8 515 428 prescriptions and 20 527 777 medicine items. The study population (patients receiving antidepressants 18 years and older) accounted for 14.8% (n = 1 220 289) of the total data set. The average age of patients receiving antidepressants was 56.1 ± 16.6 (median = 56.2) (Inter quartile range = 43.3–68.1). Results of the study showed that antidepressant prescriptions accounted for 8.3% (n = 8 515 428) of all prescriptions claimed during 2010. A total 3.5 % (n = 20 527 777) of antidepressants were claimed during the study period. Using the DU90% method it was established that the majority of antidepressant medicine items were prescribed by general practitioners (i.e. 75.7%, n = 702 285) and psychiatrists (14.9%, n = 702 285). Almost 72% (n = 702 885) of antidepressant medicine items claimed for the study population were for women. The most prescribed antidepressants (based on the DU90%) were amitriptyline (20.6%, n = 702 885), citalopram (19.2%), escitalopram (14.6%), fluoxetine (11.7%), venlafaxine (5.7%), paroxetine (5.2%), duloxetine (4.4%), sertraline (3.8%), bupropion (3.1%) and mirtazapine (2.6%). Amitriptyline accounted for 82.4% of off-label prescriptions (n = 2 635), whereas escitalopram and fluoxetine accounted for 4.2% and 3.8%, respectively. The tricyclic antidepressants (TCAs) were mostly prescribed off-label for migraine, headache and sleep disorders. The off-label prescribing of selective serotonin re-uptake inhibitors (SSRIs) included menopause, schizophrenia and headache. The off-label indicated prescriptions of the serotonin and noradrenaline re-uptake inhibitors (SNRIs) were mostly for schizophrenia and other anxiety disorders. Mirtazapine, a serotonin modulator/tetracyclic antidepressant, was mostly prescribed off-label for anxiety disorders. Off-label prescriptions for bupropion, a noradrenaline and dopamine re-uptake inhibitor mainly included other anxiety disorders and attention deficit hyperactivity disorder (ADHD). Furthermore, the prescribed daily dose (PDD) of each active antidepressant for all off-label indications was determined. In conclusion: This study investigated the off-label prescribing patterns of antidepressants among adults a section of the private health sector of a South Africa, using a large medicine claims database. Recommendations for future research were made. / MPham (Pharmacy Practice), North-West University, Potchefstroom Campus, 2014

Background: In 2007 the population density for the Gauteng Province was 614 persons per km2 and in the Northern Cape Province it was 2.9 persons per km2 . High population density leads to an increase in crime. This was evident in the percentage distribution of total crime reported from 2000 to 2003 of 27.4% in Gauteng Province, while the percentage distribution of total crime reported in the Northern Cape for the same period of time was 2,8%. Stress and insomnia can be caused by crime which is influenced by population density. Crime and high population density, may cause stress and fear, which may lead to insomnia and anxiety, which in turn may lead to an increase in benzodiazepine usage. Objective: The general objective of this study was to investigate the benzodiazepine usage in the private health care sector in South Africa based on age, sex, geographical areas, prescriber type and days between refills. Methods: The data were obtained from a medicine claims database of a pharmacy benefit management company covering the periods from 1 January 2006 to 31 December 2006 and 1 January 2008 to 31 December 2008. The statistical analysis was performed by making use of the Statistical Analysis System®. A drug utilisation review was performed. Results: Patients claiming benzodiazepines represented about 7.25% of all patients in total database in 2006 and 7.97% in 2008. Female patients claimed more benzodiazepines than male patients in both Gauteng (67.24% in 2006 & 67.36% in 2008 respectively) and Northern Cape Province (67.77% in 2006 & 67.70% in 2008 respectively). Patients aged 40 years to 65 years claimed the highest number of benzodiazepine items, while patients younger than 12 years claimed the lowest number of benzodiazepine items. The number of patients that claimed benzodiazepines in the Northern Cape was lower than those in Gauteng. The percentage of patients that claimed benzodiazepines in 2006 was 7.91% in Gauteng versus 8.96% in Northern Cape. In 2008 the percentage of patients that claimed benzodiazepines was 8.47% in Gauteng versus 9.51% in Northern Cape. The percentage of benzodiazepine prescriptions claimed in Gauteng was 4.79% in 2006 and 5.10% in 2008. In the Northern Cape the percentages of benzodiazepine prescriptions claimed in 2006 and 2008 were 4.62% and 4.30% respectively. General medical practitioners prescribed most of the benzodiazepine prescriptions in both Northern Cape and Gauteng Province. Trade name products that were mostly prescribed in the Gauteng was Adco–Alzam® 0.5 mg and in the Northern Cape it was Brazepam® 3 mg for both 2006 and 2008. Conclusion: The difference in the prescribing patterns of benzodiazepines in Gauteng and the Northern Cape was not statistically significant. Recommendations for future research were made. / Thesis (M.Pharm (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2011.

Advances in molecular immunology and rapid technical evolution during the past two decades have led to a new class of medicines called biologics. Recently, a large number of biologics, or biologic immunomodulators, directed towards an array of immune–mediated diseases, have entered the market. This has lead to a dramatic change in the immunotherapy of autoimmune diseases, as biologics present new potential to improve or substitute conventional immunosuppressive therapies. According to literature, biologics are used by only a small number of a health plan’s members, (approximately one per cent), but a single occurrence can be relatively expensive. Furthermore, there is an indication that the frequency of use and cost of biologics are on the rise, and as more biologics enter the market, health plans and employers face the challenge of controlling costs while ensuring that biologics are affordable. The general objective of this study was to determine the prevalence and cost of biologic immunomodulating medicine in the treatment of certain autoimmune diseases during the period 2005 to 2008 in a section of the private health care sector of South Africa, by employing a medicine claims database as a source to obtain necessary information. A quantitative, retrospective drug utilisation review (rDUR) was performed on computerised medication records (medicine claims data) for four consecutive years (i.e. 2005 to 2008) provided by a pharmacy benefit management company (PBM). The study population consisted of all patients on the database who received at least one medicine item with adalimumab, etanercept, infliximab, interferon beta–1a, interferon 1–b or rituximab as active ingredient and who were diagnosed with either rheumatoid arthritis (RA), multiple sclerosis (MS) or Crohn’s disease between 1 January 2005 and 31 December 2008. Between 2005 and 2008, an average of 1,305,201 patients appeared on the total database, and of these 0.055% (n = 713) received biologic immunomodulating medicine. More than two thirds of biological users were female and most patients who received these medicine items were between the ages of 39 and 64 years, followed by those patients aged between 25 and 39 years. Biologic immunomodulating medicine items (n = 11,914) and biologic prescriptions (n = 9,537) represented 0.016% of the total number of medicine items (N = 76,129,173) and 0.030% of the total number of prescriptions (N = 31,985,153). The percentage contribution of biologic immunomodulators to the total number of medicine items and prescriptions on the total database increased each year, and in four years’ time the percentage of all the medicine items on the total database that included biologic immunomodulators had tripled, from 0.009% to 0.023%. The total cost of biologic immunomodulating medicine accounted for 1.278% of the total cost (N = R7, 483,759,176.23) of all medication claimed through the PBM between 2005 and 2008. The percentage contribution of biologic immunomodulators to the total medicine expenditure also increased from one year to another for the four–year study period. The average cost of a biologic immunomodulating medicine item increased with 71.10% from 2005 (R5602.71 ± 2166.61) to (R9586.25 ± 5956.56) in 2008. The CPI for biologic immunomodulators, (CPI = 60.00 for 2005; CPI = 74.62.17 for 2006; CPI = 85.26 for 2007; and CPI = 86.96 for 2008) indicated that biologic immunomodulating medicine items were relatively expensive and the d–value between the average cost per biologic immunomodulator and the average cost per non–biological medicine item (d–value = 2.54 in 2005, d–value = 3.32 in 2006, d–value = 2.23 in 2007 and d–value = 1.59 in 2008) furthermore indicated that the impact of biological therapies was large and practically significant. Rheumatoid arthritis patients represented 19.78% of the total number of patients (n = 713) who claimed the biologic immunomodulators during the four–year period, MS patients (n = 172) represented 24.12% and Crohn’s patients (n = 11) represented 1.5%. Biological drugs prescribed to RA patients represented 0.28% (n = R20, 708,818.82) of the total cost (N = R7, 483,759,176.23) of all medication claimed through the PBM during the four–year period, while those prescribed to MS patients represented 0.41% (R30, 922,520.07) and those prescribed to Crohn’s disease patients represented 0.015% (R1, 108,568.02). Although biologic immunomodulating medicine items used in the treatment of RA, MS and Crohn’s disease are relatively expensive, it seems that the number of other medication prescribed to patients with these diseases decreased after treatment with biologics, which may influence the medicine treatment cost of these patients. It can be concluded that even though biologic immunomodulators are used by only a very small percentage of the total patient population in a section of the private health care sector of South Africa, they are relatively expensive and have a considerable impact not only the medical aid scheme, but also on the patient. / Thesis (M.Pharm (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2011.

Background: In 2007 the population density for the Gauteng Province was 614 persons per km2 and in the Northern Cape Province it was 2.9 persons per km2 . High population density leads to an increase in crime. This was evident in the percentage distribution of total crime reported from 2000 to 2003 of 27.4% in Gauteng Province, while the percentage distribution of total crime reported in the Northern Cape for the same period of time was 2,8%. Stress and insomnia can be caused by crime which is influenced by population density. Crime and high population density, may cause stress and fear, which may lead to insomnia and anxiety, which in turn may lead to an increase in benzodiazepine usage. Objective: The general objective of this study was to investigate the benzodiazepine usage in the private health care sector in South Africa based on age, sex, geographical areas, prescriber type and days between refills. Methods: The data were obtained from a medicine claims database of a pharmacy benefit management company covering the periods from 1 January 2006 to 31 December 2006 and 1 January 2008 to 31 December 2008. The statistical analysis was performed by making use of the Statistical Analysis System®. A drug utilisation review was performed. Results: Patients claiming benzodiazepines represented about 7.25% of all patients in total database in 2006 and 7.97% in 2008. Female patients claimed more benzodiazepines than male patients in both Gauteng (67.24% in 2006 & 67.36% in 2008 respectively) and Northern Cape Province (67.77% in 2006 & 67.70% in 2008 respectively). Patients aged 40 years to 65 years claimed the highest number of benzodiazepine items, while patients younger than 12 years claimed the lowest number of benzodiazepine items. The number of patients that claimed benzodiazepines in the Northern Cape was lower than those in Gauteng. The percentage of patients that claimed benzodiazepines in 2006 was 7.91% in Gauteng versus 8.96% in Northern Cape. In 2008 the percentage of patients that claimed benzodiazepines was 8.47% in Gauteng versus 9.51% in Northern Cape. The percentage of benzodiazepine prescriptions claimed in Gauteng was 4.79% in 2006 and 5.10% in 2008. In the Northern Cape the percentages of benzodiazepine prescriptions claimed in 2006 and 2008 were 4.62% and 4.30% respectively. General medical practitioners prescribed most of the benzodiazepine prescriptions in both Northern Cape and Gauteng Province. Trade name products that were mostly prescribed in the Gauteng was Adco–Alzam® 0.5 mg and in the Northern Cape it was Brazepam® 3 mg for both 2006 and 2008. Conclusion: The difference in the prescribing patterns of benzodiazepines in Gauteng and the Northern Cape was not statistically significant. Recommendations for future research were made. / Thesis (M.Pharm (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2011.

Advances in molecular immunology and rapid technical evolution during the past two decades have led to a new class of medicines called biologics. Recently, a large number of biologics, or biologic immunomodulators, directed towards an array of immune–mediated diseases, have entered the market. This has lead to a dramatic change in the immunotherapy of autoimmune diseases, as biologics present new potential to improve or substitute conventional immunosuppressive therapies. According to literature, biologics are used by only a small number of a health plan’s members, (approximately one per cent), but a single occurrence can be relatively expensive. Furthermore, there is an indication that the frequency of use and cost of biologics are on the rise, and as more biologics enter the market, health plans and employers face the challenge of controlling costs while ensuring that biologics are affordable. The general objective of this study was to determine the prevalence and cost of biologic immunomodulating medicine in the treatment of certain autoimmune diseases during the period 2005 to 2008 in a section of the private health care sector of South Africa, by employing a medicine claims database as a source to obtain necessary information. A quantitative, retrospective drug utilisation review (rDUR) was performed on computerised medication records (medicine claims data) for four consecutive years (i.e. 2005 to 2008) provided by a pharmacy benefit management company (PBM). The study population consisted of all patients on the database who received at least one medicine item with adalimumab, etanercept, infliximab, interferon beta–1a, interferon 1–b or rituximab as active ingredient and who were diagnosed with either rheumatoid arthritis (RA), multiple sclerosis (MS) or Crohn’s disease between 1 January 2005 and 31 December 2008. Between 2005 and 2008, an average of 1,305,201 patients appeared on the total database, and of these 0.055% (n = 713) received biologic immunomodulating medicine. More than two thirds of biological users were female and most patients who received these medicine items were between the ages of 39 and 64 years, followed by those patients aged between 25 and 39 years. Biologic immunomodulating medicine items (n = 11,914) and biologic prescriptions (n = 9,537) represented 0.016% of the total number of medicine items (N = 76,129,173) and 0.030% of the total number of prescriptions (N = 31,985,153). The percentage contribution of biologic immunomodulators to the total number of medicine items and prescriptions on the total database increased each year, and in four years’ time the percentage of all the medicine items on the total database that included biologic immunomodulators had tripled, from 0.009% to 0.023%. The total cost of biologic immunomodulating medicine accounted for 1.278% of the total cost (N = R7, 483,759,176.23) of all medication claimed through the PBM between 2005 and 2008. The percentage contribution of biologic immunomodulators to the total medicine expenditure also increased from one year to another for the four–year study period. The average cost of a biologic immunomodulating medicine item increased with 71.10% from 2005 (R5602.71 ± 2166.61) to (R9586.25 ± 5956.56) in 2008. The CPI for biologic immunomodulators, (CPI = 60.00 for 2005; CPI = 74.62.17 for 2006; CPI = 85.26 for 2007; and CPI = 86.96 for 2008) indicated that biologic immunomodulating medicine items were relatively expensive and the d–value between the average cost per biologic immunomodulator and the average cost per non–biological medicine item (d–value = 2.54 in 2005, d–value = 3.32 in 2006, d–value = 2.23 in 2007 and d–value = 1.59 in 2008) furthermore indicated that the impact of biological therapies was large and practically significant. Rheumatoid arthritis patients represented 19.78% of the total number of patients (n = 713) who claimed the biologic immunomodulators during the four–year period, MS patients (n = 172) represented 24.12% and Crohn’s patients (n = 11) represented 1.5%. Biological drugs prescribed to RA patients represented 0.28% (n = R20, 708,818.82) of the total cost (N = R7, 483,759,176.23) of all medication claimed through the PBM during the four–year period, while those prescribed to MS patients represented 0.41% (R30, 922,520.07) and those prescribed to Crohn’s disease patients represented 0.015% (R1, 108,568.02). Although biologic immunomodulating medicine items used in the treatment of RA, MS and Crohn’s disease are relatively expensive, it seems that the number of other medication prescribed to patients with these diseases decreased after treatment with biologics, which may influence the medicine treatment cost of these patients. It can be concluded that even though biologic immunomodulators are used by only a very small percentage of the total patient population in a section of the private health care sector of South Africa, they are relatively expensive and have a considerable impact not only the medical aid scheme, but also on the patient. / Thesis (M.Pharm (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2011.