The impact of a restricted pregabalin prescription policy on drug utilization: An observational multicenter study.

Background: The Saudi Food and Drug Authority (SFDA) classified pregabalin as a controlled substance in 2018; however, whether this policy change has affected pregabalin use is unclear. This study examined the trends in pregabalin prescriptions before and after the SFDA restriction. In addition, the co-prescription of controlled analgesics and the use of pregabalin for approved indications were also evaluated. Method: A cross-sectional study was conducted on outpatient pregabalin prescriptions from three healthcare centers in Saudi Arabia. Interrupted time series analysis was used to assess changes over time in pregabalin prescriptions and the number of patients receiving pregabalin. June 2016 to June 2017 was identified as the pre-restriction period, and July 2018 to July 2019 as the post-restriction period. Results: In this study, 77,760 pregabalin prescriptions were identified. There were 9,076 patients on pregabalin in the pre-restriction period with 16,875 prescriptions, compared with 7,123 patients and 19,484 prescriptions post-restriction. The total number of pregabalin users decreased by 21.5% post-restriction, and prescriptions increased by 15.5%. There was no significant change in the monthly trends in pregabalin prescriptions before and after the restriction. However, the of tramadol and acetaminophen/codeine prescriptions in patients who were using pregabalin increased in the post-restriction period by 21% and 16.1%, respectively. Conclusion: Pregabalin use was reduced after the SFDA-enforced prescription restriction was implemented. This was accompanied by increased narcotics use in the post-implementation phase.

Cost-Utility of Immunosuppressive Therapy Post-Renal Transplantation in Saudi Arabia: The Saudi Ministry of Health Perspective.

OBJECTIVES: Chronic kidney disease is ranked fourth among the top 10 causes of death in Saudi Arabia. Renal transplantation has been recognized as the treatment of choice compared with long-term dialysis to maintain graft survival and prolong a patient's healthy living. Immunosuppressants (ISs) must be administered lifelong. The choice between IS therapies can be challenging because of the similarity in efficacy with some differences in adverse events profile. The objective of this study was to assess the cost-effectiveness of different IS regimens in Saudi Arabia. METHODS: A 25-year Markov model was developed based on a previously published study from the Saudi Ministry of Health payer perspective. Efficacy parameters were driven from the literature, whereas cost data were estimated from the Ministry of Health database. A Monte Carlo simulation was conducted to test the base-case model results' robustness. RESULTS: All comparators resulted in 6.2 quality-adjusted life-years (QALYs) except for Advagraf® treatment (5.5 QALYs). Generic tacrolimus plus mycophenolate mofetil (MMF) will cost 70 701.45 US dollars ($) (Saudi riyal 265 130.44) per patient to gain 6.2 QALYs over 25 years' time horizon. In the improved adherence scenario, Envarsus® plus generic MMF generated 9.6 QALYs with a cost of $59 849 per patient. Monte Carlo simulation results have shown that generic tacrolimus is still the cheapest treatment option compared with other treatment arms. CONCLUSIONS: The current analysis suggested that all IS options are not cost-effective strategies relative to the willingness-to-pay threshold of $20 000. Nevertheless, Envarsus plus generic MMF regimen could become the most cost-effective regimen at different willingness-to-pay thresholds.

Cost of cardiovascular diseases and renal complications in people with type 2 diabetes mellitus in the Kingdom of Saudi Arabia: A retrospective analysis of claims database.

BACKGROUND: The burden of macro- and microvascular complications in patients with Type 2 diabetes mellitus (T2DM) is substantial in Middle East countries. The current study assessed the healthcare resource utilization (HCRU) and costs related to cardiovascular and renal complications among patients with T2DM. METHODOLOGY: This non-interventional, longitudinal, retrospective, cohort study collected secondary data from three insurance claims databases across Kingdom of Saudi Arabia (KSA) of patients diagnosed with T2DM. The study included adult patients aged ≥18 years diagnosed with first cardiovascular disease (CVD) during index time period and at least one T2DM claim anytime during the study time period. The primary analyses were conducted per database, stratified by three cohorts; patients with at least one claim every six months during the 1-year pre-index and 1-year post-index period (cohort 1), patients with at least one claim every six months during the 1-year pre-index, and two years post-index period (cohort 2) and patients with at least one claim every six months during the 1-year pre-index and 3-year post-index period (cohort 3). For each Payer database, demographics, CVD subgroups, HCRU, and costs were analysed. Descriptive statistics were used to analyse the data. RESULTS: The study sample comprised of 72-78% male and 22-28% female T2DM patients with CVD and renal complications. Patients in the age group of 35-65 years or above contributed to the significant disease burden. Nearly 68 to 80% of T2DM patients developed one CVD event, and 19 to 31% of patients developed multiple CVD events during the follow-up period. For most patients with comorbid CVD and renal disease, the average HCRU cost for post­index periods was higher compared to 1-year pre-index period across the different visit types and activities. CONCLUSION: The study findings elucidates the need for early initiation of therapies that would reduce the long-term cardiovascular and renal outcomes and the associated costs in patients with T2DM.

Restriction on antimicrobial dispensing without prescription on a national level: Impact on the overall antimicrobial utilization in the community pharmacies in Saudi Arabia.

BACKGROUND: High rates of non-prescription dispensing of antimicrobials have led to a significant increase in the antimicrobial overuse and misuse in Saudi Arabia (SA). The objective of this study was to evaluate the antimicrobial utilization following the enforcement of a new prescription-only antimicrobial dispensing policy in the community pharmacy setting in SA. METHODS: Data were extracted from the IQVIA database between May 2017 and May 2019. The antimicrobial utilization rates, based on sales, defined daily dose in grams (DDD), DDD/1000 inhabitants/day (DID), and antimicrobial-claims for the pre-policy (May 2017 to April 2018) and post-policy (June 2018 to May 2019) periods were assessed. RESULTS: Overall antimicrobial utilization declined slightly (~9-10%) in the post-policy versus pre-policy period (sales, 31,334 versus 34,492 thousand units; DDD, 183,134 versus 202,936), with higher claims (~16%) after policy implementation. There was a sudden drop in the utilization rate immediately after policy enforcement; however, the values increased subsequently, closely matching the pre-policy values. Utilization patterns were similar in both periods; penicillin was the most used antimicrobial (sales: 11,648-14,700-thousand units; DDD: 71,038-91,227; DID: 2.88-3.78). For both periods, the highest dip in utilization was observed in July (sales: 1,027-1,559 thousand units; DDD: 6,194-9,399), while the highest spike was in March/October (sales: 3,346-3,884 thousand units; DDD: 22,329-19,453). CONCLUSION: Non-prescription antimicrobial utilization reduced minimally following policy implementation in the community pharmacies across SA. Effective implementation of prescription-only regulations is necessary.

Saudi consensus recommendations on the management of multiple sclerosis: MS management in children and adolescents.

Multiple sclerosis (MS) most commonly presents in young adults, although 3-5% of patients develop MS prior to the age of 18 years. The new and comprehensive consensus for the management of MS in Saudi Arabia includes recommendations for the management of MS and other CNS inflammatory demyelinating disorders in pediatric and adolescent patients. This article summarizes the key recommendations for the diagnosis and management of these disorders in young patients. Pediatric and adult populations with MS differ in their presentation and clinical course. Careful differential diagnosis is important to exclude alternative diagnoses such as acute disseminated encephalomyelitis (ADEM) or neuromyelitis optica spectrum disorders (NMOSD). The diagnosis of MS in a pediatric/adolescent patient is based on the 2017 McDonald diagnostic criteria, as in adults, once the possibility of ADEM or NMOSD has been ruled out. Few data are available from randomized trials to support the use of a specific disease-modifying therapy (DMT) in this population. Interferons and glatiramer acetate are preferred initial choices for DMTs based on observational evidence, with the requirement of a switch to a more effective DMT if breakthrough MS activity occurs.

Tacrolimus-Induced Neurotoxicity in Early Post-Liver Transplant Saudi Patients: Incidence and Risk Factors.

BACKGROUND Tacrolimus is a calcineurin inhibitor (CNI) commonly used as an immunosuppressant to prevent the rejection of organ transplants. After liver transplantation, it can cause early neurological complications, known as early calcineurin inhibitor-induced neurotoxicity (ECIIN). Its management requires CNI withdrawal, a measure that can affect post-transplant outcomes, primarily allograft rejection. In addition, it can negatively impact the quality of life. The incidence and risk factor of ECIIN has not been reported in the Saudi population. We investigated the incidence and risk factors of ECIIN after liver transplant in Saudi patients. We also looked at the length of stay in the Intensive Care Unit, hospital, and 30-day mortality as secondary endpoints. MATERIAL AND METHODS This was a retrospective cohort study of adult patients on tacrolimus with mild, moderate, or severe neurological events within the first month after liver transplantation at a single center of patients who meet the inclusion criteria and were over age 14 years. A total of 338 patients were included in the analysis, and the sample size was calculated based on a pilot study. RESULTS Among 338 liver transplantation patients, 63 patients (19%) developed ECIIN. Forty-eight percent of patients had seizures, 23% had agitation, 21% had psychosis, 10% had severe tremors, 13% had confusion, and 6% developed coma. The median time of the incident to develop ECIIN was 9 (IQR: 5-13.5) days after transplant. Thirty-eight patients were managed by switching to cyclosporine, 12 required a reduction in the dose, and 3 were managed temporarily by discontinuing therapy. Autoimmune hepatitis as an underlying liver disease was one of the statistically significant risk factors (P=0.0311). The median length of hospital stay was 31 (IQR: 21-75.5) days, ICU length of stay was 10 (IQR: 5-20.5) days, and 8 patients died within 30 days after transplant. CONCLUSIONS The incidence of ECIIN in Saud Arabia was similar to that reported in other populations with similar risk factors. Electrolyte imbalance, mainly hyponatremia, was significantly associated with developing ECIIN. Therefore, ECIIN may potentially increase hospital and ICU length of stay.

Nebulized Amphotericin B Dosing Regimen for Aspergillus Prevention After Lung Transplant.

OBJECTIVES: Lung transplant guidelines recommend nebulized amphotericin B with or without systemic antifungal agents for fungal prophylaxis. However, amphotericin formulation, dosing, and frequency vary between studies. We assessed the safety and effectiveness of nebulized amphotericin B to prevent Aspergillus infection in 2 regimens, ie, twice daily compared with 3 times daily. MATERIALS AND METHODS: This was a single-center retrospective cohort study. We included patients at least 14 years old who underwent lung transplant and received nebulized amphotericin B alone or in combination with another antifungal agent either twice daily or 3 times daily. The primary endpoint was the incidence of lung Aspergillus infection, and the secondary endpoints were nebulized amphotericin B side effects and breakthrough Aspergillus infection. RESULTS: A total of 84 patients were included. The group given nebulized amphotericin twice daily had a higher rate of Aspergillus infection at 17% compared with 4% in the group treated 3 times daily (P = .24). No serious side effects were reported, but coughing and diarrhea were more common in patients who received amphotericin B 3 times daily. CONCLUSIONS: A systemic antifungal agent combined with nebulized amphotericin either twice or 3 times daily has been effective to prevent Aspergillus infection. Nebulized amphotericin twice daily may be a more viable option to increase a patient's adherence and decrease medication cost and side effects. However, a larger randomized controlled trial is needed to determine the best dosing regimen for nebulized amphotericin B as a fungal prophylaxis after lung transplant.

Empiric vs screening-based use of isoniazid for tuberculosis prophylaxis: Safety and effectiveness in lung transplant recipients in Saudi Arabia.

BACKGROUND: Tuberculosis (TB) is a major complication following transplantation. The likelihood of TB may be increased in transplant patients living in TB-endemic areas such as Saudi Arabia. In areas where TB is less common, guidelines recommend isoniazid (INH) for TB prophylaxis depending on patient and donor screening results. However, in TB-endemic regions, studies have supported its use in all transplant patients regardless of TB screening results. This study aimed to compare the safety and effectiveness of administering INH prophylaxis therapy based on the TB screening results of lung transplant (LT) recipients. METHODS: We conducted a single-center retrospective cohort study on LT recipients. The outcomes were compared between patients who were administered screening-based prophylaxis (SBP) with INH based on their tuberculin skin tests (TSTs) or QuantiFERON results and those who were administered empirical prophylaxis (EP) with INH regardless of TB screening results. The primary endpoint was the incidence of TB infection, and the secondary endpoints were INH-induced hepatotoxicity and INH resistance. RESULTS: A total of 50 patients received SBP and 30 received EP. TB incidences were 8% and 0%, respectively (P = .0487). One of these patients had INH resistance, and one patient experienced INH-induced hepatotoxicity (P = .1591); both were in the SBP group. CONCLUSION: The low rates of TB infection, INH-induced hepatotoxicity, and INH resistance in the EP group suggest that INH prophylaxis appears to prevent TB and can be safely used in all LT recipients. However, prospective studies using large sample sizes are required to confirm these findings.

Congenital Esophageal Atresia and Microtia in a Newborn Secondary to Mycophenolate Mofetil Exposure During Pregnancy: A Case Report and Review of the Literature.

BACKGROUND Mycophenolate mofetil (MMF) is one of the most commonly prescribed drugs to prevent organ transplant rejection in combination with calcineurin inhibitors and steroids. It has a different toxicity profile than tacrolimus and cyclosporine.  Gastrointestinal tract disturbances are the most common adverse effects. The use of MMF in pregnant women, however, holds great risk of miscarriage and fetal development defects such as external ear malformation, ocular anomalies, cleft lip and palate, and abnormality of distal limbs, heart, esophagus, and kidneys. Based on post-marketing studies, its pregnancy category was reclassified as category D by the US FDA in 2007. CASE REPORT A 20-year-old woman received a deceased-donor liver transplant for end-stage liver disease secondary to autoimmune hepatitis. She had 3 miscarriages while on MMF. In her fourth pregnancy she was exposed to MMF in the first trimester, which was stopped by week 20 of the pregnancy. Obstetric ultrasound suggested a cephalic presentation fetus with abdominal circumference. Her pregnancy resulted in an infant with tracheoesophageal fistula, esophageal atresia, and a bilateral ear canal atresia (microtia) with normal sensorineural conduction. There were no other congenital abnormalities. Thoracoscopic ligation of fistula and thoracotomy with esophageal repair were performed and a bone-anchored hearing aid for conductive hearing loss was implanted. Here, we report a case of congenital esophageal atresia and microtia secondary to mycophenolate mofetil. CONCLUSIONS MMF should be avoided during pregnancy. Transplanted female patients of reproductive age should receive appropriate counseling.

The first international residency program accredited by the American Society of Health-System Pharmacists.

The processes by which the pharmacy residency program at King Faisal Specialist Hospital and Research Centre-Riyadh, Saudi Arabia became the first American Society of Health-System Pharmacists (ASHP) accredited program outside the United States is described. This article provides key points for a successful program for other pharmacy residency programs around the world. Additionally, it points out the need for establishing international standards for pharmacy residency programs.