Evaluation of statin utilization in the Republic of Macedonia during 2013–2016

Zorica Naumovska,1 Aleksandra K Nestorovska,1 Aleksandra Grozdanova,1 Kristina Hristova,2 Aleksandar Dimovski,1 Ljubica Suturkova,1 Zoran Sterjev1 1Department of Pharmaceutical Chemistry, Faculty of Pharmacy, SS “Cyril and Methodius”, Skopje, Republic of Macedonia; 2Department of Health Insurance Fund of R. Macedonia, Skopje, Republic of Macedonia Purpose: A rational use of statins has a major and increasing importance in public health and allocation of financial resources by the health insurance funds (HIFs). The aim of this study was to evaluate the market share and utilization trends of statins in the Republic of Macedonia (R. Macedonia) from 2013 to 2016. Materials and methods: A retrospective analysis and data comparison for the utilization of HMG-CoA inhibitors (C10AA) in R. Macedonia from 2013 to 2016 were conducted. The data obtained from HIF, IMS Health, pharmaceutical industry and marketing authorization holders (MAHs) were evaluated through defined daily doses per 1000 insurers per day (DDD/TID). Results: Cardiovascular drugs are the most commonly prescribed and utilized drugs in R. Macedonia. The HIF cost for cardiovascular disease (CVD) increased to €2,243,777.00 in the period from 2013 to 2016. Since 2012, the reimbursement shows that atorvastatin accounts for the highest expenditure reaching €2,162,958.00 while rosuvastatin reached €1,645,860.00 in 2016. The increased consumption of statins is confirmed from the records obtained from IMS Health databases in the evaluated period in R. Macedonia suggesting increased expenditures with total growth of 35.65% reaching €4,421,280.24 in 2016. Evident growth of statin consumption is confirmed from the data obtained from the pharmaceutical industry and MAH. The statin use increased from 42.347 DDD/TID in 2013 to 71.697 DDD/TID in 2016, although it is lower in comparison to other European Union (EU) countries (1.1–2.5-fold). Conclusion: The rapid increase in the consumption of statins can be attributed mostly to an increase in the consumption volume. It is inevitable to widen the price reduction concept with initiatives that may control statin consumption amounts with measures such as educational programs for rational drug utilization and targeting eligible population. Keywords: statins, cardiovascular prevention, expenditures for statin utilization prescription drug expenditur

The association of C3435T single-nucleotide polymorphism, Pgp-glycoprotein gene expression levels and carbamazepine maintenance dose in patients with epilepsy

Zoran Sterjev1, Gordana Kiteva Trencevska2, Emilija Cvetkovska2, Igor Petrov2, Igor Kuzmanovski2, Jasmina T Ribarska3, Aleksandra K Nestorovska1, Nadica Matevska1, Zorica Naumovska1, Suzana Jolevska-Trajkovic3, Aleksandar Dimovski1, Ljubica Suturkova11Institute of Pharmaceutical Chemistry, Faculty of Pharmacy Skopje, Republic of Macedonia; 2Clinic of Neurology, Faculty of Medicine, Skopje, Republic of Macedonia; 3Institute of Pharmaceutical Analysis, Faculty of Pharmacy Skopje, Republic of MacedoniaAbstract: The ABCB1 gene encodes the P-glycoprotein (Pgp) protein, which is thought to transport various antiepileptic drugs. The single nucleotide polymorphism (SNP) (C3435T) in exon 26 of this gene correlates with the altered expression levels of P-glycoprotein, range of drug response and clinical conditions. In order to investigate the influence of this polymorphism on the susceptibility to and efficacy of carbamazepine therapy, we evaluated the allelic frequency and genotype distribution of this variant in 162 epilepsy patients from the Republic of Macedonia. Statistically significant differences were detected neither in the allelic frequency and genotype distribution between carbamazepine-resistant and carbamazepine-responsive epilepsy patients nor between the subgroups of carbamazepine (CBZ)-responsive patients treated with different CBZ doses. However, the T-allele was enriched in CBZ-responsive patients who required higher maintenance CBZ doses, This observation was substantiated by the findings that the median total plasma levels were the lowest in patients with CC (20 µmol/L) followed by CT (23 µmol/L) and TT (29 µmol/L) genotypes. Patients with a CC genotype also had a higher likelihood of response compared to patients with CT or TT genotypes over a wide range (400–1000 mg/day) of initial doses of CBZ. The T allele showed a reduced expression of ~5% compared to the C allele in peripheral blood mononuclear cells in heterozygotes for the variant. This difference might be translated into ~10% difference in homozygotes for the variant, which would explain the trend towards a dose-dependent efficacy of the CBZ treatment in patients with different genotypes. A larger prospective study is warranted to clarify the clinical utility of a genotype-specific individualized CBZ therapy.Keywords: multidrug resistance protein 1 (MDR1), ABCB1 C3435T polymorphism, epilepsy treatment, carbamazepin