RESEARCH LETTER Year : 2021  |  Volume : 12  |  Issue : 4  |  Page : 172-174  

Monitoring adverse drug reactions and incidence of potential statin-drug interactions

Kleva Shpati1, Gentian Stroni2, Erina Hilaj3, Aurora Napuçe3, Genta Rexha4
1 Department of Pharmacy, Faculty of Medical Science, Albanian University, Tirana, Albania
2 Department of Preclinical Courses, University of Medicine of Tirana, Tirana, Albania
3 Department of Pharmacy, Albanian University, Tirana, Albania
4 Department of Engineering, Albanian University, Tirana, Albania

Date of Submission28-Jun-2021Date of Decision06-Oct-2021Date of Acceptance20-Nov-2021Date of Web Publication09-Feb-2022

Correspondence Address:
Kleva Shpati
Department of Pharmacy, Faculty of Medical Science, Albanian University, Tirana
Albania

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/jpp.jpp_79_21

  How to cite this article:
Shpati K, Stroni G, Hilaj E, Napuçe A, Rexha G. Monitoring adverse drug reactions and incidence of potential statin-drug interactions. J Pharmacol Pharmacother 2021;12:172-4
How to cite this URL:
Shpati K, Stroni G, Hilaj E, Napuçe A, Rexha G. Monitoring adverse drug reactions and incidence of potential statin-drug interactions. J Pharmacol Pharmacother [serial online] 2021 [cited 2022 Feb 9];12:172-4. Available from: http://www.jpharmacol.com/text.asp?2021/12/4/172/337457

Cardiovascular diseases are the first disease in Albania that caused mortality and morbidity according to the Public Health Institute the Statistical Institute of Albania.[1],[2] Hydroxymethylglutaryl-CoA reductase inhibitors (known as statins) are widely used as lipid-lowering drugs. They caused adverse events such as myotoxicity, renal, and hepatic problems which are considerably elevated in combination with other drugs. Drug–drug interactions (DDIs) can result in a change in either drug efficacy or toxicity. The value of therapy is defined by ineffectiveness or increased toxicity. Statins are the therapeutic class of medicines that reduce morbidity and mortality in patients with atherosclerotic cardiovascular disease.[3],[4] Adverse events caused by DDI with clinical significance are preventable. DDIs involving statins include individual pharmacokinetics characteristics (e.g., binding affinity, half-life, dose of medications, and timing and sequence of administration duration of therapy) patients' factors (e.g., age, sex, lifestyle, disease implicating metabolism hepatic, renal impairments and cardiac failure), genetic polymorphism, hypersensitivity, etc. Physicians choose a noninteracting alternative, but if none is available, they prescribe in combination by evaluating the benefits and risks of the co-commitment of medications.[5],[6]

This is a retrospective study. We enrolled 780 hospitalized patients' files in random ways. We included patients/adults who met the following criteria: statins prescribed and other prescriptions for cardiovascular disease, diabetes mellitus, renal and hepatic disease, etc., Statistical analyses were performed with the SPSS version 22. We have received data from the Biochemistry Laboratory for the value of creatine kinase (CK), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), and international normal ratio where a value upper the limit of normal range was identified after the clinical symptoms that patients have had. Interactions were identified also using free platforms such as Drugs.com and Medscape.[7],[8]

Seven hundred and eighty hospitalized patients' files were observed their statins prescription and other drugs. There were five types of statins used: atorvastatin (10 mg, 20 mg, and 80 mg), simvastatin (10 mg, 20 mg, 40 mg, and 80 mg), rosuvastatin (10 mg and 20 mg), fluvastatin (20 mg and 40 mg), and lovastatin (10 mg and 20 mg). The most used statins remain atorvastatin, rosuvastatin followed by simvastatin, lovastatin, and fluvastatin. Treatment with statins was “more aggressive” statins such as atorvastatin and rosuvastatin. Being in the conditions of polymedications, the number of drugs used during the treatment has been high 6 (2-7). We have had in consideration, other risks factors that predispose clinically possible adverse drug events such as gender, age, and hospital duration.[7] The most affected were men in relation to women with a distribution of 77.69% (men) and 22.31% (women). Demographic characteristics of the patients receiving statins are presented below [Table 1].

The total potentially statin-drug interactions were 42, when atorvastatin was the statin most affected for DDI in values 42.8% [Table 2].

There are few studies reporting the incidence of pSDIs.[3],[4],[8],[9],[10] In our study, the statin most prescribed was atorvastatin with dosage of 20 mg [Table 2]. The second one was simvastatin considered the statin most sensitive to pharmacokinetic drug interactions due to its low bioavailability. There is no difference through young and older patients in dosage. As the possibility of interactions increases in older patients,' dosage of statins is lower than normal. Possibility of Statin-Drug Interactions (pSDIs) is increased significantly with other cardiovascular drugs used concurrently with statins which affect the cardiovascular system. The toxicity of statins during concomitant administration with other drugs is modified by different pharmacokinetic or pharmacodynamic mechanisms for example, calcium channels blockers and statins.[3],[4],[8] The most used calcium channel blockers in our clinic were amlodipine 10 mg. The pair amlodipine/simvastatin increases the plasma concentrations of simvastatin. These combinations increase the possibility of the occurrence of myopathy and rhabdomyolysis.[3],[7] By increasing the level of CK, which was identified in biochemistry results. The clinicians have modified the dosage but not interrupt the treatment. Simvastatin 20 mg and atorvastatin 10 mg were used. The combinations atorvastatin/diltiazem have followed the same clinical incidence. The antiarrhythmic (amiodarone)/simvastatin is the most prescribed. Side effects reports show increased level of ALAT and ASAT and myopathy. The patients developed muscle pain and weakness.[3],[8],[9],[10] Our clinicians do not recommend stopping taking statins. Concomitant use of atorvastatin with digoxin has shown an increase in plasma digoxin concentration to 15%–20% accompanied with arrhythmia, and the statin treatment has stopped.

In conclusion, potential statin-drug interactions in cardiovascular patients are unavoidable and should be clinically managed. Dose limits, adverse events, and biochemical data should be monitored closely and identified early to a safer statins' dosage or another statin.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 

   References 
1.Institute of Public Health. Tirana- Albania. Available from: https://www.ishp.gov.al. [Last updated on 2021 Mar 31].  
    2.INSTAT–Institute of Statistics. Tirana-Albania. Available from: https://www.instat.gov.al. [Last updated on 2021 Apr 30].  
    3.Wiggins BS, Saseen JJ, Page RL 2nd, Reed BN, Sneed K, Kostis JB, et al. Recommendations for management of clinically significant drug-drug interactions with statins and select agents used in patients with cardiovascular disease: A scientific statement from the American Heart Association. Circulation 2016;134:e468-95.  
    4.Stockley's drug interactions edition, in English - 9th ed., edited by B.K Pharmaceutical Press; 2010. Available from: https://openlibrary.org/books/OL27089479M/Stockley's_drug_interactions. [Last accessed on 2020 May 26].  
    5.Newman CB, Preiss D, Tobert JA, Jacobson TA, Page RL 2nd, Goldstein LB, et al. Statin safety and associated adverse events: A scientific statement from the American Heart Association. Arterioscler Thromb Vasc Biol 2019;39:e38-81.  
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    7.Drug Interaction Checker-Medicine.com https://www.medicine.com/interaction-checker. [Last accessed on 2021 April 30].  
    8.Drug Interactions Checker-Medscape Drug Reference Database. https://reference.medscape.com/drug-interactionchecker [Last accessed on 2021 April 30].  
    9.Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients: A meta-analysis of prospective studies. JAMA 1998;279:1200-5.  
    10.Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table; 2007. Available from: http://medicine.iupui.edu/clinpharm/ddis/. [Last accessed on 2014 Jan 23].  
    

 
 

  [Table 1], [Table 2]