Abstract
Objetivo
Determinar en el ámbito de atención primaria la frecuencia de potenciales interacciones farmacológicas de las estatinas.
Diseño
Estudio observacional transversal.
Emplazamiento
Centro de salud de características urbanas.
Participantes
Se seleccionó a 384 pacientes consumidores de estatinas mediante muestreo sistemático a partir de las cartillas de largo tratamiento (nivel de confianza del 95%, precisión del ± 5% y proporción esperada de posibles interacciones desconocida).
Mediciones principales
Consumo de estatinas, medicación concomitante, presencia de interacciones según las fichas técnicas de las estatinas (Agencia Española del Medicamento. Ministerio de Sanidad y Consumo) y variables sociodemográficas. Resultados. En 55 pacientes (14,3%; IC del 95%, 10,8–17,8%) se comprobó alguna de las interacciones de las estatinas con el resto de los fármacos, sobre todo con acenocumarol, digoxina y antiácidos. Entre los pacientes con alguna interacción, el número medio de otros medicamentos fue significativamente superior (DE, 4,5 ± 1,5 frente a 3,3 ± 1,9; p < 0,001). Presentaron interacciones el 19,1% de los varones y el 10,8% de las mujeres, resultando la diferencia estadísticamente significativa (p = 0,02). Mediante regresión logística, tanto el sexo masculino (OR= 1,8) como el consumo de otros medicamentos en número de 5 o más (OR = 2,7) aparecieron como variables asociadas a la presencia de interacciones. Conclusiones. Las potenciales interacciones farmacológicas de las estatinas alcanzan al 14,3% de los pacientes con hipercolesterolemia que consumen medicación de forma crónica. La posibilidad de alcanzar concentraciones plasmáticas elevadas de estatinas o de modificar el efecto terapéutico de diversos fármacos permite aconsejar un uso más apropiado de aquéllas, prescribiendo las que utilizan en menor medida el citocromo P-450 para su metabolismo.
Palabras clave: Estatinas, Interacciones farmacológicas, Hipercolesterolemia, Polimedicación
Abstract
Objective
To determine in primary care the frequency of pharmacological interactions of statins.
Design
Transversal observational study.
Setting
Urban health centre.
Participants
384 patients taking statins who were chosen by systematic sampling based on long-treatment cards (95% CI, accuracy ±5% and expected proportion of possible interactions unknown).
Main measurements
Consumption of statins, the accompanying medication taken, presence of interactions according to the technical details of statins (Spanish Medication Agency, Ministry of Health and Consumption) and social and demographic variables.
Results
In 55 patients (14.3%) (95% CI, 10.8%-17.8%) one of the statin interactions with the other drugs was checked, especially with acenocoumarol, digoxin and anti-acid drugs. In patients with some interaction, the mean number of other drugs was significantly higher (4.5±1.5 vs 3.3±1.9 SD; P<.001). 19.1% of men and 10.8% of women showed interactions, the difference being statistically significant (P=.02). By means of logistic regression, both masculine gender (OR=1.8) and taking of other medication in quantities of 5 or more (OR=2.7) appeared as variables associated with the presence of interactions. Conclusions. The potential pharmacological interactions of statins reach 14.3% of patients with hypercholesterolaemia who take medication long-term. The possibility of reaching high plasma concentrations of statins and/or of modifying the therapeutic effect of various drugs enables a more appropriate use of statins to be recommended, with prescription of those statins that metabolise less through the P450 cytochrome.
Key words: Statins, Pharmacological interactions, Hypercholesterolaemia, Multi-medication
Footnotes
De este estudio ha sido presentada una comunicación oral en el III Congreso de Atención Primaria de Castilla-La Mancha, celebrado en Albacete durante los días 9, 10 y 11 de mayo de 2002.
Bibliografía
- 1.Lazarou J., Pomeranz B.H., Corey P.N. Incidence of adverse drug reactions en hospitalized patiens: a metha-anaysis of prospective studies. JAMA. 1998;279:1200–1205. doi: 10.1001/jama.279.15.1200. [DOI] [PubMed] [Google Scholar]
- 2.Abajo F.J., Frías J., Lopo C.R., Garijo B., Castro M.A.S., Carcas A. Las reacciones adversas a medicamentos como motivo de consulta al servicio de urgencias de un hospital general. Med Clin (Barc) 1989;92:530–535. [PubMed] [Google Scholar]
- 3.Sica D.A., Gehr T.W. Rhabdomyolysis and statins therapy: relevance to the elderly. Am J Geriatr Cardiol. 2002;11:48–55. doi: 10.1111/j.1076-7460.2002.01422.x. [DOI] [PubMed] [Google Scholar]
- 4.Janne T.B., Kyrklund C., Kari T.K., Jun-sheng W., Pertti J.N. Plasma concentrations of active simvastatin acid are increased by gemfibrozilo. Clin Pharmacol Ther. 2000;68:122–129. doi: 10.1067/mcp.2000.108507. [DOI] [PubMed] [Google Scholar]
- 5.Shek A., Ferrill M.J. Statin-fibrate combination therapy. Ann Pharmacother. 2001;35:908–917. doi: 10.1345/aph.10315. [DOI] [PubMed] [Google Scholar]
- 6.Robertson J., Fryser J.L., O’Connell D.L., Sprogis A., Henry D.A. The impact of specialist on prescribing by general practitioners. Med J Aust. 2001;175:407–411. doi: 10.5694/j.1326-5377.2001.tb143645.x. [DOI] [PubMed] [Google Scholar]
- 7.Jan W., Smith A., Jansen G., Tjer W., De Bruin A., Erkelens W. Treatment of combined hyperlipidemia with fluvastatin and gemfibrozilo, alone or in combination, does not induce muscle damage. Am J Cardiol. 1995;76:126–128. doi: 10.1016/s0002-9149(05)80034-7. [DOI] [PubMed] [Google Scholar]
- 8.John W., Kenneth A.F. Lovastatin-induced rhabdomyolysis possibly associated with clarithromycin and azythromycin. Ann Pharmacother. 1997;31:859–863. doi: 10.1177/106002809703100710. [DOI] [PubMed] [Google Scholar]
- 9.Chong P.H., Seeger J.D., Franklin C. Clinically relevant differences between the statins: implications for therapeutic selection. Am J Med. 2001;111:390–400. doi: 10.1016/s0002-9343(01)00870-1. [DOI] [PubMed] [Google Scholar]
- 10.Chirstians U., Jacobsen W., Floren L.C. Metabolism and drug interactions of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors in transplant patients: are the statins mechanistically similar? Pharmacol Ther. 1998;80:1–34. doi: 10.1016/s0163-7258(98)00016-3. [DOI] [PubMed] [Google Scholar]
- 11.Schwartz G.G., Olsson A.G., Ezekowitz M.D., Ganz P., Oliver M.F., Waters D. Efectos de atorvastatina sobre los eventos isquémicos recurrentes precoces en los síndromes coronarios agudos. JAMA (ed. esp.) 2001;285:1711–1718. doi: 10.1001/jama.285.13.1711. [DOI] [PubMed] [Google Scholar]
- 12.Mousa O., Brater D.C., Kimberly J., Stephen D.H. The interaction of diltiazem with simvastatin. Clin Pharmacol Ther. 2000;67:267–274. doi: 10.1067/mcp.2000.104609. [DOI] [PubMed] [Google Scholar]
- 13.Licar M., Mjörndal T., Dahlquist R. HMG-CoA reductase inhibitors and myotoxicity. Drug Saf. 2000;22:441–457. doi: 10.2165/00002018-200022060-00003. [DOI] [PubMed] [Google Scholar]
- 14.Chazerain P., Hayem G., Hamza S., Best C., Ziza J.M. Four cases of tendinopathy in patients on statin therapy. Joint bone spine. 2001;68:430–433. doi: 10.1016/s1297-319x(01)00300-1. [DOI] [PubMed] [Google Scholar]
- 15.Corsini A., Bellosta S., Baetta R., Fumagalli R., Paoletti R., Bernini F. New insights into the pharmacodynamic and pharmacokinetic properties of statins. Pharmacol Ther. 1999;84:413–428. doi: 10.1016/s0163-7258(99)00045-5. [DOI] [PubMed] [Google Scholar]
- 16.Heerey A., Barry M., Kelly A. The potencial for drug interactions with statins therapy in Ireland. Irish J Med Science. 2001;169:176–179. doi: 10.1007/BF03167690. [DOI] [PubMed] [Google Scholar]
- 17.Farnier M., Dejager S., the French Fluvastatin Study Group Effect of combined fluvastatin-fenofibrate monotherapy in severe primary hypercholesterolemia. Am J Cardiol. 2000;85:53–57. doi: 10.1016/s0002-9149(99)00606-2. [DOI] [PubMed] [Google Scholar]
- 18.Spence J.D., Claudio E., Hendricks L., Latchian L., Khouri H.E. Pharmacokinetics of the combination of fluvastatin and gemfibrozilo. Am J Cardiol. 1995;76:13–16. doi: 10.1016/s0002-9149(05)80024-4. [DOI] [PubMed] [Google Scholar]
- 19.Omar M.A., Wilson J.P., Cox T.S. Rhabdomyolysis and HMGCoA reductasa inhibitors. Ann Pharmacther. 2001;35:1096–1107. doi: 10.1345/aph.10228. [DOI] [PubMed] [Google Scholar]
- 20.Boger R.H. Drug interactions of the statins and consequences for drug selection. Int J Clin Pharmacol Ther. 2001;39:369–382. doi: 10.5414/cpp39369. [DOI] [PubMed] [Google Scholar]
- 21.Davidson M.H. Does differing metabolism by cytochrome p450 have clinical importance? Curr Atheroscler Rep. 2000;2:14–19. doi: 10.1007/s11883-000-0090-4. [DOI] [PubMed] [Google Scholar]
- 22.Eliav O., Schurr D., Pfister P., Friedlander Y., Leitersdorf E. High-dose fluvastatin and bezafibrate combination treament for heterozygous familial hypercholesterolemia. Am J Cardiol. 1995;76:76–79. doi: 10.1016/s0002-9149(05)80023-2. [DOI] [PubMed] [Google Scholar]
- 23.Ballantyne C.M., Pazzuconi F., Pintó X., Reckeless J.P., Stein E., McKenney J. Efficacy and tolerability of fluvastatin extended-release delivery system: a pooled analysis. Clin Therapeutics. 2001;23:177–192. doi: 10.1016/s0149-2918(01)80001-1. [DOI] [PubMed] [Google Scholar]
- 24.Marais A.D., Blom D.J., Firth J.C. Statins in homozygous familial by hypercholesterolemia. Curr Atheroscler Rep. 2002;4:19–25. doi: 10.1007/s11883-002-0058-7. [DOI] [PubMed] [Google Scholar]
- 25.Kandus A., Kovac D., Cerne D., Koselj M., Kaplan-Pppavlovcic S., Buturovic J. Therapy of hyperlipidemia with lovastatin in kidney transplant patients on cyclosporine A immunosuppression: three-year experience. Transplant Proc. 1998;30:1307–1309. doi: 10.1016/s0041-1345(98)00253-x. [DOI] [PubMed] [Google Scholar]
- 26.Ahsan C.H., Shah A., Ezekowitz M. Acute statin treatment in reducing risk after acute coronary syndrome: the MIRACL trial. Curr Opin Cardiology. 2001;16:390–393. doi: 10.1097/00001573-200111000-00013. [DOI] [PubMed] [Google Scholar]
- 27.Takemoto M., Liao J.K. Pleiotropic effects of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors. Arterioscler Thromb Vasec Biol. 2001;21:1712–1719. doi: 10.1161/hq1101.098486. [DOI] [PubMed] [Google Scholar]
- 28.Freeman D.J., Norrie J., Sattar N., Dermot G.N., Stuart M.C., Ford I. Pravastatin and the development of diabetes mellitus. Evidence for a protective treatment effect in the west of Scotland. Coronary Prevention Study. Circulation. 2001;103:357–362. doi: 10.1161/01.cir.103.3.357. [DOI] [PubMed] [Google Scholar]