JonnyMie
New member
I'm considering the use of trimetazidine. I believe in being as proactive as I can in regards to any side effects of using exongenous hormones. What's everyone's opinions on this study and related info? Heart health and AAS is nothing new, but this is some scary stuff, and points to some proactive solutions to it. Hopefully at the least this is a helpful post. Credit to DatBTrue's board for finding this.
Here are the major parts of the full study:
Cardiac Lesions Induced by Testosterone: Protective Effects of Dexrazoxane and Trimetazidine
Dalila Dalila Belhani, Cardiovascular Toxicology Published online: 12 May 2009
Abstract
Further to our previous observation of post-mortem cardiac lesions after sudden death in several athletes with a history of anabolic steroid abuse, this study was intended to reproduce these lesions in rabbits administered testosterone oenanthate, a prototypic anabolic steroid abused by athletes, and to provide evidence for the protective effects of trimetazidine and dexrazoxane that are used as antianginal and cardioprotective drugs, respectively. Groups of six rabbits each were administered saline, testosterone, or a combination of testosterone and either trimetazidine or dexrazoxane for 3 months. Histologic cardiac lesions including necrosis, misshapen cell nuclei, interstitial and endocardial fibrosis, lymphocytic infiltrates, and vascular dystrophies were observed in testosterone-treated rabbits. In contrast, no significant lesions were observed in the animals treated with testosterone combined with either trimetazidine or dexrazoxane. This is the first study providing evidence for testosterone cardiotoxicity following sub-chronic exposure in laboratory animals. In addition, these results suggest the protective role of trimetazidine and dexrazoxane.
Introduction
Not infrequently athletes tend to abuse anabolic steroids derived from testosterone, and a number of sudden cardiac deaths have been reported in relation to this abuse [1–4]. Indeed, sudden deaths may be 4–6 fold more frequent in athletes with a history of anabolic steroid abuse [5, 6]. Overall, the incidence of sudden deaths has been estimated to be 2–3/100,000/year in athletes versus 0.08/100,000/year in the general population [7, 8].
In a recent study conducted with Lyon Institute of Forensic Medicine, we observed various cardiac lesions during the post-mortem examination of several athletes with a history of anabolic steroid abuse [9]. Concomitantly, we evidenced focalized as well as disseminated cardiac lesions in rabbits treated with norethandrolone, a potent anabolic steroid. These lesions were reminiscent of those observed in toxic myocarditis, e.g., myocarditis due to anthracyclines. They mostly consisted of myolysis, fibrosis, disorganized myocardial fibers, and misshapen cell nuclei, and were characterized by the presence of lymphocytic infiltrates. Moreover, arteriolar lesions suggested the possible involvement of myocardial ischemia.
The present study was undertaken to demonstrate whether the sub-chronic administration of testosterone to rabbits could induce similar cardiac lesions as testosterone cardiotoxicity has seldom been investigated in laboratory animals. In addition, the possible protective effects of trimetazidine, which exerts anti-ischemic and anti-anginal effects [10], and of dexrazoxane, which is used to prevent the cardiotoxicity of anthracycline derivatives in human cancer patients [11], were investigated in rabbits concomitantly treated with testosterone.
Treatment
The rabbits were randomly assigned to four groups of six animals each. All subsequent treatments were administered by the intraperitoneal route. Group I (control) animals were given saline once a day using the same volume as in treated animals. Group II animals were given 8 mg/kg of testosterone (Bayer Santé, Puteaux, France) once a month for 3 months and saline daily on the other days. Group III animals were given 8 mg/kg of testosterone once a month plus 5 mg/kg of trimetazidine (Servier laboratories, Courbevoie, France) daily for 3 months. Group IV animals were given 8 mg/kg of testosterone once a month plus 60 mg/kg of dexrazoxane (Novartis Pharma, Rueil-Malmaison, France) once a week, and saline daily on the other days for 3 months.
Discussion
In this study, the administration of testosterone was found to induce various histologic cardiac lesions in rabbits including misshapen cell nuclei, necrosis, interstitial, and endocardial fibrosis. Similar lesions of the myocardium have been previously reported in athletes with a history of anabolic steroid abuse [3, 6, 12]. We also observed dysplasia of the precapillary arterioles, which can cause ischemia leading to morphologic changes including contraction bands, acidophilia, and undulation of myocardial fibers. At a later stage, liquefaction necrosis is a common finding. Finally, we found that testosterone can induce acute inflammatory lesions of cardiomyocytes as previously reported [13–15]. Testosterone has been reported to exert pro-inflammatory effects with the release of TNF-a and IL-1ß, and this in turn resulted in apoptosis of cardiac cells [16]. Interestingly, as compared to non-castrated males, castrated rats had lesser cytokine release and reduced apoptotic response measured from caspase-1, caspase-3, and caspase-11 activation, and Bcl-2 expression. That no evidence of apoptosis was found in the present study may be explained by the sensitivity of the method used, or more probably by the conditions of exposure, i.e., sub-chronic versus acute.
No cardiac hypertrophy was observed in animals treated with testosterone alone in this study. This may be due to the rather short duration of treatment (3 months) as the development of cardiac hypertrophy in athletes has been suggested to require chronic testosterone exposure [17]. Following prolonged exposure, testosterone can induce hypertrophic cardiac lesions [2, 6] leading to sudden death via a reduction of ventricular compliance [2] and/or the induction of disorders of diastolic relaxation [18]. The sudden death of a 32-year-old transsexual woman treated with intramuscular testosterone 125 mg/kg once or twice monthly for 2 years has been reported [19]. Her post-mortem examination revealed hypertrophic cardiopathy and atheromatous plaques on the left and right coronary arteries that resulted in over 90% coronary stenosis in the proximal end of the anterior interventricular artery.
In contrast to testosterone alone, the combination of testosterone with trimetazidine was not associated with the development of any consistent cardiac lesions in rabbits after 3 months of treatment. Although the mechanism of the cardioprotection achieved by trimetazidine in this study is not clearly elucidated, several mechanisms can be proposed. Trimetazidine can decrease intracellular acidosis and alterations in transmembrane ion movements caused by ischemia, and thus reduce the migration and infiltration of neutrophils and lymphocytes to the cardiac tissue during ischemia/reperfusion [20]. Thus, trimetazidine could reduce the release of pro-inflammatory cytokines induced by testosterone. Second, trimetazidine exerts protective effects during ischemia in inhibiting the opening of mitochondrial permeability transition pores during ischemia/reperfusion [21]. Kajstura et al. [22] showed that the extent of cardiac lesions, such as myocardial necrosis and apoptosis during myocardial ischemia is significantly reduced by trimetazidine. Thirdly, Ruixing et al. [23] found that capase-3 activation and mitochondrial cytochrome C release were decreased in rabbits treated with trimetazidine as compared to untreated animals. In addition, the apoptotic index was negatively correlated to serum superoxide dismutase activity, and positively correlated to malondialdehyde levels, which suggests that trimetazidine could prevent myocardial lesions during ischemia-reperfusion. Based on these data, it is suggested that the anti-apoptotic effects of trimetazidine could inhibit apoptosis induction by testosterone, and thus prevent the development of cardiac lesions in rabbits treated with testosterone alone.
Similarly to rabbits treated with trimetazidine, rabbits treated with dexrazoxane did not develop any consistent cardiac lesions despite concomitant testosterone exposure. Dexrazoxane plays an important role in the cardioprotection of patients treated with anthracycline derivatives [11, 24]. It is indeed well recognized that these derivatives can induce various histological lesions of the heart, such as myocardial necrosis, cellular infiltrates, myofibrillar loss, and cytoplasmic vacuolization. The mechanism of this protective effect of dexrazoxane is not fully understood. It is at least in part related to the prevention of apoptotic and necrotic lesions involving the reduced formation of Fe3+-anthracycline complexes that generate the production of free radicals that induce alterations of mitochondria [25]. Therefore, the cardioprotection evidenced during the present study following treatment with either trimetazidine or dexrazoxane in testosterone-treated rabbits could result from similar mechanisms involving decreased mitochondrial alterations.
In conclusion, this study provides confirmative evidence that anabolic steroids, and in particular testosterone, induce cardiotoxic effects resulting in heart lesions similar to those seen in toxic myocarditis. The lack of cardiac lesions in testosterone-treated rabbits when given trimetazidine or dexrazoxane concomitantly suggests that either drug can have a cardioprotective effect, which warrants further investigation.
References:
NOTES:
Trimetazidine is a drug for angina pectoris, sometimes referred to by the brand name Vastarel MR. Each tablet contains 35 mg of trimetazidine. Trimetazidine is an anti-ischemic (anti-anginal) metabolic agent, which improves myocardial glucose utilization through stopping of fatty acid metabolism. Trimetazidine is usually prescribed as a long-term treatment of angina pectoris, and in some countries (including France) for tinnitus and dizziness. It is taken twice a day.
Trimetazidine has high safety and tolerability profile. It has no known drug interactions
Dexrazoxane hydrochloride (Zinecard [Pfizer for USA & Canada]; Cardioxane [Novartis for EU & ROW]) is a cardioprotective agent.
It is used to protect the heart against the cardiotoxic side effects of anthracyclines, such as doxorubicin.
FDA has also approved a dexrazoxane hydrochloride drug, brand name Totect or Savene (developed by TopoTarget), for use as a treatment of extravasation resulting from IV anthracycline chemotherapy. Extravasation is an adverse event in which chemotherapies containing anthracylines leak out of the blood vessel and necrotize the surrounding tissue.
As a derivative of EDTA, dexrazoxane chelates iron, but the precise mechanism by which it protects the heart is not known.
Here are the major parts of the full study:
Cardiac Lesions Induced by Testosterone: Protective Effects of Dexrazoxane and Trimetazidine
Dalila Dalila Belhani, Cardiovascular Toxicology Published online: 12 May 2009
Abstract
Further to our previous observation of post-mortem cardiac lesions after sudden death in several athletes with a history of anabolic steroid abuse, this study was intended to reproduce these lesions in rabbits administered testosterone oenanthate, a prototypic anabolic steroid abused by athletes, and to provide evidence for the protective effects of trimetazidine and dexrazoxane that are used as antianginal and cardioprotective drugs, respectively. Groups of six rabbits each were administered saline, testosterone, or a combination of testosterone and either trimetazidine or dexrazoxane for 3 months. Histologic cardiac lesions including necrosis, misshapen cell nuclei, interstitial and endocardial fibrosis, lymphocytic infiltrates, and vascular dystrophies were observed in testosterone-treated rabbits. In contrast, no significant lesions were observed in the animals treated with testosterone combined with either trimetazidine or dexrazoxane. This is the first study providing evidence for testosterone cardiotoxicity following sub-chronic exposure in laboratory animals. In addition, these results suggest the protective role of trimetazidine and dexrazoxane.
Introduction
Not infrequently athletes tend to abuse anabolic steroids derived from testosterone, and a number of sudden cardiac deaths have been reported in relation to this abuse [1–4]. Indeed, sudden deaths may be 4–6 fold more frequent in athletes with a history of anabolic steroid abuse [5, 6]. Overall, the incidence of sudden deaths has been estimated to be 2–3/100,000/year in athletes versus 0.08/100,000/year in the general population [7, 8].
In a recent study conducted with Lyon Institute of Forensic Medicine, we observed various cardiac lesions during the post-mortem examination of several athletes with a history of anabolic steroid abuse [9]. Concomitantly, we evidenced focalized as well as disseminated cardiac lesions in rabbits treated with norethandrolone, a potent anabolic steroid. These lesions were reminiscent of those observed in toxic myocarditis, e.g., myocarditis due to anthracyclines. They mostly consisted of myolysis, fibrosis, disorganized myocardial fibers, and misshapen cell nuclei, and were characterized by the presence of lymphocytic infiltrates. Moreover, arteriolar lesions suggested the possible involvement of myocardial ischemia.
The present study was undertaken to demonstrate whether the sub-chronic administration of testosterone to rabbits could induce similar cardiac lesions as testosterone cardiotoxicity has seldom been investigated in laboratory animals. In addition, the possible protective effects of trimetazidine, which exerts anti-ischemic and anti-anginal effects [10], and of dexrazoxane, which is used to prevent the cardiotoxicity of anthracycline derivatives in human cancer patients [11], were investigated in rabbits concomitantly treated with testosterone.
Treatment
The rabbits were randomly assigned to four groups of six animals each. All subsequent treatments were administered by the intraperitoneal route. Group I (control) animals were given saline once a day using the same volume as in treated animals. Group II animals were given 8 mg/kg of testosterone (Bayer Santé, Puteaux, France) once a month for 3 months and saline daily on the other days. Group III animals were given 8 mg/kg of testosterone once a month plus 5 mg/kg of trimetazidine (Servier laboratories, Courbevoie, France) daily for 3 months. Group IV animals were given 8 mg/kg of testosterone once a month plus 60 mg/kg of dexrazoxane (Novartis Pharma, Rueil-Malmaison, France) once a week, and saline daily on the other days for 3 months.
Discussion
In this study, the administration of testosterone was found to induce various histologic cardiac lesions in rabbits including misshapen cell nuclei, necrosis, interstitial, and endocardial fibrosis. Similar lesions of the myocardium have been previously reported in athletes with a history of anabolic steroid abuse [3, 6, 12]. We also observed dysplasia of the precapillary arterioles, which can cause ischemia leading to morphologic changes including contraction bands, acidophilia, and undulation of myocardial fibers. At a later stage, liquefaction necrosis is a common finding. Finally, we found that testosterone can induce acute inflammatory lesions of cardiomyocytes as previously reported [13–15]. Testosterone has been reported to exert pro-inflammatory effects with the release of TNF-a and IL-1ß, and this in turn resulted in apoptosis of cardiac cells [16]. Interestingly, as compared to non-castrated males, castrated rats had lesser cytokine release and reduced apoptotic response measured from caspase-1, caspase-3, and caspase-11 activation, and Bcl-2 expression. That no evidence of apoptosis was found in the present study may be explained by the sensitivity of the method used, or more probably by the conditions of exposure, i.e., sub-chronic versus acute.
No cardiac hypertrophy was observed in animals treated with testosterone alone in this study. This may be due to the rather short duration of treatment (3 months) as the development of cardiac hypertrophy in athletes has been suggested to require chronic testosterone exposure [17]. Following prolonged exposure, testosterone can induce hypertrophic cardiac lesions [2, 6] leading to sudden death via a reduction of ventricular compliance [2] and/or the induction of disorders of diastolic relaxation [18]. The sudden death of a 32-year-old transsexual woman treated with intramuscular testosterone 125 mg/kg once or twice monthly for 2 years has been reported [19]. Her post-mortem examination revealed hypertrophic cardiopathy and atheromatous plaques on the left and right coronary arteries that resulted in over 90% coronary stenosis in the proximal end of the anterior interventricular artery.
In contrast to testosterone alone, the combination of testosterone with trimetazidine was not associated with the development of any consistent cardiac lesions in rabbits after 3 months of treatment. Although the mechanism of the cardioprotection achieved by trimetazidine in this study is not clearly elucidated, several mechanisms can be proposed. Trimetazidine can decrease intracellular acidosis and alterations in transmembrane ion movements caused by ischemia, and thus reduce the migration and infiltration of neutrophils and lymphocytes to the cardiac tissue during ischemia/reperfusion [20]. Thus, trimetazidine could reduce the release of pro-inflammatory cytokines induced by testosterone. Second, trimetazidine exerts protective effects during ischemia in inhibiting the opening of mitochondrial permeability transition pores during ischemia/reperfusion [21]. Kajstura et al. [22] showed that the extent of cardiac lesions, such as myocardial necrosis and apoptosis during myocardial ischemia is significantly reduced by trimetazidine. Thirdly, Ruixing et al. [23] found that capase-3 activation and mitochondrial cytochrome C release were decreased in rabbits treated with trimetazidine as compared to untreated animals. In addition, the apoptotic index was negatively correlated to serum superoxide dismutase activity, and positively correlated to malondialdehyde levels, which suggests that trimetazidine could prevent myocardial lesions during ischemia-reperfusion. Based on these data, it is suggested that the anti-apoptotic effects of trimetazidine could inhibit apoptosis induction by testosterone, and thus prevent the development of cardiac lesions in rabbits treated with testosterone alone.
Similarly to rabbits treated with trimetazidine, rabbits treated with dexrazoxane did not develop any consistent cardiac lesions despite concomitant testosterone exposure. Dexrazoxane plays an important role in the cardioprotection of patients treated with anthracycline derivatives [11, 24]. It is indeed well recognized that these derivatives can induce various histological lesions of the heart, such as myocardial necrosis, cellular infiltrates, myofibrillar loss, and cytoplasmic vacuolization. The mechanism of this protective effect of dexrazoxane is not fully understood. It is at least in part related to the prevention of apoptotic and necrotic lesions involving the reduced formation of Fe3+-anthracycline complexes that generate the production of free radicals that induce alterations of mitochondria [25]. Therefore, the cardioprotection evidenced during the present study following treatment with either trimetazidine or dexrazoxane in testosterone-treated rabbits could result from similar mechanisms involving decreased mitochondrial alterations.
In conclusion, this study provides confirmative evidence that anabolic steroids, and in particular testosterone, induce cardiotoxic effects resulting in heart lesions similar to those seen in toxic myocarditis. The lack of cardiac lesions in testosterone-treated rabbits when given trimetazidine or dexrazoxane concomitantly suggests that either drug can have a cardioprotective effect, which warrants further investigation.
References:
- Deligiannis, A., Björnstad, H., Carre, F., Heidbüchel, H., Kouidi, E., Panhuyzen-Goedkoop, N. M., et al. (2006). ESC study group of sports cardiology position paper on adverse cardiovascular effects of doping in athletes. European Journal of Cardiovascular Prevention and Rehabilitation, 13, 687–694. doi:10.1097/01.hjr.0000224482.95597.7a.
- Kindermann, W. (2006). Cardiovascular side effects of anabolic-androgenic steroids. Herz, 31, 566–573. doi:10.1007/s00059-006-2856-0.
- Di Paolo, M., Agozzino, M., Toni, C., Luciani, A. B., Molendini, L., Scaglione, M., et al. (2007). Sudden anabolic steroid abuse-related death in athletes. International Journal of Cardiology, 114, 114–117. doi:10.1016/j.ijcard.2005.11.033.
- Fineschi, V., Riezzo, I., Centini, F., Silingardi, E., Licata, M., Beduschi, G., et al. (2007). Sudden cardiac death during anabolic steroid abuse: Morphologic and toxicologic findings in two fatal cases of bodybuilders. International Journal of Legal Medicine, 121, 48–53. doi:10.1007/s00414-005-0055-9.
- Pärssinen, M., Kujala, U., Vartiainen, E., Sarna, S., & Seppälä, T. (2000). Increased premature mortality of competitive power lifters suspected to have used anabolic agents. International Journal of Sports Medicine, 21, 225–227. doi:10.1055/s-2000-304.
- Luke, J. L., Farb, A., Virmani, R., & Sample, R. H. (1990). Sudden cardiac death during exercise in a weight lifter using anabolic androgenic steroids: Pathological and toxicological findings. Journal of Forensic Sciences, 35, 1441–1447.
- Maron, B. J., Epstein, S. E., & Roberts, W. C. (1986). Causes of sudden death in competitive athletes. Journal of the American College of Cardiology, 1, 204–214.
- Corrado, D., Basso, C., Pavei, A., Michieli, P., Schiavon, M., & Thiene, G. (2006). Trends in sudden cardiovascular death in young competitive athletes after implementation of a preparticipation screening program. Journal of the American Medical Association, 296, 1593–1601. doi:10.1001/jama.296.13.1593.
- Fanton, L., Belhani, D., Vaillant, F., Tabib, A., Gomez, L., Descotes, J., et al. (2008). Heart lesions associated with anabolic steroid abuse: Comparison of post-mortem findings in athletes and norethandrolone-induced lesions in rabbits. Experimental and Toxicologic Pathology, (Nov), 20. Epub ahead of print.
- Bertomeu-Gonzalez, V., Bouzas-Mosquera, A., & Kaski, J. C. (2006). Role of trimetazidine in management of ischemic cardiomyopathy. The American Journal of Cardiology, 98(5A), 19J–24J. doi:10.1016/j.amjcard.2006.07.005.
- Wiseman, L. R., & Spencer, C. M. (1998). Dexrazoxane. A review of its use as a cardioprotective agent in patients receiving anthracycline-based chemotherapy. Drugs, 56, 385–403. doi:10.2165/00003495-199856030-00009.
- Hartgens, F., & Kuipers, H. (2004). Effects of androgenic-anabolic steroids in athletes. Sports Medicine (Auckland, N.Z.), 34, 513–554. doi:10.2165/00007256-200434080-00003.
- Rossi, M. A. (1991). Patterns of myocardial fibrosis in idiopathic cardiomyopathies and chronic Chagasic cardiopathy. The Canadian Journal of Cardiology, 7, 287–294.
- Cavasin, M. A., Tao, Z. Y., Yu, A. L., & Yang, X. P. (2006). Testosterone enhances early cardiac remodeling after myocardial infarction, causing rupture and degrading cardiac function. American Journal of Physiology. Heart and Circulatory Physiology, 290, 2043–2050. doi:10.1152/ajpheart.01121.2005.
- Wang, M., Tsai, B. M., Kher, A., Baker, L. B., Wairiuko, G. M., & Meldrum, D. R. (2005). Role of endogenous testosterone in myocardial proinflammatory and proapoptotic signaling after acute ischemia-reperfusion. American Journal of Physiology. Heart and Circulatory Physiology, 288, H221–H226. doi:10.1152/ajpheart.00784.2004.
- Inoue, H., Nishida, N., Ikeda, N., Tsuji, A., Kudo, K., Hanagama, M., et al. (2007). The sudden and unexpected death of a female-to-male transsexual patient. Journal of Forensic and Legal Medicine, 21, 1–7.
- Hartgens, F., Cheriex, E. C., & Kuipers, H. (2003). Prospective echocardiographic assessment of androgenic-anabolic steroids effects on cardiac structure and function in strength athletes. International Journal of Sports Medicine, 24, 344–351. doi:10.1055/s-2003-40705.
- Gauthier, J. (2001). Cardiovascular effects of doping. Annales de Cardiologie et d’Angeiologie, 50, 293–298. doi:10.1016/S0003-3928(01)00032-4.
- Ren, G., Dewald, O., & Frangogiannis, N. G. (2003). Inflammatory mechanisms in myocardial infarction. Current Drug Targets. Inflammation and Allergy, 2, 242–256. doi:10.2174/1568010033484098.
- Meldrum, D. R., Wang, M., Tsai, B. M., Kher, A., Pitcher, J. M., Brown, J. W., et al. (2005). Intracellular signaling mechanisms of sex hormones in acute myocardial inflammation and injury. Frontiers in Bioscience, 10, 1835–1867. doi:10.2741/1665.
- Argaud, L., Gomez, L., Gateau-Roesch, O., Couture-Lepetit, E., Loufouat, J., Robert, D., et al. (2005). Trimetazidine inhibits mitochondrial permeability transition pore opening and prevents lethal ischemia-reperfusion injury. Journal of Molecular and Cellular Cardiology, 39, 893–899. doi:10.1016/j.yjmcc.2005.09.012.
- Kajstura, J., Liu, Y., Baldini, A., Li, B., Olivetti, G., Leri, A., et al. (1998). Coronary artery constriction in rats: necrotic and apoptotic myocyte death. The American Journal of Cardiology, 82, 30K–41K. doi:10.1016/S0002-9149(98)00535-9.
- Ruixing, Y., Wenwu, L., & Al-Ghazali, R. (2007). Trimetazidine inhibits cardiomyocyte apoptosis in a rabbit model of ischemia-reperfusion. Translational Research; the Journal of Laboratory and Clinical Medicine, 149, 152–160. doi:10.1016/j.trsl.2006.11.004.
- Paiva, M. G., Petrilli, A. S., Moises, V. A., Macedo, C. R., Tanaka, C., & Campos, O. (2005). Cardioprotective effect of dexrazoxane during treatment with doxorubicin: A study using low-dose dobutamine stress echocardiography. Pediatric Blood & Cancer, 45, 902–908. doi:10.1002/pbc.20488.
- Chen, B., Peng, X., Pentassuglia, L., Lim, C. C., & Sawyer, D. B. (2007). Molecular and cellular mechanisms of anthracycline cardiotoxicity. Cardiovascular Toxicology, 7, 114–121. doi:10.1007/s12012-007-0005-5.
NOTES:
Trimetazidine is a drug for angina pectoris, sometimes referred to by the brand name Vastarel MR. Each tablet contains 35 mg of trimetazidine. Trimetazidine is an anti-ischemic (anti-anginal) metabolic agent, which improves myocardial glucose utilization through stopping of fatty acid metabolism. Trimetazidine is usually prescribed as a long-term treatment of angina pectoris, and in some countries (including France) for tinnitus and dizziness. It is taken twice a day.
Trimetazidine has high safety and tolerability profile. It has no known drug interactions
Dexrazoxane hydrochloride (Zinecard [Pfizer for USA & Canada]; Cardioxane [Novartis for EU & ROW]) is a cardioprotective agent.
It is used to protect the heart against the cardiotoxic side effects of anthracyclines, such as doxorubicin.
FDA has also approved a dexrazoxane hydrochloride drug, brand name Totect or Savene (developed by TopoTarget), for use as a treatment of extravasation resulting from IV anthracycline chemotherapy. Extravasation is an adverse event in which chemotherapies containing anthracylines leak out of the blood vessel and necrotize the surrounding tissue.
As a derivative of EDTA, dexrazoxane chelates iron, but the precise mechanism by which it protects the heart is not known.
