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The document describes several drug-drug interactions involving statins, fibrates, ezetimibe, and other drugs. It notes that rifampin decreases ezetimibe levels, while fibrates and colchicine can cause rhabdomyolysis. Statins interact with various drugs like macrolides, protease inhibitors, and grapefruit juice in ways that increase statin levels and risk of rhabdomyolysis. Fibrates also interact with other drugs like diuretics and increase the risk of rhabdomyolysis when combined with statins.
The document describes several drug-drug interactions involving statins, fibrates, ezetimibe, and other drugs. It notes that rifampin decreases ezetimibe levels, while fibrates and colchicine can cause rhabdomyolysis. Statins interact with various drugs like macrolides, protease inhibitors, and grapefruit juice in ways that increase statin levels and risk of rhabdomyolysis. Fibrates also interact with other drugs like diuretics and increase the risk of rhabdomyolysis when combined with statins.
The document describes several drug-drug interactions involving statins, fibrates, ezetimibe, and other drugs. It notes that rifampin decreases ezetimibe levels, while fibrates and colchicine can cause rhabdomyolysis. Statins interact with various drugs like macrolides, protease inhibitors, and grapefruit juice in ways that increase statin levels and risk of rhabdomyolysis. Fibrates also interact with other drugs like diuretics and increase the risk of rhabdomyolysis when combined with statins.
Single-dose rifampicin increases ezetimibe levels without altering its effects on
sterols, whereas multiple doses of rifampicin decrease ezetimibe levels and almost totally abolish its effects. 2. Fibrates + Colchicine Case reports suggest that the current use of fibrates and colchicines can result in rhabdomyolysis or neuromyopathy 3. Fibrates + Diuretics Treatment with clofibrate in patients with nephrotic syndrome receiving furosemide has sometimes led to marked diuresis and severe and disabling adverse muscular effects. An isolated report describes rhabdomyolysis in a patient taking bezafibrate and furosemide. 4. Fibrates; Gemfibrozil + Antacids Antacids can reduce the absorption of gemfibrozil. 5. Statins + ACE inhibitors In general the statins do not appear to interact with the ACE inhibitors. An isolated report describes severe hyperkalaemia in a diabetic given lisinopril with lovastatin, and acute pancreatitis has been attributed to the use of lisinopril with atorvastatin. 6. Statins + Amiodarone There is some evidence of a high incidence of myopathy when amiodarone is given with high doses of simvastatin. Cases of myopathy and rhabdomyolysis have been reported in patients taking the combination. 7. Statins + Antacids An aluminium/magnesium hydroxide antacid (Maalox) causes a moderate reduction in the bioavailability of atorvastatin, pravastatin, and rosuvastatin, but the lipid- lowering efficacy of atorvastatin and pravastatin is not affected. 8. Statins + Azoles Fluconazole modestly increases the levels of fluvastatin and rosuvastatin, but not pravastatin. Miconazole would be expected to interact similarly. Itraconazole causes a marked rise in the serum levels of atorvastatin, lovastatin, pravastatin and simvastatin, but no change in fluvastatin or rosuvastatin levels. Ketoconazole would be expected to interact similarly. Rhabdomyolysis has been reported in some cases. Due to the risk of myopathy, the manufacturers of voriconazole caution, and the manufacturers of posaconazole contraindicate, concurrent use with atorvastatin, lovastatin and simvastatin. 9. Statins + Carbamazepine Carbamazepine dramatically reduces simvastatin levels. 10. Statins + Colchicine Three case reports describe myopathy or rhabdomyolysis in patients given colchicine with fluvastatin, pravastatin or simvastatin. It seems possible that this interaction could occur with colchicine and any statin. 11. Statins + Ezetimibe Ezetimibe does not appear to have adverse pharmacokinetic interactions with atorvastatin, fluvastatin, lovastatin, rosuvastatin or simvastatin. However, some evidence suggests that concurrent use may increase the risk of myopathy 12. Statins + Fibrates The plasma levels of lovastatin, simvastatin, atorvastatin and pravastatin are increased by gemfibrozil, the levels of fluvastatin are increased by bezafibrate, and the levels of pravastatin are increased by fenofibrate. No pharmacokinetic interactions occur with the combinations of fluvastatin with gemfibrozil, lovastatin with bezafibrate, and pravastatin, rosuvastatin or simvastatin with fenofibrate. Both statins and fibrates are known to cause rhabdomyolysis, and their concurrent use increases the risk of this reaction. 13. Statins + Grapefruit and other fruit juices Large amounts of grapefruit juice markedly increase the plasma levels of lovastatin and simvastatin, but only modestly affect the plasma levels of atorvastatin. Pravastatin seems not to interact. The clinical significance of the possible effects of pomegranate juice on rosuvastatin, and orange juice on pravastatin are unclear. 14. Statins + Macrolides Cases of acute rhabdomyolysis have been reported between lovastatin and azithromycin, clarithromycin, or erythromycin and between simvastatin and clarithromycin or roxithromycin. Macrolide antibacterials have also been potentially implicated in cases of rhabdomyolysis with atorvastatin and pravastatin. Pharmacokinetic studies suggest that the macrolides increase the levels of the statins metabolised by CYP3A4 (namely atorvastatin, lovastatin and simvastatin). 15. Statins + Nicotinic acid (Niacin) The risk of muscle toxicity, such as rhabdomyolysis, may be increased in patients taking a statin with nicotinic acid. 16. Statins + Protease inhibitors The levels of atorvastatin and simvastatin are markedly increased by lopinavir and saquinavir (with ritonavir), nelfinavir, and ritonavir alone. Pravastatin seems only moderately affected. Several cases of rhabdomyolysis have been attributed to this interaction. 17. Statins + Rifampicin (Rifampin) Rifampicin lowers the serum levels of atorvastatin, fluvastatin, pravastatin, and simvastatin. 18. Statins; Lovastatin + Fibre or Pectin Pectin and oat bran can reduce the cholesterol-lowering effects of lovastatin. TERJEMAHAN 1. Ezetimibe + Rifampicin (Rifampin) Rifampisin dosis tunggal meningkatkan kadar ezetimibe tanpa mengubah pengaruhnya pada sterol, sedangkan beberapa dosis rifampisin menurunkan kadar ezetimibe dan hampir menghilangkan efeknya secara total. 2. Fibrates + Colchicine Laporan kasus menunjukkan bahwa penggunaan fibrat dan colchicines saat ini dapat menyebabkan rhabdomyolysis atau neuromyopathy. 3. Fibrat + Diuretik Pengobatan dengan clofibrate pada pasien dengan sindrom nefrotik yang menerima furosemid kadang menyebabkan diuresis yang ditandai dengan efek samping muskular yang parah dan melumpuhkan. Laporan yang terisolasi menggambarkan rhabdomyolysis pada pasien yang memakai bezafibrate dan furosemide. 4. Fibrat; Gemfibrozil + Antasida Antasida dapat mengurangi penyerapan gemfibrozil. 5. Statin + ACE inhibitor Secara umum statin tampaknya tidak berinteraksi dengan inhibitor ACE. Laporan yang terisolasi menggambarkan hiperkalemia berat pada lisinopril yang diabetik dengan lovastatin, dan pankreatitis akut telah dikaitkan dengan penggunaan lisinopril dengan atorvastatin. 6. Statins + Amiodarone Ada beberapa bukti kejadian myopathy yang tinggi saat amiodarone diberikan dengan dosis tinggi simvastatin. Kasus miopati dan rhabdomyolysis telah dilaporkan pada pasien yang memakai kombinasi ini. 7. Statin + Antasida Antasida aluminium / magnesium hidroksida (Maalox) menyebabkan reduksi moderat pada bioavailabilitas atorvastatin, pravastatin, dan rosuvastatin, namun khasiat lipid atorvastatin dan pravastatin tidak terpengaruh. 8. Statin + Azoles Flukonazol dengan mudah meningkatkan kadar fluvastatin dan rosuvastatin, tapi tidak pravastatin. Miconazole diharapkan bisa berinteraksi sama. Itraconazole menyebabkan peningkatan kadar atorvastatin, lovastatin, pravastatin dan simvastatin dalam kadar serum, namun tidak ada perubahan pada tingkat fluvastatin atau rosuvastatin. Ketokonazol diharapkan bisa berinteraksi sama. Rhabdomyolysis telah dilaporkan dalam beberapa kasus. Karena risiko miopati, produsen kehati-hatian vorikonazol, dan produsen kontraindikasi posaconazol, penggunaan bersamaan dengan atorvastatin, lovastatin dan simvastatin. 9. Statin + Carbamazepine Carbamazepine secara dramatis mengurangi tingkat simvastatin. 10. Statin + Colchicine Tiga laporan kasus menggambarkan miopati atau rhabdomyolysis pada pasien yang diberi colchicine dengan fluvastatin, pravastatin atau simvastatin. Tampaknya mungkin interaksi ini bisa terjadi dengan colchicine dan statin lainnya. 11. Statin + Ezetimibe Ezetimibe tampaknya tidak memiliki interaksi farmakokinetik yang merugikan dengan atorvastatin, fluvastatin, lovastatin, rosuvastatin atau simvastatin. Namun, beberapa bukti menunjukkan bahwa penggunaan bersamaan dapat meningkatkan risiko miopati 12. Statin + Fibrat Tingkat plasma lovastatin, simvastatin, atorvastatin dan pravastatin meningkat dengan gemfibrozil, tingkat fluvastatin meningkat dengan bezafibrate, dan kadar pravastatin meningkat fenofibrate. Tidak ada interaksi farmakokinetik dengan kombinasi fluvastatin dengan gemfibrozil, lovastatin dengan bezafibrate, dan pravastatin, rosuvastatin atau simvastatin dengan fenofibrate. Statin dan fibrat diketahui menyebabkan rhabdomyolysis, dan penggunaan yang bersamaan dapat meningkatkan risiko reaksi ini. 13. Statin + jus jeruk Bali dan jus buah lainnya Jus jeruk Bali dalam jumlah besar secara nyata meningkatkan kadar lovastatin dan simvastatin dalam plasma, namun hanya sedikit mempengaruhi kadar atorvastatin dalam plasma. Pravastatin nampaknya tidak berinteraksi. Signifikansi klinis kemungkinan efek jus delima pada rosuvastatin, dan jus jeruk pada pravastatin tidak jelas. 14. Statin + Makrolida Kasus rhabdomyolysis akut telah dilaporkan antara lovastatin dan azitromisin, klaritromisin, atau eritromisin dan antara simvastatin dan klaritromisin atau roksitromisin. Antibakteri makrolida juga berpotensi terlibat dalam kasus rhabdomyolysis dengan atorvastatin dan pravastatin. Studi farmakokinetik menunjukkan bahwa makroidrogen meningkatkan kadar statin yang dimetabolisme oleh CYP3A4 (yaitu atorvastatin, lovastatin dan simvastatin). 15. Statin + asam nikotinat (Niacin) Risiko toksisitas otot, seperti rhabdomyolysis, dapat meningkat pada pasien yang memakai statin dengan asam nikotinat. 16. Statin + Penghambat protease Tingkat atorvastatin dan simvastatin meningkat tajam oleh lopinavir dan saquinavir (dengan ritonavir), nelfinavir, dan ritonavir sepertinya hanya terpengaruh Pravastatin saja. Beberapa kasus rhabdomyolysis dikaitkan dengan interaksi ini. 17. Statin + Rifampisin (Rifampisin) Rifampisin menurunkan kadar serum atorvastatin, fluvastatin, pravastatin, dan simvastatin. 18. Statin; Lovastatin + Serat atau Pektin Pectin dan oat bran dapat mengurangi efek penurun kolesterol dari lovastatin.