Drug search by name

Neoral and Vytorin

Determining the interaction of Neoral and Vytorin and the possibility of their joint administration.

Check result:

Neoral <> Vytorin

Relevance: 28.09.2022 Reviewer: Shkutko P.M., M.D., in

In the database of official manuals used in the service creation an interaction registered by statistical results of studies was found, which can either lead to negative consequences for the patient health or strengthen a mutual positive effect. A doctor should be consulted to address the issue of joint drug administration.

Consumer:

Using simvastatin together with cycloSPORINE is not recommended. Combining these medications may significantly increase the blood levels of simvastatin. This can increase the risk of side effects such as liver damage and a rare but serious condition called rhabdomyolysis that involves the breakdown of skeletal muscle tissue. In some cases, rhabdomyolysis can cause kidney damage and even death. You may need a dose adjustment or more frequent monitoring by your doctor to safely use both medications, or your doctor may prescribe alternative medications that do not interact. Let your doctor know immediately if you have unexplained muscle pain, tenderness, or weakness during treatment with simvastatin or similar medications, especially if these symptoms are accompanied by fever or dark colored urine. You should also seek immediate medical attention if you develop fever, chills, joint pain or swelling, unusual bleeding or bruising, skin rash, itching, loss of appetite, fatigue, nausea, vomiting, dark colored urine, and/or yellowing of the skin or eyes, as these may be signs and symptoms of liver damage. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Professional:

CONTRAINDICATED: Coadministration with cyclosporine may significantly increase the plasma concentrations of some HMG-CoA reductase inhibitors and/or their pharmacologically active metabolites. The proposed mechanism is cyclosporine inhibition of intestinal and hepatic CYP450 3A4, the isoenzyme responsible for the metabolic clearance of HMG-CoA reductase inhibitors like atorvastatin, lovastatin, and simvastatin. In addition, atorvastatin, its metabolites, and the active beta-hydroxyacid form of simvastatin, simvastatin acid, are substrates of the hepatic uptake transporter, organic anion transporting polypeptide protein (OATP) 1B1, which is also inhibited by cyclosporine. The AUC of atorvastatin increased 8.7-fold during concurrent administration of atorvastatin 10 mg/day and cyclosporine 5.2 mg/kg/day. High levels of HMG-CoA reductase inhibitory activity in plasma is associated with an increased risk of musculoskeletal toxicity. Use of cyclosporine with simvastatin or other HMG-CoA reductase inhibitors has resulted in musculoskeletal toxicity. Myopathy manifested as muscle pain and/or weakness associated with grossly elevated creatine kinase exceeding ten times the upper limit of normal has been reported occasionally. Rhabdomyolysis has also occurred rarely, which may be accompanied by acute renal failure secondary to myoglobinuria and may result in death.

MANAGEMENT: Concomitant use of simvastatin and cyclosporine is considered contraindicated by the manufacturer of simvastatin. Fluvastatin or pravastatin may be considered as alternatives in patients receiving cyclosporine as they are not extensively metabolized by CYP450 3A4. However, the benefits of the use of these medicines in combination with cyclosporine should be carefully weighed against the potential risks. Statin therapy should be initiated at a lower dosage and titrated with caution. The product labeling for fluvastatin recommends that, when used in combination with cyclosporine, the fluvastatin dose should not exceed 20 mg twice a day when given with cyclosporine. The product labeling for pravastatin recommends that the pravastatin dose should start at 10 mg/day and generally not exceed 20 mg/day when given with cyclosporine. All patients receiving statin therapy should be advised to promptly report any unexplained muscle pain, tenderness or weakness, particularly if accompanied by fever, malaise, and/or dark-colored urine. Therapy should be discontinued if creatine kinase is markedly elevated in the absence of strenuous exercise or if myopathy is otherwise suspected or diagnosed.

References

"Product Information. Lescol (fluvastatin)." Novartis Pharmaceuticals, East Hanover, NJ.
Holtzman CW, Wiggins BS, Spinler SA "Role of P-glycoprotein in statin drug interactions." Pharmacotherapy 26 (2006): 1601-7
Rifkin SI "Multiple drug interactions in a renal transplant patient leading to simvastatin-induced rhabdomyolysis: a case report." Medscape J Med 10 (2008): 264
Campana C, Iacona I, Regassi MB, et al. "Efficacy and pharmacokinetics of simvastatin in heart transplant recipients." Ann Pharmacother 29 (1995): 235-9
Southworth MR, Mauro VF "The use of HMG-CoA reductase inhibitors to prevent accelerated graft atherosclerosis in heart transplant patients." Ann Pharmacother 31 (1997): 489-91
Capone D, Stanziale P, Gentile A, Imperatore P, Pellegrino T, Basile V "Effects of simvastatin and pravastatin on hyperlipidemia and cyclosporin blood levels in renal transplant recipients." Am J Nephrol 19 (1999): 411-5
East C, Alivizatos PA, Grundy SM, Jones PH, Farmer JA "Rhabdomyolysis in patients receiving lovastatin after cardiac transplantation." N Engl J Med 318 (1988): 47-8
"Product Information. Mevacor (lovastatin)." Merck & Co, Inc, West Point, PA.
Paoletti R, Corsini A, Bellosta S "Pharmacological interactions of statins." Atheroscler Suppl 3 (2002): 35-40
Kalliokoski A, Niemi M "Impact of OATP transporters on pharmacokinetics." Br J Pharmacol 158 (2009): 693-705
Norman DJ, Illingworth DR, Munson J, Hosenpud J "Myolysis and acute renal failure in a heart-transplant recipient receiving lovastatin." N Engl J Med 318 (1988): 46-7
Cerner Multum, Inc. "Australian Product Information." O 0
Gruer PJK, Vega JM, Mercuri MF, Dobrinska MR, Tobert JA "Concomitant use of cytochrome P450 3A4 inhibitors and simvastatin." Am J Cardiol 84 (1999): 811-5
Kusus M, Stapleton DD, Lertora JJL, Simon EE, Dreisbach AW "Rhabdomyolysis and acute renal failure in a cardiac transplant recipient due to multiple drug interactions." Am J Med Sci 320 (2000): 394-7
"Product Information. Pravachol (pravastatin)." Bristol-Myers Squibb, Princeton, NJ.
Najafian B, Franklin DB, Fogo AB "Acute renal failure and myalgia in a transplant patient." J Am Soc Nephrol 18 (2007): 2870-4
Rodriguez JA, CrespoLeiro MG, Paniagua MJ, Cuenca JJ, Hermida LF, Juffe A, CastroBeiras A "Rhabdomyolysis in heart transplant patients on HMG-CoA reductase inhibitors and cyclosporine." Transplant Proc 31 (1999): 2522-3
Neuvonen PJ, Backman JT, Niemi M "Pharmacokinetic comparison of the potential over-the-counter statins simvastatin, lovastatin, fluvastatin and pravastatin." Clin Pharmacokinet 47 (2008): 463-74
Vanhaecke J, Vancleemput J, Vanlierde J, Daenen W, Degeest H "Safety and efficacy of low dose simvastatin in cardiac transplant recipients treated with cyclosporine." Transplantation 58 (1994): 42-5
Arnadottir M, Eriksson LO, Thysell H, Karkas JD "Plasma concentration profiles of simvastatin 3-hydroxy- 3-methylglutaryl-coenzyme A reductase inhibitory activity in kidney transplant recipients with and without ciclosporin." Nephron 65 (1993): 410-3
Gullestad L, Nordal KP, Berg KJ, Cheng H, Schwartz MS, Simonsen S "Interaction between lovastatin and cyclosporine A after heart and kidney transplantation." Transplant Proc 31 (1999): 2163-5
Corpier CL, Jones PH, Suki WN, et al. "Rhabdomyolysis and renal injury with lovastatin use. Report of two cases in cardiac transplant recipients." JAMA 260 (1988): 239-41
Maltz HC, Balog DL, Cheigh JS "Rhabdomyolysis associated with concomitant use of atorvastatin and cyclosporine." Ann Pharmacother 33 (1999): 1176-9
Francis L, Bonilla E, Soforo E, et al. "Fatal toxic myopathy attributed to propofol, methylprednisolone, and cyclosporine after prior exposure to colchicine and simvastatin." Clin Rheumatol 27 (2008): 129-31
"Product Information. Zocor (simvastatin)." Merck & Co, Inc, West Point, PA.
Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
Arnadottir M, Eriksson LO, Germershausen JI, Thysell H "Low-dose simvastatin is a well-tolerated and efficacious cholesterol-lowering agent in ciclosporin-treated kidney transplant recipients: double-blind, randomized, placebo-controlled study in 40 patients." Nephron 68 (1994): 57-62
Jardine A, Holdaas H "Fluvastatin in combination with cyclosporin in renal transplant recipients: a review of clinical and safety experience." J Clin Pharm Ther 24 (1999): 397-408

Neoral

Generic Name: cyclosporine

Brand name: Gengraf, Neoral, Sandimmune, Sandimmune

Synonyms: Neoral (Capsules, Modified)

What is Neoral?

Vytorin

Generic Name: ezetimibe / simvastatin

Brand name: Vytorin

Synonyms: n.a.

What is Vytorin?

+ Add a drug Remove all

In the course of checking the drug compatibility and interactions, data from the following reference sources was used: Drugs.com, Rxlist.com, Webmd.com, Medscape.com.

The list of popular interactions