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Advicor and Diltia XT

Determining the interaction of Advicor and Diltia XT and the possibility of their joint administration.

Check result:
Advicor <> Diltia XT
Relevance: 15.06.2022 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:

Talk to your doctor before using lovastatin together with dilTIAZem. Combining these medications may significantly increase the blood levels of lovastatin. 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 lovastatin 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:

ADJUST DOSE: Coadministration with diltiazem has been shown to significantly increase the plasma concentrations of lovastatin acid, the active metabolite of lovastatin. The mechanism of interaction is not fully understood, but may involve diltiazem inhibition of the CYP450 3A4 isoenzyme and/or P-glycoprotein efflux transporter, of which both lovastatin and lovastatin acid are substrates. When lovastatin 20 mg was administered with diltiazem (120 mg twice daily for 14 days) in 10 study subjects, there was an approximately 3.6-fold increase in lovastatin acid systemic exposure (AUC) compared to administration of lovastatin alone. High levels of HMG-CoA reductase inhibitory activity in plasma is associated with an increased risk of 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: Lovastatin dosage should not exceed 20 mg daily when used in combination with diltiazem. The benefits of this combination should be carefully weighed against the potentially increased risk of myopathy including rhabdomyolysis. Fluvastatin, pravastatin, and rosuvastatin are probably safer alternatives in patients receiving diltiazem, since they are not metabolized by CYP450 3A4. 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
  • Ayanian JZ, Fuchs CS, Stone RM "Lovastatin and rhabdomyolysis." Ann Intern Med 109 (1988): 682-3
  • Worz CR, Bottorff M "The role of cytochrome P450-mediated drug-drug interactions in determining the safety of statins." Expert Opin Pharmacother 2 (2001): 1119-27
  • Masica AL, Azie NE, Brater DC, Hall SD, Jones DR "Intravenous diltiazem and CYP3A-mediated metabolism." Br J Clin Pharmacol 50 (2000): 273-6
  • "Product Information. Dilacor XR (diltiazem)." Aventis Pharmaceuticals, Bridgewater, NJ.
  • Dresser GK, Spence JD, Bailey DG "Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition." Clin Pharmacokinet 38 (2000): 41-57
  • Holtzman CW, Wiggins BS, Spinler SA "Role of P-glycoprotein in statin drug interactions." Pharmacotherapy 26 (2006): 1601-7
  • Azie NE, Brater DC, Becker PA, Jones DR, Hall SD "The interaction of diltiazem with lovastatin and pravastatin." Clin Pharmacol Ther 64 (1998): 369-77
  • "Product Information. Mevacor (lovastatin)." Merck & Co, Inc, West Point, PA.
  • Huynh T, Cordato D, Yang F, et al. "HMG coA reductase-inhibitor-related myopathy and the influence of drug interactions." Intern Med J 32(9-10) (2002): 486-90
  • Garnett WR "Interactions with hydroxymethylglutaryl-coenzyme A reductase inhibitors." Am J Health Syst Pharm 52 (1995): 1639-45
  • Agbin NE, Brater DC, Hall SD "Interaction of diltiazem with lovastatin and pravastatin." Clin Pharmacol Ther 61 (1997): 201
  • Paoletti R, Corsini A, Bellosta S "Pharmacological interactions of statins." Atheroscler Suppl 3 (2002): 35-40
  • Ayanian JZ, Fuchs CS, Stone RM "Lovastatin and rhabdomyolysis." Ann Intern Med 109 (1988): 682-3
  • Williams D, Feely J "Pharmacokinetic-Pharmacodynamic Drug Interactions with HMG-CoA Reductase Inhibitors." Clin Pharmacokinet 41 (2002): 343-70
Advicor

Generic Name: lovastatin / niacin

Brand name: Advicor

Synonyms: n.a.

Diltia XT

Generic Name: diltiazem

Brand name: Cardizem CD, Cartia XT, Dilt-XR, Diltia XT, Taztia XT, Tiazac, Cardizem, Dilacor XR, Dilt-CD, Diltzac, Matzim LA, Tiazac, Cardizem LA, Tiazac Extended Release Capsules

Synonyms: n.a.

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.

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