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Drug Interactions between cerivastatin and darunavir

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Major

cerivastatin darunavir

Applies to: cerivastatin and darunavir

CONTRAINDICATED: Protease inhibitors, particularly ritonavir, may significantly increase the plasma concentrations of HMG-CoA reductase inhibitors (i.e., statins) that are primarily metabolized by CYP450 3A4. As a class, HIV protease inhibitors are well established inhibitors of CYP450 3A4, with ritonavir being the most potent. When simvastatin (40 mg once a day for 4 days) was coadministered with ritonavir (400 mg twice a day for 14 days) and saquinavir (soft gelatin capsule 400 mg twice a day for 14 days) in healthy volunteers, mean simvastatin acid peak plasma concentration (Cmax) and systemic exposure (AUC) increased by over 30-fold each. Clinically, high levels of HMG-CoA reductase inhibitory activity in plasma may be 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: Concomitant use of lovastatin or simvastatin is considered contraindicated during treatment with ritonavir due to the potential for severe interaction. Red yeast rice, which contains lovastatin, should also be avoided. Fluvastatin and pravastatin are probably safer alternatives, since they are not metabolized by CYP450 3A4. When initiating treatment with nirmatrelvir/ritonavir, the manufacturer recommends discontinuing lovastatin or simvastatin for at least 12 hours prior to treatment. All patients treated with HMG-CoA reductase inhibitors should be advised to promptly report any unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. 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

  1. (2001) "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical
  2. (2001) "Product Information. Crixivan (indinavir)." Merck & Co., Inc
  3. (2001) "Product Information. Viracept (nelfinavir)." Agouron Pharma Inc
  4. Malaty LI, Kuper JJ (1999) "Drug interactions of HIV protease inhibitors." Drug Safety, 20, p. 147-69
  5. (2001) "Product Information. Agenerase (amprenavir)." Glaxo Wellcome
  6. Barry M, Mulcahy F, Merry C, Gibbons S, Back D (1999) "Pharmacokinetics and potential interactions amongst antiretroviral agents used to treat patients with HIV infection." Clin Pharmacokinet, 36, p. 289-304
  7. Dresser GK, Spence JD, Bailey DG (2000) "Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition." Clin Pharmacokinet, 38, p. 41-57
  8. (2001) "Product Information. Fortovase (saquinavir)." Roche Laboratories
  9. Mangum EM, Graham KK (2001) "Lopinavir-Ritonavir: a new protease inhibitor." Pharmacotherapy, 21, p. 1352-63
  10. Fichtenbaum CJ, Gerber JG, Rosenkranz SL, et al. (2002) "Pharmacokinetic interactions between protease inhibitors and statins in HIV seronegative volunteers: ACTG Study A5047." AIDS, 16, p. 569-577
  11. Piliero PJ (2002) "Interaction between ritonavir and statins." Am J Med, 112, p. 510-1
  12. Cheng CH, Miller C, Lowe C, Pearson VE (2002) "Rhabdomyolysis due to probable interaction between simvastatin and ritonavir." Am J Health Syst Pharm, 59, p. 728-30
  13. Hare CB, Vu MP, Grunfeld C, Lampiris HW (2002) "Simvastatin-nelfinavir interaction implicated in rhabdomyolysis and death." Clin Infect Dis, 35, E111-2
  14. (2003) "Product Information. Reyataz (atazanavir)." Bristol-Myers Squibb
  15. (2003) "Product Information. Lexiva (fosamprenavir)." GlaxoSmithKline
  16. (2006) "Product Information. Prezista (darunavir)." Ortho Biotech Inc
  17. Schmidt GA, Hoehns JD, Purcell JL, Friedman RL, Elhawi Y (2007) "Severe rhabdomyolysis and acute renal failure secondary to concomitant use of simvastatin, amiodarone, and atazanavir." J Am Board Fam Med, 20, p. 411-6
  18. Neuvonen PJ, Backman JT, Niemi M (2008) "Pharmacokinetic comparison of the potential over-the-counter statins simvastatin, lovastatin, fluvastatin and pravastatin." Clin Pharmacokinet, 47, p. 463-74
  19. US Food and Drug Administration (2021) FACT SHEET FOR HEALTHCARE PROVIDERS EMERGENCY USE AUTHORIZATION FOR PAXLOVID. https://www.fda.gov/media/155050/download
View all 19 references

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Drug and food interactions

Moderate

cerivastatin food

Applies to: cerivastatin

GENERALLY AVOID: Coadministration with grapefruit juice may increase the plasma concentrations of atorvastatin. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. When a single 40 mg dose of atorvastatin was coadministered with 240 mL of grapefruit juice, atorvastatin peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 16% and 37%, respectively. Greater increases in Cmax (up to 71%) and/or AUC (up to 2.5 fold) have been reported with excessive consumption of grapefruit juice (>=750 mL to 1.2 liters per day). Clinically, 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.

ADJUST DOSING INTERVAL: Fibres such as oat bran and pectin may diminish the pharmacologic effects of HMG-CoA reductase inhibitors by interfering with their absorption from the gastrointestinal tract.

MANAGEMENT: Patients receiving therapy with atorvastatin should limit their consumption of grapefruit juice to no more than 1 liter per day. Patients 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. In addition, patients should either refrain from the use of oat bran and pectin or, if concurrent use cannot be avoided, to separate the administration times by at least 2 to 4 hours.

References

  1. Richter WO, Jacob BG, Schwandt P (1991) "Interaction between fibre and lovastatin." Lancet, 338, p. 706
  2. McMillan K (1996) "Considerations in the formulary selection of hydroxymethylglutaryl coenzyme a reductase inhibitors." Am J Health Syst Pharm, 53, p. 2206-14
  3. (2001) "Product Information. Lipitor (atorvastatin)." Parke-Davis
  4. Boberg M, Angerbauer R, Fey P, Kanhai WK, Karl W, Kern A, Ploschke J, Radtke M (1997) "Metabolism of cerivastatin by human liver microsomes in vitro. Characterization of primary metabolic pathways and of cytochrome P45 isozymes involved." Drug Metab Dispos, 25, p. 321-31
  5. Bailey DG, Malcolm J, Arnold O, Spence JD (1998) "Grapefruit juice-drug interactions." Br J Clin Pharmacol, 46, p. 101-10
  6. Lilja JJ, Kivisto KT, Neuvonen PJ (1999) "Grapefruit juice increases serum concentrations of atorvastatin and has no effect on pravastatin." Clin Pharmacol Ther, 66, p. 118-27
  7. Neuvonen PJ, Backman JT, Niemi M (2008) "Pharmacokinetic comparison of the potential over-the-counter statins simvastatin, lovastatin, fluvastatin and pravastatin." Clin Pharmacokinet, 47, p. 463-74
View all 7 references

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Moderate

darunavir food

Applies to: darunavir

ADJUST DOSING INTERVAL: Food enhances the absorption and oral bioavailability of darunavir administered in combination with low-dose ritonavir. The mechanism is unknown. When administered with food, the peak plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) of darunavir were approximately 30% higher than when administered in the fasting state. Darunavir exposure was similar for the range of meals studied. The total caloric content of the various meals evaluated ranged from 240 Kcal (12 grams fat) to 928 Kcal (56 grams fat).

MANAGEMENT: To ensure maximal oral absorption, darunavir coadministered with ritonavir should be taken with food. The type of food is not important.

References

  1. (2006) "Product Information. Prezista (darunavir)." Ortho Biotech Inc

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

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