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Drug Interactions between atorvastatin and nevirapine

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

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Interactions between your drugs

Moderate

nevirapine atorvastatin

Applies to: nevirapine and atorvastatin

MONITOR: Coadministration with efavirenz may decrease the plasma concentrations and pharmacologic effects of certain HMG-CoA reductase inhibitors (i.e., statins) and/or their active metabolites. The proposed mechanism is efavirenz induction of CYP450 3A4 metabolism. In 14 healthy, HIV-negative adult volunteers, coadministration of efavirenz (600 mg once daily for 15 days) and simvastatin (40 mg once daily on the last 4 days of efavirenz administration) resulted in a 58% median decrease in the systemic exposure (AUC) of simvastatin acid and a 60% median decrease in active HMG-CoA reductase inhibitory activity compared to administration of simvastatin alone. For atorvastatin (10 mg once daily in the same study), the systemic exposure was reduced by 43% and the total active atorvastatin exposure by 34% with efavirenz. Similarly, pravastatin (40 mg once daily in the same study) systemic exposure was reduced 40% by efavirenz. The median LDL cholesterol decrease associated with simvastatin was 11 mg/dL smaller with efavirenz coadministration than with simvastatin alone. For atorvastatin, the median LDL decrease was 6.5 mg/dL smaller with efavirenz, but the difference exhibited only a trend toward statistical significance. There was no significant difference in LDL decrease for pravastatin with or without efavirenz. Neither simvastatin, atorvastatin, nor pravastatin had any effect on the pharmacokinetics of efavirenz.

MANAGEMENT: Coadministration of simvastatin, atorvastatin, or other statins that are primarily metabolized by CYP450 3A4 (e.g., lovastatin) with efavirenz may result in diminished hypolipidemic efficacy. Although pravastatin is not significantly metabolized by CYP450 3A4, it has also been implicated. Dosage adjustment of these statins may be necessary if they are prescribed with efavirenz. The same precaution may be applicable during therapy with nevirapine, another nonnucleoside reverse transcriptase inhibitor that induces CYP450 3A4.

References

  1. (2001) "Product Information. Sustiva (efavirenz)." DuPont Pharmaceuticals
  2. Gerber JG, Rosenkranz SL, Fichtenbaum CJ, et al. (2005) "Effect of efavirenz on the pharmacokinetics of simvastatin, atorvastatin, and pravastatin: results of AIDS Clinical Trials Group 5108 Study." J Acquir Immune Defic Syndr, 39, p. 307-12

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Drug and food interactions

Moderate

atorvastatin food

Applies to: atorvastatin

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
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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.

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