Skip to main content

Drug Interactions between atorvastatin / ezetimibe and olaparib

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

Edit list (add/remove drugs)

Interactions between your drugs

Moderate

atorvastatin ezetimibe

Applies to: atorvastatin / ezetimibe and atorvastatin / ezetimibe

MONITOR: Coadministration with ezetimibe may rarely increase the risk of myopathy and serum transaminase elevations associated with HMG-CoA reductase inhibitors (i.e., statins). The mechanism of interaction is unknown. A case report describes two patients whose serum creatine kinase increased after ezetimibe was added to their statin therapy (atorvastatin and fluvastatin, respectively). One of the patients also developed myalgia and tendinopathy, which resolved promptly after withdrawal of both drugs. Statin therapy was subsequently reintroduced at the previous dosage without incident. In the other patient, serum creatine kinase returned to normal within 4 weeks after discontinuation of ezetimibe while the statin was continued. On the contrary, no cases of myopathy or tendinopathy occurred in a study of 33 hypercholesterolemic patients treated with ezetimibe and atorvastatin or simvastatin. There were also no reports of myopathy or significant increases in serum creatine kinase in a study of 32 subjects treated with ezetimibe and fluvastatin. In controlled clinical studies, the incidence of consecutive elevations (greater than 3 times the upper limit of normal) in serum transaminases was 1.3% for patients treated with ezetimibe in combination with a statin versus 0.4% for patients treated with a statin alone. These elevations were generally asymptomatic, not associated with cholestasis, and returned to baseline after discontinuation of therapy or with continued treatment.

MANAGEMENT: Until further information is available, use of a statin in combination with ezetimibe should be approached with caution. Patients should be advised to promptly report to their physician any unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. The drugs 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, liver function tests should be performed at initiation of therapy and according to the recommendations of the HMG-CoA reductase inhibitor.

References

  1. Gagne C, Gaudet D, Bruckert E (2002) "Efficacy and safety of ezetimibe coadministered with atorvastatin or simvastatin in patients with homozygous familial hypercholesterolemia." Circulation, 105, p. 2469-75
  2. Fux R, Morike K, Gundel UF, Hartmann R, Gleiter CH (2004) "Ezetimibe and statin-associated myopathy." Ann Intern Med, 140, p. 671-2

Switch to consumer interaction data

Moderate

atorvastatin olaparib

Applies to: atorvastatin / ezetimibe and olaparib

MONITOR: Based on in vitro inhibition data, coadministration with olaparib may increase the plasma concentrations of drugs that are substrates of CYP450 3A4 (e.g., cyclosporine, cisapride, ergot alkaloids, fentanyl, lovastatin, oral midazolam, pimozide, quetiapine, simvastatin, sirolimus, tacrolimus, triazolam, vinca alkaloids), P-glycoprotein (P-gp) (e.g., colchicine, dabigatran, digoxin, lovastatin, pravastatin, simvastatin, sirolimus, tacrolimus), breast cancer resistance protein (BCRP) (e.g., methotrexate, rosuvastatin), organic anion transporting polypeptide 1B1 (OATP1B1) (e.g., bosentan, eluxadoline, glyburide, repaglinide, statins, valsartan), organic cation transporter 1 or 2 (OCT1, OCT2) (e.g., metformin), organic anion transporter 3 (OAT3) (e.g., furosemide, methotrexate), and/or multidrug and toxin extrusion transporter 1 or 2K (MATE1, MATE-2K) (e.g., metformin).

MANAGEMENT: Caution is advised when olaparib is used concomitantly with drugs that are substrates of the affected enzymes or transporters, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever olaparib is added to or withdrawn from therapy.

References

  1. (2023) "Product Information. Lynparza (olaparib)." AstraZeneca Canada Inc
  2. (2024) "Product Information. Lynparza (olaparib)." AstraZeneca Pty Ltd, 003843410 v13.0
  3. (2024) "Product Information. Lynparza (olaparib)." AstraZeneca UK Ltd

Switch to consumer interaction data

Drug and food interactions

Major

olaparib food

Applies to: olaparib

GENERALLY AVOID: Grapefruit juice may significantly increase the plasma concentrations of olaparib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. In a drug interaction study with 57 patients, olaparib systemic exposure (AUC) was increased approximately 2.7-fold by the potent CYP450 3A4 inhibitor itraconazole. Simulations using physiologically-based pharmacokinetic (PBPK) models suggest that a moderate inhibitor (fluconazole) may increase the AUC of olaparib by 2-fold. The interaction has not been studied with grapefruit juice. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Increased exposure to olaparib may increase the risk of adverse effects such as hematologic toxicity, nausea, vomiting, diarrhea, anorexia, dyspepsia, and abdominal pain or discomfort.

MANAGEMENT: Patients treated with olaparib should avoid consumption of grapefruits, grapefruit juice, Seville oranges, and Seville orange juice. Some authorities also recommend avoiding starfruit (carambola) and pomegranate.

References

  1. (2023) "Product Information. Lynparza (olaparib)." Astra-Zeneca Pharmaceuticals
  2. (2023) "Product Information. Lynparza (olaparib)." AstraZeneca Canada Inc
  3. (2024) "Product Information. Lynparza (olaparib)." AstraZeneca Pty Ltd, 003843410 v13.0
  4. (2024) "Product Information. Lynparza (olaparib)." AstraZeneca UK Ltd
View all 4 references

Switch to consumer interaction data

Moderate

atorvastatin food

Applies to: atorvastatin / ezetimibe

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

Switch to consumer interaction data

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.


Report options

Loading...
QR code containing a link to this page

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

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.