Rosuvastatin with Lopinavir Interaction Details
Brand Names Associated with Rosuvastatin
- Crestor®
- Ezallor®
- Rosuvastatin
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 10, 2023
Interaction Effect
Increased rosuvastatin exposure and an increased risk of myopathy and rhabdomyolysis
Interaction Summary
In a pharmacokinetics study in healthy subjects (n=15), coadministration of lopinavir/ritonavir and rosuvastatin significantly increased the AUC and Cmax of rosuvastatin compared to rosuvastatin alone by approximately 2-fold and 5-fold, respectively. Rhabdomyolysis was reported in a patient taking lopinavir/ritonavir and rosuvastatin 40 mg daily, although the patient had additional risks for serious statin-related toxicity (ie, concomitant gemfibrozil, high-dose rosuvastatin, and Asian heritage) . If concomitant use of lopinavir/ritonavir and rosuvastatin is necessary, use the lowest possible rosuvastatin dose, titrate carefully, and ; the dose of rosuvastatin should not exceed 10 mg orally once daily .
Severity
Major
Onset
Delayed
Evidence
Established
How To Manage Interaction
Use caution if lopinavir/ritonavir and rosuvastatin are coadministered as this has resulted in significant increases in rosuvastatin exposure and may increase the risk of myopathy and rhabdomyolysis. If concomitant use of lopinavir/ritonavir and rosuvastatin is necessary, use the lowest possible dose of rosuvastatin, titrate carefully, and the dose of rosuvastatin should not exceed 10 mg orally once daily.
Mechanism Of Interaction
Inhibition of CYP3A4-mediated rosuvastatin metabolism
Literature Reports
A) In an open-label, single-arm, 3-phase, pharmacokinetics study, coadministration of lopinavir/ritonavir (LPV/RTV) and rosuvastatin resulted in 2.1- and 4.7-fold increases in rosuvastatin AUC and Cmax, respectively, compared to rosuvastatin alone. Healthy subjects (n=15) aged 18 to 60 years received rosuvastatin 20 mg orally once daily for 7 days, followed by LPV 400 mg/RTV 100 mg orally twice daily for 10 days, and then rosuvastatin plus LPV/RTV for 7 days. Pharmacokinetic samples were obtained on days 7, 17, and 24 of study, and data from 15 subjects was used in the statistical analysis. The mean AUC and Cmax of rosuvastatin increased from 50 +/- 15.3 ng x hr/mL and 4.7 ng x hr/mL, respectively, when given alone to 115 +/- 65.5 ng x h/mL and 25.2 +/- 16.9 ng x h/mL, respectively, when coadministered with LPV/RTV. The geometric least squares mean ratio was 2.1 (90% confidence interval (CI), 1.7 to 2.6) and 4.7 (90% CI, 3.4 to 6.4) for rosuvastatin AUC and Cmax, respectively, when coadministered with LPV/RTV versus alone (p less than 0.0001). The elimination half-life of rosuvastatin and the pharmacokinetics of LPV/RTV were not affected. However, reductions in low-density lipoprotein (LDL) cholesterol were lower with LPV/RTV plus rosuvastatin compared to rosuvastatin monotherapy (27% vs 40%, respectively; mean baseline LDL, 96 mg/dL). Grade 4 asymptomatic CPK elevation (3300 Units/Liter) occurred in 1 patient during coadministration of LPV/RTV and rosuvastatin. Also, grade 1 liver function test elevation (1.1 to 2.5 times upper limit of the normal) occurred in 1 patient receiving LPV/RTV plus rosuvastatin versus no cases with rosuvastatin alone. The mechanism for this interaction is unknown and further study is warranted .
B) A 60-year-old Indonesian-Caucasian man with HIV infection experienced rhabdomyolysis following concomitant administration of lopinavir 400 mg/ritonavir 100 mg twice daily and rosuvastatin 40 mg daily. Comorbid conditions included moderate renal impairment (estimated CrCl, 38 mL/min), polyneuropathy, and benign prostatic hyperplasia; other medications were tenofovir 245 mg every other day, abacavir 300 mg twice daily, gemfibrozil 600 mg twice daily, tamsulosin 0.4 mg daily, aspirin 80 mg daily, gabapentin 400 mg three times daily, and amitriptyline 25 mg daily. Approximately 5 months earlier, the patient had been switched from pravastatin 40 mg daily to rosuvastatin. Another recent event was a urinary tract infection, treated with ciprofloxacin for 5 days prior to admission. The patient presented with fatigue, abdominal pain and hematuria. Laboratory analysis revealed elevations in creatine kinase (CK; 37,550 international units/L), AST (828 international units/L), and ALT (298 international units/L). Rhabdomyolysis was diagnosed and treated with forced diuresis. Antiretroviral therapy, ciprofloxacin, and rosuvastatin were discontinued. Following resolution of symptoms, and CK, AST and ALT levels, the patient resumed antiretroviral therapy with atazanavir 300 mg/ritonavir 100 mg daily, abacavir 300 mg twice a day, and raltegravir 400 mg twice a day. Pravastatin 40 mg daily was restarted 5 months later, without recurrence of any signs or symptoms of rhabdomyolysis .
C) Administration of rosuvastatin 20 mg once daily for 7 days in patients receiving lopinavir 400 mg/ritonavir 100 mg twice daily for 17 days resulted in 2.1-fold increase in the AUC and 5-fold increase in the Cmax of rosuvastatin .
Rosuvastatin Overview
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Rosuvastatin is used together with diet, weight-loss, and exercise to reduce the risk of heart attack and stroke and to decrease the chance that heart surgery will be needed in people who have heart disease or who are at risk of developing heart disease. Rosuvastatin is also used to decrease the amount of cholesterol such as low-density lipoprotein (LDL) cholesterol ('bad cholesterol') and triglycerides in the blood and to increase the amount of high-density lipoprotein (HDL) cholesterol ('good cholesterol') in the blood. Rosuvastatin may also be used together with diet to decrease the amount of cholesterol and other fatty substances in the blood in children and teenagers 8 to 17 years of age who have familial heterozygous hypercholesterolemia (an inherited condition in which cholesterol cannot be removed from the body normally). Rosuvastatin is used together with diet, and alone or in combination with other medications, to decrease the amount of cholesterol and other fatty substances in the blood in adults and children and teenagers 7 to 17 years of age who have familial homozygous hypercholesterolemia (an inherited condition in which cholesterol cannot be removed from the body normally). Rosuvastatin is in a class of medications called HMG-CoA reductase inhibitors (statins). It works by slowing the production of cholesterol in the body to decrease the amount of cholesterol that may build up on the walls of the arteries and block blood flow to the heart, brain, and other parts of the body.
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Accumulation of cholesterol and fats along the walls of your arteries (a process known as atherosclerosis) decreases blood flow and, therefore, the oxygen supply to your heart, brain, and other parts of your body. Lowering your blood level of cholesterol and fats with rosuvastatin has been shown to prevent heart disease, angina (chest pain), strokes, and heart attacks.
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Definitions
Severity Categories
Contraindicated
These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.
Major
This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.
Moderate
This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.
Minor
While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.
Onset
Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.
Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.
Evidence
Level of documentation of the interaction.
Established: The interaction is documented and substantiated in peer-reviewed medical literature.
Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.
How To Manage The Interaction
Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.
It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.
Mechanism Of Interaction
The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.
Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.
Where Does Our Information Come From?
Information for our drug interactions is compiled from several drug compendia, including:
The prescribing information for each drug, as published on DailyMED, is also used.
Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.
The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.