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Purdue University
Drug Information Center
Memo
To: Dan Sage, MD
From: Jacob Martin, PharmD Student
CC: Amy Heck Sheehan, PharmD
Date: September 17, 2014
Re: Rosuvastatin Dosing for Nephrotoxicity Prophylaxis
In regards to your inquiry about the starting dose of rosuvastatin as nephrotoxicity prophylaxis
during a percutaneous coronary intervention (PCI) involving iohexol, the following information was
gathered.
Although not a labeled FDA indication, rosuvastatin has been shown to be effective as nephrotoxicity
prophylaxis in the use of radiographic contrast agents.1-3 A study of 2,998 individuals reports that
contrast-induced acute kidney injury (CI-AKI) occurred over 40% less in pre-treated patients with
diabetes mellitus (DM) compared to the control group (10 mg PO daily for 5 days total: 2 days before,
3 days after).2 A smaller study, using significantly larger doses of rosuvastatin (40 mg PO on
admission, 20 mg PO daily, thereafter), observed a 55% reduction in CI-AKI incidence.3
However, there is a drug interaction between rosuvastatin and the patient’s HIV medication,
Kaletra® (lopinavir/ritonavir).4 The statin is a known substrate of CYP3A4, while components of the
antiviral inhibit the same enzyme. This results in increased levels of rosuvastatin in plasma, carrying
a risk of myopathy and rhabdomyolysis. Co-administration has shown rosuvastatin max
concentrations 4.7 times larger than without the antiviral.5 Considering the aforementioned dosing
regimens and the drug interaction, caution must be exercised. Although tertiary sources list the
interaction of “major severity,” clinical judgment needs to consider the increased morbidity resulting
from CI-AKI.4,6 No information was found on proper short-term dosing of rosuvastatin coadministered with Kaletra®, but tertiary sources indicate that 10 mg PO daily should not be
exceeded.4 This dose is strongly recommended, all information considered. Discontinuing Kaletra®
is not recommended.7
Another drug interaction was noted, concerning the patient’s metformin and the contrast media
itself, Omnipaque® (iohexol).8 The two are contraindicated (as is metformin and all iodinated
contrast media).9 Co-administration may result in acute renal failure and lactic acidosis.8 This
interaction has a rapid onset. The elimination half-life of iohexol is 2 hours and that of metformin is
6.2 hours.8,9 If no alternative contrast agent can be used, wait 14 hours (7 half-lives) post-iohexol
administration to continue metformin doses (ideally, one would wait 40 hours after the last
metformin dose to give the contrast agent, but the current situation will not allow). In the interim, if
hyperglycemia occurs in the patient, administer insulin subQ or use another oral anti-diabetic:
repaglinide (0.5 mg PO ac 2-4 times daily) would be appropriate in this acute situation, as it quickly
reduces blood glucose.10,11 Finally, due to an interaction between the patient’s multivitamin
(containing niacin) and rosuvastatin—increasing the risk of myopathy and rhabdomyolysis—it is
recommended that multivitamin doses are held while the patient is on prophylaxis.12
This patient’s HIV treatment regimen also requires questioning. HIV monotherapy is not supported
in guidelines published by the U.S. Department of Health and Human Services, and Kaletra®’s
prescribing information explicitly states, “KALETRA must always be used in combination with other
antiretroviral drugs.”7,13 Reasons for transition to monotherapy are numerous (cost, side effects,
etc.), but such practice has not been endorsed by regulating bodies; studies showing equal or better
efficacy compared to traditional triple highly active antiretroviral therapy (HAART) cannot be
found.14 One study divided 42 HIV-positive individuals with suppressed HIV-RNA (the result of prior
HAART treatment): one group remained on HAART, and the other received lopinavir/ritonavir
monotherapy.15 After 48 weeks, the HAART cohort had 17% more individuals meeting a lab value
surrogate marker for virus progression—HAART was shown to be more effective. While there is
promise and reason in HIV monotherapy, little conclusive evidence shows better outcomes when
compared to traditional HAART.16 Until further studies show additional efficacy and safety, HIV
monotherapy does not appear prudent. It is recommended that this patient be asked about their HIV
regimen and if/why it changed. Recommended regimens include 2, if not 3, active agents—currently
the patient is on only 1.7,14
In conclusion, rosuvastatin is appropriate as a prophylactic for CI-AKI, but the patient’s HIV
treatment presents a drug interaction; conservative dosing of rosuvastatin must be used, and 10 mg
PO is a recommended starting dose, per information cited above.1-6 Further, it is recommended that
metformin and the multivitamin be discontinued while the patient is exposed to iohexol during the
PCI procedure.8,9,12 Repaglinide is suggested as an alternative anti-diabetic (0.5 mg PO ac 2-4 times
daily).10-11 The patient’s HIV monotherapy should be questioned upon PCI completion or discharge
to ensure HIV progression is controlled. As is, it is not proper therapy; consider a traditional HAART
regimen.7,13-16
Thank you for contacting the Purdue University Drug Information Center. If I can be of any
additional assistance, do not hesitate to contact me at 317-985-4876.
References:
1.
2.
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Rosuvastatin Calcium. DrugPoints Summary. Micromedex 2.0. Truven Health Analytics, Inc.
Greenwood Village, CO. Available at: http://www.micromedexsolutions.com. Accessed
September 17, 2014.
Han Y, Zhu G, Han L, et al. Short-term rosuvastatin therapy for prevention of contrastinduced acute kidney injury in patients with diabetes and chronic kidney disease. JACC
2014; 63:62-70.
Leoncini M, Toso A, Maioli M, et al. Early high-dose rosuvastatin for contrast-induced
nephropathy prevention in acute coronary syndrome : results from the PRATO-ACS study
(protective effect of rosuvastatin and antiplatelet therapy on contrast-induced acute kidney
injury and myocardial damage in patients with acute coronary syndrome). JACC 2014;
63:71-9.
Lopinavir/Ritonavir. DrugPoints Summary. Micromedex 2.0. Truven Health Analytics, Inc.
Greenwood Village, CO. Available at: http://www.micromedexsolutions.com. Accessed
September 17, 2014.
Kiser J, Gerber J, Predhomme J, et al. Drug/drug interaction between lopinavir/ritonavir and
rosuvastatin in healthy volunteers. JAIDS 2008; 47:570-8.
Stacul F. Reducing the risks for contrast-induced nephropathy. Cardiovasc Intervent Radiol
2005; 28:S12-8. doi: 10.1007/s00270-005-0197-7.
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of
antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and
Human Services. Available at
http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf. Section
accessed September 17, 2014.
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Metformin Hydrochloride. DrugPoints Summary. Micromedex 2.0. Truven Health Analytics,
Inc. Greenwood Village, CO. Available at: http://www.micromedexsolutions.com. Accessed
September 17, 2014.
Iohexol. DRUGDEX Evaluations. Micromedex 2.0. Truven Health Analytics, Inc. Greenwood
Village, CO. Available at: http://www.micromedexsolutions.com. Accessed September 17,
2014.
Joslin Diabetes Center. Oral Diabetes Medications Summary Chart. Available at:
http://www.joslin.org/info/oral_diabetes_medications_summary_chart.html. Accessed
September 17, 2014.
Repaglinide. DrugPoints Summary. Micromedex 2.0. Truven Health Analytics, Inc.
Greenwood Village, CO. Available at: http://www.micromedexsolutions.com. Accessed
September 17, 2014.
Drug Interactions. Micromedex 2.0. Truven Health Analytics, Inc. Greenwood Village,
CO. Available at: http://www.micromedexsolutions.com. Accessed September 17, 2014.
Kaletra® [package insert]. North Chicago, IL: AbbVie, Inc; 2013.
Sahali S, Chaix M, Delfraissy J, et al. Ritonavir-boosted protease inhibitor monotherapy for
the treatment of HIV-1 infection. AIDS 2008; 10:4-14.
Arribas J, Pulido F, Delgado R, et al. Lopinavir/ritonavir as single-drug therapy for
maintenance of HIV-1 viral suppression: 48-week results of a randomized, controlled, openlabel, proof-of-concept pilot clinical trial (OK study). JAIDS 2005; 40:280-7.
Bierman W, van Agtmael M, Nijhuis M, et al. HIV monotherapy with ritonavir-boosted
protease inhibitors: a systematic review. AIDS 2009; 23:279-91.