Selzentry (Maraviroc) 150 mg and 300 mg Tablets, Labeling Changes for Patients With Renal Impairment
June 1, 2010
On May 27, 2010, FDA approved changes to the labeling for Selzentry (maraviroc) 150 mg and 300 mg tablets to expand the patient population to include dosing recommendations for patients with renal impairment, add a contraindication for patients with severe renal impairment or end-stage renal disease, add a warning regarding postural hypotension for renal impaired patients, and add new Pharmacokinetics information related to renal impairment, including the following highlights:
Section 2.2 Dose Recommendations for Patients with Renal Impairment was added to provide dosing recommendations for patients based on renal function and concomitant medications.
Section 4 Contraindications was updated to state SELZENTRY should not be used in patients with severe renal impairment or end-stage renal disease (ESRD) (CrCl < 30 mL/min) who are taking potent CYP3A inhibititors or inducers
Under 5.2 Cardiovascular Events
Postural Hypotension in Patients with Renal Impairment
Under 8.6 Renal Impairment
Recommended doses of SELZENTRY for patients with impaired renal function (CrCl = 80 mL/min) are based on the results of a pharmacokinetic study conducted in healthy subjects with various degrees of renal impairment. The pharmacokinetics of maraviroc in subjects with mild and moderate renal impairment was similar to that in subjects with normal renal function [see Clinical Pharmacology (12.3)]. A limited number of subjects with mild and moderate renal impairment in the Phase 3 clinical trials (n= 131 and n= 12, respectively) received the same dose of SELZENTRY as that administered to subjects with normal renal function. In these subjects there was no apparent difference in the adverse event profile for maraviroc compared to subjects with normal renal function.
If patients with severe renal impairment or end-stage renal disease (ESRD) not receiving a concomitant potent CYP3A inhibitor or inducer experience any symptoms of postural hypotension while taking SELZENTRY 300 mg twice daily, the dose should be reduced to 150 mg twice daily. No studies have been performed in subjects with severe renal impairment or ESRD co-treated with potent CYP3A inhibitors or inducers. Hence, no dose of SELZENTRY can be recommended, and SELZENTRY is contraindicated for these patients. [see Dosage and Administration (2.2), Contraindications (4), Warnings and Precautions (5.2), and Clinical Pharmacology (12.3)].
Under 12.3 Pharmacokinetics
In addition, the study compared the pharmacokinetics of multiple dose SELZENTRY in combination with saquinavir/ritonavir 1000/100 mg twice daily (a potent CYP3A inhibitor combination) for 7 days in subjects with mild renal impairment (CLcr >50 and £80 mL/min, n=6) and moderate renal impairment (CLcr ³30 and £50 mL/min, n=6) to healthy volunteers with normal renal function (n=6). Subjects received 150 mg of SELZENTRY at different dose frequencies (healthy volunteers -- every 12 hours; mild renal impairment -- every 24 hours; moderate renal impairment -- every 48 hours). Compared to healthy volunteers (dosed every 12 hours), geometric mean ratios for maraviroc AUCtau, Cmax and Cmin were 50% higher, 20% higher and 43% lower, respectively for subjects with mild renal impairment (dosed every 24 hours). Geometric mean ratios for maraviroc AUCtau, Cmax and Cmin were 16% higher, 29% lower and 85% lower, respectively for subjects with moderate renal impairment (dosed every 48 hours) compared to healthy volunteers (dosed every 12 hours). Based on the data from this study, no adjustment in dose is recommended for patients with mild or moderate renal impairment [see Dosage and Administration (2.2)].
In addition, the Medication Guide for patients has been modified to include the following information:
Who should not take SELZENTRY?
People with severe kidney problems or who are on hemodialysis and are taking certain other medications should not take SELZENTRY. Talk to your healthcare provider before taking this medicine if you have kidney problems.
The complete revised labeling will be available soon on the FDA website at www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Label_ApprovalHistory
This article was provided by U.S. Food and Drug Administration. Visit the FDA's website to find out more about their activities and publications.
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