Subject: FDA approved changes to the SUSTIVA label
From: "U.S. Food & Drug Administration (FDA)" <fda@xxxxxxxxxxxxxxxxxxxxxxx>
Date: Wed, 07 Sep 2016 15:51:31 -0500
Title: FDA approved changes to the SUSTIVA label
Informationabout FDA HIV product approvals, safety warnings, medical product labeling changes, notices of upcoming public meetings, and notices about proposed regulatory guidances.
FDA recently approved changes to the SUSTIVA (efavirenz)
product labeling to include a new Warnings and Precautions regarding QTc
prolongation. The following main changes to the product labeling were made:
The following sub-section was added in the
WARNINGS AND PRECAUTIONS section.
5.2QTc Prolongation: QTc prolongation has been observed with the use of efavirenz
[see Drug Interactions (7.3, 7.4) and Clinical Pharmacology (12.2)]. Consider
alternatives to SUSTIVA when co-administered with a drug with a known risk of
Torsade de Pointes or when administered to patients at higher risk of Torsade
de Pointes.
The following new sub-section was added in the DRUG
INTERACTIONS section.
7.3QT Prolonging Drugs: There is limited information available on the
potential for a pharmacodynamic interaction between SUSTIVA and drugs that
prolong the QTc interval. QTc prolongation has been observed with the use of
efavirenz [see Clinical Pharmacology (12.2)]. Consider alternatives to SUSTIVA
when co-administered with a drug with a known risk of Torsade de Pointes.
Revisions were made in Table 5 and subsection
7.5 for Drugs Without Clinically Significant Interactions with SUSTIVA.
Specifically the clinical comment
for Anti-infective: Clarithromycin now states: Consider alternatives to macrolide antibiotics because of the risk of QT
interval prolongation. Likewise for Antimalarials: Artemether/lumefantrine the
clinical comment states: Consider alternatives to artemether/ lumefantrine
because of the risk of QT interval prolongation.
The following new sub-section was added in the Clinical Pharmacology section.
12.2 Pharmacodynamics-Cardiac Electrophysiology: The effect of SUSTIVA on the QTc
interval was evaluated in an open-label, positive and placebo controlled, fixed
single sequence 3-period, 3-treatment crossover QT study in 58 healthy subjects
enriched for CYP2B6 polymorphisms. The mean Cmax of efavirenz in subjects with
CYP2B6 *6/*6 genotype following the administration of 600 mg daily dose for 14
days was 2.25-fold the mean Cmax observed in subjects with CYP2B6 *1/*1
genotype. A positive relationship between efavirenz concentration and QTc
prolongation was observed. Based on the concentration-QTc relationship, the
mean QTc prolongation and its upper bound 90% confidence interval are 8.7 ms
and 11.3 ms in subjects with CYP2B6*6/*6 genotype following the administration
of 600 mg daily dose for 14 days [see Warnings and Precautions (5.2)].
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