Drug Safety-related Labeling Changes (SrLC)

Get Email Alerts | Guide

Drug Safety-related Labeling Changes (SrLC) Database

ANDA	Abbreviated New Drug Application
BLA	Biologics License Application
CDER	Center for Drug Evaluation and Research
MG	Medication Guide
NDA	New Drug Application
PCI	Patient Counseling Information
PI	Patient Information
PLR	Physician Labeling Rule
PLLR	Pregnancy and Lactation Labeling Rule
Italics	For the most part, italics indicate an FDA comment such as: Additions and/or revisions underlined These italics usually appear at the beginning of the section. In some cases, italics may be an inherent part of the label, and will most often appear in the body of the section.
Underlines	Any text that is underlined indicates text that has been added or revised. There are exceptions where underlining occurs in a section subtitle or heading. This is the case when there is just one word underlined in the body of the text.

Sections

BW	Box Warning
WP	Warnings and Precautions all in one section (PLR-format) Warnings as one section (pre-PLR format) Precautions as one section (pre-PLR format)
AR	Adverse Reactions (in pre-PLR format, this may be a subheading under precautions).
DI	Drug Interactions (in pre-PLR format, this may be a subheading under precautions).
USP	Use in Specific Populations (Inclusive on one or more of the following: Pregnancy; Lactation (PLLR- format); Nursing Mothers (pre-PLLR format); Females and Males of Reproductive Potential (PLLR format only); Pediatric Use, Geriatric Use, Renal Impairment, Hepatic Impairment, Sex, Race (these last six may be a subheading of precautions if label in pre-PLLR format.
PCI/PI/MG	Patient Counseling Information (PLR format only) - summarizes the information that a health care provider should convey to a patient (or caregiver when applicable) when a counseling discussion is taking place (e.g., a physician prescribing a drug during an office visit, a nurse providing discharge instructions at a hospital, or a pharmacist conveying information at a pharmacy). Patient Information - FDA approved patient labeling. Medication Guide - paper handouts that come with many prescription medicines. The guides address issues that are specific to particular drugs and drug classes, and they contain FDA-approved information that can help patients avoid serious adverse events.

Only NDAs and CDER regulated BLAs are included in this database. ANDAs are not included.

Applications that remain active, even if the product has been discontinued, undergo safety-related labeling changes.

CERDELGA (NDA-205494)

(ELIGLUSTAT TARTRATE)

Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)

Download Data

Expand all

08/29/2018 (SUPPL-3)

Approved Drug Label (PDF)

4 Contraindications

Additions and/or revisions underlined:

CERDELGA is contraindicated in the following patients based on CYP2D6 metabolizer status due to the risk of cardiac arrhythmias from prolongation of the PR, QTc, and/or QRS cardiac intervals.

EMs

Taking a strong or moderate CYP2D6 inhibitor concomitantly with a strong or moderate CYP3A inhibitor
Moderate or severe hepatic impairment
Mild hepatic impairment and taking a strong or moderate CYP2D6 inhibitor

IMs

Taking a strong or moderate CYP2D6 inhibitor concomitantly with a strong or moderate CYP3A inhibitor

Taking a strong CYP3A inhibitor

Any degree of hepatic impairment

PMs

Taking a strong CYP3A inhibitor
Any degree of hepatic impairment

5 Warnings and Precautions

Additions and/or revisions underlined:

5.1 ECG Changes and Potential for Cardiac Arrhythmias

CERDELGA is predicted to cause increases in ECG intervals (PR, QTc, and QRS) at substantially elevated eliglustat plasma concentrations and may increase the risk of cardiac arrhythmias.

Use of CERDELGA is contraindicated, to be avoided, or requires dosage adjustment in patients taking CYP2D6 or CYP3A inhibitors, depending on CYP2D6 metabolizer status, type of inhibitor, or degree of hepatic impairment.
Use of CERDELGA in patients with pre-existing cardiac conditions has not been studied during clinical trials. Avoid use of CERDELGA in patients with:
- pre-existing cardiac disease …

6 Adverse Reactions

6.1 Clinical Trials Experience

Additions and/or revisions underlined:

The adverse reaction profile of CERDELGA is based on two controlled studies, Trials 1 and 2. Table 3 presents the profile from the 9-month double-blind, randomized, placebo-controlled trial of 40 treatment-naive patients (Trial 1).

Table 3: Adverse Reactions Occurring in ?10% of Treatment-Naive GD1 Patients and More Frequently than Placebo (Trial 1) Table re-named.

Table 4: Adverse Reactions Occurring in ?5% of GD1 Patients Switching from Enzyme Replacement Therapy to CERDELGA and More Frequently than Imiglucerase (Trial 2)* Table re-numbered.

In a separate uncontrolled study, with up to 4 years of treatment in 26 naive GD1 patients …

7 Drug Interactions

Additions and/or revisions underlined:

7.1 Effect on Other Drugs on CERDELGA

Coadministration of CERDELGA with:

CYP2D6 or CYP3A inhibitors may increase eliglustat concentrations which may increase the risk of cardiac arrhythmias from prolongation of the PR, QTc, and/or QRS cardiac interval.

Strong CYP3A inducers decreases eliglustat concentrations which may reduce CERDELGA efficacy.

See Table 5 for prevention and management of interactions with drugs affecting CERDELGA. Use of CERDELGA is contraindicated, to be avoided, or may require dosage adjustment depending on the concomitant drug and CYP2D6 metabolizer status.

Table 5: Prevention and Management Strategies of Drug Interactions Affecting CERDELGA Based on CYP2D6 Metabolizer Status and Concomitant Interacting Drug Formerly Table 4

7.2 Effect of CERDELGA on Other Drugs

See Table 6 for clinically relevant interactions affecting P-gp or CYP2D6 substrates when coadministered with CERDELGA.

Table 6: Prevention and Management Strategies of Drug Interactions Affecting Other Drugs Formerly Table 5.

8 Use in Specific Populations

8.1 Pregnancy

PLLR conversion, additions and/or revisions underlined:

Risk Summary

Available data on CERDELGA use in pregnant women includes 20 pregnancies that occurred during the clinical development program and a small number of post-marketing case reports. These data are not sufficient to assess drug-associated risks major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies in pregnant rats administered oral eliglustat during organogenesis, a spectrum of various developmental abnormalities were observed at doses 6 times the recommended human dose. No adverse developmental outcomes were observed with oral administration of eliglustat to pregnant rabbits at dose levels 10 times the recommended human dose.

The estimated background risk of major birth defects and miscarriage in the indicated population is unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively …

Data

Animal data

… (about 10 times the recommended human dose based on body surface area) following administration of eliglustat during the period of organogenesis (gestation days 6 to 17 in the rat and 6 to 18 in the rabbit) …

… (abnormal number of ribs or lumbar vertebra). Eliglustat-related effects on fetal rats were observed in association with signs of maternal toxicity.

… based on body surface area). Mild maternal toxicity was observed at the 100 mg/kg/day dose.

In a pre and postnatal development study in rats (dosed daily from gestation day 6 to postpartum day 21), eliglustat …

8.2 Lactation

PLLR conversion, additions and/or revisions underlined:

Risk Summary

There are no human data available on the presence of eliglustat in human milk, the effects on the breastfed infant, or the effects on milk production. Eliglustat and its metabolites were present in the milk of lactating rats (see Data). When a drug is present in animal milk, it is likely that the drug will be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for CERDELGA and any potential adverse effects on the breastfed child from CERDELGA or from the underlying maternal condition.

Data

In a milk excretion study in the rat, a single oral dose of 30 mg/kg [14C]-labeled eliglustat was administered to lactating female rats at day 11 postpartum. Approximately 0.23% of the administered radioactivity was excreted into the milk within 24 hours of dose administration. The concentration in the milk at 24 hours post dose was 16.3-fold higher than the plasma concentration.

8.6 Renal Impairment

Additions and/or revisions underlined:

Use CERDELGA in patients with renal impairment based on the patient’s CYP2D6 metabolizer status.

EMs

Avoid CERDELGA in patients with end-stage renal disease (ESRD) (estimated creatinine clearance (eCLcr) less than 15 mL/min not on dialysis or requiring dialysis).
No dosage adjustment is recommended in patients with mild, moderate, or severe renal impairment (eCLcr at least 15 mL/min).

IMs and PMs

Avoid CERDELGA in patients with any degree of renal impairment.

8.7 Hepatic Impairment

Additions and/or revisions underlined:

Use CERDELGA in patients with hepatic impairment based on CYP2D6 metabolizer status and

concomitant use of CYP2D6 or CYP3A inhibitors

EMs

CERDELGA is contraindicated in patients with:
- severe (Child-Pugh Class C) hepatic impairment
- moderate (Child-Pugh Class B) hepatic impairment
- mild (Child-Pugh Class A) hepatic impairment taking a strong or moderate CYP2D6 inhibitor
Reduce dosage frequency of CERDELGA 84 mg to once daily in patients with mild hepatic impairment taking:
- a weak CYP2D6 inhibitor
- a strong, moderate, or weak CYP3A inhibitor
- No dosage adjustment is recommended in patients with mild hepatic impairment, unless otherwise specified above.

IMs and PMs

CERDELGA is contraindicated in patients with any degree of hepatic impairment