Drug Safety-related Labeling Changes (SrLC)

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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.

VIREAD (NDA-021356)

(TENOFOVIR DISOPROXIL FUMARATE)

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

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04/24/2019 (SUPPL-58)

Approved Drug Label (PDF)

8 Use in Specific Populations

8.1 Pregnancy

Risk Summary

Addition of the following:

Published studies in HBV-infected subjects do not report an increased risk of adverse pregnancy- related outcomes with the use of VIREAD during the third trimester of pregnancy.

Data

Human Data

Addition of the following:

In published data from three controlled clinical trials, a total of 327 pregnant women with chronic HBV infection were administered VIREAD from 28 to 32 weeks gestation through 1 to 2 months postpartum and followed for up to 12 months after delivery. There were no new safety findings in pregnant women compared with the known safety profile of VIREAD in HBV-infected adults. An increased risk of adverse pregnancy-related outcomes was not observed; 2 stillbirths were identified, and there was 1 major birth defect (talipes) and 1 occurrence of multiple congenital abnormalities (not further specified) in VIREAD-exposed infants. Infants were followed for up to 12 months after delivery; there were no clinically relevant drug-related safety findings in infants exposed to VIREAD during late gestation.

8.2 Lactation

Additions and/or revisions underlined:

In a study of 50 HIV-uninfected, breastfeeding women on a tenofovir-containing regimen initiated between 1 and 24 weeks postpartum (median 13 weeks), tenofovir was undetectable in the plasma of most infants after 7 days of treatment in mothers.

12/11/2018 (SUPPL-57)

Approved Drug Label (PDF)

5 Warnings and Precautions

Additions and/or revisions underlined:

5.1 Severe Acute Exacerbation of Hepatitis B in Patients with HBV Infection

All patients should be tested for the presence of chronic hepatitis B virus (HBV) before or when initiating VIREAD.

… If appropriate, resumption of anti-hepatitis B therapy may be warranted, especially in patients with advanced liver disease or cirrhosis, since posttreatment exacerbation of hepatitis may lead to hepatic decompensation and liver failure.

5.2 New Onset or Worsening Renal Impairment

… Prior to initiation and during use of VIREAD, on a clinically appropriate schedule, assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all patients. In patients with chronic kidney disease, also assess serum phosphorus.

… Persistent or worsening bone pain, pain in extremities, fractures and/or muscular pain or weakness may be manifestations of proximal renal tubulopathy and should prompt an evaluation of renal function in patients at risk of renal dysfunction.

5.4 Immune Reconstitution Syndrome

… During the initial phase of combination antiretroviral treatment, HIV-1 infected patients whose immune system responds …

5.5 Bone Loss and Mineralization Defects

Extensively changed; please refer to label for complete information.

Newly added subsection:

5.7 Risk of Adverse Reactions Due to Drug Interactions

The concomitant use of VIREAD and other drugs may result in known or potentially significant drug interactions, some of which may lead to possible clinically significant adverse reactions from greater exposures of concomitant drugs.

See Table 12 for steps to prevent or manage these possible and known significant drug interactions, including dosing recommendations. Consider the potential for drug interactions prior to and during therapy with VIREAD; review concomitant medications during therapy with VIREAD; and monitor for adverse reactions associated with the concomitant drugs.

6 Adverse Reactions

Additions and/or revisions underlined in bulleted line listing:

Severe Acute Exacerbation of Hepatitis B in Patients with HBV Infection

Immune Reconstitution Syndrome

Bone Loss and Mineralization Defects

6.1 Clinical Trials Experience

Extensively changed; please refer to label for complete information.

8 Use in Specific Populations

8.1 Pregnancy

8.2 Lactation

PLLR conversion; extensive changes. Please refer to label for complete information.

8.3 Pediatric Use

Extensive changes; please refer to label.

8.6 Renal Impairment

Additions and/or revisions underlined:

The dosing interval for VIREAD should be modified in adult patients with estimated creatinine clearance below 50 mL/min or in patients with end stage renal disease requiring dialysis.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

PATIENT COUNSELING INFORMATION

Extensively changed; please refer to label for complete information.

07/30/2018 (SUPPL-56)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.4 Coadministration with Other Products

Addition of BIKTARVY to list

7 Drug Interactions

7.1 Drugs Affecting Renal Function

Additions and/or revisions underlined:

Tenofovir is primarily eliminated by the kidneys. Coadministration of VIREAD with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir and/or the coadministered drug … Drugs that decrease renal function may increase concentrations of tenofovir …

Newly created subsection:

7.2 Established and Significant Interactions

Table 11 provides a listing of established or clinically significant drug interactions. The drug interactions described are based on studies conducted with tenofovir DF.

Table 11 Established and Significant Drug Interactions: Alteration in Dose or Regimen May Be Recommended Based on Drug Interaction Trials Newly added table, please refer to label for complete information. Includes VOSEVI clinical comments.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

PATIENT COUNSELING INFORMATION

Addition of BIKTARVY to bullet VIREAD should not be coadministered with …