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.

HARVONI (NDA-212477)

(LEDIPASVIR; SOFOSBUVIR)

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

Download Data

Expand all

12/19/2024 (SUPPL-6)

Approved Drug Label (PDF)

6 Adverse Reactions

6.1 Clinical Trials Experience

Newly added information:

In a 5-year follow-up study, 178 of the 226 subjects from the Phase 2 open-label clinical trial (Study 1116) were followed for a median (Q1, Q3) duration of 239 (143, 244) weeks. No notable effects on growth as assessed by changes from baseline through end of study were observed for height, weight, BMI percentiles, and Z-scores for any age group. No notable effects were observed on the development of secondary sexual characteristics of subjects as assessed by changes from baseline through end of study in Tanner pubertal stages [see Use in Specific Populations (8.4)].

8 Use in Specific Populations

8.4 Pediatric Use

Newly added information:

In a 5-year follow-up study, the long-term effects of HARVONI on pediatric growth were assessed in 178 pediatric subjects 3 years of age and older treated with HARVONI in Study 1116. No notable effects on growth from baseline through end of study were observed [see Adverse Reactions (6.1)]. All subjects who had achieved SVR12 maintained SVR through end of study.

03/05/2020 (SUPPL-3)

Approved Drug Label (PDF)

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

PATIENT COUNSELING INFORMATION

(Newly added information)

Hepatitis C Virus Transmission

Inform patients that the effect of treatment of hepatitis C infection on transmission is not

known, and that appropriate precautions to prevent transmission of the hepatitis C virus

during treatment or in the event of treatment failure should be taken.

For HARVONI oral pellets, advise patients or caregivers to read and follow the

Instructions for Use for preparing the correct dose.

Patient Information

(Newly added information)

See the detailed Instructions for Use for information about how to give or take a dose of HARVONI oral

pellets.

11/15/2019 (SUPPL-2)

Approved Drug Label (PDF)

6 Adverse Reactions

6.1 Clinical Trials Experience

(additions underlined)

…

Adverse Reactions in Adults with Severe Renal Impairment, Including those on Dialysis

In an open-label trial (Trial 0154) in which adults with HCV with compensated liver disease (with or without cirrhosis) and severe renal impairment received HARVONI for 12 weeks (N=18), the most common adverse reaction was fatigue (17%) .

In an open-label clinical trial, Trial 4063, a total of 95 adults with HCV with compensated liver disease (with or without cirrhosis) and ESRD requiring dialysis received HARVONI for 8 (n=45), 12 (n=31), or 24 (n=19) weeks. The most common adverse reactions were insomnia and headache (each reported in 4% of subjects overall).

…

7 Drug Interactions

7.3 Drugs without Clinically Significant Interactions with HARVONI

(addition underlined)

Based on drug interaction studies conducted with the components of HARVONI (ledipasvir or sofosbuvir) or HARVONI, no clinically significant drug interactions have been either observed or are expected when HARVONI is used with the following drugs: abacavir, atazanavir/ritonavir, cyclosporine, darunavir/ritonavir, dolutegravir, efavirenz, elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide, emtricitabine, lamivudine, methadone, midazolam, oral contraceptives, pravastatin, raltegravir, rilpivirine, tacrolimus, or verapamil. See Table 6 for use of HARVONI with certain HIV antiretroviral regimens.

8 Use in Specific Populations

8.4 Pediatric Use

(additions underlined)

…

In patients with severe renal impairment, including those requiring dialysis, exposures of GS-331007, the inactive metabolite of sofosbuvir, are increased . No data are available regarding the safety of HARVONI in pediatric patients with renal impairment.

…

8.6 Renal Impairment

(additions underlined)

No dosage adjustment of HARVONI is recommended for patients with mild, moderate, or severe renal impairment, including ESRD requiring dialysis. No safety data are available in subjects with both decompensated cirrhosis and severe renal impairment, including those on dialysis.

Additionally, no safety data are available in pediatric patients with renal impairment. Refer to ribavirin tablet prescribing information regarding use in patients with renal impairment.

09/19/2019 (SUPPL-1)

Approved Drug Label (PDF)

7 Drug Interactions

7.2 Established and Potentially Significant Drug Interactions

(additions underlined)

Clearance of HCV infection with direct acting antivirals may lead to changes in hepatic function, which may impact the safe and effective use of concomitant medications. For example, altered blood glucose control resulting in serious symptomatic hypoglycemia has been reported in diabetic patients in postmarketing case reports and published epidemiological studies. Management of hypoglycemia in these cases required either discontinuation or dose modification of concomitant medications used for diabetes treatment.

Frequent monitoring of relevant laboratory parameters (e.g. International Normalized Ratio [INR] in patients taking warfarin, blood glucose levels in diabetic patients) or drug concentrations of concomitant medications such as cytochrome P450 substrates with a narrow therapeutic index (e.g. certain immunosuppressants) is recommended to ensure safe and effective use. Dose adjustments of concomitant medications may be necessary.

Table 6 provides a listing of established or potentially clinically significant drug interactions. The drug interactions described are based on studies conducted with either HARVONI, the components of HARVONI (ledipasvir and sofosbuvir) as individual agents, or are predicted drug interactions that may occur with HARVONI.

(please refer to label to view Table 6)