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.

JYNARQUE (NDA-204441)

(TOLVAPTAN)

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

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09/15/2026 (SUPPL-16)

Approved Drug Label (PDF)

Boxed Warning

Additions and/or revisions underlined:

WARNING: RISK OF SERIOUS LIVER INJURY

JYNARQUE (tolvaptan) can cause serious and potentially fatal liver injury. Acute liver failure requiring liver transplantation has been reported [see Warnings and Precautions (5.1)].

Measure ALT, AST and bilirubin before initiating treatment, at 2 weeks and 4 weeks after initiation, then monthly for the first 18 months and every 3 months thereafter [see Warnings and Precautions (5.1)]. Prompt action in response to laboratory abnormalities, signs, or symptoms indicative of hepatic injury can mitigate, but not eliminate, the risk of serious hepatotoxicity.

Because of the risks of serious liver injury, JYNARQUE is available only through a restricted distribution program under a Risk Evaluation and Mitigation Strategy (REMS) called the Tolvaptan for ADPKD Shared System REMS [see Warnings and Precautions (5.2)].

5 Warnings and Precautions

5.2 Tolvaptan for ADPKD Shared System REMS

Subsection title revised

Additions and/or revisions underlined:

JYNARQUE is available only through a restricted distribution program under a Risk Evaluation and Mitigation Strategy (REMS) called the Tolvaptan for ADPKD Shared System REMS, because of the risks of liver injury [see Warnings and Precautions (5.1)].

Notable requirements of the Tolvaptan for ADPKD Shared System REMS include the following:

Prescribers must be certified by enrolling in the REMS program.
Prescribers must inform patients receiving JYNARQUE about the risk of hepatotoxicity associated with its use and how to recognize the signs and symptoms of hepatotoxicity and the appropriate actions to take if it occurs.
Patients must enroll in the REMS program and comply with ongoing monitoring requirements.
Pharmacies must be certified by enrolling in the REMS program and must only dispense to patients who are authorized to receive JYNARQUE.

Further information, including a list of qualified pharmacies/distributors, is available at www.TolvaptanADPKDSharedREMS.com or by telephone at 1-866-244-9446.

6 Adverse Reactions

6.2 Postmarketing Experience

Additions and/or revisions underlined:

The following adverse reactions have been identified during post-approval use of tolvaptan. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Hepatobiliary Disorders: Liver failure requiring transplant

Immune System Disorders: Anaphylaxis

Investigations: Blood creatine phosphokinase increased

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

MEDICATION GUIDE

Additions and/or revisions underlined:

…

Because of the risk of serious liver problems JYNARQUE is only available through a restricted distribution program called the Tolvaptan for ADPKD Shared System REMS.

Before you start treatment with JYNARQUE, you must enroll in the Tolvaptan for ADPKD Shared System REMS. Talk to your healthcare provider about how to enroll in the program.

JYNARQUE can only be dispensed by a certified pharmacy that participates in the Tolvaptan for ADPKD Shared System REMS. Your healthcare provider can give you information on how to find a certified pharmacy.

…

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

…

Tolvaptan for ADPKD Shared System REMS

Advise patients that JYNARQUE is only available through a restricted program called the Tolvaptan for ADPKD Shared System REMS [see Warnings and Precautions (5.2)]. Inform the patient of the following notable requirement:

Patients must enroll in the program and comply with ongoing monitoring requirements [see Warnings and Precautions (5.2)]

Advise patients that JYNARQUE is only available only through restricted distribution from certified specialty pharmacies participating in the Tolvaptan for ADPKD Shared System REMS. Therefore, provide patients with the telephone number and web site for information on how to obtain the product [see Warnings and Precautions (5.2)].

…