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.

TRIKAFTA (COPACKAGED) (NDA-217660)

(ELEXACAFTOR, IVACAFTOR, TEZACAFTOR; IVACAFTOR)

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

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03/27/2026 (SUPPL-8)

Approved Drug Label (PDF)

8 Use in Specific Populations

8.4 Pediatric Use

Additions and/or revisions underlined:

The safety and effectiveness of TRIKAFTA for the treatment of CF have been established in pediatric patients aged 2 years and older who have a clinical diagnosis of CF and who have at least one variant in the CFTR gene that is either responsive based on clinical and/or in vitro data or results in production of CFTR protein.

Use of TRIKAFTA for this indication for pediatric patients 12 years of age and older was supported by evidence from two adequate and well-controlled studies (Trials 1 and 2) in CF patients aged 12 years and older [see Adverse Reactions (6.1) and Clinical Studies (14)].

…

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

MEDICATION GUIDE

Additions and/or revisions underlined:

…

What is TRIKAFTA?

TRIKAFTA is a prescription medicine for people aged 2 years and older who have a diagnosis of cystic fibrosis (CF) and who have at least one genetic change (variant) in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that is either responsive to TRIKAFTA or results in the production of protein.
Talk to your healthcare provider to learn if you have an indicated CF gene variant.

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How should I take TRIKAFTA?

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To prepare TRIKAFTA oral granules:
- Hold the packet with the cut line on top.
- Shake the packet gently to settle the TRIKAFTA oral granules.
- Tear or cut the packet open along the cut line.
- Carefully pour all the TRIKAFTA oral granules in the packet into 1 teaspoon (5 mL) of soft food or liquid in a small container (like an empty bowl). Look inside the sachet to make sure there are no granules left inside. The food or liquid should be at or below room temperature. Some examples of soft foods or liquids include pureed fruits or vegetables, yogurt, applesauce, water, milk, or juice.
- Mix the TRIKAFTA granules with food or liquid.
- After mixing, give TRIKAFTA within 1 hour. Make sure all the medicine is taken.

…

03/17/2026 (SUPPL-10)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.4Neuropsychiatric Events, Including Suicidal Thoughts and Behaviors

Newly added subsection:

Serious neuropsychiatric events, including symptoms of anxiety, depression, suicidal ideation and behavior, and sleep disturbances, have been reported in the postmarketing setting in patients taking TRIKAFTA or drugs containing the same or similar active ingredients [see Adverse Reactions (6.2)]. The events were reported in adult and pediatric patients with and without a previous history of neuropsychiatric symptoms. Symptoms may occur within the first three months of treatment initiation.

Assess patients for baseline neuropsychiatric symptoms and monitor for new or worsening symptoms of anxiety, depression, suicidal ideation or behavior, or sleep disturbances. Consider the benefits and risks for the individual patient to determine if therapy with TRIKAFTA should be interrupted at the occurrence of neuropsychiatric symptoms and whether to resume therapy with symptom improvement.

6 Adverse Reactions

Addition of the following to the bulleted line listing:

Neuropsychiatric Events, Including Suicidal Thoughts and Behaviors [see Warnings and Precautions (5.4)]
6.2 Postmarketing Experience
The following adverse reactions have been identified during postapproval use of TRIKAFTA or drugs containing the same or similar active ingredients as TRIKAFTA. 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.
…
Psychiatric Disorders: anxiety, depression, suicidal ideation and behavior, insomnia

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

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

…

Neuropsychiatric Events, Including Suicidal Thoughts and Behaviors

Inform patients that neuropsychiatric symptoms, including anxiety, depression, suicidal thoughts and behaviors, and sleep disturbances (e.g., insomnia), have been reported with the use of TRIKAFTA or drugs containing the same or similar active ingredients as TRIKAFTA. The symptoms have been observed in patients with and without a history of similar symptoms and may occur within three months of TRIKAFTA initiation. Instruct patients to contact their healthcare provider immediately if changes in behavior or thinking that are not typical for the patient occur, or if the patient develops suicidal ideation or behavior [see Warnings and Precautions (5.4)].

…

PATIENT INFORMATION

Additions and/or revisions underlined:

What should I tell my healthcare provider before taking TRIKAFTA?

Before taking TRIKAFTA, tell your healthcare provider about all of your medical conditions, including if you:

…

have or have had mental health problems.
…
What are the possible or reasonably likely side effects of TRIKAFTA?
TRIKAFTA can cause serious side effects, including:
…

Serious mental health problems such as anxiety, depression, suicidal thoughts and behaviors, and trouble sleeping have happened in people treated with TRIKAFTA or medicines containing the same or similar ingredients as TRIKAFTA. If you experience new or worsening mental health problems, call your healthcare provider right away.
…

09/25/2025 (SUPPL-9)

5 Warnings and Precautions

5.3 Intracranial Hypertension

Newly added subsection:

Cases of intracranial hypertension (IH) have been reported in the postmarketing setting with the use of TRIKAFTA [see Adverse Reactions (6.2)]. Clinical manifestations of IH include headache, blurred vision, diplopia, and potential vision loss; papilledema can be found on fundoscopy. If an unusual headache or visual disturbances occur during treatment, and IH is suspected, interrupt TRIKAFTA and refer for prompt medical evaluation. Consider the benefits and risks for the individual patient to determine whether to resume treatment with TRIKAFTA. Patients should be monitored until IH resolution and for recurrence. Patients with elevated vitamin A levels may be at increased risk.

6 Adverse Reactions

Addition of the following to the bulleted line listing:

Intracranial Hypertension [see Warnings and Precautions (5.3)]
6.2 Postmarketing Experience
Additions and/or revisions underlined:
…
Nervous System Disorders: intracranial hypertension

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

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

…

Intracranial Hypertension

Inform patients that intracranial hypertension has occurred with the use of TRIKAFTA. Instruct patients to notify their healthcare provider right away if they experience signs and symptoms of intracranial hypertension, including headache, blurred vision, diplopia, and vision loss [see Warnings and Precautions (5.3)].

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MEDICATION GUIDE

Additions an/or revisions underlined:

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What are the possible or reasonably likely side effects of TRIKAFTA?

TRIKAFTA can cause serious side effects, including:

…

Increased pressure around the brain (intracranial hypertension) has happened in people treated with TRIKAFTA. If you experience an unusual headache, blurred vision, double vision, or vision loss, call your healthcare provider right away.
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12/20/2024 (SUPPL-3)

Approved Drug Label (PDF)

6 Adverse Reactions

6.1 Clinical Trials Experience

Extensive changes; please refer to label

8 Use in Specific Populations

8.4 Pediatric Use

Additions and revisions underlined:

The safety and effectiveness of TRIKAFTA for the treatment of CF have been established in pediatric patients aged 2 to less than 18 years who have at least one F508del mutation in the CFTR gene or a mutation in the CFTR gene that is responsive based on clinical and/or in vitro data. Use of TRIKAFTA for this indication for pediatric patients 12 years of age and older was supported by evidence from two adequate and well-controlled studies (Trials 1 and 2) in CF patients aged 12 years and older [see Adverse Reactions (6.1) and Clinical Studies (14)].

Use of TRIKAFTA for this indication in pediatric patients 2 to less than 12 years of age is based on the following:

. . .

Trial 5, 64 pediatric patients aged 6 years to less than 18 years who had a least one qualifying non-F508del TRIKAFTA-responsive mutation and did not have an exclusionary mutation [see Adverse Reactions (6) and Clinical Studies (14.2)].

08/03/2023 (SUPPL-2)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.2 Hypersensitivity Reactions, Including Anaphylaxis

New subsection added:

Hypersensitivity reactions, including cases of angioedema and anaphylaxis, have been reported in the postmarketing setting [see Adverse Reactions (6.2)]. If signs or symptoms of serious hypersensitivity reactions develop during treatment, discontinue TRIKAFTA and institute appropriate therapy. Consider the benefits and risks for the individual patient to determine whether to resume treatment with TRIKAFTA.

6 Adverse Reactions

Addition of the following to the bulleted line listing:

Hypersensitivity Reactions, Including Anaphylaxis [see Warnings and Precautions (5.2)]
6.2 Postmarketing Experience
Additions and/or revisions underlined:
…
Hepatobiliary: Liver failure leading to transplantation in a patient with pre-existing cirrhosis and portal hypertension. Liver injury characterized by concomitant transaminase (ALT and AST) and total bilirubin elevations [see Warnings and Precautions (5.1)].
Immune System Disorders: anaphylaxis, angioedema

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

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

…

Hypersensitivity Reactions, Including Anaphylaxis

Hypersensitivity reactions including angioedema and anaphylaxis are possible with use of TRIKAFTA. Inform patients of the early signs of hypersensitivity reactions including rash, hives, itching, facial swelling, tightness of the chest and wheezing. Advise patients to discontinue use of TRIKAFTA immediately and contact their physician or go to the emergency department if these symptoms occur.

…

PATIENT INFORMATION

Additions and/or revisions underlined:

Before taking TRIKAFTA, tell your doctor about all of your medical conditions, including if you:

are allergic to TRIKAFTA or any ingredients in TRIKAFTA. See the end of this patient information leaflet for a complete list of ingredients in TRIKAFTA.
…
What are the possible side effects of TRIKAFTA?
TRIKAFTA can cause serious side effects, including:
…

Serious Allergic Reactions can happen to people who are treated with TRIKAFTA. Call your healthcare provider or go to the emergency room right away if you have any symptoms of an allergic reaction. Symptoms of an allergic reaction may include:
- rash or hives
- tightness of the chest or throat or difficulty breathing
- swelling of the face, lips and/or tongue, difficulty swallowing
- light-headedness or dizziness
  …