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.

VONJO (NDA-208712)

(PACRITINIB CITRATE)

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

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10/01/2025 (SUPPL-4)

Approved Drug Label (PDF)

8 Use in Specific Populations

8.6 Hepatic Impairment

Additions and/or revisions underlined:

In patients with severe hepatic impairment [Child-Pugh C], the recommended dosage of VONJO is 100 mg twice daily. Dosage may be increased to 200 mg twice daily if the treatment is not effective after 12 weeks and there are no safety concerns. Monitor hepatically-impaired patients for adverse reactions and consider VONJO dose modifications based on safety and efficacy[see Dosage and Administration (2.5), Clinical Pharmacology (12.3)].

No dose modification is recommended for patients with mild [Child-Pugh A] or moderate [Child-Pugh B] hepatic impairment [see Clinical Pharmacology (12.3)].

08/22/2025 (SUPPL-6)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.2 Diarrhea

Additions and/or revisions underlined:

VONJO caused diarrhea in approximately 48% of patients compared to 15% of patients treated on the control arm in a clinical trial. The median time to resolution in VONJO-treated patients was 2 weeks. The incidence of reported diarrhea decreased over time with 41% of patients reporting diarrhea in the first 8 weeks of treatment, 15% in Weeks 8 through 16, and 8% in Weeks 16 through 24.Diarrhea resulted in treatment interruption in 3% of VONJO-treated patients. Serious diarrhea adverse reactions occurred in 2% of patients treated with VONJO compared to no such adverse reactions in patients in the control arm. In postmarketing reports, severe diarrhea leading to acute kidney injury and treatment discontinuation has been reported with VONJO.

Control pre-existing diarrhea before starting VONJO treatment. Manage diarrhea with antidiarrheal medications, fluid replacement, and dose-modification.

Upon initiation of therapy, prescribe an anti-diarrheal medication (e.g., loperamide), and instruct patients to treat diarrhea promptly at the first onset of symptoms (change in frequency or consistency of bowel movements) after starting VONJO. Interrupt or reduce VONJO dose in patients with significant diarrhea despite optimal supportive care [see Dosage and Administration (2.5)].

6 Adverse Reactions

6.2 Postmarketing Experience

Newly added subsection:

The following adverse reactions have been identified during post-approval use of VONJO. 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:

Renal: Acute or subacute kidney injury (secondary to diarrhea) [see Warnings and Precautions (5.2)]

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

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

…

Diarrhea

Advise patients that VONJO can cause diarrhea. Advise patients to stay hydrated while taking VONJO and to inform their physician if they experience diarrhea. Instruct patients to initiate antidiarrheal medication promptly at the first onset of symptoms (increase in frequency or change in consistency of bowel movements [loosening]) after starting VONJO. Advise patients to urgently seek emergency medical attention if diarrhea becomes severe [see Warnings and Precautions (5.2)].

…

PATIENT INFORMATION

Additions and/or revisions underlined:

…

What are the possible side effects of VONJO?

VONJO can cause serious side effects including:

…

Diarrhea. Diarrhea is common with VONJO, but can also be severe, and cause loss of too much body fluid (dehydration). Dehydration can lead to kidney problems. Tell your healthcare provider if you develop diarrhea during treatment with VONJO. Drink plenty of fluids to help prevent dehydration. Your healthcare provider will prescribe an anti-diarrheal medicine before you start VONJO. You should start taking the anti-diarrheal medicine right away if you get any symptoms of diarrhea, including any changes in consistency (such as loose stools) or increase in the number of daily bowel movements, during treatment with VONJO. Get emergency medical help right away if your diarrhea becomes severe.
…

11/12/2024 (SUPPL-3)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.9 Interactions With CYP3A4 Inhibitors or Inducers

Additions and revisions underlined:

Co-administration of VONJO with strong CYP3A4 inhibitors or inducers is contraindicated. Monitor for increased adverse reactions of VONJO when administered with moderate CYP3A4 inhibitors [see Contraindications (4), Drug Interactions (7.1), and Clinical Pharmacology (12.3)].

7 Drug Interactions

7.1 Effect of Other Drugs on VONJO

Additions and revisions underlined:

Strong and Moderate CYP3A4 Inhibitors

Pacritinib is predominantly metabolized by CYP3A4. Concomitant use of VONJO with strong and moderate CYP3A4 inhibitors increases pacritinib exposure, which may increase the risk of exposure-related adverse reactions [see Clinical Pharmacology (12.3)].

Co-administration of VONJO with strong CYP3A4 inhibitors is contraindicated [see Contraindications (4), Warnings and Precautions (5.4)].

Monitor patients concomitantly receiving moderate CYP3A4 inhibitors (e.g., fluconazole) for increased adverse reactions and consider VONJO dose modifications based on safety [see Dose Modifications for Adverse Reactions (2.5)]. Concomitant use of VONJO with doses of fluconazole greater than 200 mg once daily has not been studied.

Strong CYP3A4 Inducers

Pacritinib is predominantly metabolized by CYP3A4. Concomitant use of VONJO with strong CYP3A4 inducers decreases pacritinib exposure, which may reduce efficacy of VONJO [see Clinical Pharmacology (12.3)].

Co-administration of VONJO with strong CYP3A4 inducers is contraindicated [see Contraindications (4)].

7.2 Effect of VONJO on Other Drugs

Additions and revisions underlined:

CYP1A2 Substrates

Pacritinib is an inhibitor of CYP1A2. VONJO increases the plasma concentrations of CYP1A2 substrates [see Clinical Pharmacology (12.3)], which may increase the risk of adverse reactions from the CYP1A2 substrate.

Monitor for CYP1A2 substrate related adverse reactions more frequently, unless otherwise recommended in the substrate Prescribing Information, when VONJO is used concomitantly with CYP1A2 substrates where minimal substrate concentration changes may lead to serious adverse reactions.

CYP2C19 Substrates

Pacritinib is an inducer of CYP2C19. VONJO decreases the plasma concentrations of CYP2C19 substrates [see Clinical Pharmacology (12.3)], which may decrease the efficacy from the CYP2C19 substrate.

Monitor the efficacy of CYP2C19 substrate more frequently, unless otherwise recommended in the substrate Prescribing Information, when VONJO is used concomitantly with CYP2C19 substrates where minimal substrate concentration changes may lead to diminished efficacy. Dose adjustment of CYP2C19 substrates may be needed.

CYP3A4 Substrates

Pacritinib is an inducer of CYP3A4. VONJO decreases the plasma concentrations of CYP3A4 substrates [see Clinical Pharmacology (12.3)], which may decrease the efficacy from the CYP3A4 substrate.

Monitor the efficacy of CYP3A4 substrate more frequently, unless otherwise recommended in the substrate Prescribing Information, when VONJO is used concomitantly with CYP3A4 substrates where minimal substrate concentration changes may lead to diminished efficacy. Dose adjustment of CYP3A4 substrates may be needed.

Hormonal Contraceptives

Avoid concomitant use of VONJO with hormonal contraceptives except for intrauterine systems containing levonorgestrel. The effectiveness of hormonal contraceptives, except for intrauterine systems containing levonorgestrel, may be reduced when used with VONJO.

If contraception is needed or desired, an alternate contraceptive that is not affected by CYP3A4 inducers (e.g., an intrauterine system) or additional nonhormonal contraceptive (e.g., condoms) should be used when treated concomitantly with VONJO, and for 30 days after last dose of VONJO.

P-gp Substrates

Pacritinib is an inhibitor of P-gp. VONJO increases the plasma concentrations of P-gp substrates [see Clinical Pharmacology (12.3)], which may increase the risk of adverse reactions from the P-gp substrate.

Monitor for P-gp substrate related adverse reactions more frequently, unless otherwise recommended in the substrate Prescribing Information, when VONJO is used concomitantly with P-gp substrates where minimal substrate concentration changes may lead to serious adverse reactions.

Digoxin: Measure serum digoxin concentrations before initiating concomitant use with VONJO and continue monitoring serum digoxin concentrations as recommended in the Prescribing Information for digoxin [see Clinical Pharmacology (12.3)].

BCRP substrates

Pacritinib is an inhibitor of BCRP. VONJO increases the plasma concentrations of BCRP substrates [see Clinical Pharmacology (12.3)], which may increase the risk of adverse reactions from the BCRP substrate.

When used concomitantly with VONJO, monitor for BCRP substrate related adverse reactions more frequently and consider dose reduction of the BCRP substrate according to its Prescribing Information.

Rosuvastatin: The dose of rosuvastatin should not exceed 20 mg once daily when concomitantly used with VONJO [see Clinical Pharmacology (12.3)].

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

PATIENT COUNSELING INFORMATION

Newly added information:

Inform women of the possible reduced effectiveness of hormonal contraceptives when under treatment with VONJO and for 30 days after last dose. Advise women of childbearing potential receiving VONJO and hormonal contraception, to use additional nonhormonal contraception or use an alternative contraceptive that is not affected by CYP3A4 inducers [see Drug Interactions (7.2)].

Patient Information

Additions and revisions underlined:

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

have active bleeding, have had severe bleeding, or plan to have surgery or invasive procedures. You should stop taking VONJO 7 days before any planned surgery or invasive procedures. See “What are the possible side effects of VONJO?”
have diarrhea or commonly have loose stools
have had a blood clot, heart attack, other heart problems, or stroke
have a history of low blood levels of potassium. It is important that you get blood tests done during treatment with VONJO to monitor your body salts (electrolytes).
smoke or were a smoker in the past
have had any other cancers. See “What are the possible side effects of VONJO?”
have an infection. See “What are the possible side effects of VONJO?”
have nausea or vomiting
have liver or kidney problems
are pregnant or plan to become pregnant. It is not known if VONJO will harm your unborn baby.
are breastfeeding or plan to breastfeed. It is not known if VONJO passes into your breast milk. You should not breastfeed during treatment and for 2 weeks after your last dose of VONJO. Talk to your healthcare provider about the best way to feed your baby during this time.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Taking VONJO with certain other medicines may affect the amount of VONJO or the other medicines in your blood and may increase your risk of side effects or affect how well VONJO works.
Especially tell your healthcare provider if you take hormonal contraceptives (birth control). Hormonal birth
control methods, except for intrauterine systems containing levonorgestrel may not work during treatment with VONJO and for 30 days after your last dose. Talk to your healthcare provider about birth control methods that may be right for you during treatment with VONJO.

. . .

VONJO can cause serious side effects including:

Bleeding. VONJO can cause severe bleeding, which can be serious and, in some cases may lead to death.
- Stop taking VONJO and tell your healthcare provider right away if you develop any of these symptoms: unusual bleeding, bruising, and fever. Get medical help right away for any bleeding that you cannot stop.
  . . .
  The most common side effects of VONJO include:

low platelet counts

nausea and vomiting
low red blood cell counts (anemia)
swelling of your ankles, legs, and feet
Your healthcare provider will do blood tests and an electrocardiogram (ECG) before you start treatment with VONJO and as needed during treatment to check for side effects.

Your healthcare provider may change your dose or how often you take VONJO, temporarily stop or permanently stop treatment with VONJO if you have certain side effects.