Drug Safety-related Labeling Changes (SrLC)
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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.
DOPTELET (NDA-210238)
(AVATROMBOPAG MALEATE)
Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)
07/24/2025 (SUPPL-10)
07/18/2024 (SUPPL-9)
5 Warnings and Precautions
5.1 Thrombotic/Thromboembolic ComplicationsAdditions and/or revisions underlined:
…
Consider the
potential increased thrombotic risk when administering DOPTELET to patients
with known risk factors for thromboembolism, including genetic prothrombotic
conditions (e.g., Factor V Leiden, Prothrombin 20210A, Antithrombin deficiency
or Protein C or S deficiency) and acquired risk factors (e.g., antiphospholipid
syndrome).
…
10/14/2021 (SUPPL-6)
08/20/2020 (SUPPL-4)
06/26/2019 (SUPPL-1)
5 Warnings and Precautions
5.1 Thrombotic/Thromboembolic Complications(additions underlined)
DOPTELET is a thrombopoietin
(TPO) receptor agonist and TPO receptor agonists have been associated with
thrombotic and thromboembolic complications in patients with chronic liver
disease or chronic immune thrombocytopenia. In patients with chronic
liver disease, thromboembolic events (portal vein thrombosis) occurred in
0.2% (1/430) of patients receiving DOPTELET. In patients with
chronic immune thrombocytopenia, thromboembolic events (arterial or venous)
occurred in 7% (9/128) of patients receiving DOPTELET.
…
DOPTELET should
not be administered to patients with chronic liver disease or chronic immune
thrombocytopenia in an attempt to normalize platelet counts. Follow the
dosing guidelines to achieve target platelet counts. Monitor patients receiving
DOPTELET for signs and symptoms of thromboembolic events and institute
treatment promptly.
6 Adverse Reactions
6.1 Clinical Trials Experience(additions underlined)
…
Patients with Chronic Immune Thrombocytopenia
The safety of DOPTELET was evaluated in four clinical trials in patients with chronic immune thrombocytopenia: two Phase 3 trials (one randomized, double-blind, placebo-controlled trial, and one randomized, double-blind, active-controlled trial) and two Phase 2 trials (one randomized, double-blind, placebo-controlled, dose-ranging, trial, and one open-label extension trial) in 161 patients with chronic immune thrombocytopenia in both the double-blind and open-label extension phases.
The pooled safety data from these four clinical trials includes 128 patients who received 2.5 to 40 mg of DOPTELET once daily for a median duration of exposure of 29.1 weeks and had 1 post-dose safety assessment. The majority of patients were female (63%) and median subject age was 50.5 years (ranging from 18-88 years of age). The racial and ethnic distribution was White (84%), Black (6%), Asian (6%) and Other (6%).
The most common adverse reactions (those occurring in greater than or equal to10% of patients) in the DOPTELET-treated patients across the pooled safety data from the four trials are summarized in Table 6.
(please refer to label to view table 6)
The incidence of serious adverse reactions was 9% (12/128) in the DOPTELET treatment group. Serious adverse reactions reported in more than 1 individual DOPTELET-treated patient included headache, occurring in 1.6% (2/128).
Adverse reactions resulting in discontinuation of DOPTELET that were reported in more than 1 patient included headache, occurring in 1.6% (2/128).
7 Drug Interactions
(new subsection added)
7.1 Effect of Other Drugs on DOPTELET in Patients with Chronic Immune Thrombocytopenia
Moderate or Strong Dual Inhibitors of CYP2C9 and CYP3A4
Concomitant use with a moderate or strong dual inhibitor of CYP2C9 and CYP3A4 increases avatrombopag AUC, which may increase the risk of DOPTELET toxicities. Reduce the starting dosage of DOPTELET when used concomitantly with a moderate or strong dual inhibitor of CYP2C9 and CYP3A4 (see Table 4).
In patients starting moderate or strong dual inhibitors of CYP2C9 and CYP3A4 while receiving DOPTELET, monitor platelet counts and adjust DOPTELET dose as necessary (see Table 3) .
Moderate or Strong Dual Inducers of CYP2C9 and CYP3A4
Concomitant use with a moderate or strong dual inducer of CYP2C9 and CYP3A4 decreases avatrombopag AUC which may reduce DOPTELET efficacy. Increase the recommended starting dosage of DOPTELET when used concomitantly with a moderate or strong dual inducer of CYP2C9 and CYP3A4 (see Table 4).
In patients starting moderate or strong dual inducers of CYP2C9 and CYP3A4 while receiving DOPTELET, monitor platelet counts and adjust dose as necessary (see Table 3).
Patients with Chronic Liver Disease
No dosage adjustments are required for patients with chronic liver disease.
8 Use in Specific Populations
8.1 Pregnancy(additions underlined)
… However, these findings were observed at exposures based on an AUC substantially higher than the AUC observed in patients at the maximum recommended dose of 60 mg once daily. Advise pregnant women of the potential risk to a fetus.
…
Data
Animal Data
… Spontaneous abortions were observed at all doses tested in rabbits and were associated with decreased body weights and food consumption at 300 and 600 mg/kg/day; exposures at the lowest dose of 100 mg/kg/day were 10-times the AUC in patients at the maximum recommended dose of 60 mg once daily.
…
(additions underlined)
…
Clinical Considerations
Minimizing-Exposure
A lactating woman, receiving DOPTELET for brief periods, such as prior to an invasive procedure, should interrupt breastfeeding and pump and discard breastmilk during treatment and for two weeks after the last dose of DOPTELET in order to minimize exposure to a breastfed child. Advise lactating women receiving chronic DOPTELET therapy not to breastfeed during treatment with DOPTELET and for at least 2 weeks after the last dose.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION(additions underlined)
…
Risks
Thrombotic/Thromboembolic Complications
DOPTELET is a thrombopoietin (TPO) receptor agonist and TPO receptor agonists have been associated with thrombotic and thromboembolic complications in patients with chronic liver disease or chronic immune thrombocytopenia. Portal vein thrombosis has been reported in patients with chronic liver disease treated with TPO receptor agonists. Various thromboembolic complications (arterial and venous) have been reported in patients treated with DOPTELET .
Drug Interactions
DOPTELET may be affected by other drugs and may require a dose adjustment when co-administered with other drugs; therefore, advise patients to report their use of any other prescription or nonprescription medications or dietary supplements.
…
(additions underlined)
…
How should I take DOPTELET?
…
Your healthcare provider may change your dose of DOPTELET depending on your blood platelet counts.
…
If you take DOPTELET to treat your low blood platelet counts due to chronic immune thrombocytopenia, your healthcare provider will check your platelet count before, during and for at least 4 weeks after stopping your treatment with DOPTELET.
If you are taking DOPTELET prior to a scheduled medical procedure and you miss a dose, contact your healthcare provider for further dosing instructions.
If you are taking DOPTELET for chronic immune thrombocytopenia and you miss a dose of DOPTELET, take it as soon as you remember. Do not take 2 doses at one time to make up for a missed dose. Take your next dose at your usual scheduled time.
…
The most common side effects of DOPTELET when used to treat low blood platelet counts in adults with chronic liver disease (CLD) who are scheduled to have a medical or dental procedure are:
Fever
stomach (abdominal) pain
nausea
headache
tiredness
swelling of hands or feet
The most common side effects of DOPTELET when used to treat low blood platelet counts in adults with chronic immune thrombocytopenia (ITP) are:
headache
tiredness
bruising
nosebleed
upper respiratory tract infection
joint pain
bleeding gums
purple or red spots on your skin
runny nose
…