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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.
PEMETREXED (NDA-208419)
(PEMETREXED)
Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)
11/22/2022 (SUPPL-2)
5 Warnings and Precautions
5.1 Myelosuppression and Increased Risk of Myelosuppression without Vitamin Supplementation
Additions and/or revisions underlined:
Pemetrexed can cause severe myelosuppression resulting in a requirement for transfusions and which may lead to neutropenic infection. The risk of myelosuppression is increased in patients who do not receive vitamin supplementation. In Study JMCH, incidences of Grade 3-4 neutropenia (38% versus 23%), thrombocytopenia (9% versus 5%), febrile neutropenia (9% versus 0.6%), and neutropenic infection (6% versus 0) were higher in patients who received pemetrexed plus cisplatin without vitamin supplementation as compared to patients who were fully supplemented with folic acid and vitamin B12 prior to and throughout pemetrexed plus cisplatin treatment.
… Permanently reduce Pemetrexed Injection in patients with an ANC of less than 500 cells/mm3 or platelet count of less than 50,000 cells/mm3 in previous cycles [see Dosage and Administration (2.6)].
In Studies JMDB and JMCH, among patients who received vitamin supplementation, incidence of Grade 3-4 neutropenia was 15% and 23%, the incidence of Grade 3-4 anemia was 6% and 4%, and incidence of Grade 3-4 thrombocytopenia was 4% and 5%, respectively. In Study JMCH, 18% of patients in the pemetrexed arm required red blood cell transfusions compared to 7% of patients in the cisplatin arm [see Adverse Reactions (6.1)]. In Studies JMEN, PARAMOUNT, and JMEI, where all patients received vitamin supplementation, incidence of Grade 3-4 neutropenia ranged from 3% to 5%, and incidence of Grade 3-4 anemia ranged from 3% to 5%.
5.2 Renal Failure
Pemetrexed can cause severe, and sometimes fatal, renal toxicity. The incidences of renal failure in clinical studies in which patients received pemetrexed with cisplatin were: 2.1% in Study JMDB and 2.2% in Study JMCH. The incidence of renal failure in clinical studies in which patients received pemetrexed as a single agent ranged from 0.4% to 0.6% (Studies JMEN, PARAMOUNT, and JMEI [see Adverse Reactions (6.1)]. Determine creatinine clearance …
6 Adverse Reactions
6.1 Clinical Trials ExperienceAdditions and/or revisions underlined:
… In clinical trials, the most common adverse reactions (incidence greater than or equal to 20%) of pemetrexed, when administered as a single agent, are fatigue, nausea, and anorexia. The most common adverse reactions (incidence greater than or equal to 20%) of pemetrexed, when administered in combination with cisplatin are vomiting, neutropenia, anemia, stomatitis/pharyngitis, thrombocytopenia, and constipation. The most common adverse reactions (incidence greater than or equal to 20%) of pemetrexed, when administered in combination with pembrolizumab and platinum chemotherapy, are fatigue/asthenia, nausea, constipation, diarrhea, decreased appetite, rash, vomiting, cough, dyspnea, and pyrexia.
Non-Squamous NSCLC
Extensive changes to the rest of this section; please refer to label for complete information.
8 Use in Specific Populations
8.4 Pediatric UseAdditions and/or revisions underlined:
The safety and effectiveness of pemetrexed in pediatric patients have not been established.
The safety and pharmacokinetics of pemetrexed were evaluated in two clinical studies conducted in pediatric patients with recurrent solid tumors (NCT00070473, N=32 and NCT00520936, N=72). Patients in both studies received concomitant vitamin B12 and folic acid supplementation and dexamethasone.
No tumor responses were observed. Adverse reactions observed in pediatric patients were similar to those observed in adults.
Pharmacokinetics of pemetrexed in 22 patients age 4 to 18 years enrolled in NCT00070473 were within range of values in adults.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT INFORMATIONWhat is Pemetrexed Injection?
Pemetrexed Injection is a prescription medicine used to treat:
Additions and/or revisions underlined:
a kind of lung cancer called non-squamous non-small cell lung cancer (NSCLC). Pemetrexed Injection is used:
as the first treatment in combination with pembrolizumab and platinum chemotherapy when your lung cancer with no abnormal EGFR or ALK gene has spread (advanced NSCLC).
as the first treatment in combination with cisplatin when your lung cancer has spread (advanced NSCLC).
alone as maintenance treatment after you have received 4 cycles of chemotherapy that contains platinum for first treatment of your advanced NSCLC and your cancer has not progressed.
alone when your lung cancer has returned or spread after prior chemotherapy.
Pemetrexed Injection is not for use for the treatment of people with squamous cell, non-small cell lung cancer.
a kind of cancer called malignant pleural mesothelioma. This cancer affects the lining of the lungs and chest wall. Pemetrexed Injection is used in combination with cisplatin as the first treatment for malignant pleural mesothelioma that cannot be removed by surgery or you are not able to have surgery.
Pemetrexed Injection has not been shown to be safe and effective in children.
Before taking Pemetrexed Injection, tell your healthcare provider about all of your medical conditions, including if you: …
are pregnant or plan to become pregnant. Pemetrexed Injection can harm your unborn baby.
Females who are able to become pregnant:
Your healthcare provider will check to see if you are pregnant before you start treatment with Pemetrexed Injection. You should use effective birth control (contraception) during treatment with Pemetrexed Injection and for 6 months after the last dose. Tell your healthcare provider right away if you become pregnant or think you are pregnant during treatment with Pemetrexed Injection.
Males with female partners who are able to become pregnant should use effective birth control (contraception) during treatment with Pemetrexed Injection and for 3 months after the last dose.
are breastfeeding or plan to breastfeed …
What are the possible side effects of Pemetrexed Injection?
Pemetrexed Injection can cause serious side effects, including:
The most common side effects of Pemetrexed Injection when given with cisplatin are:
vomiting
low white blood cell counts (neutropenia)
swelling or sores in your mouth or sore throat
low platelet counts (thrombocytopenia)
constipation
low red blood cell counts (anemia)
The most common side effects of Pemetrexed Injection when given with pembrolizumab and platinum chemotherapy are:
tiredness/weakness
nausea
constipation
diarrhea
loss of appetite
rash
vomiting
cough
shortness of breath
fever
11/22/2022 (SUPPL-3)
5 Warnings and Precautions
5.1 Myelosuppression and Increased Risk of Myelosuppression without Vitamin Supplementation
Additions and/or revisions underlined:
Pemetrexed can cause severe myelosuppression resulting in a requirement for transfusions and which may lead to neutropenic infection. The risk of myelosuppression is increased in patients who do not receive vitamin supplementation. In Study JMCH, incidences of Grade 3-4 neutropenia (38% versus 23%), thrombocytopenia (9% versus 5%), febrile neutropenia (9% versus 0.6%), and neutropenic infection (6% versus 0) were higher in patients who received pemetrexed plus cisplatin without vitamin supplementation as compared to patients who were fully supplemented with folic acid and vitamin B12 prior to and throughout pemetrexed plus cisplatin treatment.
… Permanently reduce Pemetrexed Injection in patients with an ANC of less than 500 cells/mm3 or platelet count of less than 50,000 cells/mm3 in previous cycles [see Dosage and Administration (2.6)].
In Studies JMDB and JMCH, among patients who received vitamin supplementation, incidence of Grade 3-4 neutropenia was 15% and 23%, the incidence of Grade 3-4 anemia was 6% and 4%, and incidence of Grade 3-4 thrombocytopenia was 4% and 5%, respectively. In Study JMCH, 18% of patients in the pemetrexed arm required red blood cell transfusions compared to 7% of patients in the cisplatin arm [see Adverse Reactions (6.1)]. In Studies JMEN, PARAMOUNT, and JMEI, where all patients received vitamin supplementation, incidence of Grade 3-4 neutropenia ranged from 3% to 5%, and incidence of Grade 3-4 anemia ranged from 3% to 5%.
5.2 Renal Failure
Pemetrexed can cause severe, and sometimes fatal, renal toxicity. The incidences of renal failure in clinical studies in which patients received pemetrexed with cisplatin were: 2.1% in Study JMDB and 2.2% in Study JMCH. The incidence of renal failure in clinical studies in which patients received pemetrexed as a single agent ranged from 0.4% to 0.6% (Studies JMEN, PARAMOUNT, and JMEI [see Adverse Reactions (6.1)]. Determine creatinine clearance …
6 Adverse Reactions
6.1 Clinical Trials ExperienceAdditions and/or revisions underlined:
… In clinical trials, the most common adverse reactions (incidence greater than or equal to 20%) of pemetrexed, when administered as a single agent, are fatigue, nausea, and anorexia. The most common adverse reactions (incidence greater than or equal to 20%) of pemetrexed, when administered in combination with cisplatin are vomiting, neutropenia, anemia, stomatitis/pharyngitis, thrombocytopenia, and constipation. The most common adverse reactions (incidence greater than or equal to 20%) of pemetrexed, when administered in combination with pembrolizumab and platinum chemotherapy, are fatigue/asthenia, nausea, constipation, diarrhea, decreased appetite, rash, vomiting, cough, dyspnea, and pyrexia.
Non-Squamous NSCLC
Extensive changes to the rest of this section; please refer to label for complete information.
8 Use in Specific Populations
8.4 Pediatric UseAdditions and/or revisions underlined:
The safety and effectiveness of pemetrexed in pediatric patients have not been established.
The safety and pharmacokinetics of pemetrexed were evaluated in two clinical studies conducted in pediatric patients with recurrent solid tumors (NCT00070473, N=32 and NCT00520936, N=72). Patients in both studies received concomitant vitamin B12 and folic acid supplementation and dexamethasone.
No tumor responses were observed. Adverse reactions observed in pediatric patients were similar to those observed in adults.
Pharmacokinetics of pemetrexed in 22 patients age 4 to 18 years enrolled in NCT00070473 were within range of values in adults.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT INFORMATIONWhat is Pemetrexed Injection?
Pemetrexed Injection is a prescription medicine used to treat:
Additions and/or revisions underlined:
a kind of lung cancer called non-squamous non-small cell lung cancer (NSCLC). Pemetrexed Injection is used:
as the first treatment in combination with pembrolizumab and platinum chemotherapy when your lung cancer with no abnormal EGFR or ALK gene has spread (advanced NSCLC).
as the first treatment in combination with cisplatin when your lung cancer has spread (advanced NSCLC).
alone as maintenance treatment after you have received 4 cycles of chemotherapy that contains platinum for first treatment of your advanced NSCLC and your cancer has not progressed.
alone when your lung cancer has returned or spread after prior chemotherapy.
Pemetrexed Injection is not for use for the treatment of people with squamous cell, non-small cell lung cancer.
a kind of cancer called malignant pleural mesothelioma. This cancer affects the lining of the lungs and chest wall. Pemetrexed Injection is used in combination with cisplatin as the first treatment for malignant pleural mesothelioma that cannot be removed by surgery or you are not able to have surgery.
Pemetrexed Injection has not been shown to be safe and effective in children.
Before taking Pemetrexed Injection, tell your healthcare provider about all of your medical conditions, including if you: …
are pregnant or plan to become pregnant. Pemetrexed Injection can harm your unborn baby.
Females who are able to become pregnant:
Your healthcare provider will check to see if you are pregnant before you start treatment with Pemetrexed Injection. You should use effective birth control (contraception) during treatment with Pemetrexed Injection and for 6 months after the last dose. Tell your healthcare provider right away if you become pregnant or think you are pregnant during treatment with Pemetrexed Injection.
Males with female partners who are able to become pregnant should use effective birth control (contraception) during treatment with Pemetrexed Injection and for 3 months after the last dose.
are breastfeeding or plan to breastfeed …
What are the possible side effects of Pemetrexed Injection?
Pemetrexed Injection can cause serious side effects, including:
The most common side effects of Pemetrexed Injection when given with cisplatin are:
vomiting
low white blood cell counts (neutropenia)
swelling or sores in your mouth or sore throat
low platelet counts (thrombocytopenia)
constipation
low red blood cell counts (anemia)
The most common side effects of Pemetrexed Injection when given with pembrolizumab and platinum chemotherapy are:
tiredness/weakness
nausea
constipation
diarrhea
loss of appetite
rash
vomiting
cough
shortness of breath
fever
11/22/2022 (SUPPL-4)
5 Warnings and Precautions
5.1 Myelosuppression and Increased Risk of Myelosuppression without Vitamin Supplementation
Additions and/or revisions underlined:
Pemetrexed can cause severe myelosuppression resulting in a requirement for transfusions and which may lead to neutropenic infection. The risk of myelosuppression is increased in patients who do not receive vitamin supplementation. In Study JMCH, incidences of Grade 3-4 neutropenia (38% versus 23%), thrombocytopenia (9% versus 5%), febrile neutropenia (9% versus 0.6%), and neutropenic infection (6% versus 0) were higher in patients who received pemetrexed plus cisplatin without vitamin supplementation as compared to patients who were fully supplemented with folic acid and vitamin B12 prior to and throughout pemetrexed plus cisplatin treatment.
… Permanently reduce Pemetrexed Injection in patients with an ANC of less than 500 cells/mm3 or platelet count of less than 50,000 cells/mm3 in previous cycles [see Dosage and Administration (2.6)].
In Studies JMDB and JMCH, among patients who received vitamin supplementation, incidence of Grade 3-4 neutropenia was 15% and 23%, the incidence of Grade 3-4 anemia was 6% and 4%, and incidence of Grade 3-4 thrombocytopenia was 4% and 5%, respectively. In Study JMCH, 18% of patients in the pemetrexed arm required red blood cell transfusions compared to 7% of patients in the cisplatin arm [see Adverse Reactions (6.1)]. In Studies JMEN, PARAMOUNT, and JMEI, where all patients received vitamin supplementation, incidence of Grade 3-4 neutropenia ranged from 3% to 5%, and incidence of Grade 3-4 anemia ranged from 3% to 5%.
5.2 Renal Failure
Pemetrexed can cause severe, and sometimes fatal, renal toxicity. The incidences of renal failure in clinical studies in which patients received pemetrexed with cisplatin were: 2.1% in Study JMDB and 2.2% in Study JMCH. The incidence of renal failure in clinical studies in which patients received pemetrexed as a single agent ranged from 0.4% to 0.6% (Studies JMEN, PARAMOUNT, and JMEI [see Adverse Reactions (6.1)]. Determine creatinine clearance …
6 Adverse Reactions
6.1 Clinical Trials ExperienceAdditions and/or revisions underlined:
… In clinical trials, the most common adverse reactions (incidence greater than or equal to 20%) of pemetrexed, when administered as a single agent, are fatigue, nausea, and anorexia. The most common adverse reactions (incidence greater than or equal to 20%) of pemetrexed, when administered in combination with cisplatin are vomiting, neutropenia, anemia, stomatitis/pharyngitis, thrombocytopenia, and constipation. The most common adverse reactions (incidence greater than or equal to 20%) of pemetrexed, when administered in combination with pembrolizumab and platinum chemotherapy, are fatigue/asthenia, nausea, constipation, diarrhea, decreased appetite, rash, vomiting, cough, dyspnea, and pyrexia.
Non-Squamous NSCLC
Extensive changes to the rest of this section; please refer to label for complete information.
8 Use in Specific Populations
8.4 Pediatric UseAdditions and/or revisions underlined:
The safety and effectiveness of pemetrexed in pediatric patients have not been established.
The safety and pharmacokinetics of pemetrexed were evaluated in two clinical studies conducted in pediatric patients with recurrent solid tumors (NCT00070473, N=32 and NCT00520936, N=72). Patients in both studies received concomitant vitamin B12 and folic acid supplementation and dexamethasone.
No tumor responses were observed. Adverse reactions observed in pediatric patients were similar to those observed in adults.
Pharmacokinetics of pemetrexed in 22 patients age 4 to 18 years enrolled in NCT00070473 were within range of values in adults.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT INFORMATIONWhat is Pemetrexed Injection?
Pemetrexed Injection is a prescription medicine used to treat:
Additions and/or revisions underlined:
a kind of lung cancer called non-squamous non-small cell lung cancer (NSCLC). Pemetrexed Injection is used:
as the first treatment in combination with pembrolizumab and platinum chemotherapy when your lung cancer with no abnormal EGFR or ALK gene has spread (advanced NSCLC).
as the first treatment in combination with cisplatin when your lung cancer has spread (advanced NSCLC).
alone as maintenance treatment after you have received 4 cycles of chemotherapy that contains platinum for first treatment of your advanced NSCLC and your cancer has not progressed.
alone when your lung cancer has returned or spread after prior chemotherapy.
Pemetrexed Injection is not for use for the treatment of people with squamous cell, non-small cell lung cancer.
a kind of cancer called malignant pleural mesothelioma. This cancer affects the lining of the lungs and chest wall. Pemetrexed Injection is used in combination with cisplatin as the first treatment for malignant pleural mesothelioma that cannot be removed by surgery or you are not able to have surgery.
Pemetrexed Injection has not been shown to be safe and effective in children.
Before taking Pemetrexed Injection, tell your healthcare provider about all of your medical conditions, including if you: …
are pregnant or plan to become pregnant. Pemetrexed Injection can harm your unborn baby.
Females who are able to become pregnant:
Your healthcare provider will check to see if you are pregnant before you start treatment with Pemetrexed Injection. You should use effective birth control (contraception) during treatment with Pemetrexed Injection and for 6 months after the last dose. Tell your healthcare provider right away if you become pregnant or think you are pregnant during treatment with Pemetrexed Injection.
Males with female partners who are able to become pregnant should use effective birth control (contraception) during treatment with Pemetrexed Injection and for 3 months after the last dose.
are breastfeeding or plan to breastfeed …
What are the possible side effects of Pemetrexed Injection?
Pemetrexed Injection can cause serious side effects, including:
The most common side effects of Pemetrexed Injection when given with cisplatin are:
vomiting
low white blood cell counts (neutropenia)
swelling or sores in your mouth or sore throat
low platelet counts (thrombocytopenia)
constipation
low red blood cell counts (anemia)
The most common side effects of Pemetrexed Injection when given with pembrolizumab and platinum chemotherapy are:
tiredness/weakness
nausea
constipation
diarrhea
loss of appetite
rash
vomiting
cough
shortness of breath
fever