(pemetrexed for injection)

Prescribing Information
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5 WARNINGS AND PRECAUTIONS

5 WARNINGS AND PRECAUTIONS

5.1 Myelosuppression and Increased Risk of Myelosuppression without Vitamin Supplementation

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.

Initiate supplementation with oral folic acid and intramuscular vitamin B12 prior to the first dose of Pemetrexed Injection; continue vitamin supplementation during treatment and for 21 days after the last dose of Pemetrexed Injection to reduce the severity of hematologic and gastrointestinal toxicity of Pemetrexed Injection [see Dosage and Administration (2.4)]. Obtain a complete blood count at the beginning of each cycle. Do not administer Pemetrexed Injection until the ANC is at least 1500 cells/mm3 and platelet count is at least 100,000 cells/mm3. 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 before each dose and periodically monitor renal function during treatment with Pemetrexed Injection. Withhold Pemetrexed Injection in patients with a creatinine clearance of less than 45 mL/minute [see Dosage and Administration (2.3)].

5.3 Bullous and Exfoliative Skin Toxicity

Serious and sometimes fatal, bullous, blistering and exfoliative skin toxicity, including cases suggestive of Stevens-Johnson Syndrome/Toxic epidermal necrolysis can occur with pemetrexed. Permanently discontinue Pemetrexed Injection for severe and life-threatening bullous, blistering or exfoliating skin toxicity.

5.4 Interstitial Pneumonitis

Serious interstitial pneumonitis, including fatal cases, can occur with pemetrexed treatment. Withhold Pemetrexed Injection for acute onset of new or progressive unexplained pulmonary symptoms such as dyspnea, cough, or fever pending diagnostic evaluation. If pneumonitis is confirmed, permanently discontinue Pemetrexed Injection.

5.5 Radiation Recall

Radiation recall can occur with pemetrexed in patients who have received radiation weeks to years previously. Monitor patients for inflammation or blistering in areas of previous radiation treatment. Permanently discontinue Pemetrexed Injection for signs of radiation recall.

5.6 Increased Risk of Toxicity with Ibuprofen in Patients with Renal Impairment

Exposure to pemetrexed is increased in patients with mild to moderate renal impairment who take concomitant ibuprofen, increasing the risks of adverse reactions of pemetrexed. In patients with creatinine clearances between 45 mL/min and 79 mL/min, avoid administration of ibuprofen for 2 days before, the day of, and 2 days following administration of Pemetrexed Injection. If concomitant ibuprofen use cannot be avoided, monitor patients more frequently for Pemetrexed Injection adverse reactions, including myelosuppression, renal, and gastrointestinal toxicity [see Dosage and Administration (2.5), Drug Interactions (7), and Clinical Pharmacology (12.3)].

5.7 Embryo-Fetal Toxicity

Based on findings from animal studies and its mechanism of action, Pemetrexed Injection can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, intravenous administration of pemetrexed to pregnant mice during the period of organogenesis was teratogenic, resulting in developmental delays and increased malformations at doses lower than the recommended human dose of 500 mg/m2. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with Pemetrexed Injection and for 6 months after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with Pemetrexed Injection and for 3 months after the last dose [see Use in Specific Populations (8.1, 8.3) and Clinical Pharmacology (12.1)].

Medication Guide

MEDICATION GUIDE

PATIENT INFORMATION
Pemetrexed (peh-meh-TREX-ed) Injection
for intravenous use
This Patient Information has been approved by the U.S. Food and Drug Administration. Issued: 6/2022

What is Pemetrexed Injection?

Pemetrexed Injection is a prescription medicine used to treat:

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a kind of lung cancer called non-squamous non-small cell lung cancer (NSCLC). Pemetrexed Injection is used:
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as the first treatment in combination with cisplatin when your lung cancer has spread (advanced NSCLC).
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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.
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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.
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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.

Do not take Pemetrexed Injection if you have had a severe allergic reaction to any medicine that contains pemetrexed.

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

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have kidney problems.
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have had radiation therapy.
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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.
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are breastfeeding or plan to breastfeed. It is not known if Pemetrexed Injection passes into breast milk. Do not breastfeed during treatment with Pemetrexed Injection and for 1 week after the last dose.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
Tell your healthcare provider if you have kidney problems and take a medicine that contains ibuprofen. You should avoid taking ibuprofen for 2 days before, the day of, and 2 days after receiving treatment with Pemetrexed Injection.

How is Pemetrexed Injection given?

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It is very important to take folic acid and vitamin B12 during your treatment with Pemetrexed Injection to lower your risk of harmful side effects.
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Take folic acid exactly as prescribed by your healthcare provider 1 time a day, beginning 7 days (1 week) before your first dose of Pemetrexed Injection and continue taking folic acid until 21 days (3 weeks) after your last dose of Pemetrexed Injection.
o
Your healthcare provider will give you vitamin B12 injections during treatment with Pemetrexed Injection. You will get your first vitamin B12 injection 7 days (1 week) before your first dose of Pemetrexed Injection, and then every 3 cycles.
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Your healthcare provider will prescribe a medicine called corticosteroid for you to take 2 times a day for 3 days, beginning the day before each treatment with Pemetrexed Injection.
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Pemetrexed Injection is given to you by intravenous (IV) infusion into your vein. The infusion is given over 10 minutes.
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Pemetrexed Injection is usually given once every 21 days (3 weeks).

What are the possible side effects of Pemetrexed Injection?

Pemetrexed Injection can cause serious side effects, including:

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Low blood cell counts. Low blood cell counts can be severe, including low white blood cell counts (neutropenia), low platelet counts (thrombocytopenia), and low red blood cell counts (anemia). Your healthcare provider will do blood tests to check your blood cell counts regularly during your treatment with Pemetrexed Injection. Tell your healthcare provider right away if you have any signs of infection, fever, bleeding, or severe tiredness during your treatment with Pemetrexed Injection.
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Kidney problems, including kidney failure. Pemetrexed Injection can cause severe kidney problems that can lead to death. Severe vomiting or diarrhea can lead to loss of fluids (dehydration) which may cause kidney problems to become worse. Tell your healthcare provider right away if you have a decrease in the amount of urine you make.
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Severe skin reactions. Severe skin reactions that may lead to death can happen with Pemetrexed Injection. Tell your healthcare provider right away if you develop blisters, skin sores, skin peeling, or painful sores, or ulcers in your mouth, nose, throat or genital area.
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Lung problems (pneumonitis). Pemetrexed Injection can cause serious lung problems that can lead to death. Tell your healthcare provider right away if you get any new or worsening symptoms of shortness of breath, cough, or fever.
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Radiation recall. Radiation recall is a skin reaction that can happen in people who have received radiation treatment in the past and are treated with Pemetrexed Injection. Tell your healthcare provider if you get swelling, blistering, or a rash that looks like a sunburn in an area that was previously treated with radiation.

The most common side effects of Pemetrexed Injection when given alone are:

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tiredness
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nausea
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loss of appetite

The most common side effects of Pemetrexed Injection when given with cisplatin are:

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vomiting
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swelling or sores in your mouth or sore throat
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constipation
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low white blood cell counts (neutropenia)
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low platelet counts (thrombocytopenia)
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low red blood cell counts (anemia)

Pemetrexed Injection may cause fertility problems in males. This may affect your ability to father a child. It is not known if these effects are reversible. Talk to your healthcare provider if this is a concern for you.
Your healthcare provider will do blood tests to check for side effects during treatment with Pemetrexed Injection. Your healthcare provider may change your dose of Pemetrexed Injection, delay treatment, or stop treatment if you have certain side effects.
Tell your healthcare provider if you have any side effect that bothers you or that does not go away.
These are not all of the possible side effects of Pemetrexed Injection. For more information, ask your healthcare provider or pharmacist.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

General information about the safe and effective use of Pemetrexed Injection.
Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet.
You can ask your pharmacist or healthcare provider for information about Pemetrexed Injection that is written for health professionals.

What are the ingredients in Pemetrexed Injection?
Active ingredient: pemetrexed
Inactive ingredient: monothioglycerol, water for injection and may contain sodium hydroxide for pH adjustment.

Manufactured by: Zydus Hospira Oncology Private Ltd.
Ahmedabad 382-213, Gujarat, India.

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Distributed by: Hospira, Inc., Lake Forest, IL 60045 USA
LAB-1432-1.0
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