Prescription Drug Information: PEMETREXED (Page 5 of 6)

14.2 Mesothelioma

The efficacy of pemetrexed was evaluated in Study JMCH (NCT00005636), a multicenter, randomized (1:1), single-blind study conducted in patients with MPM who had received no prior chemotherapy. Patients were randomized (n=456) to receive pemetrexed 500 mg/m2 intravenously over 10 minutes followed 30 minutes later by cisplatin 75 mg/m2 intravenously over two hours on Day 1 of each 21-day cycle or to receive cisplatin 75 mg/m2 intravenously over 2 hours on Day 1 of each 21-day cycle; treatment continued until disease progression or intolerable toxicity. The study was modified after randomization and treatment of 117 patients to require that all patients receive folic acid 350 mcg to 1000 mcg daily beginning 1 to 3 weeks prior to the first dose of pemetrexed and continuing until 1 to 3 weeks after the last dose, vitamin B12 1000 mcg intramuscularly 1 to 3 weeks prior to first dose of pemetrexed and every 9 weeks thereafter, and dexamethasone 4 mg orally, twice daily, for 3 days starting the day prior to each pemetrexed dose. Randomization was stratified by multiple baseline variables including KPS, histologic subtype (epithelial, mixed, sarcomatoid, other), and gender. The major efficacy outcome measure was overall survival and additional efficacy outcome measures were time to disease progression, overall response rate, and response duration.

A total of 448 patients received at least one dose of protocol-specified therapy; 226 patients were randomized to and received at least one dose of pemetrexed plus cisplatin, and 222 patients were randomized to and received cisplatin. Among the 226 patients who received cisplatin with pemetrexed, 74% received full supplementation with folic acid and vitamin B12 during study therapy, 14% were never supplemented, and 12% were partially supplemented. Across the study population, the median age was 61 years (range: 20 to 86 years); 81% were male; 92% were White, 5% were Hispanic or Latino, 3.1% were Asian, and <1% were other ethnicities; and 54% had a baseline KPS score of 90–100% and 46% had a KPS score of 70–80%. With regard to tumor characteristics, 46% had Stage IV disease, 31% Stage III, 15% Stage II, and 7% Stage I disease at baseline; the histologic subtype of mesothelioma was epithelial in 68% of patients, mixed in 16%, sarcomatoid in 10% and other histologic subtypes in 6%. The baseline demographics and tumor characteristics of the subgroup of fully supplemented patients was similar to the overall study population.

The efficacy results from Study JMCH are summarized in Table 15 and Figure 8.

Table 15: Efficacy Results in Study JMCH
Efficacy ParameterAll Randomized and Treated Patients (N=448)Fully Supplemented Patients (N=331)
Pemetrexed/Cisplatin (N=226)Cisplatin(N=222)Pemetrexed/Cisplatin (N=168)Cisplatin (N=163)
*
Hazard ratios are not adjusted for stratification variables.
Not a pre-specified analysis.
Median overall survival(months)12.19.313.310.0
(95% CI)(10.0–14.4)(7.8–10.7)(11.4–14.9)(8.4–11.9)
Hazard ratio *0.770.75
Log rank p-value0.020NA
Figure 8
(click image for full-size original)

Figure 8: Kaplan-Meier Curves for Overall Survival in Study JMCH

Based upon prospectively defined criteria (modified Southwest Oncology Group methodology) the objective tumor response rate for pemetrexed plus cisplatin was greater than the objective tumor response rate for cisplatin alone. There was also improvement in lung function (forced vital capacity) in the pemetrexed plus cisplatin arm compared to the control arm.

15 REFERENCES

  1. “OSHA Hazardous Drugs.” OSHA. [https://www.osha.gov/hazardous-drugs]

16 HOW SUPPLIED/STORAGE AND HANDLING

How Supplied

Pemetrexed Injection is a clear, colorless to pale yellow ready-to-dilute solution in a single-dose vial for intravenous infusion.

NDC 0409-1045-01: Carton containing one (1) single-dose vial, 100 mg/4 mL (25 mg/mL).

NDC 0409-2188-01: Carton containing one (1) single-dose vial, 500 mg/20 mL (25 mg/mL).

NDC 0409-3532-01: Carton containing one (1) single-dose vial, 1 g/40 mL (25 mg/mL).

Storage and Handling

Store Pemetrexed Injection at controlled refrigerated temperature, 2°C to 8°C (36°F to 46°F).

Pemetrexed Injection is a hazardous drug. Follow applicable special handling and disposal procedures. [see References (15)]

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Patient Information).

Premedication and Concomitant Medication: Instruct patients to take folic acid as directed and to keep appointments for vitamin B12 injections to reduce the risk of treatment-related toxicity. Instruct patients of the requirement to take corticosteroids to reduce the risks of treatment-related toxicity [see Dosage and Administration (2.4) and Warnings and Precautions (5.1)].

Myelosuppression: Inform patients of the risk of low blood cell counts and instruct them to immediately contact their physician for signs of infection, fever, bleeding, or symptoms of anemia [see Warnings and Precautions (5.1)].

Renal Failure: Inform patients of the risks of renal failure, which may be exacerbated in patients with dehydration arising from severe vomiting or diarrhea. Instruct patients to immediately contact their healthcare provider for a decrease in urine output [see Warnings and Precautions (5.2)].

Bullous and Exfoliative Skin Disorders: Inform patients of the risks of severe and exfoliative skin disorders. Instruct patients to immediately contact their healthcare provider for development of bullous lesions or exfoliation in the skin or mucous membranes [see Warnings and Precautions (5.3)].

Interstitial Pneumonitis: Inform patients of the risks of pneumonitis. Instruct patients to immediately contact their healthcare provider for development of dyspnea or persistent cough [see Warnings and Precautions (5.4)].

Radiation Recall: Inform patients who have received prior radiation of the risks of radiation recall. Instruct patients to immediately contact their healthcare provider for development of inflammation or blisters in an area that was previously irradiated [see Warnings and Precautions (5.5)].

Increased Risk of Toxicity with Ibuprofen in Patients with Renal Impairment: Advise patients with mild to moderate renal impairment of the risks associated with concomitant ibuprofen use and instruct them to avoid use of all ibuprofen containing products for 2 days before, the day of, and 2 days following administration of Pemetrexed Injection [see Dosage and Administration (2.5), Warnings and Precautions (5.6), and Drug Interactions (7)].

Embryo-Fetal Toxicity: Advise females of reproductive potential and males with female partners of reproductive potential of the potential risk to a fetus [see Warnings and Precautions (5.7) and Use in Specific Populations (8.1)]. Advise females of reproductive potential to use effective contraception during treatment with Pemetrexed Injection and for 6 months after the last dose. Advise females to inform their prescriber of a known or suspected pregnancy. 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 Warnings and Precautions (5.7) and Use in Specific Populations (8.3)].

Lactation: Advise women not to breastfeed during treatment with Pemetrexed Injection and for 1 week after the last dose [see Use in Specific Populations (8.2)].

This product’s label may have been updated. For current full prescribing information, please visit www.pfizer.com.

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

Distributed by: Hospira, Inc., Lake Forest, IL 60045 USA

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LAB-1430-1.0

PATIENT INFORMATIONPemetrexed (peh-meh-TREX-ed) Injectionfor 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:
  • 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 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.
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:
  • have kidney problems.
  • have had radiation therapy.
  • 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. 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?
  • 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.
    • 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.
    • 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.
  • 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.
  • Pemetrexed Injection is given to you by intravenous (IV) infusion into your vein. The infusion is given over 10 minutes.
  • 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:
  • 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.
  • 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.
  • 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.
  • 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.
  • 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:
  • tiredness
  • nausea
  • loss of appetite
The most common side effects of Pemetrexed Injection when given with cisplatin are:
  • vomiting
  • swelling or sores in your mouth or sore throat
  • constipation
  • low white blood cell counts (neutropenia)
  • low platelet counts (thrombocytopenia)
  • 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: pemetrexedInactive 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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