Drug Formulary information is intended for use by healthcare professionals. It is not intended to be medical advice. Some of the information, including information about funding for cancer drugs, does not apply to all patients. Cancer treatment plans are unique to each patient. If you are a patient, please speak with your healthcare team to understand how this information applies to you.
PEME
Regimen is considered appropriate as part of the standard care of patients; meaningfully improves outcomes (survival, quality of life), tolerability or costs compared to alternatives (recommended by the Disease Site Team and national consensus body e.g. pan-Canadian Oncology Drug Review, pCODR). Recommendation is based on an appropriately conducted phase III clinical trial relevant to the Canadian context OR (where phase III trials are not feasible) an appropriately sized phase II trial. Regimens where one or more drugs are not approved by Health Canada for any indication will be identified under Rationale and Use.
Low
Other Supportive Care:
Also refer to CCO Antiemetic Recommendations.
Premedication:
- Vitamin supplementation starting ≥ 1 week prior to first pemetrexed dose; continue until 3 weeks after last dose to reduce treatment-related toxicities:
- Folic acid 0.4 mg - 1 mg PO daily
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Vitamin B12 1000 mcg IM q9 weeks
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Dexamethasone (e.g. 4 mg PO BID) beginning on the day before chemotherapy for a total of 3 days to reduce the incidence and severity of cutaneous reactions.
Doses should be modified according to the protocol by which the patient is being treated.
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NSAIDs should be held for at least 2-5 days prior to, and at least 2 days after pemetrexed infusion (see Interactions section).
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Patients should not begin a new treatment cycle unless:
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ANC ≥ 1.5 x 109/L
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Platelets ≥ 100 x 109/L
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Creatinine clearance is ≥ 45 mL/min
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Dosage with toxicity
Hematologic:
| Worst toxicity in previous cycle | Grade | Pemetrexed (% previous dose)* |
| Thrombocytopenic bleeding | 50% | |
| ANC | Grade 4 | 75% |
| Platelets | ≥ Grade 3 | |
| Recurrent myelosuppression after 2 dose reductions | ≥ Grade 3 | Discontinue |
*Start next cycle only when ANC ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L and related organ/non-hematologic toxicity ≤ grade 2 (or recovery to baseline).
Non-hematologic:
| Worst toxicity in previous cycle | Grade | Pemetrexed (% previous dose)* |
| Neurotoxicity | Grade 2 | 100% |
| ≥ Grade 3 | Discontinue | |
| Mucositis | ≥ Grade 3 | 50% |
| Diarrhea | ≥ Grade 3 or requiring hospitalization | 75% |
| Pneumonitis | Any | Hold and investigate; discontinue if confirmed |
| All other related organ / non-hematologic toxicity | Grade 3 | 75% |
| Grade 4 | Discontinue | |
|
Stevens-Johnson syndrome |
Any | |
| Toxic epidermal necrolysis | ||
| Recurrent non-hematologic toxicity after 2 dose reductions | ≥ Grade 3 |
*Start next cycle only when ANC ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L and related organ/non-hematologic toxicity ≤ grade 2 (or recovery to baseline).
Hepatic Impairment
Pemetrexed is not extensively metabolized in the liver. No specific studies have been performed in patients with moderate or severe hepatic impairment. Pemetrexed should be used with caution in patients with hepatic impairment.
Renal Impairment
|
Creatinine clearance (mL/min)
|
Pemetrexed (% of previous dose)
|
|
≥ 45
|
100%*
|
|
< 45
|
Discontinue
|
*Exercise caution with co-administration of NSAIDs for patients with CrCl 45-79mL/min
Dosage in the Elderly
No dose adjustments are needed but patients should be monitored closely. In maintenance therapy, more frequent myelosuppression, renal and severe GI adverse events were noted in patients ≥ 65 years of age. There was no observed effect of age on pemetrexed pharmacokinetics over the range of 26 to 80 years.
Refer to pemetrexed drug monograph(s) for additional details of adverse effects
| Common (25-49%) | Less common (10-24%) | Uncommon (< 10%), but may be severe or life-threatening |
|
|
|
Refer to pemetrexed drug monograph(s) for additional details
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Hold NSAIDs with short half-lives (eg. ibuprofen) for at least 2 days before to at least 2 days after pemetrexed administration in patients with mild to moderate renal impairment (CrCl 45–79 mL/min).
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Hold NSAIDs with long half-lives (eg. piroxicam) for at least 5 days before to at least 2 days after pemetrexed administration.
Refer to pemetrexed drug monograph(s) for additional details.
Administration:
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Reconstitute as directed with Normal Saline (preservative free).
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Dilute drug to a total volume of 100mL with normal saline only and infuse intravenously over 10 minutes.
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Reconstituted solution maybe colourless to yellow or green-yellow.
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Incompatible with calcium-containing solutions.
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Do not co-administer with other drugs and diluents.
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Keep unopened vials at room temperature. Pemetrexed is not light sensitive.
Contraindications:
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Patients with a known hypersensitivity to the drug/excipients.
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Concomitant use of yellow fever vaccine.
Other Warning/Precautions:
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Exercise caution in patients with pre-existing cardiovascular risk factors.
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Patients with moderate-severe renal dysfunction (CrCl < 45 mL/min).
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Avoid the use of live or live-attenuated vaccines.
Pregnancy/Lactation
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Pemetrexed is not recommended for use in pregnancy. Adequate contraception should be used by both sexes during treatment, and for at least 6 months after the last dose.
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Breastfeeding is not recommended.
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Pemetrexed may cause irreversible infertility.
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Sperm preservation should be considered prior to starting treatment in males.
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Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.
Recommended Clinical Monitoring
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CBC; baseline, before each cycle, on days 8 and 15 of each cycle (for nadir and recovery), and as clinically indicated
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Liver function tests; baseline and at each visit
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Renal function tests; baseline and at each visit
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Clinical toxicity assessment for fatigue, pneumonitis, thromboembolism, mucositis, diarrhea, neurotoxicity, infection, bleeding and rash; at each visit
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Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
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Jassem J, Ramlau R, Santoro A, et al. Phase III trial of pemetrexed plus best supportive care compared with best supportive care in previously treated patients with advanced malignant pleural mesothelioma. J Clin Oncol 2008;26(10):1698-704.
Taylor P, Castagneto B, Dark G, et al. Single-agent pemetrexed for chemonaïve and pretreated patients with malignant pleural mesothelioma: results of an International Expanded Access Program. J Thorac Oncol 2008;3(7):764-71.
Pemetrexed drug monograph, Cancer Care Ontario.
June 2021 removed "unfunded" flag from pemetrexed
Regimen Abstracts
A Regimen Abstract is an abbreviated version of a Regimen Monograph and contains only top level information on usage, dosing, schedule, cycle length and special notes (if available). It is intended for healthcare providers and is to be used for informational purposes only. It is not intended to constitute or be a substitute for medical advice, and all uses of the Regimen Abstract are subject to clinical judgment. Such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability, and Cancer Care Ontario disclaims all liability for the use of this information, and for any claims, actions, demands or suits that arise from such use.
Information in regimen abstracts is accurate to the extent of the ST-QBP regimen master listings, and has not undergone the full review process of a regimen monograph. Full regimen monographs will be published for each ST-QBP regimen as they are developed.
Regimen Monographs
Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.
The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.
The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.
Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.
While care has been taken in the preparation of the information contained in the Formulary, such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability.
CCO and the Formulary’s content providers shall have no liability, whether direct, indirect, consequential, contingent, special, or incidental, related to or arising from the information in the Formulary or its use thereof, whether based on breach of contract or tort (including negligence), and even if advised of the possibility thereof. Anyone using the information in the Formulary does so at his or her own risk, and by using such information, agrees to indemnify CCO and its content providers from any and all liability, loss, damages, costs and expenses (including legal fees and expenses) arising from such person’s use of the information in the Formulary.