Note: New treatment cycles should not begin unless ANC ≥1,500/mm3, platelets ≥100,000/mm3, CrCl ≥45 mL/minute, and recovery of nonhematologic toxicity to ≤ grade 2.
Premedication: Start vitamin supplements 1 week before initial pemetrexed dose: Folic acid 400 to 1,000 mcg orally once daily (begin 7 days prior to treatment initiation; continue daily during treatment and for 21 days after last pemetrexed dose) and vitamin B12 1,000 mcg IM 7 days prior to treatment initiation and then every 3 cycles. Subsequent vitamin B12 doses may be administered on the same day as pemetrexed treatments. In patients without preexisting anemia, some data suggest that pemetrexed and cyanocobalamin may be started simultaneously to avoid delaying pemetrexed initiation (Singh 2019). Administer dexamethasone 4 mg orally twice daily for 3 days, beginning the day before treatment to minimize cutaneous reactions.
Bladder cancer, metastatic (off-label use): IV: 500 mg/m2 on day 1 of each 21-day cycle until disease progression or unacceptable toxicity (Sweeney 2006).
Cervical cancer, persistent or recurrent (off-label use): IV: 500 mg/m2 on day 1 of each 21-day cycle until disease progression or unacceptable toxicity occurs (Lorusso 2010) or 900 mg/m2 on day 1 of each 21-day cycle (Miller 2008).
Malignant pleural mesothelioma: IV: 500 mg/m2 on day 1 of each 21-day cycle (in combination with cisplatin); continue until disease progression or unacceptable toxicity. The American Society of Clinical Oncology guidelines for malignant pleural mesothelioma recommend first-line platinum/pemetrexed-based therapy for 4 to 6 cycles (ASCO [Kindler 2018]).
Off-label dosing/combinations: IV:
500 mg/m2 on day 1 of each 21-day cycle in combination with carboplatin (Ceresoli 2006) or 500 mg/m2 on day 1 of each 21-day cycle (in combination with carboplatin) until disease progression, unacceptable toxicity, or for a maximum of 9 cycles (Castagneto 2008) or 500 mg/m2 on day 1 of each 21-day cycle as single-agent therapy until disease progression or unacceptable toxicity (Taylor 2008) or 500 mg/m2 on day 1 every 3 weeks (in combination with cisplatin and bevacizumab) for up to 6 cycles, followed by bevacizumab maintenance therapy until disease progression or unacceptable toxicity (Zalcman 2016).
Non–small cell lung cancer, nonsquamous:
Initial treatment of locally advanced or metastatic NSCLC: IV: 500 mg/m2 on day 1 of each 21-day cycle (in combination with cisplatin) for up to 6 cycles or until disease progression or unacceptable toxicity.
Initial treatment of metastatic NSCLC: Alimta: IV: 500 mg/m2 on day 1 of each 21-day cycle (in combination with pembrolizumab and either carboplatin or cisplatin) for 4 cycles; following platinum-based therapy, may continue pemetrexed (alone or with pembrolizumab) as maintenance therapy until disease progression or unacceptable toxicity (Gandhi 2018).
Maintenance treatment of locally advanced or metastatic NSCLC (after 4 cycles of initial platinum-based therapy): IV: 500 mg/m2 on day 1 of each 21-day cycle (as a single-agent); continue until disease progression or unacceptable toxicity.
Second-line treatment of recurrent/metastatic disease (after prior chemotherapy): IV: 500 mg/m2 on day 1 of each 21-day cycle (as a single-agent); continue until disease progression or unacceptable toxicity.
Ovarian cancer, platinum-resistant (off-label use): IV: 500 mg/m2 on day 1 of each 21-day cycle (Vergote 2009).
Thymic malignancies, metastatic (off-label use): IV: 500 mg/m2 on day 1 of each 21-day cycle for 6 cycles or until disease progression or unacceptable toxicity occurs (Loehrer 2006).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Renal function may be estimated using the Cockcroft-Gault formula.
CrCl ≥45 mL/minute: No dosage adjustment necessary.
CrCl <45 mL/minute: Use is not recommended by the manufacturer (an insufficient number of patients have been studied for dosage recommendations).
Renal toxicity during treatment: Withhold pemetrexed until CrCl is ≥45 mL/minute.
According to a phase I study in advanced cancer patients with renal impairment, pemetrexed doses up to 500 mg/m2 (with vitamin supplementation) were well tolerated in patients with glomerular filtration rate (GFR) 40 to 79 mL/minute; however, accrual was halted in patients with GFR <29 mL/minute (due to toxicity) and accrual did not occur in patients with GFR 30 to 39 mL/minute. Patients with GFR ≥80 mL/minute tolerated doses of 600 mg/m2 (Mita 2006).
Concomitant ibuprofen use with renal dysfunction:
CrCl ≥80 mL/minute: No dosage adjustment necessary.
CrCl 45 to 79 mL/minute: Avoid ibuprofen for 2 days before, the day of, and for 2 days following a dose of pemetrexed. Monitor more frequently for myelosuppression, renal, and GI toxicities if concomitant ibuprofen administration cannot be avoided.
There are no dosage adjustments provided in the manufacturer's labeling; however, elevated AST, AST, or total bilirubin do not appear to affect pemetrexed pharmacokinetics.
Refer to adult dosing.
ASCO Guidelines for appropriate chemotherapy dosing in adults with cancer with a BMI ≥30 kg/m2: Utilize patient's actual body weight (full weight) for calculation of body surface area- or weight-based dosing, particularly when the intent of therapy is curative; manage regimen-related toxicities in the same manner as for patients with a BMI <30 kg/m2; if a dose reduction is utilized due to toxicity, may consider resumption of full weight-based dosing with subsequent cycles, if cause of toxicity (eg, hepatic or renal impairment) is clearly established and fully resolved, and performance status has markedly improved (ASCO [Griggs 2021]).
Note: When used in combination with other agents (eg cisplatin, carboplatin, pembrolizumab), those agents may also require dosage modification.
Hematologic toxicity: Upon recovery to ANC ≥1,500/mm3 and platelets ≥100,000/mm3, reinitiate therapy as stated below. Note: If ANC <500/mm3 or platelets <50,000/mm3 in previous cycles, permanently reduce pemetrexed dose.
ANC <500/mm3 and platelets ≥50,000/mm3: Reduce pemetrexed dose to 75% of previous dose.
Platelets <50,000/mm3 without bleeding: Reduce pemetrexed dose to 75% of previous dose.
Platelets <50,000/mm3 with bleeding: Reduce pemetrexed dose to 50% of previous dose.
Recurrent grade 3 or 4 myelosuppression after 2 dose reductions: Discontinue pemetrexed.
Nonhematologic toxicity: Withhold treatment until recovery to ≤ grade 2; upon recovery, reinitiate or discontinue therapy as follows:
Grade 3 or 4 toxicity (excluding mucositis and neurotoxicity): Reduce pemetrexed dose to 75% of previous dose.
Grade 3 or 4 diarrhea or any diarrhea requiring hospitalization: Reduce pemetrexed dose to 75% of previous dose.
Grade 3 or 4 mucositis: Reduce pemetrexed dose to 50% of previous dose.
Grade 3 or 4 neurotoxicity: Permanently discontinue pemetrexed.
Interstitial pneumonitis: Interrupt therapy and evaluate promptly for acute onset new or progressive pulmonary symptoms (eg, dyspnea, cough, fever); if interstitial pneumonitis is confirmed, permanently discontinue pemetrexed.
Radiation recall signs/symptoms: Permanently discontinue pemetrexed.
Severe or life-threatening bullous, blistering, or exfoliating dermatologic toxicity: Permanently discontinue pemetrexed.
Recurrent grade 3 or 4 nonhematologic toxicity after 2 dose reductions: Permanently discontinue pemetrexed.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Pemfexy: 500 mg/20 mL (20 mL) [contains propylene glycol]
Solution, Intravenous [preservative free]:
Generic: 100 mg/4 mL (4 mL); 500 mg/20 mL (20 mL); 1 g/40 mL (40 mL)
Solution, Intravenous, as disodium:
Generic: 100 mg/4 mL (4 mL); 500 mg/20 mL (20 mL)
Solution, Intravenous, as disodium [preservative free]:
Generic: 100 mg/4 mL (4 mL); 500 mg/20 mL (20 mL); 1 g/40 mL (40 mL)
Solution Reconstituted, Intravenous:
Alimta: 500 mg (1 ea)
Generic: 100 mg (1 ea); 500 mg (1 ea); 1000 mg (1 ea)
Solution Reconstituted, Intravenous [preservative free]:
Alimta: 100 mg (1 ea)
Generic: 100 mg (1 ea); 500 mg (1 ea); 750 mg (1 ea); 1000 mg (1 ea)
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution Reconstituted, Intravenous:
Alimta: 100 mg (1 ea); 500 mg ([DSC])
Generic: 100 mg (1 ea); 500 mg (1 ea); 1000 mg (1 ea)
IV: Infuse over 10 minutes. When used in combination with platinum-based therapy (cisplatin or carboplatin), administer pemetrexed prior to the platinum. Administer pemetrexed after pembrolizumab if administered on the same day.
Hazardous agent (NIOSH 2016 [group 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Malignant pleural mesothelioma: Initial treatment of malignant pleural mesothelioma (in combination with cisplatin) that is unresectable or in patients who are not otherwise candidates for curative surgery.
Non–small cell lung cancer, nonsquamous:
Initial treatment of locally advanced or metastatic nonsquamous non–small cell lung cancer (NSCLC) (in combination with cisplatin).
Initial treatment of metastatic, nonsquamous NSCLC (in combination with platinum chemotherapy and pembrolizumab) in patients with no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations (Alimta only).
Maintenance treatment (single-agent) of locally advanced or metastatic nonsquamous NSCLC if no progression after 4 cycles of platinum-based first-line therapy.
Single-agent treatment (after prior chemotherapy) of recurrent/metastatic nonsquamous NSCLC.
Limitation of use: Not indicated for the treatment of squamous cell NSCLC.
Bladder cancer, metastatic; Cervical cancer, persistent or recurrent; Ovarian cancer, platinum-resistant; Thymic malignancies, metastatic
PEMEtrexed may be confused with methotrexate, pembrolizumab, PRALAtrexate
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Dermatologic: Desquamation (≤14%), skin rash (≤14%)
Gastrointestinal: Nausea (12% to 31%), anorexia (19% to 22%), vomiting (6% to 16%), stomatitis (≤15%), diarrhea (5% to 13%)
Hematologic & oncologic: Anemia (15% to 19%; grades 3/4: 3% to 5%), neutropenia (6% to 11%; grades 3/4: 3% to 5%)
Nervous system: Fatigue (18% to 34%)
Respiratory: Pharyngitis (≤15%)
1% to 10%:
Cardiovascular: Edema (5%)
Dermatologic: Pruritus (7%), alopecia (6%), erythema multiforme (≤5%)
Gastrointestinal: Constipation (6%), abdominal pain (1% to <5%)
Hematologic & oncologic: Thrombocytopenia (8%; grades 3/4: 2%), febrile neutropenia (<5%)
Hepatic: Increased serum alanine aminotransferase (8% to 10%), increased serum aspartate aminotransferase (7% to 8%)
Hypersensitivity: Hypersensitivity reaction (<5%)
Infection: Infection (1% to <5%), sepsis (1%)
Nervous system: Neuropathy (sensory: 9%; motor: ≤5%)
Ophthalmic: Conjunctivitis (≤5%), increased lacrimation (1% to <5%)
Miscellaneous: Fever (8%)
<1%, postmarketing, and/or case reports: Bullous rash, cardiac arrhythmia, colitis, depression, esophagitis, gastrointestinal obstruction, hemolytic anemia, interstitial pneumonitis, pain, pancreatitis, pulmonary embolism, radiation recall phenomenon, renal failure syndrome, Stevens-Johnson syndrome, supraventricular cardiac arrhythmia, syncope, toxic epidermal necrolysis, ventricular tachycardia
Severe hypersensitivity to pemetrexed or any component of the formulation
Canadian labeling: Additional contraindications (not in the US labeling): Concomitant yellow fever vaccine
Concerns related to adverse effects:
• Bone marrow suppression: Pemetrexed may cause severe myelosuppression, including anemia, neutropenia, thrombocytopenia and/or pancytopenia; myelosuppression is often dose-limiting. Severe myelosuppression may require blood transfusion or may lead to neutropenic infection. Prophylactic folic acid and vitamin B12 supplements are necessary to reduce hematologic toxicity, febrile neutropenia and infection; initiate supplementation 1 week before the first dose of pemetrexed and continue for 21 days after the last pemetrexed dose (the risk for myelosuppression is higher in patients who did not receive vitamin supplementation).
• Cutaneous reactions: Serious and occasionally fatal, bullous, blistering, and exfoliative dermatologic toxicity may occur; pretreatment with dexamethasone is necessary to reduce the incidence and severity of cutaneous reactions. Rarely, Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported.
• GI toxicity: GI toxicity may occur; prophylactic folic acid and vitamin B12 supplements are necessary to reduce GI toxicity. Initiate supplementation 1 week before the first dose of pemetrexed and continue for 21 days after the last pemetrexed dose.
• Hypersensitivity: Hypersensitivity (including allergic reaction) has been reported with pemetrexed.
• Nephrotoxicity: Pemetrexed may cause severe (and potentially fatal) renal toxicity (renal toxicity may occur with single-agent pemetrexed or when used in combination with other chemotherapy agents).
• Pulmonary toxicity: Interstitial pneumonitis has been observed with use; may be serious and/or fatal. Signs/symptoms indicative of interstitial pneumonitis may include acute onset new or progressive pulmonary symptoms such as dyspnea, cough, or fever.
• Radiation recall: Radiation recall may occur in patients administered pemetrexed who received radiation previously (weeks to years).
Disease-related concerns:
• Renal impairment: Pemetrexed is primarily cleared by the kidneys; decreased renal function results in increased toxicity. Concurrent nephrotoxic medications may result in delayed pemetrexed clearance.
• Third space fluid: Although the effect of third space fluid on pemetrexed pharmacokinetics has not been fully defined, studies have determined pemetrexed concentrations in patients with mild to moderate ascites/pleural effusions were similar to concentrations in trials of patients without third space fluid accumulation.
Concurrent drug therapy issues:
• Ibuprofen: Ibuprofen may reduce the clearance of pemetrexed. In patients with CrCl 45 to 79 mL/minute, interrupt ibuprofen therapy 2 days prior to, during, and 2 days after pemetrexed therapy. If concomitant use cannot be avoided, monitor for myelosuppression, renal, and gastrointestinal toxicity.
Dosage form specific issues:
• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated with hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Zar 2007).
Substrate of OAT1/3
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Baricitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Products: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
Brincidofovir: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
Cladribine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing cytotoxic chemotherapy several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification
COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider therapy modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and cytotoxic chemotherapy. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification
Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Ibuprofen: May increase the serum concentration of PEMEtrexed. Management: In patients with an estimated creatinine clearance of 45 to 79 mL/min, avoid ibuprofen for 2 days before, the day of, and 2 days following the administration of pemetrexed. Monitor for increased pemetrexed toxicities if combined. Risk D: Consider therapy modification
Inebilizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Influenza Virus Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating chemotherapy if possible. If vaccination occurs less than 2 weeks prior to or during chemotherapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents, such as cytotoxic chemotherapy. Risk D: Consider therapy modification
Lenograstim: Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider therapy modification
Lipegfilgrastim: Antineoplastic Agents may diminish the therapeutic effect of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider therapy modification
Methotrexate: PEMEtrexed may increase the serum concentration of Methotrexate. Management: Avoid coadministration of pemetrexed and methotrexate if possible. If coadministration is required, monitor closely for methotrexate toxicities (eg, hematological, gastrointestinal, nephrotoxicity toxicities). Risk D: Consider therapy modification
Natalizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Nitisinone: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy
Ocrelizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy
Palifermin: May enhance the adverse/toxic effect of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Risk D: Consider therapy modification
Pidotimod: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Pneumococcal Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification
Pretomanid: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Pyrimethamine: May enhance the adverse/toxic effect of PEMEtrexed. Risk C: Monitor therapy
Rabies Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification
Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Ruxolitinib (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants, such as cytotoxic chemotherapy, prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification
Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk C: Monitor therapy
Tacrolimus (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination
Taurursodiol: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk X: Avoid combination
Teriflunomide: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy
Tertomotide: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination
Typhoid Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of chemotherapy when possible. Patients vaccinated less than 14 days before initiating or during chemotherapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider therapy modification
Vaccines (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Vaccines (Live) may diminish the therapeutic effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Yellow Fever Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
Verify pregnancy status prior to treatment initiation in patients who could become pregnant. Patients who could become pregnant should use effective contraception during treatment and for at least 6 months after the last pemetrexed dose. Patients with partners who could become pregnant should use effective contraception during treatment and for 3 months after the last pemetrexed dose. Pemetrexed may impair fertility in males.
Based on findings in animal reproduction studies and on the mechanism of action, pemetrexed may cause fetal harm if administered during pregnancy.
It is not known if pemetrexed is present in breast milk. Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended during treatment and for 1 week after the final pemetrexed dose.
CBC with differential and platelets (at the beginning of each cycle, and on days 8 and 15 of each cycle if clinically indicated); renal function tests (serum creatinine, creatinine clearance, BUN; prior to each cycle and as needed) total bilirubin, ALT, AST (periodic). Verify pregnancy status prior to treatment initiation (in patients who could become pregnant). Monitor for signs/symptoms of mucositis and diarrhea, pulmonary toxicity, dermatologic toxicity, and radiation recall (monitor for inflammation or blistering in areas of prior radiation treatment).
The American Society of Clinical Oncology hepatitis B screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends hepatitis B virus (HBV) screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Pemetrexed is an antifolate; it disrupts folate-dependent metabolic processes essential for cell replication. Pemetrexed inhibits thymidylate synthase (TS), dihydrofolate reductase (DHFR), glycinamide ribonucleotide formyltransferase (GARFT), and aminoimidazole carboxamide ribonucleotide formyltransferase (AICARFT), the enzymes involved in folate metabolism and DNA synthesis, resulting in inhibition of purine and thymidine nucleotide and protein synthesis.
Distribution: Vdss: 16.1 L
Protein binding: 81%
Metabolism: Minimal
Half-life elimination: Normal renal function: 3.5 hours
Excretion: Urine (70% to 90% as unchanged drug)
Altered kidney function: Pemetrexed clearance decreases and AUC increases as renal function decreases; in patients with CrCl of 45, 50, and 80 mL/minute, AUC was increased 65%, 54%, and 13%, respectively, compared with patients with CrCl of 100 mL/minute.
Solution (PEMEtrexed Disodium Intravenous)
1 g/40mL (per mL): $27.00 - $31.34
100 mg/4 mL (per mL): $30.31 - $210.58
500 mg/20 mL (per mL): $27.33 - $210.57
Solution (PEMEtrexed Intravenous)
1 g/40mL (per mL): $56.48
100 mg/4 mL (per mL): $59.46
500 mg/20 mL (per mL): $59.46
Solution (Pemfexy Intravenous)
500 mg/20 mL (per mL): $244.69
Solution (reconstituted) (Alimta Intravenous)
100 mg (per each): $970.32
500 mg (per each): $4,851.60
Solution (reconstituted) (PEMEtrexed Disodium Intravenous)
100 mg (per each): $36.00 - $856.16
500 mg (per each): $180.00 - $4,280.78
750 mg (per each): $1,237.50 - $6,421.18
1000 mg (per each): $1,200.00 - $8,561.57
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
