Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
PEMETREXED DISODIUM vs PEMETREXED
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
Pemetrexed is a folate analog metabolic inhibitor that disrupts folate-dependent metabolic processes essential for cell replication. It inhibits thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT), thereby inhibiting de novo synthesis of thymidine and purine nucleotides.
Pemetrexed is a folate analog metabolic inhibitor that disrupts folate-dependent metabolic processes essential for cell replication. It inhibits thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT), leading to inhibition of de novo purine and pyrimidine synthesis.
Mesothelioma: In combination with cisplatin for treatment of malignant pleural mesothelioma in patients who are not candidates for curative surgery.,Non-small cell lung cancer: First-line treatment in combination with cisplatin for locally advanced or metastatic nonsquamous NSCLC.,Non-small cell lung cancer: Maintenance monotherapy for locally advanced or metastatic nonsquamous NSCLC with stable disease after 4 cycles of platinum-based chemotherapy.,Non-small cell lung cancer: Second-line treatment as monotherapy for locally advanced or metastatic nonsquamous NSCLC after prior chemotherapy.
Malignant pleural mesothelioma (in combination with cisplatin),Non-small cell lung cancer (NSCLC) - first-line treatment (in combination with cisplatin),NSCLC - maintenance therapy (after platinum-based chemotherapy),NSCLC - second-line treatment (single agent)
500 mg/m2 intravenously over 10 minutes on Day 1 of each 21-day cycle, with vitamin B12 and folic acid supplementation.
500 mg/m2 IV over 10 minutes on Day 1 of each 21-day cycle, with folic acid and vitamin B12 supplementation.
Terminal half-life is 3.5 hours in patients with normal renal function. Increases in renal impairment (up to 20 hours if Cr Cl <45 m L/min).
Terminal half-life is approximately 3.5 hours in patients with normal renal function (creatinine clearance ≥60 m L/min). Clinically, half-life is prolonged in renal impairment (up to 20 hours in severe impairment), requiring dose adjustment.
Pemetrexed is primarily eliminated unchanged in urine. It undergoes minimal hepatic metabolism. The drug is a substrate for multidrug resistance-associated proteins (MRPs) and possibly other transporters.
Pemetrexed is primarily eliminated unchanged in the urine. It undergoes minimal hepatic metabolism. Renal excretion accounts for approximately 70-90% of elimination.
Primarily renal excretion (70-90% as unchanged drug within 24 hours). Biliary/fecal excretion accounts for <5%.
Primarily eliminated unchanged in urine (70-90% of dose via renal excretion over 24 hours); minimal biliary/fecal excretion (<5%).
~81% bound primarily to albumin.
Approximately 81% bound to plasma proteins, primarily albumin (given its structure as a folate analog).
Vd = 0.2 L/kg (approximately 16 L in adults). Indicates limited distribution to extravascular spaces.
Volume of distribution is about 16.1 L/m² (total body water); in weight-based terms ~0.3-0.4 L/kg, indicating limited tissue distribution consistent with a polar molecule.
Intravenous: 100% (only route of administration).
Only administered intravenously; oral bioavailability is negligible (<1%) due to poor intestinal absorption and first-pass metabolism, thus no oral formulation available.
Cr Cl ≥45 m L/min: No adjustment. Cr Cl <45 m L/min: Not recommended. For Cr Cl 40-59 m L/min, no adjustment; Cr Cl <40 m L/min, not recommended based on clinical trial criteria.
Cr Cl ≥45 m L/min: no adjustment. Cr Cl <45 m L/min: not recommended; consider dose reduction to 500 mg/m2 if Cr Cl 40–45 m L/min with close monitoring; do not use if Cr Cl <40 m L/min.
No specific dose adjustment guidelines for hepatic impairment. Use caution with bilirubin >1.5 times ULN and/or AST/ALT >3 times ULN. Child-Pugh classification not formally studied.
Child-Pugh A and B: no adjustment. Child-Pugh C: insufficient data; use with caution.
Safety and efficacy not established in pediatric patients. No recommended dosing.
Not FDA approved; limited data: 500 mg/m2 IV over 10 minutes Day 1 every 21 days, with folic acid and B12 supplementation, based on adult protocol. Weight-based for patients <1.5 m²: calculate BSA and dose accordingly.
No specific dose adjustment recommended based on age alone. Monitor renal function closely as elderly patients may have reduced Cr Cl.
No specific dose adjustment; monitor renal function (Cr Cl) due to age-related decline; ensure folic acid and vitamin B12 supplementation.
Pemetrexed can cause severe myelosuppression, which may lead to infection and bleeding. Patients must be monitored for bone marrow suppression. Adequate folic acid and vitamin B12 supplementation is required to reduce toxicity.
Pemetrexed can cause severe and sometimes fatal myelosuppression, renal failure, and severe gastrointestinal toxicity. Patients must be pretreated with corticosteroids and folic acid and vitamin B12 to reduce toxicity.
Bone marrow suppression: Monitor blood counts regularly; dose adjust or hold for severe neutropenia, thrombocytopenia, or anemia.,Renal toxicity: Avoid in creatinine clearance <45 m L/min; monitor renal function.,Gastrointestinal toxicity: Severe diarrhea, mucositis may occur; manage with supportive care.,Dermatologic toxicity: Severe rash may occur; premedicate with corticosteroids.,Radiation recall: Risk of severe radiation recall in patients who have received prior radiotherapy.,Folic acid and vitamin B12 supplementation: Required to reduce hematologic and gastrointestinal toxicity.,Pregnancy: Can cause fetal harm; advise women of reproductive potential to use effective contraception.
Bone marrow suppression (including neutropenia, thrombocytopenia, anemia); renal toxicity (monitor renal function); gastrointestinal toxicity (e.g., diarrhea, mucositis); dermatologic reactions (e.g., rash, exfoliation); radiation recall reactions; increased risk of toxicity in patients with pleural effusion or ascites (consider drainage); embryo-fetal toxicity.
History of severe hypersensitivity reaction to pemetrexed or any excipient.,Patients with creatinine clearance <45 m L/min (contraindicated for use in combination with cisplatin due to increased toxicity).
History of severe hypersensitivity reaction to pemetrexed; concomitant administration of yellow fever vaccine; severe renal impairment (creatinine clearance <45 m L/min) (relative contraindication due to increased toxicity).
No known food interactions. Avoid folic acid-containing supplements beyond prescribed dose as they may interfere with pemetrexed activity. Maintain adequate hydration.
No specific food interactions are documented. However, patients should maintain adequate folic acid intake through diet and supplements as prescribed. Avoid grapefruit or grapefruit juice? There is no known interaction with grapefruit. Patients should maintain a balanced diet and avoid alcohol to prevent liver stress.
Pemetrexed is contraindicated in pregnancy. It is an antifolate antimetabolite that inhibits thymidylate synthase and other folate-dependent enzymes, essential for DNA synthesis and cell division. Based on its mechanism of action and animal studies, it is expected to cause fetal harm when administered to a pregnant woman. First trimester: High risk of teratogenicity (neural tube defects, craniofacial, cardiovascular malformations) due to folate antagonism. Second and third trimesters: Risk of fetal growth restriction, oligohydramnios, and fetal death. Embryofetal toxicity and teratogenicity have been demonstrated in mice and rats at doses lower than the human therapeutic dose.
Pemetrexed is a folate analog antimetabolite that inhibits thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase. It is teratogenic in animal studies at doses below the recommended human dose. In humans, there are no adequate studies in pregnant women; however, based on its mechanism of action, there is potential for fetal harm. First trimester exposure carries the highest risk for major congenital malformations (neural tube, cardiac, skeletal defects). Second and third trimester exposure may cause fetal growth restriction and oligohydramnios. Late pregnancy administration may cause neonatal myelosuppression and toxicity.
No data available on the presence of pemetrexed in human milk, its effects on the breastfed infant, or on milk production. Due to the potential for serious adverse reactions in the breastfed infant (including myelosuppression, gastrointestinal toxicity, and carcinogenesis), breastfeeding is not recommended during therapy and for at least 1 week after the last dose. The M/P ratio is unknown.
No human data on excretion into breast milk. Pemetrexed is a small molecule (molecular weight 427.46 g/mol) with low protein binding (~81%) and a terminal half-life of 3.5 hours; it is likely excreted into milk. M/P ratio unknown. Due to potential for serious adverse reactions (myelosuppression, gastrointestinal toxicity), breastfeeding is contraindicated during therapy and for at least 1 week after last dose.
No specific dose adjustment guidelines exist for pemetrexed in pregnancy because its use is contraindicated. However, pregnancy may alter the pharmacokinetics of pemetrexed due to increased renal clearance (increased glomerular filtration rate) and expanded plasma volume, potentially reducing drug exposure. No formal studies have been conducted. Given the high risk of fetal harm, pemetrexed should not be used in pregnant women. If treatment is deemed necessary for a life-threatening condition, the risks versus benefits must be considered, and dosing adjustments cannot be recommended due to lack of data.
No established dosing guidelines for pregnancy. Physiologic changes (increased renal blood flow, volume of distribution) may reduce pemetrexed exposure, but dose adjustments are not recommended due to lack of safety data. Use only if clearly needed and risk of maternal toxicity outweighs fetal risks. Avoid in first trimester.
Administer folic acid 350-1000 mcg orally daily beginning 7 days before first dose and continuing throughout therapy. Administer vitamin B12 1000 mcg IM 1 week before first dose and every 3 cycles thereafter. Premedicate with dexamethasone 4 mg orally twice daily the day before, day of, and day after each dose to reduce cutaneous reactions. Monitor for myelosuppression, especially neutropenia; dose reduce as needed. Contraindicated in patients with creatinine clearance <45 m L/min. Avoid NSAIDs 2-5 days before and 2 days after pemetrexed due to increased toxicity.
Pemetrexed requires vitamin B12 and folate supplementation to reduce hematologic and gastrointestinal toxicity. Administer folic acid daily (350-1000 mcg) starting 7 days before first dose and continue for 21 days after last dose. Vitamin B12 (1000 mcg IM) should be given 1 week before first dose and repeated every 3 cycles. Contraindicated in patients with creatinine clearance <45 m L/min; dose reduction required for moderate renal impairment. Monitor for severe cutaneous reactions (Stevens-Johnson syndrome) and interstitial pneumonitis. Premedicate with dexamethasone (4 mg PO BID) on the day before, day of, and day after pemetrexed to reduce skin rash incidence.
Take folic acid supplements daily, starting 7 days before your first treatment and continuing until your doctor stops it.,You will receive vitamin B12 injections before your first dose and then every 9 weeks.,Take a steroid medication (dexamethasone) as prescribed the day before, day of, and day after each infusion to prevent skin reactions.,Avoid taking NSAIDs (like ibuprofen or naproxen) for at least 2-5 days before and 2 days after your pemetrexed infusion.,Report any signs of infection (fever, chills, sore throat), unusual bleeding or bruising, or severe fatigue immediately.,Drink plenty of fluids unless otherwise instructed. There are no specific dietary restrictions, but maintain a balanced diet.,Use effective contraception during treatment and for at least 6 months after the last dose (females) or 3 months (males). Do not breastfeed during treatment.
Take folic acid daily as prescribed, starting 7 days before your first treatment and continuing for 21 days after the last dose.,You will receive a vitamin B12 injection once every three treatment cycles, beginning 1 week before the first dose.,Report any new or worsening shortness of breath, cough, or fever immediately, as this may indicate lung inflammation.,Avoid nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen or aspirin unless approved by your doctor, especially if you have kidney problems.,Use effective contraception during treatment and for 6 months after the last dose; male patients should avoid fathering a child.,Do not breastfeed while taking this medication.,Stay hydrated and inform your doctor if you experience severe diarrhea, vomiting, or signs of dehydration.,Limit sun exposure and use sunscreen, as pemetrexed may cause photosensitivity.
"The risk or severity of adverse effects can be increased when Pemetrexed is combined with Leflunomide."
"Pemetrexed may decrease the cardiotoxic activities of Acetyldigitoxin."
"Pemetrexed may increase the immunosuppressive activities of Fingolimod."
"The risk or severity of adverse effects can be increased when Pemetrexed is combined with Leflunomide."
"Pemetrexed may decrease the cardiotoxic activities of Acetyldigitoxin."
"Pemetrexed may increase the immunosuppressive activities of Fingolimod."
Explore head-to-head clinical comparisons of other medications in the same therapeutic classes.
Common clinical questions about PEMETREXED DISODIUM vs PEMETREXED, answered by our medical review team.
PEMETREXED DISODIUM is a Antineoplastic Antifolate that works by Pemetrexed is a folate analog metabolic inhibitor that disrupts folate-dependent metabolic processes essential for cell replication. It inhibits thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT), thereby inhibiting de novo synthesis of thymidine and purine nucleotides.. PEMETREXED is a Antineoplastic Antifolate that works by Pemetrexed is a folate analog metabolic inhibitor that disrupts folate-dependent metabolic processes essential for cell replication. It inhibits thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT), leading to inhibition of de novo purine and pyrimidine synthesis.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between PEMETREXED DISODIUM and PEMETREXED depend on the specific clinical indication. These are both Antineoplastic Antifolate agents and are not directly interchangeable by dose. A physician or clinical pharmacist should guide any therapeutic switching decisions.
The standard adult dose of PEMETREXED DISODIUM is: 500 mg/m2 intravenously over 10 minutes on Day 1 of each 21-day cycle, with vitamin B12 and folic acid supplementation.. The standard adult dose of PEMETREXED is: 500 mg/m2 IV over 10 minutes on Day 1 of each 21-day cycle, with folic acid and vitamin B12 supplementation.. Dosing should always be individualized based on indication, renal and hepatic function, age, and other patient factors.
A moderate-severity drug interaction has been identified when combining PEMETREXED DISODIUM and PEMETREXED. The risk or severity of adverse effects can be increased when Pemetrexed is combined with Leflunomide. Consult your prescriber before combining these medications.
The maternal-fetal safety profiles differ. PEMETREXED DISODIUM is classified as Category C. Pemetrexed is contraindicated in pregnancy. It is an antifolate antimetabolite that inhibits thymidylate synthase and other folate-dependent enzymes, essential for DNA synthesis an. PEMETREXED is classified as Category C. Pemetrexed is a folate analog antimetabolite that inhibits thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase. It is teratogenic in ani. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.