Pemetrexed Accord: Uses, Dosage & Side Effects
Pemetrexed – antifolate chemotherapy for mesothelioma and non-small cell lung cancer
Quick Facts: Pemetrexed Accord
Key Takeaways About Pemetrexed Accord
- Mandatory vitamin supplementation: You must take folic acid daily and receive vitamin B12 injections to reduce the risk of serious side effects during pemetrexed treatment
- Specifically for non-squamous NSCLC: Pemetrexed is effective in non-squamous non-small cell lung cancer and mesothelioma, but is not used for squamous cell carcinoma of the lung
- Blood monitoring required: Blood tests are performed before every infusion cycle to check blood counts, kidney and liver function
- Avoid NSAIDs around treatment: Common painkillers like ibuprofen can increase pemetrexed toxicity and must be avoided around treatment days
- Corticosteroid premedication: Dexamethasone tablets are taken the day before, the day of, and the day after each infusion to prevent skin reactions
What Is Pemetrexed Accord and What Is It Used For?
Pemetrexed Accord is a chemotherapy medicine used to treat two types of cancer: malignant pleural mesothelioma (a cancer of the lung lining often caused by asbestos exposure) and advanced non-small cell lung cancer (NSCLC) with non-squamous histology. It works by blocking folate-dependent enzymes that cancer cells need to multiply.
Pemetrexed belongs to a class of anticancer drugs known as antifolates. The active substance, pemetrexed, inhibits multiple enzymes in the folate metabolic pathway—specifically thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT). These enzymes play essential roles in DNA and RNA synthesis, meaning that when they are blocked, cancer cells cannot replicate their genetic material efficiently and eventually die.
Pemetrexed Accord is a generic formulation of pemetrexed that has been approved by the European Medicines Agency (EMA) and has demonstrated pharmaceutical equivalence to the originator product ALIMTA. Other generic brands containing the same active substance include Pemetrexed Pfizer, Pemetrexed medac, Pemetrexed Zentiva, Pemetrexed EVER Pharma, Pemetrexed Fresenius Kabi, and Armisarte.
Approved indications
Pemetrexed Accord has several approved therapeutic indications:
- Malignant pleural mesothelioma: In combination with cisplatin for patients who have not previously received chemotherapy. Mesothelioma is a rare but aggressive cancer of the pleural lining that is strongly associated with prior asbestos exposure. The landmark EMPHACIS trial demonstrated that pemetrexed plus cisplatin significantly improved median survival compared to cisplatin alone (12.1 versus 9.3 months).
- First-line treatment of advanced NSCLC: In combination with cisplatin for patients with non-squamous histology (such as adenocarcinoma or large cell carcinoma) who have not previously received chemotherapy for advanced disease. A pivotal phase III trial showed superior overall survival for pemetrexed-cisplatin versus gemcitabine-cisplatin in non-squamous NSCLC.
- Maintenance therapy for NSCLC: As a single agent for patients whose disease has responded to or remained stable after initial platinum-based chemotherapy containing pemetrexed (continuation maintenance) or other platinum-based regimens (switch maintenance).
- Second-line treatment of advanced NSCLC: As a single agent for patients whose cancer has progressed after prior chemotherapy, regardless of whether it included pemetrexed.
Pemetrexed is specifically indicated for non-squamous non-small cell lung cancer. Clinical studies have shown that patients with squamous cell histology do not benefit from pemetrexed-based regimens to the same degree as those with non-squamous histology. Your oncologist will determine your lung cancer subtype through biopsy before recommending treatment.
What Should You Know Before Taking Pemetrexed Accord?
Before starting pemetrexed treatment, your doctor will assess your kidney function, blood counts, and overall health status. You must not take pemetrexed if you are allergic to pemetrexed or any of its ingredients, if you are breastfeeding, or if you have recently received or plan to receive a yellow fever vaccine.
Contraindications
There are several situations where pemetrexed must not be used:
- Hypersensitivity: Do not use pemetrexed if you are allergic to pemetrexed disodium or any other ingredient in the formulation (citric acid, L-methionine, monothioglycerol, sodium hydroxide, hydrochloric acid, water for injections).
- Breastfeeding: Breastfeeding must be stopped during pemetrexed treatment, as the drug may pass into breast milk and cause harm to the infant.
- Yellow fever vaccine: Pemetrexed must not be given concurrently with yellow fever vaccination or if yellow fever vaccine has recently been administered, due to the risk of fatal systemic vaccine disease in immunosuppressed patients.
- Severe renal impairment: Pemetrexed is primarily eliminated through the kidneys. Patients with severely impaired kidney function (creatinine clearance below 45 ml/min) should generally not receive pemetrexed due to the risk of increased toxicity.
Warnings and Precautions
Discuss the following with your oncologist before and during pemetrexed treatment:
- Kidney function: Your kidneys play a critical role in eliminating pemetrexed from your body. Blood tests to assess renal function are mandatory before each infusion cycle. If your kidney function is reduced, your doctor may adjust the dose or delay treatment.
- Blood count monitoring: Pemetrexed suppresses bone marrow function, which means it can lower your levels of white blood cells (increasing infection risk), red blood cells (causing anaemia), and platelets (increasing bleeding risk). Complete blood counts are performed before each cycle to ensure safe levels.
- Liver function: Liver enzyme levels are monitored before each cycle, as pemetrexed can cause hepatotoxicity.
- Prior or planned radiation therapy: Inform your doctor if you have received or are scheduled for radiation therapy, as combining radiation with pemetrexed can cause enhanced toxicity at the radiation site (radiation recall dermatitis) or other complications.
- Fluid accumulation: If you have fluid around the lungs (pleural effusion) or in the abdomen (ascites), your doctor may decide to drain this fluid before treatment, as it can act as a reservoir for pemetrexed and increase toxicity.
- Heart disease: Inform your doctor if you have or have had any heart conditions, as cardiac events have been reported during pemetrexed treatment.
- Vaccinations: Live vaccines should be avoided during treatment due to your suppressed immune system. Inform your doctor if you have recently been vaccinated.
Pemetrexed Accord should not be used in children and adolescents under 18 years of age, as there is no experience with the drug in this population and safety and efficacy have not been established.
Pregnancy and Breastfeeding
Pemetrexed can cause serious harm to an unborn baby. If you are pregnant, think you may be pregnant, or are planning to become pregnant, you must discuss this with your doctor before treatment begins. Treatment with pemetrexed should be avoided during pregnancy unless the potential benefit to the mother clearly outweighs the risk to the foetus.
Women of childbearing potential must use effective contraception during treatment and for at least 6 months after the last dose of pemetrexed. Men are advised not to father a child during treatment and for up to 3 months after the last dose, and should use effective contraception throughout this period. Pemetrexed may affect fertility, and men should consider sperm preservation before starting treatment.
Breastfeeding must be discontinued during pemetrexed treatment, as it is unknown whether pemetrexed passes into breast milk, and a risk to the nursing infant cannot be excluded.
Driving and Operating Machinery
Pemetrexed treatment may cause fatigue. If you feel tired or unwell after receiving treatment, you should not drive or operate heavy machinery until you feel well enough to do so safely.
Sodium Content
Pemetrexed Accord contains sodium. The maximum recommended daily dose contains up to 304 mg of sodium per dose, which is equivalent to approximately 15.2% of the WHO recommended maximum daily intake of sodium for adults. This should be taken into account if you are on a sodium-restricted diet. Discuss this with your doctor or pharmacist if you require pemetrexed regularly.
How Does Pemetrexed Accord Interact with Other Drugs?
Pemetrexed has clinically significant interactions with NSAIDs (ibuprofen, naproxen), nephrotoxic drugs, and live vaccines. Since pemetrexed is eliminated primarily through the kidneys, any drug that impairs renal function or competes for tubular secretion can increase pemetrexed levels and toxicity.
Drug interactions are an important safety consideration during pemetrexed therapy. Because pemetrexed is primarily excreted unchanged by the kidneys through glomerular filtration and active tubular secretion, drugs that affect kidney function can significantly alter pemetrexed levels in the body. Below are the most important interactions to be aware of.
Major Interactions
| Drug / Class | Interaction | Recommendation |
|---|---|---|
| NSAIDs (short-acting) Ibuprofen, diclofenac, aspirin (high-dose) |
Reduce renal clearance of pemetrexed, increasing blood levels and risk of toxicity (myelosuppression, GI toxicity) | Avoid for at least 2 days before, the day of, and 2 days after pemetrexed administration |
| NSAIDs (long-acting) Naproxen, piroxicam, meloxicam |
Same mechanism as short-acting NSAIDs but with prolonged effect | Avoid for at least 5 days before through 2 days after pemetrexed treatment |
| Nephrotoxic drugs Aminoglycosides, amphotericin B, cisplatin |
Impair renal function, reducing pemetrexed clearance and increasing toxicity. Note: cisplatin is intentionally co-administered with careful hydration protocols | Monitor renal function closely. Ensure adequate hydration before and after cisplatin |
| Live vaccines Yellow fever, BCG, varicella, MMR |
Risk of fatal systemic vaccine disease due to immunosuppression | Contraindicated. Do not administer live vaccines during or shortly after treatment |
Minor Interactions
| Drug / Class | Interaction | Recommendation |
|---|---|---|
| Proton pump inhibitors Omeprazole, esomeprazole, pantoprazole |
May affect absorption of oral folic acid supplementation; theoretical interaction | Inform your doctor; generally can continue but monitor |
| Low-dose aspirin 75–325 mg daily |
Minimal effect on pemetrexed clearance at cardioprotective doses | Can generally be continued; discuss with your oncologist |
| Paracetamol (acetaminophen) | No significant pharmacokinetic interaction | Preferred analgesic during pemetrexed treatment |
Always inform your oncologist about all medicines you are taking, including over-the-counter medicines, herbal supplements, and vitamins. This includes any painkillers you may purchase without a prescription. Your doctor needs a complete picture to determine which medicines are safe to take around your chemotherapy cycles.
What Is the Correct Dosage of Pemetrexed Accord?
The recommended dose of pemetrexed is 500 mg per square metre of body surface area, given as an intravenous infusion over approximately 10 minutes, once every 21 days. The dose is calculated individually based on your height and weight. Mandatory premedication includes folic acid, vitamin B12, and corticosteroids.
Pemetrexed is always administered under the supervision of a qualified oncologist in a hospital or specialist cancer treatment centre. It is never self-administered. Your healthcare team will calculate your individual dose based on your body surface area (BSA), which is determined from your height and weight.
Adults
Standard Dosing Protocol
- Dose: 500 mg/m² body surface area
- Route: Intravenous infusion over approximately 10 minutes
- Frequency: Once every 21 days (3 weeks)
- When combined with cisplatin: Cisplatin is given approximately 30 minutes after completion of the pemetrexed infusion, as a separate infusion over approximately 2 hours
Dose adjustments or treatment delays may be necessary based on your blood counts and general health before each cycle. Your oncologist will use specific criteria to determine whether to proceed, reduce the dose, or postpone treatment. Criteria include absolute neutrophil count, platelet count, creatinine clearance, and the severity of any non-haematological toxicities experienced during the previous cycle.
Mandatory Supportive Medications
The following medications are required alongside pemetrexed to reduce toxicity and side effects:
| Medication | Dose | Timing | Purpose |
|---|---|---|---|
| Folic acid | 350–1000 micrograms daily (oral) | Start at least 7 days before first dose; continue daily throughout treatment and for 21 days after the last dose | Reduces haematological and GI toxicity |
| Vitamin B12 | 1000 micrograms (intramuscular injection) | 1 week before first dose, then every 9 weeks (~3 treatment cycles) | Reduces haematological toxicity |
| Dexamethasone | 4 mg twice daily (oral) | Day before, day of, and day after each pemetrexed infusion | Reduces frequency and severity of skin reactions |
Children and Adolescents
Pemetrexed is not recommended for use in children and adolescents under 18 years of age. There are no clinical data on safety or efficacy in the paediatric population, and no paediatric indication has been approved by regulatory authorities.
Elderly Patients
No specific dose adjustment is required for elderly patients based solely on age. However, elderly patients are more likely to have reduced kidney function and lower bone marrow reserve, which may necessitate dose reductions or treatment delays. Careful monitoring of renal function and blood counts is particularly important in this population.
Missed Dose
Since pemetrexed is administered in a clinical setting by healthcare professionals, missed doses due to patient error are uncommon. If a treatment cycle is delayed due to blood count abnormalities, kidney function changes, or side effects from the previous cycle, your oncologist will reschedule the infusion at the earliest safe opportunity. Treatment is not doubled to make up for a missed dose.
Overdose
Overdose with pemetrexed is rare because it is administered by trained healthcare professionals in a controlled setting. In the event of suspected overdose, the primary concerns are severe myelosuppression (dangerously low blood counts), renal toxicity, and mucositis. There is no specific antidote for pemetrexed overdose. Treatment is supportive and may include leucovorin (folinic acid), which can help rescue normal cells from folate depletion. The patient would require intensive monitoring of blood counts, renal function, and signs of infection.
What Are the Side Effects of Pemetrexed Accord?
Like all chemotherapy medicines, pemetrexed can cause side effects. The most common include fatigue, nausea, vomiting, diarrhoea, mouth sores, skin rash, loss of appetite, and low blood cell counts. Supplementation with folic acid and vitamin B12 significantly reduces the severity and frequency of many side effects.
Not everyone who receives pemetrexed will experience side effects, and when they do occur, they vary in severity. Your oncology team will monitor you closely and can provide supportive medications to manage many of these effects. The following side effects have been reported with pemetrexed, organised by frequency.
Contact your doctor or go to the emergency department immediately if you experience: fever above 38°C or signs of infection (you may have dangerously low white blood cells); chest pain or rapid heart rate; severe skin rash, blistering, or peeling skin (may indicate Stevens-Johnson syndrome); unusual bleeding or bruising; sudden breathlessness, intense chest pain, or coughing up blood (may indicate pulmonary embolism).
Very Common
- Fatigue and tiredness
- Nausea and vomiting
- Diarrhoea
- Loss of appetite (anorexia)
- Mouth sores and inflammation (stomatitis)
- Skin rash and skin peeling
- Sore throat (pharyngitis)
- Low neutrophil count (neutropenia)
- Low white blood cell count (leukopenia)
- Low haemoglobin (anaemia)
- Abnormal kidney function tests
- Infection
Common
- Blood infection (sepsis)
- Febrile neutropenia (fever with low white cells)
- Low platelet count (thrombocytopenia)
- Allergic reaction
- Dehydration
- Taste changes (dysgeusia)
- Peripheral neuropathy (numbness, tingling in hands/feet)
- Dizziness
- Conjunctivitis (eye inflammation), dry eyes, watery eyes
- Heart failure, irregular heartbeat
- Constipation, abdominal pain, indigestion
- Elevated liver enzymes
- Increased skin pigmentation, itching, hives, hair loss
- Kidney failure or decreased kidney function
- Fever, pain, swelling (oedema), chest pain
- Inflammation of mucous membranes throughout the digestive tract
Uncommon
- Pancytopenia (all blood cell types reduced)
- Stroke or transient ischaemic attack
- Intracranial haemorrhage
- Angina pectoris, myocardial infarction (heart attack)
- Coronary artery disease
- Pulmonary embolism (blood clot in lung)
- Interstitial pneumonitis (lung inflammation)
- Gastrointestinal bleeding, bowel perforation
- Oesophagitis (inflammation of the food pipe)
- Colitis (when used with cisplatin)
- Radiation recall dermatitis
Rare
- Haemolytic anaemia (destruction of red blood cells)
- Anaphylactic shock (severe allergic reaction)
- Hepatitis (liver inflammation)
- Skin redness (erythema)
- Radiation recall skin reactions
Very Rare
- Stevens-Johnson syndrome (severe skin and mucous membrane reaction)
- Toxic epidermal necrolysis (life-threatening skin reaction)
- Pemphigoid (autoimmune blistering skin condition)
- Bullous skin conditions (fluid-filled blisters)
- Pseudocellulitis (inflammation of skin and subcutaneous fat)
- Dermatitis and eczema
- Skin infections and soft tissue infections
If you experience any side effects, including those not listed above, talk to your doctor, pharmacist, or nurse. You can also report side effects directly to your national medicines regulatory authority. By reporting side effects, you help provide more information on the safety of this medicine.
How Should You Store Pemetrexed Accord?
Pemetrexed Accord should be stored below 25°C, out of the sight and reach of children. Prepared infusion solutions have demonstrated chemical and physical stability for 72 hours at room temperature. This medicine is for single use only.
As Pemetrexed Accord is administered in a hospital or clinical setting, storage is typically handled by pharmacy staff. However, the following storage guidelines apply:
- Unopened vials: Store below 25°C. Keep out of the sight and reach of children.
- Shelf life: Do not use after the expiry date (EXP) printed on the vial label and carton.
- Prepared infusion solutions: Chemical and physical in-use stability has been demonstrated for 72 hours at 20–25°C. From a microbiological perspective, the product should be used immediately after preparation. If not used immediately, in-use storage should not normally exceed 24 hours at 2–8°C unless preparation occurred under controlled and validated aseptic conditions.
- Visual inspection: Do not use if there are visible signs of deterioration, such as particles or discolouration.
- Single use only: Each vial is for single use only. Any unused solution must be disposed of in accordance with local regulations for cytotoxic waste.
- Disposal: Do not throw away via household waste or wastewater. Return unused medicines to your pharmacy for safe disposal to protect the environment.
What Does Pemetrexed Accord Contain?
Each vial of Pemetrexed Accord contains pemetrexed disodium as the active substance, available in concentrations of 25 mg/ml. Inactive ingredients include citric acid, L-methionine, monothioglycerol, sodium hydroxide, hydrochloric acid, and water for injections.
Active Substance
The active substance is pemetrexed, present as pemetrexed disodium. Each millilitre of concentrate contains pemetrexed disodium equivalent to 25 mg of pemetrexed. The available vial sizes are:
- 4 ml vial: Contains pemetrexed disodium equivalent to 100 mg pemetrexed
- 20 ml vial: Contains pemetrexed disodium equivalent to 500 mg pemetrexed
- 34 ml vial: Contains pemetrexed disodium equivalent to 850 mg pemetrexed
- 40 ml vial: Contains pemetrexed disodium equivalent to 1,000 mg pemetrexed
Inactive Ingredients (Excipients)
The other ingredients in Pemetrexed Accord concentrate for solution for infusion are:
- Citric acid (pH adjustment)
- L-methionine (antioxidant)
- Monothioglycerol (stabiliser)
- Sodium hydroxide (pH adjustment)
- Concentrated hydrochloric acid (pH adjustment)
- Water for injections (solvent)
Appearance
Pemetrexed Accord concentrate for solution for infusion is a clear, colourless to light yellow solution supplied in glass vials. The required volume is withdrawn from the vial and diluted to 100 ml with sterile 0.9% sodium chloride solution (without preservatives) before intravenous administration over 10 minutes.
Pemetrexed is incompatible with calcium-containing diluents, including Ringer’s lactate solution and Ringer’s solution. Only 0.9% sodium chloride solution should be used for dilution. Administration sets lined with polyvinyl chloride (PVC) and polyolefin are compatible.
Frequently Asked Questions About Pemetrexed Accord
Pemetrexed Accord is a chemotherapy medicine used to treat malignant pleural mesothelioma (a cancer of the lining of the lungs) in combination with cisplatin, and non-small cell lung cancer (NSCLC) with non-squamous histology. It can be used as first-line treatment with cisplatin, as maintenance therapy after initial chemotherapy, and as second-line treatment after prior chemotherapy has failed.
The most common side effects (affecting more than 1 in 10 patients) include fatigue, nausea, vomiting, diarrhoea, loss of appetite, mouth sores (stomatitis), skin rash, low blood counts (anaemia, neutropenia), and abnormal kidney function tests. Supplementation with folic acid and vitamin B12 significantly reduces the severity of these side effects.
Folic acid and vitamin B12 supplementation is mandatory during pemetrexed treatment because they significantly reduce the risk of serious side effects, particularly bone marrow suppression (low blood cell counts) and gastrointestinal toxicity. Clinical studies showed that vitamin supplementation reduced severe toxicity by approximately 50%. Folic acid (350–1000 micrograms daily) should be started at least 7 days before the first dose, and vitamin B12 (1000 micrograms by injection) should be given the week before treatment begins and then every 9 weeks.
You should be very careful with NSAIDs (such as ibuprofen, naproxen, and diclofenac) while receiving pemetrexed. NSAIDs can reduce the elimination of pemetrexed through the kidneys, leading to higher drug levels and increased toxicity. Short-acting NSAIDs should be avoided for at least 2 days before, the day of, and 2 days after pemetrexed administration. Long-acting NSAIDs should be avoided for at least 5 days before through 2 days after treatment. Paracetamol (acetaminophen) is generally the preferred painkiller during pemetrexed treatment.
Pemetrexed is given as an intravenous (IV) infusion over approximately 10 minutes in a hospital or cancer treatment centre. It is administered once every 21 days (3 weeks). The dose is calculated based on your body surface area at 500 mg/m². When used with cisplatin, the cisplatin infusion begins approximately 30 minutes after pemetrexed and takes about 2 hours. Corticosteroid tablets (dexamethasone 4 mg twice daily) must be taken the day before, the day of, and the day after treatment.
Pemetrexed Accord is a generic version of pemetrexed that contains the same active ingredient as ALIMTA (the originator brand by Eli Lilly). It has been approved by the European Medicines Agency (EMA) and has demonstrated bioequivalence to the reference product. Other available generic brands include Pemetrexed Pfizer, Pemetrexed medac, Pemetrexed Zentiva, Pemetrexed EVER Pharma, and Pemetrexed Fresenius Kabi. All generic versions contain the same active substance and are therapeutically equivalent.
References
- European Medicines Agency (EMA). Pemetrexed Accord – Summary of Product Characteristics (SmPC). Available at: www.ema.europa.eu. Accessed January 2026.
- Vogelzang NJ, Rusthoven JJ, Symanowski J, et al. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol. 2003;21(14):2636–2644. doi:10.1200/JCO.2003.11.136
- Scagliotti GV, Parikh P, von Pawel J, et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol. 2008;26(21):3543–3551. doi:10.1200/JCO.2007.15.0375
- Paz-Ares L, de Marinis F, Dediu M, et al. Maintenance therapy with pemetrexed plus best supportive care versus placebo plus best supportive care after induction therapy with pemetrexed plus cisplatin for advanced non-squamous non-small-cell lung cancer (PARAMOUNT): a double-blind, phase 3, randomised controlled trial. Lancet Oncol. 2012;13(3):247–255.
- National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology: Non-Small Cell Lung Cancer. Version 3.2025. Available at: www.nccn.org.
- World Health Organization (WHO). WHO Model List of Essential Medicines – 23rd List, 2023. Geneva: WHO; 2023.
- Hanna N, Shepherd FA, Fossella FV, et al. Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. J Clin Oncol. 2004;22(9):1589–1597.
- British National Formulary (BNF). Pemetrexed. Available at: bnf.nice.org.uk. Accessed January 2026.
About Our Medical Editorial Team
This article has been written and reviewed by the iMedic Medical Editorial Team, which includes board-certified specialists in oncology, clinical pharmacology, and internal medicine. All medical content is based on current international guidelines and peer-reviewed research.
Medical Writing
iMedic Medical Editorial Team – Specialists in Oncology and Clinical Pharmacology
Medical Review
iMedic Medical Review Board – Independent expert review following EMA, FDA, and NCCN guidelines
Evidence Standard: Level 1A – Systematic reviews and meta-analyses of randomised controlled trials
Guidelines Referenced: EMA SmPC, FDA Prescribing Information, NCCN Guidelines, WHO Essential Medicines List, BNF
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