Tomudex

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Tomudex

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Method of action: Antitumour

Treatment option: Colorectal Cancer, Cancer

Medically reviewed

Marina Burgos

Last updated on 22/12/2025

This page provides general, reference-level information compiled from official medical sources. It is not a substitute for professional medical advice, diagnosis, or treatment. For decisions about your health, please consult a qualified healthcare professional.

Overview of Tomudex

What is Tomudex? (Raltitrexed)

Tomudex is a medication whose active ingredient is Raltitrexed, a substance used in the context of systemic chemotherapy. Its fundamental role is to interfere with the rapid multiplication of abnormal cells, aligning it with the general therapeutic purpose of managing cellular proliferation. The drug is classified as an antineoplastic agent.


Quick Facts: Tomudex (Raltitrexed)

Property Description
Active ingredient Raltitrexed
Form Lyophilized powder for solution
Pharmacological class Antineoplastic agent, Antimetabolite
Common use Systemic cancer therapy
Origin Synthetic organic compound

Raltitrexed: A Targeted Antifolate Agent

The active component, Raltitrexed, is a highly selective, prescription-only drug, chemically defined as a quinazoline folate analogue. This classification places it in the family of antimetabolites, meaning it is designed to mimic the structure of essential nutrients, specifically folate, to interfere with cellular metabolic pathways. Raltitrexed acts through its unique and direct inhibitory activity against the enzyme thymidylate synthase (TS), a key step in DNA synthesis.

Composition and General Purpose

As a cytotoxic drug, the primary purpose of Tomudex is to disrupt the life cycle of uncontrolled, fast-growing cells by acting as a specific inhibitor of TS. By blocking this pathway, Raltitrexed prevents rapidly dividing cells from forming new DNA, thus arresting their ability to proliferate. A typical neutral use scenario for Tomudex involves its application as part of a regimen to control the proliferation of malignant tumors, where its selective action against the folate pathway is advantageous.

The drug is supplied as a single-ingredient product in the form of a sterile lyophilized powder for solution for infusion. The formulation requires reconstitution with a suitable aqueous solvent prior to administration via the intravenous route, ensuring systemic therapeutic effect.

What side effects are possible with Tomudex?

Tomudex (raltitrexed) is a chemotherapy drug that can cause a range of side effects by affecting the growth of both cancer cells and normal, rapidly dividing cells in the body.

Very Common and Common Side Effects

Many patients experience side effects that require careful monitoring by a healthcare provider. The most frequent and potentially serious adverse effects are related to myelosuppression (bone marrow suppression), which can lead to:

  • Neutropenia/Leukopenia: A drop in white blood cells, increasing the risk of serious infection and fever.
  • Thrombocytopenia: A decrease in platelets, leading to a higher risk of bleeding or bruising.
  • Anemia: A reduction in red blood cells, causing fatigue, weakness, and shortness of breath.

Gastrointestinal and Other Common Effects

Other very common and common side effects include significant gastrointestinal distress:

System/Effect Severity Common Symptoms
Gastrointestinal Very Common Nausea, Vomiting, Diarrhea (can be severe), Mucositis (mouth/gut sores), Abdominal Pain, Constipation, Anorexia, Weight Loss
General/Systemic Very Common Fatigue, Weakness, Flu-like symptoms
Hepatobiliary Common Elevated liver enzymes (Hepatotoxicity), Jaundice
Dermatologic Common Rash, Hair thinning (Alopecia)

Safety Information and Contraindications

Tomudex is contraindicated in patients with a known hypersensitivity to the drug, those with severe renal impairment, or during pregnancy and breast-feeding. It is also essential to avoid folic acid, leucovorin, or vitamin products containing them immediately before or during treatment, as they may interfere with Tomudex's action.

Patients must undergo regular blood tests throughout treatment to monitor blood cell counts, kidney function, and liver function. Due to the risk of fetal harm, both male and female patients of reproductive potential must use effective contraception during treatment and for at least six months following the last dose.

Overdose and Emergency Response

Overdose and when to seek help

Official regulatory documents define Tomudex (Raltitrexed) overdose as an exaggerated presentation of the anticipated adverse drug reactions, carrying an increased risk of life-threatening or fatal toxicity. The key manifestations of severe toxicity involve the haematopoietic and gastrointestinal systems.

Overdose presentations are typically characterized by severe haematological toxicity (e.g., neutropenia or thrombocytopenia) and gastrointestinal toxicity (e.g., severe diarrhoea or mucositis), often classified using WHO grade 4 severity criteria. The official guidance is to seek immediate medical attention for suspected overdose, even in the absence of initial symptoms, to ensure prompt management of these severe risks.

While no clinically proven antidote is available for Raltitrexed, supportive procedures are required. These measures include the administration of folinic acid (leucovorin) rescue, along with standard supportive care such as intravenous hydration and bone marrow support. Regulatory information notes that the efficacy of folinic acid may diminish as the time interval following administration increases.

Regulatory documents also specify that elderly patients are considered more vulnerable to toxic effects. This heightened vulnerability is attributed to the potential for the drug to accumulate due to reduced renal clearance often associated with age. Prompt and aggressive management is essential to mitigate the risk of severe outcomes.

Therapeutic Uses of Tomudex

What Tomudex Treats: Main Uses and Benefits

Tomudex (Raltitrexed) is commonly used in the therapeutic domain of systemic cancer therapy to manage advanced or metastatic colorectal cancer. The medication is applied with the aim of addressing the widespread nature of the disease and contributes to managing the progression of the disease, and may be applied with the goal of supporting tumor stabilization in a palliative context.

Raltitrexed is typically applied in clinical scenarios that involve treating advanced disease, which includes cancer of the colon and rectum. In managing the condition, the medication may assist with managing the disease process, which supports the patient during difficult episodes by easing distress and contributes to improved day-to-day comfort in the setting of advanced illness. Tomudex is an established alternative, which may support patients with specific needs in receiving ongoing supportive treatment to help ease their overall symptom burden.


Quick Fact: Relief for Advanced Cancer Symptoms

Fact Description
Primary Condition Advanced Colorectal Cancer (metastatic disease)
Clinical Context Alternative option in cases of fluoropyrimidine intolerance
Patient Benefit Applied to help with managing the condition and contributes to improved comfort

Regulatory References

  1. European Health Authority Assessment

Eligibility and Restrictions for Use

Tomudex (Raltitrexed) is primarily used in the treatment of advanced colorectal cancer. It is typically administered to patients who have not previously received chemotherapy for this condition, or as a second-line therapy.


Who Can Use Tomudex?

Patient Group Indication
Adults with Advanced Colorectal Cancer As an initial treatment (first-line) or following prior chemotherapy failure (second-line).

Tomudex is administered under the supervision of a physician experienced in the use of cancer chemotherapeutic agents.


Who Cannot Use Tomudex (Contraindications)?

Tomudex is contraindicated and should generally not be used in the following patient groups:

  • Known Hypersensitivity: Individuals with a documented severe allergic reaction to raltitrexed or any component of the formulation.
  • Severe Bone Marrow Suppression: Patients presenting with pre-existing severe depression of bone marrow function, as this drug can further suppress blood cell production.
  • Severe Kidney Impairment: Those with significantly compromised renal function, as the drug's elimination may be impaired, leading to increased toxicity. The manufacturer's instructions provide specific guidance on creatinine clearance levels.
  • Pregnant or Breastfeeding Women: Due to the potential for fetal harm and the transfer of the drug through breast milk.

Physicians must carefully assess the patient's liver and kidney function and blood cell counts before and during treatment to determine suitability and manage potential risks.

What should I know about interactions with other medicines?

Interactions with other medicines and products

This section outlines the officially documented interaction patterns for Tomudex (Raltitrexed) as specified in regulatory prescribing information.


Formal Contraindications and Restrictions

The co-administration of Tomudex with certain substances is strictly prohibited due to interaction risks:

  • Folinic acid (Leucovorin), Folic acid, or vitamin preparations containing these agents are contraindicated. These substances may interfere with Raltitrexed's intended antineoplastic action.
  • Yellow fever vaccine is contraindicated due to the risk of fatal systemic disease, a risk associated with the use of cytotoxic drugs.
  • Other live attenuated vaccines are generally not recommended for co-administration.

Exposure and Pharmacokinetic Interactions

Tomudex is primarily eliminated by the kidneys, which dictates several pharmacokinetic interaction patterns:

  • Nephrotoxic drugs (e.g., Cisplatin) may potentially lead to delayed clearance and resulting accumulation of Raltitrexed.
  • Drugs secreted actively via renal tubules, such as Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), suggest a potential competition interaction for excretion sites.
  • Elderly patients carry a potential for Raltitrexed accumulation due to the natural decline in renal function with age.

Timing and Procedural Constraints

  • Folic acid agents must not be given immediately prior to or during Tomudex administration.
  • Tomudex should not be mixed with other medicinal products in the same intravenous infusion container.

Mechanism of Action

How Tomudex Works

Selective Inhibition of Thymidylate Synthase

Tomudex (Raltitrexed) acts as a specific antimetabolite by targeting the enzyme Thymidylate Synthase ( TS). The drug gains entry into the cell primarily via the Reduced Folate Carrier ( RFC) and is then enzymatically converted by Folylpolyglutamate Synthetase ( FPGS) into its active, retained form (polyglutamated Raltitrexed).

Polyglutamated Raltitrexed competitively binds to TS, which blocks the final step in the de novo synthesis of the DNA precursor, deoxythymidine monophosphate ( dTMP). This molecular blockade defines the drug's core action as interference with the metabolic pathway required for genetic synthesis.


Cascade Leading to DNA Damage and Apoptosis

The resulting thymidylate deficiency impairs the synthesis of genetic material during the S-phase of the cell cycle. The inhibition also causes the accumulation of deoxyuridine triphosphate ( dUTP), which the cell incorporates in place of dTMP into its DNA. This combined genetic damage and strand fragmentation ultimately initiates apoptosis (programmed cell death) in highly proliferative cells, which is the physiological consequence of the enzyme blockade.

Dosage and Administration Information

Tomudex (Raltitrexed) is administered exclusively as a cyclic treatment delivered by intravenous (IV) infusion. The medication is supplied as a lyophilized powder, which requires reconstitution and subsequent dilution into 50 to 250 ml of a compatible intravenous solution, typically 0.9% sodium chloride or 5% dextrose, before it can be used.

The standard dosage regimen for adults establishes a single dose of 3 mg per square meter of the patient's body surface area (m^2). This calculated dose is given as a short infusion over approximately 15 minutes. The treatment follows a fixed cycle, where the dose is repeated once every three weeks, contingent upon meeting specific procedural criteria for continuation.

Usage protocols mandate that administration occurs only under the supervision of a physician experienced in chemotherapy; other drugs must not be mixed into the same infusion container. If a dose adjustment is required due to previous reaction, the reduced dose must not be re-escalated in subsequent cycles. Dose modifications are also required for individuals with reduced kidney function, applying specific percentage reductions based on calculated creatinine clearance thresholds. For instance, patients with moderate renal impairment may receive 50% of the standard dose on a modified schedule.

Recent Clinical Evidence

Research evidence / Overview of studies for Tomudex (Raltitrexed)


Evidence for Use in Untreated Advanced Colorectal Cancer

Research for Tomudex (Raltitrexed) includes multiple large, multi-center Randomized Controlled Trials (RCTs) designed to evaluate outcomes when measured against established chemotherapy regimens, such as protocols using 5-Fluorouracil (5-FU). These studies included adults who had not previously received treatment for advanced or metastatic colorectal cancer. Research examined key outcomes related to survival measurements (Overall Survival and Progression-Free Survival) and tumor status (Objective Response Rates).

Studies monitored how these outcomes evolved, reporting patterns observed where survival measurements were generally comparable to those documented for older 5-FU regimens. However, some trials reported an observed shorter time to disease progression for the Tomudex group when compared to specific intensified 5-FU combinations. Follow-up durations were limited in many core studies, meaning there is limited information for long-term outcomes regarding disease progression or overall survival beyond the typical observation period.


Evidence as an Alternative for Fluoropyrimidine Intolerance

Tomudex was evaluated in specific observational settings and non-randomized studies for adults with advanced colorectal cancer who had a documented history of severe side effects (e.g., cardiotoxicity) related to fluoropyrimidine-based treatments. This research explored outcomes related to managing the disease and evaluating the tolerability profile.

Due to Tomudex being studied for a different metabolic pathway than 5-FU, the research describes that patients who experienced specific toxicities with fluoropyrimidines was observed in some studies to exhibit a different pattern of reported adverse events. However, comparative evidence is lacking from controlled studies directly assessing Tomudex against all other alternatives in this specific patient group. Furthermore, data for certain groups remain insufficient, particularly regarding the effectiveness of Tomudex in patients with confirmed complete Dihydropyrimidine Dehydrogenase (DPD) deficiency.

Key Studies & References

  1. Raltitrexed in Patients With Dihydropyrimidine Dehydrogenase Deficiency (Review of non-randomized and safety studies for the intolerance/deficiency population)

Frequently Asked Questions (FAQ)

Common questions about Tomudex (FAQ)


Q: What exactly is a 'thymidylate synthase inhibitor' in simple terms?

Tomudex is an antimetabolite that acts as a thymidylate synthase inhibitor. This means the drug blocks an essential enzyme that rapidly dividing cells need to make genetic material (DNA). By interrupting the metabolic pathway used to create the molecule needed for DNA, the drug prevents the cells from growing and replicating.


Q: Why is Tomudex sometimes used as an alternative to 5-FU/leucovorin?

Official study summaries indicate that Raltitrexed provides a different mechanism of action and toxicity profile compared to the older 5-FU/leucovorin regimen. Clinical trial reports noted that patients experienced specific tolerability advantages in the initial treatment cycles, with observations of less frequent or less severe mucositis and low white blood cell counts (leucopenia).


Q: Can Tomudex be used in combination with other anti-cancer treatments?

Official clinical study data indicates that the drug has been used and studied both as a single agent and systemically in combination with other anti-cancer treatments. Raltitrexed has been part of some chemotherapy and radiotherapy regimens. Regulatory information indicates that the use of Tomudex in combination is managed by the patient's healthcare team based on established protocols.


Q: How long does the drug stay in the body after one infusion?

Official pharmacokinetic studies, which track how the drug moves through the body, indicate that Tomudex is eliminated in multiple phases. The terminal elimination half-life, which represents the time it takes for half of the drug to be eliminated from the body in the final phase, is reported to be approximately 198 to 257 hours after a single dose.


Q: Are there any restrictions on activity immediately after receiving a Tomudex infusion?

According to the official product information, the drug may cause general feelings of illness or weakness, known as asthenia, following the infusion. Due to the potential for these side effects, activities requiring full attention, such as driving or operating heavy machinery, could be temporarily impaired, and official guidance advises that these activities should be suspended if symptoms are present.


Q: What happens if a scheduled Tomudex treatment is missed or delayed?

The drug is part of a precise, scheduled cancer treatment plan. Regulatory patient guidance advises that if an appointment for an infusion is missed or delayed, patients are advised against making independent changes to the schedule. Instead, the necessary next steps are determined by contacting the specialist doctor or treatment clinic immediately for guidance on adjusting the next dose.


Q: What are the most common side effects people report after the first treatment cycle?

Official product monitoring indicates that the most frequent side effects reported in clinical trials include nausea, vomiting, and fatigue. These effects are typically mild-to-moderate, are reported to be reversible, and usually begin to occur following the first week of administration.


Q: How long do the flu-like symptoms associated with Tomudex usually last?

Official product documents classify flu-like symptoms as a common side effect of the treatment. These symptoms are generally mild or moderate in severity and are described as reversible, often resolving after the first week following administration.


Q: Why does Tomudex sometimes cause severe diarrhea?

The mechanism of action involves interrupting DNA synthesis in all cells that divide rapidly, not just cancer cells. Official documents describe that the drug’s interference affects cells in the lining of the gastrointestinal tract, which are quickly replaced, and this disruption can lead to serious gastrointestinal adverse effects such as diarrhea.


Q: Can Tomudex affect my ability to drive temporarily due to side effects?

Yes, official safety information advises caution. The feelings of generalized illness or physical weakness, known as asthenia, that may occur after treatment can temporarily impair the mental and physical abilities necessary for driving or operating machinery.


Q: Do the changes to blood cell counts (like anemia or neutropenia) eventually return to normal?

Official monitoring data reported in product documents indicates that the adverse effects on the blood-forming system, such as low red blood cells (anemia) and low white blood cells (neutropenia), are generally described as reversible after treatment ends.


Q: Are changes in liver enzymes a common but temporary side effect?

Official product monographs report that increases in liver enzymes are commonly observed. These changes are typically asymptomatic, self-limiting, and described as reversible when not associated with progression of the underlying disease.


Q: How quickly should a fever be reported after a Tomudex infusion?

Regulatory guidance advises immediate contact with the specialist team if a fever or low temperature occurs. This procedure is followed to ensure prompt monitoring and management of potential complications related to low white blood cell counts (neutropenia).


Q: Does Tomudex have the potential to interact with blood-thinning medications like Warfarin?

Official documents state that Raltitrexed is highly protein-bound in the blood. However, a review of clinical trial safety data did not reveal evidence of a clinically significant interaction when it was used at the same time as the blood thinner Warfarin.


Q: Is it safe to use herbal supplements during the course of Tomudex treatment?

Official patient information describes the importance of communication with the healthcare team regarding all co-administered products. This includes prescription, over-the-counter, and herbal medicines, as these may interfere with the way Tomudex works.


Q: Is a history of prior radiotherapy a precaution for using Tomudex?

Official clinical study data indicates that the drug has been studied in clinical trials for use in combination with radiotherapy. While combination is possible, the final decision on suitability in the context of prior radiotherapy is managed by the healthcare team based on the patient’s full medical history and established protocols.


Q: Why is Tomudex not recommended for use in children?

The official indication is for use in adults. Regulatory bodies, such as the European Medicines Agency (EMA), have issued decisions confirming that the drug is not recommended for use in children and is not approved for this age group.


Q: What are the results of studies involving Tomudex use in patients with heart conditions?

Clinical trial reports indicate that cardiac events have been reported. However, official documents emphasize that a direct causal link was often not established, as many of these abnormalities were attributed to pre-existing heart conditions or concurrent issues like sepsis or dehydration.


Q: Does the evidence indicate a difference in quality of life for patients receiving Tomudex?

Official clinical trial reports have indicated that patients receiving Raltitrexed experienced early advantages on certain quality-of-life benefits when compared to the reference regimen of 5-FU plus leucovorin.


Q: Can Tomudex cause red or itchy eyes (conjunctivitis)?

Yes, official product monographs list red or itchy eyes, known medically as conjunctivitis, as a reported adverse effect. This is classified among the less frequent effects seen in clinical trials.


Q: What kind of monitoring is typically required before each Tomudex treatment cycle?

Due to the drug’s potential effects, official documents indicate that regular monitoring is established for this drug. This involves blood tests to assess blood cell counts, kidney function, and liver function before and during each treatment cycle.


Q: What are the signs of low platelet count that patients should look out for?

Low platelet counts, known as thrombocytopenia, increase the risk of bleeding. Regulatory patient guidance identifies symptoms such as easy bruising, bleeding gums, or blood in the urine or stools as potential signs associated with low platelet counts (thrombocytopenia).


Q: Can Tomudex be used in patients with a history of liver issues?

Official documents state that careful assessment of liver function is established for this drug. While liver enzyme changes are often reversible, the patient's complete medical history is a factor considered by the prescribing doctor in determining suitability.


How should Tomudex be stored and disposed of?

Official Storage and Handling Requirements

Product State Temperature and Protection Requirements
Unopened Vials Do not store above 25 C. Must be kept in the outer carton to protect from light.
Prepared Solution From reconstitution, use immediately or store at 2 C to 8 C for a maximum of 24 hours.

The lyophilized powder must be reconstituted and diluted under aseptic conditions. Regulatory documents mandate that the product be kept out of the sight and reach of children.

Disposal of Cytotoxic Waste

Tomudex is classified as a cytotoxic agent. Any unused injection, reconstituted solution, or waste material must be discarded in a suitable manner for cytotoxics as defined by local regulations. This process typically involves handling according to standard procedures for hazardous medicinal waste and disposal by incineration. Partially used vials or admixed solutions must not be stored for future use.

Attention! Always consult to a doctor or pharmacist before using pills or medicines.

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