Raltitrexed, sold under the brand name Tomudex, is a medication used in the treatment of cancer. It belongs to a class of drugs known as antimetabolites and is specifically classified as an antimetabolite antifolate. Raltitrexed is primarily used in the treatment of colorectal cancer and is sometimes used for other types of cancer as well.

Raltitrexed (Tomudex) manufactured by AstraZeneca is an antimetabolite (a thymidylate synthase inhibitor) that is used as a chemotherapeutic drug for the treatment of advanced colorectal cancer.

Raltitrexed Uses:

• Advanced Colorectal Cancer:
  • It is indicated for the treatment of advanced colorectal cancer
• Off Label Use of Raltitrexed in Adults:
  • It is also used in the treatment of malignant pleural mesothelioma.

Raltitrexed (Tomudex) Dose in Adults

Note:

• The white blood cell count (WBC) is higher than 4,000 per cubic millimeter.
• The absolute neutrophil count (ANC) is higher than 2,000 per cubic millimeter.
• The number of platelets is higher than 100,000 per cubic millimeter.

Raltitrexed (Tomudex) Dose in the treatment of advanced colorectal cancer:

• Dose: Raltitrexed is given through an IV (intravenous) drip.
• Amount: The dose is 3 milligrams per square meter of the patient's body surface area.
• Frequency: It's given once every 3 weeks.
• Safety: The treatment schedule continues unless there are harmful side effects or toxicity observed.

Raltitrexed (Tomudex) Dose in the treatment of malignant pleural mesothelioma (off-label):

• Dose: Raltitrexed is given through an IV (intravenous) drip.
• Amount: The dose is 3 milligrams per square meter of the patient's body surface area.
• Frequency: It's given once every 3 weeks.
• Combination: It's typically used in combination with another drug called cisplatin.
• Duration: Treatment continues until one of two things happens:
  • Disease progression: If the cancer starts getting worse.
  • Unacceptable toxicity: If the patient experiences harmful side effects that can't be tolerated.

Use in Children:

It is contraindicated in children.

Pregnancy Risk Category: X

• If you're pregnant or might become pregnant, you shouldn't take this medicine.
• Animal studies showed it could harm the baby.
• Women should test to make sure they're not pregnant before starting this drug and avoid getting pregnant for at least 6 months after stopping.
• Also, if your male partner is taking this drug, the same rules apply.
• If you're pregnant, don't even touch this medication.

Breastfeeding:

• Nursing mothers shouldn't take this medicine according to the manufacturer's advice.

Dose in Kidney Disease:

If your kidney function (measured as CrCl) is:

• Above 65 mL/minute: You can take the regular dose.
• Between 55 and 65 mL/minute: Take 75% of your normal dose every 4 weeks.
• Between 25 and 54 mL/minute: Adjust the dose based on your CrCl value every 4 weeks (e.g., if CrCl is 25 mL/minute, take 25% of the usual dose).
• Below 25 mL/minute: Don't take the medicine; it's not safe for those with severe kidney issues.

Dose in Liver disease:

• If you already have clinical jaundice or severe liver disease: It's not recommended to use this medicine.
• For mild to moderate liver problems: You can take the regular dose, but be careful.
• If you have severe liver problems: Don't take the medicine, it's not safe.
• If you develop liver damage while on the medicine: Stop using it until the damage reduces to a moderate level or lower.

Common Side Effects of Raltitrexed (Tomudex):

• Dermatologic:
  • Skin Rash
• Gastrointestinal:
  • Nausea
  • Diarrhea
  • Vomiting
  • Anorexia
  • Abdominal Pain
  • Constipation
  • Mucositis
  • Stomatitis
• Hematologic & Oncologic:
  • Leukopenia
  • Anemia
• Hepatic:
  • Increased Serum AST
  • Increased Serum ALT
• Neuromuscular & Skeletal:
  • Weakness
• Miscellaneous:
  • Fever

Less Common Side Effects Of Raltitrexed (Tomudex):

• Cardiovascular:
  • Peripheral Edema
  • Cardiac Arrhythmia
  • Cardiac Abnormality
• Central Nervous System:
  • Headache
  • Dizziness
  • Chills
  • Malaise
  • Pain
  • Insomnia
  • Depression
  • Paresthesia
  • Hypertonia
• Dermatologic:
  • Alopecia
  • Diaphoresis
  • Cellulitis
  • Pruritus
• Endocrine & Metabolic:
  • Dehydration
  • Weight Loss
  • Hypokalemia
• Gastrointestinal:
  • Dysgeusia
  • Dyspepsia
  • Flatulence
  • Xerostomia
• Genitourinary:
  • Urinary Tract Infection
• Hematologic & Oncologic:
  • Thrombocytopenia
• Hepatic:
  • Hyperbilirubinemia
  • Increased Serum Alkaline Phosphatase
• Infection:
  • Infection
  • Sepsis
• Neuromuscular & Skeletal:
  • Myalgia
  • Arthralgia
• Ophthalmic:
  • Conjunctivitis
• Renal:
  • Increased Serum Creatinine
• Respiratory:
  • Flu-Like Symptoms
  • Cough
  • Dyspnea
  • Pharyngitis

Contraindications to Raltitrexed (Tomudex):

You shouldn't take raltitrexed if:

• You're allergic to it or any of its ingredients.
• You have serious kidney or liver problems.
• You're pregnant, breastfeeding, or might become pregnant.
• It's not for use in children.

Warnings and precautions

Suppression of bone marrow

• Bone marrow issues can arise from this medication.
• It can lead to a drop in white blood cells (neutropenia, leukopenia), red blood cells (anemia), or platelets (thrombocytopenia), with some cases being severe.
• Typically, these issues are mild to moderate and show up 7 to 14 days after taking the medicine.
• Fortunately, most people recover by the 21st day.
• If someone already has weakened bone marrow, they should be extra cautious when using this drug.

Gastrointestinal toxicities:

• Stomach and gut problems like nausea, vomiting, and diarrhea are frequent side effects of this medicine.
• Mouth sores (mucositis) and inflammation of the mouth (stomatitis) can also happen.
• Severe diarrhea combined with a drop in white blood cells (neutropenia) can be very dangerous and might require stopping the medication or reducing the dose.
• Anti-nausea medicines usually help with the vomiting and nausea caused by this drug.

Malaise and weakness

• This medicine can make people feel tired or weak.
• Because of this, users should be careful when driving or using machines.

Hepatic impairment

• If you have mild to moderate liver issues, use this medicine carefully.
• If you have severe liver problems, or conditions like clinical jaundice or advanced liver disease, you shouldn't take this medicine.
• If the medicine causes liver damage, you should stop taking it. You can start again when your liver tests improve to a moderate level or better.
• Some people might experience temporary and mild increases in liver enzymes (ALT and AST), even if they don't feel sick.

Renal impairment

• If you have mild to moderate kidney problems, be careful when using this medicine since its clearance is reduced by about half.
• If you have severe kidney problems, you shouldn't take this medicine.

Raltitrexed: Drug Interaction

Monitoring parameters:

Blood Tests (CBC with differential)

• When you start treatment.
• Before each treatment session.
• Every week if you're experiencing stomach-related side effects.

Liver Function Tests & Kidney Test (serum creatinine)

• When you start treatment.
• Before each treatment session.

Watch Out For

• Signs of stomach-related side effects.

How to administer Raltitrexed (Tomudex)?

• Method: Intravenously (IV)
• Duration: Infuse over 15 minutes.

Combination with Cisplatin (for a specific type of cancer)

• If using with cisplatin for malignant pleural mesothelioma (a use not officially approved but based on research):
  • First, give raltitrexed.
  • Then, give cisplatin.

Mechanism of action of Raltitrexed (Tomudex):

• Raltitrexed works as a drug that's similar to folate.
• It specifically targets and stops an enzyme called thymidylate synthase.
• By doing this, it blocks the production of purines, which are essential building blocks for DNA.
• This means that DNA synthesis, the process of creating new DNA, is slowed down and inhibited overall when you take raltitrexed.

Distribution Volume (V):

• It's distributed in the body, and the apparent volume of distribution is about 548 liters.

Protein binding:

• Raltitrexed binds to proteins in the blood, with approximately 93% of it binding to proteins.

Metabolism:

• Raltitrexed undergoes extensive metabolism inside cells, forming active polyglutamate forms.
• There doesn't appear to be significant metabolism of the drug in the bloodstream.

Half-life elimination:

• The elimination of raltitrexed from the body follows a triphasic pattern.
• The beta phase has a half-life of around 2 hours, while the terminal phase has a much longer half-life of approximately 198 hours.

Excretion:

• The drug is primarily eliminated through the urine, with about 50% of it being excreted unchanged.
• A smaller portion, approximately 15%, is excreted in the feces.

International Brand Names of Raltitrexed:

• Tomudex

Raltitrexed Brand Names in Pakistan:

Not available.