Chemotherapy: Antimetabolites

Reviewed by: HU Medical Review Board | Last reviewed: November 2023

Antimetabolites are a type of chemotherapy used to treat many cancers. Some antimetabolite drugs are used to treat certain forms of lung cancer. These drugs look like chemicals that cells need to make DNA. This allows them to interfere with cancer cell DNA, which prevents the cancer cells from dividing.1,2

Antimetabolites may be combined with other types of chemotherapy. Talk to your doctor about which treatment plan is right for you.2

How do antimetabolites work?

Antimetabolites look similar to chemicals that the body needs to make DNA, or genetic code. Antimetabolites act as decoys. They trick cancer cells into using them instead of the correct chemicals. This interferes with the cells’ DNA. Cancer cells then die because they can no longer divide.1,2

Cells use many substances to build DNA. These include:2

  • Purines – building blocks of DNA
  • Pyrimidines – building blocks of DNA
  • Folate – vitamin needed for DNA production and cell division

Each type of antimetabolite helps interfere with one of these processes. Purine antagonists take the place of the needed chemicals to make purines and thus prevent cells from making purines. Pyrimidine antagonists work the same way but with pyrimidines. Antifolates block cell division processes that need folate.2

Examples of antimetabolites

Three antimetabolites used to treat lung cancer include:2

  • Alimta® (pemetrexed)
  • Gemzar® (gemcitabine)
  • Otrexup®, Rasuvo®, Trexall® (methotrexate)

Pemetrexed is an antifolate. It is used alone or with other treatments to treat certain forms of non-squamous non-small cell lung cancer (NSCLC). Gemcitabine is a pyrimidine antagonist. It is used with other treatments to treat NSCLC. Methotrexate is an antifolate. It is rarely used to treat lung cancer. These and other antimetabolites may treat other cancers as well.1-6

What are the possible side effects?

Chemotherapy drugs, including antimetabolites, can damage cancer cells, but can also damage healthy cells. Damage to healthy cells causes side effects. Side effects can vary depending on the specific drug you are taking. They also depend on dosage and whether you take other anti-cancer drugs.2-6

Common side effects of antimetabolites include:2-6

  • Fatigue
  • Hair loss
  • Rash
  • Nausea and vomiting
  • Diarrhea or constipation
  • Swelling or sores in the mouth
  • Loss of appetite
  • Low white blood cell counts, which can increase the risk of infection
  • Low platelet counts, which can increase bleeding and bruising
  • Low red blood cell counts, which can increase fatigue

Serious side effects are possible. Methotrexate has a boxed warning, the strictest warning from the US Food and Drug Administration (FDA). It has this warning because of an increased risk of:5,6

  • Harm to an unborn baby, including birth defects or death
  • Severe allergic reactions
  • Bone marrow problems
  • Serious infections
  • Serious kidney or liver problems
  • Brain or nervous system problems
  • Stomach or intestine problems
  • Serious lung problems
  • Serious skin reactions
  • Potential for toxicity with preservative-containing formulations in certain situations

In addition, cancers can become resistant to anti-cancer drugs. This means that cancer cells adapt to survive better. This is one reason antimetabolites can become less effective over time. Combining different treatments can help lower the risk of resistance.2

These are not all the possible side effects of antimetabolites. Talk to your doctor about what to expect when taking these drugs. You should also call your doctor if you have any changes that concern you when taking an antimetabolite.

Other things to know

Take antimetabolites as your doctor prescribes. Most people take them through an intravenous (IV) line into a vein. Some antimetabolites (like methotrexate) are available as an oral tablet depending on the clinical situation.2-6

Your doctor will monitor you for side effects during treatment. They may change your dose or schedule depending on side effects. You may need to take other medicines during treatment to manage side effects. For example, folic acid and vitamin B12 can help reduce the side effects of pemetrexed when taken as prescribed by your doctor.3-6

Before beginning treatment for lung cancer, tell your doctor about all your health conditions and any other drugs, vitamins, or supplements you take. This includes over-the-counter drugs. Certain health conditions can increase the risk of side effects or complications. Tell your doctor if you:3-6

  • Have a history of kidney and liver problems
  • Have a history of radiation therapy
  • Have a history of alcohol use disorder
  • Have a history of stomach ulcers or ulcerative colitis
  • Have any allergies
  • Are pregnant or plan to become pregnant
  • Are breastfeeding or plan to breastfeed

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