Aminopterin Side Effects

Aminopterin is a chemotherapy drug that stops the body from making folic acid. Folic acid, an important B vitamin, is needed for the normal growth and division of cells. Aminopterin keeps rapidly dividing cells from utilizing folic acid, and therefore causes cell death. It was first used in the 1940s as an anti-cancer agent, as cancer cells are by nature abnormally rapidly dividing cells. However, because of serious side effects, it has been replaced by methotrexate (amethopterin), which is very similar in structure and function but with a better safety profile.

Historical Use

• Aminopterin was first used in 1947 by Sidney Farber, an American pediatric pathologist, to bring about remission in childhood leukemia.

Other Uses

• During this time, aminopterin was also used "off-label" for psoriais. In the 1960s its use as an agent to cause abortion was explored, but this was discontinued because it was found to cause serious birth defects and congenital malformations if the abortion failed.

Birth Defects

• Methotrexate and aminopterin are known for their teratogenic effects (ability to cause defects in the developing fetus), and this collection of defects has become known as fetal aminopterin syndrome. This very rare but serious syndrome can occur after a failed attempt at abortion after using aminopterin or methotrexate.

Symptoms of Fetal Aminopterin Syndrome

• Some symptoms in the fetus include deformities of the face and skull, small head, deformities of the skeleton, abnormally short limbs, central nervous system deformities such as mental retardation and water on the brain, too few fingers or toes (hypodactyly), fused fingers or toes (syndactyly) and sometimes cleft palate.

Other Side Effects

• Other side effects of aminopterin can include vomiting, anorexia, weight loss, chills, inflammation of the pharynx, inflammation of the inside of the mouth, hyperpigmentation (darkening of the skin), red rashes on the skin, abortions, liver toxicity, renal failure, and serious bleeding of the gastrointestinal tract.

Considerations

• The antidote to aminopterin overdose is folinic acid. This reduced version of folic acid has been used with success in humans to ensure that adequate dosing can be given to kill cancer cells without causing unnecessary harm to the patient. Folinic acid is routinely used today as a successful rescue remedy during treatment of certain types of cancer with methotrexate.