AGENTS FOR MEGALOBLASTIC ANEMIAS

Megaloblastic anemia is treated with folic acid and vitamin B12. Folate deficiencies usually occur secondary to increased demand (as in pregnancy or growth spurts); as a result of absorption problems in the small intestine;because of drugs that cause folate defi ciencies; or secondary to the malnutrition of alcoholism.

Vitamin B12 deficiencies can result from poor diet or increased demand,but the usual cause is lack of intrinsic factor in the stomach,which is necessary for absorption. The drugs are usually given together to ensure that the problem is addressed and the blood cells can be formed properly (Table 49.3). Folic acid derivatives include folic acid (Folvite), leucovorin (Wellcovorin), and generic, which is available only in an IV form. Vitamin B12 includes hydroxocobalamin (Hydro-Crysti-12), and cyanocobalamin (Nascobal).

Therapeutic Actions and Indications Folic acid and vitamin B12 are essential for cell growth and division and for the production of a strong stroma in RBCs (see Figure 49.3). Vitamin B12 is also necessary for maintenance of the myelin sheath in nerve tissue. Both are given as replacement therapy for dietary defi ciencies, as replacement in high-demand states such as pregnancy and lactation, and to treat megaloblastic anemia. Folic acid is used as a rescue drug for cells exposed to some toxic chemotherapeutic agents.

Leucovorin is used as a rescue drug following methotrexate therapy to decrease the toxicity of methotrexate caused by decreased elimination or overdose of folic acid antagonists such as trimethoprim and for the treatment of various megaloblastic anemias. Levoleucovorin is the newest drug in this class and is only approved to decrease the toxicity of methotrexate caused by decreased elimination or overdose of folic acid antagonists in the treatment of osteosarcomas.

Pharmacokinetics Folic acid can be given in oral, IM, IV, and subcutaneous forms. The parenteral drugs are preferred for patients with potential absorption problems; all other patients should be given the oral form if at all possible. Leucovorin is a reduced form of folic acid that is available for oral, IM, and IV use. Levoleucovorin is only available in an IV form.

Hydroxocobalamin must be given intramuscularly every day for 5 to 10 days to build up levels, then once a month for life. It cannot be taken orally because the problem with pernicious anemia is the inability to absorb vitamin B12 secondary to low levels of intrinsic factor. It can be used in states of increased demand (e.g., pregnancy,growth spurts) or dietary defi ciency, but oral vitamins are preferred in most of those cases. Cyanocobalamin is not as tightly bound to proteins and does not last in the body as long as hydroxocobalamin does. This drug is primarily stored in the liver and slowly released as needed for metabolic functions. It is available as an intranasal gel that allows vitamin B12 absorption directly through the nasal mucosa. Nascobal is used once a week as an intranasal spray in one nostril.

Folic acid and vitamin B12 are well absorbed after injection, metabolized mainly in the liver, and excreted in urine. These vitamins are considered essential during pregnancy and lactation because of the increased demands of the mother’s metabolism.

Contraindications and Cautions These drugs are contraindicated in the presence of known allergies to these drugs or to their components to avoid hypersensitivity reactions. They should be used cautiously in patients who are pregnant or lactating or who have other anemias to ensure that the correct doses of the drug are used to provide the best therapeutic effect and decrease the risk of toxic effects. Nasal cyanocobalamin should be used with caution in the presence of nasal erosion

Adverse Effects These drugs have relatively few adverse effects because they are used as replacement for required chemicals. Hydroxocobalamin has been associated with itching,rash, and signs of excessive vitamin B levels, which can also include peripheral edema and heart failure. Mild diarrhea has been reported with these drugs. Pain and discomfort can occur at injection sites. Nasal irritation can occur with the use of intranasal spray