Chemistry
Folic acid is inactive as administered and cannot support DNA synthesis. Activation takes place rapidly following absorption.
Indications
Folic acid has three uses: (1) treatment of megaloblastic anemia resulting from folic acid deficiency; (2) prophylaxis of folate deficiency, especially during pregnancy and lactation; and (3) initial treatment of severe megaloblastic anemia resulting from vitamin B12 deficiency.
Adverse Effects
Oral folic acid is nontoxic when used short term. Massive dosages (e.g., as much as 15 mg) have been taken with no ill effects. However, as noted in Chapter 81, even moderately large doses (1000 mcg/day), when taken long term, may pose a nonsignificant increase in the risk of some cancers, including colorectal cancer and cancer of the prostate.
Safety Alert
FOLIC ACID
If taken in large-enough doses, folic acid can correct the hematologic consequences of vitamin B12 deficiency, masking the fact that a vitamin B12 deficiency still exists. Since folic acid will not prevent the neurologic consequences of B12
deficiency, this masking effect may allow the development of irreversible damage to the nervous system. Therefore, folate should not be used indiscriminately. Unless specifically indicated, consumption of folic acid should not exceed 1000 mcg/day, and whenever folic acid is given to patients known to have a deficiency in vitamin B12, care must be taken to ensure that the vitamin B12 dosage is adequate.
Formulations and Routes of Administration
Folic acid is available in tablets (0.4, 0.8, and 1 mg) for oral use and in a 5-mg/mL solution for IM, IV, or subQ injection. As a rule, injections are reserved for patients with severely impaired GI absorption.
Dosage
For treatment of folate-deficient megaloblastic anemia in adults, the usual oral dosage is 1000 to 2000 mcg/day. Once symptoms have resolved, the maintenance dosage is 400 mcg/day. For prophylaxis during pregnancy and lactation, doses up to 1000 mcg/day may be used.
KEY POINTS
■ The principal cause of iron deficiency is increased iron demand secondary to (1) maternal and fetal blood volume expansion during pregnancy; (2) blood volume expansion during infancy and early childhood; or (3) chronic blood loss, usually of GI or uterine origin.
■ The major consequence of iron deficiency is microcytic, hypochromic anemia.
■ Ferrous sulfate, given PO, is the drug of choice for iron deficiency.
■ Iron-deficient patients who cannot tolerate or absorb oral ferrous salts are treated with parenteral iron—usually iron dextran administered IV.
■ The major adverse effects of ferrous sulfate are GI distur-bances. These are best managed by reducing the dosage (rather than by administering the drug with food, which would greatly reduce absorption).
■ Parenteral iron dextran carries a significant risk of fatal anaphylactic reactions. The risk is much lower with other parenteral iron products (e.g., iron sucrose).
■ When iron dextran is used, a small test dose is required before each full dose. Be aware, however, that patients can experience anaphylaxis and other hypersensitivity reactions from the test dose, and patients who did not react to the test dose may still have these reactions with the full dose.
■ The principal cause of vitamin B12 deficiency is impaired absorption secondary to lack of intrinsic factor.
■ The principal consequences of B12 deficiency are mega-loblastic (macrocytic) anemia and neurologic injury.
■ Vitamin B12 deficiency caused by malabsorption is treated lifelong with cyanocobalamin. Traditional treatment consists of IM injections administered monthly. However, large oral doses administered daily are also effective, as are intranasal doses (administered weekly with Nascobal).
■ For initial therapy of severe vitamin B12 deficiency, par-enteral folic acid is given along with cyanocobalamin.
■ When folic acid is combined with vitamin B12 to treat B12
deficiency, it is essential that the dosage of B12 be adequate because folic acid can mask continued B12 deficiency (by improving the hematologic picture), while allowing the neurologic consequences of B12 deficiency to progress.
■ The principal causes of folic acid deficiency are poor diet (usually in patients with alcohol use disorder) and malab-sorption secondary to intestinal disease.
■ The principal consequences of folic acid deficiency are megaloblastic anemia and neural tube defects in the developing fetus.
■ To prevent neural tube defects, all women who may become pregnant should ingest 400 to 800 mcg of supplemental folate daily, in addition to the folate they get in food.
Please visit http://evolve.elsevier.com/Lehne for chapter-specific NCLEX® examination review questions.
Summary of Major Nursing Implications
aIRON PREPARATIONS Carbonyl iron
Ferric ammonium citrate Ferrous aspartate Ferrous bisglycinate Ferrous fumarate Ferrous gluconate Ferrous sulfate Ferumoxytol
Heme-iron polypeptide Iron dextran
Iron sucrose
Polysaccharide iron complex
Sodium–ferric gluconate complex (SFGC)
Except where indicated, the implications summarized here apply to all iron preparations.
Preadministration Assessment Therapeutic Goal
Prevention or treatment of iron deficiency anemias.
Baseline Data
Before treatment, assess the degree of anemia. Fatigue, listless-ness, and pallor indicate mild anemia; dyspnea, tachycardia, and angina suggest severe anemia. Laboratory findings
indicative of anemia are subnormal hemoglobin levels, subnormal hematocrit, subnormal hemosiderin in bone marrow, and the presence of microcytic, hypochromic erythrocytes.
The cause of iron deficiency (e.g., pregnancy, occult bleeding, menorrhagia, inadequate diet, malabsorption) must be determined.
Identifying High-Risk Patients
All iron preparations are contraindicated for patients with anemias other than iron deficiency anemia.
Parenteral preparations are contraindicated for patients who have had a severe allergic reaction to them in the past.
Use oral preparations with caution in patients with peptic ulcer disease, regional enteritis, and ulcerative colitis.
Implementation: Administration Routes
Oral. Ferrous sulfate, ferrous fumarate, ferrous gluconate, ferrous aspartate, ferrous bisglycinate, ferric ammonium citrate, carbonyl iron, heme-iron polypeptide, polysaccharide iron complex, SFGC.
Parenteral. Iron dextran, SFGC, iron sucrose, ferumoxytol.
Oral Administration
Food reduces GI distress from oral iron but also greatly reduces absorption. Instruct patients to administer oral iron between
CHAPTER 55 Drugs for Deficiency Anemias
Continued meals to maximize uptake. If GI distress is intolerable, the
dosage may be reduced. If absolutely necessary, oral iron may be administered with meals.
Liquid preparations can stain the teeth. Instruct patients to dilute liquid preparations with juice or water, administer them through a straw, and rinse the mouth after.
Warn patients not to crush or chew sustained-release preparations.
Warn patients against ingesting iron salts together with antacids or tetracyclines.
Inform patients that oral iron preparations differ and warn them against switching from one to another.
Parenteral Administration: Iron Dextran
Iron dextran may be given IV or IM. Intravenous administra-tion is safer and preferred.
Intravenous. To minimize anaphylactic reactions, follow this protocol: (1) Infuse 25 mg as a test dose and observe the patient for at least 15 minutes. (2) If the test dose appears safe, infuse 100 mg over 10 to 15 minutes. (3) If the 100-mg dose proves uneventful, give additional doses as needed every 24 hours.
Intramuscular. Intramuscular injection can cause signifi-cant adverse reactions (anaphylaxis, persistent pain, localized discoloration, promotion of tumors) and is generally avoided.
Make injections deep into each buttock using the Z-track technique. Give a 25-mg test dose and wait 1 hour before giving the full therapeutic dose.
Parenteral Administration: SFGC
To minimize adverse reactions, precede the first full dose with a test dose (25 mg infused IV over 60 minutes).
Administer therapeutic doses by slow IV infusion (no faster than 12.5 mg/min).
Parenteral Administration: Iron Sucrose
Hemodialysis-Dependent Patients. Administer iron sucrose directly into the dialysis line. Do not mix with other drugs or with parenteral nutrition solutions. Administer by either (1) slow injection (1 mL/min) or (2) infusion (dilute iron sucrose in up to 100 mL of 0.9% saline and infuse over 15 minutes or longer).
Peritoneal Dialysis–Dependent Patients. Administer by slow infusion.
Non–Dialysis-Dependent Patients. Administer by slow injection.
Parenteral Administration: Ferumoxytol
Give 510 mg by slow IV injection, defined here as 1 mL/sec (30 mg/sec), taking about 17 seconds for the total 510-mg dose. Repeat 3 to 8 days later.
Implementation: Measures to Enhance Therapeutic Effects
If the diet is low in iron, advise the patient to increase consumption of iron-rich foods (e.g., egg yolks, brewer’s yeast, wheat germ, muscle meats, fish, fowl).
Ongoing Evaluation and Interventions Evaluating Therapeutic Responses
Evaluate treatment by monitoring hematologic status. Reticu-locyte counts should increase within 4 to 7 days, hemoglobin content and the hematocrit should begin to rise within 1 week, and hemoglobin levels should rise by at least 2 gm/
dL within 1 month. If these responses do not occur, evaluate the patient for adherence, persistent bleeding, inflammatory disease, and malabsorption.
Minimizing Adverse Effects
GI Disturbances. Forewarn patients about possible GI reactions (nausea, vomiting, constipation, diarrhea) and inform them these will diminish over time. If GI distress is severe, the dosage may be reduced, or if absolutely necessary, iron may be administered with food.
Inform patients that iron will impart a harmless dark green or black color to stools.
Anaphylactic Reactions. Parenteral iron dextran (and, rarely, SFGC, iron sucrose, and ferumoxytol) can cause potentially fatal anaphylaxis. Before giving parenteral iron, ensure that injectable epinephrine and facilities for resuscita-tion are immediately available. After administraresuscita-tion, observe the patient for 60 minutes. Give test doses as described earlier.
Precede all doses of iron dextran with a test dose; test doses are unnecessary with iron sucrose and ferumoxytol.
Managing Acute Toxicity. Iron poisoning can be fatal to young children. Instruct parents to store iron out of reach and in childproof containers. If poisoning occurs, rapid treatment is imperative. Use gastric lavage to remove iron from the stomach. Administer deferoxamine if plasma levels of iron exceed 500 mcg/mL. Manage acidosis and shock as required.
CYANOCOBALAMIN (VITAMIN B12) Preadministration Assessment Therapeutic Goal
Correction of megaloblastic anemia and other sequelae of vitamin B12 deficiency.
Baseline Data
Assess the extent of vitamin B12 deficiency. Record signs and symptoms of anemia (e.g., pallor, dyspnea, palpitations, fatigue). Determine the extent of neurologic damage. Assess GI involvement.
Baseline laboratory data include plasma vitamin B12
levels, erythrocyte and reticulocyte counts, and hemoglobin and hematocrit values. Bone marrow may be examined for megaloblasts. A Schilling test may be ordered to assess vitamin B12 absorption.
Identifying High-Risk Patients
Use with caution in patients receiving folic acid.
Implementation: Administration Routes and Administration
Administration may be IM, subQ, oral, or intranasal. For most patients, lifelong treatment is required. Traditional therapy
Summary of Major Nursing Implications
a—cont’d
consists of IM or subQ injections administered monthly.
However, treatment can be just as effective with large daily oral doses or with intranasal doses (administered weekly with Nascobal). Inform patients that intranasal doses should not be administered within 1 hour before or 1 hour after consuming hot foods or hot liquids.
Implementation: Measures to Enhance Therapeutic Effects
Promoting Adherence
Patients with permanent impairment of B12 absorption require lifelong B12 therapy. To promote adherence, educate patients about the nature of their condition, and impress upon them the need for monthly injections, daily oral therapy, or weekly intranasal therapy. Schedule appointments for injections at convenient times.
Improving Nutrition
When B12 deficiency is not due to impaired absorption, a change in diet may accelerate recovery. Advise the patient to increase consumption of B12-rich foods (e.g., muscle meats, dairy products).
Ongoing Evaluation and Interventions Evaluating Therapeutic Effects
Assess for improvements in hematologic and neurologic status.
Over a period of 2 to 3 weeks, megaloblasts should disappear, reticulocyte counts should rise, and the hematocrit should normalize. Neurologic damage may take months to improve;
in some cases, full recovery may never occur.
For patients receiving long-term therapy, vitamin B12 levels should be measured every 3 to 6 months, and blood counts should be performed.
Minimizing Adverse Effects
Hypokalemia may develop during the first days of therapy.
Monitor serum potassium levels and observe the patient for signs of potassium insufficiency. Teach patients the signs and symptoms of hypokalemia (e.g., muscle weakness, irregular heartbeat), and instruct them to report these immediately.
Minimizing Adverse Interactions
Folic acid can correct hematologic effects of vitamin B12
deficiency, but not the neurologic effects. By improving the hematologic picture, folic acid can mask ongoing B12 defi-ciency, resulting in undertreatment and progression of neu-rologic injury. Accordingly, when folic acid and cyanocobalamin are used concurrently, special care must be taken to ensure that the cyanocobalamin dosage is adequate.
FOLIC ACID (FOLACIN, FOLATE, PTEROYLGLUTAMIC ACID) Preadministration Assessment Therapeutic Goal
Folic acid is used for (1) treatment of megaloblastic anemia resulting from folic acid deficiency; (2) initial treatment of
severe megaloblastic anemia resulting from vitamin B12
deficiency; and (3) prevention of folic acid deficiency, especially in women who might become pregnant and in women who are pregnant or lactating.
Baseline Data
Assess the extent of folate deficiency. Record signs and symptoms of anemia (e.g., pallor, dyspnea, palpitations, fatigue). Determine the extent of GI damage.
Baseline laboratory data include serum folate levels, erythrocyte and reticulocyte counts, and hemoglobin and hematocrit values. In addition, bone marrow may be evaluated for megaloblasts. To rule out vitamin B12 deficiency, vitamin B12 determinations and a Schilling test may be ordered.
Identifying High-Risk Patients
Folic acid is contraindicated for patients with pernicious anemia (except during the acute phase of treatment).
Inappropriate use of folic acid by these patients can mask signs of vitamin B12 deficiency, allowing further neurologic deterioration.
Implementation: Dosage and Administration Routes
Oral, subQ, IV, and IM. Oral administration is most common and preferred. Injections are employed only when intestinal absorption is severely impaired.
Dosage
Prevention of Neural Tube Defects. To reduce the risk of neural tube defects, women who might become pregnant should consume 400 to 800 mcg of supplemental folate daily—in addition to the folate they get from food.
Treatment of Folate-Deficient Megaloblastic Anemia.
The initial oral dosage is 1000 to 2000 mcg/day. Once symptoms have resolved, the maintenance dosage is 400 mcg/day.
Implementation: Measures to Enhance Therapeutic Effects
Improving Nutrition
If the diet is deficient in folic acid, advise the patient to increase consumption of folate-rich foods (e.g., green veg-etables, liver). If alcoholism underlies dietary deficiency, offer counseling for alcoholism, as well as dietary advice.
Ongoing Evaluation and Interventions Evaluating Therapeutic Effects
Monitor hematologic status. Within 2 weeks, megaloblasts should disappear, reticulocyte counts should increase, and the hematocrit should begin to rise.
Summary of Major Nursing Implications
a—cont’d
aPatient education information is highlighted as blue text.
C H A P T E R
56 Hematopoietic Agents
HEMATOPOIETIC GROWTH FACTORS, p. 663