Vitamin Toxicity

Vitamin A

Being fat-soluble, vitamin A is stored to a variable degree in the body, making it more likely to cause toxicity when taken in excess amounts.[13] In contrast, water-soluble vitamins are generally excreted in the urine and stored only to a limited extent; hence, adverse effects occur only when extremely large amounts are taken.

The bioavailability of retinol is generally more than 80%, whereas the bioavailability and bioconversion of carotenes (ie, provitamin A) are lower. These may be affected by species, molecular linkage, amount of carotene, nutritional status, genetic factors, and other interactions.

While in general the body absorbs retinoids and vitamin A very efficiently, it lacks the mechanisms to destroy excessive loads. Thus, the possibility of toxicity exists unless intake is carefully regulated.[14] It has been suggested that earlier estimates of daily human requirements of vitamin A be revised downward.[15]

Vitamin A is highly teratogenic in pregnancy, especially in the first 8 weeks with daily intake more than 10,000 IU; however, it is also a cofactor in night vision and bone growth.

Carotenemia is the result of excessive intake of vitamin A precursors in foods, mainly carrots. Other than the cosmetic effect, carotenemia has no adverse consequences, because the conversion of carotenes to retinol is not sufficient to cause toxicity.

Isotretinoin (Accutane), a drug used for the treatment of severe forms of acne, is closely related to the chemical structure of vitamin A, which means that the pharmacology and toxicology of these two compounds are similar. Birth defects (when taken during pregnancy), intracranial hypertension, depression, and suicidal ideation have been reported with isotretinoin.[16] A careful drug history to uncover this possibility of isotretinoin use is important in patients presenting with manifestations suggestive of vitamin A intoxication.

B Vitamins

Vitamin B1 (thiamine) and vitamin B2 (riboflavin) generally are nontoxic.

Vitamin B3

Vitamin B-3 does not have a toxic dose established for humans. However, adverse effects such as skin flushing can occur at doses of 50 mg/day or greater. While therapeutic doses are considered to typically range from 1500-6000 mg/day, these doses carry a risk of liver toxicity, especially if not titrated slowly or in the presence of any preexisting liver disease.

Vitamin B6

Over time, 300-500 mg/day of vitamin B-6 may be neurotoxic (patients with impaired renal function may be more susceptible). The acute toxic dose has generally not been established.

Vitamin B12

The toxic dose for vitamin B-12 is not established.

Vitamin C

The acute toxic dose for vitamin C has not been determined. The chronic toxic dose is more than 2 g/day.

Vitamin D

The acute toxic dose for vitamin D has not been established. The chronic toxic dose is more than 50,000 IU/day in adults. In infants younger than 6 months, 1,000 IU/day may be considered unsafe. However, a wide variance in potential toxicity exists for vitamin D.

Vitamin E

Vitamin E can prolong the prothrombin time (PT) in animal models by inhibiting vitamin K–dependent carboxylase, although administration of vitamin K corrects this. High doses of vitamin E increase the vitamin K requirement; coagulopathy can occur in patients who are deficient in vitamin K.[17, 18] (Concomitant use of vitamin E and anticoagulants can also increase the risk of bleeding complications).[17, 18]

Vitamin E at dosages of 1600 IU/day reduces platelet thromboxane production. Vitamin E supplementation may impair the hematologic response to iron in children with iron-deficiency anemia.

In the Heart Protection Study, a combination of vitamin E (600 IU alpha-tocopherol only), vitamin C, and beta-carotene did not affect mortality. However, it did cause a significant, albeit small, increase in total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides, as well as a decrease in high-density lipoprotein (HDL) cholesterol. In 2 randomized trials, an antioxidant cocktail that included vitamin E (form not specified) blunted the beneficial increase in HDL2 levels associated with niacin and simvastatin therapy.[19, 20]

Vitamin E can depress leukocyte oxidative bactericidal activity and mitogen-induced lymphocyte transformation.

Although adverse effects usually are observed only at very high dosages of vitamin E, a meta-analysis showed a possible increase in mortality at dosages of 400 IU/d and higher (alpha-tocopherol only).[9]

Complications

Note that these published studies have used only the alpha-tocopherol form of vitamin E and not a balanced mixture of the 8 different forms of vitamin E that naturally occur and have important physiologic functions. Supplementing with only one form of vitamin E has been shown to suppress the other 7 forms, resulting in physiological dysfunction, which may account for some of the negative studies presented here.[21]

Most studies using up to 3200 IU/d of vitamin E did not observe significant acute clinical or biochemical adverse effects.[22] Vitamin E supplementation does not seem to significantly increase or decrease cardiovascular events,[23, 24, 25, 26] although it may increase the risk of mortality.[10, 9]

Vitamin E supplementation was shown to increase the risk of prostate cancer in healthy men, in the Selenium and Vitamin E Cancer Prevention Trial (SELECT).[27]

In the Heart Outcomes Prevention Evaluation (HOPE-TOO) study, a randomized trial examining the effects of 400 IU of vitamin E versus those of a placebo in patients with diabetes or vascular disease, vitamin E did not decrease the incidence of cancer deaths or vascular events during follow-up (mean 7.2 y). Evidence indicated, however, that it did increase the incidence of heart failure.[28, 29, 30, 31, 32, 25, 33, 34]

An increased risk of bleeding has been observed with coadministration of vitamin E and warfarin, with an increased PT due to the depletion of vitamin K–dependent clotting factors. This does not occur in healthy individuals with normal vitamin K levels. Increased gingival bleeding also was observed in patients taking vitamin E and aspirin.[35]

The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study showed that, compared with placebo, alpha-tocopherol at dosages of 50 mg/day increased the risk of fatal subarachnoid hemorrhage by 181% in men aged 50-69 years who smoked cigarettes. The risk of cerebral infarction was decreased by 14% in the vitamin E group, with no significant net effect of vitamin E on mortality from total strokes. These results had not been found in previous studies.[36, 37]

An increased risk of sepsis occurred in a clinical trial (14% vs 6%) in which vitamin E was administered to premature neonates with a birthweight of less than 1500 g. When high-dose vitamin E of up to 30 mg/kg/day was administered to this population to prevent retrolental fibroplasia, necrotizing enterocolitis occurred. The incidence of necrotizing enterocolitis increased 2-fold (12%) in 2 studies; however, others have shown no difference. These findings may be secondary to the compounding effects of prematurity and the effect of vitamin E on the immune system. No other population has demonstrated these findings.

Fatigue and weakness were reported in 2 case series in which vitamin E was administered at dosages of 800 IU/day. The symptoms resolved with removal of the drug.

Transient nausea and gastric distress have been observed in a few patients taking high dosages (2000-2500 IU/day) of vitamin E. Diarrhea and intestinal cramps have been reported at a dosage of 3200 IU/day. Other nonspecific, adverse effects of vitamin E, although reported only rarely, include delayed wound healing and headache.

Vitamin K

A toxic dose amount for vitamin has not been established. However, vitamin K3 (menadione) supplements have been banned by the US Food and Drug Administration (FDA) because of their high toxicity.

Folate

A toxic dose has not been established, but folate is generally nontoxic. Intakes more than 5000 mcg/day mask pernicious anemia.

Occurrence in the United States

The Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS) documents the number of exposures for each class of vitamins (eg, adult and pediatric multiple vitamins, individual vitamins), the outcomes, and the fatalities from that ingestion.[1]  In 2019, the NPDS reported 46,280 single exposures to vitamins, with 1836 minor adverse outcomes, 211 moderate outcomes, 12 major outcomes, and one death.[38]

Regarding vitamin D toxicity, a retrospective analysis of NPDS data from 2000 through June 30, 2014 found that the mean number of exposures, which was 196 per year from 2000 to 2005, increased 1600% between 2005 and 2011 to a new annual mean of 4535 exposures per year. Nevertheless, a decline occurred in the percentage of patients treated in a health care facility and of patients with serious medical outcome, and one death was reported.[39]

Age-related demographics

Single vitamins are consumed more often by adults, while multivitamins are administered more frequently to children. 

Premature infants with low birthweight have suffered life-threatening adverse effects from vitamin E, with sepsis and necrotizing enterocolitis having occurred in these infants but not in others.

A syndrome of ascites, hepatomegaly, and thrombocytopenia resulting in death occurred in the 1980s in association with an intravenous vitamin E preparation used in premature infants with low birthweight. The cause was presumably a polysorbate carrier of the vitamin, and the syndrome has not occurred since its removal.

The prognosis is generally excellent in patients with vitamin toxicity.[10] Patients with vitamin E toxicity, for example, have an excellent prognosis once the supplements are discontinued. Patients with mild bleeding episodes are likely to fully recover once vitamin K is administered and the vitamin E supplements are discontinued.

Patients with vitamin E toxicity who develop an intracranial hemorrhage have an increased mortality rate. However, with proper diagnosis and management, many patients with this condition survive and recover some or all of their previous functions.

Remind parents of children who ingested vitamins of the appropriate ways to childproof their homes, and emphasize the need to use child-resistant bottles.

Instruct adults who have unintentionally overdosed on vitamins as part of their megavitamin regimen on the serious adverse effects of such chemicals.

For patient education information, see the First Aid and Injuries Center, as well as Iron Poisoning in Children, Drug Overdose, Activated Charcoal, and Poison Proofing Your Home.

Be wary of large or chronic ingestions of all vitamins in children, especially the fat-soluble vitamins A and D.

Nonspecific symptoms, such as nausea, vomiting, diarrhea, and rash, are common with any acute or chronic vitamin overdose. Vitamin-related symptoms may be secondary to those associated with additives (eg, mannitol), colorings, or binders; these symptoms usually are not severe.

Vitamin A

In acute vitamin A toxicity, a history of some or all of the following may be present:

• Nausea
• Vomiting
• Anorexia
• Irritability
• Drowsiness
• Altered mental status
• Abdominal pain
• Blurred vision
• Headache
• Muscle pain with weakness
• Seizures

In chronic vitamin A toxicity, a history of some or all of the following may be present:

• Anorexia
• Hair loss
• Dryness of mucus membranes
• Fissures of the lips
• Pruritus
• Fever
• Headache
• Insomnia
• Fatigue
• Irritability
• Weight loss
• Bone fracture ^[40]
• Hyperlipidemia
• Hypercalcemia ^[41]
• Anemia
• Bone and joint pains
• Diarrhea
• Menstrual abnormalities
• Epistaxis

Carotenemia, the ingestion of excessive amounts of vitamin A precursors in food, mainly carrots, is manifested by a yellow-orange coloring of the skin, primarily the palms of the hands and the soles of the feet. It differs from jaundice in that the sclerae remain white.

Do not forget to evaluate for ingestion of other potentially toxic substances, such as other vitamins, aspirin, and acetaminophen. Inquire about the intake of other supplements and evaluate for possible overdose accordingly.

Isotretinoin (Accutane), a drug used for the treatment of severe forms of acne, is closely related to the chemical structure of vitamin A and therefore has similar pharmacologic and toxic attributes (see Pathophysiology and Etiology). A careful drug history to uncover possible isotretinoin use is important in patients presenting with manifestations suggestive of vitamin A intoxication.

Vitamin C

The effects of vitamin C toxicity can include the following:

• Renal colic (ie, nephrolithiasis)
• Diarrhea
• Nausea
• Rebound scurvy - In infants born to women taking high doses
• Hemolysis - If glucose-6-phosphate dehydrogenase (G6PD) deficiency is present
• Dental decalcification
• Increased estrogen levels
• Occult rectal bleeding

Vitamin D

The effects of acute vitamin D toxicity are characteristic of hypercalcemia and may include the following:

• Muscle weakness
• Apathy
• Headache
• Anorexia
• Irritability
• Nausea
• Vomiting
• Bone pain

Chronic toxicity effects include the above symptoms, as well as the following:

• Constipation
• Abdominal cramps
• Polydipsia
• Polyuria
• Backache

Findings may also include calcinosis, followed by hypertension and cardiac arrhythmias (due to a shortened refractory period).

In case reports of two young breast-fed infants who developed vitamin D toxicity from inadvertent overdose of highly concentrated vitamin D formulations,  the infants presented with decreased feeding, lethargy, and inconsolable crying. Toddlers with vitamin D overdose have presented with irritability, vomiting, constipation, and hypertension.[42]

Vitamin E

Patients with vitamin E toxicity are likely to have been using vitamin E supplements; obtain the dose and duration of vitamin E usage. Assess concurrent use of anticoagulants or aspirin. Since vitamin E may block absorption of vitamin K, a nutritional assessment for vitamin K deficiency is useful in patients who present with bleeding and a prolonged prothrombin time (PT).

The effects of acute vitamin E toxicity include the following:

• Nausea
• Gastric distress
• Abdominal cramps
• Diarrhea
• Headache
• Fatigue
• Easy bruising and bleeding - Prolonged PT and activated partial thromboplastin time (aPTT)
• Inhibition of platelet aggregation
• Diplopia - At dosages as low as 300 IU
• Muscle weakness
• Creatinuria

Chronic toxicity effects include all of the above, as well as suppression of other antioxidants and increased risk of hemorrhagic stroke.

Vitamin K

Vitamin K toxicity is typically seen in formula-fed infants or those receiving synthetic vitamin K-3 (menadione) injections. Because of its toxicity, menadione is no longer used for treatment of vitamin K deficiency.

The effects of vitamin K toxicity can include jaundice in newborns, hemolytic anemia, and hyperbilirubinemia. Toxicity also blocks the effects of oral anticoagulants.

Vitamin A

Acute toxicity

Acute vitamin A toxicity can result in the following:

• Headache
• Photophobia
• Abdominal pain
• Drowsiness
• Irritability
• Desquamation

Manifestations of acute toxicity also include muscle and bone tenderness, especially over the long bones of the upper and lower extremities, as well as neurologic manifestations with signs of increased intracranial pressure (eg, children may have bulging fontanelles).

Chronic toxicity

Chronic vitamin A toxicity affects the skin, the mucous membranes, and the musculoskeletal and neurologic systems. Skin and mucous membrane effects include erythema, eczema, pruritus, dry and cracked skin, angular cheilitis, conjunctivitis, palmar and plantar peeling, and alopecia.

Musculoskeletal effects include pain and tenderness, particularly in the long bones of the upper and lower extremities, which may be exacerbated by exercise. Neurologic effects include blurred vision and frontal headache, which is often the first sign of toxicity.

In addition, studies suggest that elevated levels of vitamin A may cause increased bone resorption and promote the development of osteoporosis.[3, 43]

Manifestations of chronic vitamin A toxicity also include the following:

• Alopecia
• Erythematous dermatitis
• Skin desquamation
• Brittle nails
• Exanthema
• Cheilitis
• Conjunctivitis
• Petechiae
• Liver cirrhosis
• Hepatosplenomegaly
• Peripheral neuritis
• Benign intracranial hypertension
• Ataxia
• Papilledema
• Diplopia
• Hyperostosis
• Edema
• Hepatic hydrothorax ^[44]
• Hepatomegaly
• Ascites
• Migratory arthritis
• Craniotabes (in children)
• Bulging fontanelle (in infants)
• Epiphyseal capping and premature epiphyseal closure

Vitamins B1, B2, B3, and B6

The effects of toxicity may be minimal and nonspecific for these vitamins.

Vitamin B1

Vitamin B1 (ie, thiamine) toxicity effects may include the following (single acute toxicity is rare):

• Tachycardia
• Hypotension
• Cardiac dysrhythmias
• Headache
• Anaphylaxis
• Vasodilation
• Weakness
• Convulsions

Vitamin B2

Vitamin B2 (ie, riboflavin) toxicity turns the patient’s urine yellow-orange.

Vitamin B3

Acute toxicity effects related to vitamin B3 (ie, niacin, nicotinic acid) are prostaglandin-mediated and include the following:

• Flushing
• Pruritus
• Wheezing
• Vasodilation
• Headache
• Increased intracranial blood flow
• Headache
• Diarrhea
• Vomiting

Chronic toxicity effects include the following:

• Jaundice
• Abnormal liver function test (LFT) results
• Signs and symptoms of liver toxicity - Most common with sustained-release preparations
• Acanthosis nigricans (rare)

Vitamin B6

Effects of vitamin B6 (ie, pyridoxine) toxicity include tachypnea and sensory neuropathies, such as the following:

Burning pains

• Paresthesias
• Ataxia
• Clumsiness
• Paralysis
• Perioral numbness

Findings range from normal central nervous system (CNS) function to progressive sensory ataxias, profound impairment of position and vibration sense, and diminished tendon reflexes.

Vitamin E

Physical examination findings are likely to be normal in patients with vitamin E toxicity; however, evidence of easy bleeding may be present if the PT is elevated.

Patients with intracranial hemorrhage may show signs of focal neurologic deficits on a detailed neurologic examination or may have a decreased level of consciousness.

Acetaminophen and aspirin levels should be assessed in every suspected ingestion. Electrolyte levels must be assessed in patients with severe vomiting or diarrhea.

In addition to laboratory studies, imaging and electrocardiographic studies can be used in the assessment of patients with vitamin toxicity.

Imaging Studies

Imaging studies can be employed as follows:

• Skeletal radiography - For calcifications in chronic vitamin A and vitamin D toxicity
• Hand radiography - For periosteal calcifications
• Helical computed tomography (CT) scanning and urography - Obtain a helical CT scan or an intravenous urogram (IVU) for suspected nephrolithiasis (ie, oxalate stones) in patients with vitamin C toxicity
• CT scanning of the brain - In the presence of neurologic abnormalities, perform a CT scan of the brain, without contrast, only if the prothrombin time (PT) is significantly prolonged and the patient has either a decreased level of consciousness or a focal neurologic deficit
• Kidneys, ureters, bladder (KUB) film - Indicated for suspected toxicity from iron-containing pills
• Bone mineral density testing - to evaluate the effect of long-term vitamin A intoxication on reducing bone density and causing osteoporosis ^[45]

Electrocardiography

Obtain an electrocardiogram (ECG) to evaluate for effects of hypercalcemia in patients with vitamin D toxicity.

Vitamin A

The reference range for vitamin A is 20-60 mcg/dL, and a toxic level is higher than 60-100 mcg/dL. Obtain a complete blood count (CBC) to rule out leukopenia. Also perform calcium, glucose, and liver function tests (LFTs). levels are affected by liver stores and dietary intake of vitamin A.

For serum carotene, the normal range is 50-300 mcg/dL. Carotene levels reflects dietary intake of vitamin A.

Laboratory studies in vitamin A toxicity include the following:

• Serum electrolytes - If vomiting or diarrhea is present
• Serum calcium - Hypercalcemia may be observed ^[41]
• Liver function tests (LFTs)
• Complete blood count (CBC) - For anemia, leukopenia, or thrombocytopenia
• Vitamin A assessment by serum retinol concentrations - Vitamin A assessment by serum retinol concentrations may be helpful if the level is markedly high; in mild conditions, however, it may not be sensitive
• High-performance liquid chromatography (HPLC)

Johnson-Davis et al reported that a modified form of HPLC they developed shortened analysis time for serum concentrations of vitamins A and E.[46] Using their modifications—a high-throughput analytic column and small diameter tubing—to determine pediatric reference intervals for the 2 vitamins in 1136 healthy children, the authors found that their technique reduced run-time by 60%, mobile phase consumption by 39%, and sample injection volume by 50%.

A lumbar puncture may be indicated to rule out increased intracranial pressure in patients with vitamin A toxicity.

B Vitamins

Recommended laboratory studies in patients with possible B vitamin toxicity are as follows:

• Vitamins B1, B2, and B12 - These require no specific laboratory tests.
• Vitamin B3 - Perform LFTs. Uric acid may be increased, leading to gouty arthritis. The glucose level is occasionally elevated.
• Vitamin B6 - Vitamin B6 toxicity does not require laboratory or other tests. Lumbar puncture may be considered to rule out other causes if the patient has a peripheral neuropathy.

Vitamin C

Perform urinalysis to rule out uricosuria. False-negative test results for glucosuria are possible. Also perform renal function tests.

Measure PT if the patient is taking warfarin (Coumadin), since vitamin C may interfere with this drug. Serum iron levels should also be measured, because vitamin C enhances iron absorption.

Vitamin D

Obtaining calcium levels is mandatory; they are usually above 11 mg/dL but may be much higher. Phosphate levels may increase with calcium.

Kidney function tests (ie, blood urea nitrogen [BUN] and creatine tests, as well as urinalysis) are necessary to rule out possible kidney damage from hypercalciuria.

Vitamin E

Measure PT, activated partial thromboplastin time (aPTT), and bleeding times, especially if any evidence of bruising or bleeding is present. Platelet aggregation studies may be performed if bleeding time results are abnormal.

Monitor PT in patients who are taking anticoagulants concurrently with vitamin E or in patients suggested to have vitamin K deficiency while taking vitamin E, because the PT may be elevated.

The plasma concentration of alpha tocopherol (normal, 6-14 mcg/mL) can be measured to confirm that high levels of vitamin E are in the blood.

Vitamin K

Measure PT if the patient is taking oral anticoagulants.

Emergency department care

All ingestions require supportive management and an intravenous line. Serious ingestions require hydration if vomiting or diarrhea is present. Oxygen, monitoring, and ABCs are essential if potentially life-threatening manifestations are present.

If potentially lethal coingestions are present, perform gastric lavage if the patient presents within 1 hour postingestion. Always check whether the vitamin overdose included iron supplements, and manage such an overdose aggressively.

Identify other potentially lethal coingestants, such as acetaminophen, aspirin, and dangerous prescription drugs (ie, digoxin, lithium, phenothiazines). Other care is symptomatic and supportive.

Consultations

Consult a neurosurgeon if evidence of CNS hemorrhage is present. For more information on vitamin toxicity management, consult a regional poison control center or a local medical toxicologist (certified through the American Board of Medical Toxicology or the American Board of Emergency Medicine).

Patients on isotretinoin should be evaluated by their dermatologist for consideration of stopping the drug.

Vitamin A

Symptoms of vitamin A toxicity usually resolve after stopping vitamin A and instituting supportive therapy. The pigmentation of carotenemia usually disappears with the omission of carrots from the diet.

Patients with increased intracranial pressure may need therapeutic lumbar punctures or further treatment with medications such as diuretics and mannitol.

Patients with symptomatic hypercalcemia require the following:

• Close monitoring
• Treatment with intravenous fluids and diuretics
• Additional therapy, including pamidronate, calcitonin, corticosteroids, or mithramycin
• Discontinuation of vitamin A

Vitamin D

Place patients with vitamin D toxicity on a low-calcium diet. Consider oral calcium disodium edetate to increase fecal excretion of calcium.

In cases of severe hypercalcemia, patients may require hydration, diuretics, steroids (hydrocortisone 100 mg IV q6h), calcitonin (4-8 IU/kg q6-12h), and/or mithramycin (25 mcg/kg qDay IV over 4-6 h for 1-4 days). Peritoneal or hemodialysis may be necessary if large amounts of fluids cannot be given.

Other Vitamins

Vitamins K, B1, B2, B6, B12, and C, and folate

These usually require only supportive measures.

Vitamin B3

Provide supportive treatment as needed. Aspirin taken 30 minutes before niacin decreases the flush response.

Vitamin E

Management of vitamin E toxicity consists of discontinuing vitamin E supplements and monitoring the PT if bleeding complications develop.

Vitamin K replacement through the oral or subcutaneous route should reduce the elevated PT and decrease the risk of bleeding in patients who are taking anticoagulants or who have vitamin K deficiency.

Admit patients with the following conditions:

• Risk for suicide
• Intractable emesis
• Altered mental status
• Neurologic symptoms
• Serious coingestions
• Severe dehydration
• Metabolic derangements - (Eg, hypercalcemia, severe electrolyte abnormalities, ECG changes, kidney or liver damage)

Vitamin E

Patients with vitamin E toxicity require hospitalization only if bleeding complications, including intracranial hemorrhage, occur.

If an intracranial hemorrhage is suggested or the patient has focal neurologic findings on examination, order a head CT scan without contrast to rule out an existing hemorrhage.

If hemorrhage is present, the patient should receive inpatient medical management, with a neurosurgeon consulted for possible drainage of the fluid collection.

Patients who present with other forms of bleeding should receive vitamin K and should be observed until they are stable, with follow-up evaluation provided on an outpatient basis.

Care for vitamin toxicity is generally symptomatic and supportive. Gastrointestinal decontamination may be helpful to minimize amount of vitamin absorbed systemically. Administer charcoal for acute overdoses. Antiemetics or antidiarrheals are helpful if needed.

As previously stated, patients with increased intracranial pressure from vitamin A toxicity may need treatment with medications such as diuretics and mannitol.

In cases of vitamin D toxicity, patients with severe hypercalcemia may require hydration, diuretics, steroids (hydrocortisone 100 mg IV q6h), calcitonin (4-8 IU/kg q6-12h), and/or mithramycin (25 mcg/kg IV over 4-6 h, once daily for 1-4 days).

Class Summary

In cases of vitamin E toxicity, vitamin K replacement through the oral or subcutaneous route should reduce an elevated prothrombin time (PT) and decrease the risk of bleeding in patients who are taking anticoagulants or who have vitamin K deficiency.

Vitamin K, phytonadione (MEPHYTON, K100)

Vitamin K is a fat-soluble vitamin absorbed by the gut and stored in the liver. It is necessary for the function of clotting factors in the coagulation cascade and is used to replace an essential vitamin not obtained in sufficient quantities in the diet or to further supplement levels.

Class Summary

Activated charcoal is used empirically to minimize systemic absorption of a toxin. It may be of benefit only if administered within 1 hour of ingestion.

Activated charcoal (Actidose-Aqua, EZ-Char, Kerr Insta-Char)

Activated charcoal binds vitamin within the gastrointestinal tract. Multiple doses can be administered to help enhance elimination (although little evidence supports multiple doses of activated charcoal in vitamin overdose). The initial dose may be administered with a cathartic (eg, sorbitol). Subsequent doses should be half of the original dose, without a cathartic, administered as often as every 2-6 hours. Do not administer subsequent doses in the presence of ileus.

Class Summary

Diuretics induce calciuresis. In patients with severe hypercalcemia, the individual typically is volume depleted, which means that volume should be replaced with saline prior to institution of diuretic therapy.

Furosemide (Lasix)

Furosemide inhibits the resorption of sodium and chloride in the loop of Henle and the proximal and distal tubules of the kidney. Its onset of action is rapid after an intravenous dose.

Class Summary

Patients with severe hypercalcemia may require corticosteroids. Corticosteroids have profound and varied metabolic effects.

Hydrocortisone (Cortef, Solu-Cortef)

Glucocorticoids increase urinary calcium excretion. In addition, vitamin D–mediated gastrointestinal calcium absorption is inhibited. However, 1-2 weeks may elapse before serum calcium concentrations decrease. A dosage of 100 mg IV q6h may be administered.

Class Summary

Calcitonin analogues may be used if the patient is severely hypercalcemic following the diuretic therapy. These agents directly inhibit osteoclastic bone resorption and have significant analgesic effects on bone.

Salmon calcitonin (Miacalcin, Fortical)

This agent is a peptide hormone that binds to calcitonin receptors on osteoclasts and rapidly inhibits bone resorption. Osteoclasts do not induce cytotoxic effects in bone cells.

Salmon calcitonin induces reductions in urinary hydroxyproline and serum alkaline phosphatase levels. Serum alkaline phosphatase begins to decline 4 weeks after initiation of treatment. Levels of urinary hydroxyproline may decrease quickly, indicating inhibition of bone resorption. These laboratory markers slowly increase back to pretreatment levels if treatment is stopped.

Restoration of more normal bone can be seen radiographically, especially after long-term calcitonin treatment. Bone biopsy samples also reflect reduced disease activity because decreased bone cells, marrow fibrosis, and woven bone are present. Improvement of neurologic deficits and stabilization of hearing have been noted. A dosage of 4-8 IU/kg IM/SC q6-12h may be administered.