RADIOPHARMACEUTICALS

Classification | Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

Specific Substances

1) Diagnostic radiopharmaceuticals
2) Diagnostic agents, radiopharmaceutical
3) Diagnostic agents, radiopharmaceutical imaging
4) Nuclear medicine
5) Radioactive pharmaceuticals
6) Radiopharmaceutical
7) Radiopharmaceutical agents
8) Radiopharmaceutical imaging
9) Radiopharmacy

1.2.1) MOLECULAR FORMULA
1) CHOLINE C 11: C4(11)CH14NOCl
2) FLUTEMETAMOL F 18: C14H11(18)FN2OS
3) GADOTERATE MEGLUMINE: C23H42O13Gd (anhydrous basis)

Available Forms Sources

1) CARBON-14 UREA

a) Available as a gelatin capsule containing 1 microCi of carbon-14 labeled urea for oral administration (Prod Info PYtest(R) oral capsules, 2000).

2) COPPER-64 CHLORIDE

a) Copper-64 chloride is supplied in a vial containing an activity ranging from 925 MBq to 2770 MBq which corresponds to an amount of 0.25 to 0.75 mcg of copper-64. The volume of solution in each vial varies from 1 to 3 mL (Prod Info Cuprymina intravenous injection solution, 2012).

3) FLUTEMETAMOL F 18

a) Flutemetamol F 18 is supplied as 150 MBq/mL (4.05 mCi/mL) injection at reference date and time in 10 or 30 mL multidose glass vials (Prod Info VIZAMYL(TM) intravenous injection, 2013).

4) GALLIUM CITRATE Ga 67

a) Gallium Citrate Ga 67 is available as an injection for intravenous use. Each mL contains 74 MBq (2 mCi) of Gallium Ga 67 on the calibration dates, as a complex formed from 9 ng gallium chloride Ga 67, 2 mg of sodium citrate, 6.8 mg sodium chloride, and 9 mg benzyl alcohol/mL. Vials are available in the following quantities of radioactivity: 244.2, 325.6, 488.4 and 732.6 MBq (Prod Info Gallium citrate Ga 67 , 2003).

5) INDIUM-111 IBRITUMOMAB TIUXETAN

a) Refer to "IBRITUMOMAB" document for more information.

6) SAMARIUM-153 LEXIDRONAM (SAMARIUM SM 153 LEXIDRONAM)

a) SAMARIUM SM 153 LEXIDRONAM is supplied frozen in a single dose 10 mL glass vial with 1850 +/- 185 MBq/mL (50 +/- 5 mCi/mL) of samarium -153 (Prod Info QUADRAMET(R) IV injection, 2003).
b) A 3 mL fill size containing a total activity of 5550 MBq (150 mCi) is also available (Prod Info QUADRAMET(R) IV injection, 2003).

7) SODIUM IODIDE (IODINE-131) (SODIUM IODIDE I 131)

a) Available in an oral capsule formulation in various strengths (Prod Info Sodium Iodide I 131, 90).

8) SODIUM PHOSPHATE (PHOSPHORUS-32) (SODIUM PHOSPHATE P 32)

a) Sodium phosphate P 32 is available in single dose vials of 7.5 mL for injection containing 185 MBq (5 mCi). Each milliliter contains 24.8 MBq (0.67 mCi) of sodium phosphate P 32 (Prod Info sodium phosphate P 32 solution, 2000).

9) STRONTIUM-89

a) Strontium-89 is supplied in 10 mL vials containing 148 MBq (4 millicuries) (Prod Info METASTRON(TM) IV injection, 2002).

10) TECHNETIUM TC 99M BESILESOMAB

a) Technetium TC 99M besilesomab is supplied in 10 mL vials containing 1 mg of besilesomab (Prod Info Scintimun intravenous injection solution, 2011).

11) THALLOUS CHLORIDE (THALLIUM-201) (THALLOUS CHLORIDE Tl 201)

a) Thallous chloride Tl 201 radioactive solution for intravenous injection is available as 37 MBq (1 mCi) per mL at time of calibration. Vials of thallous chloride Tl 201 are available with the following quantities of radioactivity: 81.4 MBq (2.2 mCi), 103.6 MBq (2.8 millicuries), 207.2 MBq (5.6 mCi), 233.1 megabecquerels (6.3 mCi), 366.3 MBq (9.9 mCi) (Prod Info Thallous Chloride Tl 201 Injection, 2004).

12) YTTRIUM-90 CHLORIDE

a) Yttrium-90 chloride is supplied in 2-mL vial, with 1 vial containing 0.5 to 2 mL (corresponding to 0.925 to 3.7 GBq ). 1 mL of sterile solution contains 1.85 GBq yttrium-90 chloride, corresponding to 92 ng of yttrium (Prod Info Yttriga injection solution, 2012).

1) This document covers a group of radiopharmaceutical agents used to diagnose or treat various malignancies, endocrinopathies, metabolopathies, and perfusion abnormalities. Please refer to "RADIATION" document for more information.
2) The following radiopharmaceuticals are available (CardinalHealth, 2010; Prod Info Yttriga injection solution, 2012; Prod Info Cuprymina intravenous injection solution, 2012; Prod Info Scintimun intravenous injection solution, 2011):

a) CARBON-14 UREA

1) Used to detect gastric urease as an aid in the diagnosis of H. Pylori infection in the stomach.

b) CHROMIUM-51 SODIUM CHROMATE

1) Used to determine red blood cell volume, red cell mass, red cell survival time and evaluating blood loss in a variety of conditions.

c) COPPER-64 CHLORIDE

1) Used for radiolabeling of carrier molecules. NOT intended for direct patient use.

d) FLUORINE-18 SODIUM FLUORIDE

1) Used as a PET bone imaging agent to indicate areas of altered osteogenesis.

e) FLUORINE-18 FLUORODEOXYGLUCOSE

1) Used as a PET imaging agent to evaluate abnormal glucose metabolism in oncology, evaluate myocardial hibernation, and determine regions of abnormal glucose metabolism associated with foci of epileptic seizures.

f) FLUORINE-18 FLUORODOPA

1) Used in evaluating Parkinsonian type movement disorders.

g) FLUTEMETAMOL F 18

1) Flutemetamol F 18 is indicated for Position Emission Tomography imaging of the brain to estimate beta-amyloid neuritic plaque density in adult patients with cognitive impairment who are being evaluated for Alzheimer's Disease and other causes of cognitive decline. Flutemetamol F 18 is an adjunct to other diagnostic evaluations (Prod Info VIZAMYL(TM) intravenous injection, 2013).

h) GADOTERATE MEGLUMINE

1) A contrast agent used with magnetic resonance imaging of brain, spine, and associated tissues to detect disruption of the blood brain barrier or other vascular abnormalities.

i) GALLIUM-67 CITRATE

1) Used to demonstrate the following malignancies: Hodgkin's disease, lymphomas and bronchogenic carcinoma.

j) INDIUM-111 CAPROMAB PENDETIDE

1) A diagnostic imaging agent used in patients with biopsy-proven prostate cancer.

k) INDIUM-111 CHLORIDE

1) Used for radiolabeling and in vivo diagnostic imaging procedures.

l) INDIUM-111 IBRITUMOMAB TIUXETAN

1) Used as part of a therapeutic regimen for the treatment of patients with non-Hodgkin's lymphoma. Refer to "IBRITUMOMAB" document for more information.

m) INDIUM-111 PENTETATE

1) Used in radionuclide cisternography.

n) INDIUM-111 OXYQUINOLINE

1) Used for radiolabeling autologous leukocytes to detect inflammatory processes to which leukocytes migrate (eg, abscesses or infections).

o) INDIUM-111 PENTETREOTIDE

1) Used for the scintigraphic localization of primary and metastatic neuroendocrine tumors bearing somatostatin receptors.

p) IODINE I-123 IOBENGUANE

1) Used in patients older than 1 month of age to detect primary or metastatic pheochromocytoma and neuroblastoma.

q) IODINE I-123 SODIUM IODIDE

1) Used to evaluate thyroid function and morphology.

r) IODINE I-125 HUMAN SERUM ALBUMIN

1) Used to determine total blood and plasma volume.

s) IODINE I-125 IOTHALAMTE

1) Used to evaluate glomerular filtration.

t) IODINE I-131 HUMAN SERUM ALBUMIN

1) Used to determine total blood and plasma volumes, cardiac output, cardiac and pulmonary blood volumes and circulation times, protein turnover studies, heart and great vessel delineation, localization of the placenta, and localization of cerebral neoplasms.

u) IODINE I-131 SODIUM IODIDE

1) Used to perform radioactive iodide uptake test to evaluate thyroid function; also to treat hyperthyroidism and thyroid cancer.

v) IODINE I-131 TOSITUMOMAB

1) Used to treat patients with non-Hodgkin's lymphoma.

w) MOLYBDENUM MO-99 GENERATOR

1) Generation of Tc-99m sodium pertechnetate for use or radiopharmaceutical preparation.

x) NITROGEN-13 AMMONIA

1) Used as a PET agent to evaluate myocardial blood flow (perfusion).

y) RUBIDIUM-82 CHLORIDE

1) Used as a PET myocardial perfusion agent used to determine normal from abnormal myocardium in patients with suspected myocardial infarction.

z) SAMARIUM-153 LEXIDRONAM

1) Used to relieve pain in patients with osteoblastic metastatic bone lesions that enhance on radionuclide bone scan.

aa) STRONTIUM-89 CHLORIDE

1) Used to relieve bone pain in patients with skeletal metastases.

ab) TECHNETIUM TC 99M BESILESOMAB

1) Technetium Tc 99m besilesomab is used for scintigraphic imaging, in conjunction with other appropriate imaging modalities, for determining the location of inflammation or infection in peripheral bone in adults with suspected osteomyelitis (Prod Info Scintimun intravenous injection solution, 2011).

ac) TECHNETIUM-99 M

1) TYPES: Technetium-99m bicisate, disofenin, exametazine, macroaggregated albumin, mebrofenin, medronate, mertiatide, oxidronate, pentetate, pyrophosphate, red blood cells, sestamibi, sodium pertechnetate, succimer, sulfur colloid, tetrofosmin.
2) USES: Mainly used as imaging agents to delineate areas (eg, brain, kidney, coronary arteries, gastrointestinal tract).

ad) THALLIUM-201 CHLORIDE

1) Used in myocardial perfusion imaging, diagnosis of ischemic heart disease, and localization of sites of parathyroid hyperactivity.

ae) XENON-133 GAS

1) Used to evaluate pulmonary function and for imaging the lungs, and evaluate cerebral flow.

af) YTTRIUM-90 CHLORIDE

1) Used for radiolabeling of medicinal products. NOT intended for direct patient use.

ag) YTTRIUM-90 IBRITUMOMAB TIUXETAN

1) Used for the treatment of non-Hodgkin's lymphoma.

Overview

Life Support

Clinical Effects

0.2.1)

A) USES: Radiopharmaceutical agents are used to diagnose or treat various malignancies, endocrinopathies, metabolopathies, and perfusion abnormalities.
B) PHARMACOLOGY: Pharmacology varies by agent. COLLOIDAL CHROMIC PHOSPHATE P 32 introduced into a body cavity is phagocytized by free macrophages and fixed to the lining of the cavity wall, thus providing local irradiation, via beta emission, to the affected area. SAMARIUM SM 153 is chelated to ethylenediaminetetramethylene phosphonic acid, forming a bone-seeking diphosphonate complex that concentrates in areas of bone turnover in association with hydroxyapatite crystals. SODIUM IODIDE I 131 is concentrated and retained in the thyroid gland for the synthesis of thyroid hormones and is used diagnostically to evaluate thyroid function and for localization of metastases associated with thyroid malignancies; at larger oral doses of sodium iodide I 131, it is possible to selectively damage or destroy thyroidal tissue as required in the treatment of hyperthyroidism or thyroid carcinoma. RADIOACTIVE PHOSPHORUS concentrates significantly in the rapidly proliferating tissues and bone formations associated with metastatic bone tumors; subsequent, beta emission causes radiation damage to these cells. STRONTIUM-89 concentrates at skeletal metastatic sites and provides selective systemic irradiation, with minimal irradiation of distant soft tissues. Palliation of pain may be secondary to radioactive emission as opposed to a pharmacological effect of elemental strontium. THALLOUS CHLORIDE Tl 201 accumulates in viable cells of myocardium and other tissues in a manner analogous to that of potassium. The initial distribution of thallous chloride Tl 201 is primarily related to regional perfusion. Ischemic myocardial cells take up less thallous chloride Tl 201 than nonischemic cells, in proportion to the relative change in blood flow, especially during maximal stress when the differential in perfusion is most marked between regions supplied by normal coronary arteries and those supplied by stenotic vessels. Imaging equipment can record regional differences in thallous chloride Tl 201 uptake, and thus in myocardial perfusion, confirming the presence or absence of coronary disease.
C) EPIDEMIOLOGY: Overdose is extremely rare.
D) WITH THERAPEUTIC USE

1) CHROMIC PHOSPHATE P 32: Myelosuppression, nausea and vomiting, pneumonia, bronchitis, cough, epistaxis, and pleuritis. GALLIUM-67 CITRATE: Nausea and vomiting, rash, erythema, and itching. INDIUM IN-111 CAPROMAB PENDETIDE: Hypertension, hypotension, rash, itching, injection site reactions, increased liver enzymes, myalgia, headache, asthenia, shortness of breath, hypersensitivity reaction, and fever. SAMARIUM SM 153 LEXIDRONAM: Myelosuppression, an increase in bone pain or a flare, spinal cord compression, stroke, dizziness, dysrhythmias, hypertension, nausea, vomiting, diarrhea, pneumonia, bronchitis, cough, epistaxis, pleuritis, and infection. SODIUM IODIDE I 131: Myelosuppression, tachycardia, chest pain, acute thyroid storm, hypothyroidism, nausea and vomiting, itching, rash, hives, salivary gland toxicity, pneumonia, bronchitis, cough, epistaxis, and pleuritis. SODIUM IODIDE I 123: Tachycardia, chest pain, nausea and vomiting, itching, rash, and hives. STRONTIUM-89: Myelosuppression, an increase in bone pain or a flare, flushing, and fever. TECHNETIUM TC 99M EXAMETAZIME: Hypertension. TECHNETIUM TC 99M SESTAMIBI: Dysrhythmias, syncope, angioedema, nausea and vomiting, abdominal pain, dry mouth, rash, itching, urticaria, flushing, and injection site inflammation, fatigue, and fever. TECHNETIUM TC 99 SUCCIMER: Syncope, nausea and vomiting, maculopapular skin rash, and fever. THALLOUS CHLORIDE TI 201: Blurred vision, conjunctivitis, hypotension, nausea, vomiting, diarrhea, pruritus, flushing, tremor, shortness of breath, and fever. TOSITUMOMAB/IODINE I131: Prolonged and severe cytopenias are common with the tositumomab and iodine I 131 tositumomab therapeutic regimen.

E) WITH POISONING/EXPOSURE

1) MILD TO MODERATE TOXICITY: Data are limited. An extension of the adverse effects noted with therapeutic dosing is expected with overdose of a radiopharmaceutical agent. Although overdose with samarium Sm 153 has not been reported to date, hypocalcemia is the anticipated effect with overdose of samarium Sm 153, due to the chelating component of the agent. Hypothyroidism is the anticipated effect of overdose with sodium iodide I 131 or I 123. Hepatotoxicity may develop after an inadvertent administration of copper-64 chloride.
2) SEVERE TOXICITY: Myelosuppression should be anticipated after overdose of chromic phosphate P32, sodium iodide I 131, samarium SM 153, strontium-89, or tositumomab/iodine I131. Increased bone marrow toxicity and hematopoietic stem cell damage may develop after an inadvertent administration of yttrium-90 chloride.

0.2.20)

A) RADIUM RA 223 DICHLORIDE and SODIUM IODIDE I 131 are classified as FDA pregnancy category X. SAMARIUM SM 153 LEXIDRONAM, STRONTIUM-89, and TOSITUMOMAB AND IODINE I 131 TOSITUMOMAB are classified as FDA pregnancy category D. CHOLINE C 11, FLORBETABEN F18, FLORBETAPIR F-18, FLUTEMETAMOL F18, GADOTERATE MEGLUMINE, GALLIUM CITRATE GA 67, IOBENGUANE I 123, RUBIDIUM RB 82 CHLORIDE, SODIUM PHOSPHATE P 32, TECHNETIUM TC 99M ALBUMIN AGGREGATED, TECHNETIUM TC 99M PENTETATE, TECHNETIUM TC 99M TILMANOCEPT, and THALLOUS CHLORIDE Tl 201 are classified as FDA pregnancy category C. Fetal risk cannot be ruled out with the use of CHROMIC PHOSPHATE P 32 during pregnancy. In studies of human placentas, THALLOUS CHLORIDE Tl 201 has been shown to cross the placenta. INDIUM IN 111 CAPROMAB PENDETIDE does not have an FDA pregnancy category as this agent is not indicated for use in women.
B) RADIUM RA 223 DICHLORIDE use is CONTRAINDICATED in pregnant women or in women who may become pregnant, as the drug is expected to cause fetal harm based on its mechanism of action. SODIUM IODIDE I-131 use is CONTRAINDICATED in pregnant women or in women who may become pregnant as the drug may cause harm to the fetal thyroid gland and may also cause severe, and potentially irreversible, hypothyroidism in neonates. Radioactivity in breast milk was observed in one case report following treatment with CHROMIC PHOSPHATE P 32; however, the effects on the infant are unknown because breastfeeding was held after administration. During lactation, GALLIUM CITRATE GA 67, RADIOIODINE, and THALLOUS CHLORIDE Tl 201 are excreted into human milk.

0.2.21)

A) CHOLINE C 11

1) At the time of this review, the manufacturer does not report any carcinogenic potential of choline C 11 in humans.

B) FLORBETABEN F-18

1) At the time of this review, there is no data to determine the carcinogenic potential of florbetaben F-18 in humans.

C) FLUTEMETAMOL F-18

1) At the time of this review, there is no data to determine the carcinogenic potential of flutemetamol F-18 in humans.

D) GADOTERATE MEGLUMINE

1) At the time of this review, the manufacturer does not report any carcinogenic potential of gadoterate meglumine in humans.

E) RUBIDIUM Rb 82 CHLORIDE

1) At the time of this review, the manufacturer does not report any carcinogenic potential of rubidium Rb 82 chloride in humans.

F) SODIUM IODIDE I-131

1) Postmarketing cases of leukemia and stomach, bladder, and breast cancer have been reported in patients who received sodium iodide I-131 therapy.

G) TECHNETIUM TC 99M TILMANOCEPT

1) At the time of this review, the manufacturer does not report any carcinogenic potential of technetium TC 99M tilmanocept in humans.

H) TOSITUMOMAB/IODINE I131

1) At the time of this review, the manufacturer does not report any carcinogenic potential of tositumomab/iodine I131 in humans. However, iodine I-131 is a potential carcinogen.

Laboratory Monitoring

Treatment Overview

0.4.2)

A) MANAGEMENT OF MILD TO MODERATE TOXICITY

1) Treatment is symptomatic and supportive. Manage nausea and vomiting with antiemetics. Correct electrolyte imbalances as needed. Hydration with IV fluids may promote urinary excretion of certain radiopharmaceutical agents. Hypotension has been reported in patients receiving Indium In-111 capromab pendetide or thallous chloride TI 201. Treat mild hypotension with intravenous fluids.

B) MANAGEMENT OF SEVERE TOXICITY

1) Treatment is symptomatic and supportive. Myelosuppression has been reported with therapeutic use of sodium iodide I 131, samarium Sm 153, strontium-89, and phosphate P32. For severe neutropenia, administer colony stimulating factor (eg, filgrastim, sargramostim). Transfusion of platelets and/or packed red cells may be needed in patients with severe thrombocytopenia, anemia or hemorrhage. In patients with acute allergic reaction, oxygen therapy, bronchodilators, diphenhydramine, corticosteroids, vasopressors and epinephrine may be required. Hypotension has been reported in patients receiving Indium In-111 capromab pendetide or thallous chloride TI 201. Treat hypotension with intravenous fluids; if hypotension persists, administer vasopressors.

C) DECONTAMINATION

1) Radiopharmaceutical administration routes include: injection, interstitially, intrapleurally, and orally.
2) PREHOSPITAL: Most radiopharmaceutical agents are administered in medical facilities to diagnose various malignancies, endocrinopathies, metabolopathies, and perfusion abnormalities; prehospital decontamination is not required. Consider activated charcoal for oral ingestions in a patient with a recent, significant overdose who is alert or in whom airway is protected.
3) HOSPITAL: Consider activated charcoal for oral ingestions in a patient with a recent, significant overdose who is alert or in whom airway is protected. RADIOSTRONTIUM: Oral administration of aluminum phosphate gel 100 mL as a single dose, or barium sulfate 200 to 300 g in aqueous suspension may decrease absorption of radiostrontium. CARBON-14 UREA: Ingestion of 1000 capsules of carbon-14 urea can produce only a negligible risk from radiation (0.3 rem). Overdose patients should drink one glass of water (150 mL) every hour to increase the rate of excretion of the isotope.

D) AIRWAY MANAGEMENT

1) Ensure adequate ventilation and perform endotracheal intubation early in patients with life-threatening cardiac dysrhythmias or severe allergic reaction.

E) ANTIDOTE

1) PHOSPHORUS 32: A patient who received an inadvertent overdose with phosphorus 32 was treated with daily oral sodium phosphate 5 g, intravenous calcium gluconate 540 mg daily, and 200 units of parathyroid extract intramuscularly every 6 hours for 18 days starting the 9th day after exposure. It was estimated that this therapy reduces the radiation exposure to bone marrow by 38% and that the effective half-life of P32 was reduced from a baseline of 11.2 days to 4.8 days.
2) RADIOACTIVE CALCIUM: Oral or intravenous calcium increases the urinary excretion of radioactive calcium in humans. Oral calcium gluconate (15 g daily in divided doses), calcium lactate (4 grams three times daily) or intravenous calcium gluconate may be effective.
3) RADIOACTIVE STRONTIUM:

a) CALCIUM: Oral or intravenous calcium increases the urinary excretion of radioactive strontium in humans. Oral calcium gluconate (15 g daily in divided doses), calcium lactate (4 grams three times daily) or intravenous calcium gluconate may be effective.
b) STRONTIUM: Strontium may be given orally or intravenously as a diluting agent for radioactive strontium overdose. Strontium lactate 300 mg 2 to 5 times daily or strontium gluconate 600 mg in 500 ml 5% dextrose in water infused over 4 hours for 6 consecutive days are recommended doses.
c) PHOSPHATE: Oral administration of phosphate may be used to prevent intestinal absorption of radioactive strontium. Sodium or potassium phosphate in adults: 600 to 1200 mg orally in divided doses.

4) SODIUM IODIDE I 131 OR I 123: POTASSIUM IODIDE: Administer potassium iodide as soon as possible after an overdose. Adults: 300 mg daily for 7 to 14 days. Children aged 3 to 12 years: 65 mg orally daily for 7 to 14 days. If potassium iodide is not administered within 12 hours of the overdose, propylthiouracil or methimazole may help reduce thyroid retention of radioiodine. Propylthiouracil: Adults: 100 mg every 8 hours for 8 days. Pediatric 5 to 7 mg/kg/day in divided doses every 8 hours maximum 300 mg/day. Methimazole Adults: 10 mg every 8 hours for 2 days, reduce to 5 mg every 8 hours and continue for 6 days. Pediatric 0.4 mg/kg/day in divided doses every 8 hours.
5) COPPER-64 CHLORIDE OR YTTRIUM-90 CHLORIDE: Administer Ca-DTPA or Ca-EDTA as soon as possible, ideally within 1 hour of inadvertent administration of copper-64 chloride or yttrium-90 chloride. DOSE: 1 g Ca-DTPA or Ca-EDTA by slow IV injection over 3 to 4 minutes or by infusion (1 g in 100 to 250 mL of dextrose, or sodium chloride 0.9% solution for injection).

F) HYPERSENSITIVITY REACTION

1) MILD/MODERATE: Antihistamines with or without inhaled beta agonists, corticosteroids or epinephrine. SEVERE: Oxygen, aggressive airway management, antihistamines, epinephrine, corticosteroids, ECG monitoring, and IV fluids.

G) MYELOSUPPRESSION

1) Myelosuppression, including thrombocytopenia and leukopenia, has been reported with therapeutic use of sodium iodide I 131, samarium Sm 153, strontium-89, and phosphate P32. Administer colony stimulating factor for severe neutropenia. Filgrastim: 5 mcg/kg/day IV or subQ. Sargramostim: 250 mcg/m(2)/day IV over 4 hours. Monitor CBC with differential for evidence of bone marrow suppression. If fever or infection develop during leukopenic phase, cultures should be obtained and appropriate antibiotics started. Transfusion of platelets and/or packed red cells may be needed in patients with severe thrombocytopenia, anemia or hemorrhage.

H) HYPOCALCEMIA

1) SAMARIUM SM 153 LEXIDRONAM: In animal studies, dogs that received non-radioactive samarium ethylenediaminetetramethylenephosphonic acid (EDTMP) at 6 times the human therapeutic dose based on body weight or 3 times the dose based on surface area developed hypocalcemia. This is thought to be due to the chelating effects of EDTMP. Hypocalcemia may develop following an overdose of samarium Sm 153. Aggressive calcium replacement should be instituted in patients with clinical or ECG manifestations of hypocalcemia even if laboratory confirmation of hypocalcemia is still pending. Administer 10 mL to 20 mL of 10% calcium chloride or calcium gluconate (initial bolus) IV over 10 to 15 minutes. More rapid administration may be necessary in patients with dysrhythmias. Repeat bolus or a maintenance infusion is often necessary.

I) HYPOTENSIVE EPISODE

1) Hypotension has been reported in patients receiving Indium In-111 capromab pendetide or thallous chloride TI 201. Treat hypotension with intravenous fluids; if hypotension persists, administer vasopressors.

J) SEIZURES

1) Seizures have rarely been reported after administration of technetium Tc 99m sestamibi. Administer IV benzodiazepines; barbiturates or propofol may be needed if seizures persist or recur.

K) PATIENT DISPOSITION

1) OBSERVATION CRITERIA: Patients with radiopharmaceutical overdose should be sent to a healthcare facility for evaluation. Patients who remain asymptomatic with normal laboratory tests can be sent home if careful follow-up can be assured. Follow-up instructions should include a repeat CBC in 48 hours and reevaluation following the onset of any gastrointestinal symptoms (eg, nausea, vomiting, and diarrhea).
2) ADMISSION CRITERIA: Admission is required for fluid and electrolyte therapy if severe vomiting and diarrhea are present. Patients manifesting thrombocytopenia or leukopenia, require hospital admission.
3) CONSULT CRITERIA: Consult a Poison Center for assistance in managing patients with severe toxicity or for whom diagnosis is unclear. For radiation-related medical assistance call 865-576-3131 (days), or after normal business hours: 865-576-1005 and ask for REAC/TS. A physician is available 24 hours a day.

L) PITFALLS

1) Early symptoms of radiation exposure may be delayed or not evident (eg, myelosuppression).

M) PHARMACOKINETICS

1) EXCRETION: THALLOUS CHLORIDE TI 201: Renal (4% to 8% within 24 hours) and fecal routes. SAMARIUM SM 153 LEXIDRONAM: Primarily renal after intravenous injection; 34.5 ± 15.5% is excreted in 6 hours. SODIUM IODIDE I 131: Approximately 37% to 75% of the administered dose is excreted into the urine, depending upon the thyroid and renal function of the patient. STRONTIUM-89: Most excretion occurs in the first 2 days following injection. Up to 66% (via glomerular filtration) in patients with bone metastases. Urinary elimination of strontium-89 is higher in individuals without bone lesions. Up to 33% (patients with bone metastases) of the dose is excreted in feces. ELIMINATION HALF-LIFE: SAMARIUM SM 153 LEXIDRONAM has a physical half-life of 46 hours. STRONTIUM-89: The elimination half life of the parent compound, strontium-89, was 14 days in normal bone sites and over 50 days metastatic bone sites.

N) DIFFERENTIAL DIAGNOSIS

1) Skin disease or allergy; food poisoning; chemotherapeutic agents; other agents causing myelosuppression.

0.4.4)

A) DECONTAMINATION: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility.

0.4.5)

A) OVERVIEW

1) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

0.4.6)

A) Refer to ORAL OVERVIEW AND MAIN SECTIONS for specific treatment information.

Range Of Toxicity

1) CHROMIC PHOSPHATE P 32 (ADULT): INTERSTITIAL injection 3.7 to 18.5 MBq/gram (0.1 to 1.5 mCi/gram) or INTRAPLEURAL instillation 222 to 444 MBq (6 to 12 mCi) or INTRAPERITONEAL instillation 370 to 740 MBq (10 to 20 mCi).
2) INDIUM IN-111 CAPROMAB PENDETIDE (ADULTS): 0.5 mg radiolabeled with 5 mCi of Indium In 111 chloride. Administer intravenously over 5 minutes.
3) SAMARIUM SM 153 LEXIDRONAM (ADULT): 1 mCi/kg IV, over 1 minute, through a secure in-dwelling catheter and follow with a saline flush; give a minimum of 500 mL (2 cups) of fluids either ORAL or IV prior to injection.
4) SODIUM IODIDE I 131 (ADULT): Dose range, 1.85 to 5,550 MBq (50 microCi to 150 mCi) ORALLY.
5) SODIUM PHOSPHATE P 32 (ADULT): 222 to 555 MBq (6 to 15 mCi) IV.
6) STRONTIUM 89 (ADULT): 148 MBq (4 mCi) by slow IV injection over 1 to 2 minutes; alternatively, 1.5 to 2.2 MBq/kg (40 to 60 microCi/kg) may be given.
7) THALLOUS CHLORIDE Tl 201: For myocardial planar imaging, Intravenous, 37 to 74 MBq (1 to 2 mCi). For SPECT imaging - Intravenous, 74 to 111 MBq (2 to 3 mCi) of thallous chloride Tl 201.

Clinical Effects

Summary Of Exposure

Vital Signs

3.3.3)

A) WITH THERAPEUTIC USE

1) Fever has been reported in patients receiving these agents: Indium 111 capromab pendetide, strontium-89, technetium Tc99m sestamibi, technetium Tc99m succimer, thallous chloride TI 201 (Prod Info ProstaScint(R) Kit intravenous injection, 2010; Prod Info CARDIOLITE(R) IV injection, 2008; Prod Info DMSA intravenous injection, 2006; Prod Info Thallous Chloride Tl 201 Injection, 2004; Prod Info METASTRON(TM) IV injection, 2002).

Heent

3.4.2)

A) WITH THERAPEUTIC USE

1) SALIVARY GLAND TOXICITY (SODIUM IODIDE I 131): Salivary gland toxicity leading to pain, swelling, and dry mouth has been reported with therapeutic use of sodium iodide I 131 (Hyer et al, 2007; Solans et al, 2001).
2) SIALOADENITIS (SODIUM IODIDE I 131): Severe sialoadenitis may occur with the use of sodium iodide I 131. Although, most adverse events may be mild when sodium iodide I 131 is used in the treatment of hyperthyroidism, larger doses used in the treatment of thyroid carcinoma may evoke more severe reactions (Prod Info IODOTOPE(R) oral capsules, 2001).

3.4.3)

A) WITH THERAPEUTIC USE

1) EPISCLERITIS

a) SODIUM PHOSPHATE P 32 AND CHROMIC PHOSPHATE P 32 - Histopathologic examination of 5 eyes containing choroidal melanomas revealed presence of traumatic episcleritis occurring 1 to 4 weeks after P 32 testing. The patients were aged 40 to 79 years (3 women and 2 men) and all had malignant melanomas of the posterior choroid, in close association with the macula in 4 cases. Enucleation had been delayed in all patients for logistical reasons, with a time lapse of 6 to 27 days from P 32 testing to enucleation. In all 5 cases, traumatic episcleritis, with foreign body granulomas, and invasion of the sclera or intrascleral canals were present. Clinicians may need to consider that in cases of delayed enucleation following P 32 testing, development of such episcleral inflammation may have an adverse stimulatory effect on some melanomas (Goldfarb & Streeten, 1980).

2) BLURRED VISION

a) THALLOUS CHLORIDE Tl 201: Blurred vision has been reported with the use of thallous chloride Tl 201 (Prod Info Thallous Chloride Tl 201 Injection, 2004).

3) CONJUNCTIVITIS

a) THALLOUS CHLORIDE Tl 201: Conjunctivitis has been reported with the use of thallous chloride Tl 201 (Prod Info Thallous Chloride Tl 201 Injection, 2004).

3.4.5)

A) WITH THERAPEUTIC USE

1) NASOLACRIMAL OBSTRUCTION

a) SODIUM IODIDE I 131: Nasolacrimal obstruction has been reported with therapeutic use of sodium iodide I 131 (Burns et al, 2004; Solans et al, 2001).

Cardiovascular

3.5.2)

A) CONDUCTION DISORDER OF THE HEART

1) WITH THERAPEUTIC USE

a) SAMARIUM SM 153 LEXIDRONAM: In randomized, double-blind, clinical trials in patients who had painful, refractory, metastatic bone lesions, dysrhythmias were reported in 5% (n=10/199) of samarium-treated patients (doses of 0.5 to 1 millicurie/kilogram) compared to 2.2% (n=2/90) of placebo-treated patients. Overall, the incidence of cardiovascular effects was lower in the samarium group (16%; n=32/199) compared to the placebo group (21%; n=19/90) (Prod Info QUADRAMET(R) IV injection, 2003).
b) SODIUM IODIDE I 131 AND I 123: Tachycardia has rarely been reported in patients receiving sodium iodide I 123 or I 131 (Prod Info sodium iodide I 123 diagnostic oral capsules, 2007; Prod Info sodium iodide I 131 diagnostic oral capsules, 2005).
c) TECHNETIUM TC 99M SESTAMIBI: Dysrhythmias have rarely been reported after administration of technetium Tc 99m sestamibi (Prod Info CARDIOLITE(R) IV injection, 2008). The causal relationship has not been established.

B) HYPERTENSIVE EPISODE

1) WITH THERAPEUTIC USE

a) INDIUM IN-111 CAPROMAB PENDETIDE: Hypertension has been reported in patients receiving Indium In-111 capromab pendetide (Prod Info ProstaScint(R) Kit intravenous injection, 2010).
b) SAMARIUM SM 153 LEXIDRONAM: In randomized, double-blind, clinical trials in patients who had painful, refractory, metastatic bone lesions, hypertension was reported in 3% (n=6/199) of samarium-treated patients (doses of 0.5 to 1 millicurie/kilogram) compared to no reports in placebo-treated patients. Overall, the incidence of cardiovascular effects was lower in the samarium group (16%; n=32/199) compared to the placebo group (21%; n=19/90) (Prod Info QUADRAMET(R) IV injection, 2003).
c) TECHNETIUM TC 99M EXAMETAZIME: A transient hypertension has been reported in 8% of patients receiving technetium Tc99M exametazime (Prod Info CERETEC(TM) intravenous injection, 2006).

C) HYPOTENSIVE EPISODE

1) WITH THERAPEUTIC USE

a) INDIUM IN-111 CAPROMAB PENDETIDE: Hypotension has been reported in patients receiving Indium In-111 capromab pendetide (Prod Info ProstaScint(R) Kit intravenous injection, 2010).
b) THALLOUS CHLORIDE TI 201: Hypotension has been reported with the use of thallous chloride Tl 201 (Prod Info Thallous Chloride Tl 201 Injection, 2004).

D) CHEST PAIN

1) WITH THERAPEUTIC USE

a) SODIUM IODIDE I 123 OR I 131: Chest pain has rarely been reported in patients receiving sodium iodide I 123 or I 131 (Prod Info sodium iodide I 123 diagnostic oral capsules, 2007; Prod Info sodium iodide I 131 diagnostic oral capsules, 2005) .

E) SYNCOPE

1) WITH THERAPEUTIC USE

a) TECHNETIUM TC99M SESTAMIBI OR SUCCIMER: Syncope has rarely been reported after administration of technetium Tc 99m sestamibi or succimer (Prod Info CARDIOLITE(R) IV injection, 2008; Prod Info DMSA intravenous injection, 2006). The causal relationship has not been established.

F) ANGIOEDEMA

1) WITH THERAPEUTIC USE

a) TECHNETIUM TC 99M SESTAMIBI: Angioedema has rarely been reported after administration of technetium Tc 99m sestamibi (Prod Info CARDIOLITE(R) IV injection, 2008).

Respiratory

3.6.2)

A) RESPIRATORY FINDING

1) WITH THERAPEUTIC USE

a) Pneumonia, bronchitis, cough, epistaxis, pleuritis have been reported with use of chromic phosphate-32, sodium iodide I 131, or samarium Sm 153 (Prod Info QUADRAMET(R) IV injection, 2003; Prod Info PHOSPHOCOL(R) P 32 injection suspension, 2000; Prod Info IODOTOPE(R) oral capsules, 2001).

B) DYSPNEA

1) WITH THERAPEUTIC USE

a) INDIUM IN-111 CAPROMAB PENDETIDE: Shortness of breath was reported in a study in which 529 single doses of Indium In-111 capromab pendetide were administered (Prod Info ProstaScint(R) Kit intravenous injection, 2010).
b) THALLOUS CHLORIDE Tl 201: Shortness of breath has been reported with the use of thallous chloride Tl 201 (Prod Info Thallous Chloride Tl 201 Injection, 2004).

Neurologic

3.7.2)

A) SPINAL CORD COMPRESSION

1) WITH THERAPEUTIC USE

a) SAMARIUM SM 153 LEXIDRONAM: In randomized, double-blind, clinical trials in patients who had painful, refractory, metastatic bone lesions, spinal cord compression was reported in 6.5% (n=13/199) of samarium-treated patients (doses of 0.5 to 1 millicurie/kilogram) compared to 5.5% (n=5/90) of placebo-treated patients (n=90). Overall, the incidence of neurological effects was lower in the samarium group (30%; n=59/199) compared to the placebo group (43%; n=39/90) (Prod Info QUADRAMET(R) IV injection, 2003).

B) CEREBROVASCULAR ACCIDENT

1) WITH THERAPEUTIC USE

a) SAMARIUM SM 153 LEXIDRONAM: In randomized, double-blind, clinical trials in patients who had painful, refractory, metastatic bone lesions, stroke was reported in 1% (n=2/199) of samarium-treated patients (doses of 0.5 to 1 millicurie/kilogram) compared to no reports in placebo-treated patients (n=90). Overall, the incidence of neurological effects was lower in the samarium group (30%; n=59/199) compared to the placebo group (43%; n=39/90) (Prod Info QUADRAMET(R) IV injection, 2003).

C) DIZZINESS

1) WITH THERAPEUTIC USE

a) SAMARIUM SM 153 LEXIDRONAM: In randomized, double-blind, clinical trials in patients who had painful, refractory, metastatic bone lesions, dizziness was reported in 4% (n=8/199) of samarium-treated patients (doses of 0.5 to 1 millicurie/kilogram) compared to 1.1% (n=1/90) of placebo-treated patients. Overall, the incidence of neurological effects was lower in the samarium groups (30%; n=59/199) compared to the placebo group (43%; n=39/90) (Prod Info QUADRAMET(R) IV injection, 2003).
b) TECHNETIUM TC 99M SESTAMIBI: Dizziness has rarely been reported after administration of technetium Tc 99m sestamibi (Prod Info CARDIOLITE(R) IV injection, 2008).

D) TREMOR

1) WITH THERAPEUTIC USE

a) THALLOUS CHLORIDE Tl 201: Tremor has been reported with the use of thallous chloride Tl 201 (Prod Info Thallous Chloride Tl 201 Injection, 2004).

E) HEADACHE

1) WITH THERAPEUTIC USE

a) INDIUM IN-111 CAPROMAB PENDETIDE: Headache was reported in a study in which 529 single doses of Indium In-111 capromab pendetide were administered (Prod Info ProstaScint(R) Kit intravenous injection, 2010).

F) ASTHENIA

1) WITH THERAPEUTIC USE

a) INDIUM IN-111 CAPROMAB PENDETIDE: Asthenia was reported in a study in which 529 single doses of Indium In-111 capromab pendetide were administered (Prod Info ProstaScint(R) Kit intravenous injection, 2010).

G) FATIGUE

1) WITH THERAPEUTIC USE

a) TECHNETIUM TC 99M SESTAMIBI: Fatigue has rarely been reported after administration of technetium Tc 99m sestamibi (Prod Info CARDIOLITE(R) IV injection, 2008).

H) SEIZURE

1) WITH THERAPEUTIC USE

a) TECHNETIUM TC 99M SESTAMIBI: Seizures have rarely been reported after administration of technetium Tc 99m sestamibi (Prod Info CARDIOLITE(R) IV injection, 2008). The causal relationship has not been established.

Gastrointestinal

3.8.2)

A) DIARRHEA

1) WITH THERAPEUTIC USE

a) SAMARIUM SM 153 LEXIDRONAM: In randomized, double-blind, clinical trials in patients who had painful, refractory, metastatic bone lesions, diarrhea was reported in 6% (n=12/199) of samarium-treated patients (doses of 0.5 to 1 millicurie/kilogram) compared to 3.3% (n=3/90) of placebo-treated patients. Overall, the incidence of gastrointestinal effects was lower in the samarium group (41%; n=82/199) compared to the placebo group (49%; n=44/90) (Prod Info QUADRAMET(R) IV injection, 2003).
b) THALLOUS CHLORIDE Tl 201: Mild diarrhea has been reported with the use of thallous chloride Tl 201 (Prod Info Thallous Chloride Tl 201 Injection, 2004).

B) NAUSEA AND VOMITING

1) WITH THERAPEUTIC USE

a) Nausea and/or vomiting have been associated with the use of chromic phosphate P 32, gallium-67 citrate, sodium iodide I 131 or I123, samarium SM 153, technetium TC 99 M sestamibi or succimer, and thallous chloride Tl 201 (Prod Info DMSA intravenous injection, 2006; Prod Info CARDIOLITE(R) IV injection, 2008; Prod Info sodium iodide I 123 diagnostic oral capsules, 2007; Prod Info sodium iodide I 131 diagnostic oral capsules, 2005; Prod Info Gallium citrate Ga 67 , 2003; Prod Info PHOSPHOCOL(R) P 32 injection suspension, 2000; Albert et al, 1997; Prod Info Thallous Chloride Tl 201 Injection, 2004).

C) ABDOMINAL PAIN

1) WITH THERAPEUTIC USE

a) TECHNETIUM TC 99M SESTAMIBI: Abdominal pain has rarely been reported after administration of technetium Tc 99m sestamibi (Prod Info CARDIOLITE(R) IV injection, 2008).

D) APTYALISM

1) WITH THERAPEUTIC USE

a) TECHNETIUM TC 99M SESTAMIBI: Dry mouth has rarely been reported after administration of technetium Tc 99m sestamibi (Prod Info CARDIOLITE(R) IV injection, 2008).

E) PERITONITIS

1) WITH THERAPEUTIC USE

a) CHROMIC PHOSPHATE P 32: Peritonitis has been associated with the use of chromic phosphate P 32 for intraperitoneal chemotherapy (Prod Info PHOSPHOCOL(R) P 32 injection suspension, 2000).

Hepatic

3.9.2)

A) INCREASED BILIRUBIN LEVEL

1) WITH THERAPEUTIC USE

a) INDIUM IN-111 CAPROMAB PENDETIDE: Increased bilirubin levels was one of the most commonly reported adverse effects occurring in 1% of patients in a study in which 529 single doses of Indium In-111 capromab pendetide were administered (Prod Info ProstaScint(R) Kit intravenous injection, 2010).

B) INCREASED LIVER ENZYMES

1) WITH THERAPEUTIC USE

a) INDIUM IN-111 CAPROMAB PENDETIDE: Increased liver enzymes was reported in slightly less than 1% of patients in a study in which 529 single doses of Indium In-111 capromab pendetide were administered (Prod Info ProstaScint(R) Kit intravenous injection, 2010).

C) TOXIC LIVER DISEASE

1) WITH THERAPEUTIC USE

a) IODINE I-131: Hepatotoxicity developed in a 57-year-old woman with thyroid cancer after being treated with I-131 ablation therapy following a thyroidectomy. Symptoms included a week long history of jaundice, itching and dark urine. Laboratory studies included elevated total liver enzymes and bilirubin. Viral hepatitis and serology studies were negative. Following hepatic protection (including glutathione, magnesium and dietary changes) for over a month, total bilirubin continued to increase and the patient was treated with a course of methylprednisone with laboratory improvement (Lin et al, 2015).

2) WITH POISONING/EXPOSURE

a) COPPER-64 CHLORIDE: Hepatotoxicity may develop after an inadvertent administration of copper-64 chloride (Prod Info Cuprymina intravenous injection solution, 2012).

Genitourinary

3.10.2)

A) BLOOD IN URINE

1) WITH THERAPEUTIC USE

a) SAMARIUM SM 153 LEXIDRONAM: In randomized, double-blind, clinical trials in patients who had painful, refractory, metastatic bone lesions, hematuria was reported in 5% (n=10/199) of samarium-treated patients (doses of 0.5 to 1 millicurie/kilogram) compared to 3.3% (n=3/90) of placebo-treated patients (Prod Info QUADRAMET(R) IV injection, 2003).

Hematologic

3.13.2)

A) HEMATOLOGIC TOXICITY

1) WITH THERAPEUTIC USE

a) Myelosuppression, including thrombocytopenia and leukopenia, has been reported with therapeutic use of sodium iodide I 131, samarium SM 153, strontium-89, and phosphate P32 (Prod Info PHOSPHOCOL(R) P 32 injection suspension, 2000; Prod Info QUADRAMET(R) IV injection, 2003; Prod Info IODOTOPE(R) oral capsules, 2001; Prod Info METASTRON(TM) IV injection, 2002).
b) TOSITUMOMAB/IODINE I131: Prolonged and severe cytopenias (neutropenia, thrombocytopenia, and anemia) were the most frequently reported adverse events observed in patients with non-Hodgkin's lymphoma enrolled in 5 clinical trials (n=230) who received the tositumomab and iodine I 131 tositumomab therapeutic regimen at the recommended dose and schedule. Grade 3 or 4 neutropenia, thrombocytopenia, and anemia were reported in 63% (n=145), 53% (n=123), and 29% (n=66) of patients, respectively, with time to nadir of approximately 4 to 7 weeks. The cytopenias lasted roughly 30 days. Following the therapeutic dose, 27% of patients (n=63) received 1 or more hematologic supportive care measures, including granulocyte colony stimulating factor, epoetin alfa, platelet transfusion, and red blood cell transfusions. Twelve percent of patients (n=28) experienced hemorrhagic adverse reactions (Prod Info BEXXAR(R) intravenous injection, 2012).

2) WITH POISONING/EXPOSURE

a) YTTRIUM-90 CHLORIDE: Increased bone marrow toxicity and hematopoietic stem cell damage may develop after an inadvertent administration of yttrium-90 chloride (Prod Info Yttriga injection solution, 2012).
b) TOSITUMOMAB/IODINE I131: The incidence of NCI grade 4 cytopenias was increased in 4 patients who received 85 cGy to 88 cGy total body irradiation (the maximum radiation activity of the I-131 component of the tositumomab/iodine I131 tositumomab therapeutic regimen) compared with patients who received the recommended therapeutic doses of tositumomab/iodine I131 tositumomab (Prod Info BEXXAR(R) intravenous injection, 2012).
c) PHOSPHATE P32: An unintentional overdose of phosphate P 32 resulted in progressive anemia and leukopenia. A patient receiving treatment for thrombocytosis was given a dose of phosphate P32 from a mislabeled stock solution. The month of the initial assay for the stock solution was erroneously recorded one month off from the actual time. This resulted in administration of 16.2 millicuries instead of the intended 4.05 millicuries. Both the red blood cell count and white blood cell count fell over the next six weeks. With supportive care, recovery began approximately 45 days after the exposure with near complete recovery at 300 days post-exposure. The patient was asymptomatic throughout the recovery period (Cobau et al, 1967).

B) ANEMIA

1) WITH THERAPEUTIC USE

a) SODIUM IODIDE I 131: Anemia may occur with the use of sodium iodide I 131. Although most immediate adverse events may be mild when sodium iodide I 131 is used in the treatment of hyperthyroidism, larger doses used in the treatment of thyroid carcinoma may evoke more severe reactions (Prod Info IODOTOPE(R) oral capsules, 2001).
b) SAMARIUM SM 153 LEXIDRONAM: Anemia has been reported with use of samarium (Coronado et al, 2006).
c) SAMARIUM SM 153 LEXIDRONAM: In randomized, double-blind clinical trials in patients who had painful, refractory, metastatic bone lesions, decreased hemoglobin was reported in 40.7% (n=81/199) of samarium-treated patients (doses of 0.5 to 1 millicurie/kilogram) compared to 23.3% (n=21/90) of placebo-treated patients (Prod Info QUADRAMET(R) IV injection, 2003).

C) THROMBOCYTOPENIC DISORDER

1) WITH THERAPEUTIC USE

a) SODIUM IODIDE I 131: Thrombocytopenia may occur with the use of sodium iodide I 131. Although, most immediate adverse events may be mild when sodium iodide I 131 is used in the treatment of hyperthyroidism, larger doses used in the treatment of thyroid carcinoma may evoke more severe reactions (Prod Info IODOTOPE(R) oral capsules, 2001).
b) SAMARIUM SM 153 LEXIDRONAM: In randomized, double-blind clinical trials in patients who had painful, refractory, metastatic bone lesions, thrombocytopenia was reported in 69.3% (n=138/199) of samarium treated patients (doses of 0.5 to 1 millicurie/kilogram) compared to 8.9% (n=8/90) of placebo-treated patients (Prod Info QUADRAMET(R) IV injection, 2003). Thrombocytopenia associated with samarium use has also been reported in other clinical trials (Coronado et al, 2006; Dolezal et al, 2007).
c) STRONTIUM-89: Thrombocytopenia has been reported in most patients treated with strontium-89. The most common clinical picture is a decrease in platelet counts of 20% to 30%, and the nadir occurs 5 to 16 weeks after an intravenous dose; a corresponding reduction in white blood cell counts by 15% to 20% has been reported. Recovery to pretreatment levels usually occurs by the 6th month after treatment in patients with a normal baseline bone marrow (Prod Info METASTRON(TM) IV injection, 2002; Robinson et al, 1987; Laing et al, 1991a; Lewington et al, 1991a; Ackery & Yardley, 1993a).

D) LEUKOPENIA

1) WITH THERAPEUTIC USE

a) SODIUM IODIDE I 131: Leukopenia may occur with the use of sodium iodide I 131. Although, most immediate adverse events may be mild when sodium iodide I 131 is used in the treatment of hyperthyroidism, larger doses used in the treatment of thyroid carcinoma may evoke more severe reactions (Prod Info IODOTOPE(R) oral capsules, 2001).
b) SAMARIUM SM 153 LEXIDRONAM: In randomized, double-blind, clinical trials in patients who had painful, refractory, metastatic bone lesions, leukopenia was reported in 59.3% (n=118/199) of samarium-treated patients (doses of 0.5 to 1 millicurie/kilogram) compared to 6.7% (n=6/90) of placebo-treated patients (Prod Info QUADRAMET(R) IV injection, 2003). Leukopenia associated with samarium use has also been reported in other clinical trials (Coronado et al, 2006; Dolezal et al, 2007).
c) STRONTIUM-89: A reduction in white blood cell counts by 15% to 20% has been reported. Recovery to pretreatment levels usually occurs by the 6th month after treatment in patients with a normal baseline bone marrow (Robinson et al, 1987; Laing et al, 1991a; Lewington et al, 1991a; Ackery & Yardley, 1993a; Prod Info METASTRON(TM) IV injection, 2002).
d) STRONTIUM-89: One case of fatal septicemia following leukopenia was reported during clinical trials (Prod Info METASTRON(TM) IV injection, 2002).

E) BLOOD COAGULATION DISORDER

1) WITH THERAPEUTIC USE

a) SAMARIUM SM 153 LEXIDRONAM: In randomized, double-blind clinical trials in patients who had painful, refractory, metastatic bone lesions, coagulopathies were reported in 1.5% (n=3/199) of samarium-treated patients (doses of 0.5 to 1 millicurie/kilogram) compared to no reports in the placebo group (n=90). Disseminated intravascular coagulation (DIC) was evident in 1 patient and suspected in another (Prod Info QUADRAMET(R) IV injection, 2003).

Dermatologic

3.14.2)

A) SKIN FINDING

1) WITH THERAPEUTIC USE

a) GALLIUM-67 CITRATE: Rash, erythema, and severe itching have rarely been reported in patients receiving gallium-67 citrate (Prod Info Gallium citrate Ga 67 , 2003).
b) INDIUM IN-111 CAPROMAB PENDETIDE: Rash, itching, and injection site reactions were reported in a study in which 529 single doses of Indium In-111 capromab pendetide were administered (Prod Info ProstaScint(R) Kit intravenous injection, 2010).
c) SODIUM IODIDE I 131 OR I 123: Itching, rash, and hives have been reported with use of sodium iodide I 131 for diagnostic and therapeutic purposes (Prod Info sodium iodide I 123 diagnostic oral capsules, 2007; Prod Info sodium iodide I 131 diagnostic oral capsules, 2005).
d) TECHNETIUM TC 99M SESTAMIBI: Rash, itching, urticaria, flushing, and injection site inflammation have rarely been reported after administration of technetium Tc 99m sestamibi (Prod Info CARDIOLITE(R) IV injection, 2008).
e) TECHNETIUM TC99M SUCCIMER: Maculopapular skin rash has rarely been reported in patients receiving technetium Tc99m succimer (Prod Info DMSA intravenous injection, 2006).
f) THALLOUS CHLORIDE Tl 201: Pruritus has been reported with the use of thallous chloride Tl 201 (Prod Info Thallous Chloride Tl 201 Injection, 2004).

B) FLUSHING

1) WITH THERAPEUTIC USE

a) STRONTIUM-89: Flushing has been reported in some patients treated with intravenous strontium-89, particularly after rapid injection (less than 30 seconds). This appears related to calcium-like effects (Porter et al, 1993a; Prod Info METASTRON(TM) IV injection, 2002).
b) THALLOUS CHLORIDE Tl 201: Flushing has been reported with the use of thallous chloride Tl 201 (Prod Info Thallous Chloride Tl 201 Injection, 2004).

Musculoskeletal

3.15.2)

A) BONE PAIN

1) WITH THERAPEUTIC USE

a) STRONTIUM-89: An increase in bone pain (flare) may occur in some patients (10% to 20%) between 36 and 72 hours after an injection of strontium-89, which can be controlled effectively by analgesics. This effect is considered predictive of a positive clinical response (Ackery & Yardley, 1993a; Prod Info Metastron(R), 1995a; Robinson et al, 1993a).
b) SAMARIUM SM 153 LEXIDRONAM: In randomized, double-blind, clinical trials in patients who had painful, refractory, metastatic bone lesions, a pain flare reaction was reported in 7% (n=14/199) of samarium-treated patients (doses of 0.5 to 1 millicurie/kilogram) compared to 5.6% (n=5/90) of placebo-treated patients (Prod Info QUADRAMET(R) IV injection, 2003).

1) A transient exacerbation of pre-existing pain (flare reaction) has been observed in 16% to 18% of cancer patients, particularly those with prostate cancer, treated with samarium Sm 153 lexidronam for painful skeletal metastases (Turner et al, 1989; Farhanghi et al, 1992a). This phenomenon occurs 2 to 5 days after treatment and persists for up to 4 days. PAIN EXACERBATION is often in the cervical spine. The pain is self-limiting but may respond to analgesics (Prod Info Quadramet(TM), 1997a).
2) Short hospitalization has been required for management of flare reactions (Farhanghi et al, 1992a).

B) FRACTURE OF BONE

1) WITH THERAPEUTIC USE

a) SAMARIUM SM 153 LEXIDRONAM: In randomized, double-blind, clinical trials in patients who had painful, refractory, metastatic bone lesions, pathologic fracture was reported in 2.5% (n=5/199) of samarium-treated patients (doses of 0.5 to 1 millicurie/kilogram) compared to 2.2% (n=2/90) in placebo-treated patients. Overall, the incidence of musculoskeletal adverse events was lower in the samarium group (27%; n=55/199) compared to the placebo group (31%; n=28/90) (Prod Info QUADRAMET(R) IV injection, 2003).

C) MUSCLE PAIN

1) WITH THERAPEUTIC USE

a) INDIUM IN-111 CAPROMAB PENDETIDE: Myalgia was reported in a study in which 529 single doses of Indium In-111 capromab pendetide were administered (Prod Info ProstaScint(R) Kit intravenous injection, 2010).

Endocrine

3.16.2)

A) THYROTOXIC CRISIS

1) WITH THERAPEUTIC USE

a) SODIUM IODIDE I 131: Acute thyroid crises may occur with the use of sodium iodide I 131. Although, most adverse events may be mild when sodium iodide I 131 is used in the treatment of hyperthyroidism, larger doses used in the treatment of thyroid carcinoma may evoke more severe reactions (Prod Info sodium iodide I 131 diagnostic oral capsules, 2005).

B) HYPOTHYROIDISM

1) WITH THERAPEUTIC USE

a) SODIUM IODIDE I 131: In a study of 1,168 patients with goiter treated with sodium iodide I 131 for hyperthyroidism, 54.4% were found to be hypothyroid at the end of the first year post treatment (Alevizaki et al, 1985).

Immunologic

3.19.2)

A) HYPERSENSITIVITY REACTION

1) WITH THERAPEUTIC USE

a) Hypersensitivity reactions have been reported in patients receiving the following agents: gallium-67 citrate, indium In-111 capromab pendetide, iobenguane I 123, and sodium iodide I 131 (Prod Info ProstaScint(R) Kit intravenous injection, 2010; Prod Info ADREVIEW(R) IV injection, 2008; Prod Info Gallium citrate Ga 67 , 2003; Prod Info IODOTOPE(R) oral capsules, 2001).
b) TECHNETIUM TC 99M SESTAMIBI: Severe hypersensitivity reaction, characterized by dyspnea, hypotension, bradycardia, asthenia, and vomiting, has rarely been reported after administration of technetium Tc 99m sestamibi (Prod Info CARDIOLITE(R) IV injection, 2008).
c) THALLOUS CHLORIDE Tl 201: Anaphylactoid type reactions have been reported with the use of thallous chloride Tl 201. Cardiovascular, respiratory, and cutaneous symptoms were involved with these reactions (Prod Info Thallous Chloride Tl 201 Injection, 2004).

B) LYMPHADENOPATHY

1) WITH THERAPEUTIC USE

a) SAMARIUM SM 153 LEXIDRONAM: In randomized, double-blind, clinical trials in patients who had painful, refractory, metastatic bone lesions, lymphadenopathy was reported in 2% (n=4/199) of samarium-treated patients (doses of 0.5 to 1 millicurie/kilogram) compared to no reports in placebo-treated patients (n=90) (Prod Info QUADRAMET(R) IV injection, 2003).

C) SEPTICEMIA

1) WITH THERAPEUTIC USE

a) STRONTIUM-89: One case of fatal septicemia following leukopenia was reported during clinical trials (Prod Info METASTRON(TM) IV injection, 2002).

D) ANTIBODY DEVELOPMENT

1) WITH THERAPEUTIC USE

a) TECHNETIUM TC 99M BESILESOMAB: In a clinical trial of 123 patients and a noninterventional safety survey, development of human anti-mouse antibodies (HAMA) was the most common adverse effect, reported in 16 of 116 (14%) assays evaluated at 1 and/or 3 months after administration of technetium Tc 99m besilesomab (Prod Info Scintimun intravenous injection solution, 2011).

1) Patients treated with murine monoclonal antibodies may develop HAMA, and as a result, may have a greater risk for hypersensitivity reactions with technetium Tc 99m besilesomab. A positive HAMA screening test contraindicates use of technetium Tc 99m besilesomab (Prod Info Scintimun intravenous injection solution, 2011).

Reproductive

3.20.1)

3.20.3)

A) LACK OF INFORMATION

1) At the time of this review, no data were available to assess the potential effects of exposure to these agents during pregnancy in humans:

a) CHROMIC PHOSPHATE P 32
b) FLORBETABEN F18 (Prod Info NEURACEQ(TM) intravenous injection, 2014)
c) FLORBETAPIR F-18 (Prod Info Amyvid intravenous injection, 2012)
d) FLUTEMETAMOL F18 (Prod Info VIZAMYL(TM) intravenous injection, 2013)
e) GADOTERATE MEGLUMINE (Prod Info DOTAREM(R) intravenous injection solution, 2013)
f) GALLIUM CITRATE GA 67 (Prod Info GALLIUM CITRATE Ga 67 intravenous injection solution, 2011)
g) GALLIUM GA 68 DOTATATE (Prod Info NETSPOT intravenous injection kit, 2016)
h) IOBENGUANE I 123 (Prod Info ADREVIEW(R) IV injection, 2008)
i) RADIUM RA 223 DICHLORIDE (Prod Info Xofigo intravenous injection, 2013)
j) RUBIDIUM RB 82 CHLORIDE (Prod Info CARDIOGEN-82(R) IV injection, 2010).
k) SAMARIUM SM 153 LEXIDRONAM (Prod Info QUADRAMET(R) IV injection, 2003)
l) SODIUM PHOSPHATE P 32 (Prod Info sodium phosphate P 32 solution, 2000)
m) TECHNETIUM TC 99M ALBUMIN AGGREGATED (Prod Info DRAXIMAGE(R) MAA intravenous injection, 2011)
n) TECHNETIUM TC 99M PENTETATE (Prod Info DRAXIMAGE(R) DTPA intravenous injection, 2011)
o) TECHNETIUM TC 99M TILMANOCEPT (Prod Info LYMPHOSEEK injection powder, 2014)
p) THALLOUS CHLORIDE Tl 201 (Prod Info thallous chloride TI 201 IV injection, 2011)
q) TOSITUMOMAB AND IODINE I 131 TOSITUMOMAB (Prod Info BEXXAR(R) intravenous injection, 2012)

2) CHOLINE C 11

a) There are no adequate and well controlled studies of choline C 11 use in pregnant women. Animal reproduction studies have not been conducted. It is unknown whether choline C 11 can cause fetal harm when administered during pregnancy, however, all radiopharmaceuticals have the potential to cause fetal harm. Pregnancy status should be evaluated in female patients of childbearing age prior to choline C 11 administration. The manufacturer recommends the use of choline C 11 in pregnant women only if clearly needed (Prod Info choline C 11 intravenous injection, 2012).

3) FLORBETABEN F18

a) There are no adequate or well-controlled studies of florbetaben F18 use in human pregnancy. Animal reproduction studies have not been conducted. It is not known whether florbetaben F18 can cause fetal harm or affect reproductive capacity when administered to a pregnant woman. Because radiopharmaceuticals, including florbetaben F18, have the potential to cause fetal harm, the manufacturer recommends the use of florbetaben F18 in pregnant women only if clearly needed. The likelihood of fetal harm is dependent upon the stage of fetal development and the radiopharmaceutical dosage. Determine pregnancy status in women of reproductive potential prior to administration (Prod Info NEURACEQ(TM) intravenous injection, 2014).

4) FLUCICLOVINE F 18

a) Fluciclovine F 18 is not indicated for use in women; therefore, no data are available about outcomes of its use during pregnancy (Prod Info AXUMIN(TM) intravenous injection, 2016).

5) FLUTEMETAMOL F18

a) There are no adequate or well-controlled studies of flutemetamol F18 use in human pregnancy. Animal reproduction studies have not been conducted. It is not known whether flutemetamol F18 can cause fetal harm or affect reproductive capacity when administered to a pregnant woman. Because radiopharmaceuticals, including flutemetamol F18, have the potential to cause fetal harm, the manufacturer recommends the use of flutemetamol F18 in pregnant women only if clearly needed. The likelihood of fetal harm is dependent upon the stage of fetal development and the radiopharmaceutical dosage. Determine pregnancy status in women of reproductive potential prior to administration (Prod Info VIZAMYL(TM) intravenous injection, 2013).

6) INDIUM IN 111 CAPROMAB PENDETIDE

a) Indium In 111 capromab pendetide is not indicated for use in women (Prod Info ProstaScint(R) Kit intravenous injection, 2010). Therefore, no data are available regarding the effects of this radiopharmaceutical agent during pregnancy.

7) TECHNETIUM TC 99M TILMANOCEPT

a) There are no adequate or well-controlled studies of technetium TC 99m tilmanocept use during human pregnancy. Animal studies have not yet been conducted. It is unknown if technetium TC 99m tilmanocept use during pregnancy can affect reproduction capacity or cause fetal harm. Due to the lack of human and animal safety data and because unbound technetium is known to cross the placental barrier, the manufacturer recommends use during pregnancy only if clearly needed (Prod Info LYMPHOSEEK injection powder, 2014).

B) IODINATED 131

1) Bilobar thyroid agenesis was reported in an infant following inadvertent maternal exposure to iodinated I-131 during pregnancy (12 to 14 gestational weeks). At 4 days of age, the infant had high levels of TSH (80 mUnits/L) and low levels of free T3 (0.5 mcg/dL) and free T4 (0.4 ng/dL). According to the mother's dosimeter, a level of 1.92 mSv was reached during gestational weeks 12 to 14. It was estimated that approximately 4 mCi of I-131 were administered and the estimated fetal absorbed dose was higher than 30 mGy. There is also a possibility that the infant was exposed to I-131 during breastfeeding (Zhao et al, 2013).

C) PREGNANCY CATEGORY

1) RADIUM RA 223 DICHLORIDE and SODIUM IODIDE I 131 have been classified as FDA pregnancy category X (Prod Info SODIUM IODIDE I 131 CAPSULES THERAPEUTIC oral capsules, 2014; Prod Info SODIUM IODIDE I 131 SOLUTION THERAPEUTIC oral solution, 2014; Prod Info Xofigo intravenous injection, 2013).
2) SAMARIUM SM 153 LEXIDRONAM, STRONTIUM-89, and TOSITUMOMAB AND IODINE I 131 TOSITUMOMAB have been classified as FDA pregnancy category D (Prod Info QUADRAMET(R) IV injection, 2003; Prod Info METASTRON(TM) IV injection, 2002; Prod Info BEXXAR(R) intravenous injection, 2012).
3) CHOLINE C 11, FLORBETABEN F18, FLORBETAPIR F-18, FLUTEMETAMOL F18, GADOTERATE MEGLUMINE, GALLIUM CITRATE GA 67, IOBENGUANE I 123, RUBIDIUM RB 82 CHLORIDE, SODIUM PHOSPHATE P 32, TECHNETIUM TC 99M ALBUMIN AGGREGATED, TECHNETIUM TC 99M PENTETATE, TECHNETIUM TC 99M TILMANOCEPT, and THALLOUS CHLORIDE Tl 201 have been classified as FDA pregnancy category C (Prod Info NEURACEQ(TM) intravenous injection, 2014; Prod Info choline C 11 intravenous injection, 2012; Prod Info Amyvid intravenous injection, 2012; Prod Info VIZAMYL(TM) intravenous injection, 2013; Prod Info DOTAREM(R) intravenous injection solution, 2013; Prod Info GALLIUM CITRATE Ga 67 intravenous injection solution, 2011; Prod Info ADREVIEW(R) IV injection, 2008; Prod Info CARDIOGEN-82(R) IV injection, 2010; Prod Info sodium phosphate P 32 solution, 2000; Prod Info DRAXIMAGE(R) MAA intravenous injection, 2011; Prod Info DRAXIMAGE(R) DTPA intravenous injection, 2011; Prod Info LYMPHOSEEK injection powder, 2014; Prod Info thallous chloride TI 201 IV injection, 2011).
4) CHROMIC PHOSPHATE P 32 and GALLIUM GA 68 DOTATATE do not have an FDA pregnancy category; however, fetal risk cannot be ruled out (Prod Info NETSPOT intravenous injection kit, 2016; Carlson, 1983).
5) INDIUM IN 111 CAPROMAB PENDETIDE does not have an FDA pregnancy category as this agent is not indicated for use in women (Prod Info ProstaScint(R) Kit intravenous injection, 2010).

D) RADIUM RA 223 DICHLORIDE

1) Radium Ra 223 dichloride use is contraindicated in pregnant women or in women who may become pregnant. Administration of radium Ra 223 dichloride during pregnancy may cause fetal harm based on its mechanism of action (Prod Info Xofigo intravenous injection, 2013).

E) SODIUM IODIDE I 131

1) Sodium iodide I-131 use is contraindicated in pregnant women or in women who may become pregnant. Administration of sodium iodide I-131 during pregnancy may cause harm to the fetal thyroid gland. Additionally, passage of the radioiodide through the placenta may cause severe, and potentially irreversible, hypothyroidism in neonates. In women of childbearing age, rule out pregnancy prior to use of sodium iodide I-131. If the drug is administered to a woman of childbearing potential or if a patient becomes pregnant while on the drug, apprise the patient of the potential hazard to the fetus. Two effective methods of contraception should be used by women and men of childbearing potential for at least 6 months after sodium iodide I-131 treatment to avoid pregnancy. If additional sodium iodide I-131 therapy or radionuclide imaging is required, 2 effective methods of contraception should be used for an even longer period of time (eg, 1 year) to avoid pregnancy (Prod Info HICON(TM) oral capsules, oral solution, 2011; Prod Info SODIUM IODIDE I 131 SOLUTION THERAPEUTIC oral solution, 2014; Prod Info SODIUM IODIDE I 131 CAPSULES THERAPEUTIC oral capsules, 2014).

F) STRONTIUM-89

1) Strontium-89 may cause fetal harm when administered during pregnancy (Prod Info METASTRON(TM) IV injection, 2002).

G) TOSITUMOMAB AND IODINE I 131 TOSITUMOMAB

1) Radiolabeled iodine I 131, a component of the tositumomab and iodine I 131 tositumomab regimen, may harm the fetal thyroid gland if administered to pregnant women. Infants born to mothers treated with the tositumomab and iodine-131 tositumomab combination regimen should be evaluated for hypothyroidism during the time of delivery and the neonatal period. Iodine I 131 may also cause an increased risk of miscarriage for up to 1 year following treatment. Contraceptive methods are recommended during and for 12 months after treatment with the tositumomab regimen (Prod Info BEXXAR(R) intravenous injection, 2012).

H) PLACENTAL BARRIER

1) GADOTERATE MEGLUMINE

a) It is unknown whether gadoterate meglumine crosses the human placenta; however, other gadolinium-based contrast agents do cross the placenta (Prod Info DOTAREM(R) intravenous injection solution, 2013).

2) SODIUM IODIDE I-131

a) Sodium iodide I-131 crosses the human placenta (Prod Info SODIUM IODIDE I 131 CAPSULES THERAPEUTIC oral capsules, 2014; Prod Info SODIUM IODIDE I 131 SOLUTION THERAPEUTIC oral solution, 2014; Prod Info HICON(TM) oral capsules, oral solution, 2011).

3) THALLOUS CHLORIDE Tl 201

a) Studies of human placentas have shown that thallous chloride Tl 201 crosses the placenta (Prod Info thallous chloride TI 201 IV injection, 2011).

4) TOSITUMOMAB AND IODINE I 131 TOSITUMOMAB

a) Radiolabeled iodine I 131, a component of the tositumomab and iodine I 131 tositumomab regimen, crosses the placenta (Prod Info BEXXAR(R) intravenous injection, 2012).

I) ANIMAL STUDIES

1) At the time of this review, no data were available to assess the potential effects of exposure to these agents during pregnancy in animals:

a) CHOLINE C 11 (Prod Info choline C 11 intravenous injection, 2012)
b) FLORBETABEN F18 (Prod Info NEURACEQ(TM) intravenous injection, 2014)
c) FLORBETAPIR F-18 (Prod Info Amyvid intravenous injection, 2012)
d) FLUCICLOVINE F 18 (Prod Info AXUMIN(TM) intravenous injection, 2016)
e) FLUTEMETAMOL F18 (Prod Info VIZAMYL(TM) intravenous injection, 2013)
f) GALLIUM CITRATE GA 67 (Prod Info GALLIUM CITRATE Ga 67 intravenous injection solution, 2011)
g) GALLIUM GA 68 DOTATATE (Prod Info NETSPOT intravenous injection kit, 2016)
h) RADIUM RA 223 DICHLORIDE (Prod Info Xofigo intravenous injection, 2013)
i) SODIUM IODIDE I-131 (Prod Info HICON(TM) oral capsules, oral solution, 2011)
j) TECHNETIUM TC 99M ALBUMIN AGGREGATED (Prod Info DRAXIMAGE(R) MAA intravenous injection, 2011)
k) TECHNETIUM TC 99M PENTETATE (Prod Info DRAXIMAGE(R) DTPA intravenous injection, 2011)
l) TECHNETIUM TC 99M TILMANOCEPT (Prod Info LYMPHOSEEK injection powder, 2014)
m) THALLOUS CHLORIDE Tl 201 (Prod Info thallous chloride TI 201 IV injection, 2011)
n) TOSITUMOMAB AND IODINE I 131 TOSITUMOMAB (Prod Info BEXXAR(R) intravenous injection, 2012)

2) GADOTERATE MEGLUMINE

a) In animal studies, there was no evidence of teratogenicity with gadoterate meglumine. IV doses administered to female rats of up to 10 mmol/kg/day (16.2 times the recommended human dose based on body surface area) for 14 days before mating through the mating period and until gestation (GD) 17 and to pregnant rabbits of up to 3 mmol/kg/day (10 times the human dose based on body surface area) from GD6 to GD19 resulted in no observed effects on embryofetal development. Doses of 10 mmol/kg/day (16.2 times the recommended human dose based on body surface area) in rats and 7 mmol/kg/day (23 times the recommended human dose based on body surface area) in rabbits were maternally toxic (Prod Info DOTAREM(R) intravenous injection solution, 2013).

3.20.4)

A) LACK OF INFORMATION

1) FLORBETABEN F18

a) At the time of this review, no data were available to assess the potential effects of exposure to this agent during lactation in humans (Prod Info NEURACEQ(TM) intravenous injection, 2014).

2) FLORBETAPIR F-18

a) At the time of this review, no data were available to assess the potential effects of exposure to this agent during lactation in humans (Prod Info Amyvid intravenous injection, 2012).

3) FLUCICLOVINE F 18

a) Fluciclovine F 18 is not indicated for use in women; therefore, no data are available about whether it is excreted into human milk or has adverse effects on milk production or the breastfeeding infant (Prod Info AXUMIN(TM) intravenous injection, 2016).

4) GADOTERATE MEGLUMINE

a) It is unknown whether gadoterate meglumine is excreted into human milk, and the effects on the nursing infant from exposure to the drug in milk have not been determined (Prod Info DOTAREM(R) intravenous injection solution, 2013).

5) GALLIUM CITRATE GA 67

a) At the time of this review, no data were available to assess the potential effects of exposure to this agent during lactation in humans (Prod Info GALLIUM CITRATE Ga 67 intravenous injection solution, 2011).

6) GALLIUM GA 68 DOTATATE

a) At the time of this review, no data were available to assess the potential effects of exposure to this agent during lactation in humans (Prod Info NETSPOT intravenous injection kit, 2016).

7) IOBENGUANE I 123

a) At the time of this review, no data were available to assess the potential effects of exposure to this agent during lactation in humans (Prod Info ADREVIEW(R) IV injection, 2008).

8) INDIUM IN 111 CAPROMAB PENDETIDE

9) RADIUM RA 223 DICHLORIDE

a) Radium Ra 223 dichloride is not indicated for use in women. No data are available regarding the effects of this radiopharmaceutical agent during lactation(Prod Info Xofigo intravenous injection, 2013).

10) SAMARIUM SM 153 LEXIDRONAM

a) At the time of this review, no data were available to assess the potential effects of exposure to this agent during lactation in humans (Prod Info QUADRAMET(R) IV injection, 2003).

11) SODIUM PHOSPHATE P 32

a) At the time of this review, no data were available to assess the potential effects of exposure to this agent during lactation in humans (Prod Info sodium phosphate P 32 solution, 2000).

12) TECHNETIUM TC 99M TILMANOCEPT

a) At the time of this review, no data were available to assess the potential effects of exposure to this agent during lactation in humans (Prod Info LYMPHOSEEK injection powder, 2014).

B) BREAST MILK

1) CHOLINE C 11

a) Lactation studies have not been conducted with choline C 11 and its use is not indicated in women. It is not known whether choline C 11 is excreted into human breast milk; however, there is the potential for serious adverse effects in nursing infants from choline C 11. Therefore, a decision should be made to discontinue nursing, pump and discard breast milk for 8 hours (greater than 10 half lives of radioactive decay for C 11 isotope) after choline C 11 administration, or discontinue drug taking into account the importance of the drug to the mother (Prod Info choline C 11 intravenous injection, 2012).

2) CHROMIC PHOSPHATE P 32

a) CASE REPORT: Radioactivity in breast milk was observed in 1 case report following treatment with chromic phosphate P 32. As breastfeeding was held in this case following administration of the radiopharmaceutical, the effects on the infant are unknown. However, it may be possible for the dissociated radioactive phosphorus from the breast milk to assimilate into the infant's normal phosphate metabolism (Carlson, 1983).

3) FLORBETABEN F18

a) Lactation studies have not been conducted with florbetaben F18. It is not known whether florbetaben F18 is excreted in human milk. Because many drugs are excreted in human milk and there is a potential for radiation exposure in nursing infants, a decision should be made to avoid the use of florbetaben F18 during breastfeeding or interrupt breastfeeding for a period of 24 hours after florbetaben 18 exposure (greater than 10 half-lives of radioactive decay for F18 isotope). If breastfeeding is interrupted, milk should be pumped and discarded for at least 24 hours after florbetaben F18 administration and alternative nutritional sources (eg, stored breast milk, infant formula) should be used (Prod Info NEURACEQ(TM) intravenous injection, 2014).

4) FLORBETAPIR F-18

a) Lactation studies with florbetapir F-18 have not been conducted in humans and it is unknown whether it is excreted in human milk. Due to the potential for radiation exposure to nursing infants, avoid using florbetapir F-18 in women who are nursing. If use is necessary, the nursing woman can interrupt breastfeeding for 24 hours (represents greater than 10 half-lives of radioactive decay for the F-18 isotope) after exposure to florbetapir F-18. During this time, the breast milk should be pumped and discarded, and alternate infant nutrition sources (e.g. stored breast milk or infant formula) are recommended (Prod Info Amyvid intravenous injection, 2012).

5) FLUMETAMOL F18

a) Lactation studies have not been conducted with flutemetamol F18. It is not known whether flutemetamol F18 is excreted in human milk. Because many drugs are excreted in human milk and there is a potential for radiation exposure in nursing infants, a decision should be made to avoid the use of flutemetamol F18 during breastfeeding or interrupt breastfeeding for a period of 24 hours after flutemetamol 18 exposure (greater than 10 half-lives of radioactive decay for F18 isotope). If breastfeeding is interrupted, milk should be pumped and discarded for at least 24 hours after flutemetamol F18 administration and alternative nutritional sources (eg, stored breast milk, formula) should be used (Prod Info VIZAMYL(TM) intravenous injection, 2013).

6) GADOTERATE MEGLUMINE

a) Nonclinical data show that minimal amounts (less than 0.1% of the IV dose) of gadoterate meglumine is excreted into breast milk and absorption via the gastrointestinal tract is poor. Nonetheless, caution should be exercised when administering gadoterate meglumine to a nursing woman, because many drugs are excreted into human milk (Prod Info DOTAREM(R) intravenous injection solution, 2013).

7) GALLIUM CITRATE GA 67

a) Gallium citrate Ga 67 is excreted into breast milk. Due to the potential for adverse events in the nursing infant, the manufacturer recommends substituting formula feeding for breastfeeding (Prod Info GALLIUM CITRATE Ga 67 intravenous injection solution, 2011).

8) GALLIUM GA 68 DOTATATE

a) Instruct a lactating mother to interrupt breastfeeding and pump and discard milk for 12 hours after taking gallium Ga 68 dotatate to minimize the breastfed infant's exposure to radiation (Prod Info NETSPOT intravenous injection kit, 2016).

9) RADIUM RA 223 DICHLORIDE

a) It is unknown whether radium Ra 223 dichloride is excreted in human milk. Because many drugs are excreted into human milk and the potential for serious adverse reactions in the nursing infant exists, it is recommended to either discontinue nursing or radium Ra 223 dichloride, after considering the importance of the drug to the mother (Prod Info Xofigo intravenous injection, 2013).

10) RUBIDIUM RB 82 CHLORIDE

a) Although definitive studies are lacking, the drug has a short half-life, so it will most likely not be excreted in the breast milk of a nursing mother (Prod Info CARDIOGEN-82(R) IV injection, 2010).

11) SODIUM IODIDE I 131

a) Sodium iodide I-131 is contraindicated in nursing women. During lactation, radioiodine is excreted into human milk and concentrations may meet or exceed maternal plasma concentrations. Breastfeeding and breast pumping should be discontinued for a minimum of 4 weeks prior to sodium iodide I-131 administration to minimize the amount of radiation absorbed into the breast tissue (Prod Info SODIUM IODIDE I 131 SOLUTION THERAPEUTIC oral solution, 2014; Prod Info SODIUM IODIDE I 131 CAPSULES THERAPEUTIC oral capsules, 2014; Prod Info HICON(TM) oral capsules, oral solution, 2011). Instead, formula feedings should be used (Prod Info HICON(TM) oral capsules, oral solution, 2011).

12) STRONTIUM-89

a) Although definitive studies are lacking, the manufacturer indicates that as a calcium analog, strontium-89 would probably appear in breast milk (Prod Info METASTRON(TM) IV injection, 2002).

13) TECHNETIUM TC 99M ALBUMIN AGGREGATED

a) Technetium Tc 99m albumin aggregated is excreted into breast milk. Due to the potential for adverse events in the nursing infant, the manufacturer recommends substituting formula feeding for breastfeeding (Prod Info DRAXIMAGE(R) MAA intravenous injection, 2011).

14) TECHNETIUM TC 99M PENTETATE

a) Technetium Tc 99m pentetate is excreted into breast milk. Due to the potential for adverse events in the nursing infant, the manufacturer recommends substituting formula feeding for breastfeeding (Prod Info DRAXIMAGE(R) DTPA intravenous injection, 2011).

15) TECHNETIUM TC 99M TILMANOCEPT

a) Technetium TC 99m tilmanocept is excreted into breast milk. Due to the potential for adverse events in the nursing infant, exercise caution when administering this agent to nursing mothers. The manufacturer recommends expressing and discarding the milk for at least 60 hours (10 half lives) after receiving technetium TC 99m tilmanocept (Prod Info LYMPHOSEEK injection powder, 2014). In general, the radioactivity of technetium 99m is present in breast milk for 15 hours to 3 days after the diagnostic study. The American Academy of Pediatrics Committee on Drugs suggests that the nursing mother pump her breasts before the radionuclide study, storing enough milk to feed her infant. After the study, the mother should continue to pump to maintain milk production, but discard the milk for the required time that radioactivity is present (Anon, 2001).

16) THALLOUS CHLORIDE Tl 201

a) Thallous chloride Tl 201 has been shown to be excreted in human milk. Close contact with infants should be kept to a minimum if the administered dose of thallous chloride Tl 201 to the nursing mother could result in an effective dose greater than 1 mSv (0.1 rem) to the infant (Prod Info thallous chloride TI 201 IV injection, 2011).

17) TOSITUMOMAB AND IODINE I 131 TOSITUMOMAB

a) Although definitive studies are lacking, tositumomab is expected to be present in human milk, as immunoglobulins are known to be excreted in breast milk. Also, radiolabeled iodine is excreted into milk at concentrations that approach or exceed maternal plasma concentrations and is known to harm the human thyroid gland. (Prod Info BEXXAR(R) intravenous injection, 2012).

3.20.5)

A) LACK OF INFORMATION

1) At the time of this review, no data were available to assess the potential effects on fertility from exposure to these agents :

a) FLORBETAPIR F-18 (Prod Info Amyvid intravenous injection, 2012)
b) GALLIUM CITRATE GA 67 (Prod Info GALLIUM CITRATE Ga 67 intravenous injection solution, 2011)
c) GALLIUM GA 68 DOTATATE (Prod Info NETSPOT intravenous injection kit, 2016)
d) INDIUM IN 111 CAPROMAB PENDETIDE (Prod Info ProstaScint(R) Kit intravenous injection, 2010)
e) RADIUM RA 223 DICHLORIDE (Prod Info Xofigo intravenous injection, 2013)
f) RUBIDIUM RB 82 CHLORIDE (Prod Info CARDIOGEN-82(R) IV injection, 2010)
g) THALLOUS CHLORIDE Tl 201 (Prod Info thallous chloride TI 201 IV injection, 2011)

B) SODIUM IODIDE I-131

1) Sodium iodide I-131 therapy has been associated with transient, dose-related impairment of testicular function in men and transient ovarian failure in women (Prod Info SODIUM IODIDE I 131 CAPSULES THERAPEUTIC oral capsules, 2014; Prod Info SODIUM IODIDE I 131 SOLUTION THERAPEUTIC oral solution, 2014); however, a follow-up study of 627 women treated for differentiated thyroid carcinoma with sodium iodide I 131 revealed no evidence of fertility impairment (Dottorini et al, 1995).

Carcinogenicity

3.21.2)

A) CHOLINE C 11

1) At the time of this review, the manufacturer does not report any carcinogenic potential of choline C 11 in humans.

B) FLORBETABEN F-18

1) At the time of this review, there is no data to determine the carcinogenic potential of florbetaben F-18 in humans.

C) FLUTEMETAMOL F-18

1) At the time of this review, there is no data to determine the carcinogenic potential of flutemetamol F-18 in humans.

D) GADOTERATE MEGLUMINE

1) At the time of this review, the manufacturer does not report any carcinogenic potential of gadoterate meglumine in humans.

E) RUBIDIUM Rb 82 CHLORIDE

1) At the time of this review, the manufacturer does not report any carcinogenic potential of rubidium Rb 82 chloride in humans.

F) SODIUM IODIDE I-131

1) Postmarketing cases of leukemia and stomach, bladder, and breast cancer have been reported in patients who received sodium iodide I-131 therapy.

G) TECHNETIUM TC 99M TILMANOCEPT

1) At the time of this review, the manufacturer does not report any carcinogenic potential of technetium TC 99M tilmanocept in humans.

H) TOSITUMOMAB/IODINE I131

1) At the time of this review, the manufacturer does not report any carcinogenic potential of tositumomab/iodine I131 in humans. However, iodine I-131 is a potential carcinogen.

3.21.3)

A) LACK OF INFORMATION

1) CHOLINE C 11

a) At the time of this review, the manufacturer does not report any carcinogenic potential of choline C 11 in humans (Prod Info choline C 11 intravenous injection, 2012).

2) FLORBETABEN F-18

a) At the time of this review, the manufacturer does not report any carcinogenic potential of florbetaben F-18 in humans (Prod Info NEURACEQ(TM) intravenous injection, 2014).

3) FLUTEMETAMOL F-18

a) At the time of this review, the manufacturer does not report any carcinogenic potential of flutemetamol F-18 in humans (Prod Info VIZAMYL(TM) intravenous injection, 2013).

4) GADOTERATE MEGLUMINE

a) At the time of this review, the manufacturer does not report any carcinogenic potential of gadoterate meglumine in humans (Prod Info DOTAREM(R) intravenous injection solution, 2013).

5) TECHNETIUM TC 99M TILMANOCEPT

a) At the time of this review, the manufacturer does not report any carcinogenic potential of technetium TC 99M tilmanocept in humans (Prod Info Lymphoseek injection powder, 2013).

6) TOSITUMOMAB/IODINE I131

a) At the time of this review, the manufacturer does not report any carcinogenic potential of tositumomab/iodine I131 in humans. However, iodine I-131 is a potential carcinogen (Prod Info BEXXAR(R) intravenous injection, 2012).

B) SODIUM IODIDE I-131

1) Postmarketing cases of leukemia and stomach, bladder, and breast cancers have been reported in patients who received sodium iodide I-131 therapy (Prod Info sodium iodide I 131 oral therapeutic capsules, 2012).

3.21.4)

A) CHOLINE C 11

1) At the time of this review, the manufacturer does not report any carcinogenic potential of choline C 11 in animals (Prod Info choline C 11 intravenous injection, 2012).

B) FLORBETABEN F-18

1) Animal studies to evaluate the carcinogenic potential of florbetaben F-18 have not been performed (Prod Info NEURACEQ(TM) intravenous injection, 2014).

C) FLORBETAPIR F-18

1) Animal studies to evaluate the carcinogenic potential of florbetapir F-18 have not been performed (Prod Info Amyvid intravenous injection, 2012).

D) FLUTEMETAMOL F-18

1) Animal studies to evaluate the carcinogenic potential of flutemetamol -18 have not been conducted (Prod Info VIZAMYL(TM) intravenous injection, 2013).

E) GADOTERATE MEGLUMINE

1) Long-term animal studies to evaluate carcinogenic potential of gadoterate meglumine have not been performed (Prod Info DOTAREM(R) intravenous injection solution, 2013).

F) INDIUM IN 111 CAPROMAB PENDETIDE

1) Long-term animal studies to evaluate carcinogenic potential of indium IN 111 capromab pendetide have not been performed (Prod Info ProstaScint(R) Kit intravenous injection, 2010).

G) RUBIDIUM Rb 82 CHLORIDE

1) At the time of this review, the manufacturer does not report any carcinogenic potential of rubidium Rb 82 chloride in animals.

H) SAMARIUM SM 153 LEXIDRONAM

1) OSTEOSARCOMAS occurred in a 2-year toxicity/carcinogenicity study in male and female rats given EDTMP by gastric intubation in daily doses of 50 mg and 150 mg per kg of body weight, respectively (Prod Info QUADRAMET(R) IV injection, 2003).

I) SODIUM IODIDE I 131

1) THYROID ADENOMAS AND CARCINOMAS: Animal studies have found that therapy with sodium iodide I-131 may produce thyroid adenomas and carcinomas (Graham & Burman, 1986; Safa et al, 1975; Braverman & Utiger, 1991). However, human studies found no conclusive evidence of thyroid carcinoma associated with sodium iodide I-131 therapy for hyperthyroidism (Prod Info HICON(TM) oral capsules, oral solution, 2011; Prod Info sodium iodide I 131 diagnostic oral capsules, 2005; Graham & Burman, 1986; Safa et al, 1975; Holm et al, 1980; Braverman & Utiger, 1991).

J) SODIUM PHOSPHATE P 32

1) Long-term animal studies to evaluate carcinogenic potential of sodium phosphate P 32 have not been performed (Prod Info sodium phosphate P 32 solution, 2000).

K) STRONTIUM 89

1) Thirty-three out of 40 rats receiving 10 consecutive monthly doses of either 250 or 350 microcuries per kg of body weight of strontium chloride Sr 89 developed malignant bone tumors after a latency period of approximately 9 months (Prod Info METASTRON(TM) IV injection, 2002).

L) TECHNETIUM TC 99M TILMANOCEPT

1) At the time of this review, the manufacturer does not report any carcinogenic potential of technetium TC 99M tilmanocept in animals (Prod Info Lymphoseek injection powder, 2013).

M) THALLOUS CHLORIDE Tl 201

1) Long-term animal studies to evaluate carcinogenic potential of thallous chloride Tl 201 have not been performed (Prod Info Thallous Chloride Tl 201 Injection, 2004).

Genotoxicity

1) At the time of this review, the manufacturer does not report any mutagenic potential of choline C 11 in animals or humans (Prod Info choline C 11 intravenous injection, 2012).

1) There was no evidence of mutagenicity in the following tests: Ames test or in vitro chromosomal aberration assay (Prod Info NEURACEQ(TM) intravenous injection, 2014).

1) The nonradioactive form of florbetapir F-18, 19F-AV-45, produced increases in revertant colonies in 2 of 5 strains tested in an in vitro bacterial reverse mutation assay (Ames test); however, no increases in the number of micronucleated polychromatic erythrocytes were noted with 19F-AV-45 at the highest achievable dose level (372 mcg/kg/day) given twice daily for 3 consecutive days in a mouse micronucleus study. No increase in structural aberrations were reported with 3-hour exposure (with or without activation) to 19-AV-45 in a chromosomal aberration in vitro study with cultured human peripheral lymphocytes; however, a statistically significant increase in structural aberrations were noted with 22-hour exposure (Prod Info Amyvid intravenous injection, 2012).

1) There was no evidence of genotoxicity after in vivo exposure of flutemetamol F18 at the highest cumulative dose level tested in rats )157 and 27 mcg/kg/day for 2 and 14 days, respectively) and during an unscheduled DNA synthesis assay in rat hepatocytes (39 mcg/kg/day). Flutemetamol was positive for mutagenicity in the following tests: bacterial reverse mutation assay (Ames test) and the mouse lymphoma assay (Prod Info VIZAMYL(TM) intravenous injection, 2013).

1) Negative results were observed with gadoterate meglumine in the Salmonella reverse mutation (Ames) test, in vitro chromosomal aberration assay in Chinese hamster ovary cells, in vitro gene mutation assay in Chinese hamster lung cells, and in vivo mouse micronucleus assay (Prod Info DOTAREM(R) intravenous injection solution, 2013).

1) Long-term animal studies to evaluate mutagenic potential of indium IN 111 capromab pendetide have not been performed (Prod Info ProstaScint(R) Kit intravenous injection, 2010).

1) At the time of this review, the manufacturer does not report any genotoxic or mutagenic potential of rubidium Rb 82 chloride in humans or animals.

1) Negative results were observed (with nonradioactive samarium-EDTMP) in the Salmonella reverse mutation (Ames) test, unscheduled DNA synthesis in rat liver primary cell culture, chromosomal aberration assay in rat lymphocytes, CHO/HGPRT forward mutation assay, and mouse bone marrow micronucleus test (Prod Info QUADRAMET(R) IV injection, 2003).

1) Clinical studies have not clearly established mutagenic effects associated with sodium iodide I-131. However, chromosomal changes have been reported (Prod Info HICON(TM) oral capsules, oral solution, 2011; Prod Info sodium iodide I 131 diagnostic oral capsules, 2005; Graham & Burman, 1986).

1) Long-term animal studies to evaluate mutagenic potential of sodium phosphate P 32 have not been performed (Prod Info sodium phosphate P 32 solution, 2000).

1) Adequate studies to evaluate mutagenic potential have not been conducted with strontium 89 (Prod Info METASTRON(TM) IV injection, 2002).

1) There was no evidence of genotoxicity or mutagenicity in the following tests: in vitro Ames bacterial mutation assay, in vitro mouse lymphoma test, or in vivo micronucleus test (Prod Info Lymphoseek injection powder, 2013).

1) Long-term animal studies to evaluate mutagenic potential of thallous chloride Tl 201 have not been performed (Prod Info Thallous Chloride Tl 201 Injection, 2004).

1) At the time of this review, the manufacturer does not report any mutagenic potential of tositumomab/iodine I131 in humans. However, iodine I-131 is a potential mutagen (Prod Info BEXXAR(R) intravenous injection, 2012).

Laboratory Monitoring

Monitoring Parameters Levels

4.1.1)

A) Monitor CBC with differential and platelet count. Myelosuppression has been reported with the use of sodium iodide I 131, samarium Sm 153, strontium-89, and phosphate P32.
B) Monitor vital signs, fluid and electrolyte balance, and liver enzymes (with Indium In-111 capromab pendetide).
C) Obtain a baseline ECG; institute continuous cardiac monitoring as indicated. Dysrhythmias have rarely been reported after the administration of technetium Tc 99m sestamibi and samarium SM 153. Tachycardia has rarely been reported in patients receiving sodium iodide I 123 or I 131.
D) Monitor thyroid function after radioiodine exposure.
E) Monitor urine output and radioactivity.

4.1.2)

A) Monitor CBC with differential and platelet count.

B) Monitor vital signs, fluid and electrolyte balance, and liver enzymes (with Indium In-111 capromab pendetide).
C) Monitor thyroid function after radioiodine exposure.

Treatment

Life Support

Patient Disposition

6.3.1)

6.3.1.1) ADMISSION CRITERIA/ORAL

A) Admission is required for fluid and electrolyte therapy if severe vomiting and diarrhea are present. Patients manifesting thrombocytopenia or leukopenia, require hospital admission.

6.3.1.3) CONSULT CRITERIA/ORAL

A) Consult a Poison Center for assistance in managing patients with severe toxicity or for whom diagnosis is unclear. For radiation-related medical assistance call 865-576-3131 (days), or after normal business hours: 865-576-1005 and ask for REAC/TS. A physician is available 24 hours a day.

6.3.1.5) OBSERVATION CRITERIA/ORAL

A) Patients with radiopharmaceutical overdose should be sent to a healthcare facility for evaluation. Patients who remain asymptomatic with normal laboratory tests can be sent home if careful follow-up can be assured. Follow-up instructions should include a repeat CBC in 48 hours and reevaluation following the onset of any gastrointestinal symptoms (eg, nausea, vomiting, and diarrhea).

Monitoring

Oral Exposure

6.5.1)

A) PREHOSPITAL: Radiopharmaceutical administration routes include: injection, interstitially, intrapleurally and orally. Most radiopharmaceutical agents are administered in medical facilities to diagnose various malignancies, endocrinopathies, metabolopathies, and perfusion abnormalities; prehospital decontamination is not required. Consider activated charcoal for oral ingestions in a patient with a recent, significant overdose who is alert or in whom airway is protected.
B) ACTIVATED CHARCOAL

1) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION

a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).

1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
2) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).

2) CHARCOAL DOSE

a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).

1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).

b) ADVERSE EFFECTS/CONTRAINDICATIONS

1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).

6.5.2)

A) STRONTIUM: Oral administration of aluminum phosphate gel 100 mL as a single dose, or barium sulfate 200 to 300 g in aqueous suspension may decrease absorption of radiostrontium (National Council on Radiation Protection & Measurements, 2006).
B) CARBON-14 UREA: Ingestion of 1000 capsules of carbon-14 urea can produce only a negligible risk from radiation (0.3 rem). Overdose patients should drink one glass of water (150 mL) every hour to increase the rate of excretion of the isotope (Prod Info PYtest(R) oral capsules, 2000).
C) ACTIVATED CHARCOAL

1) CHARCOAL ADMINISTRATION

a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.

2) CHARCOAL DOSE

b) ADVERSE EFFECTS/CONTRAINDICATIONS

6.5.3)

A) MONITORING OF PATIENT

1) Monitor CBC with differential and platelet count. Myelosuppression has been reported with the use of sodium iodide I 131, samarium Sm 153, strontium-89, and phosphate P32.
2) Monitor vital signs, fluid and electrolyte balance, and liver enzymes (with Indium In-111 capromab pendetide).
3) Obtain a baseline ECG; institute continuous cardiac monitoring as indicated. Dysrhythmias have rarely been reported after the administration of technetium Tc 99m sestamibi and samarium Sm 153. Tachycardia has rarely been reported in patients receiving sodium iodide I 123 or I 131.
4) Monitor thyroid function after radioiodine exposure.
5) Monitor urine output and radioactivity.

B) ANTIDOTE

1) COPPER-64 CHLORIDE

a) Hepatotoxicity may develop after an inadvertent administration of copper-64 chloride directly to a patient. Administer an intravenous chelator, Ca-DTPA or Ca-EDTA, as soon as possible, ideally within 1 hour of inadvertent administration of copper-64 chloride, to increase the elimination of the radionuclide from the body. DOSE: 1 g of Ca-DTPA or Ca-EDTA by slow IV injection over 3 to 4 minutes or by infusion (1 g in 100 to 250 mL of dextrose, or sodium chloride 0.9% solution for injection) (Prod Info Cuprymina intravenous injection solution, 2012).

2) PHOSPHORUS 32

a) A patient who received an inadvertent overdose with phosphorus 32 was treated with daily oral sodium phosphate 5 g, intravenous calcium gluconate 540 mg daily, and 200 units of parathyroid extract intramuscularly every 6 hours for 18 days starting the 9th day after exposure. It was estimated that this therapy reduces the radiation exposure to bone marrow by 38% and that the effective half life of P32 was reduced from a baseline of 11.2 days to 4.8 days (National Council on Radiation Protection & Measurements, 2006).

3) RADIOACTIVE CALCIUM

a) CALCIUM: Oral or intravenous calcium increases the urinary excretion of radioactive calcium in humans. Oral calcium gluconate (15 g daily in divided doses), calcium lactate (4 grams three times daily) or intravenous calcium gluconate may be effective (National Council on Radiation Protection & Measurements, 2006).

4) RADIOACTIVE STRONTIUM

a) CALCIUM: Oral or intravenous calcium increases the urinary excretion of radioactive strontium in humans. Oral calcium gluconate (15 g daily in divided doses), calcium lactate (4 grams three times daily) or intravenous calcium gluconate may be effective (National Council on Radiation Protection & Measurements, 2006).
b) STRONTIUM: Strontium may be given orally or intravenously as a diluting agent for radioactive strontium overdose. Strontium lactate 300 mg 2 to 5 times daily or strontium gluconate 600 mg in 500 ml 5% dextrose in water infused over 4 hours for 6 consecutive days are recommended doses (National Council on Radiation Protection & Measurements, 2006).
c) PHOSPHATE: Oral administration of phosphate may be used to prevent intestinal absorption of radioactive strontium. Sodium or potassium phosphate in adults: 600 to 1200 mg orally in divided doses (National Council on Radiation Protection & Measurements, 2006).

5) SODIUM IODIDE I 131 OR I 123

a) POTASSIUM IODIDE: Administer potassium iodide as soon as possible after an overdose. Adults 300 mg daily for 7 to 14 days. Children aged 3 to 12 years: 65 mg orally daily for 7 to 14 days. If potassium iodide is not administered within 12 hours of the overdose, propylthiouracil or methimazole may help reduce thyroid retention of radioiodine. Propylthiouracil: Adults: 100 mg every 8 hours for 8 days. Pediatric 5 to 7 mg/kg/day in divided doses every 8 hours maximum 300 mg/day. Methimazole Adults: 10 mg every 8 hours for 2 days, reduce to 5 mg every 8 hours and continue for 6 days. Pediatric 0.4 mg/kg/day in divided doses every 8 hours (National Council on Radiation Protection & Measurements, 2006).

6) YTTRIUM-90 CHLORIDE

a) Increased bone marrow toxicity and hematopoietic stem cell damage may develop after an inadvertent administration of yttrium-90 chloride directly to a patient. Administer an intravenous chelator, Ca-DTPA or Ca-EDTA, as soon as possible, ideally within 1 hour of inadvertent administration of yttrium-90 chloride, to increase the elimination of the radionuclide from the body. DOSE: 1 g of Ca-DTPA or Ca-EDTA by slow IV injection over 3 to 4 minutes or by infusion (1 g in 100 to 250 mL of dextrose, or sodium chloride 0.9% solution for injection) (Prod Info Yttriga injection solution, 2012).

C) MYELOSUPPRESSION

1) Myelosuppression, including thrombocytopenia and leukopenia, has been reported with therapeutic use of sodium iodide I 131, samarium Sm 153, strontium-89, and phosphate P32 (Prod Info PHOSPHOCOL(R) P 32 injection suspension, 2000; Prod Info QUADRAMET(R) IV injection, 2003; Prod Info IODOTOPE(R) oral capsules, 2001; Prod Info METASTRON(TM) IV injection, 2002). Increased bone marrow toxicity and hematopoietic stem cell damage may develop after an inadvertent administration of yttrium-90 chloride (Prod Info Yttriga injection solution, 2012).
2) There is little data on the use of hematopoietic colony stimulating factors to treat neutropenia after drug overdose or idiosyncratic reactions. These agents have been shown to shorten the duration of severe neutropenia in patients receiving cancer chemotherapy (Hartman et al, 1997; Stull et al, 2005). They have also been used to treat agranulocytosis induced by nonchemotherapy drugs (Beauchesne & Shalansky, 1999). They may be considered in patients with severe neutropenia who have or are at significant risk for developing febrile neutropenia.

a) Filgrastim: The usual starting dose in adults is 5 micrograms/kilogram/day by intravenous infusion or subcutaneous injection (Prod Info NEUPOGEN(R) injection, 2006).
b) Sargramostim: Usual dose is 250 micrograms/square meter/day infused IV over 4 hours (Prod Info LEUKINE(R) injection, 2006).
c) Monitor CBC with differential.

3) Transfusion of platelets, packed red cells, or both may be needed in patients with severe thrombocytopenia, anemia, or hemorrhage.

D) HYPOTENSIVE EPISODE

1) Hypotension has been reported in patients receiving Indium In-111 capromab pendetide or thallous chloride TI 201 (Prod Info ProstaScint(R) Kit intravenous injection, 2010; Prod Info Thallous Chloride Tl 201 Injection, 2004).
2) SUMMARY

a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.

3) DOPAMINE

a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).

4) NOREPINEPHRINE

a) PREPARATION: 4 milligrams (1 amp) added to 1000 milliliters of diluent provides a concentration of 4 micrograms/milliliter of norepinephrine base. Norepinephrine bitartrate should be mixed in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since dextrose-containing solutions protect against excessive oxidation and subsequent potency loss. Administration in saline alone is not recommended (Prod Info norepinephrine bitartrate injection, 2005).
b) DOSE

1) ADULT: Dose range: 0.1 to 0.5 microgram/kilogram/minute (eg, 70 kg adult 7 to 35 mcg/min); titrate to maintain adequate blood pressure (Peberdy et al, 2010).
2) CHILD: Dose range: 0.1 to 2 micrograms/kilogram/minute; titrate to maintain adequate blood pressure (Kleinman et al, 2010).
3) CAUTION: Extravasation may cause local tissue ischemia, administration by central venous catheter is advised (Peberdy et al, 2010).

E) SEIZURE

1) TECHNETIUM TC 99M SESTAMIBI: Seizures have rarely been reported after administration of technetium Tc 99m sestamibi (Prod Info CARDIOLITE(R) IV injection, 2008). The causal relationship has not been established.
2) SUMMARY

a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).

3) DIAZEPAM

a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .

4) NO INTRAVENOUS ACCESS

a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).

5) LORAZEPAM

a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2009; Chin et al, 2008).

6) PHENOBARBITAL

a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).

7) OTHER AGENTS

a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):

1) VALPROATE SODIUM: ADULT DOSE: An initial dose of 20 to 40 mg/kg IV, at a rate of 3 to 6 mg/kg/minute; may give an additional dose of 20 mg/kg 10 minutes after loading infusion. PEDIATRIC DOSE: 1.5 to 3 mg/kg/minute (Brophy et al, 2012).
2) LEVETIRACETAM: ADULT DOSE: 1000 to 3000 mg IV, at a rate of 2 to 5 mg/kg/min IV. PEDIATRIC DOSE: 20 to 60 mg/kg IV (Brophy et al, 2012; Loddenkemper & Goodkin, 2011).
3) LACOSAMIDE: ADULT DOSE: 200 to 400 mg IV; 200 mg IV over 15 minutes (Brophy et al, 2012). PEDIATRIC DOSE: In one study, median starting doses of 1.3 mg/kg/day and maintenance doses of 4.7 mg/kg/day were used in children 8 years and older (Loddenkemper & Goodkin, 2011).
4) TOPIRAMATE: ADULT DOSE: 200 to 400 mg nasogastric/orally OR 300 to 1600 mg/day orally divided in 2 to 4 times daily (Brophy et al, 2012).

F) ACUTE ALLERGIC REACTION

1) SUMMARY

a) Mild to moderate allergic reactions may be treated with antihistamines with or without inhaled beta adrenergic agonists, corticosteroids or epinephrine. Treatment of severe anaphylaxis also includes oxygen supplementation, aggressive airway management, epinephrine, ECG monitoring, and IV fluids.

2) BRONCHOSPASM

a) ALBUTEROL

1) ADULT: 2.5 to 5 milligrams in 2 to 4.5 milliliters of normal saline delivered per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 2.5 to 10 mg every 1 to 4 hours as needed, or 10 to 15 mg/hr by continuous nebulization as needed (National Heart,Lung,and Blood Institute, 2007). CHILD: 0.15 milligram/kilogram (minimum 2.5 milligrams) per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 0.15 to 0.3 mg/kg (up to 10 mg) every 1 to 4 hours as needed, or 0.5 mg/kg/hr by continuous nebulization (National Heart,Lung,and Blood Institute, 2007).

3) CORTICOSTEROIDS

a) Consider systemic corticosteroids in patients with significant bronchospasm.
b) PREDNISONE: ADULT: 40 to 80 milligrams/day. CHILD: 1 to 2 milligrams/kilogram/day (maximum 60 mg) in 1 to 2 divided doses divided twice daily (National Heart,Lung,and Blood Institute, 2007).

4) MILD CASES

a) DIPHENHYDRAMINE

1) SUMMARY: Oral diphenhydramine, as well as other H1 antihistamines can be used as indicated (Lieberman et al, 2010).
2) ADULT: 50 milligrams orally, or 10 to 50 mg intravenously at a rate not to exceed 25 mg/min or may be given by deep intramuscular injection. A total of 100 mg may be administered if needed. Maximum daily dosage is 400 mg (Prod Info diphenhydramine HCl intravenous injection solution, intramuscular injection solution, 2013).
3) CHILD: 5 mg/kg/24 hours or 150 mg/m(2)/24 hours. Divided into 4 doses, administered intravenously at a rate not exceeding 25 mg/min or by deep intramuscular injection. Maximum daily dosage is 300 mg (Prod Info diphenhydramine HCl intravenous injection solution, intramuscular injection solution, 2013).

5) MODERATE CASES

a) EPINEPHRINE: INJECTABLE SOLUTION: It should be administered early in patients by IM injection. Using a 1:1000 (1 mg/mL) solution of epinephrine. Initial Dose: 0.01 mg/kg intramuscularly with a maximum dose of 0.5 mg in adults and 0.3 mg in children. The dose may be repeated every 5 to 15 minutes, if no clinical improvement. Most patients respond to 1 or 2 doses (Nowak & Macias, 2014).

6) SEVERE CASES

a) EPINEPHRINE

1) INTRAVENOUS BOLUS: ADULT: 1 mg intravenously as a 1:10,000 (0.1 mg/mL) solution; CHILD: 0.01 mL/kg intravenously to a maximum single dose of 1 mg given as a 1:10,000 (0.1 mg/mL) solution. It can be repeated every 3 to 5 minutes as needed. The dose can also be given by the intraosseous route if IV access cannot be established (Lieberman et al, 2015). ALTERNATIVE ROUTE: ENDOTRACHEAL ADMINISTRATION: If IV/IO access is unavailable. DOSE: ADULT: Administer 2 to 2.5 mg of 1:1000 (1 mg/mL) solution diluted in 5 to 10 mL of sterile water via endotracheal tube. CHILD: DOSE: 0.1 mg/kg to a maximum of 2.5 mg administered as a 1:1000 (1 mg/mL) solution diluted in 5 to 10 mL of sterile water via endotracheal tube (Lieberman et al, 2015).
2) INTRAVENOUS INFUSION: Intravenous administration may be considered in patients poorly responsive to IM or SubQ epinephrine. An epinephrine infusion may be prepared by adding 1 mg (1 mL of 1:1000 (1 mg/mL) solution) to 250 mL D5W, yielding a concentration of 4 mcg/mL, and infuse this solution IV at a rate of 1 mcg/min to 10 mcg/min (maximum rate). CHILD: A dosage of 0.01 mg/kg (0.1 mL/kg of a 1:10,000 (0.1 mg/mL) solution up to 10 mcg/min (maximum dose 0.3 mg) is recommended for children (Lieberman et al, 2010). Careful titration of a continuous infusion of IV epinephrine, based on the severity of the reaction, along with a crystalloid infusion can be considered in the treatment of anaphylactic shock. It appears to be a reasonable alternative to IV boluses, if the patient is not in cardiac arrest (Vanden Hoek,TL,et al).

7) AIRWAY MANAGEMENT

a) OXYGEN: 5 to 10 liters/minute via high flow mask.
b) INTUBATION: Perform early if any stridor or signs of airway obstruction.
c) CRICOTHYROTOMY: Use if unable to intubate with complete airway obstruction (Vanden Hoek,TL,et al).
d) BRONCHODILATORS are recommended for mild to severe bronchospasm.
e) ALBUTEROL: ADULT: 2.5 to 5 milligrams in 2 to 4.5 milliliters of normal saline delivered per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 2.5 to 10 mg every 1 to 4 hours as needed, or 10 to 15 mg/hr by continuous nebulization as needed (National Heart,Lung,and Blood Institute, 2007).
f) ALBUTEROL: CHILD: 0.15 milligram/kilogram (minimum 2.5 milligrams) per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 0.15 to 0.3 milligram/kilogram (maximum 10 milligrams) every 1 to 4 hours as needed OR administer 0.5 mg/kg/hr by continuous nebulization (National Heart,Lung,and Blood Institute, 2007).

8) MONITORING

a) CARDIAC MONITOR: All complicated cases.
b) IV ACCESS: Routine in all complicated cases.

9) HYPOTENSION

a) If hypotensive give 500 to 2000 milliliters crystalloid initially (20 milliliters/kilogram in children) and titrate to desired effect (stabilization of vital signs, mentation, urine output); adults may require up to 6 to 10 L/24 hours. Central venous or pulmonary artery pressure monitoring is recommended in patients with persistent hypotension.

1) VASOPRESSORS: Should be used in refractory cases unresponsive to repeated doses of epinephrine and after vigorous intravenous crystalloid rehydration (Lieberman et al, 2010).
2) DOPAMINE: Initial Dose: 2 to 20 micrograms/kilogram/minute intravenously; titrate to maintain systolic blood pressure greater than 90 mm Hg (Lieberman et al, 2010).

10) H1 and H2 ANTIHISTAMINES

a) SUMMARY: Antihistamines are second-line therapy and are used as supportive therapy and should not be used in place of epinephrine (Lieberman et al, 2010).

1) DIPHENHYDRAMINE: ADULT: 25 to 50 milligrams via a slow intravenous infusion or IM. PEDIATRIC: 1 milligram/kilogram via slow intravenous infusion or IM up to 50 mg in children (Lieberman et al, 2010).

b) RANITIDINE: ADULT: 1 mg/kg parenterally; CHILD: 12.5 to 50 mg parenterally. If the intravenous route is used, ranitidine should be infused over 10 to 15 minutes or diluted in 5% dextrose to a volume of 20 mL and injected over 5 minutes (Lieberman et al, 2010).
c) Oral diphenhydramine, as well as other H1 antihistamines, can also be used as indicated (Lieberman et al, 2010).

11) DYSRHYTHMIAS

a) Dysrhythmias and cardiac dysfunction may occur primarily or iatrogenically as a result of pharmacologic treatment (epinephrine) (Vanden Hoek,TL,et al). Monitor and correct serum electrolytes, oxygenation and tissue perfusion. Treat with antiarrhythmic agents as indicated.

12) OTHER THERAPIES

a) There have been a few reports of patients with anaphylaxis, with or without cardiac arrest, that have responded to vasopressin therapy that did not respond to standard therapy. Although there are no randomized controlled trials, other alternative vasoactive therapies (ie, vasopressin, norepinephrine, methoxamine, and metaraminol) may be considered in patients in cardiac arrest secondary to anaphylaxis that do not respond to epinephrine (Vanden Hoek,TL,et al).

G) HYPOCALCEMIA

1) SAMARIUM SM 153 LEXIDRONAM: Dogs that received non-radioactive samarium ethylenediaminetetramethylenephosphonic acid (EDTMP) at 6 times the human therapeutic dose based on body weight or 3 times the dose based on surface area developed hypocalcemia. This is thought to be due to the chelating effects of EDTMP (Prod Info QUADRAMET(R) IV injection, 2003).
2) Hypocalcemia may develop abruptly after samarium Sm 153 overdose. Aggressive calcium replacement should be instituted in patients with clinical or ECG manifestations of hypocalcemia even if laboratory confirmation of hypocalcemia is still pending.

a) For emergent treatment of hypocalcemia in cases involving dysrhythmias, 10 mL to 20 mL of 10% calcium chloride or calcium gluconate (initial bolus) IV over 10 to 15 minutes. Rapid administration may be necessary. Repeat bolus or a maintenance infusion may be necessary.
b) Correct known or suspected hypocalcemia with intravenous Calcium Chloride (10% Solution): ADULT: 2 to 4 mg/kg (0.02 to 0.04 mL/kg) with repeat doses as necessary. PEDIATRIC: 10 to 30 mg/kg (0.1 to 0.3 mL/kg) infused slowly with repeat doses as necessary. Ideally, repeat doses should be based on measured deficits of ionized calcium. Calcium gluconate (10% solution) may also be used, but the dose is three times the amount of calcium chloride.

1) Monitor ECG continuously and at least hourly serial total or ionized calcium, magnesium, potassium levels during therapy. Suspect hypocalcemia and/or hypomagnesemia when QTc interval is prolonged.
2) Treat aggressively with intravenous calcium in the presence of any ECG or clinical signs of hypocalcemia while serum calcium levels are pending.

Eye Exposure

6.8.1)

A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).

Dermal Exposure

6.9.1)

A) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).
B) MINOR SPILL DECONTAMINATION

1) A minor spill involves small volumes, small areas, low activity of radioactive material, no volatile materials, and is one that can be readily cleaned without spreading the spill (US Nuclear Regulatory Commission, 1987).

C) MAJOR SPILL DECONTAMINATION

1) A major spill involves large volumes, large areas, high activity of radioactive material, volatile materials, contamination of body or clothing, or contamination that may spread or occur outside the lab (US Nuclear Regulatory Commission, 1987).

a) Primary consideration should be given to protection of personnel and containment of the radioactivity.
b) Notify nearby personnel of the hazard and actions to be followed. Individuals directly contaminated by a spill should immediately remove contaminated clothing and wash hands and other contaminated areas of the body. Confine all personnel potentially contaminated to an isolated area in or near lab. Secure the area of the spill to prevent entrance and further contamination.
c) Notify the institution's Radiation Safety Officer or equivalent immediately. The trained personnel will guide you on the proper clean up and management of the spill.
d) Locate decontamination kit if available.
e) Appropriate protective clothing should be worn.
f) Before beginning decontamination, assess the magnitude and extent of the spill and begin clean up of the least contaminated area and work into the most highly contaminated areas.
g) Cover the spill with absorbent paper. Spills can be cleaned up using disposable absorbant towels, working from the outside of the spill inward.
h) Thoroughly wash any contaminated sites with water and commercially available cleaners or detergents. Monitor for residual contamination and record site and levels.
i) Properly label and dispose of all materials used to clean the spill.

D) PERSONNEL PROTECTION

1) Appropriate personal protective clothing should be worn; including gloves, overshoes, laboratory coat or gown, and protective eye wear. Additional protection may also be required.

E) DISPOSAL GUIDELINES

1) The disposal of radioactive material is strictly controlled. Assure compliance with state and federal laws and regulations, as well as with institutional policies and procedures.

Abstracts

Range Of Toxicity

Summary

Therapeutic Dose

7.2.1)

A) SPECIFIC SUBSTANCE

1) CHOLINE C 11

a) The recommended dose is 370 to 740 megabecquerels (10 to 20 millicuries) IV (Prod Info choline C 11 intravenous injection, 2012).

2) CHROMIC PHOSPHATE P 32

a) NEOPLASTIC PLEURAL EFFUSION (average patient, 70 kg): 222 to 444 megabecquerels (6 to 12 millicuries) by INTRAPLEURAL instillation (Prod Info PHOSPHOCOL(R) P 32 injection suspension, 2000).
b) PERITONEAL EFFUSION, SECONDARY MALIGNANT NEOPLASTIC DISEASE (average patient, 70 kg): 370 to 740 megabecquerels (10 to 20 millicuries) by INTRAPERITONEAL instillation (Prod Info PHOSPHOCOL(R) P 32 injection suspension, 2000).
c) INTERSTITIAL INJECTION: Dose based on the estimated gram weight of the tumor. The usual dose range is 3.7 to 18.5 megabecquerels/g (0.1 to 0.5 millicuries/g) injected INTERSTITIALLY (Prod Info PHOSPHOCOL(R) P 32 injection suspension, 2000).

3) COPPER-64 CHLORIDE

a) Copper-64 chloride is NOT intended for direct patient use. It is used for the radiolabeling of carrier molecules. The effective dose from an IV injected activity of 925 megabecquerels is 65.86 millisieverts for a 60-kg woman and 88.99 millisieverts for a 70-kg man (Prod Info Cuprymina intravenous injection solution, 2012).

4) FLORBETABEN F-18

a) The recommended dose is a single slow IV bolus (6 sec/mL) of 300 megabecquerels (8.1 millicuries) in 10 mL or less total volume (Prod Info NEURACEQ(TM) intravenous injection, 2014).

5) FLORBETAPIR F-18

a) The recommended dose is 370 megabecquerels (10 millicuries) IV single bolus in 10 mL or less total volume (MAXIMUM: 50 mcg mass dose) (Prod Info Amyvid intravenous injection, 2012).

6) FLUCICLOVINE F 18

a) The recommended dose is 370 megabecquerels (10 millicuries) administered as an IV bolus injection (Prod Info AXUMIN(TM) intravenous injection, 2016).

7) FLUTEMETAMOL F-18

a) The recommended dose is 185 megabecquerels (5 millicuries) IV single bolus in 10 mL or less total volume (MAXIMUM: 20 mcg mass dose) (Prod Info VIZAMYL(TM) intravenous injection, 2013).

8) GADOTERATE MEGLUMINE

a) The recommended dose is 0.1 mmol/kg (0.2 mL/kg) administered as an IV bolus injection at a flow rate of approximately 2 mL/sec (Prod Info DOTAREM(R) intravenous injection solution, 2013).

9) IOBENGUANE I 123

a) The recommended dose is 10 millicuries IV over 1 to 2 minutes (Prod Info AdreView(TM) intravenous injection, 2013).

10) INDIUM IN 111 CAPROMAB PENDETIDE

a) The recommended dose is 0.5 mg radiolabeled with 5 millicuries of Indium In 111 chloride. Administer IV over 5 minutes; do NOT mix with any other drugs during administration (Prod Info ProstaScint(R) Kit intravenous injection, 2010).
b) Indium In 111 capromab pendetide is NOT indicated for readministration for evaluation of treatment response (Prod Info ProstaScint(R) Kit intravenous injection, 2010).

11) RADIUM Ra 223 DICHLORIDE

a) The recommended adult dose is 55 kilobecquerels/kg (1.49 microcuries/kg) by slow IV injection over 1 minute at 4-week intervals for 6 injections (Prod Info XOFIGO intravenous injection solution, 2016).

12) RUBIDIUM Rb 82 CHLORIDE

a) The recommended adult dose is 1480 megabecquerels (40 millicuries), with a range of 1110 to 2220 megabecquerels (30 to 60 millicuries); administered at 50 mL/min, not to exceed a total infusion volume of 100 mL. MAXIMUM single dose, 2220 megabecquerels (60 millicuries) (Prod Info CARDIOGEN-82(R) intravenous injection, 2012).

13) SAMARIUM SM 153 LEXIDRONAM

a) PAIN FROM BONE METASTASIS THAT IS ENHANCED ON RADIONUCLIDE BONE SCAN: 1 millicurie/kg IV over 1 minute through a secure indwelling catheter and follow with a saline flush; give a minimum of 500 mL (2 cups) of fluids either orally or IV prior to injection (Prod Info QUADRAMET(R) IV injection, 2003).

14) SODIUM IODIDE I 123

a) DIAGNOSTIC (average patient, 70 kg): The recommended dose is 3.7 to 14.8 megabecquerels (100 to 400 microcuries) ORALLY (Prod Info Sodium Iodide I 123 oral capsules, 2007).

15) SODIUM IODIDE I 131

a) HYPERTHYROIDISM: The usual recommended dose is 148 to 370 megabecquerels (4 to 10 millicuries) ORALLY; in severely hyperthyroid patients, discontinuation of antithyroid therapy 3 or 4 days prior to administration of radioiodide may be necessary (Prod Info sodium iodide I 131 oral therapeutic capsules, 2012; Prod Info HICON(TM) oral capsules, oral solution, 2011).
b) THYROID CARCINOMA: The usual recommended dose is 1850 to 7400 megabecquerels (50 to 200 millicuries) ORALLY (Prod Info sodium iodide I 131 oral therapeutic capsules, 2012; Prod Info HICON(TM) oral capsules, oral solution, 2011).

16) SODIUM PHOSPHATE P 32

a) CHRONIC LYMPHOID LEUKEMIA: 222 to 555 megabecquerels (6 to 15 millicuries) IV, with concurrent hormone manipulation (Prod Info sodium phosphate P 32 solution, 2000).
b) CHRONIC MYELOID LEUKEMIA: 222 to 555 megabecquerels (6 to 15 millicuries) IV, with concurrent hormone manipulation; do not administer if leukocyte count is below 20,000/mm(3) (Prod Info sodium phosphate P 32 solution, 2000).
c) POLYCYTHEMIA VERA: 37 to 296 megabecquerels (1 to 8 millicuries) IV; do not administer if leukocyte count is below 5000/mm(3) or platelet count is below 150,000/mm(3) (Prod Info sodium phosphate P 32 solution, 2000).

17) STRONTIUM 89

a) PAIN FROM METASTASES: 148 megabecquerels (4 millicuries) by slow IV injection over 1 to 2 minutes; alternatively, 1.5 to 2.2 megabecquerels/kg (40 to 60 microcuries/kg) may be given (Prod Info METASTRON(TM) IV injection, 2002).

18) TECHNETIUM TC 99M BESILESOMAB

a) The recommended dose is 0.25 to 1 mg (400 to 800 megabecquerels) IV (Prod Info Scintimun intravenous injection solution, 2011).

19) TECHNETIUM TC 99M SODIUM PERTECHNETATE

a) NASOLACRIMAL DRAINAGE SYSTEM: MAX dose 3.7 megabecquerels (100 microcuries) (Prod Info TechneLite(R) intravenous injection, 2014; Prod Info Ultra-TechneKow(TM) DTE intravenous injection solution, 2014).
b) SALIVARY GLAND IMAGING: The recommended dose 37 to 185 megabecquerels (1 to 5 millicuries) (Prod Info TechneLite(R) intravenous injection, 2014; Prod Info Ultra-TechneKow(TM) DTE intravenous injection solution, 2014).
c) THYROID GLAND IMAGING: The recommended dose 37 to 370 megabecquerels (1 to 10 millicuries) (Prod Info TechneLite(R) intravenous injection, 2014; Prod Info Ultra-TechneKow(TM) DTE intravenous injection solution, 2014).
d) VESICO-URETERAL: The recommended dose 18.5 to 37 megabecquerels (0.5 to 1 millicuries) (Prod Info TechneLite(R) intravenous injection, 2014; Prod Info Ultra-TechneKow(TM) DTE intravenous injection solution, 2014).

20) TECHNETIUM TC 99M TILMANOCEPT

a) MASS DOSE: The recommended dose is 50 mcg administered at least 15 minutes before initiation of intraoperative lymphatic mapping (Prod Info LYMPHOSEEK injection powder, 2014).
b) RADIOACTIVE DOSE: The recommended dose is 18.5 megabecquerels (0.5 millicuries) administered at least 15 minutes before initiation of intraoperative lymphatic mapping. Route of administration: intradermal, subQ, subareolar, and peritumoral injections (Prod Info LYMPHOSEEK injection powder, 2014).

21) THALLOUS CHLORIDE Tl 201

a) FOR MYOCARDIAL PLANAR IMAGING: Intravenous, 37 to 74 megabecquerels (1 to 2 millicuries) of thallous chloride Tl 201 (Prod Info Thallous Chloride Tl 201 Injection, 2004).
b) FOR SPECT IMAGING: Intravenous, 74 to 111 megabecquerels (2 to 3 millicuries) of thallous chloride Tl 201 (Prod Info Thallous Chloride Tl 201 Injection, 2004).

22) TOSITUMOMAB/IODINE I131

a) Dosimetric dose, days 1 through 7: 450 mg tositumomab via IV infusion; iodine I-131 tositumomab (5 millicuries I-131 and 35 mg protein) via IV infusion (Prod Info BEXXAR(R) intravenous injection, 2012).
b) Therapeutic dose, days 7 through 14: Tositumomab 450 mg via IV infusion; iodine I-131 tositumomab 35 mg via IV infusion 7 to 14 days after dosimetric dose (Prod Info BEXXAR(R) intravenous injection, 2012).
c) Platelet counts greater than or equal to 150,000 platelets/mm(3): recommended dose is Iodine 131 calculated to deliver 75 centigray units total body radiation (Prod Info BEXXAR(R) intravenous injection, 2012).
d) Platelet counts 100,000 to 149,000 platelets/mm(3): recommended dose is Iodine 131 calculated to deliver 65 centigray units total body radiation (Prod Info BEXXAR(R) intravenous injection, 2012).

23) YTTRIUM-90 CHLORIDE

a) Yttrium-90 chloride is NOT intended for direct patient use. It is used for the radiolabeling of carrier molecules. The effective dose from an IV injected activity of 1 gigabecquerel is 700 millisieverts for a 57-kg woman and 650 millisieverts for a 70-kg man (Prod Info Yttriga injection solution, 2012).

7.2.2)

A) Safety and efficacy of radiopharmaceutical agents have not been established in pediatric patients (Prod Info AXUMIN(TM) intravenous injection, 2016; Prod Info LYMPHOSEEK injection powder, 2014; Prod Info Xofigo intravenous injection, 2013; Prod Info Yttriga injection solution, 2012; Prod Info Cuprymina intravenous injection solution, 2012; Prod Info Scintimun intravenous injection solution, 2011; Prod Info choline C 11 intravenous injection, 2012; Prod Info BEXXAR(R) intravenous injection, 2012; Prod Info sodium iodide I 131 oral therapeutic capsules, 2012; Prod Info CARDIOGEN-82(R) intravenous injection, 2012; Prod Info Scintimun intravenous injection solution, 2011; Prod Info HICON(TM) oral capsules, oral solution, 2011; Prod Info ProstaScint(R) Kit intravenous injection, 2010; Prod Info Sodium Iodide I 123 oral capsules, 2007; Prod Info PHOSPHOCOL(R) P 32 injection suspension, 2000; Prod Info QUADRAMET(R) IV injection, 2003; Prod Info sodium iodide I 131 diagnostic oral capsules, 2005; Prod Info sodium phosphate P 32 solution, 2000; Prod Info METASTRON(TM) IV injection, 2002; Prod Info Thallous Chloride Tl 201 Injection, 2004).
B) FLORBETABEN F-18

1) FLORBETABEN F-18 is not indicated for use in pediatric patients (Prod Info NEURACEQ(TM) intravenous injection, 2014).

C) FLORBETAPIR F-18

1) FLORBETAPIR F-18 is not indicated for use in pediatric patients (Prod Info Amyvid intravenous injection, 2012).

D) FLUTEMETAMOL F-18

1) FLUTEMETAMOL F-18 is not indicated for use in pediatric patients (Prod Info VIZAMYL(TM) intravenous injection, 2013).

E) GADOTERATE MEGLUMINE

1) 2 YEARS OR OLDER: The recommended dose is 0.1 mmol/kg (0.2 mL/kg) administered as an IV bolus injection at a flow rate of approximately 1 to 2 mL/sec (Prod Info DOTAREM(R) intravenous injection solution, 2013).

F) IOBENGUANE I 123

1) LESS THAN 16 YEARS OF AGE AND LESS THAN 70 KG: The dose should be calculated according to patient body weight. Dose range: 1 millicurie to 9.9 millicuries (Prod Info AdreView(TM) intravenous injection, 2013).
2) LESS THAN 16 YEARS OF AGE GREATER THAN OR EQUAL TO 70 KG: The recommended dose is 10 millicuries IV over 1 to 2 minutes (Prod Info AdreView(TM) intravenous injection, 2013).

G) INDIUM IN 111 CAPROMAB PENDETIDE

1) INDIUM IN 111 CAPROMAB PENDETIDE is not indicated for use in pediatric patients (Prod Info ProstaScint(R) Kit intravenous injection, 2010).

H) TECHNETIUM TC 99M SODIUM PERTECHNETATE

1) THYROID GLAND IMAGING: The recommended dose 2.22 to 2.96 megabecquerels/kg (60 to 80 microcuries) (Prod Info TechneLite(R) intravenous injection, 2014)lym
2) VESICO-URETERAL: The recommended dose 18.5 to 37 megabecquerels (0.5 to 1 millicuries) (Prod Info TechneLite(R) intravenous injection, 2014; Prod Info Ultra-TechneKow(TM) DTE intravenous injection solution, 2014).

Minimum Lethal Exposure

Maximum Tolerated Exposure

1) A dose of sodium iodide I 131 in the range of 148 to 370 MBq (4 to 10 mCi) will cause hypothyroidism in normal patients (Prod Info IODOTOPE(R) oral capsules, 2001).

Pharmacology Toxicology

Pharmacologic Mechanism

1) Colloidal chromic phosphate P 32 introduced into a body cavity is phagocytized by free macrophages and fixed to the lining of the cavity wall, thus providing local irradiation, via beta emission, to the affected area (Hladik, 1987; Prod Info PHOSPHOCOL(R) P 32 injection suspension, 2000).

1) Samarium Sm 153 is chelated to ethylenediaminetetramethylene phosphonic acid, forming a bone-seeking diphosphonate complex that concentrates in areas of bone turnover in association with hydroxyapatite crystals (Prod Info QUADRAMET(R) IV injection, 2003).

1) Sodium iodide I 131 is concentrated and retained in the thyroid gland for the synthesis of thyroid hormones and is used diagnostically to evaluate thyroid function and for localization of metastases associated with thyroid malignancies; at larger oral doses of sodium iodide I 131, it is possible to selectively damage or destroy thyroidal tissue as required in the treatment of hyperthyroidism or thyroid carcinoma (Prod Info sodium iodide I 131 diagnostic oral capsules, 2005; Prod Info IODOTOPE(R) oral capsules, 2001)

1) Radioactive phosphorus concentrates significantly in the rapidly proliferating tissues and bone formations associated with metastatic bone tumors; subsequent, beta emission causes radiation damage to these cells (Prod Info sodium phosphate P 32 solution, 2000; Swanson, 1990)

1) Strontium-89 concentrates at skeletal metastatic sites and provides selective systemic irradiation, with minimal irradiation of distant soft tissues (Prod Info METASTRON(TM) IV injection, 2002). Palliation of pain may be secondary to radioactive emission as opposed to a pharmacological effect of elemental strontium (Lewington et al, 1991; Ackery & Yardley, 1993).

1) Thallous chloride Tl 201 accumulates in viable cells of myocardium and other tissues in a manner analogous to that of potassium. The initial distribution of thallous chloride Tl 201 is primarily related to regional perfusion. Ischemic myocardial cells take up less thallous chloride Tl 201 than nonischemic cells, in proportion to the relative change in blood flow, especially during maximal stress when the differential in perfusion is most marked between regions supplied by normal coronary arteries and those supplied by stenotic vessels. Imaging equipment can record regional differences in thallous chloride Tl 201 uptake, and thus in myocardial perfusion, confirming the presence or absence of coronary disease (Prod Info Thallous Chloride Tl 201 Injection, 2004).

Physicochemical

Physical Characteristics

Ph

Molecular Weight

Animal Toxicology

References

General Bibliography

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RADIOPHARMACEUTICALS

Classification | Detailed evidence-based information

Therapeutic Toxic Class

Specific Substances

Available Forms Sources

Life Support

Clinical Effects

Laboratory Monitoring

Treatment Overview

Range Of Toxicity

Summary Of Exposure

Vital Signs

Heent

Cardiovascular

Respiratory

Neurologic

Gastrointestinal

Hepatic

Genitourinary

Hematologic

Dermatologic

Musculoskeletal

Endocrine

Immunologic

Reproductive

Carcinogenicity

Genotoxicity

Monitoring Parameters Levels

Life Support

Patient Disposition

Monitoring

Oral Exposure

Eye Exposure

Dermal Exposure

Summary

Therapeutic Dose

Minimum Lethal Exposure

Maximum Tolerated Exposure

Pharmacologic Mechanism

Physical Characteristics

Ph

Molecular Weight

General Bibliography