Medication Guide App

Iobenguane, Radioiodinated (Systemic—Therapeutic )


VA CLASSIFICATION
Primary: AN600



A commonly used name for iobenguane is
meta-iodobenzylguanidine or mIBG .
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).

*Not commercially available in the U.S.

Not commercially available in Canada.



Category:


Antineoplastic—

Indications

Note: Because I 131 iobenguane ( 131I-mIBG) sulfate injection is not commercially available in the U.S. or Canada, the bracketed information and the use of the superscript 1 in this monograph reflect the lack of labeled (approved) indications for this product.

Accepted

[Carcinoid syndrome (treatment)]1or
[Pheochromocytoma (treatment)]1131I-mIBG is used in the treatment of pheochromocytoma and may be useful in other neuroendocrine tumors (e.g., carcinoid syndrome). {04} {06} {10} {18} {20}

[Neuroblastoma (treatment)]1131I-mIBG is used in the treatment of neuroblastomas unresponsive to conventional chemotherapy. Although complete remissions have been achieved in only a few cases, partial remissions have occurred in nearly half the reported cases in which 131I-mIBG has been used. {04} {05} {07} {09} {11} {12} {14} {26}

1 Not included in Canadian product labeling.



Physical Properties

Nuclear data:



Radionuclide
(half-life)
Decay
constant
Mode of
decay
Principal
emissions
(keV)
Mean number
of emissions/
disintegration
I 131
(8.08 days)
0.00358 h -1
Beta (90%)
Beta (191.6)
Gamma
(364.5)
0.90
0.81


Pharmacology/Pharmacokinetics

Mechanism of action/Effect:

Iobenguane or meta-iodobenzylguanidine (mIBG) is a physiological analog of the guanidines, such as guanethidine and phenethylguanidine. In adrenergic nerves, guanidines are believed to share the same transport pathway as norepinephrine and to accumulate in, and displace norepinephrine from, intraneuronal storage granules. Similarly, 131I-mIBG is concentrated in, stored in, and released from chromaffin granules. The retention of 131I-mIBG in the adrenal medulla may be a result of its uptake in adrenergic neurons and subsequent sequestration into chromaffin storage granules. Due to its selective uptake mechanism, when 131I-mIBG is used at high levels of administered activity, the radionuclidic emissions can result in localized radiation therapy of tumor tissue. {01} {02} {03} {04} {06} {10} {11} {16} {20} {24} {29}

Distribution:

After intravenous administration, there is rapid uptake of mIBG mainly in the liver, and in lesser amounts in the lungs, heart, spleen, and salivary glands. Although the uptake in normal adrenal glands is very low, hyperplastic adrenals and tumors such as pheochromocytoma, neuroblastoma, and other tumors with neurosecretory granules have a relatively higher uptake. {16} {19}

Onset of therapeutic action:

In malignant pheochromocytoma—Variable (after 1 to 8 doses). {10}

Radiation dosimetry:


Estimated absorbed radiation dose*
Organ
mGy/MBq
rad/mCi
Liver
0.83
3.07
Bladder wall
0.59
2.18
Spleen
0.49
1.81
Salivary glands
0.23
0.85
Lungs
0.19
0.70
Adrenals
0.17
0.63
Kidneys
0.12
0.44
Pancreas
0.10
0.37
Intestine wall (upper)
0.080
0.29
Uterus
0.080
0.29
Stomach wall
0.077
0.28
Small intestine
0.074
0.27
Heart
0.072
0.26
Breast
0.069
0.25
Intestine wall (lower)
0.068
0.25
Red marrow
0.067
0.25
Ovaries
0.066
0.24
Bone surface
0.061
0.23
Testes
0.059
0.22
Thyroid (blocked)
0.050
0.18
Other tissue
0.062
0.23
Effective dose: 0.20 mSv/MBq (0.74 rem/mCi)
* For adults; intravenous injection. Data based on the International Commission on Radiological Protection (ICRP) Publication 53—Radiation dose to patients from radiopharmaceuticals.
 Thyroid dose listed assumes 0% thyroid uptake. However, uptakes ranging from 0.5 to 2% are more typical; consequently the absorbed radiation dose to the thyroid will be many times higher than listed. {20}

Elimination:
    Renal; about 40 to 50% of the injected activity is eliminated within 24 hours and about 70 to 90% within 4 days (mainly as unchanged drug with small amounts of 131I-m-iodohippuric acid [ 131I-mIHA], 131I iodide, and 131I-m-iodobenzoic acid [ 131I-mIBA]). {15} {27}


Precautions to Consider

Pregnancy/Reproduction

Pregnancy—
131I-mIBG is not recommended for the treatment of disease during pregnancy.

To avoid the possibility of fetal exposure to radiation, in those circumstances where the patient's pregnancy status is uncertain a pregnancy test will help to prevent inadvertent administration of this preparation during pregnancy. {15} {29}

Breast-feeding

It is not known whether 131I-mIBG is distributed into breast milk. However, this preparation may be contaminated with free radioiodide, which may be distributed into breast milk. In addition, free radioiodide will be produced during normal metabolism. In order to decrease the absorbed radiation dose to the breast and to avoid risk to the infant, complete cessation of nursing is recommended after 131I-mIBG is administered. {20} {21} {22} {23} {29}

Pediatrics

131I-mIBG is used in children; however, the therapeutic benefit should be judged to outweigh the potential risk of radiation. {07} {08} {09} {12} {15} {17} {20}


Geriatrics


Treatment performed to date has not demonstrated geriatrics-specific problems that would limit the usefulness of 131I-mIBG in the elderly.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

» Amphetamines or
» Antidepressants, tricyclic or
» Bretylium or
» Calcium channel blocking agents or
» Cocaine or
» Guanethidine or
» Haloperidol or
» Labetalol or
» Loxapine or
» Metaraminol or
» Phenothiazines or
» Reserpine or
» Sympathomimetics or
» Thiothixene    (these medications may interfere with the uptake of 131I-mIBG; although the ideal amount of time to stop treatment with potential interacting medicines is 1 week prior to administration of 131I-mIBG, the following withdrawal periods are usually recommended based on the individual half-life of each medication: 24 hours for bretylium, cocaine, and metaraminol; 48 hours for amphetamines, calcium channel blocking agents, guanethidine, haloperidol, loxapine, tricyclic antidepressants, phenothiazines, sympathomimetics, and thiothixene; 72 hours for labetalol and reserpine {01} {25})


Blood dyscrasia–causing medications (See Appendix II )    (leukopenic and/or thrombocytopenic effects of 131I-mIBG may be increased with concurrent or recent therapy with these medications)


Bone marrow depressants, other (See Appendix II )    (concurrent use of bone marrow depressants with 131I-mIBG may increase leukopenic and/or thrombocytopenic effects {10})


Chemotherapy and/or
Radiation therapy    (previous chemotherapy and/or radiotherapy may impair effectiveness of 131I-mIBG therapy {12})



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With physiology/laboratory test values
Alanine aminotransferase (ALT [SGPT]), serum and
Aspartate aminotransferase (AST [SGOT]), serum    (concentrations may be increased {10})


Catecholamines, urinary    (concentration may be increased transiently {10})



Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence rare
    
Leukopenia and thrombocytopenia {09}{10}{24}{26}(pale skin, sore throat and fever, unusual bleeding or bruising, unusual tiredness or weakness)



Those indicating need for medical attention only if they continue or are bothersome
Incidence less frequent or rare
    
Flushing of skin
    
nausea
    
slight and transient increase in blood pressure{10}{24}





Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Iobenguane, Radioiodinated (Therapeutic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Description of use
Action in the body: Localization of 131I-mIBG in adrenal medulla and neuroendocrine tumors; large doses are used therapeutically to damage or destroy tissue in management of adrenal carcinoma, pheochromocytomas, and other neuroendocrine tumors

Before using this medication
»   Conditions affecting use, especially:

Pregnancy—Use not recommended because of risk to fetus {29} from radiation exposure





Breast-feeding—Not known if distributed into breast milk; however, free radioiodide, if present, may be distributed; cessation of nursing is recommended because of risk to infant from radiation exposure {29}





Use in children—Benefit derived from treatment should be judged to outweigh potential risk of radiation

Other medications, especially amphetamines, tricyclic antidepressants, bretylium, calcium channel blocking agents, cocaine, guanethidine, haloperidol, labetalol, loxapine, phenothiazines, reserpine, sympathomimetics, and thiothixene

Proper use of this medication
Special preparatory instructions may apply; patient should inquire in advance

Administration of potassium iodide or Lugol's solution to block thyroid uptake of radioiodide contaminants before and for several weeks after treatment {29}


Side/adverse effects
Signs of potential side effects, especially leukopenia and thrombocytopenia


General Dosing Information
Radiopharmaceuticals are to be administered only by or under the supervision of physicians who have had extensive training in the safe use and handling of radioactive materials and who are authorized by the Nuclear Regulatory Commission (NRC) or the appropriate Federal or Agreement State agency, if required, or, outside the U.S., the appropriate authority.

To minimize uptake of radioactive iodine by the thyroid, potassium iodide (SSKI, 60 mg twice a day) or Lugol's solution (1 drop three times a day) may be used, beginning at least 24 hours before and continuing for at least 4 weeks after therapy with 131I-mIBG. {01} {13} {20} {24} {25} {29}

When 131I-mIBG is used for the treatment of pheochromocytoma, concurrent use of an alpha-adrenergic blocking agent, such as phenoxybenzamine is recommended to control episodes of hypertension. {20} {24} {29}

Following administration of 131I-mIBG the patient should be observed for possible reactions; competent personnel and emergency facilities should be available during this period. {24}

Safety considerations for handling this radiopharmaceutical
Improper handling of this radiopharmaceutical may cause radioactive contamination. Guidelines for handling radioactive material have been prepared by scientific, professional, state, federal, and international bodies and are available to the specially qualified and authorized users who have access to radiopharmaceuticals. {30}


Parenteral Dosage Forms

Note: Because I 131 iobenguane ( 131I-mIBG) sulfate injection is not commercially available in the U.S. or Canada, the bracketed information and the use of the superscript 1 in the Dosage Forms section reflect the lack of labeled (approved) indications for this product.


I 131 IOBENGUANE SULFATE INJECTION

Usual adult administered activity
[Treatment of malignant pheochromocytoma]1
A safe and effective dosage has not been established. However, dosages in the range of 2.9 to 9.25 gigabecquerels (80 to 250 millicuries) of 131I-mIBG, with a specific activity of 103.6 to 199 megabecquerels (2.8 to 5.38 millicuries) per mg (at time of calibration), administered by slow intravenous infusion over a 20- to 30-second period every three to six months, have been used. {01} {10} {20} {24}


Usual pediatric administered activity
[Treatment of neuroblastoma]1
A safe and effective dosage has not been established for children up to 18 years of age. However, dosages in the range of 2.6 to 6.8 gigabecquerels (70 to 184 millicuries), administered in two fractions by slow (four to eight hours) intravenous infusion at two- to four-day intervals have been used. {29}

Note: Dosages ranging from 1.3 to 8 gigabecquerels (35 to 215 millicuries) have also been used. {05} {09} {14}



Usual geriatric administered activity
See Usual adult administered activity .

Strength(s) usually available
U.S.—
Not commercially available for therapeutic use. In most cases, may be obtained from the University of Michigan Nuclear Pharmacy (UMNP) by physicians who have filed their own Investigational New Drug Application (IND). {29}

Canada—
Not commercially available. In most cases, may be obtained by physicians who have filed their own IND. {29}

Packaging and storage:
Store between 2 and 8 °C (35.6 and 46.4 °F), but preferably between -20 and -10 °C (-4 and -14 °F), unless otherwise specified by manufacturer. {01}

Note: Caution—Radioactive material.




Revised: 08/02/1994



References
  1. Information packets for potential investigators, University of Michigan Nuclear Pharmacy 1990.
  1. Adolph JM, Kimmig BN, Georgi P, et al. Carcinoid tumors: CT and I-131 meta-iodobenzylguanidine scintigraphy. Radiology 1987; 164(1): 199-203.
  1. Beierwaltes WH. Endocrine imaging: part II. J Nucl Med 1991; 32(8): 1634-8.
  1. Beierwaltes WH. Applications of [I 131]m-iodobenzylguanidine ([I 131]MIBG). Int J Rad Appl Instrum [B] 1987; 14(3): 183-9.
  1. Beierwaltes WH. Treatment of neuroblastoma with 131 I-MIBG: dosimetric problems and perspectives. Med Pediatr Oncol 1987; 15(4): 188-91.
  1. Beierwaltes WH. Update on basic research and clinical experience with metaiodobenzylguanidine. Med Pediatr Oncol 1987; 15(4): 163-9.
  1. Edeling CJ, Frederiksen PB, Kamper J, et al. Diagnosis of neuroblastoma using metaiodobenzylguanidine. Clin Nucl Med 1987; 12(8): 632-7.
  1. Feine U, Müller-Schauenburg W, Treuner J, et al. Metaiodobenzylguanidine (MIBG) labeled with 123 I/131 I in neuroblastoma diagnosis and follow-up treatment with a review of the diagnostic results of the International Workshop of Pediatric Oncology held in Rome, Sept 1986. Med Pediatr Oncol 1987; 15(4): 181-7.
  1. Hartmann O, Lumbroso J, Lemerle J, et al. Therapeutic use of 131 I-metaiodobenzylguanidine (MIBG) in neuroblastoma: a phase II study in nine patients. Med Pediatr Oncol 1987; 15(4): 205-11.
  1. Krempe M, Lumbroso J, Mornex R, et al. Use of m-[ 131I]iodobenzylguanidine in the treatment of malignant pheochromocytoma. J Clin Endocrinol Metab 1991; 72: 455-61.
  1. Maisey MN, Britton KE, Gilday DL. Clinical nuclear medicine. 2nd ed. Philadelphia: J.B. Lippincott, 1991: 31.
  1. Sanguineti M. Considerations on 131 I-metaiodobenzylguanidine therapy of six children with neuroblastoma. Med Pediatr Oncol 1987; 15(4): 212-5.
  1. Ferris J, Caballero O, Verdeguer A, et al. 131I-MIBG-meta-iodobenzylguanidine ( 131I-MIBG) in the study of neuroblastoma. An Esp Pediatr 1987; 26(3): 164-70.
  1. Troncone L, Riccardi R, Montemaggi P, et al. Treatment of neuroblastoma with 131 I-metaiodobenzylguanidine. Med Pediatr Oncol 1987; 15(4): 220-3.
  1. USP Radiopharmaceuticals Advisory Panel comments as of meeting on 05/08/91.
  1. Task Group of Committee 2 of the International Commission on Radiological Protection. Annals of the ICRP. ICRP Publication 53—Radiation dose to patients from radiopharmaceuticals. New York: Pergamon Press, 1988: 61.
  1. van der Steen J, Maessen HJ, Hoefnagel CA, et al. Radiation protection during treatment of children with 131 I-meta-iodobenzylguanidine. Health Phys 1986; 50(4): 515-22.
  1. Shapiro B, Sisson JC, Eyre P, et al. 131 I-MIBG—a new agent in diagnosis and treatment of pheochromocytoma. Cardiology 1985; 72(Suppl 1): 137-42.
  1. Nakajo M, Shapiro B, Sisson JC, et al. Salivary gland accumulation of meta-[ 131I]iodobenzylguanidine. J Nucl Med 1984; 25(1): 2-6.3
  1. USP Radiopharmaceuticals Advisory Panel comments during meeting of 08/04/92.
  1. Romney BM, et al. Excretion of radioiodine in breast milk (editoral). J Nucl Med 1989; 30: 124-6.
  1. Blue PW, Dydek GJ. Excretion of radioiodine in breast milk (letter). J Nucl Med 1989; 30: 127-8.
  1. Mountford PJ, Coakley AJ. A review of the secretion of radioactivity in human breast milk: data, quantitative analysis and recommendations. Nucl Med Commun 1989; 10: 15-27.
  1. McEwan AJ, Shapiro B, Sisson JC, et al. Radio-iodobenzylguanidine for the scintigraphic location and therapy of adrenergic tumors. Semin Nucl Med 1985; 15(2): 132-53.
  1. Solanki KK, Bomanji J, Moyes J, et al. A pharmacological guide to medicines which interfere with the biodistribution of radiolabelled meta-iodobenzylguanidine (MIBG). Nucl Med Commun 1992; 13: 513-21.
  1. Treuner J, Klingebiel T, Bruchelt G, et al. Treatment of neuroblastoma with metaiodobenzylguanidine: results and side effects. Med Pediatr Oncol 1987; 15(4): 199-202.
  1. Oishi S, Sasaki M, Sato T, et al. Imaging and uptake mechanism of 131 I-meta-iodobenzylguanidine in medullary thyroid carcinoma. Endocrinol Jpn 1986; 33(3): 309-15.
  1. Mangner TJ, Tobes MC, Wieland DW, et al. Metabolism of iodine-131 metaiodobenzylguanidine in patients with metastatic pheochromocytoma. J Nucl Med 1986; 27(1): 37-44.
  1. Reviewers' comments, 08/11/92 monograph revision.
  1. Reviewers' responses to Ballot of 5/11/94.
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