iobenguane I 123

Iobenguane I 123 is a diagnostic radiopharmaceutical agent used as an adjunct to other tests to detect primary or metastatic pheochromocytoma or neuroblastoma, types of tumors that secrete the hormones (catecholamines) epinephrine and norepinephrine, and to evaluate heart function in patients with congestive heart failure. Iobenguane I 123 is an intravenously administered radioactive drug that accumulates in tissues stimulated by these catecholamines, and images are captured with a medical device in a procedure known as gamma scintigraphy.

Pheochromocytoma and neuroblastoma are neuroendocrine tumors that secrete extra epinephrine and norepinephrine, the neurotransmitters in the sympathetic nervous system that drive the fight-or-flight response, increasing the heart rate, blood pressure, blood sugar and metabolism to deal with stress. Excessive secretions of catecholamines by these tumors keep these parameters high increasing the risk for associated cardiovascular and other diseases. A small percentage of tumors may turn malignant and spread to other organs.

Iobenguane has a structure similar to norepinephrine and undergoes uptake and accumulation in the same tissues such as adrenal medulla, heart, liver, lungs, salivary glands, and spleen, as well as the norepinephrine-secreting tumors. The addition of radioactive chemical (radionuclide) iodine 123 to iobenguane helps in the imaging of the areas where iobenguane accumulates, and the detection of neuroendocrine tumors. Iobenguane is used with iodine-123, at low dosage, for diagnosing, and with iodine-131, a higher dosage, for destroying tumor cells.

FDA-approved uses of iobenguane I 123 include:

• Detection of primary or metastatic pheochromocytoma or neuroblastoma
• Assessment of the heart muscle (myocardial) sympathetic innervation in patients with congestive heart failure and left ventricle ejection fraction of 35% or less, and their mortality risk.

• Do not use iobenguane in patients with hypersensitivity to any component of the formulation.
• There have been reports of hypersensitivity reactions. Use with extreme caution in patients with iodine or iodine-contrast agent hypersensitivity. Keep required emergency medications and equipment readily available, should a patient have such reactions.
• Iobenguane I 123 emits radiation and must be handled with appropriate safety measures to minimize exposure to the patients and the medical personnel. Radiopharmaceutical drugs should only be used by physicians qualified with specific training in their use.
• Advise patients to hydrate well to promote frequent urination and minimize radiation dose to the bladder.
• Administer thyroid blockade medications, at least one hour before administering iobenguane I 123 to reduce the risk of thyroid accumulation of the drug and long-term risk of thyroid tumor (neoplasia).
• Many medications can interfere with iobenguane I 123 leading to false negative imaging results. Review the patient’s medications and, if clinically feasible, discontinue these drugs before administering iobenguane I 123.
• Radiation exposure may be increased in patients with severe impairment of kidney function, due to delayed elimination of the drug, and may also affect the quality of the scintigraphic images.
• Iobenguane I 123 contains benzyl alcohol which can cause serious and sometimes fatal reactions known as “gasping syndrome” in newborn babies, a condition that leads to metabolic acidosis with respiratory distress, gasping respirations, central nervous system (CNS) depression and hypotension.
• Conditions that affect the sympathetic nervous system such as Parkinson’s disease or multiple system atrophy can cause imaging errors because they may show decreased uptake of iobenguane I 123 independent of heart disease.
• Iobenguane I 123 can increase norepinephrine release and cause transient hypertension. Monitor the patient’s pulse and blood pressure before and for 30 minutes following administration of iobenguane I 123. Keep emergency cardiac and anti-hypertensive treatments readily available.
• Evaluate pregnancy status in women of pregnancy potential before administering iobenguane I 123, and apprise them of the potential risks to the fetus from radiation exposure.

Common side effects of iobenguane I 123 include:

• Injection site reactions including:
  • Bruising
  • Blood pooling and clotting (hematoma)
  • Bleeding (hemorrhage)
• Dizziness
• Flushing
• Skin rash
• Itching (pruritus)
• Headache
• Transient high blood pressure (hypertension)
• Hypersensitivity reactions (rare)

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Intravenous (IV) Solution

• 2 mCi/mL at calibration time (0.08 mg/mL iobenguane sulfate 74 MBq/mL of I 123)

Gamma Scintigraphy

Diagnostic radiopharmaceutical agent for gamma-scintigraphy

Pheochromocytoma or neuroblastoma

• Indicated for detection of primary or metastatic pheochromocytoma or neuroblastoma as an adjunct to other diagnostic tests
• 10 mCi (5 mL; 370 MBq) IV
• Begin whole body planar scintigraphy imaging 24 ± 6 hours following administration

Congestive heart failure

• Indicated for assessment of myocardial sympathetic innervation in patients with The New York Heart Association [NYHA] class 2-3 heart failure with a left ventricle ejection fraction [LVEF] below 35%; among these patients, may help identify those with lower 1 and 2 year mortality risks as indicated by an H/M ratio 1.6 or lower
• 10 mCi (5 mL; 370 MBq) IV (2 mCi/mL at calibration time)
• Begin anterior planar imaging of the chest at 4 hours (± 10 minutes) following administration

Pediatric:

Gamma Scintigraphy

• Indicated for detection of primary or metastatic pheochromocytoma or neuroblastoma as an adjunct to other diagnostic tests, and also for assessment of myocardial sympathetic innervation in patients with NYHA class 2-3 heart failure with an LVEF below 35%
• Pheochromocytoma or neuroblastoma: Begin whole body planar scintigraphy imaging 24 (± 6 hours) following administration
• CHF: Begin anterior planar imaging of the chest at 4 hours (± 10 minutes) following administration

Neonates <1 month: Safety and efficacy not established

Children below 16 years and weight 70 kg or more

• 10 mCi (5 mL; 370 MBq)

Children below 16 years (3-18 kg)

• 3 kg: 1 mCi (37 MBq)
• 4 kg: 1.4 mCi (52 MBq)
• 6 kg: 1.9 mCi (70 MBq)
• 8 kg: 2.3 mCi (85.1 MBq)
• 10 kg: 2.7 mCi (99.9 MBq)
• 12 kg: 3.2 mCi (118.4 MBq)
• 14 kg: 3.6 mCi (133.2 MBq)
• 16 kg: 4 mCi (148 MBq)
• 18 kg: 4.4 mCi (162.8 MBq)

Children below 16 years (20-40 kg)

• 20 kg: 4.6 mCi (170.2 MBq)
• 22 kg: 5 mCi (185 MBq)
• 24 kg: 5.3 mCi (196.1 MBq)
• 26 kg: 5.6 mCi (207.2 MBq)
• 28 kg: 5.8 mCi (214.6 MBq)
• 30 kg: 6.2 mCi (229.4 MBq)
• 32 kg: 6.5 mCi (240.5 MBq)
• 34 kg: 6.8 mCi (251.6 MBq)
• 36 kg: 7.1 mCi (262.7 MBq)
• 38 kg: 7.3 mCi (270.1 MBq)
• 40 kg: 7.6 mCi (281.2 MBq)

Children below 16 years (42-50 kg)

• 42 kg: 7.8 mCi (288.6 MBq)
• 44 kg: 8 mCi (296 MBq)
• 46 kg: 8.2 mCi (303.4 MBq)
• 48 kg: 8.5 mCi (314.5 MBq)
• 50 kg: 8.8 mCi (325.6 MBq)

Children below 16 years (52 kg to under 70 kg)

• 52-54 kg: 9 mCi (333 MBq)
• 56-58 kg: 9.2 mCi (340.4 MBq)
• 60-62 kg: 9.6 mCi (355.2 MBq)
• 64-66 kg: 9.8 mCi (362.6 MBq)
• 68 kg: 9.9 mCi (366.3 MBq)

Administration

• Administer IV over 1-2 minutes, then flush with 0.9% sodium chloride (NaCl) to ensure full dose delivery

Radiation safety

• Emits radiation and must be handled with appropriate safety measures to minimize radiation exposure to clinical personnel and patients
• Minimize bladder exposure by encouraging hydration before and after to permit frequent voiding, particularly for the first 48 hours after administration

Thyroid blockade

• Administer potassium iodide oral solution or Lugol’s solution (equivalent to 100 mg iodide for adults, body-weight adjusted for children) or potassium perchlorate (400 mg for adults, body-weight adjusted for children) to block uptake of iodine 123 by the patient’s thyroid
• Individualize according to the patient; blockade may not be needed for patients who have undergone thyroidectomy or those with limited life expectancy

Overdose

Iobenguane I 123 overdose primarily involves increased radiation exposure resulting in the expected radiation adverse effects. Overdose also increases the long term risk for tumor growth (neoplasia).

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Iobenguane I 123 has severe interactions with at least 32 different drugs.
• Serious interactions of iobenguane I 123 include:
  • methylphenidate
  • pseudoephedrine
• Iobenguane I 123 has no listed moderate interactions with other drugs.
• Iobenguane I 123 has no listed mild interactions with other drugs.

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

Any radioactive iodine product, including iobenguane I 123 can cause fetal harm and should be administered to a pregnant woman only if clearly needed. Appropriate thyroid-blocking agent must be used to protect the mother and fetus from accumulation of I 123.

Iodine 123 is present in breast milk. Depending on the importance of the drug to the mother, administration of iobenguane I 123 should be avoided in nursing mothers, or nursing should be interrupted for 6 days after administration of iobenguane I 123, to minimize the risks to breastfed infants.

Start increasing your fluid intake before administration of iobenguane I 123 and continue to maintain high levels of hydration to promote frequent urination for the first 48 hours after administration of the drug.

Notify your physician immediately if you develop hypersensitivity reactions.