Iobenguane I 131 (Monograph)

Drug class: Antineoplastic Agents
- Radiopharmaceutical
Chemical name: (m-[131I]Iodobenzyl)guanidine
Molecular formula: (C₈H₁₀131IN₃)₂•H₂SO₄
CAS number: 77679-27-7

Medically reviewed by Drugs.com on Jan 17, 2024. Written by ASHP.

Introduction

Highly specific radiopharmaceutical; an iodine I 131 radiolabeled synthetic norepinephrine analog (iobenguane; also referred to as metaiodobenzylguanidine [MIBG]).

Uses for Iobenguane I 131

Pheochromocytoma and Paraganglioma

Treatment of iobenguane scan-positive unresectable, locally advanced, or metastatic pheochromocytoma or paraganglioma in patients who require systemic cytotoxic chemotherapy (designated an orphan drug by FDA for these cancers).

Efficacy based on ≥50% reduction in antihypertensive therapy for ≥6 months in 25% of patients who received at least one therapeutic dose of iobenguane I 131.

Iobenguane I 131 Dosage and Administration

General

• Consult specialized references for procedures for proper handling (i.e., use of waterproof gloves, shields, tongs) and disposal of radiopharmaceuticals.

• Use only by qualified clinicians (i.e., authorized by an appropriate regulatory agency) experienced in the safe use and handling of radiopharmaceuticals.

• To minimize risk of radiation-induced hypothyroidism or thyroid neoplasm, initiate a thyroid protective agent (i.e., potassium iodide) ≥24 hours prior to each dosimetric and therapeutic dose of iobenguane I 131 and continue for 10 days after each dose. (See Hypothyroidism under Cautions.)

• To minimize risk of nausea and vomiting, administer an antiemetic 30 minutes prior to each dose of iobenguane I 131.

• To minimize irradiation to the bladder, maintain adequate hydration with ≥2 liters of fluids daily starting ≥1 day prior to and continuing for 1 week after each dose.

Administration

IV Administration

Dosimetric dose: Administer by IV injection.

Therapeutic dose: Administer by IV infusion.

Observe standard precautions for minimizing risk of radiation exposure (i.e., use of waterproof gloves, shielding, tongs).

Confirm level of radioactivity in vial(s) containing iobenguane I 131 with an appropriate calibrated radioactivity measurement system prior to and after administration of the radiopharmaceutical.

Injection concentrate must be diluted prior to IV administration.

Consult manufacturer’s labeling and dosing and administration guide for detailed information on infusion system requirements (e.g., components, set-up) and procedures for IV infusion of therapeutic doses of iobenguane I 131.

Discard administration sets and any partially used vials according to local and federal regulations.

Dilution (Dosimetric Dose)

Completely thaw frozen solutions of iobenguane I 131 at room temperature for approximately 90 minutes in the lead shielded container; do not use heat sources or refreeze vial(s). (See Storage under Stability.)

Mix injection concentrate by gentle swirling to ensure homogeneity.

Insert venting needle (or other suitable venting device) with a 0.2-µm filter and charcoal filter into vial labeled for dosimetric use; gently swirl vial to ensure homogeneity of the injection concentrate.

Add appropriate volume of 0.9% sodium chloride injection to the dosimetric dose vial labeled as containing 15 mCi/mL (equivalent to 555 MBq/mL) of iobenguane I 131 to achieve a final radioactive concentration of 1 mCi/mL (equivalent to 37 MBq/mL). Gently swirl vial.

Withdraw appropriate amount of diluted iobenguane I 131 solution using a 10-mL shielded syringe. Confirm level of radioactivity is within 10% of dose.

Dilution (Therapeutic Dose)

Completely thaw frozen solutions of iobenguane I 131 at room temperature for approximately 90 minutes in the lead shielded container; do not use heat sources or refreeze vial(s). (See Storage under Stability.)

Mix injection concentrate by gentle swirling to ensure homogeneity.

Insert venting needle (or other suitable venting device) with a 0.2-µm filter and charcoal filter into each of the required number of vials labeled for therapeutic use; gently swirl each vial to ensure homogeneity of the injection concentrate.

Insert another venting needle (or other suitable venting device) into an empty sterile 50-mL glass vial. Transfer entire contents of 2 vials labeled as containing iobenguane I 131 for therapeutic use to the glass vial and confirm level of radioactivity.

If radioactivity of iobenguane I 131 in the glass vial exceeds the therapeutic dose, withdraw appropriate volume of injection concentrate from the vial using a shielded syringe and then add an appropriate volume of 0.9% sodium chloride injection to the glass vial to achieve a final admixture volume of 50 mL.

If radioactivity of iobenguane I 131 in the glass vial is less than the therapeutic dose, withdraw appropriate volume of iobenguane I 131 injection concentrate from a third vial labeled as containing iobenguane I 131 for therapeutic use using a shielded syringe and add to glass vial along with an appropriate volume of 0.9% sodium chloride injection to achieve a final admixture volume of 50 mL.

Gently swirl the glass vial.

Confirm level of radioactivity is within 10% of dose.

Rate of Administration

Dosimetric dose: Administer by IV injection over 60 seconds.

Therapeutic dose (pediatric patients ≥12 years of age): Administer by IV infusion at a rate of 50 mL/hour over 60 minutes.

Therapeutic dose (adults): Administer by IV infusion at a rate of 100 mL/hour over 30 minutes.

Dosage

A single dosimetric dose (for confirmation of tumor avidity and individualization of the therapeutic dosage) must be administered prior to administration of the initial therapeutic dose.

Pediatric Patients

Pheochromocytoma and Paraganglioma

Dosimetric Dose

IV

Children ≥12 years of age who weigh ≤50 kg: 0.1 mCi/kg (equivalent to 3.7 MBq/kg).

Children ≥12 years of age who weigh >50 kg: 5–6 mCi (equivalent to 185–222 MBq).

Following administration of a single dosimetric dose, use dosimetry schema (e.g., internal dosimetry schema of the Medical Internal Radiation Dose [MIRD] Committee of the Society of Nuclear Medicine) to calculate the estimated radiation dose to normal organs and tissues per unit activity (D_organ) using combined data from the imaging studies described in Table 1. Use patient-specific organ masses (estimated from imaging) when possible.

Use same gamma camera and imaging parameters (other than scanning rate).

Therapeutic Dose

IV

Administer a total of 2 therapeutic doses ≥90 days apart. For ANC <1200/mm³ or platelet counts <80,000/mm³, withhold first therapeutic dose.

Children ≥12 years of age who weigh ≤62.5 kg: 8 mCi/kg (equivalent to 296 MBq/kg).

Children ≥12 years of age who weigh >62.5 kg: 500 mCi (equivalent to 18,500 MBq).

Dosage adjustment based on estimated absorbed dose to critical organs may be necessary.

If estimated absorbed dose to critical organs (calculated by multiplying D_organ by the cumulative activity of 2 therapeutic doses [Aw]) is less than the absorbed dose threshold for radiation toxicity to critical organs (T_organ) (see Table 2), no dosage adjustment is necessary. If estimated absorbed dose to a critical organ exceeds T_organ, reduction of cumulative activity of 2 therapeutic doses (Aw) is necessary. Calculate adjusted Aw using the following formula.

Formula for Reduced Cumulative Therapeutic Activity (Aw):

Reduced cumulative therapeutic activity (in mCi) = Aw × (T_organ ÷ [Aw × D_organ]) (where Aw is in mCi, T_organ is in Gy, and D_organ is in Gy/mCi)

Dosage Modification for Toxicity

Follow recommendations for dosage modification for toxicity in adults.

Adults

Pheochromocytoma and Paraganglioma

Dosimetric Dose

IV

Adults weighing ≤50 kg: 0.1 mCi/kg (equivalent to 3.7 MBq/kg).

Adults weighing >50 kg: 5–6 mCi (equivalent to 185–222 MBq).

Following administration of a single dosimetric dose, use dosimetry schema (e.g., internal dosimetry schema of the MIRD Committee) to calculate the estimated radiation dose to normal organs and tissues per unit activity (D_organ) using combined data from the imaging studies described in Table 1. Use patient-specific organ masses (estimated from imaging) when possible.

Therapeutic Dose

IV

Administer a total of 2 therapeutic doses ≥90 days apart. For ANC <1200/mm³ or platelet counts <80,000/mm³, withhold first therapeutic dose.

Body weight ≤62.5 kg: 8 mCi/kg (equivalent to 296 MBq/kg).

Body weight >62.5 kg: 500 mCi (equivalent to 18,500 MBq).

Dosage adjustment based on estimated absorbed dose to critical organs may be necessary.

If estimated absorbed dose to critical organs (calculated by multiplying D_organ by the cumulative activity of 2 therapeutic doses [Aw]) is less than the absorbed dose threshold for radiation toxicity to critical organs (T_organ) (see Table 2), no dosage adjustment is necessary. If estimated absorbed dose to a critical organ exceeds T_organ, reduction of cumulative activity of 2 therapeutic doses (Aw) is necessary. Calculate adjusted Aw using the following formula.

Formula for Reduced Cumulative Therapeutic Activity (Aw):

Reduced cumulative therapeutic activity (in mCi) = Aw × (T_organ ÷ [Aw × D_organ]) (where Aw is in mCi, T_organ is in Gy, and D_organ is in Gy/mCi)

Dosage Modification for Toxicity

Hematologic Toxicity

IV

If hematologic toxicity occurs following the first therapeutic dose of iobenguane I 131, reduce second therapeutic dose based on method used to individualize the first therapeutic dose (i.e., weight-based, adjusted for critical organ limits).

If platelet count <25,000/mm³ or platelet count <50,000/mm³ with active bleeding occurs following the first therapeutic dose of iobenguane I 131, interrupt therapy until platelet counts improve to normal values or baseline; therapy may then be resumed at a reduced dosage (see Table 3).

If ANC <500/mm³ or febrile neutropenia occurs following the first therapeutic dose of iobenguane I 131, interrupt therapy until ANC improves to normal values or baseline; therapy may then be resumed at a reduced dosage (see Table 3).

If life-threatening anemia lasting >7 days occurs following the first therapeutic dose of iobenguane I 131, interrupt therapy until anemia improves to normal values or baseline; therapy may then be resumed at a reduced dosage (see Table 3).

Pneumonitis

IV

If pneumonitis occurs after the first therapeutic dose, do not administer the second therapeutic dose. (See Pneumonitis under Cautions.)

Prescribing Limits

Pediatric Patients

Pheochromocytoma and Paraganglioma

IV

Maximum of 2 therapeutic doses.

Adults

Pheochromocytoma and Paraganglioma

IV

Maximum of 2 therapeutic doses.

Special Populations

Hepatic Impairment

No specific dosage recommendations. (See Hepatic Impairment under Cautions.)

Renal Impairment

Mild to moderate renal impairment (Cl_cr 30–89 mL/minute): Adjust first therapeutic dose based on estimated absorbed dose to critical organs. Monitor renal function more frequently. (See Renal Impairment under Cautions.)

Severe renal impairment (Cl_cr <30 mL/minute) or end-stage renal disease: Not studied.

Geriatric Patients

No specific dosage recommendations. (See Geriatric Use under Cautions.)

Related/similar drugs

propranolol, labetalol, Inderal, phentolamine, Normodyne, Trandate, Azedra

Cautions for Iobenguane I 131

Contraindications

• Manufacturer states none known.

Warnings/Precautions

Radiation Exposure

Radioactive component of iobenguane I 131 (I 131) contributes to a patient's lifetime cumulative radiation exposure. Development of new malignancies is a known risk of long-term radiation exposure. Increased risk of developing new malignancies in pediatric patients. (See Myelodysplastic Syndrome [MDS], Acute Leukemia, and Other Malignancies and also see Pediatric Use under Cautions.)

Employ institutional good radiation safety practices and patient management procedures during and after administration of iobenguane I 131 to minimize exposure of patients, medical personnel, and household contacts to radiation.

Hematologic Effects

Severe and prolonged adverse hematologic effects (e.g., anemia, neutropenia, thrombocytopenia), including febrile neutropenia, reported. Median time to nadir neutrophil count in patients experiencing grade 4 neutropenia was 36–43 days; median time to improvement to grade 3 or less was 12–18.5 days.

Monitor CBC counts prior to initiation of therapy and weekly for up to 12 weeks following each therapeutic dose. Treatment delay followed by dosage reduction may be required if hematologic toxicity occurs; monitor CBC counts until hematologic parameters recover to baseline or normal range. (See Hematologic Toxicity under Dosage and Administration.)

Myelodysplastic Syndrome (MDS), Acute Leukemia, and Other Malignancies

MDS and acute leukemia reported in patients who received ≥1 therapeutic dose of iobenguane I 131; time to occurrence was 12 months to 7 years.

New primary colon cancer and adenocarcinoma of the lung individually reported in one patient each following the first therapeutic dose of iobenguane I 131; time to occurrence of colon cancer or lung adenocarcinoma was 18 and 27 months, respectively.

Hypothyroidism

New-onset or worsening hypothyroidism reported in patients who received ≥1 therapeutic dose of iobenguane I 131. In one patient with preexisting hypothyroidism, worsening of hypothyroidism occurred in 4 months. Time to development of new-onset hypothyroidism was <1 month to 18 months.

Initiate a thyroid protective agent (i.e., potassium iodide) ≥24 hours prior to each dosimetric or therapeutic dose and continue for 10 days following each dose.

Monitor patients for manifestations of hypothyroidism. Assess thyroid function (e.g., TSH) prior to initiation of therapy and indefinitely once a year thereafter.

Hypertension

Worsening hypertension (SBP ≥160 mm Hg with a 20-mm Hg increase from baseline or DBP ≥100 mm Hg with a 10-mm Hg increase from baseline) reported, generally ≤24 hours following completion of iobenguane I 131 infusion.

Monitor BP frequently for the first 24 hours after each therapeutic dose of iobenguane I 131.

Renal Effects

Renal failure or acute kidney injury following ≥1 therapeutic dose of iobenguane I 131 reported. Clinically important decreases in GFR at 6 or 12 months also reported.

Increased risk of nephrotoxicity in patients with preexisting renal impairment.

Monitor renal function more frequently in patients with mild or moderate renal impairment.

Pneumonitis

Fatal pneumonitis reported in one patient 9 weeks following administration of a single dose of iobenguane I 131.

Monitor patients for manifestations of pneumonitis (e.g., cough, dyspnea, difficulty breathing) and treat as clinically indicated. If pneumonitis occurs following the first therapeutic dose of iobenguane I 131, do not administer the second therapeutic dose.

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm. No available data on use in pregnant women.

Verify pregnancy status prior to initiating therapy.

Avoid pregnancy during therapy. Females of reproductive potential should use an effective method of contraception while receiving iobenguane I 131 and for 7 months after the final dose. Men who are partners of such women should use effective contraception during therapy and for 4 months after the final dose.

If used during pregnancy or if patient becomes pregnant while receiving the drug, apprise patient of potential fetal hazard. (See Advice to Patients.)

Impairment of Fertility

May impair male and female fertility.

Specific Populations

Pregnancy

May cause fetal harm. (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Lactation

Not known whether iobenguane I 131 distributes into milk. Effects on nursing infants and milk production also unknown. Discontinue nursing during therapy and for 80 days after the final dose.

Pediatric Use

Safety and efficacy not established in children <12 years of age with unresectable, locally advanced, or metastatic pheochromocytoma or paraganglioma.

Safety and efficacy in pediatric patients ≥12 years of age with unresectable, locally advanced, or metastatic pheochromocytoma or paraganglioma established in principal efficacy study.

Because absorbed dose of radiation is greater in pediatric patients and pediatric patients have longer life expectancy than adults, risk of adverse effects associated with radiation therapy is increased in pediatric patients. Prior to initiating therapy, assess whether benefits of therapy outweigh the risks of radiation exposure.

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.

Hepatic Impairment

Not studied in patients with hepatic impairment; however, iobenguane I 131 does not undergo hepatic elimination.

Renal Impairment

Clearance may be delayed resulting in an increased radiation dose to the kidney in patients with renal impairment. Reduction of the therapeutic dosage based on the estimated absorbed dose to critical organs was required in 19% of patients with mild or moderate renal impairment (Cl_cr 30–89 mL/minute). Safety and pharmacokinetics not established in patients with severe renal impairment (Cl_cr <30 mL/minute) or end-stage renal disease.

Increased risk for developing treatment-related nephrotoxicity in patients with preexisting renal impairment. (See Renal Effects under Cautions.)

Adjust therapeutic dosage based on estimated absorbed dose to critical organs in patients with mild or moderate renal impairment (see Dosage under Dosage and Administration); monitor renal function more frequently.

Common Adverse Effects

Grade 3 or 4 adverse effects: Lymphopenia, neutropenia, thrombocytopenia, fatigue, anemia, elevated INR, nausea, dizziness, hypertension, vomiting.

Drug Interactions

In vitro, nonradioactive iobenguane does not inhibit CYP isoenzymes 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, or 3A and does not induce CYP isoenzymes 1A, 2B6, 2C9, 2C19, or 3A.

In vitro, nonradioactive iobenguane is not a substrate or inhibitor of P-glycoprotein (P-gp).

Drugs that Reduce Catecholamine Uptake or Deplete Catecholamine Stores

Possible interference with estimated absorbed dose calculations and reduced iobenguane I 131 efficacy.

Withhold catecholamine-reducing or -depleting drugs for ≥5 half-lives prior to and for ≥7 days following dosimetric or therapeutic doses of iobenguane I 131.

Specific Drugs

Iobenguane I 131 Pharmacokinetics

Distribution

Extent

Not known whether iobenguane I 131 is distributed into milk.

Plasma Protein Binding

Nonradioactive iobenguane: 61–63%.

Elimination

Elimination Route

Eliminated primarily in urine. Following IV administration, 50 or 80% of the dose is excreted in urine within 24 or 120 hours, respectively. Unchanged I 131 accounts for a mean of 94 or 93% of radioactivity recovered in urine at 0–6 or 6–24 hours, respectively.

Half-life

Physical half-life of I 131: 8 days.

Mean terminal half-life of iobenguane I 131: Approximately 35 hours.

Special Populations

In patients with mild to moderate renal impairment (Cl_cr 30–89 mL/minute), clearance may be delayed.

Stability

Storage

Parenteral

Concentrate, for Injection, for IV Infusion

≤-70°C. Store in manufacturer-provided lead shielded container. Shelf-life of injection concentrate is 144 hours. Do not heat or refreeze. If manufacturer-provided temperature monitor indicates exposure to temperatures >-70°C, do not use vial(s).

Final diluted solutions: Stable for 8 hours (including thawing time) at room temperature.

Compatibility

Parenteral

Solution Compatibility1

Actions

• Highly specific radiopharmaceutical; an I 131 radiolabeled synthetic norepinephrine analog (iobenguane; also referred to as metaiodobenzylguanidine [MIBG]).

• Undergoes similar uptake, accumulation, and release pathways as norepinephrine.

• Structural similarity to norepinephrine allows iobenguane I 131 to accumulate in highly sympathetically innervated tissues with high levels of norepinephrine transporters (e.g., heart, lung, adrenal medulla, salivary gland, liver, spleen, pheochromocytoma, paraganglioma). Radioactive component of iobenguane I 131 (I 131) induces apoptosis and tumor necrosis.

Advice to Patients

• Importance of advising patients to follow standard precautions for minimizing radiation exposure to household contacts.

• Importance of advising patients to drink ≥2 liters of fluids daily beginning ≥1 day prior to and continuing for 1 week following administration of each iobenguane I 131 dose.

• Risk of myelosuppression (e.g., neutropenia, thrombocytopenia, anemia). Importance of monitoring CBC counts prior to and weekly during therapy. Importance of informing clinician promptly if any signs or symptoms of myelosuppression or infection (e.g., fever, chills, dizziness, shortness of breath, bleeding, easy bruising) occur.

• Risk of secondary cancers, including MDS and acute leukemia.

• Risk of hypothyroidism. Importance of advising patients to take thyroid protective agent as directed. Advise patients of the necessity of indefinite monitoring of thyroid function.

• Risk of elevations in BP. Importance of informing clinician if signs and symptoms of tumor-hormone catecholamine release or elevations in BP occur during and 24 hours after administration of a therapeutic dose.

• Risk of pneumonitis. Importance of informing clinician if signs and symptoms of pneumonitis (e.g., shortness of breath, difficulty breathing, cough) occur.

• Risk of fetal harm. Necessity of advising females of reproductive potential that they should use an effective method of contraception while receiving iobenguane I 131 and for 7 months after the final dose. Necessity of advising male patients with female partners of reproductive potential that they should use an effective method of contraception while receiving the drug and for 4 months after the final dose. Importance of women informing clinicians if they are or plan to become pregnant. Apprise patient of potential fetal hazard if used during pregnancy. (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

• Importance of advising women to avoid breast-feeding while receiving iobenguane I 131 and for 80 days after the final dose.

• Risk of impaired male and female fertility.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant diseases.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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