Iobenguane ¹³¹I Other names: Iobenguane I-131

Risk Summary

Based on its mechanism of action, iobenguane ¹³¹I can cause fetal harm. There are no available data on iobenguane ¹³¹I use in pregnant women. No animal studies using iobenguane ¹³¹I have been conducted to evaluate its effect on female reproduction and embryo-fetal development; however, all radiopharmaceuticals, including iobenguane ¹³¹I, have the potential to cause fetal harm. Advise pregnant women of the risk to a fetus.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Risk Summary

There are no data on the presence of iobenguane ¹³¹I in human milk or its effects on the breastfed infant or milk production. No lactation studies in animals were conducted. Because of the potential risk for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment with iobenguane ¹³¹I and for 80 days after the final dose.

Carcinogenicity studies with iobenguane ¹³¹I have not been conducted; however, radiation is a carcinogen and a mutagen. No animal studies were conducted to determine the effects of iobenguane ¹³¹I on fertility.

• Myelosuppression
• Secondary Myelodysplastic Syndrome, Leukemia and Other Malignancies
• Hypothyroidism
• Elevations in Blood Pressure
• Renal Toxicity
• Pneumonitis

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The data in Warnings and Precautions reflect exposure to iobenguane ¹³¹I in 88 patients with iobenguane-scan positive recurrent or unresectable, locally advanced or metastatic pheochromocytoma or paraganglioma (PPGL) who received a therapeutic dose of iobenguane ¹³¹I in one of two clinical studies (IB12 or IB12B). The Warnings and Precautions also include data from 11 patients enrolled in an expanded access program for Study IB12B.

The safety data below was evaluated in two studies in patients with recurrent or unresectable, locally advanced or metastatic PPGL. Study IB12 was an open-label, multi-center, single-arm dose-finding study in adult patients with malignant or recurrent PPGL. The study consisted of a 12-month efficacy phase with a 1 year follow-up. Twenty-one patients received a dosimetric dose (~5 mCi), followed by one therapeutic dose (~500 mCi) of iobenguane ¹³¹I. Study IB12B was an open-label, multi-center, single-arm study in 68 adult and pediatric patients age 12 years and older with recurrent or unresectable, locally advanced or metastatic PPGL.

Patients with evidence of liver dysfunction (aspartate aminotransferase or alanine aminotransferase ≥2.5 times the upper limit of normal or total bilirubin >1.5 times the upper limit of normal), a history of liver disease (including hepatitis and chronic alcohol abuse), or severe renal impairment (creatinine clearance <30 mL/min) were excluded. Patients who had received external beam radiation to >25% of bone marrow, received whole body radiotherapy, or who had received any systemic radiotherapy resulting in myelosuppression within 3 months of study entry, were also excluded. The safety data described below are based on pooled safety data from studies IB12 and IB12B. A total of 88 patients received at least one therapeutic dose of iobenguane ¹³¹I and 50 patients received two therapeutic doses (one patient received treatment in both studies).

Adverse reactions from studies IB12 and IB12B are presented in Table 1. The most common severe (Grade 3-4) adverse reactions were lymphopenia (78%), neutropenia (59%), thrombocytopenia (50%), fatigue (26%), anemia (24%), increased international normalized ratio (18%), nausea (16%), dizziness (13%), hypertension (11%), and vomiting (10%). Twelve percent of patients discontinued treatment due to adverse reactions (thrombocytopenia, anemia, lymphopenia, nausea and vomiting, multiple hematologic adverse reactions).

Table 1. Adverse Reactions Occurring in ≥10% of Patients with PPGL Receiving Therapeutic Dose of Iobenguane ¹³¹I in Studies IB12B and IB12:

^a NCI CTCAE version 3.0.
^b Based on laboratory data.
^c Includes vomiting and retching.
^d Includes sialoadenitis, salivary gland pain, and salivary gland enlargement.
^e Includes abdominal pain, abdominal pain upper, and abdominal pain lower.
^f Incudes fatigue, asthenia.
^g Includes upper respiratory tract infection, sinusitis, rhinorrhea, upper-airway cough syndrome, nasopharyngitis.
^h Only assessed in Study IB12B (N=68).
ⁱ Includes dizziness and dizziness postural.
^j Includes dysgeusia, hypogeusia and ageusia.
^k Includes blood pressure increased and hypertension.

The following clinically significant adverse reactions were observed in <10% of patients treated with iobenguane ¹³¹I:

Cardiac: palpitations (9%), syncope and presyncope (8%)

Endocrine: decreased TSH (5%), hypothyroidism (3%)

Gastrointestinal: dysphagia (7%), abdominal distension (6%), gastroesophageal reflux disease (6%), stomatitis (3%)

General: insomnia (9%), chills (8%), chest pain (6%)

Infections: candida infection (6%)

Investigations: prolonged prothrombin time (9%)

Musculoskeletal and connective tissue: arthralgia (8%), neck pain (8%), pain in jaw (7%), muscle spasms (6%)

Renal and urinary disorders: proteinuria (9%), renal failure (7%),

Respiratory: epistaxis (9%), nasal congestion (7%), pulmonary embolism (3%)

Skin and subcutaneous tissue: dry skin (8%), rash (8%), petechiae (7%)

Vascular: orthostatic hypotension (9%)