Iobenguane I 131

Iobenguane I 131 is a prescription medication used for the treatment of iobenguane scan-positive, unresectable, locally advanced or metastatic pheochromocytoma or paraganglioma in patients who require systemic anticancer therapy. 

• Iobenguane I 131is available under the following different brand names: Azedra

Common side effects of Iobenguane I 131 include:

• Low blood cell counts,
• Tiredness,
• Nausea,
• Vomiting,
• Dizziness,
• Low blood pressure, and
• Lightheadedness  

Serious side effects of Iobenguane I 131 include:

• Hives,
• Difficulty breathing,
• Swelling of the face, lips, tongue, or throat,
• Chest pressure,
• Dry cough,
• Shortness of breath,
• Easy bruising,
• Unusual bleeding,
• Purple or red spots under the skin,
• Extreme tiredness,
• Dry skin,
• Joint pain or stiffness,
• Muscle pain or weakness,
• Hoarse voice,
• Increased sensitivity to cold temperatures,
• Weight gain,
• Fever,
• Mouth sores,
• Skin sores,
• Sore throat,
• Cough,
• Pale skin,
• Unusual tiredness,
• Lightheadedness, and
• Cold hands and feet

Rare side effects of Iobenguane I 131 include:

• None 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

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

Adult and pediatric dosage

Solution for injection

• 555 MBq/mL (15 mCi/mL)

Pheochromocytoma or Paraganglioma

Adult and pediatric dosage

• Dosimetric dose
• The recommended dosimetric dose administered as an Intravenous injection is:
  • Patients weighing above 50 kg: 185-222 MBq (5 or 6 mCi)
  • Patients weighing below 50 kg: 3.7 MBq/kg (0.1 mCi/kg)
• Dosimetry and biodistribution assessment
• Following the dosimetric dose:
  • Acquire anterior/posterior whole body gamma camera images within 1 hour of the dosimetric dose and before patient voiding (Day 0; Scan 1)
  • Acquire additional images on Day 1 or 2 following patient voiding (Scan 2)
  • Acquire additional images between Days 2-5 following patient voiding (Scan 3)
  • For each patient, calculate the radiation dose estimates to normal organs and tissues per unit activity (D [organ]) of administered dose using data extracted from the 3 images scanned.
  • Calculate by the Medical Internal Radiation Dose (MIRD) schema or related methodology.
  • Whenever possible, use patient-specific organ masses (. g, estimated from imaging)
• Therapeutic dose
• Recommended therapeutic dose is based on body weight and reduced, if necessary, based on the dosimetry data
• Administer a total of 2 therapeutic doses intravenous a minimum of 90 days apart.
• Weight-based dose per therapeutic cycle:
  • Patients weighing above 62.5 kg: 18,500 MBq (500 mCi)
  • Patients weighing below 62.5 kg: 296 MBq/kg (8 mCi/kg)
  • Determine if dose reduction is needed based on critical organ limits.
  • Calculate the estimated critical organ absorbed dose by multiplying the dosimetry-derived radiation absorbed dose per unit activity (D [organ]) by weight-based therapeutic total activity (Aw)
  • See full prescribing information for details regarding adsorbed dose threshold values for radiation toxicity in critical organs and determine if vital dose adjustments are needed.

Thyroid blockade and other pre- and concomitant medication

Thyroid blockade

• Administer inorganic iodine starting at least 24 hours before and continuing for 10 days after each iobenguane I 131 dose.

Hydration

• Instruct patients to increase fluid intake to at least 2 liters a day starting at least 1 day before and continuing for 1 week after each dose to minimize irradiation to the bladder.
• Drugs that reduce catecholamine uptake or deplete stores.
• Discontinue drugs that reduce catecholamine uptake or deplete catecholamine stores for at least 5 half-lives before administration of either the dosimetry dose or a therapeutic dose of iobenguane I 131
• Do not administer these drugs until at least 7 days after each dose.
• See Cautions and Interactions

Antiemetics

• Administer antiemetics 30 minutes before administering each iobenguane I 131 dose.

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Iobenguane I 131 has no noted severe interactions with any other drugs.
• Iobenguane I 131 has serious interactions with at least 65 other drugs.
• Iobenguane I 131 has moderate interactions with the following drugs:
  • Siponimod
• Iobenguane I 131 has no noted minor interactions with any other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Iobenguane I 131?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Iobenguane I 131?”

Cautions

• Treatment contributes to a patient’s overall long-term radiation exposure; cumulative radiation exposure is associated with an increased risk for cancer; risks of radiation are greater in pediatric patients than in adults.
• Severe and prolonged myelosuppression reported; monitor blood cell counts weekly for up to 12 weeks or until levels return to baseline or the normal range; withhold and dose reduce as recommended based on the severity of cytopenia (see Dosage Modifications)
• Secondary malignancies may develop, including myelodysplastic syndrome, leukemia, and nonhematologic malignancies.
• Hypothyroidism may occur; initiate thyroid-blocking medication starting at least 1 day before and continuing for 10 days after each dose to reduce the risk of hypothyroidism or thyroid neoplasia; evaluate for hypothyroidism and measure TSH levels before initiating and annually thereafter.
• May worsen preexisting hypertension; monitor blood pressure frequently during the first 24 hours after each dose.
• Renal toxicity reported, including decreased GFR, renal failure, or acute kidney injury; monitory renal function during and after treatment; patients with baseline renal impairment may be at higher risk; perform more frequent assessments of renal function in patients with mild or moderate impairment.
• Fatal pneumonitis was reported in 1 patient in clinical trials; monitor for signs and symptoms of pneumonitis and treat appropriately.
• Based on its mechanism of action, can cause fetal harm (see Pregnancy)
• May cause infertility in males and females; the recommended cumulative dose of 37 GBq results in a radiation-absorbed dose to the testes and ovaries within the range where temporary or permanent infertility can be expected following external beam radiotherapy (see Pregnancy)
• Drug interaction overview
  • Based on the mechanism of action of iobenguane, drugs that reduce catecholamine uptake or that deplete catecholamine stores may interfere with iobenguane uptake into cells and therefore interfere with dosimetry calculations or the efficacy of iobenguane I 131
  • Discontinue drugs that reduce catecholamine uptake or deplete catecholamine stores (see list below) for at least 5 half-lives before administration of either the dosimetry or a therapeutic dose of iobenguane I 131
  • Do not administer the following list of drugs until at least 7 days after each iobenguane I 131 dose.
  • Drugs that may interfere with iobenguane cell uptake.
  • CNS stimulants or amphetamines (. g, cocaine, methylphenidate, dextroamphetamine)
  • Norepinephrine and dopamine reuptake inhibitors (. g, phentermine)
  • Norepinephrine and serotonin reuptake inhibitors (. g, tramadol)
  • Monoamine oxidase inhibitors (. g, phenelzine, linezolid)
  • Central monoamine-depleting drugs (. g, reserpine)
  • Nonselective beta-adrenergic blocking drugs (. g, labetalol)
  • Alpha agonists or alpha/beta agonists (. g, pseudoephedrine, phenylephrine, ephedrine, phenylpropanolamine, naphazoline)
  • Tricyclic antidepressants or norepinephrine reuptake inhibitors (. g, amitriptyline, bupropion, duloxetine, mirtazapine, venlafaxine)
  • Botanicals that may inhibit the reuptake of norepinephrine, serotonin, or dopamine (. g, ephedra, ma huang, St John’s Wort, yohimbine)

Pregnancy and Lactation

• There are no available data regarding use in pregnant women.
• Based on its mechanism of action, can cause fetal harm (see Mechanism of Action)
• No animal studies using iobenguane I 131 have been conducted to evaluate its effect on female reproduction and embryo-fetal development; however, all radiopharmaceuticals have the potential to cause fetal harm.
• Advise pregnant women of the risk to a fetus.
• Pregnancy testing
  • Verify pregnancy status in females of reproductive potential before initiating treatment.
  • Contraception
  • Females: Advise women of reproductive potential to use effective contraception during treatment with and for 7 months following the final dose
  • Males: Advise males with female partners of reproductive potential to use effective contraception during treatment and for 4 months following the final dose
• Infertility
  • The recommended cumulative dose of 37 GBq results in a radiation-absorbed dose to the testes and ovaries within the range where temporary or permanent infertility can be expected following external beam radiotherapy.
• Lactation
  • There are no data on the presence of iobenguane I 131 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 and for 80 days after the final dose.