iobenguane I 131 (Rx)

Brand and Other Names:Azedra
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

solution for injection

  • 555MBq/mL (15mCi/mL)

Pheochromocytoma or Paraganglioma

Indicated for iobenguane scan-positive, unresectable, locally advanced or metastatic pheochromocytoma or paraganglioma in patients who require systemic anticancer therapy

Administer thyroid blockade and other pre- and concomitant medications as recommended

Dosimetric dose

  • The recommended dosimetric dose administered as an IV injection is
    • Patients weighing >50 kg: 185-222 MBq (5 or 6 mCi)
    • Patients weighing &lge;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 hr of the dosimetric dose and prior to 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 individual 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 in accordance with the Medical Internal Radiation Dose (MIRD) schema or related methodology
    • Whenever possible, use patient-specific organ masses (eg, 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 IV a minimum of 90 days apart
  • Weight-based dose per therapeutic cycle
    • Patients weighing >62.5 kg: 18,500 MBq (500 mCi)
    • Patients weighing &lge;62.5 kg: 296 MBq/kg (8 mCi/kg)
  • Determine if dose reduction 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 hr 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 Modifications

Myelosuppression

  • Do not administer the first therapeutic dose for platelet counts <80,000/mcL or ANC counts <1,200/mcL
  • Do not administer the second therapeutic dose until platelets and neutrophils return to baseline or to the normal range
  • Reduce the second therapeutic dose for the following
    • Platelet count <25,000/mcL, ANC <500/mcL, or life-threatening anemia for >7 days
    • Febrile neutropenia
    • Platelet count <50,000/mcL with active bleeding

Myelosuppression, recommended dose reduction for second dose

  • Weight >62.5 kg
    • If first therapeutic dose was weight based: Reduce the second therapeutic dose to 425 mCi
    • If first therapeutic dose was reduced based on critical organ limits: Reduce second therapeutic dose to 85% of the first dose
  • Weight &lg;62.5 kg
    • If first therapeutic dose was weight based: Reduce the second therapeutic dose to 7 mCi/kg
    • If first therapeutic dose was reduced based on critical organ limits: Reduce second therapeutic dose to 85% of the first dose

Pneumonitis

  • Do not administer the second therapeutic dose if pneumonitis is diagnosed after the first therapeutic dose

Renal impairment

  • The radiation dose to patients with renal impairment may be increased owing to the delayed elimination of the drug
  • Adjust the therapeutic dose based on radiation exposure estimates from the dosimetry assessment
  • Severe renal impairment (CrCl <30 mL/min) or end-stage renal disease: Not studied

Dosage Forms & Strengths

solution for injection

  • 555MBq/mL (15mCi/mL)

Pheochromocytoma or Paraganglioma

Indicated in adults and children aged ≥12 years for iobenguane scan positive, unresectable, locally advanced or metastatic pheochromocytoma or paraganglioma in who require systemic anticancer therapy

Administer thyroid blockade and other pre- and concomitant medications as recommended

Dosimetric dose

  • The recommended dosimetric dose administered as an IV injection is
    • Patients weighing >50 kg: 185-222 MBq (5 or 6 mCi)
    • Patients weighing &lge;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 hr of the dosimetric dose and prior to 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 individual 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 in accordance with the Medical Internal Radiation Dose (MIRD) schema or related methodology
    • Whenever possible, use patient specific organ masses (eg, 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 IV a minimum of 90 days apart
  • Weight-based dose per therapeutic cycle
    • Patients weighing >62.5 kg: 18,500 MBq (500 mCi)
    • Patients weighing &lge;62.5 kg: 296 MBq/kg (8 mCi/kg)
  • Determine if dose reduction 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 hr 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 update 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 Modifications

Myelosuppression

  • Do not administer the first therapeutic dose for platelet counts <80,000/mcL or ANC counts <1,200/mcL
  • Do not administer the second therapeutic dose until platelets and neutrophils return to baseline or to the normal range
  • Reduce the second therapeutic dose for the following
    • Platelet count <25,000/mcL, ANC <500/mcL, or life-threatening anemia for >7 days
    • Febrile neutropenia
    • Platelet count <50,000/mcL with active bleeding

Myelosuppression, recommended dose reduction for second dose

  • Weight >62.5 kg
    • If first therapeutic dose was weight based: Reduce the second therapeutic dose to 425 mCi
    • If first therapeutic dose was reduced based on critical organ limits: Reduce second therapeutic dose to 85% of the first dose
  • Weight &lg;62.5 kg
    • If first therapeutic dose was weight based: Reduce the second therapeutic dose to 7 mCi/kg
    • If first therapeutic dose was reduced based on critical organ limits: If first therapeutic dose was reduced based on critical organ limits: Reduce second therapeutic dose to 85% of the first dose

Pneumonitis

  • Do not administer the second therapeutic dose if pneumonitis is diagnosed after the first therapeutic dose

Renal impairment

  • The radiation dose to patients with renal impairment may be increased owing to the delayed elimination of the drug
  • Adjust the therapeutic dose based on radiation exposure estimates from the dosimetry assessment
  • Severe renal impairment (CrCl <30 mL/min) or end-stage renal disease: Not studied
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Interactions

Interaction Checker

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            Adverse Effects

            >10% All Grades

            Lymphopenia (96%)

            Anemia (93%)

            Thrombocytopenia (91%)

            Increased INR (85%)

            Neutropenia (84%)

            Nausea (78%)

            Fatigue (71%)

            Vomiting (58%)

            Increased alkaline phosphatase (53%)

            Increased AST (50%)

            Dry mouth (48%)

            Increased ALT (43%)

            Sialadenitis (39%)

            Dizziness (34%)

            Headache (32%)

            Decreased appetite (30%)

            Diarrhea (25%)

            Dysgeusia (24%)

            Hypotension (24%)

            Abdominal pain (23%)

            Hypertension (20%)

            Constipation (19%)

            Cough (18%)

            Dyspnea (18%)

            Back pain (17%)

            Dehydration (16%)

            Decreased weight (16%)

            Upper respiratory tract infection (16%)

            Pain in extremity (15%)

            Oropharyngeal pain (14%)

            Pyrexia (14%)

            Urinary tract infection (11%)

            >10% Grades 3-4

            Lymphopenia (78%)

            Neutropenia (59%)

            Thrombocytopenia (50%)

            Fatigue (26%)

            Anemia (24%)

            Increased INR (18%)

            Nausea (16%)

            Dizziness (13%)

            Hypertension (11%)

            1-10% All Grades

            Dyspepsia (10%)

            Injection site pain (10%)

            Hyperhidrosis (10%)

            Alopecia (10%)

            Tachycardia (10%)

            1-10% Grades 3-4

            Vomiting (10%)

            Constipation (7%)

            Dyspnea (7%)

            Abdominal pain (6%)

            Headache (6%)

            Increased alkaline phosphatase (5%)

            Decreased appetite (5%)

            Dehydration (4%)

            Hypotension (4%)

            Diarrhea (3%)

            Tachycardia (3%)

            Dry mouth (2%)

            Pyrexia (2%)

            Upper respiratory tract infection (2%)

            Increase AST/ALT (2%)

            Back pain (2%)

            Urinary tract infection (1%)

            Sialadenitis (1%)

            Decreased weight (1%)

            Dysgeusia (1%)

            1-10% Other

            Prolonged prothrombin time (9%)

            Palpitations (9%)

            Proteinuria (9%)

            Insomnia (9%)

            Epistaxis (9%)

            Orthostatic hypotension (9%)

            Chills (8%)

            Syncope and presyncope (8%)

            Arthralgia (8%)

            Neck pain (8%)

            Dry skin (8%)

            Rash (8%)

            Petechiae (7%)

            Pain in jaw (7%)

            Dysphagia (7%)

            Renal failure (7%)

            Nasal congestion (7%)

            Chest pain (6%)

            Muscle spasms (6%)

            Candida infection (6%)

            Abdominal distension (6%)

            Gastroesophageal reflux disease (6%)

            Decreased TSH (5%)

            Hypothyroidism (3%)

            Stomatitis (3%)

            Pulmonary embolism (3%)

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            Warnings

            Contraindications

            None

            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 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 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 hr 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 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 (eg, cocaine, methylphenidate, dextroamphetamine)
              • Norepinephrine and dopamine reuptake inhibitors (eg, phentermine)
              • Norepinephrine and serotonin reuptake inhibitors (eg, tramadol)
              • Monoamine oxidase inhibitors (eg, phenelzine, linezolid)
              • Central monoamine-depleting drugs (eg, reserpine)
              • Nonselective beta-adrenergic blocking drugs (eg, labetalol)
              • Alpha agonists or alpha/beta agonists (eg, pseudoephedrine, phenylephrine, ephedrine, phenylpropanolamine, naphazoline)
              • Tricyclic antidepressants or norepinephrine reuptake inhibitors (eg, amitriptyline, bupropion, duloxetine, mirtazapine, venlafaxine)
              • Botanicals that may inhibit reuptake of norepinephrine, serotonin, or dopamine (eg, ephedra, ma huang, St John’s Wort, yohimbine)
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            Pregnancy

            Pregnancy

            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 prior to 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

            Pregnancy Categories

            A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA:Information not available.

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            Pharmacology

            Mechanism of Action

            Iobenguane is similar in structure to the neurotransmitter norepinephrine (NE) and is subject to the same uptake and accumulation pathways as NE; iobenguane is taken up by the NE transporter in adrenergic nerve terminals and accumulates in adrenergically innervated tissues (eg, heart, lungs, adrenal medulla, salivary glands, liver, spleen) as well as tumors of neural crest origin

            Pheochromocytoma and paraganglioma (PPGL) are tumors of neural crest origin that express high levels of the NE transporter on their cell surfaces; following IV administration, iobenguane I 131 is taken up and accumulates within pheochromocytoma and paraganglioma cells, and radiation resulting from radioactive decay of I 131 causes cell death and tumor necrosis

            Absorption

            Characterized following a dosimetric dose

            Peak plasma concentration: 0.06 microCi/mL

            AUC: 1 microCi·h/mL

            Distribution

            Protein bound: 61-63%

            Vd: 2893 mL/kg

            Half-life, distribution: 0.37 hr

            Metabolism

            Does not undergo hepatic metabolism

            Elimination

            Half-life, terminal: 35 hr

            Clearance: 62 mL/hr/kg

            Excretion

            • 50% urine (within 24 hr); 80% (within 120 hr)
            • Excreted most unchanged (93-94%)
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            Administration

            IV Preparation

            Refer to the Package Handling Instructions supplied with the frozen vial

            Discard if the temperature recording device displays an alarm icon indicating that the temperature exceeded -70°C during shipment

            Use aseptic technique and radiation shielding when administering solution

            Use tongs when handling vial to minimize radiation exposure

            Confirm the amount of radioactivity in the radiopharmaceutical vial with an appropriate dose calibrator before and after administration

            Inspect visually for particulate matter and discoloration prior to administration whenever solution and container permit; should solution should appear clear, colorless to pale yellow, and without any particulate matter; discard if particulate matter or discoloration is observed

            Dosimetric dose

            • Thaw the vial to room temperature in lead pot
            • Do not heat or refreeze
            • Confirm complete thawing and gently swirl to ensure homogeneity
            • Insert a venting unit (consisting of a needle, 0.2-micron sterile filter, and a charcoal filter) to avoid pressurizing the contents of the vial during dilution; swirl gently to ensure homogeneity
            • Add sufficient volume of 0.9% NaCl to the vial to yield a concentration of 1 mCi/mL (37 MBq/mL); again, swirl gently to ensure homogeneity
            • Draw the dosimetric dose into a 10-mL shielded syringe and place in the dose calibrator to ensure that the activity is within 10% of dose; discard unused medicinal product or waste material in accordance with local and federal laws for biohazards
            • Maintain at room temperature and administer within 8 hr of retrieval from frozen storage

            Therapeutic dose

            • Thaw the appropriate number of vials (2 or 3) to room temperature in lead pots; do not heat or refreeze; swirl vial(s) to ensure homogeneity
            • Insert a venting unit into each vial to avoid pressurizing the contents of the vial during dilution; insert a venting unit into a sterile 50-mL glass vial and transfer the entire contents of the 2 therapeutic vial(s) into a 50-mL glass vial
            • Measure the radioactivity
              • If radioactivity in the 50-mL glass vial exceeds the therapeutic dose, withdraw and discard the appropriate volume using a shielded syringe and then add 0.9% NaCl to a total volume of 50 mL
              • If radioactivity in the 50-mL glass vial is less than the therapeutic dose, use a shielded syringe to withdraw the appropriate volume from a third vial and add to the 50-mL glass vial; add 0.9% NaCl to a total volume of 50 mL
            • Swirl gently to ensure homogeneity
            • Remove the venting unit and place the 50-mL glass vial into a dose calibrator to ensure that the activity is within 10% of therapeutic dose
            • Maintain at room temperature and administer within 8 hr of retrieval from frozen storage
            • Discard unused medicinal product or waste material in accordance with local and federal laws for biohazards

            IV Administration

            Dosimetric dose

            • Administer IV over 60 seconds

            Therapeutic dose

            • Verify line patency by infusing 250 mL of 0.9% NaCl (primary IV line) at recommended rate of 200 mL/hr
            • Insert a venting unit into the 50-mL glass vial containing the therapeutic dose
            • Assemble a second IV line using a 19-ga x 5-in aspirating needle, 24-in M-M arterial pressure tubing, and a primary set specific connector
            • Clamp the second IV line and connect it to the primary IV line using the primary set specific connector
            • Flush the second intravenous line by releasing the clamp and then reclamp the second IV line
            • Insert the needle of the second IV line into the 50-mL glass vial containing the therapeutic dose
            • Ensure the needle reaches the bottom of the glass vial without touching the sides of the vial
            • Clamp the primary IV line just above the second intravenous line and remove the clamp from the secondary IV line
            • Administer the therapeutic dose over 30 minutes at a recommended rate of 100 mL/hr for adults; for pediatric patients 12 years and older, administer over 60 minutes at a recommended rate of 50 mL/hr
            • Clamp the secondary IV line when the first air bubbles form
            • Remove the clamp from the primary IV line to flush any residual therapeutic dose within this IV line with at least 50 mL of 0.9% NaCl
            • Remove the clamp from the secondary IV line to flush any residual drug in the secondary IV line into the 50-mL glass vial

            Storage

            Product vial is in a lead-shielded container placed in a resealable plastic bag

            Product shipped on dry ice in a USA DOT Type A Radioactive package

            Store frozen at -70°C (-94°F)

            Shelf life: 6 days post calibration time

            Discard appropriately at 144 hr

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            Images

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            Formulary

            FormularyPatient Discounts

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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
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            NC NOT COVERED – Drugs that are not covered by the plan.
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