AZEDRA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for AZEDRA (AZEDRA).
Iobenguane is taken up by adrenergic tissues via the norepinephrine transporter and accumulates in cells of the adrenal medulla and pheochromocytoma/paraganglioma tumors. Its guanidinoethyl group inhibits catecholamine uptake, but the primary therapeutic effect is from the beta emission of I-131, causing DNA damage and cell death.
| Metabolism | Iobenguane is not significantly metabolized; the drug is primarily excreted unchanged in urine. Radioactive decay of I-131 occurs via beta and gamma emission, with a physical half-life of 8.02 days. |
| Excretion | Renal excretion of intact drug and metabolites accounts for approximately 90% of administered radioactivity within 96 hours; the remainder is eliminated via feces (approximately 10%). The major route is renal, with about 40-50% excreted unchanged. |
| Half-life | The terminal elimination half-life of AZEDRA (iobenguane I-131) ranges from 30 to 40 hours (mean approximately 35 hours) based on total radioactivity. The effective half-life, accounting for both physical decay of I-131 (8.02 days) and biological elimination, is approximately 24-50 hours. This informs the duration of radiation safety precautions and tumor dose delivery. |
| Protein binding | Approximately 55-65% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | The volume of distribution is approximately 10-15 L/kg (mean 12 L/kg), indicating extensive tissue distribution, particularly into tumors expressing the norepinephrine transporter (NET). |
| Bioavailability | AZEDRA is administered only intravenously; thus, oral bioavailability is not applicable. By IV route, bioavailability is 100%. |
| Onset of Action | Therapeutic effect (tumor uptake and radiation delivery) begins within hours after intravenous infusion, but clinical response (e.g., symptom improvement, tumor shrinkage) is typically not observed for 4-8 weeks after treatment. |
| Duration of Action | The duration of therapeutic action is prolonged due to the cumulative radiation effect; clinical benefit may last 6-12 months or longer, depending on tumor response. Myelosuppression, a key adverse effect, manifests 4-6 weeks post-dose and may persist for several weeks. |
| Action Class | Nootropic agent |
| Brand Substitutes | Citibral 250mg Injection, Strolife Mono 250mg Injection, Citrok 250mg Injection, Cholinecad 250mg Injection, Citizac 250mg Injection |
Intravenous infusion of iobenguane I-131 at 3.7 MBq/kg (0.1 mCi/kg) for diagnostic imaging; treatment dose is 296 MBq/kg (8 mCi/kg) up to a maximum of 22.2 GBq (600 mCi) administered intravenously over 30-60 minutes every 12-16 weeks for up to 4 cycles.
| Dosage form | SOLUTION |
| Renal impairment | No formal dose adjustment guidelines available. Use with caution in patients with severe renal impairment (eGFR <30 mL/min/1.73 m²) due to potential for increased exposure and delayed clearance. |
| Liver impairment | No formal dose adjustment guidelines available. Use with caution in patients with moderate to severe hepatic impairment (Child-Pugh class B or C) due to limited data. |
| Pediatric use | Not approved for pediatric patients; safety and efficacy not established. Clinical trials have included patients aged ≥12 years with dosing based on body surface area (BSA) and disease status, but no standard pediatric dose is defined. |
| Geriatric use | No specific dose adjustment recommended. Use caution due to age-related decline in renal function and potential for increased sensitivity; monitor renal function and thyroid status. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for AZEDRA (AZEDRA).
| Breastfeeding | Iobenguane I-131 is excreted in breast milk. M/P ratio: not determined. Due to radioactive iodine exposure, breastfeeding must be discontinued permanently after administration. Advise to pump and discard milk for at least 4 weeks post-dose. |
| Teratogenic Risk | Fetal risk based on animal studies: embryo-fetal mortality and teratogenicity at exposures below human dose. No human studies. First trimester: high risk of malformations and spontaneous abortion. Second and third trimesters: potential for fetal tissue damage from radiation (iobenguane I-131). Contraindicated in pregnancy; pregnancy test required before administration. |
■ FDA Black Box Warning
Radiation exposure from I-131 iobenguane can cause severe and potentially fatal bone marrow suppression, including myelodysplastic syndrome and leukemia, especially in heavily pretreated patients. Strict radiation safety measures must be followed to minimize exposure to healthcare personnel, family members, and the public.
| Serious Effects |
["Known hypersensitivity to iobenguane or any component","Pregnancy (unless benefit justifies fetal risk)","Breastfeeding","Severe bone marrow suppression (absolute neutrophil count <1,000/mm3 or platelet count <80,000/mm3) or evidence of myelodysplasia/leukemia at baseline","Patients whose tumors do not concentrate iobenguane on diagnostic scan"]
| Precautions | ["Bone marrow suppression: Monitor complete blood counts weekly; dose reduction or discontinuation may be needed.","Myelodysplastic syndrome/acute leukemia: Increased risk with prior chemotherapy or external radiation.","Radiation exposure: Isolate patient in lead-lined room; follow institutional radiation safety protocols.","Secondary malignancies: Potential risk from radiation.","Renal impairment: Increased radiation exposure; adjust dose based on renal function.","Hormonal crisis: Release of catecholamines may cause hypertensive crisis; pretreat with alpha- and beta-blockers as needed.","Carcinoid crisis: In patients with carcinoid tumors.","Pregnancy: Can cause fetal harm; verify pregnancy status before treatment.","Lactation: Discontinue breastfeeding due to radiation exposure."] |
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| Fetal Monitoring | Monitor complete blood count, thyroid function, and renal function prior to and during therapy. Perform pregnancy test in females of childbearing potential within 24 hours before each dose. Radiation safety precautions: monitor for radiation exposure to patient and environment. |
| Fertility Effects | Iobenguane I-131 may cause temporary or permanent infertility due to radiation exposure to gonads. Advise men to consider sperm cryopreservation before treatment. Women may experience premature ovarian failure; fertility preservation options should be discussed. |
| Food/Dietary | Avoid foods rich in iodine (e.g., iodized salt, seafood, dairy, eggs, multivitamins with iodine) for at least 2 weeks before and during treatment to reduce competitive uptake. Maintain a low-iodine diet during thyroid blockade. No specific food restrictions otherwise. |
| Clinical Pearls | AZEDRA (iobenguane I-131) is a radioactive therapeutic agent for pheochromocytoma/paraganglioma. Thyroid blockade with SSKI or Lugol’s solution must be initiated 24 hours prior to infusion and continued for 10 days to minimize thyroid uptake of free I-131. Monitor for hematologic toxicity, particularly thrombocytopenia and leukopenia, for up to 8 weeks post-treatment. Premedicate with antiemetics and maintain adequate hydration to reduce radiation cystitis. Not for use in pregnancy; verify negative pregnancy test prior to administration. |
| Patient Advice | This drug is radioactive and will make you emit radiation; follow all radiation safety precautions provided by your care team. · You must start taking potassium iodide drops or tablets 24 hours before your treatment and continue for 10 days to protect your thyroid. · Drink plenty of water and urinate frequently for the first 48 hours to help flush the radioactive drug out of your body. · Avoid close contact with pregnant women, infants, and children for at least 7 days after treatment. · Use effective birth control during and for at least 6 months after treatment due to risk of fetal harm. · You may experience nausea, vomiting, bone marrow suppression, and fatigue; report any unusual bleeding, bruising, or signs of infection. |