Azedra

Azedra (iobenguane I 131) is a radioactive therapeutic agent indicated for the treatment of adult and pediatric patients 12 years and older with iobenguane scan positive, unresectable, locally advanced or metastatic pheochromocytoma or paraganglioma who require systemic anticancer therapy. Common side effects of Azedra include:

• low white blood cell count (lymphopenia, neutropenia),
• low blood platelets (thrombocytopenia),
• fatigue,
• anemia,
• increased international normalized ratio (INR),
• nausea,
• dizziness,
• high blood pressure (hypertension), and
• vomiting

The recommended dose of Azedra for patients greater than 50 kg is 185 to 222 MBq (5 to 6 mCi) and for patients 50 kg or less the dose is 3.7 MBq/kg (0.1 mCi/kg). The recommended therapeutic dose of Azedra for each of the 2 doses for patients greater than 62.5 kg is 18,500 MBq (500 mCi), and for patients 62.5 kg or less the dose is 296 MBq/kg (8 mCi/kg). Azedra may interact with CNS stimulants or amphetamines, norepinephrine and dopamine reuptake inhibitors, norepinephrine and serotonin reuptake inhibitors, monoamine oxidase inhibitors (MAOIs), central monoamine depleting drugs, beta-blockers, alpha agonists or alpha/beta agonists, tricyclic antidepressants or norepinephrine reuptake inhibitors, and some botanicals (ephedra, ma huang, St John's wort, yohimbine). Tell your doctor all medications and supplements you use. Azedra is not recommended for use during pregnancy; it may harm a fetus. It is unknown if Azedra passes into breast milk. Because of the potential for adverse effects on nursing infants, breastfeeding while using Azedra is not recommended.

Our Azedra (iobenguane I 131) Injection, for Intravenous Use Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

 

Azedra Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• chest pressure, dry cough, feeling short of breath;
• easy bruising, unusual bleeding, purple or red spots under your skin;
• thyroid symptoms--extreme tired feeling, dry skin, joint pain or stiffness, muscle pain or weakness, hoarse voice, feeling more sensitive to cold temperatures, weight gain;
• low white blood cell counts--fever, mouth sores, skin sores, sore throat, cough, trouble breathing; or
• low red blood cells (anemia)--pale skin, unusual tiredness, feeling light-headed or short of breath, cold hands and feet.

Common side effects may include:

• low blood cell counts;
• feeling tired;
• nausea, vomiting;
• dizziness; or
• low blood pressure (feeling light-headed).

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Azedra (Iobenguane I 131 Injection)

 

Azedra Professional Information

SIDE EFFECTS

The following serious adverse reactions are described elsewhere in the labeling:

• Myelosuppression [see WARNINGS AND PRECAUTIONS]
• Secondary Myelodysplastic Syndrome, Leukemia and Other Malignancies [see WARNINGS AND PRECAUTIONS]
• Hypothyroidism [see WARNINGS AND PRECAUTIONS]
• Elevations in Blood Pressure [see WARNINGS AND PRECAUTIONS]
• Renal Toxicity [see WARNINGS AND PRECAUTIONS]
• Pneumonitis [see WARNINGS AND PRECAUTIONS]

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 AZEDRA in 88 patients with iobenguane-scan positive recurrent or unresectable, locally advanced or metastatic pheochromocytoma or paraganglioma (PPGL) who received a therapeutic dose of AZEDRA 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 [see WARNINGS AND PRECAUTIONS].

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 AZEDRA. 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 [see Clinical Studies].

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 AZEDRA 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 5. 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 5: Adverse Reactions Occurring in ≥10% of Patients with PPGL Receiving Therapeutic Dose of AZEDRA in Studies IB12B and IB12

Adverse Reaction	All Gradesa, (%)	Gradesa 3 - 4, (%)
Hematologicb
Lymphopenia	96	78
Anemia	93	24
Thrombocytopenia	91	50
Neutropenia	84	59
Gastrointestinal
Nausea	78	16
Vomitingc	58	10
Dry mouth	48	2
Sialadenitisd	39	1
Diarrhea	25	3
Abdominal paine	23	6
Constipation	19	7
Oropharyngeal pain	14	0
Dyspepsia	10	0
General
Fatiguef	71	26
Pyrexia	14	2
Injection site pain	10	0
Hyperhidrosis	10	0
Alopecia	10	0
Infections
Upper respiratory tract infectiong	16	2
Urinary tract infection	11	1
Investigationsb
Increased international normalized ratioh	85	18
Increased blood alkaline phosphatase	53	5
Increased aspartate aminotransferase	50	2
Increased alanine aminotransferase	43	2
Metabolism and nutrition
Decreased appetite	30	5
Dehydration	16	4
Decreased weight	16	1
Musculoskeletal and connective tissue disorders
Back pain	17	2
Pain in extremity	15	0
Nervous system
Dizzinessi	34	13
Headache	32	6
Dysgeusiaj	24	1
Respiratory, thoracic, and mediastinal disorders
Cough	18	0
Dyspnea	18	7
Vascular
Hypotension	24	4
Hypertensionk	20	11
Tachycardia	10	3
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 AZEDRA:

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%)

Read the entire FDA prescribing information for Azedra (Iobenguane I 131 Injection)