HICON - sodium iodide i 131 solution
Jubilant DraxImage Inc., dba Jubilant Radiopharma
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use HICON® safely and effectively. See full prescribing information for HICON®.
HICON® (for the preparation of sodium iodide I 131 solution or sodium iodide I 131 capsules), therapeutic, for oral use.
Initial U.S. Approval: 1971
INDICATIONS AND USAGE
HICON® is a radioactive therapeutic agent indicated for the treatment of hyperthyroidism and selected cases of carcinoma of the thyroid. (1)
DOSAGE AND ADMINISTRATION
DOSAGE FORMS AND STRENGTHS
Vials: Sodium Iodide I 131 Solution (9,250 MBq, 18,500 MBq, and 37,000 MBq at time of calibration) for the preparation of sodium iodide I 131 capsules, therapeutic or sodium iodide I 131 solution, therapeutic. (3)
WARNINGS AND PRECAUTIONS
Common adverse reactions reported with therapeutic doses of sodium iodide I 131 include local swelling, radiation sickness, sialadenitis, salivary gland dysfunction, bone marrow depression, lacrimal gland dysfunction, hypothyroidism, hyperthyroidism, thyrotoxic crisis, acute leukemia, solid cancer. (6)
To report SUSPECTED ADVERSE REACTIONS, contact Jubilant DraxImage Inc. at 1-888-633-5343 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
USE IN SPECIFIC POPULATIONS
See 17 for PATIENT COUNSELING INFORMATION.
FULL PRESCRIBING INFORMATION: CONTENTS*
HICON® is indicated for the treatment of hyperthyroidism and selected cases of thyroid carcinoma.
Individualization of Therapy
The recommended dose for orally administered sodium iodide I 131 capsules or solution is based on the thyroid gland uptake as well as the size of the gland. Thyroidal uptake and size should be determined by the physician prior to treatment and may be useful in calculating the therapeutic dose to be administered to the individual patient.
Treatment of Hyperthyroidism
The recommended dose is 148 to 370 MBq (4 to 10 mCi) administered orally. Toxic nodular goiter may require a larger dose.
Treatment of Thyroid Carcinoma
The recommended dose is 1100 to 3700 MBq (30 to 100 mCi) administered orally. For subsequent ablation of metastases, the recommended dose is 3700 to 7400 MBq (100 to 200 mCi) administered orally.
Preparation of Dilute Sodium Iodide I 131 Solution USP
Preparation of Sodium Iodide I 131 Capsules USP
|Absorbed dose per unit activity sodium iodide I 131 administered orally (mGy/MBq) in adult (73.7-kg reference model)|
|Organ||Thyroid uptake of I 131 (% administered activity A0)
24 h after oral administration
|Small intestine wall||0.035||0.033||0.032||0.032|
|(Upper large intestine wall)||0.12||0.12||0.12||0.12|
|(Lower large intestine wall)||0.17||0.17||0.17||0.16|
|Urinary bladder wall||0.54||0.45||0.39||0.34|
|Effective dose per administered activity (mSv/MBq)||0.28||14‡||22‡||29‡|
HICON® is available in 1 mL size, clear vials containing a colorless, aqueous, concentrated Sodium Iodide I 131 Solution [9,250 MBq, 18,500 MBq, and 37,000 MBq at time of calibration] for the preparation of sodium iodide I 131 capsules, therapeutic or sodium iodide I 131 solution, therapeutic. Refer to Table 2 for the radioactivity and volume in each vial. Large gelatin capsules (empty) and small gelatin capsules containing approximately 300 mg of dibasic sodium phosphate anhydrous as the absorbing buffer are supplied along with HICON® for the preparation of sodium iodide I 131 capsules, therapeutic.
|*At time of calibration.|
|9,250 (250 mCi)||0.25|
|18,500 (500 mCi)||0.5|
|37,000 (1000 mCi)||1|
HICON® is contraindicated in:
Sodium iodide I 131 may cause thyroiditis with release of thyroid hormone, which may aggravate hyperthyroidism and thyrotoxic cardiac disease [see Adverse Reactions (6)]. When treating hyperthyroidism, consider pre-treatment anti-thyroid medication to help deplete the thyroid hormone. Discontinue the anti-thyroid therapy three days before administration of sodium iodide I 131 [see Drug Interactions (7)]. Consider a beta-blocker pre or post-treatment to minimize the risk of hyperthyroidism and thyroid storm.
The thyroiditis may cause gland enlargement resulting in tenderness and swelling of the neck, pain on swallowing, sore throat, and cough; which may occur approximately the third day after sodium iodide I 131 administration. Consider management with pain-reliever or anti-inflammatory medications.
Sodium Iodide I 131 may cause radiation induced toxicities [see Adverse Reactions (6)]:
Obtain a complete blood count within one month of therapy. If patients show leukopenia or thrombocytopenia, dosimetry should be used to determine a safe sodium iodide I 131 activity, while delivering less than 2 Gy to the bone marrow.
Advise good hydration for one week following sodium iodide I 131 administration and stimulate salivary flow via a sialagogue (e.g. sugar-free candy or gum, pilocarpine, and ascorbic acid) to reduce radiation exposure to the salivary glands.
Advise patients to void frequently after administration of radioiodide to enhance excretion.
Hypersensitivity reactions including anaphylaxis may occur in patients who receive sodium iodide I 131. Although iodide is not considered an allergen, hypersensitivity reactions may occur in relation with excipients or chemical component of the capsule, such as sodium thiosulfate. Obtain and document an allergy history, particularly a sulfite allergy. Emergency resuscitation equipment and personnel should be immediately available [see Adverse Reactions (6)].
HICON® is contraindicated in pregnancy because sodium iodide I 131 crosses the placenta and fetal exposure can lead to neonatal hypothyroidism. Multiple reports in the published literature describe hypothyroidism in the neonates following in utero exposure to sodium iodide I 131. Some cases of neonatal hypothyroidism were severe and irreversible. Verify pregnancy status of females of reproductive potential prior to initiating HICON® treatment. Advise females and males of reproductive potential to use effective contraception during treatment with HICON® and for at least six months after the last dose [see Use in Specific Populations (8.1, 8.3)].
HICON® is contraindicated in lactating women because sodium iodide I 131 concentrates in the breast via the increased expression of the sodium iodide symporter in breast tissue with lactation. The literature describes moderate to marked radioiodine uptake in the breast tissue for 5-32 weeks post cessation of breast feeding. Advise lactating women to discontinue breast feeding at least 6 weeks prior to administration of sodium iodide I 131 to allow sufficient time for involution to occur and to avoid excess concentration of sodium iodide I 131 in breast tissue. Consider administration of drugs to suppress lactation. Consider diagnostic scintigraphy before administration of sodium iodide I 131 to assess the persistence of uptake by breast tissue. If sodium iodide I 131 is administered in the postpartum period, the lactating mother should not breastfeed the infant [see Use in Specific Populations (8.2)].
Transient dose-related impairment of testicular function in men and transient ovarian insufficiency in women has been reported after sodium iodide I 131 therapy. Consider sperm banking for men who are anticipated to receive cumulative sodium iodide I 131 doses greater than 19,000 MBq (520 mCi) [see Use in Specific Populations (8.3)].
Instruct patients to follow radiation safety precautions after receiving HICON® to minimize the radiation contamination of other persons or the environment. Patients should avoid close contact with others, especially pregnant women and children, and take care to avoid contamination of other persons or the environment with body fluids.
Patients and Healthcare Providers
HICON® contributes to a patient’s overall long-term cumulative radiation exposure, which is associated with an increased risk of cancer. Follow safe handling and administration to minimize radiation exposure to the patient and healthcare providers.
Certain food or drugs may alter the thyroid uptake of sodium iodide I 131 and diminish its effectiveness. Recent intake of stable iodide in any form, or the use of thyroid or anti-thyroid drugs may diminish thyroid uptake of sodium iodide I 131 [see Drug Interactions (7)].
The following serious adverse reactions are described below and elsewhere in labeling:
The following adverse reactions have been identified during post-approval use of sodium iodide I 131. Because these reactions are voluntarily reported by from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
* In patients with iodide-avid brain metastases
** In patients with iodide-avid lung metastases
|Type of Medication||Recommended time of withdrawal|
| Thionamide medications|
(e.g., propylthiouracil, methimazole, carbimazole)
|Multivitamins containing iodide||10 days|
|Natural or synthetic thyroid hormones
|Iodide-containing foods: iodized salt, dairy products, egg yolks, seafood, turkey and liver||2 weeks|
|Kelp, agar, carrageenan, Lugol solution||3 weeks|
|Saturated solution of potassium iodide||3 weeks|
| Topical iodide|
(e.g., surgical skin preparation)
|Intravenous radiographic contrast agents
HICON® is contraindicated in pregnancy because fetal exposure can lead to neonatal hypothyroidism, which in some cases is severe and irreversible. Data from the published literature describe thyroid abnormalities after fetal exposure; including agenesis of the thyroid and hypothyroidism (see Data). No animal reproductive studies have been conducted.
Fetal/ Neonatal Adverse Reactions
A fetus exposed to sodium iodide I 131 can develop neonatal hypothyroidism. Delay in diagnosis of neonatal hypothyroidism after exposure to sodium iodide I 131 in utero can result in severe sequelae such as decreased mental capacity and delayed bone age. Monitor thyroid function in any infant born after in utero exposure to sodium iodide I 131.
Sodium iodide I 131 crosses the placenta and the fetal thyroid begins to concentrate iodide during the 10-12th week of gestation. In literature reports of maternal exposures to sodium iodide I 131 at doses of 333 – 8325 MBq (9 – 225 mCi) during 4-26 weeks gestational age, the most common adverse outcomes were hypothyroid infants and children.
HICON® is contraindicated during lactation because I 131 concentrates in the breast during lactation via the increased expression of the sodium iodide symporter in breast tissue [see Warnings and Precautions (5.5)]. If sodium iodide I 131 is administered in the postpartum period, the lactating mother should not breastfeed. In addition, to minimize the absorbed radiation dose to the breast tissue, breastfeeding and breast-pumping should be discontinued for at least 6 weeks before administration of sodium iodide I 131 (see Data). Women may breast feed with the birth of another child.
Infants exposed to sodium iodide I 131 through breast milk are at risk for development of hypothyroidism because sodium iodide I 131 is distributed into breast milk and may reach concentrations equal to or greater than concentrations in maternal plasma (see Data).
Limited published literature describes sodium iodide I 131 transfer into breast milk and thyroidal uptake by the breastfed infant. The amount of sodium Iodide I 131 detected in the breast milk at 36-48 hours after administration is 1-27% of the injected dose (with injected doses between 1.1 – 5143 MBq).
HICON® is contraindicated in pregnancy because of the risk of fetal hypothyroidism [see Use in Specific Populations (8.1)].
Obtain a pregnancy test in females of reproductive potential and verify the absence of pregnancy before initiating treatment [see Dosage and Administration (2.2), Warnings and Precautions (5.4)].
Advise females and males of reproductive potential to use effective contraception during treatment with HICON® and for at least six months after the last dose of HICON®.
Fertility may be impaired with HICON® treatment. Transient amenorrhea and ovarian insufficiency have been observed after sodium iodide I 131 therapy in females. The literature describes reports of transient menstrual cycle irregularities, including amenorrhea, and ovarian failure in females treated with cumulative doses of 1000 – 59,000 MBq (27 – 1594 mCi) sodium iodide I 131.
Fertility may be impaired with HICON® treatment. Discuss sperm banking for males who are expected to receive a high cumulative dose of sodium iodide I 131. Transient dose-related impairment of testicular function after sodium iodide I 131 therapy has been reported in the published literature. The literature describes reports of males treated with sodium iodide I 131 at doses of 370 MBq – 22,000 MBq (10 – 595 mCi) resulting in transiently impaired testicular function (including spermatogenesis). Permanent impairment is described with high cumulative doses ranging from 19,000 – 29,000 MBq (520 – 800 mCi).
Safety and efficacy in pediatric patients have not been established. Pediatric patients are at an increased lifetime risk for malignancy from radiation exposure
Clinical experience has not identified differences in safety or effectiveness in geriatric patients compared to younger patients. However, elderly patients are more likely to have decreased renal function and radiation exposure is greater in patients with impaired renal function [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].
HICON® is primarily excreted by the kidneys. Renal function impairment decreases excretion of sodium iodide I 131 and increases the radiation exposure and risk of radiation toxicity. For patients with a history of renal impairment, evaluate renal function for therapeutic planning and consider dosimetry. Sodium Iodide I 131 is dialyzable. Hemodialysis can be used to reduce total body radiation exposure [see Clinical Pharmacology (12.3)].
In case of exposure to a radioactive dose of sodium iodide I 131 exceeding the intended therapeutic dose, provide general supportive care, promote frequent voiding, monitor for bone marrow and thyroid suppression. Consider administering a thyroid blocking agent (e.g. potassium iodide (KI) or perchlorate) promptly within 4 to 6 hours after the exposure. Assess the benefit of administering a thyroid blocking agent against the risk of failure of sodium iodide I 131 therapy. Appropriate replacement therapy is recommended if hypothyroidism occurs.
HICON®, a radioactive therapeutic agent, provides a concentrated solution of sodium iodide I 131 with a radioconcentration of 37,000 MBq/mL (1,000 mCi/mL). Each mL of the concentrated solution contains 37,000 MBq of no-carrier-added sodium iodide I 131, disodium edetate dihydrate USP as a stabilizer, sodium thiosulfate pentahydrate USP as a reducing agent, and dibasic sodium phosphate anhydrous USP. The pH of the concentrated solution is between 7.5 and 10.
The concentrated solution provided with HICON® is used for the preparation of sodium iodide I 131 capsules or sodium iodide I 131 solution of varying strengths for oral administration for therapy.
Sodium iodide I 131 solution is designated chemically as Na 131I and has a molecular weight of 153.99. Hard gelatin capsules, provided for the preparation of the sodium iodide I 131 capsules final dosage form, contain approximately 300 mg of dibasic sodium phosphate anhydrous USP as the absorbing buffer.
Iodine I-131 decays by beta emission and associated gamma emission with a physical half-life of 8.04 days. The principal radiation emissions are listed in Table 4.
|Radiation||Mean % per |
The specific gamma-ray constant for iodide I 131 is 4.26 × 10-13 C·m2·kg-1·MBq-1·s-1 (2.2 R·cm2/mCi·hr). The first half-value thickness of lead (Pb) for iodide I 131 is 0.27 cm. A range of values for the relative attenuation of the radiation emitted by iodide I 131 that results from interposition of various thicknesses of Pb is shown in Table 5. For example, the use of 2.59 cm of Pb will decrease the external radiation exposure by a factor of about 1,000.
|Coefficient of Attenuation|
To correct for physical decay of iodine I 131, the fractions that remain at selected intervals after the time of calibration are shown in Table 6.
|Days||Fraction Remaining||Days||Fraction Remaining||Days||Fraction Remaining|
Iodide is actively transported by the sodium-iodide symporter (NIS) protein, in thyroid follicular cells. Iodide is concentrated in follicular cells to levels up to 50 times higher than in the plasma. Iodide is metabolically oxidized by thyroid peroxidase to iodinium (I+) which in turn iodinates tyrosine residues of thyroglobulin (tri or tetra-iodinated tyrosine). The beta emission of I 131 is responsible for the therapeutic effect.
The relationship between the extent of iodide I 131 exposure and pharmacologic effects has not been explored in clinical trials.
Following oral administration of HICON®, 90% of the administered radioactivity of Iodide I 131 is systemically absorbed in the first 60 minutes.
Following absorption, I 131 is distributed within the extra-cellular space. It is actively transported by the sodium-iodide symporter (NIS) protein, and binds to thyroglobulin resulting in accumulation in the thyroid. The thyroid uptake of iodide is usually increased in hyperthyroidism and in goiter, and is decreased in hypothyroidism. Sodium Iodide I 131 also accumulates in the stomach, choroid plexus, salivary glands, breast, liver, gall bladder, and kidneys.
In thyroidal follicular cells iodide is oxidized through the action of thyroid peroxidase to iodinium (I+) which in turn iodinates tyrosine residues of thyroglobulin.
Sodium iodide I 131 is excreted in urine and feces. The normal range of urinary excretion is 37% to 75% of the administered dose, varying with the thyroid and renal function of the patient. Fecal excretion is about 10%.
HICON® is supplied in 1 mL clear vials that contain approximately 37,000 MBq (250 mCi), 18,500 MBq (500 mCi), and 37,000 MBq (1,000 mCi) at the time of calibration.
|NDC||Volume of Concentrated Solution||Total Radioactivity per Vial|
|65174-880-25||0.25 mL||9,250 <MBq (250 mCi)|
|65174-880-50||0.50 mL||18,500 MBq (500 mCi)|
|65174-880-00||1 mL||37,000 MBq (1,000 mCi)|
A minimum of one blister package of 10 empty large hard gelatin capsules and a minimum of one blister package of 10 small hard gelatin capsules containing approximately 300 mg of dibasic sodium phosphate anhydrous as the absorbing buffer are supplied along with HICON® for the preparation of sodium iodide I 131 capsules, therapeutic.
HICON® should be stored between 2°C and 25°C (36°F and 77°F). Store and dispose of HICON® in compliance with the appropriate regulations of the government agency authorized to license the use of this radionuclide.
Discard unused capsules after all HICON® solution has been dispensed or expired. New blister packages of hard gelatin capsules are provided with each new shipment of HICON®.
This radiopharmaceutical is approved for use by persons under license by the Nuclear Regulatory Commission or the relevant regulatory authority of an Agreement State.
Radiation Safety Precautions [see Warnings and Precautions (5.7)].
Review the most recent professional society guidelines and publications that describe important components of the patient counseling process and discuss measures to minimize inadvertent radiation exposure to the patient.
• Instruct women to stop breastfeeding and breast-pumping at least 6 weeks prior to HICON® administration [see Contraindications (4), Warnings and Precautions (5.5) and Use in Specific Populations (8.2)].
Effects on Fertility
• Advise females and males of reproductive potential of the potential for impaired fertility with HICON® treatment [see Warnings and Precautions (5.6) and Use in Specific Populations (8.3)].
Jubilant DraxImage Inc., Kirkland, Québec Canada, H9H 4J4
Art rev.: 1.0
sodium iodide i 131 solution
|Labeler - Jubilant DraxImage Inc., dba Jubilant Radiopharma (243604761)|
|Registrant - Jubilant DraxImage Inc., dba Jubilant Radiopharma (243604761)|
|Jubilant DraxImage Inc., dba Jubilant Radiopharma||243604761||MANUFACTURE(65174-880)|