(Potassium Iodide) KI in Radiation Emergencies-Questions and Answers

Administrative guidance, not enacted legislation. This captured publisher edition preserves the listed document and attachments; later developments are not independently consolidated.

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12/20/02
Guidance for Industry
KI in Radiation Emergencies —
Questions and Answers
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Drug Evaluation and Research (CDER)
December 2002
Procedural
Revision 1

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12/20/02

Guidance for Industry
KI in Radiation Emergencies —
Questions and Answers
Additional copies are available from:
Division of Drug Information, HFD-240
Center for Drug Evaluation and Research
Food and Drug Administration
5600 Fishers Lane
Rockville, MD 20857
(Tel) 301-827-4573
http://www.fda.gov/cder/guidance/index.htm
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Drug Evaluation and Research (CDER)
December 2002
Procedural
Revision 1

Draft — Not for Implementation
TABLE OF CONTENTS
I. 	INTRODUCTION................................................................................................................. 1
II. 	BACKGROUND ................................................................................................................... 1
III. QUESTIONS AND ANSWERS........................................................................................... 2

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Guidance for Industry1
KI in Radiation Emergencies —
Questions and Answers
This guidance represents the Food and Drug Administration's (FDA's) current thinking on this topic. It
does not create or confer any rights for or on any person and does not operate to bind FDA or the public.
An alternative approach may be used if such approach satisfies the requirements of the applicable statutes
and regulations.
I. 	INTRODUCTION
This guidance provides answers to questions that FDA has received as state and local
governments develop emergency response plans involving the use of potassium iodide (KI) to
protect against the effects of radioactive iodine accidentally or intentionally released into the
atmosphere. KI is recommended for use as an adjunct to other emergency measures, such as
evacuation and control of the food supply to avoid ingestion of contaminated foodstuffs. When
used correctly, KI can prevent or reduce the uptake of radioiodine by the thyroid gland. KI
provides optimal protection when administered immediately prior to or in conjunction with
passage of a radioactive cloud. The incorporation of KI into radiation emergency response plans
is at the discretion of state and local governments.
This is a revision of the question and answer guidance published in April 2002. The revision
incorporates two additional questions (question 4 and question 7) raised about KI intervention
and makes minor editorial changes to the previous questions and answers.
II. 	BACKGROUND
In a guidance entitled Potassium Iodide as a Thyroid Blocking Agent in Radiation Emergencies
(December 2001), the Food and Drug Administration (FDA) updated its 1982 recommendations
for the safe and effective use of KI to prevent or reduce the uptake of radioiodine by the thyroid
gland. The current recommendations are based on conclusions reached after reviewing data on
radioiodine exposure and thyroid cancer risk gathered after the Chernobyl nuclear reactor
accident in 1986. The data suggest that the risk of thyroid cancer is inversely related to age.
Fetuses, infants, and young children are at greatest risk and may be harmed by small amounts of
radioiodine.
1 This guidance has been prepared by the Division of Metabolic and Endocrine Drug Products in the Center for
Drug Evaluation and Research (CDER) .

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Although special precautions should be taken when administering KI to pregnant women and
newborns within the first month of life (adherence to the recommended dose, avoidance of repeat
dosing, and monitoring of thyroid function in neonates), the benefits of short-term administration
of KI as a thyroid blocking agent far exceed the risks of administration to any age group.
For complete information, please refer to FDA’s December 2001 guidance.
III. 	QUESTIONS AND ANSWERS
Q1: 	Does FDA have specific recommendations about radiation emergency preparedness
plans and the use of KI?
A1: 	No. Decisions about the details of their preparedness plans are up to state and local
authorities. FDA's guidance provides general recommendations about the use of KI
prophylaxis in the event of a radiological emergency. These recommendations are
discussed in Section V. of the guidance.
Q2: 	Is the graded dosing scheme recommended by FDA the only safe and effective way to
take KI?
A2: 	No. FDA has made recommendations on the lowest effective dose. Higher doses (e.g.,
up to 130 mg) would be equally effective and, particularly among school-age children,
extremely safe (see also question 9).
Q3: 	If a graded dosing approach is considered, how does FDA suggest that
fractional doses (i.e., 65, 32, 16 mg) be administered?
A3: 	KI tablets can be dissolved in liquids and the appropriate volume administered. For
example, if a 130 mg tablet were dissolved in 8 ounces of liquid, one ounce would
contain about 16 mg of KI. FDA has conducted studies of the palatability, solubility, and
stability of KI dissolved in a number of different liquids, including juice and formula.
(See the Home Preparation Procedure for Emergency Administration of Potassium
Iodide Tablets to Infants and Small Children .2 ) 	Emergency planners and others should
understand that absolute precision in dosing is generally not critical to safety or efficacy
(see also question 4).
Q4. 	FDA guidance recommends graded dosing by age, with neonates receiving the lowest
dose (16 mg daily) and adults receiving the highest (130 mg). FDA approved KI tablets
are available in two dosage strengths: 65 and 130 mg. At a minimum, dosing based on
FDA guidance would require either splitting tablets or dissolving tablets in liquids.
This may be impractical while responding to a radiological emergency. In this context,
what is the impact of uniform dosing across all age groups eligible for KI prophylaxis?
2 This is available at http://www.fda.gov/cder/drugprepare/default.htm.

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A4. 	The FDA’s guidance on dosing KI in radiation emergencies adheres to principles of
minimum effective dose and therefore recommends graded dosing according to age (and
thus, in effect, body size). There is ample evidence that the recommended doses, as well
as higher doses (e.g., up to 130 mg), will effectively block thyroidal uptake of radioactive
iodine if taken in advance of exposure. Furthermore, particularly among school-age
children, higher milligram doses are extremely safe.
We also realize that a scheme of graded dosing may be difficult to implement during a
radiological emergency involving large numbers of people. However, we continue to
emphasize attention to KI dosing in infants. Excess iodine intake can lead to transient
iodine-induced hypothyroidism. As we have said in our guidance, individuals who are
intolerant of KI at protective doses, as well as neonates, pregnant, and lactating women,
should be given priority with regard to other protective measures (i.e., sheltering,
evacuation, and control of the food supply).
In summary, if local emergency planners conclude that graded dosing is logistically impractical,
FDA believes that for populations at risk for radioiodine exposure, the overall benefits of taking
up to 130 mg of KI instead of the lower doses recommended for certain age groups far exceed
the small risks of overdosing. However, where feasible, adherence to FDA guidance should be
attempted when dosing infants.
Q5: 	Will dosage strengths of KI below 130 mg be available in the United States?
A5: 	Yes. An FDA approved 65-mg KI tablet is being marketed now in the United States.
Q6: 	Are there plans to update the labeling for marketed KI products to conform to the
revised FDA recommendations on dosing?
A6: 	Yes. FDA is working with manufacturers to amend the “Drug Facts” labeling for KI
products, which are sold over the counter, to incorporate the new dosing
recommendations.
Q7: 	How critical to public health is adherence to FDA’s recommendations with regard to
projected thyroid radioactive exposure thresholds for intervention by risk category?
Specifically, the existence of different thresholds for neonates, children through age
18, and pregnant or lactating women (> 5 cGy) versus adults aged 18 through 40 years
(> 10 cGy) versus adults over age 40 (> 500 cGy) are confusing and logistically
complex to follow in responding to a radiological emergency.
A7. 	The FDA recommendations for KI intervention encompass different threshold thyroid
radioactive exposures for different groups within the population. Several factors were
involved in this approach:
• 	During the Chernobyl accident, younger people exposed to radioactive iodine
(especially children 0 to 4 years old) were most sensitive to its carcinogenic effects.

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In the years following the accident, most children who subsequently developed
thyroid cancer apparently received internal thyroid radioactive exposures of less than
30 cGy, and the best dose-response information supports increased risk in children
receiving 5 cGy or more.
• 	As age increases, the risk of thyroidal side effects following excess (i.e.,
nonradioactive) iodine ingestion increases. This is due to the increasing prevalence of
underlying thyroidal illness with older age (e.g., Graves’ disease, thyroid nodules,
Hashimoto's thyroiditis).
• 	Thyroid irradiation in older adults (e.g., over 40 years of age) is associated with an
extremely low incidence of cancer. Therefore, KI is only recommended if a very
large internal radioactive dose to the thyroid is projected. In such a situation, KI
would be ingested to prevent destruction of the thyroid gland, which, if it occurred,
would lead to lifelong dependence on thyroid hormone replacement therapy.
In short, the recommended stepped intervention approach to KI use during radiation
emergencies is based on differences in overall benefit versus risk in different population
groups. Specifically, the benefits from thyroid blockade with KI predominate in the
young in whom the risks of thyroid cancer from radioiodine are the greatest. The risks of
KI take on more prominence in older adults in whom the risks of thyroid cancer are very
small.
Notwithstanding the above, it is important to note that among 7 million adults who took
stable iodine in Poland following Chernobyl, only two severe adverse reactions were
reported, both in persons with known allergy to iodine. Based on these data, we have
concluded that even if the risks associated with excess stable iodine are greater in adults
than in children, the risk of serious adverse reactions overall is exceedingly small.
In summary, FDA understands that a KI administration program that sets different
projected thyroid radioactive exposure thresholds for treatment of different population
groups may be logistically impractical to implement during a radiological emergency. If
emergency planners reach this conclusion, FDA recommends that KI be administered to
both children and adults at the lowest intervention threshold (i.e., > 5 cGy projected
internal thyroid exposure in children).
As a rule, however, individuals with known allergy to KI or with pre-existing thyroid
disease (e.g., Graves’ disease, thyroid nodules, Hashimoto's thyroiditis) that might
predispose them to adverse reactions should avoid KI. Most likely these will be adults,
who have little or no risk of developing thyroid cancer from radioactive exposure to the
thyroid and who may, in these cases, incur substantial risks from taking KI.
Q8: 	Does the FDA guidance apply to residents outside of the 10-mile emergency
planning zone for nuclear poser plants?
A8: 	Yes. KI administered in advance of an exposure will successfully block thyroidal uptake
of radioiodine, wherever one may reside.