Provident Provisions

What is Potassium Iodide?
Potassium iodide is a white crystalline salt with chemical formula KI, used in radiation treatment. Potassium iodide may also be used to protect the thyroid from radioactive iodine in the event of an accident or terrorist attack at a nuclear power plant, or other nuclear attack. Radioiodine is a particularly dangerous radionuclide because the body concentrates it in the thyroid gland. Potassium iodide cannot protect against other causes of radiation poisoning, however.

How many tablets are in each package?
There are 14 tablets in each package of IOSAT. One package is enough to protect one adult for a one month period.

What is the daily dosage required?
Current FDA guidelines call for the daily administration of one IOSAT tablet (130 mg. of potassium iodide (KI)) for up to 14 days for adults and children over 60 pounds. Smaller children should take one_half tablet for 14 days.

Recent findings and the experience at Chernobyl (where 18 million children were given KI) suggest KI is even more effective than previously realized, and that thyroid blocking can take place at smaller doses. As a result, FDA is considering reducing the amount of the dosage, and is studying dose levels as small as 16 mg. for infants and 32 mgs. for small children for shorter periods. Currently, however, package instructions should be followed in the event of a large release of radioactive iodine from a power_plant accident or a nuclear weapon.

How long is the shelf life of potassium iodide?
Potassium Iodide is inherently stable. If kept dry in an unopened container at room temperature, it can be expected to last indefinitely. No IOSAT™ (Anbex brand of potassium iodide, USP) has ever failed to meet all specifications by the US Food and Drug Administration. In a recent test, product produced over 10 years ago was assayed and found to be within 1% of its labeled value.

How long does it usually take from the time I submit my electronic order until the time I get my product?
Orders received are normally shipped Priority Mail within 24 hours and should arrive within 2-3 days.

How long does the protection last?
IOSAT works by "saturating" the thyroid with stable iodide so it will not absorb radioactive iodine that might be released in an accident. Under current dosing guidelines, a fully saturated thyroid would be protected for up to one month, which is long enough for radioactive iodine (which has a half_life of 8 days) to disappear from the environment.

How long has Iosat been around?
Shortly after the Three Mile Island accident in 1979. The company received its NDA (the FDA approval to sell the product) in 1982 after FDA review of the product and its manufacturing process.

Does KI help prevent other cancers that might occur other places in the body?
IOSAT only protects against radioactive iodine which can injure the thyroid and cause thyroid cancer, thyroid nodules, and other thyroid problems. The product is essentially ineffective against other radioactive products. However, since radioactive iodine would probably be the cause of 90% to 95% of all "off_site" injuries in a power_plant accident, the protection provided by IOSAT is extremely valuable. (At Chernobyl, for example, thyroid cancer, which is now epidemic in some areas as a result of the accident, was the only health effect seen in areas more than a few miles from the plant.)

What is the US Government position on providing KI to workers and the public in the event of another nuclear emergency?
The U S Nuclear Regulatory Commission (NRC) does not dispute the safety or effectiveness of KI. In fact, they require nuclear power_plants to stockpile it to protect plant workers, and FEMA (Federal Emergency Management Agency) plans call for KI to protect those individuals who would be unable to be evacuated in a nuclear accident _ especially those under the care of the government (such as prisoners or patients in government hospitals).

But the NRC is resisting the calls for a national stockpile of KI, claiming it is "unnecessary." As a result, the US remains the only major nuclear power that does not have a supply to protect its citizens. Recently, to counter the widespread criticism of this policy, the government announced it had established a "national stockpile" of KI. This news was welcomed by many in the scientific community. However, at a recent meeting, the NRC admitted that its operational "national stockpile" consisted of only 2500 tablets, not even enough for 200 people.

As a reaction to criticism by US medical groups and the World Health Organization, the NRC has announced it would make KI available (free of charge) to state or local governments desiring it. Again, this news was greeted with enthusiasm. However, following this announcement, the NRC "clarified" its position, and now says it will provide KI only to those people living in communities within the 10 mile "EPZ" (Emergency Planning Zone) surrounding nuclear plants. Given that most casualties in a nuclear accident would take place more than 50 miles from the plant (following Chernobyl, thousands of cases of childhood thyroid cancer developed hundreds of miles away), the current NRC position is probably of questionable value.

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What is Potassium Iodide?

• Potassium Iodide (chemical name 'KI') is much more familiar to most than they might first expect. It is the ingredient added to your table salt to make it iodized salt.
• Potassium Iodide (KI) is approximately 76.5% iodine.
• In 1978, the U.S. Food and Drug Administration found KI "safe and effective" for use in radiological emergencies and approved its over-the-counter sale. COMSECY-98-016 - FEDERAL REGISTER NOTICE ON POTASSIUM IODIDE
• "FDA maintains that KI is a safe and effective means by which to prevent radioiodine uptake by the thyroid gland, under certain specified conditions of use, and thereby obviate the risk of thyroid cancer in the event of a radiation emergency." FDA

How Does Potassium Iodide Provide Anti-Radiation Protection?

• "The thyroid gland is especially vulnerable to atomic injury since radioactive isotopes of iodine are a major component of fallout." New England Journal of Medicine. Vol. 274 on Page 1442
  
  
• "There is no medicine that will effectively prevent nuclear radiations from damaging the human body cells that they strike.However, a salt of the elements potassium and iodine, taken orally even in very small quantities 1/2 hour to 1 day before radioactive iodines are swallowed or inhaled, prevents about 99% of the damage to the thyroid gland that otherwise would result. The thyroid gland readily absorbs both non-radioactive and radioactive iodine, and normally it retains much of this element in either or both forms.

  When ordinary, non-radioactive iodine is made available in the blood for absorption by the thyroid gland before any radioactive iodine is made available, the gland will absorb and retain so much that it becomes saturated with non-radioactive iodine. When saturated, the thyroid can absorb only about l% as much additional iodine, including radioactive forms that later may become available in the blood: then it is said to be blocked. (Excess iodine in the blood is rapidly eliminated by the action of the kidneys.) page 111 Nuclear War Survival Skills, Original Edition,Cresson H. Kearny. Published September, 1979, by Oak Ridge National Laboratory, a Facility of the U.S. Department of Energy (Updated and Expanded 1987 Edition)
  
  

• "Potassium iodide, if taken in time, blocks the thyroid gland's uptake of radioactive iodine and thus could help prevent thyroid cancers and other diseases that might otherwise be caused by exposure to airborne radioactive iodine that could be dispersed in a nuclear accident." The Nuclear Regulatory Commission (NRC. July 1, 1998 in USE OF POTASSIUM IODIDE IN EMERGENCY RESPONSE
  
  
  
  Buy Potassium Iodide
  
  
  
• "Stable iodine administered before, or promptly after, intake of radioactive iodine can block or reduce the accumulation of radioactive iodine in the thyroid."World Health Organization (WHO) Guidelines for Iodine Prophylaxis following Nuclear Accidents. Updated 1999.

  "The effectiveness of KI as a specific blocker of thyroid radioiodine uptake is well established (Il'in LA, et al., 1972) as are the doses necessary for blocking uptake. As such, it is reasonable to conclude that KI will likewise be effective in reducing the risk of thyroid cancer in individuals or populations at risk for inhalation or ingestion of radioiodines."

  "Thus, the studies following the Chernobyl accident support the etiologic role of relatively small doses of radioiodine in the dramatic increase in thyroid cancer among exposed children. Furthermore, it appears that the increased risk occurs with a relatively short latency. Finally, the Polish experience supports the use of KI as a safe and effective means by which to protect against thyroid cancer caused by internal thyroid irradiation from inhalation of contaminated air or ingestion of contaminated food and drink when exposure cannot be prevented by evacuation, sheltering, or food and milk control." FDA

Dosage and Safety Regarding Potassium Iodide (KI) Usage

"Based on the FDA adverse reaction reports and an estimated 48 x 106 [48 million] 300-mg doses of potassium iodide administered each year [in the United States], the NCRP [National Council on Radiation Protection and Measurements] estimated an adverse reaction rate of from 1 in a million to 1 in 10 million doses." (It should be pointed out that this extremely low adverse reaction rate is for doses over twice as large as the 130-mg prophylactic dose.)

Additional copies are available from:
Office of Training and Communications
Division of Communications Management
Drug Information Branch, HFD-210
5600 Fishers Lane
Rockville, MD 20857
(Tel) 301-827-4573
(Internet) http://www.fda.gov/cder/guidance/index.htm

Guidance

Potassium Iodide as a Thyroid Blocking

Agent in Radiation Emergencies

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

The objective of this document is to provide guidance to other Federal agencies, including the Environmental Protection Agency (EPA) and the Nuclear Regulatory Commission (NRC), and to state and local governments regarding the safe and effective use of potassium iodide (KI) as an adjunct to other public health protective measures in the event that radioactive iodine is released into the environment. The adoption and implementation of these recommendations are at the discretion of the state and local governments responsible for developing regional emergency-response plans related to radiation emergencies.

This guidance updates the Food and Drug Administration (FDA) 1982 recommendations for the use of KI to reduce the risk of thyroid cancer in radiation emergencies involving the release of radioactive iodine. The recommendations in this guidance address KI dosage and the projected radiation exposure at which the drug should be used.

These recommendations were prepared by the Potassium Iodide Working Group, comprising scientists from the FDA's Center for Drug Evaluation and Research (CDER) and Center for Devices and Radiological Health (CDRH) in collaboration with experts in the field from the National Institutes of Health (NIH). Although they differ in two respects (as discussed in Section IV.B), these revised recommendations are in general accordance with those of the World Health Organization (WHO), as expressed in its Guidelines for Iodine Prophylaxis Following Nuclear Accidents: Update 1999 (WHO 1999).

II.BACKGROUND

Under 44 CFR 351, the Federal Emergency Management Agency (FEMA) has established roles and responsibilities for Federal agencies in assisting state and local governments in their radiological emergency planning and preparedness activities. The Federal agencies, including the Department of Health and Human Services (HHS), are to carry out these roles and responsibilities as members of the Federal Radiological Preparedness Coordinating Committee (FRPCC). Under 44 CFR 351.23(f), HHS is directed to provide guidance to state and local governments on the use of radioprotective substances and the prophylactic use of drugs (e.g., KI) to reduce the radiation dose to specific organs. This guidance includes information about dosage and projected radiation exposures at which such drugs should be used.

The FDA has provided guidance previously on the use of KI as a thyroid blocking agent. In the Federal Register of December 15, 1978, FDA announced its conclusion that KI is a safe and effective means by which to block uptake of radioiodines by the thyroid gland in a radiation emergency under certain specified conditions of use. In the Federal Register of June 29, 1982, FDA announced final recommendations on the administration of KI to the general public in a radiation emergency. Those recommendations were formulated after reviewing studies relating radiation dose to thyroid disease risk that relied on estimates of external thyroid irradiation after the nuclear detonations at Hiroshima and Nagasaki and analogous studies among children who received therapeutic radiation to the head and neck. Those recommendations concluded that at a projected dose to the thyroid gland of 25 cGy or greater from ingested or inhaledradioiodines, the risks of short-term use of small quantities of KI were outweighed by the benefits of suppressingradioiodine-induced thyroid cancer.¹ The amount of KI recommended at that time was 130 mg per day for adults and children above 1 year of age and 65 mg per day for children below 1 year of age. The guidance that follows revises our 1982 recommendations on the use of KI for thyroid cancer prophylaxis based on a comprehensive review of the data relating radioioidine exposure to thyroid cancer risk accumulated in the aftermath of the 1986 Chernobyl reactor accident.

III. DATA SOURCES

A. Reliance on Data from Chernobyl

In epidemiological studies investigating the relationship between thyroidal radioiodine exposure and risk of thyroid cancer, the estimation of thyroid radiation doses is a critical and complex aspect of the analyses. Estimates of exposure, both for individuals and across populations, have been reached in different studies by the variable combination of (1) direct thyroid measurements in a segment of the exposed population; (2) measurements of ¹³¹I (iodine isotope) concentrations in the milk consumed by different groups (e.g., communities) and of the quantity of milk consumed; (3) inference from ground deposition of long-lived radioisotopes released coincidentally and presumably in fixed ratios with radioiodines; and (4) reconstruction of the nature and extent of the actual radiation release.

All estimates of individual and population exposure contain some degree of uncertainty. The uncertainty is least for estimates of individual exposure based on direct thyroid measurements. Uncertainty increases with reliance on milk consumption estimates; is still greater with estimates derived from ground deposition of long-lived radioisotopes, and is highest for estimates that rely heavily on release reconstruction.

Direct measurements of thyroid radioactivity are unavailable from the Hanford, Nevada Test Site, and Marshall Islands exposures. Indeed, the estimates of thyroid radiation doses related to these releases rely heavily on release reconstructions and, in the former two cases, on recall of the extent of milk consumption 40 to 50 years after the fact. In the Marshall Islands cohort, urinary radioiodine excretion data were obtained and used in calculating exposure estimates.

Because of the great uncertainty in the dose estimates from the Hanford and Nevada Test Site exposures and due to the small numbers of thyroid cancers occurring in the populations potentially exposed, the epidemiological studies of the excess thyroid cancer risk related to these radioiodine releases are, at best, inconclusive. As explained below, the dosimetric data derived in the studies of individual and population exposures following the Chernobyl accident, although not perfect, are unquestionably superior to data from previous releases. In addition, the results of the earlier studies are inadequate to refute cogent case control study evidence from Chernobyl of a cause-effect relationship between thyroid radioiodine deposition and thyroid cancer risk.²

The Chernobyl reactor accident of April 1986 provides the best-documented example of a massive radionuclide release in which large numbers of people across a broad geographical area were exposed acutely to radioiodines released into the atmosphere. Therefore, the recommendations contained in this guidance are derived from our review of the Chernobyl data as they pertain to the large number of thyroid cancers that occurred. These are the most comprehensive and reliable data available describing the relationship between thyroid radiation dose and risk for thyroid cancer following an environmental release of ¹³¹I. In contrast, the exposures resulting from radiation releases at the Hanford Site in Washington State in the mid-1940s and in association with the nuclear detonations at the Nevada Test Site in the 1950s were extended over years, rather than days to weeks, contributing to the difficulty in estimating radioactive dose in those potentially exposed (Davis et al., 1999; Gilbert et al., 1998). The exposure of Marshall Islanders to fallout from the nuclear detonation on Bikini in 1954 involved relatively few people, and although the high rate of subsequent thyroid nodules and cancers in the exposed population was likely caused in large part by radioiodines, the Marshall Islands data provide little insight into the dose-response relationship between radioactive iodine exposure and thyroid cancer risk (Robbins and Adams 1989).

Beginning within a week after the Chernobyl accident, direct measurements of thyroid exposure were made in hundreds of thousands of individuals, across three republics of the former Soviet Union (Robbins and Schneider 2000, Gavrilin et al., 1999, Likhtarev et al., 1993, Zvonova and Balonov 1993). These thyroid measurements were used to derive, in a direct manner, the thyroid doses received by the individuals from whom the measurements were taken. The thyroid measurements were also used as a guide to estimate the thyroid doses received by other people, taking into account differences in age, milk consumption rates, and ground deposition densities, among other things. The thyroid doses derived from thyroid measurements have a large degree of uncertainty, especially in Belarus, where most of the measurements were made by inexperienced people with detectors that were not ideally suited to the task at hand (Gavrilin et al., 1999 and UNSCEAR 2000). However, as indicated above, the uncertainties attached to thyroid dose estimates derived from thyroid measurements are, as a rule, lower than those obtained without recourse to those measurements.

It is also notable that the thyroid radiation exposures after Chernobyl were virtually all internal, from radioiodines. Despite some degree of uncertainty in the doses received, it is reasonable to conclude that the contribution of external radiation was negligible for most individuals. This distinguishes the Chernobyl exposures from those of the Marshall Islanders. Thus, the increase in thyroid cancer seen after Chernobyl is attributable to ingested or inhaled radioiodines. A comparable burden of excess thyroid cancers could conceivably accrue should U.S. populations be similarly exposed in the event of a nuclear accident. This potential hazard highlights the value of averting such risk by using KI as an adjunct to evacuation, sheltering, and control of contaminated foodstuffs.

B. Thyroid Cancers in the Aftermath of Chernobyl

The Chernobyl reactor accident resulted in massive releases of ¹³¹I and other radioiodines. Beginning approximately 4 years after the accident, a sharp increase in the incidence of thyroid cancer among children and adolescents in Belarus and Ukraine (areas covered by the radioactive plume) was observed. In some regions, for the first 4 years of this striking increase, observed cases of thyroid cancer among children aged 0 through 4 years at the time of the accident exceeded expected number of cases by 30- to 60-fold. During the ensuing years, in the most heavily affected areas, incidence is as much as 100-fold compared to pre-Chernobyl rates (Robbins and Schneider 2000; Gavrilin et al., 1999; Likhtarev et al., 1993; Zvonova and Balonov 1993). The majority of cases occurred in children who apparently received less than 30 cGy to the thyroid (Astakhova et al., 1998). A few cases occurred in children exposed to estimated doses of < 1 cGy; however, the uncertainty of these estimates confounded by medical radiation exposures leaves doubt as to the causal role of these doses of radioiodine (Souchkevitch and Tsyb 1996).

The evidence, though indirect, that the increased incidence of thyroid cancer observed among persons exposed during childhood in the most heavily contaminated regions in Belarus, Ukraine, and the Russian Federation is related to exposure to iodine isotopes is, nevertheless, very strong (IARC 2001). We have concluded that the best dose-response information from Chernobyl shows a marked increase in risk of thyroid cancer in children with exposures of 5 cGy or greater (Astakhova et. al., 1998; Ivanov et al., 1999; Kazakov et al., 1992). Among children born more than nine months after the accident in areas traversed by the radioactive plume, the incidence of thyroid cancer has not exceeded preaccident rates, consistent with the short half-life of ¹³¹I.

The use of KI in Poland after the Chernobyl accident provides us with useful information regarding its safety and tolerability in the general population. Approximately 10.5 million children under age 16 and 7 million adults received at least one dose of KI. Of note, among newborns receiving single doses of 15 mg KI, 0.37 percent (12 of 3214) showed transient increases in TSH (thyroid stimulating hormone) and decreases in FT4 (free thyroxine). The side effects among adults and children were generally mild and not clinically significant. Side effects included gastrointestinal distress, which was reported more frequently in children (up to 2 percent, felt to be due to bad taste of SSKI solution) and rash (~1 percent in children and adults). Two allergic reactions were observed in adults with known iodine sensitivity (Nauman and Wolff 1993).

Thus, the studies following the Chernobyl accident support the etiologic role of relatively small doses of radioiodine in the dramatic increase in thyroid cancer among exposed children. Furthermore, it appears that the increased risk occurs with a relatively short latency. Finally, the Polish experience supports the use of KI as a safe and effective means by which to protect against thyroid cancer caused by internal thyroid irradiation from inhalation of contaminated air or ingestion of contaminated food and drink when exposure cannot be prevented by evacuation, sheltering, or food and milk control.

IV.CONCLUSIONS AND RECOMMENDATIONS

A. Use of KI in Radiation Emergencies: Rationale, Effectiveness, Safety

For the reasons discussed above, the Chernobyl data provide the most reliable information available to date on the relationship between internal thyroid radioactive dose and cancer risk. They suggest that the risk of thyroid cancer is inversely related to age, and that, especially in young children, it may accrue at very low levels of radioiodine exposure. We have relied on the Chernobyl data to formulate our specific recommendations below.

The effectiveness of KI as a specific blocker of thyroid radioiodine uptake is well established (Il'in LA, et al., 1972) as are the doses necessary for blocking uptake. As such, it is reasonable to conclude that KI will likewise be effective in reducing the risk of thyroid cancer in individuals or populations at risk for inhalation or ingestion of radioiodines.

Short-term administration of KI at thyroid blocking doses is safe and, in general, more so in children than adults. The risks of stable iodine administration include sialadenitis (an inflammation of the salivary gland, of which no cases were reported in Poland among users after the Chernobyl accident), gastrointestinal disturbances, allergic reactions and minor rashes. In addition, persons with known iodine sensitivity should avoid KI, as should individuals with dermatitis herpetiformis and hypocomplementemic vasculitis, extremely rare conditions associated with an increased risk of iodine hypersensitivity.

Thyroidal side effects of stable iodine include iodine-induced thyrotoxicosis, which is more common in older people and in iodine deficient areas but usually requires repeated doses of stable iodine. In addition, iodide goiter and hypothyroidism are potential side effects more common in iodine sufficient areas, but they require chronic high doses of stable iodine (Rubery 1990). In light of the preceding, individuals with multinodular goiter, Graves' disease, and autoimmune thyroiditis should be treated with caution, especially if dosing extends beyond a few days. The vast majority of such individuals will be adults.

The transient hypothyroidism observed in 0.37 percent (12 of 3214) of neonates treated with KI in Poland after Chernobyl has been without reported sequelae to date. There is no question that the benefits of KI treatment to reduce the risk of thyroid cancer outweigh the risks of such treatment in neonates. Nevertheless, in light of the potential consequences of even transient