> > POISINDEX MANAGEMENTS (from MICROMEDEX)
> > F. RADIONUCLIDE BLOCKERS
> > 1. Ingestion of radionuclides mandates special
> > considerations. Following ingestion, there is usually a
> > variable period of time before absorption and uptake by
> > cells occurs. It is of utmost importance to determine the
> > specific radionuclide ingested, inhaled, or injected, as
> > therapy with chelating, diluting, or blocking agents is
> > determined by the radioelement(s) involved.
> > 2. A blocking agent is a substance which saturates a tissue
> > with a nonradioactive element, thereby reducing the uptake
> > of the radionuclide. An example of this is potassium iodide
> > (Lugol's solution) which reduces the uptake of radioactive
> > iodine (I-131).
> > 3. IODINE-131 -
> > a. LUGOL'S SOLUTION -
> > (1) Potassium iodide (Lugol's solution) reduces
> > radioactive iodine uptake by the thyroid by 90 percent if
> > given within 2 hours after exposure (Lincoln, 1976;
> > Jarrett, 1999).
> > (2) RECOMMENDATION - Mix 5 grams iodine and 10 grams
> > potassium iodide with water to a final amount of 100
> > milliliters. Give 100 milligrams, 2 to 3 drops in glass
> > of water. Alternatively, give 130 mg potassium iodide, or
> > 0.8 milliliter Lugol's solution for adults
> > and adolescents (Jarrett, 1999).
> > (¯`·.¸¸.·´¯`·.¸¸.·´¯`·.¸¸.·´¯`·.¸¸.·´¯`·.¸¸.·´¯`·.¸¸.·´¯`·.¸¸.·´¯)
> > Via FedWorld.gov
> > - Analysis of Potassium Iodide (KI) Prophylaxis for the General Public
> > in the Event of a Nuclear Accident. Performing Org.: Cohen (S.) and
> > Associates, Inc., McLean, VA.; SCIENTECH, Inc., Rockville, MD.;
> > Nuclear Regulatory Commission, Washington, DC. Office of Nuclear
> > Regulatory Research.
> > NTIS Order No: NUREG/CR-6310INZ. No summary is available on this web
> > site for this publication.
> > In Fed Register:
> > SUMMARY: The Nuclear Regulatory Commission (NRC) is amending its
> > emergency planning regulations governing the domestic licensing of
> > production and utilization facilities. The final rule requires that
> > consideration be given to including potassium iodide (KI) as a
> > protective measure for the general public that would supplement
> > sheltering and evacuation. KI would help prevent thyroid cancers in
> > the unlikely event of a major release of radioactivity from a nuclear
> > power plant. The final rule responds to petitions for rulemaking (PRM
> > 50-63 and PRM 50-63A) submitted by Mr. Peter G. Crane concerning the
> > use of KI in emergency plans.
> > EFFECTIVE DATES: April 19, 2001.
> > On June 16, 1997, the NRC staff forwarded to the Commission a staff
> > version of the FRPCC- proposed Policy Regarding Use of Potassium
> > Iodide After a Severe Accident at a Nuclear Power Plant. In its SRM of
> > June 30, 1997, the Commission endorsed the Federal offer to fund the
> > purchase of KI for States. On June 26, 1998, the Commission directed
> > that the FRPCC proposed Policy be modified to include a statement to
> > the effect that State and local decision makers, provided with proper
> > information, may find the use of KI as a protective supplement is
> > reasonable and prudent for specific local conditions. As noted above,
> > the Commission also reiterated its endorsement of the Federal offer to
> > fund KI stockpiles for States. Subsequently, on April 22, 1999, the
> > Commission directed the staff to amend the draft FRN on the Federal KI
> > Policy to conform to the Commission decision on the petitions for
> > rulemaking, and the decision not to fund State KI stockpiles.
> > On April 29, 1999, the Director of FEMA, Mr. James Lee Witt, forwarded
> > a letter to the Commission commenting on the issue of funding of
> > stockpiles of KI for States. The letter objected to the Commission's
> > ``unilateral'' decision on funding, and also noted ``FEMA has always
> > opposed the notion that Federal regional stockpiles of KI would be
> > effective [and believes that] regional stockpiles would complicate,
> > not strengthen radiological emergency preparedness.'' FEMA believes
> > that if a State opts to use KI as a supplemental protective measure,
> > the NRC should provide the funds for such a purchase.
> > The NRC responded to Mr. Witt's letter on June 15, 1999. This letter
> > noted the Commission's decision not to fund state stockpiles of KI as
> > well as the reasons underlying that decision. The letter also referred
> > to the Commission's direction to ``the NRC staff to work with FEMA
> > staff to establish and maintain regional KI stockpiles to be used in
> > the event that local stockpiles prove to be insufficient, or when a
> > state without a stockpile elects to use KI on an ad hoc basis in the
> > case of a nuclear emergency.'' The letter expressed confidence that
> > the staffs, working together would successfully resolve the KI supply
> > issue. The status of the stockpile and funding issues are discussed
> > later in this notice. NRC is working closely with the other Federal
> > agencies to determine appropriate changes to the 1985 policy. A
> > decision regarding policy changes will be reached after the conclusion
> > of this rulemaking.
> > (¯`·.¸¸.·´¯`·.¸¸.·´¯`·.¸¸.·´¯`·.¸¸.·´¯`·.¸¸.·´¯`·.¸¸.·´¯`·.¸¸.·´¯)
> > [Federal Register: January 4, 2001 (Volume 66, Number 3)]
> > [Notices]
> > [Page 801-802]
> > >From the Federal Register Online via GPO Access [wais.access.gpo.gov]
> > [DOCID:fr04ja01-65]
> > -----------------------------------------------------------------------
> > DEPARTMENT OF HEALTH AND HUMAN SERVICES
> > Food and Drug Administration
> > [Docket No. 00D-1681]
> > Draft Guidance on Potassium Iodide as a Thyroid Blocking Agent in
> > Radiation Emergencies; Availability
> > AGENCY: Food and Drug Administration, HHS.
> > ACTION: Notice.
> > -----------------------------------------------------------------------
> > SUMMARY: The Food and Drug Administration (FDA) is announcing the
> > availability of a draft guidance entitled ``Potassium Iodide as a
> > Thyroid Blocking Agent in Radiation Emergencies.'' This draft guidance
> > updates a notice of availability entitled ``Potassium Iodide as a
> > Thyroid-Blocking Agent In a Radiation Emergency: Final Recommendations
> > On Use'' published in the Federal Register on June 29, 1982,
> > concerning the prophylactic use of potassium iodide (KI) in the event
> > of release of radioactive isotopes of iodine. In the draft guidance,
> > FDA maintains its position that KI is a safe and effective means by
> > which to prevent radioiodine uptake by the thyroid gland, under
> > certain specified condition for use, and thus to obviate the risk of
> > thyroid cancer in the event of a radiation emergency.
> > DATES: February 5, 2001.
> > ADDRESSES: Copies of this draft guidance are available on the Internet
> > at http://www.fda.gov/cder/guidance/index.htm. Submit written requests
> > for single copies of the draft guidance to the Drug Information Branch
> > (HFD-210), Center for Drug Evaluation and Research, Food and Drug
> > Administration, 5600 Fishers Lane, Rockville, MD 20857. Send one self-
> > addressed adhesive label to assist that office in processing your
> > requests. Submit written comments on the draft guidance to the Dockets
> > Management Branch (HFA-305), Food and Drug Administration, 5630
> > Fishers Lane, rm. 1061, Rockville, MD 20852.
> > FOR FURTHER INFORMATION CONTACT: Rose E. Cunningham, Executive
> > Operations (HFD-06), Center for Drug Evaluation and Research, Food and
> > Drug Administration, 5600 Fishers Lane, Rockville, MD 20857, 301-594-
> > 6779.
> > SUPPLEMENTARY INFORMATION: FDA is announcing the availability of a
> > draft guidance entitled ``Potassium Iodide as a Thyroid Blocking Agent
> > in Radiation Emergencies.''
> > The Federal Emergency Management Agency 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 (DHHS), are expected to accomplish these roles and
> > responsibilities as part of the Federal Radiological Preparedness
> > Coordinating Committee. Among other responsibilities, the DHHS is to
> > provide guidance on the use of radioprotective substances to reduce
> > radiation doses to specific organs from the release into the
> > environment of large quantities of radioactivity. FDA is specifically
> > charged with providing guidance on the prophylactic use of KI in the
> > event of release of radioactive isotopes of iodine.
> > FDA is announcing the availability of a draft guidance that updates
> > the notice of availability, ``Potassium Iodide as a Thyroid-Blocking
> > Agent In a Radiation Emergency: Final Recommendations On Use,''
> > published in the Federal Register of June 29, 1982 (47 FR 28158). In
> > this draft guidance, FDA maintains its position 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 thus to lessen
> > the risk of thyroid cancer in the event of a radiation emergency. In
> > this draft guidance, FDA proposes lower radioactive exposure
> > thresholds for KI prophylaxis as well as lower doses of KI for
> > neonates, infants, and children than previously recommended. FDA's
> > revised recommendations are in general accordance with those of the
> > World Health Organization (WHO), as expressed in its ``Guidelines for
> > Iodine Phrophylaxis Following Nuclear Accidents'' (1999), though they
> > differ from those of the WHO in two areas.
> > First, for the sake of logistical simplicity, FDA recommends the
> > 65-milligram (mg) dose of KI for all school-age children while
> > allowing for the full adult dose of 130 mg in adolescents approaching
> > adult size. WHO recommends 130 mg KI for adults and adolescents (over
> > 12 years of age). Second, FDA recommends that KI prophylaxis in those
> > under age 19 and in pregnant or lactating women be triggered at a
> > predicted thyroid radioiodine exposure of 5 centiGray (cGy), while WHO
> > establishes 1 cGy as the threshold for intervention. FDA has concluded
> > from the Chernobyl data that the most reliable evidence demonstrates a
> > significant increase in risk of childhood thyroid cancer at exposures
> > of 5 cGy or greater.
> > The recommendations in the draft guidance were prepared by scientists
> > from the Center for Drug Evaluation and Research and from the Center
> > for Devices and Radiological Health of FDA in consultation with other
> > governmental experts.
> > This draft guidance is being issued consistent with FDA's good
> > guidance practices (65 FR 56468, September 19, 2000). The draft
> > guidance represents the agency's current thinking on use of potassium
> > iodide as a thyroid blocking agent in radiation emergencies. 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.
> > Interested persons may submit to the Dockets Management Branch
> > (address above) written comments on the draft guidance. Two copies of
> > any comments are to be submitted, except that individuals may submit
> > one copy. Comments are to be identified with the docket number found
> > in brackets in the heading of this document. The draft guidance and
> > received comments are available for public examination in the Dockets
> > Management Branch between 9 a.m. and 4 p.m., Monday through Friday.
> > Dated: December 26, 2000.
> > Margaret M. Dotzel,
> > Associate Commissioner for Policy.
> > [FR Doc. 01-189 Filed 1-3-01; 8:45 am]
> > BILLING CODE 4160-01-F
> > = - = - = - = - = - = - = - = - = - = - = - =
> > http://www.fda.gov/cder/guidance/3698dft.htm#P177_18126
> > Potassium Iodide as a Thyroid Blocking Agent in Radiation Emergencies
> > DRAFT GUIDANCE
> > This guidance document is being distributed for comment purposes only.
> > Comments and suggestions regarding this draft document should be
> > submitted within 30 days of publication in the Federal Register of the
> > notice announcing the availability of the draft guidance. Submit
> > comments to Dockets Management Branch (HFA-305), Food and Drug
> > Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. All
> > comments should be identified with the docket number listed in the
> > notice of availability that publishes in the Federal Register.
> > For questions regarding this draft document contact (CDER) Rose
> > Cunningham 301-594-6779.
> > U.S. Department of Health and Human Services
> > Food and Drug Administration
> > Center for Drug Evaluation and Research (CDER)
> > December 2000
> > Procedural
> > 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
> > ...
> > IV. CONCLUSIONS AND RECOMMENDATIONS
> > A. Use of KI in radiation emergencies: rationale, effectiveness,
> > safety
> > The direct relationship between exposure to inhaled or ingested
> > radioiodines and thyroid cancer risk, if ever in doubt, is firmly
> > established in the aftermath of the 1986 Chernobyl accident. 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 (Sternthal et al., 1980) as are the doses
> > necessary for blockade. 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 (of which no cases were
> > reported in Poland among users after the Chernobyl accident), GI
> > disturbances, and minor rashes. In addition, persons with known iodide
> > 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 iodide-induced
> > thyrotoxicosis, which is more common in older people and in
> > iodide-deficient areas and usually requires repeated doses of stable
> > iodine. In addition, iodide goiter and hypothyroidism, potential side
> > effects more common in iodine-sufficient areas, 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 (12/3214) of
> > neonates treated with KI in Poland after Chernobyl has been without
> > 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 hypothyroidism for intellectual
> > development, we recommend that neonates (within the first month of
> > life) treated with KI be monitored for this effect by measurement of
> > TSH (and FT4, if indicated) and that thyroid hormone therapy be
> > instituted in cases in which hypothyroidism develops (Fisher,
> > Calaciura).
> > B.KI use in radiation emergencies: treatment recommendations
> > After careful review of the data from Chernobyl relating estimated
> > thyroid radiation dose and cancer risk in exposed children, FDA
> > recommends administration of KI to children aged 0-18 years and
> > pregnant or lactating women in the event of a projected radiation dose
> > to the thyroid of 5 cGy or greater. For adults up to 40 years of age,
> > KI should be administered at a projected radiation dose of 10 cGy or
> > greater. Adults over 40 need only take KI in the case of a projected
> > large internal radiation dose to the thyroid (>500 cGy) to prevent
> > hypothyroidism (see table).
> > Threshold Thyroid Radioactive Exposures and Recommended Doses of KI
> > for Different Risk Groups
> > For the radiation produced by I-131, the radiation quality factor is
> > approximately equal to 1, so that 1 cGy = 1 rem.
> > Pop'n Predicted KI dose # 130mg # of 65mg Lugol's
> > Exposed Thyroid mg tablets tablets solution
> > exposure(cGy)
> > Adults
> > >40 yrs >500 130 1 2 0.8 ml
> > Adults
> > >18-40 yrs >10 130 1 2 0.8 ml
> > Pregnant or
> > lactating women >5 130 1 2 0.8 ml
> > Adolesc.
> > >12-18 yrs* >5 65 1/2 1 0.4 ml
> > Children
> > >3-12 yrs >5 65 1/2 1 0.4 ml
> > >1 month-3 yrs >5 32 1/4 1/2 0.2 ml
> > birth-1 month >5 16 1/8 1/4 0.1 ml
> > * adolescents approaching adult size (> 70 kg) should receive the full
> > adult dose (130 mg)
> > [OEM: Lugol's sol'n dosing based on Poisondex conversion see above.
> > -Mod]
> > These FDA recommendations differ from those put forward in the World
> > Health Organization (WHO) 1999 guidelines for iodine prophylaxis in
> > two areas. WHO recommends the 130 mg dose of KI for adults and
> > adolescents (over 12 years). For the sake of logistical simplicity in
> > the dispensing and administration of KI to children, FDA recommends
> > the 65 mg dose as standard for all school- age children while allowing
> > for the adult dose (130 mg, 2 X 65 mg tablets) in adolescents
> > approaching adult size. The other difference lies in the threshold for
> > predicted exposure to those up to 18 years of age and to pregnant or
> > lactating women that will trigger KI prophylaxis. WHO recommends a 1
> > cGy threshold for this group. As stated earlier, FDA has concluded
> > from the Chernobyl data that the most reliable evidence supports a
> > significant increase in the risk of childhood thyroid cancer at
> > exposures of 5 cGy or greater.
> > The downward KI dose adjustment by age group, based on body size
> > considerations, adheres to the principle of minimum effective dose.
> > The recommended standard dose of KI for all school-age children is the
> > same (65 mg). However, adolescents approaching adult size (i.e., >70
> > kg) should receive the full adult dose (130 mg) for maximal blockade
> > of thyroid radioiodine uptake. Neonates ideally should receive the
> > lowest dose (16 mg) of KI to minimize the risk of hypothyroidism
> > during that critical phase of brain development (Calaciura et al.,
> > 1995). KI from tablets (either whole or fractions) or as fresh
> > saturated KI solution may be diluted in milk or water and the
> > appropriate volume administered to babies. As stated above, we
> > recommend that neonates (within the first month of life) treated with
> > KI be monitored for the potential development of hypothyroidism by
> > measurement of TSH (and FT4, if indicated) and that thyroid hormone
> > therapy be instituted in cases in which hypothyroidism develops
> > (Fisher 2000; Calaciura et al., 1995).
> > Pregnant women should be given KI for their own protection and for
> > that of the fetus, as iodine (whether stable or radioactive) readily
> > crosses the placenta. However, because of the risk of blocking fetal
> > thyroid function with excess stable iodine, repeat dosing with KI of
> > pregnant women should be avoided. Lactating females should be
> > administered KI for their own protection, as for other young adults,
> > potentially to reduce the radioiodine content of the breast milk, but
> > not as a means to deliver KI to infants, who should get their KI
> > directly. As for direct administration of KI, stable iodine as a
> > component of breast milk may also pose a risk of hypothyroidism in
> > nursing neonates. Therefore, if repeat dosing of the mother is
> > necessary, the nursing neonate should be monitored as recommended
> > above.
> > The protective effect of KI lasts approximately 24 hours. For optimal
> > prophylaxis, KI should therefore be dosed daily, until a risk of
> > significant exposure to radioiodines by either inhalation or ingestion
> > no longer exists. Individuals intolerant of KI at protective doses and
> > pregnant and lactating women (in whom repeat administration of KI
> > raises particular safety issues, see above) should be given priority
> > with regard to other protective measures (i.e., sheltering,
> > evacuation, and control of the food supply).