Source: https://www.federalregister.gov/documents/2012/01/25/2012-1446/products-containing-imidazolines-equivalent-to-008-milligrams-or-more
Timestamp: 2018-07-18 13:42:54
Document Index: 333938559

Matched Legal Cases: ['§\u20091700', '§\u20091700', '§\u20091700', '§\u20091700', '§\u20091700', '§\u20091700', '§\u20091700', '§\u20091700']

Federal Register :: Products Containing Imidazolines Equivalent to 0.08 Milligrams or More
A Proposed Rule by the Consumer Product Safety Commission on 01/25/2012
3646-3653 (8 pages)
https://www.federalregister.gov/d/2012-1446 https://www.federalregister.gov/d/2012-1446
The Consumer Product Safety Commission (“CPSC,” “Commission,” or “we”) is proposing a rule to require child-resistant (“CR”) packaging for any over-the-counter or prescription product containing the equivalent of 0.08 milligrams or more of an imidazoline, a class of drugs that includes tetrahydrozoline, naphazoline, oxymetazoline, and xylometazoline, in a single package. Imidazolines are a family of drugs that are vasoconstrictors indicated for nasal congestion and/or ophthalmic irritation. Products containing imidazolines can cause serious adverse reactions, such as central nervous system (“CNS”) depression, decreased heart rate, and depressed ventilation in children treated with these drugs or who accidentally ingest them. Based on the scientific data, the Commission preliminarily finds that availability of 0.08 milligrams or more of an imidazoline in a single package, by reason of its packaging, is such that special packaging is required to protect children under 5 years old from serious personal injury or illness due to handling, using, or ingesting such a substance. We are taking this action under the Poison Prevention Packaging Act of 1970 (“PPPA”).[1]
Eye drops 4,571 0.19 138 2,831-6,311
Nose Sprays 2 1,104 0.31 34 426-1,782
Total 5,675 0.18 172 3,666-7,684
The following table of NEISS In-Depth Investigations qualitatively illustrates that children were able to obtain access to imidazoline packages.
991018HEP9007 13-month-old Eye drops Eye drops were on counter. Bottle may have been partially open. Child found with open bottle of eye drops with cap in her mouth.
050525HEP9006 15-month-old Eye drops Parents saw child playing with bottle of eye drops. She had gotten cap off. Parents noted cap was broken on examination.
080714HEP9016 15-month-old Eye drops Child found playing with empty bottle of eye drops.
980430HEP9006 18-month-old Eye drops Older sibling opened bottle and gave to victim.
050907HEP9001 20-month-old Eye drops Eye drops on low dresser, child was able to reach with her hands. Parents say child can open “anything.”
011023HEP9001 23-month-old Eye drops Child pulled eye drops off counter and removed lid.
000531HEP9005 2-year-old Nasal Spray Child came out of bathroom with empty bottle. Bottle had not been put away properly and was within victim's reach.
000601HEP9015 2-year-old Eye drops Mother left bottle on sink in bathroom after using it. Victim came out of bathroom sucking on bottle. Not clear if child or mother took cap off.
011023HEP9003 2-year-old Eye drops Used chair to get to medicine cabinet in kitchen. Took out eye drops and opened them. Mother found child on kitchen counter with open eye drops in hand.
020130HEP9003 2-year-old Eye drops Took eye drops out of mother's purse and opened tightly closed cap.
970306HEP9001 2-year-old Eye drops Child found in bedroom with open bottle of eye drops. She opened bottle with her teeth.
990301HEP9015 2-year-old Eye drops Child took bottle of eye drops off of dresser and unscrewed top.
990416HEP9008 2-year-old Nasal Spray Child was in bedroom watching TV on bed. Took nasal spray off of nightstand next to bed. Open, empty bottle found on bed.
990419HEP9022 2-year-old Eye drops Bottle left on counter in bathroom was found empty in child's hand.
991018HEP9012 2-year-old Eye drops Child found holding bottle of eye drops; cap had been removed and was in his mouth.
020321HEP9004 3-year-old Eye drops Child found in bedroom with opened bottle of eye drops.
091009HEP9010 4-year-old Eye drops Bottle left on counter. Child was found with open bottle.
2.8-5.6 mg oxymetazoline Within 5 minutes. Child passed out and stopped breathing. Given CPR and taken to ER 18 mos Given fluids and admitted to ICU. Aroused from coma 8-10 hours later. Released later that day. Having headaches 3-4 times daily FDA MedWatch 439578450001 6/2004.
3-4 mg naphazoline “Soon” became “quite drowsy” for several hours 3 yrs Several hours Waring 1945.
3-4 mg naphazoline One hour after ingestion. Became hypothermic, lethargic, irritable, pale, irregular gasping respirations, hypertension, bradycardia. Followed by unconsciousness and imperceptible respirations 22 mos Child warmed and treated with caffeine and oxygen. Symptoms resolved after 15 hrs Hainsworth 1948.
2-2.5 mg tetrahydrozoline 90 minutes Lethargic, decreased heart rate, decreased blood pressure 17 mos Pediatric intensive care unit Recovered 24 hrs Jensen et al. 1989.
Up to 2 mg tetrahydrozoline Sharp increase and then decrease of heart rate 22 mos Pediatric intensive care unit FDA540321.
1.25-2.5 mg tetrahydrozoline Decreased heart rate Lethargic, difficult to arouse, depressed respiration 16 mos Admitted to hospital overnight FDA671307.
1.25-2.5 mg tetrahydrozoline 2 hrs. Ataxic, pale, drowsy, decreased heart rate, decreased respiration 1 yr Admitted to hospital Recovered 24 hrs Mindlin 1966.
1.3 mg tetrahydrozoline 30 min. Lethargic, difficulty breathing, vomiting, loss of consciousness 2 yrs Admitted to hospital, treated with charcoal. Released from hospital same day, symptoms resolved FDA 43222810001.
1-1.5 mg tetrahydrozoline 2-3 hrs Lethargy, decreased blood pressure, decreased respiration 2 yrs Pediatric intensive care unit Mechanical respiration for 18 hrs Recovered 48 hrs Tobias 1996.
0.25 mg x 3 or 0.75 * tetrahydrozoline 2 hrs. Apnea, decreased respirations, slowed heart rate 25 days Admitted to hospital Naloxone, Continuous positive airway pressure, oxygen Recovered 2 days Katar et al. 2010.
* Due to diminished clearance of drugs by the liver and kidney of the newborn, the three doses are considered additive.
Mindlin (1966) reported a case in which a 1-year-old girl ingested between 1/2 to 1 teaspoon (2.5-5 mL) of tetrahydrozoline eye drops and suffered CNS depression with slowed respiration and decreased heart rate. Based on this ingestion, recent publications define 2.5 mL tetrahydrozoline (0.05 percent, 1.25 mg) as the dose at which serious toxicity from imidazoline exposure can occur after ingestion (Holmes and Berman, 1999; Eddy and Howell 2000). In the preamble to the proposed FDA rule for OTC nasal decongestants, it was reported that the minimum oral dose of oxymetazoline in an adult causing measurable cardiovascular effects (on blood pressure and heart rate) was 1.8 mg of oxymetazoline (41 FR 38312, 38398 (September 9, 1976)). This minimum dose may be lower for children because they appear to be more sensitive to imidazoline effects than adults (Brainerd and Olmstead, 1956). Cases indicate that ingestion of as little as 0.75 mg of imidazolines can result in serious illness in children, requiring supportive therapy (Katar et al., 2010; Summary see Table 3). The most recent case of imidazoline ingestion is reviewed above in section III.C of this preamble. It involved a 25-day-old infant who suffered apnea after being treated with tetrahydrozoline nasal drops (0.05 percent). CPSC staff reviewing this case report calculated the total dose for this case to be 0.75 mg, which is the lowest dose of ingestion of which we are aware that caused severe adverse symptoms in a child.
Because serious effects on the heart and breathing rates occur with the ingestion of as little as 0.75 mg of tetrahydrozoline, we consider this the lowest observed adverse effect level (“LOAEL”). All of the imidazolines cause potent central and peripheral sympathetic effects, but tetrahydrozoline has the highest potency for CNS sedative/depressive effects and the lowest potency for cardiac effects. Oxymetazoline and naphazoline are the most potent imidazolines for peripheral cardiac effects and have an 8-10 times lower maximum daily dose than tetrahydrozoline (0.4 mg, 0.3 mg and 3.2 mg, respectively). Xylometazoline and oxymetazoline have a longer duration of action than tetrahydrozoline (12 hrs, 10 hrs, and 4-6 hrs, respectively).
The proposed rule would add a new paragraph 33 to 16 CFR 1700.14(a), which contains a list of substances requiring special packaging. Pursuant to § 1700.14(a), all substances listed in § 1700.14 must meet the requirements for special packaging contained in § 1700.20(a) (on testing procedures for special packaging). Proposed § 1700.14(a)(33) would provide that any over-the-counter or prescription product containing the equivalent of 0.08 milligrams or more of an imidazoline (tetrahydrozoline, naphazoline, oxymetazoline, or xylometazoline) in a single package, must be packaged in accordance with the provisions of § 1700.15(a), (b), and (c). Section 1700.15(a) contains general requirements for special packaging, such as the special packaging must continue to function with the effectiveness specifications set forth in § 1700.15(b). Section 1700.15(b), on effectiveness specifications, provides criteria that special packaging tested pursuant to § 1700.20 must meet. Finally, § 1700.15(c) provides that special packaging subject to this paragraph (c) may not be reused.
Authority: Pub. L. 91-601, secs. 1-9, 84 Stat. 1670-74, 15 U.S.C. 1471-76. Secs. 1700.1 and 1700.14 also issued under Pub. L. 92-573, sec. 30(a), 88 Stat. 1231. 15 U.S.C. 2079(a). 2. Section 1700.14 is amended to add paragraph (a)(33) to read as follows: