Efficacy of Flow Restrictors in Limiting Access of Liquid Medications by Young Children

      Objective

      To assess whether adding flow restrictors (FRs) to liquid medicine bottles can provide additional protection against unsupervised medication ingestions by young children, even when the child-resistant closure is not fully secured.

      Study design

      In April and May 2012, we conducted a block randomized trial with a convenience sample of 110 3- and 4-year-old children from 5 local preschools. Participants attempted to remove test liquid from an uncapped bottle with an FR and a control bottle without an FR (with either no cap or an incompletely closed cap).

      Results

      All but 1 (96%; 25 of 26) of the open control bottles and 82% (68 of 83) of the incompletely closed control bottles were emptied within 2 minutes. Only 6% (7 of 110) of the bottles with FRs were emptied during the 10-minute testing period, none before 6 minutes. Overall, children removed less liquid from the bottles with FRs than from the open or incompletely closed control bottles without FRs (both P < .001). All children assigned open control bottles and 90% of those assigned incompletely closed control bottles removed ≥25 mL of liquid. In contrast, 11% of children removed ≥25 mL of liquid from uncapped bottles with FRs. Older children (aged 54-59 months) were more successful than younger children at removing ≥25 mL of liquid (P = .002) from bottles with FRs.

      Conclusion

      Our findings suggest that adding FRs to liquid medicine bottles limits the accessibility of their contents to young children and could complement the safety provided by current child-resistant packaging.
      CDC (Centers for Disease Control and Prevention), ED (Emergency department), FR (Flow restrictor), OTC (Over-the-counter), PPPA (Poison Prevention Packaging Act)
      The Poison Prevention Packaging Act (PPPA) of 1970 requires child-resistant packaging for most medicines sold in the US.

      Poison Prevention Packaging Act, 15 USC §1471-1476; 1970.

      Since passage of the PPPA, the use of child-resistant packaging has contributed to the prevention of hundreds, if not thousands, of pediatric deaths from unsupervised medication ingestions.
      • Rodgers G.B.
      The safety effects of child-resistant packaging for oral prescription drugs: two decades of experience.
      • US Consumer Product Safety Commission
      Poison prevention packaging: a guide for healthcare professionals.
      Nevertheless, each year, 500 000 calls are made to poison centers regarding medication ingestion by young children.
      • Bronstein A.C.
      • Spyker D.A.
      • Cantilena Jr., L.R.
      • Green J.L.
      • Rumack B.H.
      • Dart R.C.
      2010 annual report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 28th annual report.
      The number of emergency department (ED) visits for unsupervised medication ingestions is rising, with more than 60 000 visits by young children annually.
      • Budnitz D.S.
      • Salis S.
      Preventing medication overdoses in young children: an opportunity for harm elimination.
      • Centers for Disease Control and Prevention
      National Poison Prevention Week: 50th anniversary—March 18-24, 2012.
      National data on the dosage forms of medicines involved in unsupervised ingestions are limited; however, approximately 80% of ED visits for ingestion of cough and cold medicines and 37% of ED visits for ingestion of acetaminophen products involved liquid medicines.
      • Shehab N.
      • Schaefer M.K.
      • Kegler S.R.
      • Budnitz D.S.
      Adverse events from cough and cold medications after a market withdrawal of products labeled for infants.
      • Budnitz D.S.
      • Lovegrove M.C.
      • Crosby A.E.
      Emergency department visits for overdoses of acetaminophen-containing products.
      A study of poison center calls identified liquid antibiotics prescribed for the child or a sibling as the most frequently ingested prescription medicines.
      • Jacobson B.J.
      • Rock A.R.
      • Cohn M.S.
      • Litovitz T.
      Accidental ingestions of oral prescription drugs: a multicenter survey.
      Most ED visits for unsupervised medication ingestions involve children under age 5 years, with a peak incidence at age 2.
      • Schillie S.F.
      • Shehab N.
      • Thomas K.E.
      • Budnitz D.S.
      Medication overdoses leading to emergency department visits among children.
      • Chien C.
      • Marriott J.L.
      • Ashby K.
      • Ozanne-Smith J.
      Unintentional ingestion of over-the-counter medications in children less than 5 years old.
      Although research on the circumstances surrounding these ingestions is limited, previous studies have shown that most occur in home environments,
      • Jacobson B.J.
      • Rock A.R.
      • Cohn M.S.
      • Litovitz T.
      Accidental ingestions of oral prescription drugs: a multicenter survey.
      • Wiseman H.M.
      • Guest K.
      • Murray V.S.
      • Volans G.N.
      Accidental poisoning in childhood: a multicentre survey, 2: the role of packaging in accidents involving medications.
      • Ozanne-Smith J.
      • Day L.
      • Parsons B.
      • Tibballs J.
      • Dobbin M.
      Childhood poisoning: access and prevention.
      during a brief moment when the caregiver is not watching,
      • Ozanne-Smith J.
      • Day L.
      • Parsons B.
      • Tibballs J.
      • Dobbin M.
      Childhood poisoning: access and prevention.
      and when medicines are not in their usual storage location.
      • Jacobson B.J.
      • Rock A.R.
      • Cohn M.S.
      • Litovitz T.
      Accidental ingestions of oral prescription drugs: a multicenter survey.
      • Wiseman H.M.
      • Guest K.
      • Murray V.S.
      • Volans G.N.
      Accidental poisoning in childhood: a multicentre survey, 2: the role of packaging in accidents involving medications.
      • Ozanne-Smith J.
      • Day L.
      • Parsons B.
      • Tibballs J.
      • Dobbin M.
      Childhood poisoning: access and prevention.
      Children also gain access to medicines when caregivers do not use child-resistant packaging correctly (eg, when caps are left off or incompletely secured).
      • Jacobson B.J.
      • Rock A.R.
      • Cohn M.S.
      • Litovitz T.
      Accidental ingestions of oral prescription drugs: a multicenter survey.
      • Lembersky R.B.
      • Nichols M.H.
      • King W.D.
      Effectiveness of child-resistant packaging on toxin procurement in young poisoning victims.
      The bottle-and-cap system commonly used for medication packaging in the US requires the adult user to correctly reengage the child-resistant closure each time the bottle is opened; otherwise, the entire contents may be accessible. Flow restrictors (FRs), adapters added to the neck of a bottle to limit the release of liquid, have been suggested as a means of limiting the amount of liquid medicine that a young child can access even if the child-resistant closure is breached.
      • Budnitz D.S.
      • Salis S.
      Preventing medication overdoses in young children: an opportunity for harm elimination.
      • Bond G.R.
      • Woodward R.W.
      • Ho M.
      The growing impact of pediatric pharmaceutical poisoning.
      Manufacturers began adding FRs to over-the-counter (OTC) infant acetaminophen in 2011

      Consumer Healthcare Products Association. OTC industry announces voluntary transition to one concentration of single-ingredient pediatric liquid acetaminophen medicines. News release, May 4, 2011. Available from: http://www.chpa-info.org/05_05_11_PedAceConv.aspx. Accessed August 27, 2012.

      ; however, the efficacy of FRs in limiting the accessibility of medicines to young children has not been assessed.
      In the present study, we aimed to evaluate whether adding FRs affects the proportion of preschool-aged children who can access medicine bottle contents, the amount of liquid contents accessed, and the time required to empty bottles compared with traditional bottles without FRs.

      Methods

      To assess the efficacy of FRs in limiting children’s access to liquid medicines, we used a modified version of the standard child test protocol for reclosable packages outlined in the PPPA.

      Code of Federal Regulations, 16 CFR §1700.20.

      The study was approved by the Institutional Review Board of the Centers for Disease Control and Prevention (CDC) with concurrence of the Institutional Review Board of Emory University School of Medicine and the Research Oversight Committee of Grady Health System. Legal guardians provided written permission. This trial was not prospectively registered in a clinical trials database, because it assessed the interface between safety packaging for medicines and human factors. No health-related measures were obtained, participants were not followed over time, and no biomedical or health outcomes were assessed. The Institutional Review Boards of CDC and the Emory University School of Medicine did not recommend study registration as a clinical trial.
      In the standard PPPA protocol, children participate in pairs and are asked to open a bottle with a child-resistant closure. In the present study, children participated individually to ensure statistical independence among participants. Each child participated in 2 consecutive trials. In both trials, children were asked to “get everything out” of a bottle filled with a test liquid. To isolate the effect of FRs and simulate improper child-resistant closure use, children were given an uncapped bottle with an FR for 1 trial. For the other trial, children were given a traditional bottle without a cap (open control) or with an incompletely closed child-resistant cap (incompletely closed control). To simulate what they might find at home, children were given the specific dosing device packaged with each bottle (ie, dosing syringes with FR bottles and dosing cups with control bottles).
      Testers instructed the children using a script based on the PPPA protocol. A second investigator recorded observations and timed the trials. If a child did not empty the bottle after 5 minutes, then the tester demonstrated removal of liquid to simulate what the child might observe at home. As in the PPPA protocol, the tester then reminded the child that teeth could be used, and gave the child 5 additional minutes to remove liquid. Once both trials were complete, the children were given age-appropriate messages about medication safety.
      The study was conducted in a convenience sample of 5 preschools in the Atlanta metropolitan area in April and May 2012. Although the PPPA protocol includes children aged 42-51 months, to facilitate enrollment, permission forms and information materials were distributed to guardians of children in classrooms with students aged 36-59 months. As in the PPPA protocol, children with overt illnesses, injuries, or physical or mental disabilities (as assessed by the guardians) were excluded. Guardians also confirmed that their children were English speakers and had no dietary restrictions or allergies to test liquid ingredients.

       Test Products

      FRs, bottles, and dosing devices that were currently in use or in production for use with oral OTC liquid medicines in the US were provided by 3 manufacturers (designated designs A, B, and C). In design A, the FR is a rubber septum that reseals after syringe removal. In design B, the FR contains a small orifice engineered to match a corresponding syringe. Design C incorporates a “lock-and-key” mechanism requiring alignment of a specific syringe and an FR with a self-closing valve (Figure 1).
      Figure thumbnail gr1
      Figure 1FR designs. The adapters are added to the neck of a standard liquid medicine bottle to limit the release of liquid. The FR marked with an asterisk is no longer on the market

      McNeil Consumer Healthcare Division of McNeil-PPC, Inc. McNeil Consumer Healthcare announces voluntary nationwide recall of Infants' TYLENOL® Oral Suspension, 1 oz grape, due to dosing system complaints. News release, February 17, 2012. Available from http://www.fda.gov/Safety/Recalls/ucm292537.htm. Accessed June 25, 2013.

      ; it has been improved to minimize the risk of pushing the FR into the bottle during syringe insertion.
      Bottles were filled to their intended volume (two 30-mL bottles and one 120-mL bottle) with a test liquid with similar fluid characteristics as the medicines for which the FRs were intended (Nesquik Strawberry Syrup, Nestlé, Toronto, Ontario, Canada). Incompletely closed control bottles were prepared at the preschools immediately before testing by aligning the threading on bottles and caps and rotating the “push-down-and-turn” caps 270 degrees clockwise, closing the bottle but not engaging the child-resistant locking mechanism.

       Sample Size

      The study was powered to detect a difference in the proportion of children who removed ≥5 mL of test liquid from their FR bottle compared with their control bottle. We predicted that ≥5 mL of liquid would be removed from 90% of open control bottles, 50% of incompletely closed control bottles, and 15% of FR bottles. We calculated that 30 incompletely closed/FR bottle trials and 9 open control/FR bottle trials for each of the 3 FR designs (A, B, and C) would be required to achieve 80% power at a 5% significance level.

       Sample Allocation

      Children were assigned bottles for testing by randomizing a fixed block size of 12 pairs to attain an even distribution of the 3 FR bottle designs (A, B, and C) at each site, an even distribution of FR bottle designs throughout the duration of the testing period at each site, and a 3:1 allocation of incompletely closed (n = 3) and open (n = 1) control bottles across each FR bottle design and the duration of the testing period at each site. Each assigned pairing of FR bottle and control bottle was tested by 2 children. To ensure even distribution of testing order, 1 child tested an FR bottle first, and the other child tested a control bottle first.
      Before the start of testing, each of the 5 sites was assigned a randomly selected block from 120 possible block permutations. If a block assignment was not completed at 1 testing site, then the untested bottle assignments were completed at another site where additional participants were available.

       Outcome Measures

      Data include observational measures. The primary outcome measures were the proportions of children who emptied bottles, removed ≥25 mL (≥5 typical doses), and removed ≥5 mL (≥1 typical dose) of test liquid from FR bottles compared with incompletely closed control bottles or open control bottles. To determine the amount of liquid removed, bottles were weighed before the trials, after 5 minutes, after the full 10-minute testing period, and when emptied. Weights were converted to milliliters for analysis.
      Secondary outcome measures included time required to empty the bottles and proportion of liquid removed. For FR bottles, amounts of liquid removed by age, sex, and site, and approaches used to remove liquid from bottles were assessed as well. Although our primary objective was to assess the 3 FR designs in combination, we also assessed the amount of test liquid removed for each FR bottle design.

       Statistical Analyses

      For the primary outcomes, a McNemar test for paired proportions was used to assess differences in the proportion of children who removed specified amounts of test liquid from FR bottles compared with each type of control bottle. The sign test was used to assess differences in the proportion of liquid removed from FR bottles compared with control bottles. The χ2 or Fisher exact test was used to determine whether age, sex, or site was associated with removal of specified amounts of liquid from FR bottles. Two-sided P values <.05 were considered statistically significant. Data were analyzed using SAS version 9.2 (SAS Institute, Cary, North Carolina).

      Results

      Across the 5 sites, guardians of 120 children who met the criteria for study inclusion provided permission, and 110 children (92%) participated. Five children were absent on testing days, and 5 (all 3-year-olds) refused to participate. The mean age of participants was 49 months (range, 36-59 months); 57% were boys (Table I). Assignment to a specific FR bottle design (A, B, or C) was similar by age and sex of participants and by site.
      Table IDemographic data
      CharacteristicNumber (%) of participants
      Age, months
       36-4114 (13)
       42-4737 (34)
       48-5323 (21)
       54-5936 (33)
      Sex
       Female47 (43)
       Male63 (57)
      Site
       122 (20)
       222 (20)
       326 (24)
       418 (16)
       522 (20)
      Total110 (100)
      Children emptied the incompletely closed control bottles almost as frequently as they emptied the open control bottles. Within 2 minutes, 96% of open control bottles (25 of 26) and 82% of incompletely closed control bottles (68 of 83) were emptied (Figure 2). In contrast, none of the FR bottles were emptied before 6 minutes. Of 110 participants, only 7 children (6%) emptied an FR bottle within the full 10-minute testing period.
      Figure thumbnail gr2
      Figure 2Time required for children to empty open control bottles, incompletely closed control bottles, and bottles with FRs. The bottles were considered empty when the tester noted pauses of ≥1 second between drops of test liquid when fully inverted (control bottles), or following manual inspection by the tester after a child who had been successfully removing test liquid appeared unable to remove additional amounts (FR bottles). Weighing of all bottles confirmed removal of ≥88% of test liquid in all cases. Time was not recorded for 1 trial with an incompletely closed control bottle.
      The proportions of children who removed specified amounts of test liquid were lower for each FR bottle design compared with the control bottles. Among children who tested FR designs A or B, 17% (6 of 36) removed ≥25 mL of liquid from each design (P < .001 compared with paired incompletely closed controls). Almost one-quarter (22%; 8 of 36) of children who tested design A and one-third (12 of 36) of those who tested design B removed ≥5 mL of liquid (P < .001 and P = .001, respectively, compared with paired incompletely closed controls). Only 1 child removed ≥5 mL of liquid (5.7 mL) from FR design C (P < .001 compared with paired incompletely closed controls).
      Considering the 3 FR designs together, children removed less liquid from FR bottles than from open control or incompletely closed control bottles (P < .001, sign test). All children assigned open control bottles (26 of 26) and 90% of those assigned incompletely closed control bottles (76 of 84) removed ≥25 mL of liquid, almost always during the first 5-minute test period (Table II). Overall, 12 children (11%) removed ≥25 mL of liquid from FR bottles, but only 1 child did so during the first 5 minutes. Twenty-one children (19%) removed ≥5 mL of liquid from FR bottles, but only 4 (4%) did so within 5 minutes. Pairwise comparisons of removal of ≥25 mL of liquid and ≥5 mL of liquid from the FR bottles compared with each type of control bottle were statistically significant (P < .001).
      Table 2Proportion of children who removed ≥25 mL or ≥5 mL of test liquid by bottle type
      Bottle pairingTotal numberPredemonstrationOverall
      n%P Valuen%P Value
      ≥25 mL removed
      Open control262596<.00126100<.001
      FR bottle0014
      Incompletely closed control847488<.0017690<.001
      FR bottle111113
      ≥5 mL removed
      Open control262596<.00126100<.001
      FR bottle0028
      Incompletely closed control847690<.0017792<.001
      FR-bottle451923
      All correlations were statistically significant, P < .0001.
      Older children were more successful than younger children at removing ≥25 mL (P = .002) and ≥5 mL (P = .02) of liquid from the FR bottles. Of the 12 children who removed ≥25 mL of liquid, 10 were from the oldest age group (aged 54-59 months). None of the youngest children (aged 36-41 months) removed even 5 mL of liquid. No significant differences in the ability to remove ≥25 mL or ≥5 mL of liquid by sex or study site were detected.
      Children attempted various strategies to remove liquid from FR bottles, including using the dosing syringe (102 of 110; 93%); pouring, shaking, or squeezing from the bottle (66 of 110; 60%); using teeth or attempting to manually remove the FR (50 of 110; 45%); and drinking from the bottle (4 of 110; 4%). All children who removed ≥25 mL used the syringe. One child also used teeth to remove the FR and subsequently emptied the bottle.

      Discussion

      Designing safety packaging that limits the amount of medication that a child can remove even when the child-resistant closure is breached is a new approach to addressing unsupervised medication ingestion. In this study, we assessed the efficacy of FRs in limiting young children’s access to liquid medicines. Compared with open bottles and bottles with incompletely closed child-resistant caps, the addition of FRs to bottles decreased the proportion of children who accessed liquid, and in those who accessed liquid, decreased the amount of liquid accessed and increased the amount of time required to empty a bottle. Our findings suggest that adding FRs to bottles with child-resistant closures could provide a complementary dose-limiting barrier for liquid medicines.
      Standard child-resistant packaging is designed to prevent, or at least delay, young children from opening bottles for a “reasonable time” to increase the likelihood of caregiver intervention.

      Code of Federal Regulations, 16 CFR §1700.1.

      Two limitations of current reclosable child-resistant packaging are the reliance on caregivers to correctly resecure the cap after each use and the ready accessibility of the entire bottle contents once the cap is removed. Although data are limited, imperfect practices have been implicated in unsupervised ingestions,
      • Jacobson B.J.
      • Rock A.R.
      • Cohn M.S.
      • Litovitz T.
      Accidental ingestions of oral prescription drugs: a multicenter survey.
      • Lembersky R.B.
      • Nichols M.H.
      • King W.D.
      Effectiveness of child-resistant packaging on toxin procurement in young poisoning victims.
      and in 1 study, 80% of ingestions occurred within 5 minutes.
      • Ozanne-Smith J.
      • Day L.
      • Parsons B.
      • Tibballs J.
      • Dobbin M.
      Childhood poisoning: access and prevention.
      In this trial, when the “push-down-and-turn” style child-resistant cap was not completely resecured, 82% of children emptied the bottle within 2 minutes. The addition of FRs delayed access to bottle contents, even in bottles without a child-resistant cap. None of the children emptied an FR bottle before 6 minutes (and after demonstration of liquid removal), and only 6% emptied an FR bottle within the full 10-minute testing period. The additional time needed for children to access contents of FR bottles may provide an opportunity for caregiver intervention before substantial amounts are removed. Furthermore, study participants were asked to remove all liquid from their bottles and, as specified in the PPPA protocol, were gently but repeatedly encouraged to keep trying. In a home environment, at least some young children might stop trying without such encouragement.
      FRs also limited the dose accessed by preschool-aged children. For a 2- to 3-year-old child, the recommended dose of infant acetaminophen is 5 mL. Given an uncapped bottle, 10 minutes, and gentle encouragement, FRs prevented 81% of participants from removing even a single 5-mL dose and prevented 89% from removing 5 or more doses (≥25 mL). In contrast, an incompletely closed control bottle prevented only 10% of participants from removing 5 or more doses.
      Expanding the use of FRs beyond infant acetaminophen could reduce the severity of ingestions and the number of children referred for costly emergency evaluation and treatment. The addition of FRs to infant acetaminophen bottles may reduce parental distress and unnecessary ED visits, but the reformulated concentration (160 mg/5 mL) and small bottle size (30 mL) limit the maximum available dose to nontoxic levels for most children. However, if a child under age 5 years ingested a full 120-mL bottle of liquid children’s acetaminophen, he or she would likely be referred for emergency evaluation.
      • Dart R.C.
      • Erdman A.R.
      • Olson K.R.
      • Christianson G.
      • Manoguerra A.S.
      • Chyka P.A.
      • et al.
      Acetaminophen poisoning: an evidence-based consensus guideline for out-of-hospital management.
      The threshold dose for emergency evaluation is lower for other children’s OTC medicines. Children under age 5 years likely would be referred to an ED for suspected ingestion of one-half of a 120-mL bottle of children’s diphenhydramine
      • Scharman E.J.
      • Erdman A.R.
      • Wax P.M.
      • Chyka P.A.
      • Caravati E.M.
      • Nelson L.S.
      • et al.
      Diphenhydramine and dimenhydrinate poisoning: an evidence-based consensus guideline for out-of-hospital management.
      and for one-fifth of a 120-mL bottle of some dextromethorphan products.
      • Chyka P.A.
      • Erdman A.R.
      • Manoguerra A.S.
      • Christianson G.
      • Booze L.L.
      • Nelson L.S.
      • et al.
      Dextromethorphan poisoning: an evidence-based consensus guideline for out-of-hospital management.
      This study focused on assessing innovative safety packaging used with OTC pediatric liquid medicines because these medicines are intended for the children at the greatest risk for unsupervised ingestions. Of course, children get into medicines other than OTC pediatric liquids. Bailey et al
      • Bailey J.E.
      • Campagna E.
      • Dart R.C.
      • RADARS System Poison Center Investigators
      The underrecognized toll of prescription opioid abuse on young children.
      suggested that current child-resistant closures might not provide sufficient protection from some medications, particularly opioids, that can be lethal to a young child with a single dose. Prescription medicines that are harmful to young children at low doses,
      • Michael J.B.
      • Sztajnkrycer M.D.
      Deadly pediatric poisons: nine common agents that kill at low doses.
      such as opioid-containing liquid medicines, may be good candidates for incorporating FRs in addition to child-resistant closures.
      The present study has several limitations. First, to isolate the effect of FRs and replicate the circumstances of improper use of child-resistant closures, we tested FRs alone, without child-resistant caps. In practice, medicine bottles with FRs are packaged with child-resistant closures, so we likely underestimated the efficacy of concurrent use of both safety barriers.
      Second, we did not assess the usability or acceptability of FR bottles and accompanying dosing syringes with adults. Even though previous studies have shown that adults measure doses more accurately using oral syringes compared with other devices,
      • Yin H.S.
      • Mendelsohn A.L.
      • Wolf M.S.
      • Parker R.M.
      • Fierman A.
      • van Schaick L.
      • et al.
      Parents' medication administration errors: role of dosing instruments and health literacy.
      • Sobhani P.
      • Christopherson J.
      • Ambrose P.J.
      • Corelli R.L.
      Accuracy of oral liquid measuring devices: comparison of dosing cup and oral dosing syringe.
      the usability and acceptability of each design should be assessed. As with some early child-resistant closures, if adults cannot use them with relative ease, they circumvent them.
      Requirements for the special packaging of household substances: final rule.
      Third, our results might not be generalizable to all FR designs or all medication formulations and viscosities. Because we assessed products in which a specific FR is mated to a bottle of a specific size, the effect of bottle size cannot be separated from FR design. Specific FRs, bottles, and their intended contents should be compatible, and design–content combinations should have demonstrated efficacy.
      Fourth, this study was not designed to assess differences in performance among FR designs; however, findings from this study and feedback from user experience may inform future design refinements. Fifth, the preschools were located in urban and suburban settings and served children from a range of socioeconomic groups, but we did not assess the knowledge or experience of individual children with child-resistant closures or FRs before study participation.
      Finally, the experimental study design also might affect the generalizability of our findings to all children and home settings. We were surprised that only 4 children attempted to drink from FR bottles, but we suspect that observation by adults might have discouraged them. This apparent reluctance to drink directly from bottles also might have been related to the children’s age. In general, study participants were slightly older than the ages specified in the PPPA protocol (42-51 months). Younger children may have been more likely to put the bottles in their mouths, but younger children have not participated reliably in previous studies.
      • Done A.K.
      • Jung A.L.
      • Wood M.C.
      • Klauber M.R.
      Evaluations of safety packaging for the protection of children.
      • Thien W.M.A.
      • Rogmans W.H.J.
      Testing child-resistant packaging for access by infants and the elderly.
      Nonetheless, because none of the youngest children in our study (aged 36-41 months) removed even 5 mL of liquid and most ED visits for unsupervised medication ingestions are by even-younger children (1- and 2-year-olds),
      • Schillie S.F.
      • Shehab N.
      • Thomas K.E.
      • Budnitz D.S.
      Medication overdoses leading to emergency department visits among children.
      • Chien C.
      • Marriott J.L.
      • Ashby K.
      • Ozanne-Smith J.
      Unintentional ingestion of over-the-counter medications in children less than 5 years old.
      we likely underestimated the efficacy of FRs for the children at greatest risk.
      In summary, child-resistant caps are efficacious in delaying children from accessing medicines only when completely resecured after every use. Our findings suggest that FRs may limit the amount of liquid medicine that young children can access even when child-resistant closures are not fully secured. Future studies might focus on application of similar passive engineering and dose-limiting features to solid-dose medication packaging. Importantly, FRs are designed as a secondary barrier, and caregivers should not rely on FRs alone. Although improved packaging can limit ingestions, educational interventions should continue to highlight the importance of locking child-resistant caps after each use and storing medicines up and away, and out of sight of young children.

      UpAndAway.org. Put your medicines up and away and out of sight. Available from: http://www.upandaway.org/. Accessed August 31, 2012.

      Acknowledgments available at www.jpeds.com.

      Acknowledgments.

       Acknowledgments

      We thank the children and school administrators, staff, and teachers who participated in and assisted with this study. We also thank Mark Plezia (Associate Director Research and Development, McNeil Consumer Healthcare), Ed Kuffner (Vice President Medical Affairs and Clinical Research, McNeil Consumer Healthcare), David A. Manera (Innovations Manager, Comar), Amit Shah (Technical Advisor, Accudial Pharmaceutical), and Mark D. Kairalla (Project Manager, Accudial Pharmaceutical) for advice on issues related to product specifications. We also thank David Kleinbaum, PhD (CDC), and Jonathan Edwards, MStat (CDC) for statistical consultation and Andrew Geller, MD (CDC) for a thoughtful review of the manuscript. Packaging improvements to prevent unsupervised medication ingestions have been a key activity of the CDC-led public-private PROTECT Initiative (www.cdc.gov/medicationsafety/protect/protect_initiative.html), and we thank the PROTECT members for valuable discussions that helped shape this study.

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