Review of Reported Adverse Events and Poisonings Associated with Cough and Cold Products in Young Children Joint Meeting of the Nonprescription Drugs Advisory

Review of Reported Adverse Review of Reported Adverse Events and Poisonings Events and Poisonings Associated with Cough and Cold Associated with Cough and Cold Products in Young ChildrenProducts in Young Children

Review of Reported Adverse Review of Reported Adverse Events and Poisonings Events and Poisonings Associated with Cough and Cold Associated with Cough and Cold Products in Young ChildrenProducts in Young Children

Joint Meeting of the Nonprescription Drugs Advisory Committee Joint Meeting of the Nonprescription Drugs Advisory Committee and the Pediatric Advisory Committee and the Pediatric Advisory Committee

October 18, 2007October 18, 2007Silver Spring, MarylandSilver Spring, Maryland

Gita Akhavan-Toyserkani, Pharm.D., MBAGita Akhavan-Toyserkani, Pharm.D., MBAYoo Jung Chang, Pharm.D.Yoo Jung Chang, Pharm.D.Syed Rizwanuddin Ahmad, M.D., MPHSyed Rizwanuddin Ahmad, M.D., MPHDivision of Drug Risk EvaluationDivision of Drug Risk EvaluationOffice of Surveillance and EpidemiologyOffice of Surveillance and Epidemiology

Joint Meeting of the Nonprescription Drugs Advisory Committee Joint Meeting of the Nonprescription Drugs Advisory Committee and the Pediatric Advisory Committee and the Pediatric Advisory Committee

October 18, 2007October 18, 2007Silver Spring, MarylandSilver Spring, Maryland

Gita Akhavan-Toyserkani, Pharm.D., MBAGita Akhavan-Toyserkani, Pharm.D., MBAYoo Jung Chang, Pharm.D.Yoo Jung Chang, Pharm.D.Syed Rizwanuddin Ahmad, M.D., MPHSyed Rizwanuddin Ahmad, M.D., MPHDivision of Drug Risk EvaluationDivision of Drug Risk EvaluationOffice of Surveillance and EpidemiologyOffice of Surveillance and Epidemiology

Center for Drug Evaluation and ResearchCenter for Drug Evaluation and Research

2Joint meeting of the Nonprescription Drugs Advisory Joint meeting of the Nonprescription Drugs Advisory Committee and the Pediatric Advisory Committee Committee and the Pediatric Advisory Committee October 18 & 19, 2007October 18 & 19, 2007

OutlineOutline• Objectives

• Adverse Event Reporting System (AERS) database– AERS review of pediatric deaths– AERS review of serious* adverse events in children

• Toxic Exposure Surveillance System (TESS) database– Database of the AAPCC

• Overall Summary

• Points to Consider

• Objectives

• Adverse Event Reporting System (AERS) database– AERS review of pediatric deaths– AERS review of serious* adverse events in children

• Toxic Exposure Surveillance System (TESS) database– Database of the AAPCC

• Overall Summary

• Points to Consider

* Serious outcomes per regulatory definition includes death, hospitalization, life-threatening, disability, congenital anomaly, requiring intervention, and other.

* Serious outcomes per regulatory definition includes death, hospitalization, life-threatening, disability, congenital anomaly, requiring intervention, and other.


ObjectivesObjectivesObjectivesObjectives• Present AERS cases of serious adverse

events, including deaths associated with cough/cold medications in children < 6 years of age

• Discuss contribution of drug overdoses to serious adverse events

• Show most AE cases were reported in age groups where there are no dosing recommendations on the OTC product label

• Present AERS cases of serious adverse events, including deaths associated with cough/cold medications in children < 6 years of age

• Discuss contribution of drug overdoses to serious adverse events

• Show most AE cases were reported in age groups where there are no dosing recommendations on the OTC product label


ObjectivesObjectivesObjectivesObjectives• Discuss association of single vs. multi-

ingredient cough/cold products to serious adverse events

• Discuss association of Rx vs. OTC cough/ cold products to serious adverse events

• Review overdose and poisoning exposure cases in association with cough/cold products reported to the AAPCC

• Discuss association of single vs. multi-ingredient cough/cold products to serious adverse events

• Discuss association of Rx vs. OTC cough/ cold products to serious adverse events

• Review overdose and poisoning exposure cases in association with cough/cold products reported to the AAPCC


• Voluntary, “spontaneous” reporting

• Facilitated by the FDA MedWatch Program

• Reports stored and retrieved via Adverse Event Reporting System (AERS) database

• Voluntary, “spontaneous” reporting

• Facilitated by the FDA MedWatch Program

• Reports stored and retrieved via Adverse Event Reporting System (AERS) database

AERS: Spontaneous AE AERS: Spontaneous AE ReportingReporting

AERS: Spontaneous AE AERS: Spontaneous AE ReportingReporting


AERS StrengthsAERS StrengthsAERS StrengthsAERS Strengths

• Includes all U.S. marketed products

• Detection of events not seen in clinical trials

• Especially good for events with rare background rate, short latency

• Includes all U.S. marketed products

• Detection of events not seen in clinical trials

• Especially good for events with rare background rate, short latency


AERS LimitationsAERS LimitationsAERS LimitationsAERS Limitations• Extensive underreporting

– New reporting requirements for OTC monograph products (effective December 22, 2007)

• Quality of reports is variable• Reporting biases• Actual numerator & denominator not

known• Causality of drug-event association

often in question

• Extensive underreporting– New reporting requirements for

OTC monograph products (effective December 22, 2007)

• Quality of reports is variable• Reporting biases• Actual numerator & denominator not

known• Causality of drug-event association

often in question


AERS Review of Pediatric DeathsAERS Review of Pediatric DeathsAERS Review of Pediatric DeathsAERS Review of Pediatric Deaths


AERS Pediatric DeathsAERS Pediatric Deaths (1969 – September 2006) (1969 – September 2006)AERS Pediatric DeathsAERS Pediatric Deaths

(1969 – September 2006) (1969 – September 2006)

Search Criteria• AERS database:

– Fatalities in children ≤ 6 years of age• Includes U.S. only, single/combination, and Rx/OTC

products• Associated with the following ingredients:

Search Criteria• AERS database:

– Fatalities in children ≤ 6 years of age• Includes U.S. only, single/combination, and Rx/OTC

products• Associated with the following ingredients:

Decongestants:1. pseudoephedrine 2. phenylephrine 3. ephedrine

Decongestants:1. pseudoephedrine 2. phenylephrine 3. ephedrine

Antihistamines:1. diphenhydramine2. brompheniramine 3. chlorpheniramine

Antihistamines:1. diphenhydramine2. brompheniramine 3. chlorpheniramine


AERS Review of Pediatric Deaths: AERS Review of Pediatric Deaths: DecongestantsDecongestants

AERS Review of Pediatric Deaths: AERS Review of Pediatric Deaths: DecongestantsDecongestants

Number of cases:– Pseudoephedrine (46)– Phenylephrine (4)– Ephedrine (4)

• Majority (83%) of the decongestant cases were reported in children < 2 years of age

• Drug overdose 72%

• Rx (46%) and OTC (33%) cough/cold products were reported

• Majority (83%; 24/28) of the cases with a reported postmortem blood level were above the adult therapeutic level

Number of cases:– Pseudoephedrine (46)– Phenylephrine (4)– Ephedrine (4)

• Majority (83%) of the decongestant cases were reported in children < 2 years of age



• Majority (83%; 24/28) of the cases with a reported postmortem blood level were above the adult therapeutic level


AERS Review of Pediatric DeathsAERS Review of Pediatric DeathsAERS Review of Pediatric DeathsAERS Review of Pediatric DeathsDrug Pseudoephedrine

(n=46)Phenylephrine

(n=4)Ephedrine

(n=4)

Overdose N=35: Use of multiple cough/cold preparations (7), medication error (10), accidental exposure (1), intentional overdose (2), drug interaction (1), opiate intoxication (2), unknown (12)

N=1: Intentional overdose (1)

N=3: Multiple drug intoxication (2), drug intoxication (1)

Reported Cause of Death

Drug intoxication/overdose (12), SIDS (7), apnea of prematurity (1), subarachnoid hemorrhage (1), cardiorespiratory arrest (2), head trauma (1), unknown (22)

Overdose (1), SIDS (1), unknown (2)

Drug intoxication (2), SIDS/ suspected drug intoxication (1), unknown (1)


AERS Review of Pediatric Deaths: AERS Review of Pediatric Deaths: AntihistaminesAntihistamines

AERS Review of Pediatric Deaths: AERS Review of Pediatric Deaths: AntihistaminesAntihistamines

Number of cases:– diphenhydramine (33)– brompheniramine (9)– chlorpheniramine (27)

• Majority (59%) of the antihistamine cases were reported in children < 2 years of age



• Majority (64%;18/28) of the cases with a reported postmortem blood level were above the adult therapeutic level

Number of cases:– diphenhydramine (33)– brompheniramine (9)– chlorpheniramine (27)

• Majority (59%) of the antihistamine cases were reported in children < 2 years of age



• Majority (64%;18/28) of the cases with a reported postmortem blood level were above the adult therapeutic level


AERS Review of Pediatric DeathsAERS Review of Pediatric DeathsAERS Review of Pediatric DeathsAERS Review of Pediatric DeathsDrug Diphenhydramine

(n=33)Brompheniramine

(n=9)Chlorpheniramine

(n=27)

Drug Overdose

N=20: Intentional overdose (4), medication error (5), multi-drug intoxication (3), accidental exposure (3), unknown (5)

N=5: Intentional overdose (2) use of multiple cough/cold products (1), medication error (1), accidental exposure (1)

N=20: Intentional overdose (4), medication error (5), multi-drug intoxication (3), accidental exposure (3), unknown (5)

Reported Cause of Death

Drug intoxication/ overdose(12), SIDS (1), ARDS (1), asphyxiation (2), septic shock (1), multi-organ failure (1), acute febrile illness (1), unknown (14)

Drug intoxication/ overdose (3), SIDS (1), viral pneumonia (1), apnea (1), head trauma (1), unknown (2)

Drug intoxication/overdose (9), opiate intoxication (1), SIDS (1), subarachnoid hemorrhage (1), pulmonary edema (1), cardiopulmonary arrest (1), unknown (12)


AERS Review of Serious* Adverse AERS Review of Serious* Adverse Events in ChildrenEvents in Children

AERS Review of Serious* Adverse AERS Review of Serious* Adverse Events in ChildrenEvents in Children

* Serious per regulatory definition includes death, hospitalization, life-threatening, disability, congenital anomaly, requiring intervention, and other.

* Serious per regulatory definition includes death, hospitalization, life-threatening, disability, congenital anomaly, requiring intervention, and other.


AERS Serious AE in Children AERS Serious AE in Children (January 1, 2002 – May 11, 2007)(January 1, 2002 – May 11, 2007)

AERS Serious AE in Children AERS Serious AE in Children (January 1, 2002 – May 11, 2007)(January 1, 2002 – May 11, 2007)

• AERS database:– Serious adverse events in children < 6

years

• Includes U.S. only, single/combination, and Rx/OTC products

• Associated with the following ingredients:– Decongestant: pseudoephedrine– Antitussive: dextromethorphan– Antihistamines: chlorpheniramine, diphenhydramine

• AERS database:– Serious adverse events in children < 6

years

• Includes U.S. only, single/combination, and Rx/OTC products

• Associated with the following ingredients:– Decongestant: pseudoephedrine– Antitussive: dextromethorphan– Antihistamines: chlorpheniramine, diphenhydramine


AERS Serious AE in Children: AERS Serious AE in Children: DemographicsDemographics

AERS Serious AE in Children: AERS Serious AE in Children: DemographicsDemographics

Drug Pseudo-ephedrine

(n=150)

Dextro-methorphan

(n=105)

Chlorphen-iramine(n=63)

Diphen-hydramine

(n=83)

Age: range median (month)

2 wks–5 yrs18

1 mo–5 yrs18

1 mo–5 yrs24

3 wks–5 yrs24

0 – < 2 yrs 2 – 5 yrs

82 (55%)65 (43%)

57 (54%)48 (46%)

22 (35%)41 (65%)

39 (47%)44 (53%)

Gender: female male unspecified

548610

43566

22401

35444


AERS Serious AE in Children: AERS Serious AE in Children: Dose and OnsetDose and Onset

AERS Serious AE in Children: AERS Serious AE in Children: Dose and OnsetDose and Onset


(n=150)

Dextro-methorphan

(n=105)


Diphen-hydramine

(n=83)

Single Dose (mg)

2.25 – 150median: 15

(n=61)

<1 – 50median: 5

(n=61)

0.05 – 12median: 1

(n=32)

1 – 100median: 12.5

(n=28)

Time to Onset

1 dose–> 2 wks

median: 1 dose

(n=89)

1 dose–> 2 wks

median: 1 dose

(n=55)

1 dose–10 days

median: 1 dose

(n=36)

1 dose– 2 wks

median: 1 dose

(n=29)

Recommended dosage for 2-6 years of age: pseudoephedrine 15 mg q4-6 hours; dextromethorphan 2.5 - 5 mg

q4 hours; chlorpheniramine 1 mg q4-6 hours; diphenhydramine 6.25 mg q4-6 hours

Recommended dosage for 2-6 years of age: pseudoephedrine 15 mg q4-6 hours; dextromethorphan 2.5 - 5 mg

q4 hours; chlorpheniramine 1 mg q4-6 hours; diphenhydramine 6.25 mg q4-6 hours


AERS Serious AE in Children:AERS Serious AE in Children:Product ClassificationProduct Classification

AERS Serious AE in Children:AERS Serious AE in Children:Product ClassificationProduct Classification


(n=150)

Dextro-methorphan

(n=105)


Diphen-hydramine

(n=83)

Product Classification OTC Rx Unknown

1061925

82176

35208

530

30

Product Type SI* Combo** Unknown

1511322

78711

0558

441128

SI*=single ingredient product, Combo**=combination/multiple ingredient product


AERS Review of Serious AE:AERS Review of Serious AE: Drug Overdose Drug Overdose

AERS Review of Serious AE:AERS Review of Serious AE: Drug Overdose Drug Overdose


(n=150)

Dextro-methorphan

(n=105)


Diphen-hydramine

(n=83)

Drug Overdose 74 (49%)

41 (39%)

31 (49%)

46 (55%)

Manner of Overdose:• Accidental exposure• Intentional overdose• Medication error *

• Undetermined

322

1327

165

119

125

104

261145

* Medication errors to include prescribing errors, dispensing errors, administration errors, duplication of therapy, and wrong drug administration.


AERS Serious AE in Children: AERS Serious AE in Children: By System Organ Class By System Organ Class

AERS Serious AE in Children: AERS Serious AE in Children: By System Organ Class By System Organ Class


(n=150)

Dextro-methorphan

(n=105)


Diphen-hydramine

(n=83)

Cardiac Disorders 21 10 9 13

Nervous System Disorders: Convulsion Depressed LOC

2422

2224

1417

727

Respiratory Disorders

14 15 18 20

LOC=level of consciousness, AE=adverse events


AERS Serious AE in Children:AERS Serious AE in Children:Overdoses vs. Non-OverdosesOverdoses vs. Non-OverdosesAERS Serious AE in Children:AERS Serious AE in Children:Overdoses vs. Non-OverdosesOverdoses vs. Non-Overdoses

0

5

10

15

20

25

30P

SE

DX

M

CP

M

DP

H

PS

E

DX

M

CP

M

DP

H

PS

E

DX

M

CP

M

DP

H

PS

E

DX

M

CP

M

DP

H

Cardiac AE Convulsion Depressed LOC Respiratory AE

Nu

mb

er o

f C

ases

Non-overdose Overdose

PSE=pseudoephedrine, CPM=chlorpheniramine, DPH=diphenhydramine, DXM=dextromethorphan, LOC=level of consciousness, AE=adverse events


AERS Serious AE in Children:AERS Serious AE in Children:Children < 2 yrs vs. 2-5 yrsChildren < 2 yrs vs. 2-5 yrs

AERS Serious AE in Children:AERS Serious AE in Children:Children < 2 yrs vs. 2-5 yrsChildren < 2 yrs vs. 2-5 yrs

0

5

10

15

20

25

30P

SE

DX

M

CP

M

DP

H

PS

E

DX

M

CP

M

DP

H

PS

E

DX

M

CP

M

DP

H

PS

E

DX

M

CP

M

DP

H

Cardiac AE Convulsion Depressed LOC Respiratory AE

Nu

mb

er

of

Ca

se

s

< 2 yrs 2 - 5 yrs

PSE=pseudoephedrine, CPM=chlorpheniramine, DPH=diphenhydramine, DXM=dextromethorphan, LOC=level of consciousness, AE=adverse events


AERS Serious AE in Children:AERS Serious AE in Children:HallucinationsHallucinations



(n=8)

Dextro-methorphan

(n=4)

Chlorphen-iramine

(n=3)

Diphen-hydramine

(n=9)

Age < 2

1 1 1 1

Age 2 – 5

≤ Therapeutic Dose

> Therapeutic Dose

7

5

2

3

2

1

2

2

0

8

1

7

Time to Onset 1 dose– 2 days(n=6)

1 dose–2 days(n=4)

1 dose–3 days(n=3)

1 dose–1 day (n=5)

Type ofHallucination

Visual – 3 Unknown – 5



Visual – 4Auditory – 1Unknown – 4




• Description of visual hallucinations:– “bubbles” – “snakes and frogs” – “big creature” – “snakes, spiders, and scorpions” – “imaginary things” – “spiders” – “bugs everywhere, balls were coming

after her, and raining in her room”

• Description of visual hallucinations:– “bubbles” – “snakes and frogs” – “big creature” – “snakes, spiders, and scorpions” – “imaginary things” – “spiders” – “bugs everywhere, balls were coming

after her, and raining in her room”


AERS Serious AE in Children:AERS Serious AE in Children:Postmortem Blood LevelsPostmortem Blood Levels

AERS Serious AE in Children:AERS Serious AE in Children:Postmortem Blood LevelsPostmortem Blood Levels


(n=150)

Dextro-methorphan

(n=105)


Diphen-hydramine

(n=83)

Death 43 28 20 26

Postmortem blood levels

median

<0.05 – 29.9 mg/L

2.75 mg/L(n=33)

9 – 1200 mcg/L

140 mcg/L (n=16)

0.04 – 0.21 mg/L

0.07 mg/L(n=6)

0.07 – >10 mg/L

1.6 mg/L(n=14)

Therapeutic blood concentrations: pseudoephedrine1 <1 mg/L, dextromethorphan2 2.4 – 207 mcg/L, chlorpheniramine1 0.01 – 0.02 mg/L, diphenhydramine1 0.1 – 1 mg/L

1Toxic Drug Concentrations. Office of the Chief Medical Examiner. Chapel Hill, NC 27713 Last revision: May 22, 2003. 2Gunn VL, et al. Toxicity of Over-the-Counter Cough and Cold Medications. Pediatrics. Sept 2001;108:3.


Cardiac Case #1Cardiac Case #1Cardiac Case #1Cardiac Case #1

• 2 month old, female– Infant PediaCare Decongestant and Cough

Concentrated Drops, recommended by a pharmacist

– Indication, PMHx and concomitant meds unknown

– 1 hr after a single dose of 0.4 mL (pseudoephedrine 3.75 mg and dextromethorphan 1.25 mg)

– heart rate of 240 bpm and was hospitalized– AEs resolved within 7 days

• 2 month old, female– Infant PediaCare Decongestant and Cough

Concentrated Drops, recommended by a pharmacist

– Indication, PMHx and concomitant meds unknown

– 1 hr after a single dose of 0.4 mL (pseudoephedrine 3.75 mg and dextromethorphan 1.25 mg)

– heart rate of 240 bpm and was hospitalized– AEs resolved within 7 days


Cardiac Case #2Cardiac Case #2Cardiac Case #2Cardiac Case #2• 2 week old, male

– Infant PediaCare Decongestant Concentrated Drops (pseudoephedrine 9.375 mg/mL), recommended by a physician

– to treat nasal congestion – no reported PMHx and no concurrent

medications– immediately after 1st dose (dose unspecified) – cardiac failure & supraventricular tachycardia – treated with digoxin and an unspecified

medication– discharged after 2 weeks with events resolved

• 2 week old, male– Infant PediaCare Decongestant Concentrated

Drops (pseudoephedrine 9.375 mg/mL), recommended by a physician

– to treat nasal congestion – no reported PMHx and no concurrent

medications– immediately after 1st dose (dose unspecified) – cardiac failure & supraventricular tachycardia – treated with digoxin and an unspecified

medication– discharged after 2 weeks with events resolved


Convulsion CaseConvulsion CaseConvulsion CaseConvulsion Case

• 5 year old, female– Triaminic Cough and Sore Throat– used for cough – 1 dose (5 mL) of 15 mg of

pseudoephedrine, 5 mg dextromethorphan, and 160 mg acetaminophen

– seizures (lasted 10 sec) next morning– “all vitals were fine” – outcome and interventions unknown – At 3 y/o age experienced same event with

the same medication – on multivitamins

• 5 year old, female– Triaminic Cough and Sore Throat– used for cough – 1 dose (5 mL) of 15 mg of

pseudoephedrine, 5 mg dextromethorphan, and 160 mg acetaminophen

– seizures (lasted 10 sec) next morning– “all vitals were fine” – outcome and interventions unknown – At 3 y/o age experienced same event with

the same medication – on multivitamins


AERS Review of Serious AE in Children:AERS Review of Serious AE in Children:SummarySummary


• > 50% of pseudoephedrine and dextromethorphan cases occurred in children < 2 years of age

• > 50% of chlorpheniramine and diphenhydramine cases occurred in children 2 – 5 years of age

• Rx and OTC cold/cough products were reported; however, the majority were OTC (56 – 78%)

• > 75% pseudoephedrine, chlorpheniramine, and dextromethorphan cases involved a multi-ingredient product

• > 50% of pseudoephedrine and dextromethorphan cases occurred in children < 2 years of age

• > 50% of chlorpheniramine and diphenhydramine cases occurred in children 2 – 5 years of age

• Rx and OTC cold/cough products were reported; however, the majority were OTC (56 – 78%)

• > 75% pseudoephedrine, chlorpheniramine, and dextromethorphan cases involved a multi-ingredient product




• Deaths 30%• Overdoses 48%• Among all cases:

– 22% accidental exposures– 6% intentional overdoses– 9% medication errors– 11% indeterminable

• Serious adverse events related to the cardiac, nervous, and respiratory systems have been reported both in the setting of an overdose and outside of an overdose– Convulsions: more common outside of an overdose and

appear more in children 2 – 5 years of age– Cardiac & respiratory events: more common in the setting

of an overdose

• Deaths 30%• Overdoses 48%• Among all cases:

– 22% accidental exposures– 6% intentional overdoses– 9% medication errors– 11% indeterminable

• Serious adverse events related to the cardiac, nervous, and respiratory systems have been reported both in the setting of an overdose and outside of an overdose– Convulsions: more common outside of an overdose and

appear more in children 2 – 5 years of age– Cardiac & respiratory events: more common in the setting

of an overdose


TESS ReviewTESS ReviewTESS ReviewTESS Review


TESS ReviewTESS ReviewTESS ReviewTESS Review

• TESS - Toxic Exposure Surveillance System is the poisoning surveillance database of the AAPCC– Reviewed reports from 2001-2005– Cases that listed cough/cold

preparations or diphenhydramine– Caveat: Underreporting to TESS

may be extensive

• TESS - Toxic Exposure Surveillance System is the poisoning surveillance database of the AAPCC– Reviewed reports from 2001-2005– Cases that listed cough/cold

preparations or diphenhydramine– Caveat: Underreporting to TESS

may be extensive


TESS Review – Cough/ColdTESS Review – Cough/ColdTESS Review – Cough/ColdTESS Review – Cough/Cold

• In children < 6 yrs– Total # cases increased slightly from

59,949 in 2001 to 70,398 in 2005– Overall % of cases involving children < 6 yrs remained constant at about 61-

62% in the 5-yr review period

• For all ages, majority of these cases resulted from unintentional exposures – 24% were treated in a health care

facility

• In children < 6 yrs– Total # cases increased slightly from

59,949 in 2001 to 70,398 in 2005– Overall % of cases involving children < 6 yrs remained constant at about 61-

62% in the 5-yr review period

• For all ages, majority of these cases resulted from unintentional exposures – 24% were treated in a health care

facility


TESS Review - DiphenhydramineTESS Review - DiphenhydramineTESS Review - DiphenhydramineTESS Review - Diphenhydramine

• In children < 6 yrs– Total # of cases increased very slightly

from 13,044 in 2001 to 13,445 in 2005– Overall % of cases involving children < 6

yrs remained constant at about 43-46%

• For all ages, 45-75% of diphenhydramine cases resulted from unintentional exposure– 42% required treatment in a health care

facility

• In children < 6 yrs– Total # of cases increased very slightly

from 13,044 in 2001 to 13,445 in 2005– Overall % of cases involving children < 6

yrs remained constant at about 43-46%

• For all ages, 45-75% of diphenhydramine cases resulted from unintentional exposure– 42% required treatment in a health care

facility


TESS Review - FatalitiesTESS Review - FatalitiesTESS Review - FatalitiesTESS Review - Fatalities• In children < 6 yrs, 14 fatalities were reported in

association with cough/cold and diphenhydramine products

• Age range 2m-5yrs• Majority of deaths (N=8) occurred in children 12m

or younger• Product

– 3 fatalities were noted in association with the use of single ingredient cough/cold or diphenhydramine products

– 11 fatalities noted with combination products or use of multiple products

• In children < 6 yrs, 14 fatalities were reported in association with cough/cold and diphenhydramine products

• Age range 2m-5yrs• Majority of deaths (N=8) occurred in children 12m

or younger• Product

– 3 fatalities were noted in association with the use of single ingredient cough/cold or diphenhydramine products

– 11 fatalities noted with combination products or use of multiple products


TESS Review - SummaryTESS Review - SummaryTESS Review - SummaryTESS Review - Summary• Data from poison control centers suggest

substantial number of overdose and poisonings in association with cough/cold and diphenhydramine products– Both OTC and Rx products involved

• Children < 6 years old make up 40% to 60% of all poisoning cases in association with cough/cold and diphenhydramine products

• Data from poison control centers suggest substantial number of overdose and poisonings in association with cough/cold and diphenhydramine products– Both OTC and Rx products involved

• Children < 6 years old make up 40% to 60% of all poisoning cases in association with cough/cold and diphenhydramine products


Overall SummaryOverall SummaryOverall SummaryOverall Summary

• Use of OTC and Rx cough/cold medications in children < 6 years of age have been associated with serious adverse events, including death

• Drug overdoses commonly contributed to serious adverse events and deaths

• Manner of overdose was identified as:– accidental exposure, intentional overdose,

and medication errors

• Use of OTC and Rx cough/cold medications in children < 6 years of age have been associated with serious adverse events, including death

• Drug overdoses commonly contributed to serious adverse events and deaths

• Manner of overdose was identified as:– accidental exposure, intentional overdose,

and medication errors


Overall SummaryOverall SummaryOverall SummaryOverall Summary

• Most occurred in age groups where there are no dosing recommendations on the OTC product label

• Most involved multi-ingredient cough/cold products

• Data from poison control centers suggest substantial number of overdose and poisonings cases reported with cough/cold and diphenhydramine products

• Most occurred in age groups where there are no dosing recommendations on the OTC product label

• Most involved multi-ingredient cough/cold products

• Data from poison control centers suggest substantial number of overdose and poisonings cases reported with cough/cold and diphenhydramine products


Points to ConsiderPoints to ConsiderPoints to ConsiderPoints to Consider

• An educational campaign directed towards healthcare providers and parents about the use of cough/cold products

• The labeling of cough/cold products should include prominent language to describe the risk of overdose in children

• Label should indicate that cough/cold products are not recommend in children under 2 years of age

• Consider having only single ingredient cough/cold products for pediatric formulations

• An educational campaign directed towards healthcare providers and parents about the use of cough/cold products

• The labeling of cough/cold products should include prominent language to describe the risk of overdose in children

• Label should indicate that cough/cold products are not recommend in children under 2 years of age

• Consider having only single ingredient cough/cold products for pediatric formulations


AcknowledgementsAcknowledgementsAcknowledgementsAcknowledgements

Mark Avigan, M.D., C.M.Allen Brinker, M.D., M.S.Gerald Dal Pan, M.D., M.H.SRosemary Johann-Liang, M.D.Lauren Lee, Pharm.D.Ann McMahon, M.D., M.S. Ellis Unger, M.D.

Mark Avigan, M.D., C.M.Allen Brinker, M.D., M.S.Gerald Dal Pan, M.D., M.H.SRosemary Johann-Liang, M.D.Lauren Lee, Pharm.D.Ann McMahon, M.D., M.S. Ellis Unger, M.D.

Documents

Review of Reported Adverse Events and Poisonings Associated with Cough and Cold Products in Young Children Joint Meeting of the Nonprescription Drugs Advisory