CONSULTATION RESPONSE OFFICE OF POST-MARKETING DRUG RISK ASSESSMENT HFD-400) DATE RECEIVED: DUE DATE: OPDRA CONSULT January 30, 2001 October 1, 200i 01-01?? TO: Charles Ganley, MD. Director, Division of Over-The-Counter Drug Products (HFD-560) THROUGH: Walter Ellenberg Project Manager (HFD-560) PRODUCT NAMES: MANUFACTURER: *Jl1'1i0" Strength TYLENOL (150 mg) McNeil Consumer Products oChildren's TYLENOL Chewable Tablets (80 mg) or Unspecified Children's Acetaminophen Tablets ?Children's TYLENOL Liquid (160 mg/5 mL) or Unspecified Children's Acetaminophen Liquid 9 Infants' TYLENOL Concentrated Drops (80 mgf0.8 mL) 0 Unspecified Children's Acetaminophen Suppositories 0 Unspecified ChiIdren's Acetaminophen Product 4 Unspecified TYLENOL Acetaminophen Product 9 Unspecified Acetaminophen Product 0 Multiple Preparations of TYLENOL Acetaminophen or Other Acetaminophen Products 1' NBA 19-872 SAFETY EVALUATOR: Carol Holquist, SUMMARY: In response to a request from the Division of Over-The-Counter Drug Products (HF D-560), OPDRA summarized the December 20, 2000 McNeil submission. Jerry Phillips, Martin I-Iimmel, MD Associate Director for Medication Error Prevention Deputy Director Office of Post-Marketin Drug Risk Assessment Office of Post--Marketing Drug Risk Assessment Phone: (301) 327-3242 Center for Drug Evaluation and Research Fax: (301) 480-3173 Food and Drug Administration DATE OF REVIEW: NDA: NAME OF DRUGS: MANUFACTURED BY: 1. Office of Post-Marketing Drug Risk Assessment Rm. 15B-32 Center for Drug Evaluation and Research SUMMARY OF DECEMBER 20, 2000 McNeil SUBMISSION August 16, 2001 19-872 clunior Strength TYLENOL (160 mg) oChildren's TYLENOL Chewable Tablets (80 mg) or Unspecified Children's Acetaminophen Tablets ?Children's TYLENOL Liquid (160 mg!5 mL) or Unspecified Chi!dren's Acetaminophen Liquid 9 Infants' TYLENOL Concentrated Drops (80 mg/0.8 mL) 0 Unspecified Children's Acetaminophen Suppositories 0 Unspecified Children's Acetaminophen Product 0 Unspecified TYLENOL Acetaminophen Product 0+ Unspecified Acetaminophen Product 9 Multiple Preparations of TYLENOL Acetaminophen or Other Acetaminophen Products McNeil INTRODUCTION: This submission is a follow--up to an Agency request of information on adverse drug experience reports and consumer inquiries for all McNeil's pediatric acetaminophen dosage forms for the time period N00. The pediatric dosage forms covered in this submission include the following: 0 Junior Strength TYLENOL (160 mg) 0 Children's TY LENOL Chewable Tablets (80 mg) or Unspecified Childrc-n's Acetaminophen Tablets 0 Children's TYLENOL Liquid (160 mgffi mL) or Unspecified Children's Acetaminophen Liquid 0 Infants' TYLENOL Concentrated Drops (80 mg/0.8 mL) 0 Unspecified Children's Acetaminophen Suppositories 0 Unspecified Childre-n's Acetaminophen Product 0 Unspecified TYLENOL Acetaminophen Product 0 Unspecified Acetaminophen Product 0 Multiple Preparations Acetaminophen or Other Acetaminophen Products II. A. McNeil searched their database for all drug misadministration cases and dosing inquiries associated with all pediatric dosage forms using the COSTART terms ACCIDENTAL OVERDOSE. INTENTIONAL OVERDOSE, and OVERDOSE. McNeil defines an overdose as any atiministration to any child under 12 years of age that exceeds the maximttm daily dose of 75 mg/'kg in any 24 hour period. The sponsor has used this definition since 1995. Before 1995 there were occasions when cases exceeded the single recommended dose and these cases were coded as an OVERDOSE or ACCIDENTAL OVERDOSE. In addition, the sponsor attempted to identify reports that were coded with the tenn "Drug Misadministration", however were unsuccessful. it should he noted that the Agency requested the search be conducted using the tertn "Drug Maiadministration rather than "Drag Misadtninistration The sponsor screened each case narrative for any mention of drug misadministration by the caregiver. The sponsor excluded cases in which there was no mention of misadministration and cases in which a child obtained the product and self-ingested an overdose. McNeil retrieved 973 reports, 117 of which could be identified as cases of misadministration. Only these I I 7 reports of misadministration were provided for review. The sponsor does not eiahorate on the cause of the remaining 856 reports of overdose that were not self-ingested. McNeil also provided a summary of questions relating to the dosing of pediatric TYLENDL acetaminophen products in children for the 20 month period of January 1999 to August 2000. This data was generated from their Consumer Response System (CRS) which records questions received from consumers. Reports were generated from this database by product. The sponsor screened each report for dosing questions specifically related to pediatric TYLENOL acetaminophen products. SUBMISSION SUMMARY CASE REPORT SUMMARY McNeil submitted one hundred and seventeen case reports (n=1 I 7) for review. Eighty-six (n=86) of these reports the mode of administration indicated that a therapeutic error or product misadministration occurred with a children's product, and thirty--one (n=3 1) involved an unknown dosage form which may or may not have been a pediatric product. Eight-four (n=84) of the 1 I7 reports submitted were not previously reported in our May 5, 2000 consult (OPDRA consult For purposes of this review. all case reports are summarized in attachment A. An overwhelming number of reports involved the Infant's Tylenol Concentrated Drops formulation (43 forty-four of which involved children under two years of age. In total, sixty-eight reports involved children under two years of age. The drug products and age breakdown are summarized in Table I (see page 4). TABLE I - A Range of tient by Product Age Range Junior Child. Unk Child. Infant': Unk Unk Unk Unk Panadol Strength Tylenol APAP Tylenol Tylenol APAP APAP Tylenol Paracet. Tylenol Chew Syrup Susp. Concen. Suppository Product Product Product Tabs or or Drops (n=l7} Elixir Elixir (n=50) (n=l4>2Unknown 0 3 0 2 0 0 Overall, there were fifty instances that identified some type of hepatic involvement, twelve of which resulted in death and three in liver transplants (see table II below). All reports describe multiple dosing of an acetaminophen or paracetamol product. Three cases described concomitant administration of two drug products containing acetaminophen. The majority of indications for use were fever, viral ear pain, and abdominal pain. TABLE I1 - Hepatic Involvement by Drug Product and Patient Outcome Concomitant administration of two products containing acetaminophen. Drug Product Death Liver Transplant Liver Liver Liver {n=l2) Damagelliailure Abnormalities Abnormalities Unk. Outcome Unk. Outcome Resolved (n=l9) lnfant's Tylenol I 4 3 6 Cone. Drops month] month) 9, I3 and 2] months) |3 month (6.5, 9. Ill, I2 month 3.5 yr.) and 2 3: IS months) ChildrenlenollAPAP Efixir (1 El month) {6 and 4 yr.) monlh and 3-5 yr.) Unknown Tylenol I 0 0 0 Product {3 yr.) Junior Strength I3 0 I 0 0 Tylenol 13.5 yr.) Unknown APAP 4 4 2 Product (9 and '5 {ll month) (4, 9, and 11 (24 month, 2 yr.) *9 and "10 yr.) months, 4 yr.) Children's 0 0 0 I Tylenol Chewable Age 6 yr. Paracetamol 4 0 I 9 Product (1.5, 2, 3 and (3 yr.) (I7 and 21 month, 5.25 yr.) 2, 2.5, 4, 4.5. 6, 6.4, 3.8 yr.) DOSING INQUIRIES FROM CONSUMERS McNeil generated reports from their Consumer Response System (CRS) of all dosing inquiries related to pediatric TYLENOL acetaminophen products for the period of 1! 1199 to 88 M00. During this period the sponsor received 2209 dosing questions for their pediatric TYLENOL products, 2163 via telephone, I by letter, and 45 via Intemet. The sponsor reported that each verbatim was also reviewed for situations that had the potential for misadministration had the consumer not contacted McNeil before patient administration. The majority of overall inquiries involved the Infants' Tylenol Concentrated Drops and the Children's Tylenol Liquid Questions involving children $2 years of age in addition to patients weighing 524 lbs. account for 48% of the consumer inquiries. Again, the majority of these inquires involved the Infants' Tylenol Concentrated Drops. In total, the sponsor received 722 inquiries for lnfant's Tylenol Drops, 258 for Children's Tylenol Elixirfsuspension, 48 for Unspecified Tylenol Formulation, 26 for Children's Tylenol Chewable Tablets, and 3 for the Junior Strength Tylenol for this agefweight range. The total number and type of questions are summarized in table Table - Total Number of Product and Type Dosage Form Tara! Reports No. affnqufres Type Children': Tylenol 285 I26 How much or How many based on age Chewable or many in I day.'How soon can I administer after another Tylenol Product? 16 Can I give to my child based on 1 give a reduced doses' Dose by age or by an Adult take this? 120 Verify RX dosing instructions. 2 What is the dosing equivalency between different dosage forms. Chew tabs vs. Jr. Strength} 21 Overdose by parentfcaregiver. How much is an overdose. Children': Tylenol 650 333 How much for agefweight."How much for Suspensiontlilirtir Adultffeenager? 47 Can I give this formulation to my child given agefvvt'? 33 Verify Dose ordered or Calculated 35 Equivalency between products 38 Overdose (Did or How much is considered an Overdose?) 27 Dosing Interval (How often, when can I redose) 93 Dosing Cup (lost, can I use something else, use dropper instead of cup, What does stand for . ordered in tsp. and no marking on cup, etc) I3 Do I dose by age or weight? I I Max per day? 5 How many mL tsp. or dropperful'? 15 Other (Need dosing chart, Dye contained in product, Need dosing info in another language, do I give more or redose because expiredfvomited. etc.) Infants Tylenol 105? 75] How much do I give for child agefwt, Concentrated and What is the recommended dosing given Infants Tylenol Drops ageiwt? 32 Can I give to my child based on their agehvt; Can 1 give to an adultfteen? 33 Verify dosing (M D, Nurse. own calculation) Max Daily Dosing? 22 Equivalency between products 50 Dosing lntervalffluration of 'l'herapy.r'Dose on Age or Weight!Dose Chart'? 28 Overdose (Did I 3: How much} 99 Dropper 25 Other (Put dose on bottle, How soon before immunizations, How many dropperfuls in bottle?) Junior Strength I20 37 How much do I give based on agefwt'? I4 Can I give this formulation? 3 Check on Rx 3 Equivalency between products 3 Overdose (Did I, How much is too much, etc.) Unspecified Children': 63 How much do give based on agefwt, Tylenol Products why don't you publish closing below certain age? 3 Can I give this formulation to child; can I use a different measuring device'? 15 Check on Rx 6 Equivalency (formulations. mL=cc. etc) 5 Overdose (How much is too much, Did I overdose, etc.) ASSESSMENT OF TYPE AND CAUSALITY OF ERRORS We can classify the one hundred and seventeen medication error reports submitted by McNeil into three types, wrong improper dose, and wrong time. For purposes of this review, wrong is defined as the wrong formulation utilized by the caregiver; Improper dose is defined as a higherflower dose administered than that which is recommended in the product labeling based on the age/weight of the patient; Wrong time is defined as an inappropriate dosing interval. The actual root cause of each medication error could not be accurately assessed for many reporters were not identified andfor could not be reached for an interview. Therefore, we can only speculate on the actual root cause of each error based on the information acquired from the narratives of each case report and numerous dosing inquiries. The following graph represents the timelines for manufacturer's receipt of the medication error reports that appear in attachment A: 72 ii . ., .. natty .I 1 1952 1993 1995 1998199921"! From the 17 case reports and 2209 dosing inquiries provided for review, we can determine the circumstances that lead to the actual misadministration of each drug product as well as those with the potential to cause a medication error if the consumer had not contacted the sponsor for dosing clarification. There were three recurring types of errors. The first were "wrong These errors involved consumers who confused the concentrated drops and the children's suspensionfelixir. The second type of error identified was "improper dose". These errors involved consumers who misinterpreted physicianlnurse orders, used an inappropriate administration device, misread the dosing chart, exceed the daily maximum, physician ordered an inappropriate dosage, misinterpreted the abbreviation on the dosing device, did not follow the labeled dosing amount, and miscalculation when convening teaspoonfirl to cc's, mL, or dropperful. The third type of error identified was "wrong time". These errors involved consumers who gave consecutive doses not knowing a spouse had just administered a dose or did not follow the labeled dosing interval. Overall, the majority of inquiries involved general dosing questions relating to children less than 2 years of age. Others requested a dose be provided based on the child's agefwt, could a certain formulation be utilized in a particular age group (peds adults), how often can the product be administered (interval), and clarification on the daily maximum dose. However, the consumer inquiries actually provided causality for many of the types of errors identified. Several consumers requested information on the equivalency of different Tylenol formulations. Consumers were confused about the different concentrations between products, dosing equivalencies between fonnulations, and/or needed to use a different formulation because they ran out of the formulation that they nonnally administer to their child. There were also numerous inquiries regarding the measuring cup supplied with the elixirfsuspension formulation and dropper supplied with the infant drops. Several consumers lost the requested to use a different device, and wanted to know why they had to use the cupldropper supplied and could not use a teaspoon. Moreover, the markings on the cup were misinterpreted as many caregivers interpreted the as a "Tablespoon" rather than a "Teaspoonful", in addition to not being able to determine the correct measurement of a full or half dropperfizl based on the dropper markings. Another contributing factor is that most practitioners prescribed the acetaminophen in teaspoonfirls or cc's rather than mL or dropperful. Consumers could not convert or equate the prescribed amount with the markings provided on the measuring devices currently supplied with each drug product. in addition, several questions described confusion over what constitutes a 24 hour dosing interval. The case reports and inquiries also reveal a knowledge deficit in relation to acetaminophen toxicity among prescribers, heath care practitioners, and consumers. Everyone must be educated on the potential for toxicity when the labeled instructions for use are not followed. Prescribers and health care providers are ordering acetaminophen with out specifying a daily maximum amount andfor ordering an incorrect dosage. Additionally, several case reports describe multiple emergency room visits before detecting acetaminophen toxicity. Consumers clearly have no conception of the dangers of misadministration of this product. This is evidenced by the many reports and inquiries that describe administration of acetaminophen around the clock based on the prescriber's instructions despite the labeled maximum daily amount, not following the labeled instructions for use or dosing intervals because they are utilizing the drug for some benign treatment such as pain associated with teething andfor immunizations. In summary, the reports and consumer inquiries reflect the need for education on the toxicity associated with acetaminophen in addition to the need for standardization of product labeling with safety standards that all manufactures of acetaminophen products would need to meet. The following should be considered. 0 Standardization of concentration of all liquid acetaminophen formulations or at a minimum standardization of the concentration of formulations and expression of strength. Currently there are products that contain 160 mg/5 mL, 120 mg/5 mL, 80 mg/5 mL and 80 mg/2.5 mL. Consumers believe that all brands of acetaminophen elixir are equivalent. ?Provide dosing information on the infant formulation to at least 2 months of age for this is the age when immunizations begin and sometimes teething. The dosing instructions should clearly convey the dosing interval, maximum daily dosage, and potential consequences if these instructions are not followed. Almost all of the maladministration case reports and at least half of the consumer inquiries could have been avoided had this information been readily available. ODef1ne the measurement of dropperful and dropperful in addition to mL and cc on the labels and labeling. OAII manufacturers of infant drops should provide the same internal safety barrier (cusps) that prohibits emptying the contents into a teaspoon or some other measuring device. 0 Possibly, redesign the elixirfsuspension bottle so that the cap can be utilized as the measuring device. This would diminish the risk of using another inappropriate measuring device as well as diminish the risk of the cup being misplaced. 0 Replace the abbreviation with "tsp." and provide the mL equivalent as well. 0 Educate health care providers on the differences of acetaminophen formulations and on the signs and of acetaminophen toxicity along with proper treatment. Carol Holquist, Safety Evaluator Office of Postmarketing Drug Risk Assessment (OPDRA) Concur: Jerry Phillips, Associate Director for Medication Error Prevention Office of Postmarketing Drug Risk Assessment (OPDRA) ATTACHMENT A Patient Age, Dosage Form Dose Administered Concomitant APAP Adverse Event Final Weight, and Dose Product Level Outcome Gender if Administered known and McNeil MFG .5 yr. Junior Strength 400 mg once of' None None Unknown Unknown Female Tylenol and Junior Strength and (28.6 kg) Tylenol Cough 312.5 mg of Tylenol #3 391 IA Medication Cough for fever and cough (25 mg/kggday) 21 month Junior Strength U3 tablet once Unknown Unknown Unknown Unknown Female Chewable Tablet 3.5 yr. Unknown 320 mg 2 for Amoxicillin and 137.2 Liver Damage, Unknown Female APAP Tablet fever, cough and Unknown supp. mg!L 22 Kidney Failure, suspected vomiting For vomiting 2 from and Pancytopenia 13 kg Junior Strength days prior to event last dose Tylenol (295 mg/kgfday) 5 yr. Children's 240 mg 2 (60-90 Unknown Unknown None Reported Unknown (19 kg) Tylenol minutes apart} #46l'l'1A Chewable Tablets (25 mg/kg/day) 5 yr. Children's 320 mg once Unknown Unknown None Reported Unknown Male Tylenol (17.7 kg) Chewable (I8 mg/kg/day) Tablets 5 yr. Children's 32!) mg for fever Unknown Unknown Hallucinations Unknown Female Tylenol (16 kg) Chewable (20 mg/kg/day) Tablets 4 yr. Children's 160 mg 30 minutes Unknown Unknown None Unknown Tylenol apart Chewable Tablets 12 yr. Children's 560 mg at 5 pm. and Unknown Unknown None Unknown Male Tylenol 6 p.m. Chewable Tablets 5 yr. Children's 560 mg once Unknown None None Unknown Female Tylenol (25 kg) Chewable (22 mg"kg."day) #5 83 73A Tablets 4 yr. Children's 240 mg at 6:30 am Unknown Unknown None Unknown (20.5 to 26.7 Tylenol and 8:30 am kg) Chewable #60'l'23A Tablets (23-I 8 mgikg/day) 5 yr. Children's 160 mg q4h for fever Unknown Unknown None Reported Unknown Female Tylenol (13.6 kg) Chewable (70 mg/kg/day) #6200815: Tablets 3 yr. Children's 160-480 mg 2 Unknown Unknown None Reported Unknown (33 kg) Tylenol doses; approx. 640 Chewable mg total dose Tablets [19 8 yr. Children's 320 mg q4h, 2240 Unknown Unknown None Reported Unknown Female Tylenol mgf24 hr for fever (20 kg) Chewable Tablets (112 mg;'kglday) 7 yr. Children's 320 mg 6 times daily None None None Unknown Female Tylenol for post-operative (22.7 kg) Chewable tonsillectomy pain #3 6698213 Tablets (85 23 month Children's 160 mg q4h around None Unknown No Drug Effect Unknown Male Tylenol the clock of Chew #36'!0l3A Chewable tabs and 80 mg q4h Tablets of Children's Tylenol Cold Liquid 4 yr. Children's 640 mg 1 dose for Unknown None None Reported Unknown Female Tylenol cold (20.5 kg) Chewable Tablets (31 mg/kgfday) 3 yr. Children's Up to 320 mg once Amoxicillin None None Reported Unknown Male Tylenol because child felt (17.3 kg) Chewable very warm Tablets (I9 6 yr. Children's Approx. 320 mg q4- None Unknown Stupor, Liver Female Tylenol Sh while awake for Somnolence, enzymes (19 kg) Chewable fever Liver function reported #6967029: Tablets test abnormal normal on (l0l-67 mg/kgiday) follow-up exam 8 yr. Children's 900 mg q4h 2 doses None None None Reported Unknown Male Tylenol (25 kg) Chewable #8641 19A Tablets 5 yr. Children's 240 mg of Chewable Unknown Unknown None Reported Unknown Male Tylenol tablets at 9:30 am (19.5 kg) Chewable then around noon #5013415. Tablets gave 240 mg of Tylenol Elixir (25 mg/kgfday) Child Children's 3840 mg over 3 days Unknown In the 90 TX with Unknown #5541 IA Tylenol Elixir range and evaluated for a liver transplant, but did not reqgire one. I 8 months ChildrenUnknown Mid 40 Hepatic Coma, Unknown Female Tylenol Elixir days mcg/mL Overdose, Liver 36 hours Failure post last dose 6 yr. Tylenol Elixir 320-640 mg q4h for Cortisporin Otic 714.2 Liver Failure, Liver Male fever and ear pain Suspension Dehydration, Gl Transplant (27 kg) (4 to 7 doses over 2 on day 2 Hemorrhage, #3 1573223; days) Coagulation Disorder, Coma (47-I66 I3 yr. Children's 960 mg once for cold None None None Reported Unknown Male Tylenol Elixir (40 kg) (27 mg/kg/day) #3436914. 7 yr. Children's I920 mg once None None None Reported Unknown Female Tylenol (18 kg) Suspension (I06 mg/kg/day) 4 yr. Unknown 15 mg/kg dose of Unknown Unknown Liver Failure, Liver Female APAP Syrup acetaminophen syrup Kidney Failure Transplant #633 STTA q4h around the clock for fever, vomiting and diarrhea 3.5 yr. Tylenol Elixir 15 cc ql5 minutes None 132 Somnolence, Unknown Female day then less meg/mL Vomiting, Liver (l 1 kg) frequently 2 days Failure, #74 635A for abdominal pain Encephalopathy (>350 6 yr. 224-320 mg q4h of Cefazolin Less than Sweating, 24 hours Male acetaminophen elixir Injection 10 Vomiting, post mcgr'mL 5 Abnormal Liver with APAP with Codeine after Function Tests Mucomyst Elixir; total dose 3.6 last dose all liver over 30 hours values returned to (193 over 30 nonnal. hours) 22 month Children's 160 mg q3h for fever Cefzil None None Reported Unknown Male Tylenol Elixir (I3 kg) and Children's (101 mg/kglday) Motrin for fever 8 yr. Children's 480 mg q3h post None None Vomiting and Female Tylenol tonsillectomy Diarrhea Resolved (28 kg) Suspension (136 mg/kgfday) 12 month Children's 480 mg tid -- Used None None None Reported Unknown Male Tylenol syringe to give (12 kg) Suspension tablespoonful instead #100! 835A of teaspoonful for teething pain-- The capital on the dosing cup led consumer to believe dose was a tablespoonful (I I7 5 month Children's 480 mg 1 dose for None None None Reported Unknown Female Tylenol teething pain (6.4 kg) Suspension (75 3 yr. Children's 160 mg q3 U2 Keflex None None Unknown Male Tylenol around the clock for (15 kg) Suspension pain from #l236853A tonsillectomy 19 month Children's 280 mg TID for fever None None None Reported Unknown Female Tylenol for 3 days (10 kg) Suspension (84 5 month lnfant's 160 mg following Unknown Unknown None Reported Unknown (6.4 kg) Tylenol Drops DPT shot (2 dropperfuls) Child Infant's 400 mg Unknown Unknown None Reported Unknown (6.14 kg) Tylenol Drops (ADME 4 mL vs. 0.4 #l07224A mL) (65 mg/kglday) 1' month Infant's 240 mg q4h for 3 None 53 Shock, Hepatic Death Male Tylenol Drops days for fever Failure, (9 kg) Coagulation #l6l637A (160 mg/kg-lday) Defects, Hypoglycemia, Heart Arrest and Liver Transplant I4 month Infant's 120 mg 7 doses for Unknown Unknown None Reported Unknown #l68735A Tylenol Drops fever 5 month Infant's 800 mg 1 Unknown Unknown Unknown Unknown (6.8 kg) Tylenol Drops (188 mg/kg/day) 10 month Infant's 400 mg q6h 3 doses Unknown Unknown None Reported Unknown Female Tylenol Drops over 36 hr period for (8.6 kg) fever. #540fl6SA 15 month lnfant's 400 mg 2: 3 doses Unknown Unknown None Reported Unknown Female Tylenol Drops over 2 days for cold (10 kg) #65999lA 2 month Infant's 80 mg qid 4 doses None Unknown Unknown Female Tylenol Drops (4.2 kg) (76 mg/kgfday) 2 month Infant's Total of 640 mg None Unknown None Reported Unknown Female Tylenol Drops (3 dropperfuls 2 (5.9 kg) and 2 dropperfuls #799l38A 1) (109 mg/kgfday) 6 month Infant's 160 mg qid for fever Unknown Unknown None Reported Unknown (7.7 kg) Tylenol Drops #36l975A (83 9 month Infant's 160 mg qt}: (5 to 8 Amoxicillin Unknown Jaundiee Female Tylenol Drops times a day) for fever Resolved (8.6 kg) (93-149 mg/kgfday) Infant Infant's I60 mg q4h around Unknown Unknown None Reported Unknown Male Tylenol Drops the clock per MD (8.2 kg) order for teething 3 #89] 740A days (88 I3 3 month Infant's I00 mg q4h around None Unknown None Reported Unknown Male Tylenol Drops the clock per MD for (6.8 kg) teething pain for 3 #925 l67A days (38 18 month Infant's 360-400 mg q3h 8 Unknown 58 Liver Function Unknown Male Tylenol Drops doses for influenza mcg:'mL. Abnormal, (9 kg) Vomiting, and #93 I 533A (320-356 Fever 8 month Infant's 160 mg qid for 4 days Unknown Unknown None Reported Unknown Male Tylenol Drops for fever (7.3 kg) (88 mg/kg/day) 60 days Infant's 60 mg 4 None None Somnolence Unknown Male Tylenol Drops (4.55 kg) (79 mg./kgfday) I5 month lnfant's 320 mg q4h for fever Unknown Unknown None Reported Unknown Male Tylenol Drops (9 kg) (211 mg/kg/day) #l 7 month lnfant's I60 mg qid for None None Unknown Male Tylenol Drops immunizations (7.3 kg) #1 1766] SA (38 4 month lnf'ant's 320 mg bid 2 doses None None Unknown Male Tylenol Drops (6.8 kg) (94 #1 341571.45. 2 month lnfant's I25 mg None Unknown None Reported Unknown Female Tylenol Drops (5.9 kg) (21 mg/kgfday) yr. Infant's 1500 mg, 1000 mg Unknown Unknown Dyspepsia and Unknown Male Tylenol Drops for roseola, fever Vomiting (10.7 kg) #13362 IA 93-140 mg/kg/day) 2.5 yr. lnfant's 500 mg 2; 1 for Children's Advil is Unknown Stomatitis Unknown Male Tylenol Drops prevention of febrile seizures 14 month lnfant's 160 mg q4h for viral Pediaprofen 1 48 Somnolence, Liver Female Tylenol Drops Liver Failure Transplant (10 kg) 00430.4. 2 yr. lnfant's 500 mg qid for fever None Unknown None Reported Unknown Male Tylenol Drops (13.64 kg) (147 mg/kgfday) 15 month Infant's Approx. 320 mg 3 Unknown Unknown None Reported Unknown Male Tylenol Drops doses status post (11.36 kg) MMR and DPT vaccinations (84 mg/kg./day) 9 month Infant's 500 mg 4 to 6 times None Unknown None Reported Unknown Male Tylenol Drops daily for fever, sore (l 1.36 kg) throat for 2 to 3 days (175-263 mgikgfday) 19 month Infant's 500 mg q4-6h 4 None l4 None Reported pt Recovered Female Tylenol Drops doses for fever received TX with and (1 1.3 kg) Mucomyst Discharged #5769461'-\ 166 6.5 month Infant': 750 mg q4h 8 doses Amoxicillin 23 Encephalopathy, TX with Male Tylenol Drops mcgImL Liver Function Mucomyst (7.9 kg) (570 mg/kglday) Abnormal, and #741583.-tr Tremor, Syncope Recovered and Cyanosis l5 month Infant's 375 mg tid for 3 days None Unknown Liver Function Male Tylenol Drops for fever Abnormal Resolved (9.55 kg) #83301 SA (1 I8 2 month Infant's 250 mg tid 3 closes None Unknown None Reported Unknown Male Tylenol Drops for pain and fever (5.46 kg) from immunizations (136 mfig/day) 16 month lnfant's 1000 mg for fever Unknown Unknown None Reported Unknown Male Tylenol Drops (I0 kg) (100 12 month Infant's 750 mg once for None Unknown None Reported Unknown Female Tylenol Drops fever (3.6 kg) (87 12 month lnfant's 500 mg q3-4h pm (9 Unknown 25 Liver Function TX with Male Tylenol Drops tsp. Over 36 hours) mcg/mL Abnormal, Mucomyst (4.55 kg) Prothrombin Discharged #93 l690A (25 mg/kglday) Increased, Home in Albuminuria Good Condition 24 month Infant's 2250 mg/24 hours 6 Unknown 10.9 None Reported Unknown Female Tylenol Drops doses for fever, 9 kg vomiting, and #93 I 578A diarrhea (250 mgfiggday) I0 month Infant's 750 mg tid for 2 days Unknown 33 Somnolence, TX with Female Tylenol Drops mcg:'mL Abnormal Liver Mucomyst (9 kg) (250 Function and LFT's #93 1 74 IA normalized 9 month Infant': 750 mg 8 doses Unknown 46.8 Convulsion, Unknown Male Tylenol Drops over 2 days for post mcg!mL Hypoglycemia, 8.3 kg hypospadias repair Liver Failure, #93 1621A Vomiting and (360 Encephalopathy 10 day Infant's 250 mg 3 times Unknown 56 Prothrombin TX with Male Tylenol Drops within a 12 hour mcg.r'mL Increased Mucomyst (4.5 kg) period 4.75 hours and #93 1448A after last Recovered I67 close 8 month Infant's 250 mg bid for 3 days None 146 None Reported Unknown Female Tylenol Drops for fever and flu mcg/mL (8.6 kg) 4 month lnfant's 375 mg tid for 1 day None Unknown None Reported Unknown Female Tylenol Drops for immunization (7.7 kg) pain (I46 mg/'kg/day) 12 month lnfant's 500 mg bid for 2 days Advil and Motrin Unknown None Reported Unknown Male Tylenol Drops for strep throat (ll kg) (91 9 month lnfant's 375 mg od-tid for 2 Amoxicillin and Unknown None Reported Unknown Male Tylenol Drops days for fever Children's Motrin (9.55 kg) #99l093A (39-I18 mg/kg/day) 13 month Infant's 0.5 day 1, 1.5-2 Nystatin Cream, Negative Diarrhea. Unknown Male Tylenol Drops day 2; up to 1.5 day Mycelex Nervousness, (10 kg) 3 for fever Somnolence, #l086l22A vomiting, (50-200 Abnonnal Stool Abnormal LFT's. TX with NAC 21 month Infant's 2l5 mg/kg over a 15 None 12.8 Abnormal Liver Unknown Male Tylenol Drops period for viral Function (Liver #1 l30722A Damage) TX with Mucomyst (215 15 month Infant's 350 mg q?lh for fever None Unknown Liver Failure, LFT's Male Tylenol Drops Vomiting, returned to (9 kg) (233 Somnolence, normal #1 l49638A Abnormal Liver approx. I Function, week post Encephalopathy completion of treatment with NAC 11 month Infant's 640 mg once Unknown Unknown Somnolence Unknown Female Tylenol Drops #12] 3006A Unknown Infant's 500 mg q4h for fever Unknown 25 Liver Function Unknown Male Tylenol Drops and earache Abnormal, No 1 236358A Drug Effect, Received TX with NAC 8 month Infant's 500 mg bid for 1 day Unknown Unknown None Reported Unknown Male Tylenol Drops for fever (7.72 kg) #l275756A (130 3.5 yr. Infant's 1.6 at 8 p.m. and None 163 SGOT Increased Unknown Female Tylenol Drops 0.8 at 10 am; 160 micromol TX with (17 kg) mg 3-4 times a day 2 Mucomyst #1 302l68A days prior for high charcoal fever (141 7 month lnfar1t's Approx. 375 mg/kg None Unknown Liver Failure, Unknown Female Tylenol Drops over 24h for fever Thinking (8.6 kg) Abnormal, #1 324632A (Approx. 375 Hepatomegaly, mg/kg/day) SGOT and SGPT increased, increased. Pt TX with NAC 30 month lnfant's 500 mg bid for fever Unknown Unknown None Reported Unknown Male Tylenol Drops (12.3 kg) (81 35347'.v'A 1 month Unknown 15 q4h for a Unknown Unknown Convulsion, Unknown Male Children's total of 150 mg in 24 Encephalopathy (I 1 kg) APAP hours for febrile Liver Failure, #1 356546A Suppository illness Hepatomegaly, follow-up Coagulation reported (150 mg/kg/day) Disorder, specified Abnormal Lab Tylenol Supp. Test and Liver Necrosis 1.5 yr. Unknown Unknown dose and Unknown Unknown None Reported Unknown Female Children's Frequency #l3345l9A Tylenol Product Infant Unspecified Unknown dose and Unknown Unknown None Reported Discharged Tylenol APAP frequency However, infant in Product (Accidental admitted for satisfactory Overdose) overdose condition. management Did not receive a Liver transplant. Child Unspecified Unknown dose and Unknown Unknown None Reported Unknown #l393819A Tylenol APAP frequency Product "Accidental Overdose" 5 yr. Unspecified 3.18 in 2 days for Ampicillin, 93 Coma Death Female APAP fever, cold and cough Metaclopramide mcgl'mL #14 874AA (paracetamol) Tablet and Powder Product 3 yr. Unspecified At least 1025 mg to Ampicillin, 38.9 l-iepato-Renal Death Male APAP 1200 mg daily [Given Salbutamol, Failure #1425 53A (paracetamol) q4h MD prescribed day after Product qoh (4 times admin. 1.5 yr. Unspecified 250 mg q4h (1500 Benadryl, 85.9 Hepatic Failure, Death Male APAP mg daily) for fever mcg:'L Encephalopathy (paracetamol) cough and runny nose Salbutarnol, Product Cephalothin and Danazol Su 9 yr. 1000 mg q4h for 3-4 38.3 mg;'L Convulsion, Death Male days; additionally more than Cardiopulmonary (48 kg) received combination 24h afier Arrest, Abnonnal #21 1965A product with 500 mg last dose Lab Test, APAP intermittently Hematemesis, for fever, headache Abdominal Pain, and myalgias Confusion ASTIALT High 10 year Repetitive doses over 49 Liver Necrosis, Death Female Product 12 days of APAP mcg!mL Acute Kidney non-ASA Alka- day failure, Grand Seltzer 2 Extra after last Mal Convulsion Strength tablets for dose Infection flu like 16 month Unknown 100 for 1 Unknown 40 Liver Failure, Death #5 l2558A APAP Product week for fever, URI mcg/mL Encephalopathy, Infection, Prothrombin Increased, Kidney Failure 2 yr. Unknown 80 for None 15 Encephalopathy, Recovered #5 1 3010A APAP Product 3days for 1 week mcg/mL Liver Failure, with normal varicella Prothrombin Liver Increased. Pt Function received within ID supportive TX. days 1? month Unknown Unknown dose at Unspecified 205.88 Acidosis, Pt. Female Paracetamol home for 3 days; Antibiotic umol/'L Abnormal Liver recovered (1 I kg) Product unknown antipyretic Function, and administration in Jaundice, Stupor, discharged hospital for fever Vomiting and after l8 adynamia, days. hepatomegaly and bradycardia No specific TX for poisoning was carried out 4 yr. Unknown Unknown dose for 4 None 67.8 mgr'L Abnormal LFT's, TX with Female APAP Product days for rhinorrhea, Abnormal NAC. cough and subjective Kidney Function, Renal fever Hypertension, Function Abnormal lab test returned to normal and hepatic function improved. 1 1 month Unknown 60 4 doses in Unknown 46 Abnormal LFT's Liver test Male APAP Product I day for fever meg,/mL TX with NAC results (9.7 kg) improved. #74] 605A 24 month Unknown 40 4 doses Unknown 159 Abnormal LFT's Liver test Female APAP Product for 1 day for fever mcg!mL results (12 kg) remained #74 16] SA normal. 3 yr. Unknown 100 mg/kg/day in 6 Unknown Unknown Liver Necrosis Death Male Tylenol divided doses for 3 #7443 IOA Product days for post- operative frontotemporal craniotomy and debridement of skull fractLu*e underlying brain contusion 4 month Unknown 90-180 mg/kg/day for Unknown 180 Abnom1alLFT's Unknown #8l776lA APAP Product 1 day mcg:'mL 4-6 hours post last dose 9 month Unknown 400 for 2 Unknown 46.8 Abnormal LFT's Pt status #3130404-'3. APAP Product days meg/mL listed as 24-3011 alive. post last dose 17 month Unknown 160 mg did then 650 Reglan, Zantac, Unknown Somnolence, Discharged Male Tylenol mg tid for fever Lasix, Intal, Convulsion, 10 months Product Albuterol, KCI Hypematremia, later with and other Apnea, Hypoxia, unspecified unspecified Respiratory injuries medications Arrest resulting from Hypoxia 19 2.5 yr. Unknown Approx. 90 None 551 Liver Failure, Pt recovered Female Paracetamol mg/kg/day for 4 days umolf 4 Hypoglycemia, after (11 kg) Product for fever, malaise, hours after hepatomegaly, intensive #12496] SA nausea vomiting last dose Acidosis, NPN medical TX and BUN for 4 days increased, with no Increased evidence of coagulation time. hepatitits no underlying metabolic abnorms. 21 month Unknown 20 mg/kg/day for 21 Unknown 10 umol/L Liver Failure, Reported as #l266508A Paracetamol days I71 2 days Coagulation resolved. Product for 1 day post Disorder, for a prodromal admin. Bilirubinemia, illness. Hypoglycemia Acute Brain 63 month Unknown 100 for 6 Unknown 560 Liver Failure, Death (5.25 yr.) Paracetamol days umol.-' Coagulation awaiting a #l267482A Product 1 day post Disorder, Liver admin. Bilirubinemia, Transplant. Hypoglycemia, Hepatic Coma, Liver Necrosis month Unknown 200 for I Unknown 30 umolfL Liver Failure, Reported as (6.4 yr.) Paracetamol days for prodromal 6 day post Coagulation resolved. #12679] SA Product illness admin. Disorder, Bilirubinemia, Acute Brain 106 month Unknown 175 mg/kgfday for 7 Unknown 30 umol."L Liver Failure, Reported as (8.8 yr.) Paracetamol days for prodromal 3 days Coagulation resolved. #1 268253A Product illness post Disorder, admin. Bilirubinemia, Acute Brain 54 month Unknown 75 for 5 Unknown 900 Liver Failure, Reported as (4.5 yr.) Paracetamol days then 150 umol/L Coagulation resolved. #l268308A Product mg/kgfday for 1 day. 1 day post Disorder, admin. Bilirubinemia, Acute Brain 4 yr. Panadol 2.4 over 72h and Cefaclor 55 umolfL Abdominal Pain, TX with Female 2.8 over l7h for 22h after Vomiting, NAC and (20 kg) otitis media. last dose Hypoxia, had a Abnonnal LFT's. complete (40-l 50 mgikgfday) Bilirubinemia. recovery. Prothrombin w/nL Increased, 3 months Ascites following event 20 2 yr. Unknown 90 mg/kgiday for 5 Unknown Unknown Liver Failure Reported as Female Paracetamol days for pyrexia, Recovered. #13007-=l6A Product nausea, vomiting and for malaise. 6 yr. Unknown 400 mg/kgiday for 4 Unknown l-4.5 Liver Damage, Discharged Male Paracetamol days for fever. Encepahlopathy, well 4 days (16 kg) Syrup 40h after Jaundice, post hospital 352 IOTA last dose Hepatomegaly, admin. Hypoglycemia Dehydration, Increased Prothrombin 3 yr. Unknown 6 gfday for 2 days, Unknown l9.2 Liver Damage. Responded Female Paracetamol 500 mg/day for 1 day meg/mL Vomiting, well to kg) Suspension for fever l2h after Somnolence, supportive #1352 1 89A last dose Encepahlopathy, care and Dehydration, was Bilirubinemia, discharged Prothrombin from hosp. 4 Increased days post admin. 2 yr. Unknown 300 for 2 Unknown 7.44 Liver Necrosis, Death Female Paracetamol days for persistent Hypoglycemia, (13 kg) Syrup fever, cough runny 72h after Liver Failure, #1 352247A nose. last dose Encephalopathy, GI Hemorrhage, Kidney Failure, Drowsy, Lethargic 10 month Chi|dren's Unknown amt. of None 60 mg;'dL Encepahlopathy, Death Female APAP Elixir Elixir q4h then adult 24h post Infection, Grand (9.5 kg) and Adult tablets dissolved in last dose Mal Convulsion APAP Tablet bottle q4h for fever and Liver Failure and respiratory 9 month Unknown I tsp. q4h of elixir Unspecified OTC 60 Liver Failure, Death Female APAP Elixir then chewable APAP cold medication Cardiac Arrest, (9.5 kg) Product after running out Sepsis, Kidney #6347049. And Unknown then adult strength Failure, Shock Chewable APAP over 4 days APAP Product period (crushed and mixed in formula) for rhinorrhea :51: cough I0 month Tylenol Elixir Unknown dose of Unspecified cough 60 Abnormal Ll-'T's Death Female and Tylenol Elixir q4h then 80 mg syrup meg/rnL (9.5 kg) chewable chewable tabs q4h #705l96A tablets then Regular Strength Tylenol (325 mg) dosing for 4 days (Ran out of each drug and went to the next strength) 21 This is a representation of an electronic record that was signed electronically and this page is the manifestation of the electronic signature. Carol Holquist 9/7/01 08:41:25 AM PHARMACIST Jerry Phillips 9/7/01 03:51:23 AM DIRECTOR Martin Himmel 9/13/01 02:11:19 PM MEDICAL OFFICER