Front Matter (PDF)

Not al drgfr the treatmnentofAH are iaentical- infrmnulation, clinicalactity1 or dosingfeqency

te onl protduct tat contains both dextro ()and levo aI)apetamnine

Usae dtaaorADRl indiae tat nmostpatients can be mnaintained on a once- or twice-diladIosing re( i?en

n=611 children aged 3 to 12 who had at least three office visits during the 1-year, ADDERALL usage period (March 1995 to February 1996)- 34 patients receiving greater than 40 mg per day were excluded from this analysis.' Clinical actvyVI

* ADDERALL has a product half-life of 8 to 12 hours',' * The safety profile of amphetamine products like ADDERALL has been confirmed over years of clinical use * ADDERALL is generally well tolerated- adverse reactions have seldom been reported (most frequently reported adverse reactions include anorexia, insomnia, stomach pain, headache, irritability, and weight loss)' * As with most psychostimulants indicated for ADHD, the possibility of growth suppressil'on and the potential for precipitating motor tics and Tourette's syndrome exists wvith ADDERALL treatment, and, in rare cases, exacerbations of psychosis have been reported' . Since amphetamnines have a hig potential for abuse, ADDERALL should only be prescribed as part of an overall multimodal treatment program,for ADHD wvith -dose physilciaii supervision * ADDERALL is safe and effective in younger children~ indicated for use in children 3 years of age anld older' . The starting dose ofADDERALL: 3 to 5 years: 2.5 mg daily; 6 years of age and older: 5 mg once or twvice daily . ADDERALL is available in 10 mg and 20 mg double-scored tablets for optimal dosing flexibility ~~Offers precise dosage coffelation with individual therapeutic needs T4itrate to optimal dose with a singl prescription

10 mgblue double-scored tablet 20 mgorange double-scored tablet

-1 O nag &k 20 nag YABL-EYS (Mixed Salts of a Single-Entity Amphetamine Product) Dextroamphetamine Sulfate Amphetamine Sulfate Pleaseseereferencesand briefsummary Dextroamphetamine Saccharate Amphetamine Aspartate ofprescribing information on adjacentpage.

J&Ow ce g ...working to becomeyourADIID support company 11 w hom, -~e j {~atastth ereare athree tievv acellular vaccines clairming , ~~ r4 an W to be evateet a

T Infanrixll: The only U.S.olicensed acellular DTP vaccine proven more efecive than whole-cell DTP Acellular DTP vaccines cause fewer local and systemic side effects than whole-cell vaccines.'-4But only one, Infanrix, has been proven more effective against pertussis than a U.S.-licensed whole-cell DTP vaccine, manufactured by Connaught Laboratories, in an NIH-sponsored study recently published in The New England Journal of Medicine.'

InfanrixT: Why 3 components? The results of two NIH-sponsored clinical trials reported in The New England Joumal of Medicine supported the efficacy of three-pertussis-antigen Intanfix.1 4,5

Infanrixll: Because children deserve all the proection they can get.

Local adverse events may occur at the site of injection and include erythema, swelling and tenderness. Systemic adverse events may include fever, irritability and drowsiness. Hypersensitivity to any component of Infannix is a contraindication. As with any vaccine, vaccination with Infantix may not protect 1 00°h of susceptible individuals.

Rene: 1. Greco D, Salmaso S, Mastrantonio P, et a]. A controlled trial of two acellular vaccines and one whole-cell vaccine against pertussis. N Engl J Med 1996;334:341 -348. 2. Decker MD, Edwards KM, Steinhoff MC, et a]. Compa~rison of 13 acellular pertussis vaccines: adverse reactions. Pediatnics 1995;96(suppl):557-566. 3. Infanrnx Prescribing Information, SmithKline Beecham Pharrna- ceuticals. 4. Gustafsson L, Hallander HO, Olin P, et a]. A controlled trial of a two-component acellular, a five-component acellular, and a whole-cell pertussis vaccine. N Engl J Med 1996;334:349-355. 5. Edwards KM, Decker MD. Acellular pertussis vaccines for infants. N Engl J Med 1996;334:391 -392. Editorial. Please see brief summary of prescribing information on adjacent page.

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Lock up medicines S f g;0f Keep up with the times Keep all medicines and potentially Discard substances used for old- Idangerous household substances fashioned treatments, such as: oil of out of reach of children, in cabinets with wintergreen, boric acid, ammoniated child-protection safety latches. Store mercury, oil of turpentine and camphor- medicines away from household prod- ated oil. ucts. Keep household products away from food. Do not be distracted 7If the phone or doorbell rings while Use original Iyou are administering medicine containers or using a potentially poisonous product, secure the product you are using: Keep medicines or household prod- Replace its cap, put it back in the Cucts in their properly labeled original cupboard, or take it or the child with containers. Original packaging is usually you while dealing with the distraction. required to contain child safety pre- cautions. Labels include information Plan ahead for control centers in case of poison QEducate your children. Post the poi- an Never emergency. put dangerous son control center phone number products in containers from which with other emergency numbers by every people eat or drink. phone. Keep ipecac syrup on hand so that if the poison control center advises Use child-resistant you to administer it, you are prepared. packaging Support poison control centers. (2Credited with saving at least 700 zJchildren's lives since its introduction Set a good example in 1970, child-resistant packaging Do not take medicines in front of is still often used improperly, according ;7children. Do not drink from contain- to the U.S. Consumer Product Safety ers, such as cough syrup bottles. Never Commission (CPSC). Be sure to replace refer to medicine as "candy." Children caps securely. Adult-friendly packaging are likely to imitate and could adopt now makes it easier for arthritic these behaviors. hands or frustrated adults to protect children without inconvenienced from home being The of are - Away themselves. signs potential poisoning frightening vomiting, appearing sluggish or drowsy, substance or burns around the mouth or a smell on the child's breath. dnSome 23 percent of poisonings But clear and deliberate actions will ensure the most efficient care for |Jinvolve prescription drugs belong- Read the label thinking ing to someone the child does not live the child. A plan of attack will help in such an emergency. ADo not administer medicine in the with, most often grandparents, according dark. Do not trust your memory for 1. Remain calm. to an American Association of Poison dosage instructions. Use your eyeglass- Control Centers study. Thirteen percent of es or contacts to read the fine print. 2. Call the poison control center prepared to give: all child poisonings occur in homes other LJvictim's age than the child's, according to the CPSC. Dispose of outdated Li victim's weight - Rebecca Palmer medicines Li any pre-existing health conditions or problems ,When you regularly clean out your LI substance involved vJmedicine cabinets, flush medicine FiVQ plants most (ommonM4 down the drain or toilet, and then rinse LI quantity of substance associated with poisoning~s the bottles before throwing them in Li time of exposure the trash. OJ whether substance was swallowed, inhaled, absorbed C) Pepper (the spice) through skin, splashed into eyes C) Philodendron (Philoclendron scandens or P. selloum) Li progression of symptoms Most Dangerous Medidffls Dieffenbtachia _ LI your location a'nd how long it takes to reach a hospital O) Ironsupplements (Dieffenbachia 3. Follow the specific instructions of the poison control center. maculata or CO Cardiovasculardrugs 4. Continue poison prevention. D. sequinwe)_ Anti-depressants pi II Be prepared for a poisoning emergency: Post the poison control center phone number by every phone. TO LOCATE THE NEAREST POISON CONTROL CENTER, call (202) 362-7217, or write to the American Association of Poison Control Centers, 3201 New Mexico Avenue, NW, Suite 310, Washington, DC 20016. ma[Ch 16-22 ~~~~~1 March 1997AAPNews IS ,g.

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IPCDlease see briefsummary for ZYRTEC tablets and syrup on the following page. Based on a comparison of the list price to wholesalers (wholesale acquisidon cost) of ZYKTEC tablets, Claridn, Seldane, Hismanal, Clarittin-D, Seldane-D, and Allegra on a cost/day basis; Actual cost to patients may vary. Medispon, December, 1996. Due caution should be exemised when driving a car or opemting potentially dangerous machinery. BRIEF SUMMARY ZYRTEV (CETIRIZINE HYDROCHLORIDE) TABLETS MD SYRUP FOR ORAL USE FOR FULL PRESCRIBING INFORMATION, CONSULT PACKAGE INSERT) INDICATIONS AND USAGE Seasonal Allergic Rhinitis: ZYRTEC is indicated for the relief of symptoms associated with seasonal allergic rhinitis due to allergens such as ragweed, grass and tree pollens in adufts and children 6 yearsof age Md older. Symptoms treated effectively include sneezing, rhinorrhea, nasal pruritus, ocular pruritus, tearing and redness of the eyes. Perennial Allergic Rhinitis: ZYRTEC is indicated for the relief of sym toms associated with perennial allergic rhinitis due to aller ens such as dust mites, animal dan- der and molds in adults and children T years of age and older. Symptoms treated effectively include sneezing, rhinorrhea, postnasal discharge, nasal ruritus, ocular pruritus and tearing. Chmnit UrOcaria: ZYRTEC is indicated for the treatrnent ot the uncomplicated skin manifestations ofchronic idiopathic udicaria in adufts and children 6 years of age and older. It significantly reduces the occurrence, severity and duration of hives and si nificantly reduces pruritus. CONTRAINDICATIONS ZYR?EC is contraindicated in those patientswith a known hypersensitivityto it or any of its ingredients or hydrox- yzine. PFIECAUTIONS Activities Requiring Mental Alertness: In clinical trials, the occurrence of somnolence has been reponed in some patients tak'ing ZYRTEC; due caution should therefore be exercised when driving a car or operating potentially dan erous rnachinery. Concurrent use of ZYRTEC with alcohol or other CNS depressants should be avoided because additionai reductions in aillebm and additional impairment of CNS edormance may occur. Drug-drug Interactions: No clinically si nificant drug interactions have been found with theopnylline at a low Tose, azithromycin, pseudoephedrine, ketoconazole, or erythromycin.%ere was a small decrease in the clearance of cetirizine caused by a 400 mg dose of theophylline; it is possible that larger theophylline doses could have a greater effect. Carcino...... 113, go an lrment of Fert idence ofcarcinogenicity was observed in a 2-yearcarcinogenicity study in rats at dieta up to 20 (approxim the maximum recommended human daily oral dose on a Mg/M2 basis). An increased ce of benign r t mors was fo n a r carcinogenicity study in male mice at a dietary dose of 16 mg/kg/day (approximately 4 times the maximum recommend h dai oral dose on a Mg/M2 basis). The clinical significance offtm findings during long-term use of ZYRTEC is not known. Cetirizine was not mutagenic in the Ames test, and not clastogenic in the human assay, the mouse lymphoma assay, and in vivo micronucleus test in rats. No impairment of fertility .w found in a feftiliV and e uctive performance study in mice at an oral dose of64 m day(approximately 26 times the maximum recommended adult Can ral dose on a Mg/M2 basis). Pregnancy Category B: te(tirizine was not teratogenic in mice, rats and rabbits at oral doses up to 96 and 135 mg/kray (or approximately 40,180, and 215 times the maximum recommended aduft human daily oral dose on a m basis), respectiveiy. Ihere are no adequate and well-controlled studies in pregnant women. Because animal studies are not always pre ctive of human response, ZYRTEC should be used in pregnancy only if clearly needed. Nursing Mothers: Retarded pup weight gain was und in mice durin lactation when dams were given cetirizine at 96 mg/kgtday (approximately 40 times the maximum recommended adult human daily oral glose on a Mg/M2 basis). Studies in beagle dogs indicate that approximately 3% of the dose is excreted in milk. Cetirizine has been repofted to be excreted in human breast milk. Because rnany drugs are excreted in human milk, use of ZYRTEC in nursing mothers is not recommended. GorleMc Use: In placebo-controlled trials, 186 patients aged 65 to 94 years received doses of 5 to 20 mg of ZYRTEC per day. Adverse events were similar in this group to patients under age 65. Subset analysis of efficacy in this roup was not done. Pedishic Use: The safety of ZYRTEC, at daily doses of 5 or 10 mg, has been demonstrated in 376 pediatric patien I years of in placebo-controlled trials iasting up to four weeks and in 254 patients in a non-placebo-controlled 12 week triai. The iveness of NPRTEC for the treatment of seasonal ana perennial allergic rhinitis and chronic idiopathic udicaria in this pediatric age group is based on an extrapolation of the demonstrated efricacy of ZYRTEC in adults in these conditions and the likelihood that the disease course, patho- physiology and the drug's effect are substantially similar beMwn ftm two populations. The recommended doses for the pediatric popula- tion are based on a cross-study comparison of the pharmacokinetics and pharmacodynamics of cetirizine in adults and pediatric subjects and on the safe rofile of cetirizine in both adults and pediatric patients at doses equai to or h gher than the recommended doses. The cetirizine AUC and?&w in pediatric subjects 6-11 years oT age who received a single dose of 11) mg of cetirizine syrup was estirriated to be intermediate between that observed in adults who received a single dose of 10 mg of cetirizine ablets and those wno received a single dose of20 mg of cotirizinetablets. ADVERSE RUCTIONS Controlled and uncontrolled clinical trialsconducted in the United Statesand Canada include more than 6000 patients aged 12 years and older, with more than 3900 receiving ZYRTEC at doses of5 to 20 mg per day. The duration of treatment ranged from 1 week to 6 months, with a mean exposure of 30 days. Most adverse reactions reported during therapy with ZYRTEC were mild or moderate. In placebo-controlled trials, the incidence of disconfinuafions due to adverse reactions in patients receiv- ng ZYRTEC 5 mg or 10 mg was not significantly different trom placebo (2.9% vs. 2.4%, respectively). The most common aaverse reaction in patients aqed 12 years and older that occurred more frequently on ZYRTEG than placebo was somnolence. The incidence of somnolence associated with ZYRTEC was dose related, 6% in placebo, 1 1% at 5 mg and 14% at 10 mg. Discontinuations due to somnolenceforZYRTEC were unc,ommon (1.0% on ZYRTEC vs. 0.6% on placebo). Fatigue and dry mouth also appeared to be treahmnt-related adverse reactions. There were no differences by age, race, gender or by weight wfth regard to the incidence of adverse reactions. Table 1 lists adverse experiencesinpatientsagedl.yearsandolderwhic we reportedforZYRTEC5andl0mgincontrolledclinicaltrialsintheUnftedStates and that were more common with ZYRTEC than placebo. ble 1. Aftrse Experionm Reported in Patients aged 12 years and older In Placebo-Contmiled United States ZYRTEC Trials (Maximum Dose of 10 mg) at Rates of 2% or Greater (Percent Incidence), ZYRTEC (N--2034) vs Placebo (N-1612) respedively: Somnolence (13.7% vs 6.3%); Fatigue (5.9% vs 2.6%); Dry Mouth (5.0% vs 2.3%); Pharyngitis (2.0% vs 1.9%); Dizziness (2.0% vs 1.2%). In addWion, headache ana nausea occurred in more than 2% of the patients, but were more common in placebo patients. Pediatric studies were also conducted with ZYRTEC. More than 1300 pediatric patients (6 to 11 years) with more than 900 treated with ZYRTEC at doses of 1.25 to 10 mg per day were included in controlled and uncontrolled clinical trials conducted in the United States. The duration of treatment ranged trom 2 to 12 weeks. The majority of repofted adverse reactions reponed in pediatric patients (6 to 11 years) with ZYRTEC were mild or moderate. In placebo-controlled trials, the incidence of discontinuations due to adverse reactions in pediatric patients receiving up to ZYRTEG 10 mg was uncommon (0.4% on ZYRTEC vs. 1.0% on placebo). Table 2 lists adverse experiences which were reported for ZYRTEC 5 and 10 mg in pediatric patients (6 to 11 years) in placebo-controlle( clinical trials in the United States and were more common with ZYRTEC than placebo. Of ftm, abdominal pain was considered treatment-related and somnolence appeared to be dose related, 1.3% in placebo, 1.9% at 5 mg and 4.2% at 10 mg. Table 2. Adverse Experiences R orted in Pedlaffle hUents (6 to 11 yeam) in Placebo-Controlled Unked States > ZYRTEC Trials (5 or 1U mg d lch Occurred at a Frequency of 21V6 In Eitherthe 5 mg or the IO mg ZYRTEC Gmup , and More Frequently Than acebo Cmup. ZYRTEC 5 mg (N-161). 10 mg (N vs Placebo (N=309): Headache (11.0%, 5 mg; 14.0%, 10 mg; 12.3%, placebo); Pharyngitis (6.2%, 5 mg; 2.8%, 10 mg; 2.9%, ; Abdominal pain (4.4%,5 mg; 5.6%, 10 mg; 1.9%, placebo); Coulhing(4.4%,5 mg; 2.8%, 10 mg; 3.9%, placebo); Somnolence %, 5 mg; 4.2%, 10 mg; 1.3%, placebo); Diarrhea (3.1%,5 mg; 1.9%, 0 mg, 1.3%, placebo); Epistaxis (3.7%,5 rng; 1.9%, 10 mg; plaoebo); Bronchospasm (3.1%,5 mg; 1.9%, 10 mg; 1.9%, placebo); Nausea (1.9%,5 mg; 2.8%, 10 mg; 1.9%, placebo ; Vomfting (2.5%,5 mg; 2.3%, 10 mg; 1.0%, placebo). The following events were observed intrequentiT (less than 2%., in eftr 3w adults and children 12 years and older or in 659 pediatric (6 to 11 years) patients who receivi ZYR EC in U.S. ti 's, including-an open adult study of six months duration; a causal relationship with ZYRTEL; administration has not bwn established. kftnomic Nervous System: anorexia, urinary retention, flushin increased salivation, dry mouth. Cardimsculan palpitation, tachycardia, hypedension, cardiac failure. Commi aiiu rlu erd-1 Nervous nfusion, hyperkinesia, hypedonia, T%aine, tremor, venigo, leg cramps,ataxia, dysphonia, Znlol'rmal coordinati itis, paralysis, ptosis, twitching, visual field defect, syncope, dizziness. uastmintestinal: increased diarrhea, flatulenoe, constipation, vomiting, ulcerative stomatitis, aggravated tooth caries, stomatitis, tongue sco orat on, ton gastritis, rectal hemorrhage, hemorrhoids, melena, abnormal hepatic function, eructation. Genitourinary: polyuria, urinary t n cysbtis, dysuria, hematuria, micturition kequency, urinary incontinence. H and Vesflbular: earache, tinnitus, deafnes MetanellefiNublfflonal: thirst, dehydration, diabetes mellitus. Muscul etal: myalgia, arthralgia, arthrosis, irthritis, muscle weakness. Psychiatric: insomnia, sleep disorder, nervousness, depression, emotional labil- it,impaired concentration, anxiety, depersonalization, paroniria, abnormnal thinking, agitation, amnesia, decreased libido, euphoria. Repratory System: epistaxis, rhinitis, coughing, broncnhospasm, dyspnea, upPer respiratory tract infection, hyperventilation,s sinusitis, increased sputum, bronchitis, pneumonia, rsiaoydisorder. Ropmoductive: aysmenoffhea, female breast pain, intermenstrul bleed- ing, leukorrhea, menorrhagia, vaginitis. R luo nothelial: lymphadenopathy. Skidn: pruritus, rash, dry skin, uiticaria, acne, dermati- tis, erythematous rash, increased weting, alopecia, angioedema, furunculosis, bullous eruption, eczema, nyperkeratosis, hypertrichosis, photosensitivity reaction, photosensitivity toxic reaction, maculopapular rash, seborrhea, purpura, skin disorder, skin nodule. Special mmse: tase perversion, taste loss, parosmia. Vision: blindrness, loss of accommodation, eye pain, conjunctivitis, xerophthalmia, glau- coma, ocular hemorrhage. Body as a Whole: Increased weight, back pain, malaise, fever, asthenia, generalized edema, periorbital edema, peripheral edema, rigors, leg eaema, face edema, hot flashes, enlargea abdomen, nasal polyp, pain, pallor, chest pain, accidental injury. Occasional instances of transient, reversible hepatic transaminase elevations have occurrea during cetirizine therapy. A single case of posible drug-induced hepatitis with significant transaminase elevarion (500 to 1000 IU/L) and elevated bilirubin has been reported. In foreiign marketing experience thefollowing additional rare, butpotential sever adverse events have been reported: hemolytic anemia, throm- orofacial dskinesia, severe nypotension, anaphylaxis, hepatitis, QlomerulonephrHis, stillbirth, and cholestasis. DRUG ABUSE bolyopenia,MN DEPENDENCE There is no information to indicate that abuse or de endency occurs with ZYRTEC. OVERDOSAGE Overdosage has been reported with ZYRTEC. In one adult patient who took 150 mg of M9TEC, the ptetwas somnolent but did not display ther clnclsigns oabomlbodceityor hematology results. In an 18-month-ol pediatric Daient who took an overdose ofanYZYTEC (aproxmatly 80 g),restlessness and irritability were observed initially, this was followed by drowsiness. Should overdose occur, treat- mentshold b syptomticor supportive, taking into account any concomitantly ingested medications. There is no known specific antiotetoZRTE. ZYTECis not effectively removed by dialysis, and dialysis will be ineffective unless a dialyzble agent has been concorritantly ingested. The acute minimal lethal oral doses in mice and rat were 237 and 562 mg/kg, respectively (approximately 55 and 265 times the maximum recommended human daily oral dose on a /m2 basis). In rodents, the target of acute toxicity was the central nervous system, anid the target of multiple-dose toxicity was the liver.M-DOSAGE AND ADMINISTRATION Adulls and Children 12 years and older. The recommended initial dose of ZYRTEC is 5 or 10 mg per lay in adults and children 12 years and older, depending on symptom severity. Most patients in clinical trials started at 10 mg. ZYRTEC is given as a single daily dose, with or without food. the time of administration may be varied to suit individual patient needs. In patients with decreased renal junction (creatinine clearance 11-31 mUlmin), patients on hemodialysis (creatinine clearanc lessfthn 7 mL/min), and in hepatically. impaired patients, a dose of5 mg once dily is recommended. Children 6 to 11 years: The recommended initial dose of ZYRTEC in children aged 6 to 11 years is 5 or 10 mg (1 or 2 teaspoons) once daily depending on symptom severity. The time of administration may be varied to suit individual pafient needs.HO SUPPLIED ZYRTEC" tablets are white, film-coated, rounded-off rectangular shaped containing 5 rmg or 10 mg cetirizine hydrochloride. S mg tablets are engraved with "PFIZER" on one side and with '5500 on the othier. Bottles of 100: DC 0069-5500 66. 10 mg tablets are engraved with ZPFIZERN on one side and with '551" on the other. Bottles of 100: NDC 0069-5510 66. STORAGE: Store at room temperature 590 to 86°F (15° - 300C). ZYRTECO syrup is colorless to slightly yellow with a banana-grape flavor. Each teaspoonful (5 mL) contains 5 mg cetirizine hydrochloride. ZYRTEC" syrup is supplied as follows: 120 mL amber ulass bottles, NDC 0069-5530 47 1 pint amber gTalss bottles NDC 0069-5530-93 STORAGE: Store at 41°0 to 86°F (5° - 30°C). Cetirkine is licensed from UCB Pharrna, Inc. (M996 PFIZER INC Pfizer Labs Division of Prizer Inc NY, NY 10017 Printed in U.S.A 70-4573-001 Revised September 1996 tatilitil NCI MWWbX&h~b AbdmWby CL086A97A 01997,PfizerInc U.S. PharaceuticaL Group Fhj