Science & Research

New Pediatric Information in Labeling

Resulting from the Best Pharmaceuticals for Children Act (BPCA) Pediatric Research Equity Act (PREA) through April 19, 2009

Products in this table are listed alphabetically by the trade name and fall within the scope of the Best Pharmaceuticals for Children Act (BPCA) and/or the Pediatric Research Equity Act (PREA), and contain new pediatric information. Some products appearing on this list may have had studies completed under both BPCA and PREA. All BPCA products participated in the pediatric incentive program. The PREA products which participated in the BPCA incentive program by the same sponsor are marked with an asterisk (*). The PREA products marked with a (#) are labeling changes that were not based on information from clinical trials in pediatric patients. All other labeling changes are based on information from clinical trials in pediatric patients.

†All products in this table, except biologics with a solid dot (•) by the proper name, will have a link to labeling that reflects the labeling at the time of pediatric changes and may not be the latest labeling. Biologics will always have a link to the most recent labeling. This list only serves to highlight key information affecting the pediatric population resulting from BPCA and/or PREA at the time that particular application was approved. For the most recent labeling please go to Drugs@FDA.

N=274

Pediatric Labeling Date	Trade Name	Generic or Proper (biologics•) Name	Indications Studied	Sponsor	Product Labeling	Summary of Labeling Changes	BPCA (B)/PREA (P)
10/29/2007	Abilify	aripiprazole	Schizophrenia	Otsuka	Label Medical Review Clinical Pharmacology Review	Extended schizophrenia indication from adults to adolescents 13–17 years Safety and effectiveness in pediatric patients with bipolar mania or agitation associated with schizophrenia or bipolar mania have not been established Efficacy for the maintenance treatment of schizophrenia in the pediatric population has not been evaluated In 6-week placebo controlled efficacy trial in patients 13 – 17 years with Schizophrenia 30 mg/day was not shown to be more efficacious than 10 mg/day Common adverse events observed were extrapyramidal disorder, somnolence, and tremor; these 3 AEs appear to have a possible dose response relationship Information on dose, AEs, clinical studies	B

10/21/2008	Acanya Gel	clindamycin/ benzoyl peroxide combination	Acne vulgaris in patients 12 years of age and older	Dow	Medical Clinical pharmacology Statistical	Safety and effectiveness established in 2 clinical studies in patients 12 years of age and older Safety and effectiveness in pediatric patients under the age of 12 have not been evaluated New drug
5/2/2002	Accutane	isotretinoin	Severe recalcitrant nodular acne	Hoffman La-Roche	Label	Safety and effectiveness information on pediatric patients 12-17 years of age Identified an increased incidence of back pain, arthralgia and myalgia in pediatric patients New General Precautions subsection- caution when prescribing Accutane to pediatric patients with disorders of bone metabolism, such as osteoporosis and osteomalacia Adolescents who participate in sports with a repetitive impact may be at increased risk for bone related injuries In an open-label study of pediatric patients (n=217) given a single course of therapy, 16 (7.9%) had decreases in lumbar spine bone mineral density (BMD) >4% (adjusted for body mass index); 21 (10.6%) patients had decreases in total hip BMD >5% (adjusted for body mass index)
6/30/2008	Aciphex	rabeprazole	Gastroesophageal reflux in adolescent patients 12 years of age and above	Eisai Medical Research	Label Medical Review Clinical Pharmacology Review	Use in adolescent patients 12 years of age and older is supported by extrapolation of results from studies in adults and safety and PK studies performed in adolescent patients Safety and effectiveness for GERD have not been established for pediatric patients <12 years of age Safety and effectiveness for other uses have not been established in pediatric patients Adverse events (AEs) similar to those seen in adults Information on dose, AEs, clinical studies
2/7/2007	Actiq	fentanyl	Treatment of breakthrough pain in opioid tolerant children	Cephalon	Label Medical Review Clinical Pharmacology Review	Safety and efficacy in patients below the age of 16 years was not established in a clinical trial of 15 patients 5 to 15 years Information on PK parameters and clinical studies	B
2/8/2002	Acular & Acular PF	ketorolac	Relief of ocular itching due to seasonal allergic rhinitis and postoperative inflammation after cataract extraction	Allergan	Label	Safety and effectiveness established down to 3 years; previously approved down to 12 years	B
7/21/2005	Adderall XR	amphetamines, mixed salts	ADHD	Shire	Label Medical Review Clinical Pharmacology Review	Expanded labeling for 13-17 year olds On a mg/kg body weight basis children 6-12 years have a higher clearance than adolescents or adults. Body weight is the primary determinant There was not adequate evidence that doses greater than 20 mg/day conferred additional benefit in a placebo-controlled study conducted in adolescents aged 13-17 with ADHD In a single-dose PK study in adolescents, isolated increases in systolic blood pressure (SBP) were observed in patients receiving 10 mg and 20 mg Adderall XR. Higher single doses were associated with a greater increase in SBP Sustained increases in blood pressure should be treated with dose reduction and/or appropriate medication Information on dose, PK parameters, and AE profile	B
1/12/2000	Advil	ibuprofen	Fever, minor aches & pain, cold symptoms	Whitehall	Label	Extended age range from 2 years to 6 months for the over-the-counter use based on a large safety database (14,291 patients)	B
4/18/2002	Advil Suspension	ibuprofen / pseudoephedrine	Temporary relief of nasal and sinus congestion, headache, stuffy nose, sore throat, minor aches and pains, and fever	Whitehall	Label	Information on the over-the-counter use in pediatric patients 2 to 11 years of age	B
9/28/2007	Afluria	influenza virus vaccine●	For active immunization of adults 18 years of age and older against influenza disease caused by influenza virus subtypes A and type B present in the vaccine	CSL	Package Insert Clinical Review Statistical Review and Evaluation		P
12/10/2004	Agrylin	anagrelide	Myeloproliferative disorders	Shire	Label Medical Review Clinical Pharmacology Review	An open-label study evaluated PK/PD but not efficacy. Information on PK/PD profile, dosing, AEs, and safety in patients > 6 years to 17 years No overall difference in dosing and safety were observed between pediatric and adult patients Established recommended starting dose based on limited data. Dosage should be adjusted to the lowest effective dosage	B
10/07/2008	Akten Ophthalmic gel 3.5%	lidocaine hydrochloride	Ocular surface anesthesia during ophthalmologic procedures	Akorn	Label	Summary pending	P
9/24/2000	Alamast	pemirolast	Allergic Conjunctivitis	Santen	Label	Safety and effectiveness established down to 3 years	B
3/22/2007	Aldara	imiquimod	Molluscum contagiosum	Graceway Pharmaceuticals	Label Medical Review Clinical Pharmacology Review	Efficacy in patients 2 – 12 years for the treatment of molluscum contagiosum was not demonstrated in two clinical trials in 702 patients Information on clinical studies and AEs	B
5/12/2003	Allegra	fexofenadine	Allergic rhinitis	Aventis	Label	Three clinical safety studies in 845 children with allergic rhinitis are described in the label	B
10/16/2006	Allegra	fexofenadine	Seasonal allergic rhinitis (SAR) uncomplicated skin manifestations of chronic idiopathic urticaria (CIU)	Aventis	Label Medical Review Clinical Pharmacology Review	New suspension developed Suspension indicated for the treatment of SAR in 2 – 11 years based on the PK comparisons in adult and pediatric patients and an extrapolation of efficacy in adults; Suspension indicated for the treatment of CIU in 6 months – 11 years based on the PK comparisons in adults and children and an extrapolation of efficacy in adults Safety and effectiveness of suspension in pediatric patients under 6 months of age have not been established Additional information on dose, PK parameters, safety and AEs
12/20/2001	Alphagan	brimonidine	Prevention of post-operative IOP elevations	Allergan	Label	Safety and effectiveness established down to 2 years Somnolence in patients 2 to 6 years (50-83%) versus patients 7 years of age or older (25%)
4/12/2007	Altabax Ointment 1%	retapamulin	Treatment of impetigo in patients 9 months of age and older	GlaxoSmithKline	Label	Safety and effectiveness established in studies that included 588 pediatric patients from 9 months of age to 17 years of age Studies waived in children 0-2 months of age and deferred in children 2-9 months of age New active ingredient
1/10/2008	Alvesco Inhalation Aerosol, 80 mcg & 160 mcg	ciclesonide	Treatment of asthma in patients 12 years of age and older.	Nycomed US Inc.	Label Medical Review Clinical Pharmacology Review Statistical Review	Not indicated for children under the age of 12 years Five clinical studies evaluated safety in children 12 years of age and older Safety and effectiveness have not been established in children under 12 years of age Waiver of studies in children 0 to less than 6 months of age due to too few patients with the disease New dosage form
11/28/2005	Amaryl	glimepiride	Type-2 Diabetes Mellitus	Aventis	Label Medical Review Clinical Pharmacology Review	Data are insufficient to recommend pediatric use of glimepiride In an active-controlled, single-blind, 24-week trial, 272 pediatric patients aged 8 to 17 years with Type 2 diabetes were randomized to treatment with glimepiride or metformin. Trial suggested differences favoring metformin AE profile in the pediatric population was similar to that for adults Information on PK parameters
3/28/2007	Ambien	zolpidem	Insomnia associated with ADHD	Sanofi Aventis	Label Medical Clinical Pharmacology	Safety and effectiveness have not been established in pediatric patients with insomnia associated with ADHD In an 8-week controlled study in 201 pediatric patients 6-17 years, psychiatric and nervous system disorders comprised > 5% of treatment emergent adverse events, including dizziness (23.5%) headache (12.5%) and hallucinations (7.4%); treatment was discontinued due to an adverse event in 7.4%	B
9/29/2004	Amlexanox Mucoadhesive Patch	amlexanox	Treatment of apthous ulcers in children 12 years of age and older	Access Pharmaceuticals	Label	Approval based on monograph and previous studies for other indication No new studies submitted Studies in children birth – 12 years of age waived New indication	P
12/27/2007	AndroGel	testosterone	Use in adolescent boys with delayed puberty	Unimed	Label Medical Review Clinical Pharmacology Review	Safety and efficacy in males < 18 years old have not been established Improper use may result in acceleration of bone age and premature closure of epiphyses	B
7/21/2006	Anthelios SX Cream	avobenzone; ecamsule; octocrylene	Prevention of sunburn and protection from UVA and UVB rays in children 6 months of age and older OTC	L’Oreal USA	Label	Effectiveness extrapolated from adult studies Safety studies included pediatric patients 6 months of age and older Age range based on monograph Deferred studies in children < 6 months of age New active ingredient	P
10/24/2008	Apidra	insulin glulisine recombinant	Diabetes Mellitus	Sanofi-Aventis	Label Medical Review Clinical Pharmacology Review Statistical Review	Extended indication from adults to pediatric patients 4 years and older with type 1 diabetes Has not been studied in pediatric patients less than 4 years with type 1 diabetes and in pediatric patients with type 2 diabetes Pediatric patients had a higher incidence of severe symptomatic hypoglycemia compared to adults in the clinical study New indication
6/23/2008	Aptivus	tipranavir	Co-administered with ritonavir for combination antiretroviral in patients who are treatment-experienced and infected with HIV-1 strains resistant to more than one protease inhibitor	Boehringer Ingelheim	Label Medical Review Clinical Pharmacology Review Statistical Review	Extended indication from adults to children 2 years and older The risk-benefit has not been established in patients <2 years of age Dosing is based on body weight or body surface area not to exceed adult dose AEs are generally similar to those seen in adults however, rash was more frequent in pediatric patients than in adults; The frequency of rash through 48 weeks of treatment was 21%. Most rashes were mild and 5% were moderate. Overall 3% interrupted treatment due to rash Information on dose, AEs, PK parameters, lab abnormalities, and clinical study
3/5/2004	Arava	leflunomide	Polyarticular Juvenile Rheumatoid Arthritis	Aventis	Label Medical Review Clinical Pharmacology Review	Safety and efficacy in pediatric patients with polyarticular JRA have not been fully evaluated 94 patients with polyarticular JRA were studied in a double-blind active controlled trial (1:1 randomization); approximately 68% of pediatric patients receiving Arava versus 89% receiving active comparator demonstrated improvement on the primary endpoint by week 16 Pediatric patients with a body weight ≤ 40 kg have a reduced clearance relative to adult rheumatoid arthritis patients Information on PK of M1, the active metabolite responsible for in vivo activity in children 3-17 years old Most common adverse events in 74 polyarticular JRA patients 3-17 years old included abdominal pain, diarrhea, nausea, vomiting, oral ulcers, upper respiratory tract infections, alopecia, rash, headache, and dizziness 14 of the 74 patients experienced ALT and/or AST elevations; 5/14 were between 3 and 8 fold the upper limit of normal
5/5/2008	Argatroban	argatroban	Heparin-Induced Thrombocytopenia (HIT) or HIT with Thrombosis	Encysive	Label Medical Review Clinical Pharmacology Review	Safety and effectiveness, including the appropriate anticoagulation goals and duration of therapy, have not been established in pediatric patients Population PK/PD analysis of sparse data in 15 seriously ill pediatric patients ages <6 months – 16 years diagnosed with HIT or suspected HIT requiring an alternative to heparin anticoagulation showed clearance in pediatric patients was 50% lower compared to healthy adults and led to dose recommendations Information on dose, AEs and PK
12/5/2008	Arimidex	anastrozole	Male pubertal patients with gynecomastia and female pediatric patients with McCune-Albright syndrome with progressive precocious puberty	AstraZeneca	Label	Efficacy has not been demonstrated in clinical studies of anastrozole in the treatment of pubertal gynecomastia in adolescent boys 11-18 years and in the treatment of precocious puberty in girls with McCune-Albright Syndrome 2 to < 10 years Information on clinical studies, AEs, and PK parameters	B
3/19/2008	ARTISS	fibrin sealant (human)●	To adhere autologous skin grafts to surgically prepared wound beds resulting from burns in adult and pediatric populations	Baxter	Package Insert Pharmacology / Toxicology Review Statistical Review		P
2/1/2008	Asmanex Twisthaler 110mcg inhalation powder [Label not available]	mometasone furoate	Maintenance treatment of asthma as prophylactic therapy in children 4 years of age and older	Schering Corporation	Medical Review Clinical Pharmacology Review Statistical Review	Not indicated for relief of acute bronchospasm or in children less than 4 years of age Clinical studies, including 52 week safety trial conducted in children 4 – 11 years of age Pediatric dosing information provided Child may not get the most benefit for 1 to 2 weeks or longer after starting treatment New dosage form	P
12/17/2004	Augmentin ES-600 Powder for Oral Suspension#	amoxicillin; clavulanate	Treatment of acute bacterial sinusitis (ABS) (sinus infection) in children 3 months of age and older	GlaxoSmithKline	Label	No new pediatric studies Effectiveness extrapolated from adult studies for Augmentin XR for ABS and from studies in pediatric patients with otitis media and by similar pharmacokinetics in pediatric patients New indication	P
7/29/2005	Avandia	rosiglitazone	Type 2 Diabetes Mellitus	SB Pharmco	Label Medical Review Clinical Pharmacology Review	Data are insufficient to recommend pediatric use of rosiglitazone In a 24 week double-blind controlled trial in children with type 2 diabetes mellitus, aged 10 to 17 years, with a baseline BMI of 33 kg/m2 were randomized to treatment with rosiglitazone or metformin Mean change from baseline in HbA1c was -0.14% with rosiglitazone and -0.49% with metformin There was an insufficient number of patients to establish statistically whether these observed mean treatment effects were similar or different Weight gain similar to that in adults Information on PK parameters, and AE profile	B
3/16/2006	Avapro	irbesartan	Hypertension	Sanofi-Synthelabo	Label Medical Review Clinical Pharmacology Review	In a study at a dose up to 4.5 mg/kg once daily, irbesartan did not appear to lower blood pressure effectively in pediatric patients ages 6 to 16 years	B
4/30/2000	Axert	almotriptan	Acute treatment of pediatric migraine in adolescent patients age 12-17 years	Ortho-McNeil		Summary pending
5/25/2004	Axid	nizatidine	Esophagitis, and heartburn due to GERD	Reliant Pharms	Label	Indicated in pediatric patients 12 years and older Information on dose, PK parameters, and AE profile
4/27/2007	Azasite Ophthalmic Solution 1%	azithromycin	Treatment of bacterial conjunctivitis caused by certain microorganisms in patients down to 1 year of age	InSite Vision	Label	Effectiveness and safety were established in controlled clinical trials including patients down to 1 years of age Dosing information provided New dosage form
9/28/2006	Azopt ophthalmic suspension	brinzolamide	Elevated intraocular pressure	Alcon	Label Medical Review	IOP-lowering efficacy was not demonstratedin a 3-month controlled clinical study in which brinzolamide was dosed only twice a day in pediatric patients 4 weeks to 5 years of age
10/1/2001	Betapace	sotalol	Arrhythmia	Berlex	Label	Analysis of 2 trials provided information on PK and PD in children 3 days – 12 years; safety and efficacy have not been established Information on dose, pharmacokinetics and AE's Pharmacokinetics: BSA most important covariate and more relevant than age Smaller children (BSA < 0.33 m2) showed tendency for larger change in QTc and increased frequency of prolongation of the QTc interval as well as greater beta-blocking effects Individualized dosing on a mg/m2 basis Information on preparation of a suspension
9/28/2006	Betaxon ophthalmic suspension	levobetaxolol	Elevated intraocular pressure	Alcon	Label Medical Review No clin pharm	Extended indication from adults to pediatric patients The adverse event profile was comparable to that seen in adults and elderly patients
6/8/2007	Betoptic S	betaxolol	Elevated intraocular pressure in patients with chronic open-angle glaucoma or ocular hypertension	Alcon	Label Medical Review	Extended indication from adults to pediatric patients The adverse reaction profile was comparable to that seen in adults
7/19/2001	Buspar	buspirone	General Anxiety Disorder	Bristol-Myers Squibb	Label	Safety and effectiveness were not established in patients 6 to 17 years of age for treatment of General Anxiety Disorder at doses recommended for use in adults PK parameters (AUC and Cmax) of buspirone and its active metabolite were found to be equal to or higher in children and adolescents than that of adults
1/13/2003	Busulfex	busulfan	Part of a conditioning regimen administered prior to hematopoietic progenitor cell transplantation for a variety of malignant hematologic or non-malignant diseases	Orphan Medical	Label	The population pharmacokinetic estimates of busulfan for clearance and volume of distribution were determined in an open-label, uncontrolled PK study in 24 pediatric patients 5 months to 16 years who received busulfan as part of a conditioning regimen administered prior to hematopoietic progenitor cell transplantation for a variety of malignant hematologic or non-malignant diseases Suggested dosing regimen
11/16/2001	Calcijex	calcitriol	Management of hypocalcemia in patients undergoing chronic renal dialysis	Abbott	Label	The safety and effectiveness of calcitriol was examined in a double-blind placebo-controlled trial of 35 pediatric patients (13-18 years of age) with end-stage renal disease and on dialysis. The primary efficacy endpoint favored the calcitriol-treated versus the placebo-treated patients Transient hypercalcemia was seen in 1 of 16 calcitriol-treated patients; 6 of 16 (38%) calcitriol-treated patients and 2 of 19 (11%) placebo-treated patients had Ca x P >75
6/24/2004	Camptosar	irinotecan	Refractory solid tumors	Pfizer	Label Medical Review Clinical Pharmacology Review	Effectiveness in pediatric patients has not been established Adverse event profile from a Phase 2 trial with 170 children with refractory solid tumors comparable to that seen in adults; Grade 3-4 neutropenia experienced by 54 (31.8%) patients, neutropenia complicated by fever in 15 (8.8%) patients, Grade 3-4 diarrhea observed in 35 (20.6%) patients. Accrual for phase 2 study with 21 children with previously untreated rhabdomyosarcoma halted due to high rate (23.6%) of progressive disease and early deaths (14%) Adverse event profile seen in the 21 children different than that observed in adults; most significant Grade 3 or 4 adverse events were dehydration experienced by 6 patients (28.6%) associated with severe hypokalemia in 5 patients (23.8%) and hyponatremia in 3 patients (14.3%); in addition Grade 3-4 infection was reported in 5 patients (23.8%)(across all courses of therapy and irrespective of causal relationship) PK parameters comparable to adults Minimal accumulation of irinotecan and SN-38 (active metabolite) observed in children on daily dosing
7/29/2008	Cancidas	caspofungin	Empirical therapy for presumed fungal infections in febrile, neutropenic patients; Candidemia and certain Candida infections; Esophageal Candidiasis; Invasive Aspergillosis in patients who are refractory to or intolerant of other therapies	Merck	Label Medical Review Clinical Pharmacology Review Statistical Review	Extended indication from adults to children 3 months and older based upon evidence from adequate and well-controlled studies in adults and PK data in pediatric patients and additional data from pediatric studies The efficacy and safety have not been adequately studied in infants < 3 months The ability of caspofungin to penetrate the blood-brain barrier and to treat patients with meningitis and endocarditis is unknown Dosing should be based on the patient’s body surface area. Maximum loading dose and daily maintenance dose should not exceed 70 mg The safety profile in pediatrics is comparably to adults Information on dose, AEs, PK parameters, clinical studies and infusion preparation instructions	B
4/30/2008	Cardiolite	technetium tc99m sestamibi	Medical imaging in Kawasaki disease	Lantheus Medical Imaging	Label Medical Review Clinical Pharmacology Review Statistical Review	Safety and effectiveness have not been established in the pediatric population No evidence of diagnostic efficacy or clinical utility of scan was found in 3 clinical studies of children and adolescents with Kawasaki disease A study of 445 pediatric patients failed to demonstrate the predictive value of Cardiolite rest and stress myocardial perfusion imaging to define children with Kawasaki disease at risk of developing cardiac events 6 months after receiving Cardiolite; only 3cardiac events were observed. In all 3 cases, the scan was negative Adverse events similar to that of adults Information on dose, PK, and clinical studies	B
12/19/2008	Casodex	bicalutamide	Gonadotropin-independent precocious puberty in boys with familial male-limited precocious puberty (testotoxicosis)	AstraZeneca	Label	Safety and effectiveness have not been established in pediatric patients Bicalutamide was studied in combination with anastrozole in an open-label, non-comparative, multi-center study that assessed the efficacy and safety of this combination regimen over 12 months in the treatment of testotoxicosis in patients ≥2 years Of the 14 patients exposed to study treatment, 13 had at least one adverse event. Adverse reactions considered possibly related to bicalutamide included gynecomastia (43%), central precocious puberty (14%), breast tenderness (14%), breast pain (7%), asthenia (7%), increased alanine aminotransferase (7%), increased aspartate aminotransferase (7%), and musculoskeletal chest pain (7%). Headache was the only adverse reaction considered possibly related to anastrozole Information on clinical studies, AEs, and PK parameters	B
12/15/2006	Celebrex	celecoxib	Relief of the signs and symptoms of juvenile rheumatoid arthritis (JRA)	Pfizer	Label Medical Review Clinical Pharmacology Review	New indication in 2 years and older Has not been studied in patients < 2 years, in patients with body weight < 10 kg, or in patients with active systemic features Celecoxib should be used only with caution in patients with systemic onset JRA due to the risk for serious adverse reactions including the risk of disseminated intravascular coagulation The long-term cardiovascular toxicity in children has not been evaluated; it is unknown if the long-term risk may be similar to that seen in adults New 50 mg capsule developed Information on adding contents of a capsule to applesauce. for patients with difficulty swallowing capsules Information on dose, clinical studies, PK parameters, AEs	B
2/18/2005	Celexa	citalopram	Major Depressive Disorder	Forest	Label Medical Review Clinical Pharmacology Review	Safety and effectiveness in the pediatric population have not been established FDA required boxed warning for all antidepressants: Suicidality in Children and Adolescents - Antidepressants increased the risk of suicidal thinking and behavior (suicidality) in short-term studies in children and adolescents with Major Depressive Disorder (MDD) and other psychiatric disorders. Anyone considering the use of Celexa or any other antidepressant in a child or adolescent must balance this risk with the clinical need. Patients who are started on therapy should be observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Celexa is not approved for use in pediatric patients. (See Warnings and Precautions: Pediatric Use) Pooled analyses of short-term (4 to 16 weeks) placebo-controlled trials of 9 antidepressant drugs (SSRIs and others) in children and adolescents with major depressive disorder (MDD), obsessive compulsive disorder (OCD), or other psychiatric disorders (a total of 24 trials involving over 4400 patients) have revealed a greater risk of adverse events representing suicidal thinking or behavior (suicidality) during the first few months of treatment in those receiving antidepressants. The average risk of such events in patients receiving antidepressants was 4%, twice the placebo risk of 2%. No suicides occurred in these trials Two placebo-controlled trials in 407 pediatric patients with MDD have been conducted with Celexa, and the data were not sufficient to support a claim for use in pediatric patients	B
12/4/2002	Centany Ointment 2%	mupirocin	Treatment of impetigo in children 2 months of age and older	Clay-Park Labs	Label	New dosage form: ointment that differed from already approved ointment with pediatric clinical trials to demonstrate equivalence	P
2/24/2004	Children's Advil Allergy Sinus Suspension	chlorpheniramine; ibuprofen; pseudoephedrine	Symptoms of allergic rhinitis (runny nose) and the common cold in children 6 years of age and older	Wyeth Consumer Healthcare	Label	Effectiveness extrapolated from adult studies Bioequivalence studies in healthy adults PK and safety studies in children 6 to 12 years of age New dosage form	P
3/25/2004	Cipro	ciprofloxacin	Complicated UTI and pyelonephritis	Bayer	Label Medical Review Clinical Pharmacology Review	Indicated for the treatment of complicated urinary tract infections (cUTIs) and pyelonephritis in pediatric patients 1 – 17 years of age Not drug of first choice due to increased adverse events compared to controls including events related to joints and/or surrounding tissues Information on PK and dose in pediatric patients 1 – 17 years of age The most frequent adverse events observed within 6 weeks of treatment initiation during the cUTI clinical trial were gastrointestinal 15% compared to 9% and musculoskeletal 9.3% compared to 6% in ciprofloxacin-treated compared to control-treated patients, respectively	B
7/18/2003	Ciprodex Sterile Otic Suspension	ciprofloxacin*; dexamethasone	Treatment of acute otitis media in patients with tympanostomy tubes (inner ear infection) in children 6 months of age and older treatment of acute otitis externa (outer ear infection) in children 6 months of age and older	Alcon	Label Medical Review	Over 700 pediatric patients in safety and effectiveness studies to support both indications Pediatric dosing information added New dosage form	P
9/1/2004	Clarinex	desloratadine	Seasonal and perennial allergic rhinitis, and the symptomatic relief of pruritus, and hives	Schering	Label	Indicated for seasonal allergic rhinitis down to 2 years of age. Extended age range down to 6 months for perennial allergic rhinitis and chronic idiopathic urticaria Safety and effectiveness of tablets or syrup has not been established in pediatric patients less than 6 months of age Information on dose, PK parameters, and AE profile in pediatric patients 6 months - 11 years of age	B
3/3/2005	Clarinex D 24 Hour Extended Release Tablets	desloratadine*/pseudoephedrine	Relief of nasal and non-nasal symptoms of seasonal allergic rhinitis, including nasal congestion, in patients 12 years of age and older	Schering	Label	Two safety and effectiveness studies conducted in patients 12 years of age and older PK study Studies waived in children < 12 years of age New active ingredient; new dosing regimen	P
2/1/2006	Clarinex-D 12 Hour Extended Release Tablets	desloratadine*/ pseudoephedrine	Relief of nasal and non-nasal symptoms of seasonal allergic rhinitis in children 12 years of age and older	Schering	Label	Approval based on two safety and effectiveness studies in patients down to 12 years of age Not an appropriate dosage form for use in pediatric patients below 12 years of age. Studies waived in children < 12 years of age New dosing regimen	P
12/4/2000	Claritin	loratadine	Allergic rhinitis/Urticaria	Schering	Label	Labeling for 2 - 5 year olds including information on dose, PK parameters and AE profile PK parameter in 2-5 year olds given a 5mg dose was comparable to the 10mg dose in children 6 years to adolescence	B
7/30/2004	Claritin-D 12 Hour Extended-Release Tablets# Claritin-D 24 Hour Extended-Release Tablets#	loratadine*; pseudoephedrine	Temporary relief of nasal congestion due to the common cold in children 12 years of age and older OTC	Schering-Plough	Label	Approval based on monograph and previous studies for other indication No new studies submitted Studies in children birth - 12 years of age waived New indication	P
12/28/2004	Clolar	clofarabine	Relapsed or refractory acute lymphoblastic leukemia after at least two prior regimens	Genzyme	Label Medical Review Clinical Pharmacology Review	Labeling for patients 1 to 21 years old. This use is based on the induction of complete responses Randomized trials demonstrating increased survival or other clinical benefit have not been conducted Information on dose, PK parameters, and AE profihe	B
6/21/2004	Codeprex Extended-Release Suspension#	chlorpheniramine; codeine	Temporary relief of cough associated with the common cold or inhaled irritants; temporary relief of symptoms of hay fever, other upper respiratory allergies, or allergic rhinitis in children 6 years of age and older OTC	Celltech Pharmaceuticals	Label	Approval and age range based on monograph for antitussives and antihistamine No clinical studies submitted Studies in children < 6 years of age deferred New dosage form; new dosing regimen	P
12/20/2006	Colazal	balsalazide	Mildly to moderately active ulcerative colitis in patients 5 years of age and older	Salix	Label Medical Review Clinical Pharmacology Review	Extended indication from adults to patients 5 years and older Dosing can be initiated at either 6.75 or 2.25 g/day PK of balsalazide, and metabolites showed very large inter-patient variability similar to that seen in adults AEs were similar to those seen in adults	B
10/30/2007	Combigan 0.2%/0.5% ophthalmic solution	brimonidine tartrate/timolol maleate	Reduction of elevated intraocular pressure in patients with glaucoma or ocular hypertension	Allergan	Label Medical Review Clinical Pharmacology Review Statistical Review	Safety and effectiveness supported by evidence from clinical studies in adults with additional data from a study in children with glaucoma ages 2 – 7 years old Not recommended for use in children under the age of 2 years due to safety concerns based on reports of apnea, bradycardia, hypotension, hypothermia, hypotonia, and somnolence in infants Safety and effectiveness have not been studied in children below the age of two years New active ingredient	P
10/21/2004	Concerta	methylphenidate	ADHD	Alza	Label Medical Review Clinical Pharmacology Review	Expanded labeling for 13-17 year olds including information on dose, PK parameters, and AE profile Increase in age resulted in increased apparent oral clearance For patients new to methylphenidate: higher maximum recommended dosage for adolescents compared to children 6-12 years of age Data are inadequate to determine whether chronic use of stimulants in children may cause suppression of growth. Therefore, growth should be monitored during treatment Safety and efficacy in children <6 years have not been established	B
2/23/2007	Coreg	carvedilol	Heart failure	GlaxoSmithKline	Label Medical Review Clinical Pharmacology Review	Effectiveness has not been established in patients < 18 years In a double-blind trial of 161 children, 2 months to 17 years with chronic heart failure receiving standard background treatment, randomized to placebo or carvedilol, carvedilol demonstrated reduction of heart rate 4-6 beats per minute There was no significant effect of treatment on clinical outcomes after 8 months of follow-up AEs occurring in ≥ 10% of patients treated with carvedilol included chest pain (17%), dizziness (13%), and dyspnea (11%)	B
4/1/2004	Corlopam	fenoldopam	Indicated for the in-hospital, short-term reduction in blood pressure	Hospira	Label Medical Review Clinical Pharmacology Review	Indicated for the in-hospital, short-term (up to 4 hours) reduction in blood pressure in pediatric patients <1 month (at least 2 kg) to 12 years of age Information on PK, dose and AE profile Clinical studies did not include patients 12 – 16 years of age	B
3/11/2004	Cozaar	losartan	Hypertension	Merck	Label	Antihypertensive effects established in hypertensive patients 6-16 years of age Not recommended for pediatric patients less than 6 years or with glomerular filtration rate < 30mL/ min/1.73 m2 due to no data Information on PK and dose in pediatric patients 6-16 years of age. No relevant differences between the AE profile for pediatric patients compared to reported AEs for adults Information on preparation of a suspension
3/12/2008	Daptacel	diphtheria and tetanus toxoids and acellular pertussis vaccine adsorbed●	Active immunization against diphtheria, tetanus & pertussis as a five dose series in children 6 weeks through 6 years of age (prior to 7th birthday)	Sanofi Pasteur	Package Insert Committee Chair Approval Memo Clinical Review
1/25/2002	Daypro	xaprozin	Relief of signs and symptoms of Juvenile Rheumatoid Arthritis	Searle	Label	New indication in 6 years -16 years
10/10/2003	Denavir Cream	penciclovir	Treatment of recurrent herpes labialis (cold sores) in children 12 years of age and older	Novartis	Label	Extended indication down from 18 years of age to 12 years of age Effectiveness extrapolated from adult studies Safety study in patients 12-17 years of age Pediatric submission
3/24/2008	Depakote ER Depakote Sprinkles	divalproex disodium	Pediatric Bipolar Disorder; Prophylaxis of Migraine	Abbott	Label Medical Review Medical Review Medical Review Clinical Pharmacology Review Medical Review Sprinkles Clinical Pharmacology Review Sprinkles	Efficacy was not established in a double-blind, placebo controlled study of patients 10-17 years conducted to evaluate efficacy in the treatment of pediatric bipolar disorder Efficacy was not established in a double-blind, placebo-controlled study of patients 12 – 17 years conducted to evaluate the efficacy in the prophylaxis of migraine The safety and tolerability was similar to adults in 5 long-term safety studies Additional information on clinical studies, AE profile in Depakote ER labeling
12/12/2007	Derma-Smoothe/FS Topical Oil, 0.01% (Body Oil)	fluocinolone acetonide	Treatment of atopic dermatitis in pediatric patients 3 months and older for up to 4 weeks.	Hill Dermaceuticals, Inc.	Medical Review Clinical Pharmacology Review Statistical Review	Extended age range down to 3 months Effectiveness and safety are not established in children less than 3 months old Safety was evaluated in two pediatric clinical studies (including facial use) Pediatric dosing and administration information provided Studies waived in children under 3 months of age due to safety concerns of adrenal suppression New indication
5/8/2008	Desmopressin acetate Tablets, 0.1 mg and 0.2 mg	desmopressin acetate	Determine the capacity of the kidney to concentrate urine in pediatric patients (Renal Concentration Capacity Test or RCCT) and management of primary nocturnal enuresis (PNE)	Ferring	Medical Clinical pharmacology	Eficacy in RCCT was evaluated in a single trial with children 3 to 18 years old Three studies evaluated efficacy in children 5 to 17 years old with PNE; an additional study evaluated efficacy in adolescents 12 to 17 years old Fluid intake should be adjusted downward in children to decrease the potential occurrence of water intoxication and hyponatremia Dosing information provided for children 3 to 18 years old for RCCT Dosing information provided for pediatric patients 6 years of age and older with PNE Tablet dosage and administration information provided for children with central diabetes insipidus Pharmacokinetics and pharmacodynamics were evaluated in children New indications and dosing regimen
10/20/2006	Desonate Gel	desonide	Treatment of mild to moderate atopic dermatitis in children 3 months of age and older	Dow	Label	Effectiveness established from two studies in patients 3 months to 18 years of age Not recommended for use in patients under 3 months of age Treatment should not exceed 4 consecutive weeks HPA axis suppression studied in patients 6 months of age to 6 years of age New dosage form
4/14/2004	Detrol LA	tolterodine	Urinary frequency and urge incontinence due to neurogenic conditions	Pfizer	Label Medical Review Clinical Pharmacology Review	Efficacy in pediatric population has not been demonstrated The dose-plasma concentration relationship is linear in patients from 11 to 15 years Parent/ metabolite ratios differed according to CYP2D6 metabolizer status 710 pediatric patients ages 5 -10 years with urinary frequency and urge incontinence were studied in 2 randomized placebo controlled trials. Urinary tract infections were higher in patients treated with Detrol LA (6.6%) compared to placebo (4.5%) Aggressive, abnormal and hyperactive behavior and attention disorders occurred in 2.9% of children treated with Detrol LA compared to 0.9% treated with placebo
11/29/2007	Diovan	valsartan	Hypertension	Novartis	Label Medical Review Clinical Pharmacology Statistical	Labeling for 6-16 years of age Not recommended for pediatric patients less than 6 years due to safety findings possibly related to treatment or with glomerular filtration rate < 30mL/min/1.73m2 Information on dose, clinical studies in 1-16 years and pharmacokinetics No relevant differences were identified between adverse experience profile for pediatric patients and that previously reported for adult patients Information on preparation of a suspension
2/23/2001	Diprivan	propofol	Induction and/or maintenance of anesthesia	AstraZeneca	Label	Maintenance of anesthesia- age decreased down to 2 months from 3 years Induction of anesthesia remains the same- 3 years of age and above Concomitant administration with fentanyl may result in serious bradycardia Abrupt discontinuation following prolonged infusion may result in flushing of hands and feet, agitation, tremulousness and hyperirritability Propofol is not indicated for pediatric ICU sedation as safety has not been established. In a single multicenter trial of ICU sedation in critically ill pediatric patients (patients with upper respiratory tract infections excluded), the incidence of mortality (causality not established) was 9% in the propofol arm versus 4% in the standard sedative agents arm
10/3/2001	Diprolene AF, Diprosone, Lotrisone	betamethasone	Diprolene AF and Diprosone - Relief of inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses Lotrisone- Treatment of symptomatic inflammatory tinea pedis, tinea cruris and tinea corporis	Schering	Label	Diprolene AF Cream In an open-label study for the treatment of atopic dermatitis, 19 of 60 (32%) evaluable patients (ages 3 mo-12 years) showed HPA axis suppression. The younger the age group, the greater the proportion of patients with adrenal suppression. Indicated in patients 13 years and older. Not recommended in pediatric patients 12 years and younger Strengthened labeling in Clinical Pharmacology, Precautions- General and Pediatric Use subsections Local adverse reactions including signs of skin atrophy (telengiectasia, bruising, shininess) occurred in 10% of pediatric patients (3mo-12 years) Diprosone Cream, Ointment, Lotion A separate open-label study was performed in pediatric patients with atopic dermatitis for each Diprosone formulation Testing for HPA axis suppression was positive with each formulation in the age groups studied: Cream - 23% (ages 2yr-12yr); Ointment - 28% (ages 6mo-12yr); and Lotion - 73% (ages 6yr-12yr) Indicated in patients 13 years and older. Not recommended in pediatric patients 12 years and younger Strengthened labeling in Clinical Pharmacology, Precautions- General and Pediatric Use subsections Local adverse reactions including signs of skin atrophy (telengiectasia, bruising, shininess) occurred in the cream and ointment studies Lotrisone Not recommended for patients under the age of 17 years and not recommended for diaper dermatitis; previously not recommended for patients under the age of 12 years In an open-label study of Lotrisone cream for the treatment of tinea pedis, 17 of 43 (39.5%) evaluable patients (ages 12-16 years) demonstrated adrenal suppression as determined by cosyntropin testing In an open-label study of Lotrisone cream for the treatment of tinea cruris, 8 of 17 (47.1%) evaluable patients (ages 12-16 years) demonstrated adrenal suppression by cosyntropin testing Indicated in patients 17 years and older	b
4/15/2003	Ditropan & Ditropan XL	xybutynin	Detrusor Overactivity Associated with a Neurological Condition	Johnson & Johnson	Label Medical Review Clinical Pharmacology Review	Ditropan Additional information on dose and PK parameters Precautions section of label updated Ditropan XL Safety and effectiveness established down to 6 years of age	B
5/6/2005	Doryx Delayed-Release Tablets#	doxycycline	Treatment of infections	Warner Chilcott	Label Medical Review No Clin Pharm	No new clinical studies submitted PK data Dosing information for new dosage form (to decrease esophagitis seen from capsules) New dosage form	P
5/23/2003	Duocaine Injection#	bupivacaine; lidocaine	Local regional anesthesia for ophthalmologic surgery by peripheral nerve block techniques in children 12 years of age and older	Amphastar	Label	Safety and effectiveness extrapolated from existing clinical database Safety and effectiveness not established in patients < 12 years of age Partial waiver 0-12 years of age because general anesthesia is preferred in that population New active ingredient	P
5/20/2003	Duragesic	fentanyl	Management of chronic pain	Alza	Label Medical Review Clinical Pharmacology Review	Safety evaluated in three open-label trials in 291 patients 2 years through 18 years of age with chronic pain New Warning: Duragesic should be administered to children only if they are opioid-tolerant and age 2 years or older New information on pharmacokinetics, dosage and administration and patient information Precaution to guard against accidental ingestions by children Adverse Events: no apparent pediatric-specific risk associated with Duragesic use in children as young as 2 years old when used as directed. Most common adverse events were fever (35%), vomiting (33%), and nausea (24%)	B
9/29/2006	DuraPrep Surgical Solution#	iodine; isopropyl alcohol	Preoperative skin preparation for use in children 2 months of age and older OTC	3M Health	Review	Effectiveness based on determination that permeability of skin in children > 2 months of age is essentially that of adult skin Studies waived in children under 2 months of age for safety reasons and includes the following statement in the label: Do not use in children under 2 months of age due to excessive skin irritation and transient hypothyroidism. New active ingredient	P
5/5/2004 and 2/18/2005	Effexor and Effexor XR	venlafaxine	Major Depressive Disorder	Wyeth	Label Medical Review Clinical Pharmacology Review	Effectiveness in pediatric patients has not been established FDA required boxed warning for all antidepressants: Suicidality in Children and Adolescents - Antidepressants increased the risk of suicidal thinking and behavior (suicidality) in short-term studies in children and adolescents with Major Depressive Disorder (MDD) and other psychiatric disorders. Anyone considering the use of Effexor or any other antidepressant in a child or adolescent must balance this risk with the clinical need. Patients who are started on therapy should be observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Effexor is not approved for use in pediatric patients. (See Warnings and Precautions: Pediatric Use) Pooled analyses of short-term (4 to 16 weeks) placebo-controlled trials of 9 antidepressant drugs (SSRIs and others) in children and adolescents with major depressive disorder (MDD), obsessive compulsive disorder (OCD), or other psychiatric disorders (a total of 24 trials involving over 4400 patients) have revealed a greater risk of adverse events representing suicidal thinking or behavior (suicidality) during the first few months of treatment in those receiving antidepressants. The average risk of such events in patients receiving antidepressants was 4%, twice the placebo risk of 2%. No suicides occurred in these trials. 18% of Effexor XR treated patients (6-17 years) versus 3.6 % of placebo treated patients experienced a weight loss of at least 3.5 % in both MDD and the GAD studies In an open-label study increases in weight were less than expected based on data from age and sex matched peers. The difference between observed weight gain was larger for children less than 12 years than for adolescents older than 12 years During an 8 week placebo controlled GAD trial, Effexor XR treated patients ages 6-17 years grew an average of 0.3 cm, while placebo treated patients grew an average of 1 cm. In a 6 month open-label study, height increases that were less than expected based on data from age and sex matched pairs. The difference between observed and expected growth rates were larger for children less than 12 years than for adolescents older than 12 years Decreased appetite observed in 10% of patients ages 6-17 years old receiving Effexor XR Occurrence of blood pressure and cholesterol increases considered clinically relevant in pediatric patients similar to that observed in adults	B
12/1/2005	Effexor XR Extended-Release Capsules	venlafaxine*	Social anxiety disorder	Wyeth	Label Medical Review Clinical Pharmacology Review	Provided additional safety data for changes in weight, height, and appetite occurring in pediatric patient Information based on a clinical study of patients with SAD New indication (not approved in pediatric patients)	P
10/16/2003	Elestat Ophthalmic Solution	epinastine	Prevention of itching associated with allergic conjunctivitis in children 3 years of age and older	Allergan	Label	Based on effectiveness and safety studies that included children down to 10 years of age Partial waiver for children < 3 years of age because the condition does not exist in the age group New drug	P
5/5/2004 and 2/18/2005	Effexor and Effexor XR	venlafaxine	Major Depressive Disorder	Wyeth	Label Medical Review Clinical Pharmacology Review	Effectiveness in pediatric patients has not been established FDA required boxed warning for all antidepressants: Suicidality in Children and Adolescents - Antidepressants increased the risk of suicidal thinking and behavior (suicidality) in short-term studies in children and adolescents with Major Depressive Disorder (MDD) and other psychiatric disorders. Anyone considering the use of Effexor or any other antidepressant in a child or adolescent must balance this risk with the clinical need. Patients who are started on therapy should be observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Effexor is not approved for use in pediatric patients. (See Warnings and Precautions: Pediatric Use) Pooled analyses of short-term (4 to 16 weeks) placebo-controlled trials of 9 antidepressant drugs (SSRIs and others) in children and adolescents with major depressive disorder (MDD), obsessive compulsive disorder (OCD), or other psychiatric disorders (a total of 24 trials involving over 4400 patients) have revealed a greater risk of adverse events representing suicidal thinking or behavior (suicidality) during the first few months of treatment in those receiving antidepressants. The average risk of such events in patients receiving antidepressants was 4%, twice the placebo risk of 2%. No suicides occurred in these trials. 18% of Effexor XR treated patients (6-17 years) versus 3.6 % of placebo treated patients experienced a weight loss of at least 3.5 % in both MDD and the GAD studies In an open-label study increases in weight were less than expected based on data from age and sex matched peers. The difference between observed weight gain was larger for children less than 12 years than for adolescents older than 12 years During an 8 week placebo controlled GAD trial, Effexor XR treated patients ages 6-17 years grew an average of 0.3 cm, while placebo treated patients grew an average of 1 cm. In a 6 month open-label study, height increases that were less than expected based on data from age and sex matched pairs. The difference between observed and expected growth rates were larger for children less than 12 years than for adolescents older than 12 years Decreased appetite observed in 10% of patients ages 6-17 years old receiving Effexor XR Occurrence of blood pressure and cholesterol increases considered clinically relevant in pediatric patients similar to that observed in adults	B
12/1/2005	Effexor XR Extended-Release Capsules	venlafaxine*	Social anxiety disorder	Wyeth	Label Medical Review Clinical Pharmacology Review	Provided additional safety data for changes in weight, height, and appetite occurring in pediatric patient Information based on a clinical study of patients with SAD New indication (not approved in pediatric patients)	P
10/16/2003	Elestat Ophthalmic Solution	epinastine	Prevention of itching associated with allergic conjunctivitis in children 3 years of age and older	Allergan	Label	Based on effectiveness and safety studies that included children down to 10 years of age Partial waiver for children < 3 years of age because the condition does not exist in the age group New drug	P
12/13/2001	Elidel	pimecrolimus	Treatment of mild/moderate atopic dermatitis	Novartis	Label	Indicated for short-term and intermittent long-term therapy for mild to moderate atopic dermatitis in non-immunocompromised patients 2 years and older Not recommended for use in pediatric patients less than 2 years of age. Infants on Elidel Cream had an increased incidence of some adverse events compared to vehicle which included pyrexia, URI, nasopharyngitis, gastroenteritis, otitis media, and diarrhea.	B
1/10/2007	Eloxatin	xaliplatin	Solid tumors	Sanofi-Aventis	Label Medical Review Clinical Pharmacology Review	The effectiveness of oxaliplatin in children has not been established No significant activity observed in 2 Phase I and 2 Phase II trials in 159 patients ages 7 months to 22 years with solid tumors Information on clinical studies and AEs	B
9/28/2005	Emtriva	emtricitabine	HIV-1 infection in combination with other antiretroviral agents	Gilead Sciences	Label	Safety and effectiveness in pediatric patients 3 months and older supported by data from 3 open-label, nonrandomized clinical studies Safety and effectiveness in patients < 3 months have not been established Relative bioavailability of Emtriva oral solution is approximately 80% of Emtriva capsules. Thus, maximum dosage is different for these 2 formulations: Solution max - 240 mg once daily; Capsules max - children weighing > 33 kg one 200 mg capsule once daily The AE profile in pediatric patients was comparable to that observed in adults Information on dose, PK parameters, AE profile and clinical studies	B
12/22/2006	Emtriva	emtricitabine	HIV-1 infection in combination with other antiretroviral agents	Gilead Sciences	Label Medical Review 1 Medical Review 2 Clinical Pharmacology Review	Efficacy in preventing or treating HIV in neonates to 3 month olds could not be determined after a PK study in 20 neonates born to HIV positive mothers Information on dose in 0-3 months, additional safety and PK parameters	B
12/17/2008	Epiduo	adapalene and benzoyl peroxide	Topical treatment of acne vulgaris in patients 12 years of age and older	Galderma	Label	Safety and effectiveness established in patients 12 years of age and older Safety and effectiveness in pediatric patients under the age of 12 have not been established New drug	P
10/8/2002	Epivir	lamivudine	HIV	GlaxoSmithKline	Label	Lamivudine clearance substantially reduced in 1-week-old neonates relative to pediatric patients >3 months of age	B
8/16/2001	Epivir-HBV	lamivudine	Treatment of Chronic Hepatitis B	GlaxoSmithKline	Label	Safety and effectiveness established down to 2 years Established a dose of 3mg/kg/day up to a maximum of 100mg/day (adult dose)	B
12/10/2003	Ertaczo Cream	sertaconazole	Treatment of interdigital tinea pedis (athlete's foot) in children 12 years of age and older	Mylan	Label	Safety and effectiveness established in clinical trials involving adolescent patients Studies in patients less than 12 years of age waived because there are too few children with the disease to study New drug	P
1/2/2008	EVICEL	fibrin sealant (human)●	Adjunct to hemostasis for use in patients undergoing surgery, when control of bleeding by standard surgical techniques is ineffective or impractical	Johnson/Johnson Wound Management	Package Insert Clinical Review Statistical Review		P
6/12/2007	Extina Foam, 2%	ketoconazole	Topical treatment of seborrheic dermatitis in immunocompetent patients 12 years of age and older	Stiefel Laboratories	Label	Effectiveness and safety were established in a clinical study that included 44 patients from 12-17 years of age Studies waived in children 0-12 years of age New dosage form	P
8/13/2004	Ferrlecit	sodium ferric gluconate complex	Iron deficiency anemia in chronic hemodialysis patients receiving supplemental erythropoietin therapy	Watson	Label Medical Review Clinical Pharmacology Review	Safety and effectiveness established in pediatric patients 6 -15 years old Patients <6 years of age not studied Information on dose, PK parameters and AE profile	B
5/1/2003 and 1/18/2002	Flonase Nasal Spray & Cutivate Ointment	fluticasone	Flonase - nasal symptoms of seasonal and perennial allergic and nonallergic rhinitis Cutivate Ointment - corticosteroid-responsive dermatoses	GlaxoSmithKline	Label - Flonase Label - Cutivate Medical Review No clin pharm	Flonase New data from 1-year placebo-controlled clinical growth study in pediatric patients 3-9 years of age; no statistically significant effect on growth was noted compared to placebo. No evidence of clinically relevant changes in HPA axis function or bone mineral density was observed as assessed by 12-hour urinary cortisol excretion and dual-energy x-ray absorptiometry, respectively. Cutivate Indicated for use only in adult patients In a study of 35 pediatric patients treated for atopic dermatitis, subnormal adrenal function was observed with cosyntropin stimulation testing	B
9/30/2003	Floxin Otic Solution	floxacin	Treatment of otitis externa (outer ear infection) in children 6 months of age and older	Daiichi	Label Medical Review	Dosing change from 2 times daily to 1 time daily for 7 days based on effectiveness and safety studies that included pediatric patients New dosing regimen	P
8/1/2003	Fludara	fludarabine	Refractory acute leukemia and solid tumors	Berlex	Label Medical Review Clinical Pharmacology Review	Fludarabine was evaluated in 62 pediatric patients and the data were insufficient to establish efficacy in any childhood malignancy	B
11/9/2005	Fluocinolone Acetonide Oil	fluocinolone	Chronic eczematous external otitis (outer ear) in children 2 years of age and older	Hill Dermaceuticals	Label	Effectiveness established in studies of patients 2 years of age and older New indication	P
5/26/2005	Focalin XR Extended-Release Capsules	dexmethylphenidate	Treatment of Attention-Deficit Hyperactivity Disorder in children 6 years of age and older	Novartis	Label	Should not be used in children under 6 years of age Effectiveness in patients age 6 years of age and older was established in clinical studies PK studies also conducted Long-term effects in children have not been established New dosage form	P
7/21/2006	Formoterol Symbicort Inhalation Aerosol	budesonide*	Long-term maintenance treatment of asthma in children 12 years of age and older	AstraZeneca	Label Medical Review	Effectiveness and safety in patients 12 years of age and older established in studies up to 12 months long PK studies in patients 6-11 years of age Effectiveness in patients 6 to < 12 years of age has not been established Overall safety profile in patients 6 to < 12 years of age was similar to that observed in patients 12 years of age and older Studies waived in children 0-6 years of age; deferred in children 6-12 years of age New active ingredient	P
12/21/2005	Fosamax	alendronate	Severe osteogenesis imperfecta	Merck	Label Medical Review Clinical Pharmacology Review	Alendronate is not indicated for use in children The efficacy and safety were examined in a randomized, double-blind, placebo-controlled two-year study of 139 patients, 4-18 years old, with severe osteogenesis imperfecta Treatment with alendronate did not reduce the risk of fracture There were no statistically significant differences between the alendronate and placebo groups in reduction of bone pain Information on PK parameters, AE profile, and clinical studies	B
9/29/2006	Fuzeon	enfuvirtide	HIV-1 infection in treatment-experienced patients with evidence of HIV-1 replication despite ongoing antiretroviral therapy	Hoffmann-La Roche	Label	Additional safety and efficacy data and AE information from clinical study in 5-16 year olds Insufficient data to provide dosing recommendations in patients < 6 years	B
9/12/2008	Gardasil	human papillomavirus quadrivalent (types 6, 11, 16, 18) vaccine, recombinant●	Prevention of vulvar and vaginal cancer	Merck	Package Insert Clinical Review Statistical Review		P
4/26/2005	Gemzar	gemcitabine	Refractory leukemia	Lilly	Label Medical Review	Effectiveness in pediatric patients has not been demonstrated Phase 1 trial in pediatric patients with refractory leukemia demonstrated a maximum tolerated dose; however, no meaningful clinical activity observed in a Phase 2 trial of gemcitabine in 22 patients with relapsed acute lymphoblastic leukemia and 10 patients with acute myelogenous leukemia Toxicities observed were similar to those reported in adults	B
4/27/2006	Genotropin Injection	somatropin	Long-term treatment of growth failure associated with Turner syndrome	Pharmacia & Upjohn	Label	Indicated for use in pediatric patients with open epiphyses Effectiveness and safety based on studies in pediatric patients New indication	P
9/27/2006	Gleevec	imatinib mesylate	Treatment of newly diagnosed pediatric patients with Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) in chronic phase	Novartis	Label Medical Review Clinical Pharmacology Review	Extended age range for the treatment of newly diagnosed CML down to pediatric patients There are no data in children < 2 years of age Follow-up in children with newly diagnosed Ph+ chronic phase CML is limited Information on hematologic toxicities, AE profile, clinical studies and dosing guidelines new for newly diagnosed pediatric patients	B
12/15/2000	Glucophage (immediate release)	metformin	Diabetes Mellitus	Bristol-Myers Squibb	Label	Safety and effectiveness as monotherapy established in patients 10-16 years of age	B
3/15/2004	Glucovance	glyburide / metformin	Type 2 Diabetes Mellitus	Bristol-Myers Squibb	Label Medical Review Clinical Pharmacology Review	As studied in active-controlled, double blind trial in pediatric patients (9 – 16 years of age), Glucovance was not statistically superior to either metformin or glyburide in reducing HbA1C from baseline No unexpected safety findings	B
12/19/2007	Hepsera	adefovir dipivoxil	Chronic hepatitis B virus infection	Gilead	Label Medical Review Clinical Pharmacology Review Statistical Review	Extended indication from adults to pediatric patients 12 years and older Not recommended for children <12 years of age. Efficacy was not significantly different from placebo in a clinical study in children <12 years Safety ≥12 – < 18 years was similar to that observed in adults Information on PK, AEs, clinical study, clinical resistance	B
6/2/2004	Humalog Injection	insulin lispro	Treatment of patients with diabetes mellitus for the control of hyperglycemia (high blood sugar) in children 3-11 years of age	Lilly	Label	Safety and effectiveness established from studies in patients 3-11 years of age Dosing information added for external insulin pumps New route of administration	P
11/1/2006	Humatrope for injection	somatropin [rDNA origin]	Treatment of short stature or growth failure in children with short stature homeobox-containing gene (SHOX) deficiency	Lilly	Label	Effectiveness established from one 2-year study for SHOX in 52 pediatric patients Information on adverse events provided Dosing information provided New indication	P
2/21/2008	Humira	adalimumab	Treatment of juvenile idiopathic arthritis	Abbott	Label Medical Clinical pharmacology Statistical	Summary pending	P
10/13/2004	Imitrex Nasal Spray	sumatriptan	Migraine	Glaxo	Label Medical Review Clinical Pharmacology Review	Five clinical trials evaluating oral sumatriptan in pediatric patients ages 12 -17 years did not establish the safety and effectiveness when compared to placebo Postmarketing experience documents that serious AEs rarely reported in adults, including stroke, visual loss, and death have occurred in the pediatric population after use of subcutaneous, oral, and/ or nasal sumatriptan. Since clinical data to determine the frequency of serious adverse events in pediatric patients who might receive injectable, oral, and/ or intranasal sumatriptan are not presently available, the use of sumatriptan in patients aged younger than 18 years is not recommended	B
1/31/2008	Inspra	eplerenone	Hypertension	Pfizer	Label Medical Review Clinical Pharmacology Review Statistical Review	Effectiveness was not established in a study of 304 hypertensive pediatric patients 4 - 17 years; eplerenone, at doses up to 100 mg/ day, did not lower blood pressure effectively Therefore, it has not been studied in hypertensive patients <4 years old Eplerenone has not been studied in hypertensive patients < 4 years or in pediatric patients with heart failure Adverse events similar to that of adults	B
5/18/2005	Invanz	ertapenem	Complicated Intra-abdominal Infections; Complicated Skin and Skin Structure Infections; Community Acquired Pneumonia; Complicated Urinary Tract Infections; Acute Pelvic Infections	Merck	Label	Approved for use down to 3 months of age. Efficacy extrapolated from studies in adults and supported by PK and safety studies in pediatric patients Not recommended in infants under 3 months of age as no data are available Not recommended in the treatment of meningitis in the pediatric population due to lack of sufficient CSF penetration Information on dose, PK parameters, AE profile and clinical studies	B
3/30/2009	Ixiaro	Japanese Encephalitis Vaccine, Inactivated, Adsorbed●	Active immunization for the prevention of disease caused by Japanese encephalitis virus in persons 17 year of age and older	Intercell Biomedical	Package Insert - Military Package Insert - Commercial		P
6/20/2008	Kaletra	lopinavir/ ritonavir	Use in combination with other antiretroviral agents for HIV-1 infection	Abbott	Label Medical Review Clinical Pharmacology Review	Extended indication from 6 months - 12 years to 14 days - 18 years The safety, efficacy, and pharmacokinetic profiles in pediatric patients < 14 days have not been established Dose should be calculated based on body weight or body surface area not to exceed adult dose Because no data exists for dosage when administered with efavirenz, nevirapine, (fos)amprenavir, or nelfinavir, it is recommended that lopinavir/ ritonavir not be administered in combination with these drugs in patients < 6 months of age Infants <6 months of age generally had lower lopinavir AUC12 than children 6 months - 12 years of age Information on dose, PK parameters, clinical studies, and AEs	B
11/9/2007	Kaletra Oral Solution, 80 mg/20 mg & Kaletra (1opinavir/ritonavir) Tablets, 200 mg/50 mg	lopinavir/ ritonavir	HIV -1 protease inibitor indicated in combination with other antiretroviral agents for the treatment of HIV -1 infection.	Abbott Laboratories	Label	Dosing and administration information provided for children Use of a lower strength tablet in a twice daily dosing regimen for pediatric patients weighing greater than 15 kg New dosing regimen	P
6/21/2005	Keppra	levetiracetam	Adjunctive therapy in the treatment of partial onset seizures in patients with epilepsy	UCB Pharma	Label Medical Review Clinical Pharmacology Review	Extended indication from adults to patients 4 years and older Safety and effectiveness have not been established in patients less than 4 years of age PK analysis showed that clearance increased with an increase in body weight Approximately 22% increase of apparent total body clearance of levetiracetam when co-administered with enzyme-inducing Anti-Epileptic Drugs (AEDs). Dose adjustment not necessary 37.6% of pediatric patients reported behavioral symptoms compared to 13.3% in adults Somnolence occurred in 22.8% in pediatric patients compared to 14.8% in adults Information on dose, PK parameters, AE profile and clinical studies	B
3/19/2007	Keppra Tablets Keppra Oral Solution (levetiracetam*)	levetiracetam*	Adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in children 6 years of age and older with idiopathic generalized epilepsy	UCB	Label	Safety and effectiveness established in study that included patients down to 4 years of age Pediatric dosing information added Studies waived in children 1 month to 2 years of age and deferred in children 2-6 years of age New indication	P
6/24/2008	Kinrix	diphtheria and tetanus toxoids and acellular pertussis adsorbed and inactivated poliovirus vaccine●	Active immunization against diphtheria, tetanus, pertussis, & poliomyelitis as the fifth dose in the diphtheria, tetanus, & acellular pertussis (DTaP) series & the fourth dose in the inactivated poliovirus vaccine (IPV) in children 4 - 6 years of age whose previous DTaP vaccine doses have been INFANRIX and/or PEDIARIX for the first three doses & INFANRIX for the fourth dose	GlaxoSmithKline Biologicals	Package Insert Clinical Review Statistical Review		P
10/10/2008	Kogenate FS	antihemophilic factor (recombinant)●	Routine prophylaxis to reduce the frequency of bleeding episodes and the risk of joint damage in children with hemophilia A with no pre-existing joint damage	Bayer	Package Insert Final review		P
8/25/2000	Lac-Hydrin	ammonium lactate	Xerosis, ichthyosis	Westwood-Squibb	Label	Safety and effectiveness established in patients 2 – 11 years of age; previously approved ³12 years of age	B
1/17/2003	Lamictal	lamotrigine	Adjunctive therapy for partial seizures	GlaxoSmithKline	Label Medical Review Clinical Pharmacology Review	Extended indication from adults to pediatric patients ≥ 2 years Patients aged 2 - 18 years had clearance influenced predominantly by total body weight and concurrent antiepileptic drug (AED) therapy. The oral clearance was higher, on a body weight basis, in pediatric patients than in adults Because of increased clearance in pediatrics, maintenance doses in patients weighing < 30 kg may need an increase of as much as 50% based upon clinical response Evidence shows that the inclusion of VPA in a multi-drug regimen increases the risk of serious, potentially life-threatening rash in pediatric patients Approximately 11.5% of the 1,081 pediatric patients who received the drug as adjunctive therapy in clinical trials discontinued treatment because of an AE	B
9/22/2006	Lamictal Tablets Lamictal Chewable Dispersible Tablets	lamotrigine*	Adjunctive therapy for primary generalized tonic-clonic seizures in children 2 years of age and older	GlaxoSmithKline	Label	Effectiveness established in study with patients down to 2 years of age Revised boxed warning to remove restrictions on use in pediatric patients New indication	P
9/28/2007	Lamisil Oral Granules	terbinafine	Tinea capitis	Novartis	Label Medical Review Clinical Pharmacology Review Statistical Review	New indication in 4 years and older Two randomized safety and efficacy trials were conducted in patients 4 to 12 years old with tinea capitis. Terbinafine was dosed on a mg/kg basis and treated for 6 weeks Although no hepatotoxicity was seen during trials, pre-treatment serum transaminases tests are advised. The most common adverse events observed in the trials were nasopharyngitis, headache, pyrexia, cough, vomiting, and upper respiratory tract infection New 125 mg and 187.5 mg oral granule formulations developed; take with food Information on dose, PK parameters, AE profile, and instructions for use	B
3/31/2008	Lancôme UV Expert 40 La Roche-Posay Anthelios 40 Vichy Capital Soleil 40	avobenzone, ecamsule, octocrylene, titanium dioxide cream	OTC	L’Oreal USA		Summary pending	P
4/20/2000	Lantus	insulin glargine	Type 1 Diabetes	Aventis	Label	Safety and effectiveness established down to 6 years	B
4/10/2006	Lescol and Lescol XL	fluvastatin	Heterozygous familial hypercholesterolemia as an adjunct to diet	Novartis	Label Medical Review	New indication in adolescent boys and girls (at least one year post-menarche) 10-16 years of age, with heterozygous familial hypercholesterolemia Information on dose, AE profile and clinical studies	B
9/11/2007	Levaquin	levofloxacin	Community-acquired pneumonia	Ortho-McNeil	Label Medical Review Clinical Pharmacology Review	Levofloxacin is not indicated for pediatric patients < 18 years of age In a prospective, long-term, surveillance study, levofloxacin treated children had a significantly higher incidence of musculoskeletal (MS) disorders (arthralgia, arthritis, tendonopathy, and gait abnormality) compared to non-fluoroquinolone-treated children Information on clinical studies, AE profile	B
5/5/2008	Levaquin Tablets, 250 mg, 500 mg, and 750 mg# Levaquin Oral Solution, 25 mg/mL# Levaquin Injection and Levaquin Injection, 5 mg/mL#	levofloxacin levofloxacin in 5% dextrose injection	Reduce the incidence or progression of disease following exposure to aerosolized Bacillus anthracis (inhalational anthrax post-exposure)	Ortho-McNeil-Janssen Pharmaceutical, Inc.		New indication Dosing information provided for children less than and greater than 50 kg Efficacy is based on plasma concentrations achieved in humans, a surrogate endpoint reasonably likely to predict clinical benefit, and animal studies were used to evaluate survival; the product has not been tested in humans for the post-exposure prevention of inhalation anthrax Safety in pediatric patients treated for more than 14 days has not been studied Long-term safety data, including effects on cartilage, following administration in pediatric patients is limited Due to possible side effects, use is not recommended for pediatric patients except in the prevention of anthrax after inhalational exposure Pharmacokinetics were investigated in pediatric patients 6 months to 16 years old	P
3/19/2009	Lexapro Tablets 5 mg, 10 mg, and 20 mg and Oral solution 5 mg/mL	escitalopram oxalate	Major depressive disorder in adolescents	ForestLaboratories		Summary pending	B
6/14/2007	Lexiva Oral Suspension	fosamprenavir	Treatment of HIV infection in patients 2-18 years of age	GlaxoSmithKline	Label	Effectiveness and safety were established in two clinical studies of pediatric patients 2-18 years of age Adverse event profile is similar to that of adults with the exception of vomiting, which, regardless of causality, occurred more frequently among pediatric patients Dosing information provided Studies waived in children 0-1 month of age and deferred in children 1 month - 2 years of age New dosage form	P
6/29/2006	Lidocaine and Tetracaine Cream	lidocaine; tetracaine	Topical local analgesia for superficial dermatological procedures	ZARS	Label	Studies failed to show effectiveness over placebo in reducing the pain associated with venipuncture in pediatric patients 5-17 years of age New active ingredient	P
5/6/2004	Lidosite Topical System Kit	epinephrine; lidocaine	Topical local analgesia for superficial dermatological procedures in children 5 years of age and older	Vyteris	Label	505(b)(2) with clinical studies Safety and effectiveness established in studies of pediatric patients 5-18 years of age PK study in pediatric patients 6-15 years of age dosing regimen established in clinical trials Studies in patients 0-5 years of age deferred New dosage form; new route of administration	P
10/18/2002	Lipitor	atorvastatin	Heterozygous Familial Hypercholesterolemia	Pfizer	Label	New indication in adolescent boys and girls (post-menarche) 10-17 years of age	B
5/18/2007	Locoid Lotion 0.1%	hydrocortisone butyrate ww	Treatment of mild to moderate atopic dermatitis in children 3 months of age and older	Ferndale Labs	Label	Effectiveness established in one study of 284 patients from 3 months to 18 years of age Information provided on HPA axis suppression from one safety study with Locoid Lotion of 84 pediatric patients from 3 months to 18 years of age with moderate to severe atopic dermatitis affecting at least 25% of body surface area Studies waived in children < 3 months of age New dosage form	P
8/11/2000	Lodine	etodolac	Relief of signs & symptoms of Juvenile Rheumatoid Arthritis	Wyeth Ayerst	Label	New indication in 6 years -16 years Higher dose (per kg basis) in younger children which is approximately 2 times the lower dose recommended for adults	B
8/4/2005	Loperamide Hydrochloride Soft Gelatin Capsules#	loperamide	Control symptoms of diarrhea in children 12 years of age and older	Banner Pharmacaps	Label	New dosage form; new dosing regimen No new clinical studies Bioequivalence study in adults compared the current OTC drug (Imodium caplet) and this drug Studies waived in children 0-2 years of age	P
3/2/2004	Lotensin	benazepril	Hypertension	Novartis	Label Medical Review Clinical Pharmacology Review	Information on dose, PK in pediatric patients 6-16 years of age Not recommended for pediatric patients less than 6 years or with glomerular filtration rate < 30mL/min/1.73 m2 due to insufficient data Infants below the age of 1 year should not be given ACE inhibitors due to concerns over possible effects on kidney development The clearance rate was substantially higher in hypertensive children and adolescents than that of healthy adults The terminal half life (t1/2) in pediatric patients was one third of that observed in adults Adverse event profile in pediatric patients was similar to that seen in adults Information on preparation of a suspension	B
9/28/2000 and 2/18/2005	Luvox	fluvoxamine	Treatment of obsessions and compulsions in patients with OCD	Solvay	Label	Determined that a dose adjustment (increased dose) may be necessary in adolescents and girls 8-11 years of age may require lower doses FDA required boxed warning for all antidepressants: Suicidality in Children and Adolescents - Antidepressants increased the risk of suicidal thinking and behavior (suicidality) in short-term studies in children and adolescents with Major Depressive Disorder (MDD) and other psychiatric disorders. Anyone considering the use of fluvoxamine or any other antidepressant in a child or adolescent must balance this risk with the clinical need. Patients who are started on therapy should be observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Fluvoxamine is not approved for use in pediatric patients except for patients with obsessive compulsive disorder (OCD). (See Warnings and Precautions: Pediatric Use) Pooled analyses of short-term (4 to 16 weeks) placebo-controlled trials of 9 antidepressant drugs (SSRIs and others) in children and adolescents with major depressive disorder (MDD), obsessive compulsive disorder (OCD), or other psychiatric disorders (a total of 24 trials involving over 4400 patients) have revealed a greater risk of adverse events representing suicidal thinking or behavior (suicidality) during the first few months of treatment in those receiving antidepressants. The average risk of such events in patients receiving antidepressants was 4%, twice the placebo risk of 2%. No suicides occurred in these trials The efficacy of fluvoxamine for the treatment of OCD was demonstrated in a 10-week multicenter placebo controlled study with 120 outpatients ages 8 to 17. In addition, 99 of these outpatients continued open-label fluvoxamine treatment for up to another one to three years, equivalent to 94 patient years	B
12/2/2003	Malarone	atovaquone/ proguanil	Treatment of malaria	GlaxoSmithKline	Label Medical Review Clinical Pharmacology Review	Safety and efficacy for treatment of malaria established down to5 kg. Attributable AE occurring in ≥ 5% of the pediatric patients (5-< 11 kg) was diarrhea (6%) Malarone tablets may be crushed and mixed with condensed milk just prior to administration for children who may have difficulty swallowing. The apparent clearance (CL/F) of both atovaquone and proguanil are related to body weight	B

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New Pediatric Information in Labeling

Resulting from the Best Pharmaceuticals for Children Act (BPCA) Pediatric Research Equity Act (PREA) through April 19, 2009