aripiprazole

Label

• 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

aripiprazole

 Label

• Extended treatment of acute Bipolar Disorder indication from adults to pediatrics 10–17 years
• The efficacy for the maintenance treatment of Bipolar Disorder in the pediatric population has not been evaluated
• The recommended target dose in Bipolar Disorder is 10 mg/day.
• In the study of pediatric patients 10 - 17 years with Bipolar Mania, 4 common adverse reactions had a possible dose response relationship at 4 weeks; extrapyramidal disorder, somnolence,  akathisia and salivary hypersecretion
• Information on dose, AEs, clinical studies

isotretinoin

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)

fentanyl

Label

• 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

amphetamines mixed salts

Label

• 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

ibuprofen

Label

ibuprofen/
pseudoephedrine

Label

Anagrelide

Label

• 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

pemirolast

Label

imiquimod

Label

• 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

fexofenadine

Label

fexofenadine

Label  

• 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

brimonidine

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%)

glimepiride

Label

• 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

zolpidem

Label

• 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%

testosterone

Label

• 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

leflunomide

Label

• 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

argatroban

Label

• 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

rosiglitazone

Label

• 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

irbesartan

• 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

nizatidine

Label

• Indicated in pediatric patients 12 years and older
• Information on dose, PK parameters, and AE profile

brinzolamide

Label

• IOP-lowering efficacy was not demonstrated in 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

sotalol

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

levobetaxolol

Label

• Extended indication from adults to pediatric patients
• The adverse event profile was comparable to that seen in adults and elderly patients

betaxolol

Label

• Extended indication from adults to pediatric patients
• The adverse reaction profile was comparable to that seen in adults

buspirone

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

busulfan

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

calcitriol

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

irinotecan

Label

• 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

technetium tc99m sestamibi

Label

• 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

celecoxib

Label

• 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

citalopram

Label

• 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

ciprofloxacin

Label

• 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

desloratadine

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

loratadine

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

clofarabine

Label

• 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 profile

balsalazide

Label

• 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

methylphenidate

Label

• 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

carvedilol

Label

• 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%)

fenoldopam

Label

•   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

losartan

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

oxaprozin

Label

divalproex disodium

Label

• 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

tolterodine

Label

• 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

valsartan

Label

• 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

propofol

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

oxybutynin

Label

• Additional information on dose and PK parameters
• Precautions section of label updated

• Safety and effectiveness established down to 6 years of age

fentanyl

Label

• 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%)

venlafaxine

• 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

pimecrolimus

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.

mometasone

Label

• Extended age range from 3 years down to 2 years
• In a clinical study in which pediatric patients 2-5 years were treated with mometasone nasal spray for up to 42 consecutive days, no significant effect on adrenal function was found
• Upper respiratory tract infection was more common with Nasonex (2/28) compared to placebo (0/28)

• Evidence of HPA axis suppression in pediatric patients 6-23 months of age
• Outlined local AE's as well as skin atrophy in pediatric patients 6-23 months of age
• Approved down to 2 years of age as in previous labeling

• Safety and effectiveness have not been established in pediatric patients below 12 years of age and use <12 year old is not recommended
• Should not be used for the treatment of diaper dermatitis

oxaliplatin

Label  

• 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

emtricitabine

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

emtricitabine

Label

• 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

lamivudine

lamivudine

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)

sodium ferric gluconate complex

Label

• 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

fluticasone

Label  

Label

• 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.

• 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

fludarabine

Label

• Fludarabine was evaluated in 62 pediatric patients and the data were insufficient to establish efficacy in any childhood malignancy

alendronate

Label

• 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

enfuvirtide

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

gemcitabine

Label

• 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

imatinib mesylate

Label

• 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

metformin

Label

glyburide/ metformin

Label

• 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

adefovir dipivoxil

Label

• 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

sumatriptan

Label

• 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

eplerenone

Label

• 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

ertapenem

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

levetiracetam

Label

• 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

ammonium lactate

Label

lamotrigine

Label

• 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

terbinafine

Label  

• 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

insulin glargine

Label

fluvastatin

Label

• 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

levofloxacin

Label  

• 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

atorvastatin

Label

etodolac

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

benazepril

Label

• 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

betamethason;betamethasone/ clotrimazole

Label

• 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)

• 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

• 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

fluvoxamine

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

• Safety and effectiveness established down to ³ 11kg
• Information on dose, efficacy, PK parameters and AE profile
• Elimination half-life is shorter in pediatric patients (1 to 2 days) than in adults (2 to 3 days)
• Attributable AE's occurring in ³ 5% of the pediatric patients were vomiting (10%) and pruritus (6%)

atovaquone/
proguanil

Label

• 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

sibutramine

Label

• The data are inadequate to recommend the use of sibutramine for the treatment of obesity in pediatric patients
• Efficacy in obese adolescents has not been adequately studied
• Sibutramine's mechanism of action inhibiting the reuptake of serotonin and norepinephrine is similar to that of some antidepressants
  -It is unknown if sibutramine increases the risk of suicidal behavior or thinking in pediatric patients
• In a study of adolescents with obesity in which 368 patients were treated with sibutramine and 130 patients with placebo, one patient in each group attempted suicide. Suicidal ideation was reported by 2 sibutramine-treated patients and none of the placebo patients

lovastatin

Label

meloxicam

Label

• Safety and efficacy established in patients 2 years of age and older
• Clinical studies evaluated doses ranging from 0.125 mg/kg/day to 0.375 mg/kg/day.  There was no additional benefit demonstrated by doses above 0.125 mg/kg/day in the clinical trials.  The lowest effective dose should be used
• Adverse events in children were similar to those in adults including skin reactions and gastrointestinal bleed risk
• Information on dose, PK parameters, AE profile and clinical studies

fosinopril

Label

• New data from a double-blind study in 252 patients 6-16 years of age
• New recommended dose in children weighing more than 50kg
• New Information on PK parameters
• An appropriate dosage strength is not available for children weighing less than 50kg

ibuprofen

Label

ibuprofen/
pseudoephedrine

Label

cromolyn

Label

vinorelbine

Label

gabapentin

Label

• Safety and effectiveness established down to 3 years