1.

7/1/98
(4/15/99)

Ibuprofen - Motrin (McNeil)
Label [PDF ]

Fever, minor aches & pain, cold symptoms

Extended age range from 2 years to 6 months for the over-the-counter use based on a large safety database (27,000 patients)

7/1/98
(4/15/99)

Ibuprofen - Advil (Whitehall)
Label [PDF ]
 

Fever, minor aches & pain, cold symptoms

Extended age range from 2 years to 6 months for the over-the-counter use based on a large safety database (14,291 patients)

9/18/98
(10/15/98)

Midazolam - Versed (Roche)
Label [Word]

Pediatric Formulation

Sedation/anxiolysis/
amnesia

• Specified the effective dose, effective dose range, and time of onset
• Defined volume of distribution and similarity to adult protein binding and elimination
• Additional information on AE's and warnings about concomitant medications
• Identified a subpopulation (children with congenital heart disease and pulmonary hypertension) at higher risk for AE's and the need to start therapy at the lower end of the dosing range

12/14/98
(12/17/98)

*Abacavir - Ziagen (Glaxo)
Label [Word 97]
Pediatric Formulation

HIV infection

• Labeling for 3 months - 12 years
• Information on dose, efficacy, PK parameters and AE profile

1/19/99
(10/22/99)

Ranitidine - Zantac (Glaxo)
Label [PDF ]

Gastroesophageal Reflux

Extended age range to include 0 to 1 month, characterized PK in single and continuous infusions

7/12/99
(4/20/00)

*Insulin glargine - Lantus (Aventis)|
Label [PDF ]

Type 1 Diabetes

Safety and effectiveness established down to 6 years

8/11/99
(9/24/00)

*Pemirolast - Alamast (Santen)
Label [PDF ]

Allergic Conjunctivitis

Safety and effectiveness established down to 3 years

(7/14/00)

also see additional approval at #61

*Atovaquone / Proguanil -  Malarone
(Glaxo)
Label [PDF ]

Pediatric Formulation

Prophylaxis and treatment of malaria

• Safety and effectiveness established down to ≥ 11 kg
• 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 ≥ 5% of the pediatric patients were vomiting (10%) and pruritus (6%)

(7/28/00)

*Ibuprofen / pseudoephedrine Motrin Suspension (McNeil)
Label [Word 97]

Pediatric Formulation

Temporary relief of nasal and sinus congestion, minor body aches and pains, fever, stuffy nose, headache and sore throat

Information on the over-the-counter use in pediatric patients 2 to 11 years of age

8/11/99
(5/22/00)

*Azelastine - Optivar (Asta)
Label [Word 97]

Itching associated with Allergic Conjunctivitis

Safety and effectiveness established down to 3 years

10/1/99
(8/25/00)

Ammonium lactate - Lac-Hydrin (Westwood-Squibb)
Label [PDF ]

Xerosis, ichthyosis

Safety and effectiveness established in patients 2 - 11 years of age; previously approved ≥ 12 years of age

12/6/99
(8/11/00)

Etodolac-Lodine   (Wyeth Ayerst)
Label [PDF ]

Relief of signs & symptoms of Juvenile Rheumatoid Arthritis

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

1/3/00
(9/28/00)

Fluvoxamine - Luvox (Solvay)
Label [Word]

Treatment of obsessions and compulsions in patients with OCD

Determined that a dose adjustment (increased dose) may be necessary in adolescents and girls 8-11 years of age may require lower doses

2/2/00
(10/12/00)

Gabapentin - Neurontin (Parke-Davis)       Pediatric Formulation
Label [PDF ]

Adjunctive therapy in the treatment of partial seizures

• Safety and effectiveness established down to 3 years
• Neuropsychiatric AE's identified in 3-12 year olds
• Oral clearance normalized per body weight increased in children <5 years
• Higher doses of gabapentin required in children <5 years

8/14/00
(12/4/00)

Loratadine - Claritin (Schering)
Label [PDF ]

Allergic rhinitis/Urticaria

• 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

3/15/00
(12/15/00)

Metformin - Glucophage
(immediate release) (Bristol-Myers
Squibb)
Label [Word 97]

Diabetes Mellitus

Safety and effectiveness as monotherapy established in patients 10-16 years of age

2/2/00
(2/13/01)

Enalapril
(Merck)
Label [PDF ]

Hypertension

• Labeling for 1 month-16 years of age
• Information on dose, efficacy and pharmacokinetics
• Information on preparation of a suspension

8/11/99
(2/23/01)

Propofol - Diprivan (AstraZeneca)
Label [PDF ]

Induction and/or maintenance of anesthesia

• 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

11/2/99
(3/27/01)

Cromolyn - Nasalcrom (Pharmacia & UpJohn)
Label [Word]

Prevention and relief of nasal symptoms of hay fever and other nasal allergies

Established proper dose in 2 year - 6 year olds and provided additional safety and compliance data for this age group

8/2/00
(3/30/01)

Sevoflurane - Ultane (Abbott)
Label [PDF ]

Induction and maintenance of general anesthesia

• New study in pediatric patients 9 days-12 years comparing sevoflurane and halothane
• Precautions section and Adverse Events During Post-Marketing subsection updated to add information on the rare cases of seizures that have been reported in pediatric patients in association with sevoflurane use. The majority of cases were in children and young adults, most of whom had no medical history of seizures
• Pediatric information consolidated into new Pediatric Use subsection

5/22/01
(7/19/01)

Buspirone - 
Buspar
(Bristol-Myers Squibb)
Label [PDF ]

• 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

7/25/01
(8/16/01)

Lamivudine - 
Epivir-HBV
(Glaxo
SmithKline)
Label [Word 97]

Treatment of Chronic Hepatitis B

• Safety and effectiveness established down to 2 years
• Established a dose of 3mg/kg/day up to a maximum of 100mg/day (adult dose)

(10/3/01)

Betamethasone - 
Diprolene AF,
Diprosone,
Lotrisone
(Schering)
Label [PDF ]

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

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)

• 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

1/6/00

(10/3/01)

Sotalol -
Betapace
(Berlex)
Label [PDF ]

• Labeling for 3 days-12 years of age
• 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

2/14/01

(11/16/01)

Calcitriol -
Calcijex
(Abbott)
Label [PDF ]

Management of hypocalcemia in patients undergoing chronic renal dialysis

• 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

9/24/01
(12/13/01)

*Pimecrolimus -
Elidel
(Novartis)
Label [PDF ]

Treatment of mild/moderate atopic dermatitis

• 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.

10/10/01
(12/20/01)

Brimonidine -
Alphagan
(Allergan)
Label [PDF ]

Prevention of post-operative IOP elevations

• 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%)

5/9/01
(12/28/01)

Ribavirin/Intron A -
Rebetron
(Schering)
Label [Word 97]

• Pharmacokinetic information on patients 5 to 16 years with chronic hepatitis C virus infection
• Increased incidence of suicidal ideation or attempts (2.4% versus 1%) among pediatric patients compared to adult patients
• Decrease in rate of linear growth and in rate of weight gain during 48 weeks of treatment; a general reversal was noted during the 24 week post treatment period

12/6/99
(1/25/02)

Oxaprozin -
Daypro
(Searle)
Label [PDF ]

Relief of signs and symptoms of Juvenile Rheumatoid Arthritis

New indication in 6 years -16 years

Ketorolac - Acular & Acular PF  (Allergan)
Label [PDF ]

Relief of ocular itching due to seasonal allergic rhinitis and postoperative inflammation after cataract extraction

Lovastatin -  Mevacor 
(Merck)
Label [PDF ]

Heterozygous Familial Hypercholesterolemia

Stavudine - Zerit  (Bristol-Myers Squibb)
Label [PDF ]

HIV infection

• Safety and effectiveness established down to birth
• Established a dose for newborns from birth to 13 days

Didanosine - Videx (Bristol-Myers Squibb)
Label [PDF ]

HIV infection

Ibuprofen / pseudoephedrine Advil Suspension (Whitehall)
Label [PDF]

Temporary relief of nasal and sinus congestion, headache, stuffy nose, sore throat, minor aches and pains, and fever

Isotretinoin - Accutane (Hoffman La-Roche)
Label [PDF ]

Severe recalcitrant nodular acne

• 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)

Famotidine - Pepcid (Merck)
Label [PDF ]

Gastroesophageal reflux

• Labeling for patients less than 1 year of age including information on dose, PK/PD parameters and AE profile
• Lower dose recommended in patients <3 months of age
• Pediatric patients 0-3 months of age had clearance values 2 to 4-fold less than those in older patients and adults
• In a clinical study of 35 pediatric patients <1 year of age, agitation was observed in 5 patients on famotidine and resolved upon discontinuation of the drug

Omeprazole - Prilosec (AstraZeneca)
Label [PDF ]

Gastroesophageal reflux and erosive esophagitis

• Safety and effectiveness established in pediatric patients 2-16 years of age
• Information on dose, PK parameters, exposure/response and AE profile

Mometasone - 
 Nasonex-nasal  (Schering)
Label [PDF ]

Mometasone - Elocon-topical (Schering)
Cream Label [PDF ]
 Ointment Label [PDF ]
Lotion Label [PDF ]
   

Nasonex - Perennial and seasonal allergic rhinitis

Elocon - Relief of inflammatory and pruritic manifestations of corticosteroid dermatoses

• 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)

Elocon Cream & Ointment

• 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

Elocon Lotion

• 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

Montelukast - Singulair (Merck)
Label [PDF ]

Prophylaxis and chronic treatment of asthma

• Safety and effectiveness established in patients 12 months to 5 years of age
• Information on dose, PK parameters and AE profile in patients 12-23 months and 2-5 years
• New 4mg chewable tablet and 4mg oral granule formulations developed. The chewable tablets contain aspartame whereas the oral granule formulation does not

Tamoxifen - Nolvadex (AstraZeneca)
Label [PDF ]

• Safety and effectiveness of tamoxifen studied in female patients aged 2-10 years with McCune-Albright Syndrome and precocious puberty treated for up to 12 months. Long term effects have not been established.
• Effect of treatment was assessed relative to prestudy baseline:
• ~50% reduction in frequency of vaginal bleeding
• ~ reduction in mean rate of increase of bone age
• ~ linear growth rate reduced in majority of patients during treatment
• Mean uterine volume increased after 6 months of therapy and doubled at end of 1-year study

• Extended the age range from 2 years to 6 months
• Information on dose, PK parameters and AE profile

• Safety and effectiveness established down to 6 years of age
• The effectiveness of atomoxetine beyond 9 weeks and safety beyond 1 year in pediatric patients, has not been systematically evaluated in controlled trials
• It is unknown whether final adult height or weight is affected by treatment. Patients on long-term treatment should be monitored

• Effectiveness established in patients 7-17 years of age for OCD
• Effectiveness established in patients 8-17 years of age for MDD
• Decreased weight gain has been observed in association with the use of fluoxetine, as with other SSRIs. In one 19-week clinical trial pediatric subjects treated with fluoxetine gained an average of 1.1cm less in height (p=0.004) and 1.1 kg less in weight (p=0.008) than those treated with placebo. Therefore, height and weight should be monitored periodically in pediatric patients treated with fluoxetine.
• Mania/hypomania led to discontinuation of 1.8% of fluoxetine treated patients vs. 0% of placebo controlled patients in the three placebo-controlled trials combined. Regular monitoring for the occurrence of mania/hypomania is recommended
• Higher average steady state fluoxetine and norfluoxetine concentrations were observed in children than in adolescents. These differences were almost entirely explained by differences in weight.
• Separate dosing recommendations in lower weight children

3/12/02 (1/13/03)

• 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

• Safety information in pediatric patients 6 to 12 months of age
• A dose dependent effect on growth was observed in the 12-week trial which supports the finding that the use of Pulmicort Respules in infants 6 to 12 months of age may result in systemic effects and is consistent with the findings of growth suppression in other studies with inhaled corticosteroids
• Pneumonia was observed more frequently in patients treated with Pulmicort Respules than in patients treated with placebo

• Temozolomide effectiveness in children has not been demonstrated
• New data from 2 open-label Phase 2 studies in pediatric patients 3-18 years of age. In one study there were 29 patients with recurrent brain stem glioma and 34 patients with recurrent high grade astrocyoma.  In a second study there were 122 patients enrolled with various types of tumors; 113 CNS tumors and 9 non-CNS tumors
• The temozolomide toxicity profile in children is similar to adults

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

Ditropan XL

Safety and effectiveness established down to 6 years of age

• 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 Ointment

• 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

• 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%)

• 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

• Labeling for 6-16 years of age

• Not recommended for pediatric patients with glomerular filtration rate < 30ml/min/1.73m²

• Information on dose, efficacy 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

• Labeling for 6-16 years of age

• Not recommended for pediatric patients less than 6 years or with glomerular filtration rate < 30mL/min/1.73m²

• Information on dose, efficacy 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

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

8/6/03 (12/2/03)

 also see prior approval at  #8

• Safety and efficacy for treatment of malaria established down to5 kg. 

• Attributable AE occurring in ≥ 5% of the pediatric patients (≤ 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.

9/12/03 (12/12/03)

Obesity management

• Use in 12-16 year olds is supported by studies in adults with additional data from a 54 week safety and efficacy study in obese adolescent patients

• Since orlistat can reduce absorption of fat soluble vitamins, all patients should take a daily multivitamin supplement containing fat soluble vitamins

• Adverse event profile in adolescent patients was similar to that seen in adults

11/27/01 (1/8/04)

• Information on dose, PK in pediatric  patients 6-17 years of age

• Adverse event profile in pediatric patients was similar to that seen in adults

7/2/03 (3/2/04)

• 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

11/10/03 (3/5/04)

• 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

3/15/00 (3/9/04)

• Safety and efficacy for the maintenance of anesthesia established from birth to 1 year of age
• Recommended dosing guidelines for maintenance of anesthesia for patients from birth to 2 months
• The clearance rate observed in neonates was highly variable � approximately 2 times higher than young healthy adults 
• Individual doses for each patient should be carefully titrated

3/20/02 (3/11/04)

Hypertension

• 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

10/8/03 (3/15/04)

• 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

9/4/03 (3/19/04)

•  Safety and effectiveness established in patients 2 � 13 years of age
• New twice daily dosing regimen and modified three times daily dosing for pediatric patients >2 years
• A reliably effective dose not established in patients <2 years of age
• PK information in pediatric patients from birth to 13 years of age
• Highly variable drug exposure is a significant problem in pediatric patients
• Adverse event profile was similar to that for adults

12/18/03 (3/25/04)

• 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

12/8/03 (3/31/04)

• Safety and effectiveness were examined in a 12 week randomized, double-blind, placebo-controlled study of 29 pediatric patients aged 5-19 years old with end stage renal disease on hemodialysis
• Primary efficacy analysis revealed 9 of 15 patients in Zemplar group had 2 consecutive 30 % decreases from baseline intact PTH compared with 3 of 14 patients in placebo group
• No patients in either group developed hypercalcemia (defined as at least one  calcium value >11.2 mg/dL) during study

1/5/04 (4/15/04)

Reduction in intraocular pressure

• Safety and IOP-lowering effects have been demonstrated in pediatric patients

• Adverse event profile was comparable  to that seen in adults

1/5/04 (4/17/04)

Tolterodine - Detrol LA                  (Pfizer) 
Label [PDF ]

• 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

12/2/02 (5/5/04)

Venlafaxine - Effexor and Effexor XR  (Wyeth)

• Effectiveness in pediatric patients  has not been established

• FDA requested that a warning be added in the labeling for Celexa, Effexor, Lexapro, Luvox, Paxil, Prozac, Remeron, Serzone, Wellbutrin, and Zoloft to encourage close observation of adult and pediatric patients treated with these agents for worsening depression or the emergence of suicidality based on data resulting from pediatric clinical trials of  various antidepressants

• Patients with major depressive disorder, both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior.  Patients being treated with antidepressants should be observed closely for clinical worsening and suicidality, especially at the beginning of a course of drug therapy, or at the time of dose changes, either increases or decreases

• 18% of Effexor XR treated patients (6-17 years) verses 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

3/10/04 (6/24/04)

Irinotecan-Camptosar      (Pfizer)
Label [PDF ]

• 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%)

3/22/04 (6/24/04)

Oseltamivir - Tamiflu  (Roche)
Label [PDF ]

Treatment of uncomplicated acute illness due to influenza infection in patients 1 year and older

• Safety and efficacy in pediatric patients less than 1 year of age have not been studied

• Not recommended in pediatric patients less than 1 year of age because of uncertainties regarding the rate of development of the human blood-brain barrier and the unknown clinical significance of animal toxicology data for human infants