Moxifloxacin Hydrochloride (Page 8 of 14)

8.4 Pediatric Use

Effectiveness in pediatric patients and adolescents less than 18 years of age has not been established. Moxifloxacin Tablets cause arthropathy in juvenile animals. Limited information on the safety of moxifloxacin in 301 pediatric patients is available from the cIAI trial [see Boxed Warning, Warnings and Precautions (5.11) and Nonclinical Toxicology (13.2)].

Active Controlled Trial in Complicated Intra-Abdominal Infection (cIAI)

The safety and efficacy of Moxifloxacin Tablets in pediatric patients for the treatment of cIAI has not been demonstrated.

Pediatric patients 3 months to <18 years of age (mean age of 12 ± 4 years) were enrolled in a single randomized, double-blind, active controlled trial in cIAI including appendicitis with perforation, abscesses and peritonitis.

Pediatric patients were randomized (2:1) to receive either moxifloxacin or comparator. This study enrolled 451 patients who received study medication, 301 treated with moxifloxacin, and 150 with comparator. Of the 301 pediatric patients treated with moxifloxacin, 15 were below the age of 6 years and 286 were between the ages of 6-<18 years.

Patients received sequential intravenous/oral moxifloxacin or comparator (intravenous ertapenem followed by oral amoxicillin/clavulanate) for 5 to 14 days (mean duration was 9 days with a range of 1 to 24 days).

The overall adverse reaction profile in pediatric patients was comparable to that of adult patients. The most frequently occurring adverse reactions in pediatric patients treated with moxifloxacin were QT prolongation 9.3% (28/301), vomiting 6.6% (20/301) diarrhea 3.7% (11/301), arthralgia 3.0% (9/301), and phlebitis 2.7% (8/301) (see Table 5). Discontinuation of study drug due to an adverse reaction was reported in 5.3% (16/301) of moxifloxacin-treated patients versus 1.3% (2/150) of comparator-treated patients. The adverse reaction profile of moxifloxacin or comparator was similar across all age groups studied.

Musculoskeletal adverse reactions were monitored and followed up to 5 years after the end of study treatment. The rates of musculoskeletal adverse reactions were 4.3% (13/301) in the moxifloxacin-treated group versus 3.3% (5/150) in the comparator-treated group. The majority of musculoskeletal adverse reactions were reported between 12 and 53 weeks after start of study treatment with complete resolution at the end of the study [see Warnings and Precautions (5.11) and Nonclinical Toxicology (13.2)] .

Table 5: Incidence (%) of Selected Adverse Reactions in ≥2.0% of Pediatric Patients Treated with Moxifloxacin in cIAI Clinical Trial

System Organ Class	Adverse Reactions	Moxifloxacin N=301 (%)	Comparator N=150 (%)
Gastrointestinal disorders	Abdominal pain	8 (2.7)	3 (2.0)
	Diarrhea	11 (3.7)	1 (0.7)
	Vomiting	20 (6.6)	12 (8.0)
General disorders and administration site conditions	Pyrexia	6 (2.0)	4 (2.7)
Investigations	Aspartate aminotransferase increased	2 (0.7)	3 (2.0)
	Electrocardiogram QT prolonged	28 (9.3)	4 (2.7)
Musculoskeletal and connective tissue disorders	Arthralgia	9 (3.0)	2 (1.3)
Nervous system disorders	Headache	6 (2.0)	2 (1.3)
Vascular disorders	Phlebitis	8 (2.7)	0 (0)

Clinical response was assessed at the test-of-cure visit (28 to 42 days after end of treatment). The clinical response rates observed in the modified intent to treat population were 83.9% (208/248) for moxifloxacin and 95.5% (127/133) for comparator; see Table 6.

Table 6: Clinical Response Rates at 28-42 Days After End of Treatment in Pediatric Patients with cIAI

* Difference in clinical cure rates (moxifloxacin -comparator) and 95% confidence intervals, presented as percentages, are based on stratified analysis by age group using Mantel-Haenszel methods. † The modified intent-to-treat (mITT) population is defined as all subjects who were treated with at least one dose of study medication and who have at least one pre-treatment causative organism from the intra-abdominal site of infection or from blood cultures.
	Moxifloxacin n (%)	Comparator n (%)	Difference *(95% CI)
mITT Population †	N=248	N=133
Cure	208 (83.9)	127 (95.5)	-12.2 (-17.9, -6.4)
Failure	17 (6.9)	3 (2.3)
Indeterminate	21 (8.5)	3 (2.3)
Missing	2 (0.8)	0