Safety Comparative Study on Azithromycin Oral and IV Dosage Form in Pediatric Respiratory Infection Therapy
X Li, X Jielai
adverse event, azithromycin, children, intravenous, oral
X Li, X Jielai. Safety Comparative Study on Azithromycin Oral and IV Dosage Form in Pediatric Respiratory Infection Therapy. The Internet Journal of Pediatrics and Neonatology. 2007 Volume 8 Number 2.
Azithromycin is widely used for treatment in various of pediatric respiratory infections and there is no any strict requirement for selection of oral or intravenous (IV) dosage form. There is few comparative data in respective of safety between these two dosage forms. The purpose of this study was to review safety data between oral and IV for the treatment under 16-year-old children and intend to give pediatricians reference in the two dosage forms of azithromycin. This paper has reviewed adverse events ( AEs) data which include 3960 cases of children in 79 published paper for treatment in respiratory infection. There are 1628 cases in oral group,2302 cases in IV group and 30 AE individuals case reports (IV). The study result shows that the AE incidence is 14.12% in IV group and 9.28% in the oral group. It is significant different between the two groups (u=4.699, P<0.0005). In conclusion, Azithromycin oral dosage form resulted in better tolerance in children than that of IV, suggest pediatricians to prescribe oral dosage form as first line therapy.
Material and methods
All data came from the Wanfang Data-base and Weipu Data-base. The publishing date of literature used is from Jan.1 1997 to Dec. 1 2007. Meanwhile, we traced every reference literature. The index keyword included children, azithromycin, intravenous and oral administration.
Inclusion and exclusion criteria
It is concomitantly demanded to meet next conditions:
Patients under16 years old;
Children are confirmed respiratory infection;
IV group children are treated only by azithromycin IV administration and oral group children are treated only by azithromycin oral dosage form;
Classified recording of AE in details.
If the case has any following AE before administration of azthiromycin should be excluded:
Combination therapy with any other drug will be excluded.
There are 79 paper have been collected in this review which include 22 paper[1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22] for oral administration ,42 paper[2,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63] for IV administration and 16 individual case report[64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79] for IV. Detailed see table 1.
Refer to azithromycin oral and IV administration paper, the total number of children who have been used azithromycin oral and IV administration, the total number of children who have AE experience and total number for each kind of AE respectively were extracted from the qualified screening paper.
Calculate the incidence of AE. The difference between oral group and IV group in AE incidence is tested through U test. All data will be processed using SAS 8.2 statistics software.
The total number of AE reported and incidence in azithromycin oral and IV group see table 2: the incidence of AE is 9.28% (151/1628) in oral group. The most common AE are gastrointestinal (GI) (122 cases), rash (20 cases), liver enzyme (ALT) increasing (5 cases) and headache (3 cases). The rate of AE is 14.12% (325/2302) in IV group which include rash (22 cases), wheal (3 cases), Injected site pain (16 cases), Phlebitis (4 cases), ALT elevated (13 cases). The incidence of AE between oral and IV groups were examined through u test (u=4.699, P<0.0005), it can be determined that it is different between the two groups in AE incidence, and AE incidence of IV group is higher than that of oral group.
Azithromycin is the most widely used macrolide antibiotics for treatment of pediatric respiratory infections caused by common pathogens such as
From the detailed individual AE reports of IV administration, we found that there are 1 dead case of anaphylaxis and 3 allergic shock cases[71,72,73] happened. The results suggest that it should pay attention to allergic shock at the beginning of azithromycin IV administration. All 16 liver enzyme (ALT) elevated cases[64,65] have a long therapy experience from 4 to 12 continue days. The result suggest that it should be paid attention to the liver functions damage risk after 3 days duration therapy because azithromycin is eliminated through liver and an elimination half-life is 65.2 hours in 0.5 to 16 years old children and children's liver functions are premature in necessary enzymes synthesis. Contrast to IV dosage form, oral dosage form has not been found the report of dead of anaphylaxis or allergic shock yet. It is only found ALT minor reversible increasing, lower AE rate and safer than IV dosage form. So, we suggest pediatrician to prescribe azithromycin oral dosage form as priority choice in under-16-years-old children respiratory infection treatment.
Because we only reviewed the clinical observation data, it is possible that there are some shortages in this paper. First, the AE diagnosis criteria are different. Secondly, collected literatures sample can not represent the whole situation of China children. Last, lack of detailed information of every AE case and AE happened history and so on has hindered us to accurately analyze these data.