A prospective survey on safety of sustained-release theophylline in treatment of asthma and COPD.
BACKGROUND
Theophylline is a useful drug for the treatment of asthma. The Asthma Prevention and Management Guidelines (JGL) recommend use of sustained-release theophylline products as controllers and of injectable aminophylline products as relievers. The Global Initiative for Asthma: Global Strategy for Asthma Management and Prevention, the NHLB/WHP Workshop Report 1995 (GINA, 1995) and guidelines in Western countries recommend sustained-release theophylline, but not as positively as in the JGL. The aim of this survey was to determine the occurrence of serious adverse reactions.


METHODS
The survey was conducted in 66 institutions staffed by physicians certified by the Japanese Society of Allergology (JSA). The target diseases were asthma and COPD including chronic bronchitis and pulmonary emphysema, which are indications for use of sustained-release theophylline products in Japan.


RESULTS
3,921 patients were included in the safety evaluation. No serious adverse reactions were observed among the patients in this survey, although 54 patients (1.38%) exhibited non-serious adverse reactions. The incidence of adverse reactions was found to be high in patients who had begun use of sustained-release theophylline products at the time of registration in this survey, and in patients who were concomitantly taking macrolide antibiotics.


CONCLUSIONS
The present survey demonstrates that sustained-release theophylline is safe, as long as used appropriately, although adverse reactions tend to develop early after initiation of administration.
Makino
Sohei
S
Internal Medicine, Jobu Hospital for Respiratory Disease, Maebashi, Gunma, Japan. s-makino@dokkyomed.ac.jp
Adachi
Mitsuru
M
Ohta
Ken
K
Kihara
Norio
N
Nakajima
Sigenori
S
Nishima
Sankei
S
Fukuda
Takeshi
T
Miyamoto
Terumasa
T
D000293:Adolescent; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy*; D001991:Bronchitis / Q000188:drug therapy; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000139:chemically induced; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D002908:Chronic Disease; D003625:Data Collection; D003692:Delayed-Action Preparations; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D033461:Hyperuricemia / Q000139:chemically induced; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000139:chemically induced; D011358:Product Surveillance, Postmarketing; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D011656:Pulmonary Emphysema / Q000188:drug therapy; D013806:Theophylline / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use
D018927:Anti-Asthmatic Agents; D001993:Bronchodilator Agents; D003692:Delayed-Action Preparations; D013806:Theophylline