Adverse events to Houttuynia injection: A systematic review

To systematically assess the main clinical features of Houttuynia injection-associated adverse drug reactions (ADRs), as described in published reports, and to contribute to the post-marketing re-evaluation and clinical practices of Houttuynia injection.

We searched the electronic databases- PubMed, EMBASE, the Chinese National Knowledge Infrastructure (CNKI), the Chinese Science and Technology Journal Full-text Database (VIP) and the Chinese Biomedical Disc (CBMdisc), for articles published through June 2010. We then extracted and analyzed the data.

A total of 645 articles were included, with a total of 1232 ADR cases reported. Respiratory diseases accounted for 52.44% of all cases of Houttuynia injection ADRs, followed by reproductive system diseases (4.30%) and urinary system diseases (3.73%). Multiple systems or organs were involved in the ADRs, the top five were: respiratory system (37.42%), skin (34.66%), digestive system (25.49%), circulatory system (25.41%), and nervous system (23.96%). Serious systemic adverse reactions accounted for 22.56% of total ADRs. Of the reported 1,232 ADR cases, 286 ADR cases reported previous allergies in detail; allergy to penicillin accounted for 15.03% of the total cases with the allergic history, followed by unknown drugs (8.05%), and sulfonamides (3.15%). Among the ADR cases, Houttuynia injection was commonly used together with cephalosporins, penicillins, and macrolides. Macrolides combined with Houttuynia injection showed higher ADR risk than Houttuynia injection used alone (RR = 8.80, 95% CI 6.12 to 12.65, P < 0.0001). The ADR risk for intravenous injection of Houttuynia injection was higher than that of intramuscular injection (OR = 6.86, 95% CI 1.88 to 56.95, P= 0.0016). We used the WHO ADR Classification Criteria to divide the ADR cases into four grades. There were 22.56%, 36.28%, 16.48%, and 24.68% cases of Grade I, II, III, and IV, respectively. Anaphylactic shock accounted for 58.99% of the most serious ADRs (Grade I). All cases of death were caused by allergic shock, except one, who died of multiple organ failure caused by anaphylactic purpura. The fastest-onset three ADR cases occurred in one minute after injection.

The respiratory system was the most common system treated in Houttuynia injection ADR cases. It was also the most common site of ADR symptoms. The ADRs of Houttuynia injection were serious. The precautions should be taken to prevent the anaphylactic shock. Intravenous injection and the combination with with cephalosporins, penicillins, and macrolides increased the ADR risk of Houttuynia injection.