Korean J Clin Pharm.  2016 Jun;26(2):172-180. 10.0000/kjcp.2016.26.2.172.

A Systematic Review on Drug Safety for Molsidomine, Nicorandil and Trimetazidine

• Jeong KH
• Lee E

• KMID: 2358069
• DOI: http://doi.org/10.0000/kjcp.2016.26.2.172

Abstract

BACKGROUND
Ischemic heart disease is the most common type of heart disease and an important cause of death in Korea. Among marketed anti-anginal medications, molsidomine, nicorandil, and trimetazidine are approved in Korea with unique mechanism of actions. As these drugs are not approved by the US Food and Drug Administration, the access to the up-to-dated and comprehensive safety-related information has been less than optimal from drug information resources used by Korean pharmacists.
METHODS
A systematic review was conducted using Embase and Korean manuscripts to compile safety updates for these medications. Out of 418 articles from keyword searches, 52 studies were reviewed in full to compare adverse effects (AEs) with the approved package inserts (PI).
RESULTS
Molsidomine related adverse effects were mostly mild or moderate, but anxiety, palpitation, epigastric pain, and sexual potency reduction were additional AEs found from the review not listed in PI. Although PI has included ulceration in oral cavity and gastrointestinal tracts including anus by nicorandil, the Korea FDA recently recommended adding corneal, genital, and skin ulcers to the approved PI. Trimetazidine induced Parkinsonism, worsening of the symptoms for patients diagnosed with Parkinson's disease, gastrointestinal burning, and muscle cramps were additionally identified AEs not listed in PI for trimetazidine.
CONCLUSION
Continuous evaluations of the safety profile of these agents are needed to balance the risks and benefits to provide evidence-based safety counseling to the patients. In addition, more focused efforts on spontaneous reporting are warranted by healthcare professionals to safeguard patients against AEs.

Keyword

Molsidomine; nicorandil; trimetazidine; safety; adverse effects

MeSH Terms

Anal Canal
Anxiety
Burns
Cause of Death
Counseling
Delivery of Health Care
Gastrointestinal Tract
Heart Diseases
Humans
Korea
Molsidomine*
Mouth
Muscle Cramp
Myocardial Ischemia
Nicorandil*
Parkinson Disease
Parkinsonian Disorders
Pharmacists
Product Labeling
Risk Assessment
Skin Ulcer
Trimetazidine*
Ulcer
United States Food and Drug Administration
Molsidomine
Nicorandil
Trimetazidine