Integrated FAERS and JADER Databases

The US Food and Drug Administration (FDA) adverse event reporting system (FAERS) is an SRS and the largest and best-known database worldwide. The regulatory authority in Japan, the Pharmaceuticals and Medical Devices Agency (PMDA), controls the SRS of the JADER database. Adverse events recorded in the FAERS database from January 2004 to June 2014 were downloaded from the FDA website (http://www.fda.gov). Relevant information from the JADER database from April 2004 to November 2016 was downloaded from the PMDA website (http://www.pmda.go.jp). We constructed a database that integrated each FAERS and JADER dataset using the FileMaker Pro 13 (FileMaker Inc.). For duplicate entries, we followed the FDA recommendation (http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Surveillance/AdverseDrugEffects), and adopted the most recent case number to identify duplicate patient reports and excluded them from the analysis.
We analyzed four immunosuppressants (CsA, everolimus, sirolimus, and mycophenolate mofetil), four calcium channel blockers (amlodipine, benidipine, nicardipine and nifedipine), and 11 anticonvulsants (carbamazepine, clobazam, diazepam, gabapentin, levetiracetam, phenobarbital, phenytoin, primidone, topiramate, valproic acid, and zonisamide). For drug definitions, we used both the general and brand names based on the DrugBank 3.0 and 4.0 (Table 1). Drugs in the FAERS were classified into four categories: Primary Suspect drug (PS), Secondary Suspect drug (SS), Concomitant (C), and Interacting (I); according to their anticipated degree of involvement in adverse events. The analysis was restricted to reports where drugs were recorded as PS and SS in the FAERS database. In the “drug information” table of the JADER database, each drug was assigned a code according to its association with adverse drug reactions: “suspected drug,” “concomitant drug,” or “interacting drug.” The analysis was restricted to reports where drugs were recorded as “suspected drugs” in the JADER database.Table 1

Brand names of drugs

Generic namea	Number of brand name	Brand name
Immunosuppressants
Cyclosporine	6	Gengraf, Neoral, etc.
Everolimus	1	Certican
Sirolimus	1	Rapamune
Mycophenolate mofetil	2	Cellcept, Mucoloc
Calcium Channel Blockers
Amlodipine	7	Amlocard, Amlodis, etc.
Benidipineb	-	-
Nicardipine	3	Cardene, Cardene IV, etc.
Nifedipine	106	Adalat, Adalat 10, etc.
Anticonvulsants
Carbamazepine	29	Apo-Carbamazepine, Atretol, etc.
Clobazam	6	Chlorepin, Clorepin, etc.
Diazepam	116	Alboral, Aliseum, etc.
Gabapentin	3	Aclonium, Neurontin, etc.
Levetiracetam	1	Keppra
Phenobarbital	138	Adonal, Aephenal, etc.
Phenytoin	130	Aleviatin, Antisacer, etc.
Primidone	36	Apo-Primidone, Cyral, etc.
Topiramate	2	Topamax, Topamax Sprinkle, etc.
Valproic acid	25	Alti-Valproic, Avugane, etc.
Zonisamide	4	Excegran, Exegram, etc.

^a Generic name and brand name were used in this analysis ^b Benidipine exists only generic name