PMID- 33415500
OWN - NLM
STAT- MEDLINE
DCOM- 20211115
LR  - 20220531
IS  - 1432-1041 (Electronic)
IS  - 0031-6970 (Print)
IS  - 0031-6970 (Linking)
VI  - 77
IP  - 6
DP  - 2021 Jun
TI  - Safety and efficacy of tolcapone in Parkinson's disease: systematic review.
PG  - 817-829
LID - 10.1007/s00228-020-03081-x [doi]
AB  - PURPOSE: Tolcapone is an efficacious catechol-O-methyltransferase inhibitor for 
      Parkinson's disease (PD). However, safety issues hampered its use in clinical 
      practice. We aimed to provide evidence of safety and efficacy of tolcapone by a 
      systematic literature review to support clinicians' choices in the use of an 
      enlarging PD therapeutic armamentarium. METHODS: We searched PubMed for studies 
      on PD patients treated with tolcapone, documenting the following outcomes: liver 
      enzyme, adverse events (AEs), daily Off-time, levodopa daily dose, unified 
      Parkinson's disease rating scale (UPDRS) part-III, quality of life (QoL), and 
      non-motor symptoms. FAERS and EudraVigilance databases for suspected AEs were 
      interrogated for potential additional cases of hepatotoxicity. RESULTS: 
      Thirty-two studies were included, for a total of 4780 patients treated with 
      tolcapone. Pertaining safety, 0.9% of patients showed liver enzyme elevation > 2. 
      Over 23 years, we found 7 cases of severe liver injury related to tolcapone, 3 of 
      which were fatal. All fatal cases did not follow the guidelines for liver 
      function monitoring. FAERS and EudraVigilance database search yielded 61 reports 
      of suspected liver AEs possibly related to tolcapone. Pertaining efficacy, the 
      median reduction of hours/day spent in Off was 2.1 (range 1-3.2), of levodopa was 
      108.9 mg (1-251.5), of "On" UPDRS-III was 3.6 points (1.1-6.5). Most studies 
      reported a significant improvement of QoL and non-motor symptoms. CONCLUSION: 
      Literature data showed the absence of relevant safety concerns of tolcapone when 
      strict adherence to hepatic function monitoring is respected. Given its high 
      efficacy on motor fluctuations, tolcapone is probably an underutilized tool in 
      the therapeutic PD armamentarium.
FAU - Artusi, Carlo Alberto
AU  - Artusi CA
AUID- ORCID: 0000-0001-8579-3772
AD  - Department of Neuroscience "Rita Levi Montalcini", University of Torino, Via 
      Cherasco 15, 10126, Torino, Italy. caartusi@gmail.com.
FAU - Sarro, Lidia
AU  - Sarro L
AD  - Department of Neurology, Martini Hospital, ASL Citta di Torino, Torino, Italy.
FAU - Imbalzano, Gabriele
AU  - Imbalzano G
AD  - Department of Neuroscience "Rita Levi Montalcini", University of Torino, Via 
      Cherasco 15, 10126, Torino, Italy.
FAU - Fabbri, Margherita
AU  - Fabbri M
AD  - Department of Neurosciences, Clinical Investigation Center CIC 1436, Parkinson 
      Toulouse Expert Center, NS-Park/FCRIN Network and NeuroToul COEN Center, Toulouse 
      University Hospital; INSERM; University of Toulouse 3, Toulouse, France.
FAU - Lopiano, Leonardo
AU  - Lopiano L
AD  - Department of Neuroscience "Rita Levi Montalcini", University of Torino, Via 
      Cherasco 15, 10126, Torino, Italy.
LA  - eng
PT  - Journal Article
PT  - Systematic Review
DEP - 20210107
PL  - Germany
TA  - Eur J Clin Pharmacol
JT  - European journal of clinical pharmacology
JID - 1256165
RN  - 0 (Antiparkinson Agents)
RN  - 0 (Catechol O-Methyltransferase Inhibitors)
RN  - 46627O600J (Levodopa)
RN  - CIF6334OLY (Tolcapone)
SB  - IM
MH  - Antiparkinson Agents/adverse effects/*therapeutic use
MH  - Catechol O-Methyltransferase Inhibitors/adverse effects/*therapeutic use
MH  - Chemical and Drug Induced Liver Injury/epidemiology
MH  - Humans
MH  - Levodopa/administration & dosage
MH  - Liver Function Tests
MH  - Parkinson Disease/*drug therapy
MH  - Quality of Life
MH  - Randomized Controlled Trials as Topic
MH  - Severity of Illness Index
MH  - Tolcapone/adverse effects/*therapeutic use
PMC - PMC8128808
OTO - NOTNLM
OT  - Catechol-O-methyltransferase
OT  - Efficacy
OT  - Liver
OT  - Parkinson's disease
OT  - Safety
OT  - Tolcapone
COIS- Dr. Artusi received travel grants from Zambon and Abbvie, and educational grants 
      from Ralpharma and Neuraxpharm. Dr. Sarro reports no financial disclosures. Dr. 
      Imbalzano reports no financial disclosures. Dr. Fabbri received speaker honoraria 
      from Abbvie. Prof. Lopiano received honoraria for lecturing and travel grants 
      from, UCB Pharma, AbbVie, DOC, Zambon and Bial.
EDAT- 2021/01/09 06:00
MHDA- 2021/11/16 06:00
PMCR- 2021/01/07
CRDT- 2021/01/08 06:15
PHST- 2020/08/18 00:00 [received]
PHST- 2020/12/28 00:00 [accepted]
PHST- 2021/01/09 06:00 [pubmed]
PHST- 2021/11/16 06:00 [medline]
PHST- 2021/01/08 06:15 [entrez]
PHST- 2021/01/07 00:00 [pmc-release]
AID - 10.1007/s00228-020-03081-x [pii]
AID - 3081 [pii]
AID - 10.1007/s00228-020-03081-x [doi]
PST - ppublish
SO  - Eur J Clin Pharmacol. 2021 Jun;77(6):817-829. doi: 10.1007/s00228-020-03081-x. 
      Epub 2021 Jan 7.