PMID- 33821768
OWN - NLM
STAT- MEDLINE
DCOM- 20210622
LR  - 20220423
IS  - 1941-9260 (Electronic)
IS  - 0032-5481 (Linking)
VI  - 133
IP  - 5
DP  - 2021 Jun
TI  - Safety and tolerability of fixed-dose combinations of ibuprofen and 
      acetaminophen: pooled analysis of phase 1-3 clinical trials.
PG  - 565-571
LID - 10.1080/00325481.2021.1912466 [doi]
AB  - OBJECTIVES: An ibuprofen (IBU)/acetaminophen (APAP) fixed-dose combination (FDC) 
      for over-the-counter (OTC) use was developed with the goal of providing the same 
      effective analgesic activity as full doses of the individual monocomponents, 
      while reducing individual monocomponent drug exposures. Here, the safety and 
      tolerability of the FDC is characterized using pooled safety data from phase 1-3 
      clinical trials in the FDC development program. METHODS: We conducted a pooled 
      safety analysis of data from 7 clinical trials: three phase 1 pharmacokinetic 
      trials, a phase 2 proof-of-concept trial, and three phase 3 trials (a single- and 
      a multiple-dose trial in a dental pain model and a single-dose trial in an 
      induced-fever model). Safety and tolerability of the FDC were assessed by adverse 
      events (AEs) for the total group and subgroups (age, sex, race). RESULTS: A total 
      of 1,477 participants were enrolled in the 7 trials; 715 were treated with FDC 
      IBU/APAP, 432 with IBU monotherapy, 330 with APAP monotherapy, and 156 with 
      placebo. Most subjects were white (86.5%), and 44% were female. Two trials 
      enrolling 195 adolescents accounted for 13.2% of the overall study population. 
      All-causality treatment-emergent AEs (TEAEs) occurred in 19.7% of the 1477 
      participants. Nausea (13.5%), vomiting (7.4%), dizziness (4.5%), headache (1.2%), 
      and feeling hot (1.0%) were the only TEAEs reported in >/=1% of subjects. 
      Treatment-related AEs occurred in 1.8% of the subjects in the overall population. 
      The incidence of AEs, including treatment-related AEs, was consistently lower in 
      all active treatment groups than in the placebo group; this also applied to 
      subgroups according to sex, race, and age, including adolescents aged 
      12-17 years. The higher rate of AEs with placebo was likely due to lack of 
      pain/fever control. CONCLUSION: Single-dose or short-course FDC IBU/APAP OTC use 
      was well tolerated, with an AE profile similar to its IBU and APAP 
      monocomponents. CLINICALTRIALS.GOV REGISTRATION: NCT01559259; NCT02912650; 
      NCT02837952; NCT02761980. The pharmacokinetic studies (n = 3) did not require 
      registration.
FAU - Su, Jiangfeng
AU  - Su J
AD  - Pfizer Consumer Healthcare, Pfizer Inc., Collegeville, PA, USA.
FAU - Leyva, Rina
AU  - Leyva R
AUID- ORCID: 0000-0001-8537-9731
AD  - Pfizer Consumer Healthcare, Pfizer Inc., Madison, NJ, USA.
FAU - Kellstein, David
AU  - Kellstein D
AD  - Pfizer Consumer Healthcare, Pfizer Inc., Madison, NJ, USA.
FAU - Cruz-Rivera, Mario
AU  - Cruz-Rivera M
AD  - Pfizer Consumer Healthcare, Pfizer Inc., Madison, NJ, USA.
FAU - Meeves, Suzanne
AU  - Meeves S
AD  - Pfizer Consumer Healthcare, Pfizer Inc., Madison, NJ, USA.
LA  - eng
PT  - Journal Article
DEP - 20210426
PL  - England
TA  - Postgrad Med
JT  - Postgraduate medicine
JID - 0401147
RN  - 0 (Analgesics, Non-Narcotic)
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 362O9ITL9D (Acetaminophen)
RN  - WK2XYI10QM (Ibuprofen)
SB  - IM
MH  - Acetaminophen/*administration & dosage
MH  - Adult
MH  - Analgesics, Non-Narcotic/administration & dosage
MH  - Anti-Inflammatory Agents, Non-Steroidal
MH  - Clinical Trials, Phase I as Topic/*methods
MH  - Clinical Trials, Phase II as Topic/*methods
MH  - Clinical Trials, Phase III as Topic/*methods
MH  - Disorders of Excessive Somnolence
MH  - Drug Therapy, Combination
MH  - *Drug Tolerance
MH  - Female
MH  - Humans
MH  - Ibuprofen/*administration & dosage
MH  - Male
MH  - Randomized Controlled Trials as Topic/*methods
MH  - Young Adult
OTO - NOTNLM
OT  - Acetaminophen
OT  - analgesia
OT  - fixed-dose combination
OT  - ibuprofen
OT  - safety
EDAT- 2021/04/07 06:00
MHDA- 2021/06/23 06:00
CRDT- 2021/04/06 12:22
PHST- 2021/04/07 06:00 [pubmed]
PHST- 2021/06/23 06:00 [medline]
PHST- 2021/04/06 12:22 [entrez]
AID - 10.1080/00325481.2021.1912466 [doi]
PST - ppublish
SO  - Postgrad Med. 2021 Jun;133(5):565-571. doi: 10.1080/00325481.2021.1912466. Epub 
      2021 Apr 26.