Safety profile of meropenem: an updated review of over 6,000 patients treated with meropenem.
Meropenem is a broad-spectrum carbapenem antibacterial with potent antimicrobial activity against a broad range of Gram-negative, Gram-positive and anaerobic bacteria. The second parenteral carbapenem to be introduced worldwide, meropenem has been in clinical use since 1994. Two previous safety reviews have established that meropenem has a favourable and acceptable safety profile. This new review was conducted after the approval of meropenem in the US in 2005 for the treatment of patients with complicated skin and skin-structure infections, in addition to the previously approved indications of intra-abdominal infections and paediatric bacterial meningitis. The analysis includes the clinical trial data from the previous safety reviews, updated with expanded experience across a number of serious bacterial infections, including a large international study in patients with skin or skin-structure infections and further experience in patients with intra-abdominal infections and bacterial meningitis. A total of 6154 patients with 6308 meropenem exposures were compared with 4483 patients treated with comparator agents (4593 exposures), and the paediatric population base for which safety data are available has doubled to over 1000 patients. The data presented reinforce the favourable safety profile of meropenem. In general, the incidence and pattern of adverse events occurring with meropenem were similar to those of the first carbapenem, imipenem/cilastatin, and to those of the cephalosporin- and clindamycin-based regimens to which it had been compared. The most common adverse events reported for meropenem were diarrhoea (2.5%), rash (1.4%) and nausea/vomiting (1.2%). No adverse event occurred in more than 3% of patient exposures to meropenem, indicating a low overall frequency of adverse events as well as excellent gastrointestinal tolerability. Furthermore, no unexpected adverse events were identified, and the very low incidence of seizures in patients with meningitis was not considered to be drug related. In infections other than meningitis, the incidence of seizures considered by investigators to be related to meropenem treatment was 0.07%. In the new studies that updated the earlier safety data, no new cases of drug-related seizure were reported for any treatment or patient group (meningitis/non-meningitis infections). In conclusion, meropenem is well tolerated and has good CNS and gastrointestinal tolerability when used for the treatment of serious bacterial infections in a wide range of adult and paediatric patient populations.
Linden
Peter
P
University of Pittsburgh Medical Center, Pittsburgh, PA 15261, USA. lindenpk@ccm.upmc.edu
D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001424:Bacterial Infections / Q000188:drug therapy; D002986:Clinical Trials as Topic; D006801:Humans; D000077731:Meropenem; D013845:Thienamycins / Q000009:adverse effects* / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D013845:Thienamycins; D000077731:Meropenem
Pediatr Infect Dis J. 1999 Jul;18(7):581-90
10440432
J Child Neurol. 2005 May;20(5):456-7
15968935
J Antimicrob Chemother. 2003 Jun;51(6):1339-50
12746372
Scand J Infect Dis. 1999;31(1):3-10
10381210
Clin Microbiol Infect. 2000 Jun;6(6):294-302
11168137
Scand J Infect Dis Suppl. 1987;52:65-78
3331044
J Antimicrob Chemother. 1998 Oct;42(4):563-4
9818768
J Antimicrob Chemother. 1986 Dec;18 Suppl E:193-202
3469194
Diagn Microbiol Infect Dis. 2005 Dec;53(4):247-56
16360548
Drugs. 2003;63(17):1855-78
12921489
Am J Med. 1988 May;84(5):911-8
3284342
J Antimicrob Chemother. 2001 Jan;47(1):43-50
11152430
Diagn Microbiol Infect Dis. 2005 Dec;53(4):257-64
16360549
Drugs. 1996 Jan;51(1):99-136
8741235
Int J Antimicrob Agents. 1998 May;10(2):107-17
9716287
Surg Infect (Larchmt). 2005 Fall;6(3):269-82
16201937
Pharmacotherapy. 2007 Jan;27(1):137-42
17192167
Antimicrob Agents Chemother. 2006 Oct;50(10):3473-5
17005836
Antimicrob Agents Chemother. 2002 Nov;46(11):3506-11
12384357
Clin Ther. 2006 Aug;28(8):1164-74
16982293
Curr Med Res Opin. 2005 May;21(5):785-94
15969878
Rev Infect Dis. 1985 Jul-Aug;7 Suppl 3:S528-36
3901217
Clin Infect Dis. 2005 Jun 1;40(11):1586-90
15889354
Ann Pharmacother. 2005 Mar;39(3):533-7
15701769
Diagn Microbiol Infect Dis. 2007 Feb;57(2):207-15
16949243
Drugs. 2000 Mar;59(3):653-80
10776838
J Microbiol Immunol Infect. 2001 Dec;34(4):275-80
11825008
Pediatr Infect Dis J. 2001 Jan;20(1):19-24
11176562
Diagn Microbiol Infect Dis. 2005 Dec;53(4):265-71
16360550
Xenobiotica. 1993 Nov;23(11):1311-23
8310714
Int J Antimicrob Agents. 1999 Feb;11(2):107-13
10221413
Intensive Care Med. 2005 Sep;31(9):1293-4
16170544
Rev Esp Quimioter. 2005 Mar;18(1):39-44
15915231
Chin Med J (Engl). 2002 Dec;115(12):1849-54
12622937
J Antimicrob Chemother. 1995 Jul;36 Suppl A:207-23
8543496
CMAJ. 2004 Jul 6;171(1):51-8
15238498
J Antimicrob Chemother. 1997 Feb;39(2):295-6
9069562
Drugs. 2000 Sep;60(3):619-46
11030471
Int J Antimicrob Agents. 2006 Jan;27(1):69-72
16343857
Arch Intern Med. 1989 Aug;149(8):1881-3
2669668
J Clin Pharm Ther. 2006 Aug;31(4):393-6
16882111
J Allergy Clin Immunol. 1988 Aug;82(2):213-7
2457043
J Antimicrob Chemother. 2006 Feb;57(2):176-89
16344285
Ther Drug Monit. 1998 Aug;20(4):396-400
9712464
Pediatr Infect Dis J. 1991 Feb;10(2):122-5
2062603